# Annex E. E pidemiologic Studies

E.1. Short-Term Exposure and Cardiovascular Outcomes

E.1.1. Cardiovascular Morbidity Studies

Table E-1 Short-term exposure – car diovascular morbidity outcomes: PM 10



### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Baccarelli et al. (2007, 091310 ) Period of Study: Jan 1995-Aug 2005

Location: Lombardia region, Italy Outcome: Fasting and postmethionineload total homocysteine (tHcy) Age Groups: 11-84 yr Study Design: Cross-sectional / Panel

N: 1,213 participants Statistical Analyses: Generalized additive models

Covariates: Age, sex, BMI, smoking, alcohol, hormone use, temperature, day of the yr, and long-term trends

Season: Adjusted for long-term trends to account for season Dose-response Investigated? No Statistical Package: R v2.2.1 Lags Considered: 1-day, 7-day ma. Pollutant: PM 10 (some TSP measures used to predict PM 10 ) Averaging Time: 24 h Mean (SD): NR

Percentiles: 25th: 20.1 50th: 34.1 75th: 52.6

Max: 390.0 Monitoring Stations: 53 Copollutant: CO, NO 2 , SO 2 , O 3 PM Increment: IQR Percent Change: [Lower CI, Upper CI]: Homocysteine, fasting: 0.4 (-2.4, 3.3) Homocysteine, postmethionine-load: 1.1 (-1.5, 3.7) Percent Change: per 25.7m3 increase in 7-day ma of PM 10 Homocysteine, fasting: 1.0 (-1.9, 3.9) Homocysteine, postmethionine-load: 2.0 (-0.6, 4.7) Percent Change: on fasting homocysteine per IQR increase in 24-h PM 10 levels Among smokers: 6.2 (0.0, 12.7) Among non-smokers: -1.6 (-5.5, 2.5)Percent Change: on postmethionineload homocysteine per IQR increase in 24-h PM 10 levels: Among smokers: 6.0 (0.5, 11.8) Among non-smokers: -0.1 (-3.6, 3.5)



### December 2009 E-1

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Baccarelli et al. (2007, 090733 ) Period of Study: Jan 1995-Aug 2005

Location: Lombardia region, Italy Outcome: Prothrombin time (PT) Activated partial thromboplastin time (APTT) Fibrinogen Functional antithrombin Functional protein C Protein C, antigen Functional protein S Free protein S Age Groups: 11-84 yr Study Design: Cross-sectional / Panel

N: 1,218 participants Statistical Analyses: Generalized additive models

Covariates: Age, sex, BMI, smoking, alcohol, hormone use, temperature, day of the yr, and long-term trends

Season: Adjusted for long-term trends to account for season Dose-response Investigated? No Statistical Package: R software v2.2.1 Pollutant: PM 10 (some TSP measures used to predict PM 10 ) Averaging Time: Hourly concentrations used to calculate lags of same day, 7- day, 30-day, and h 0-6 Mean (SD): NR

Percentiles: Sep-Nov: 5th: 33.1 50th: 51.2 75th: 76.5 Max: 148.9

Dec-Feb: 25th: 47.9 50th: 68.5 75th: 95.3 Max: 238.3 Mar-May: 25th: 30.0 50th: 64.1 75th: 64.8 Max: 158.5 Jun-Aug: 25th: 28.0 50th: 44.3 75th: 61.3 Max: 94.7 Monitoring Stations: 53 sites Copollutant: CO, NO 2 , SO 2 , O 3 PM Increment: SD Effect Estimate [Lower CI, Upper CI]: Estimated changes in endpoint PT (international no rmalized ratio): At time of blood sample: -0.06 (-0.12, 0.00) Avg levels 7 days prior: -0.03 (-0.10, 0.04) Avg levels 30 days prior: -0.08 (-0.14, - 0.01) (Hourly ma presented in Fig 2) APTT (ratio to reference plasma): At time of blood sample: 0.02 (-0.04, 0.08) Avg levels 7 days prior: 0.00 (-0.07, 0.06) Avg levels 30 days prior: 0.01 (-0.06, 0.08) Fibrinogen: At time of blood sample: 0.01 (-0.05, 0.07) Avg levels 7 days prior: -0.03 (-0.09, 0.04) Avg levels 30 days prior: -0.02 (-0.09, 0.05)

Functional antithrombin: At time of blood sample: -0.02 (-0.09, 0.04) Avg levels 7 days prior: -0.06 (-0.13, 0.01) Avg levels 30 days prior: -0.06 (-0.13, 0.02) Functional protein C: At time of blood sample: 0.00 (-0.06, 6.1) Avg levels 7 days prior: -0.06 (-0.12, 0.01) Avg levels 30 days prior: -0.06 (-0.14, 0.01) Protein C, antigen: At time of blood sample: 0.00 (-0.06, 6.0) Avg levels 7 days prior: -0.04 (-0.10, 0.03) Avg levels 30 days prior: -0.06 (-0.14, 0.01) Functional protein S: At time of blood sample: 0.04 (-0.03, 0.10) Avg levels 7 days prior: -0.03 (-0.11, 0.06) Avg levels 30 days prior: -0.14 (-0.23, -0.05) Free protein S: At time of blood sample: 0.05 (-0.01, 0.10) Avg levels 7 days prior: 0.01 (-0.05, 0.07) Avg levels 30 days prior: -0.01 (-0.08, 0.06)



### December 2009 E-2

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Barclay et al. (2009, 179935 ) Period of Study: Jan 2003-May 2005

Location: Aberdeen, Scotland Outcome: Haematological outcomes, Heart Rhythm outcomes, & Heart Rate Variability outcomes Age Groups: 70.4 (8.9) Study Design: Panel

N: 132 patients w/ chronic heart failure Statistical Analyses: Linear & Mixed Effects Regression Model

Covariates: Age, temperature, humidity, pressure Dose-response Investigated? No Statistical Package: NR Lags Considered: Lags 0-2 day Pollutant: PM 10 Averaging Time: daily Mean (SD): 20.25

Min: 7.375

Max: 68.3 Monitoring Stations: 1 Copollutant: PM 2.5 , PNC, NO 2 Co-pollutant Correlation: NO 2 city: 0.294 NO city: 0.112 NO 2 personal: 0.055 PNC DEOM: 0.241 PM 2.5 total: 0.476* PM 2.5 traffic: 0.882* PNC total: 0.125 PNC traffic: 0.190 *Correlations based on 3-day avg concentrations PM Increment: NR Beta (Lower CI, Upper CI): Haemoglobin: 0.136 (-0.274, 0.546) Mean corpuscular haemoglobin: 0.030 (-0.232, 0.291) Platelets: 0.096 (-0.923, 1.115) Haematocrit: 0.131 (-0.289, 0.551) White blood cells: 0.034 (-1.175, 1.244) C reactive protein: -4.872 (-12.094, 2.351) IL-6: 2.207 (-4.995, 9.410) von Willebrand factor: 0.660 (-2.651, 3.970) E-selectin: -0.536 (-2.528, 1.457) Fibrinogen: -0.432 (-2.470, 1.607) Factor VII: 0.990 (-1.265, 3.245) day-dimer: -1.225 (-4.505, 2.055) All arrhythmias: -3.447 (-11.521, 4.627) Ventricular ectopic beats: -2.110 (- 12.135, 7.915) Ventricular couplets: -1.561 (-10.811, 7.689) Ventricular runs: -0.709 (-6.677, 5.259) Supraventricular ectopic beats: 0.033 (-9.242, 9.308) Supraventricular couplets: 0.006 (-8.618, 8.629) Supraventricular runs: 3.710 (-2.847, 10.266) Avg HR: 0.321 (-0.197, 0.838) 24 h SDNN: 1.040 (-0.415, 2.494) 24 h SDANN: 1.195 (-0.473, 2.863) 24 h RMSSD: 0.321 (-0.197, 0.838) 24 h PNN: 2.837 (-3.791, 9.465) 24 h LF power: 0583 (-3.622, 4.787) 24 h LF normalized: -3.137 (-5.540, -0.733)* 24 h HF power: 0.872 (-4.649, 6.392) 24 h HF normalized: -2.223 (-4.952, 0.505) 24 h LF/HF ratio: -0.296 (-3.832, 3.240) *p < 0.05

Notes: LF= low frequency HF= high frequency

Reference: Briet et al. (2007, 093049 ) Period of Study: NR

Location: Paris, France Outcome: Endothelial Function Age Groups: 20-40 yr Study Design: Panel

N: 40 white male nonsmokers Statistical Analyses: Multiple Robust Regrssion

Covariates: R53R/R53H genotype, diet, subject factor, visit, temperature Dose-response Investigated? No Statistical Package: NCSS Lags Considered: 0-5 day Pollutant: PM 10 Averaging Time: 24 h 5 day Mean (SD): 43 (10) Monitoring Stations: NR Co-pollutant: PM 2.5 , SO 2 , NO, NO 2 , CO Co-pollutant Correlation: N/A PM Increment: 1 SD Beta (Lower CI, Upper CI), P, R2: Flow-mediated brachial artery dilation: 0.07 (-0.62, 0.76), NS, 0.03 Reactive hyperemia: 15.91 (7.74, 24.0), <0.001, 0.16



### December 2009 E-3

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Choi et al. (2007, 093196 ) Period of Study: 2001-2003

Location: Incheon, South Korea Outcome: Blood pressure Study Design: Cross-sectional

N: 10459 subjects with a hospital health examination Statistical Analyses: Linear regression

Covariates: Season: Effect modification by season Pollutant: PM 10 Averaging Time: Measured hourly and calculated 24-h means

Percentiles: Warm season: Median: 36.7 Cold season: Median: 45.7 Monitoring Stations: 9 stations Copollutant: NO 2 , SO 2 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Estimate (p-value) for the relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) and an increase in PM 10 on lag day 1

SBP: Warm season: 0.0798 (p < 0.001) DBP: Warm season: 0.0240 (p < 0.001)

Note: No evidence of associations between PM 10 and BP during the cold

season

Reference: Chuang et al. (2007, 091063 ) Period of Study: Between Apr-Jun 2004 or 2005

Location: Taipei, Taiwan Outcome: High-sensitivity C-reactive protein (hs-CRP) Fibrinogen, plasminogen activatorfibrinogen inhibitor-1 (PAI-1), tissuetype plasminogen activator (tPA), 8- hydroxy-2’-deoxyguanosine (8-OHdG), and log-transformed HRV indices (SDNN = standard de viation of NN intervals, r-MSSD = square root of the mean of the sum of the squares of differences between adjacent NN intervals, LF = low frequency [0.04- 0.15Hz], and HF = high frequency [0.15-0.40Hz]) Age Groups: 18-25 yr Study Design: Panel (cross-sectional)

N: 76 students Statistical Analyses: Linear mixedeffects models

Covariates: Age, sex, BMI, weekday, temperature of previous day, relative humidity

Season: Only 1 season of data collection Dose-response Investigated? No Statistical Package: NR Pollutant: PM 10 Averaging Time: Hourly data used to calculate avg over 1- to 3-day periods Mean (SD): 1-day avg: 49.2 (18.0) 2-day avg: 55.3 (18.6) 3-day avg: 54.9 (18.2) Range (Min, Max): 1-day avg: 29.5, 83.4 2-day avg: 25.5, 85.1 3-day avg: 22.2, 87.2 Monitoring Stations: 2 sites (each pollutant measured at one site only) Copollutant: PM 2.5 , Sulfate, Nitrate, OC, EC, NO 2 , CO, SO 2 , O 3 PM Increment: IQR (1-day avg: 32.7 2-day avg: 34.5 3-day avg: 26.0) Effect Estimate [Lower CI, Upper CI]: % change in health endpoint per increase in IQR of PM 10 (1-3 day averaging period single pollutant models)

hs-CRP: 1-day: 135.8 (1.8, 269.7) 2-day: 108.2 (-10.9, 227.3) 3-day: 109.6 (2.5, 216.7)

8-OHdG: 1-day: -9.2 (-21.5, 3.2) 2-day: -6.1 (-17.0, 4.8) 3-day: -5.6 (-13.8, 2.6)

PAI-1: 1-day: 30.0 (12.4, 47.7) 2-day: 19.1 (3.6, 34.7) 3-day: 21.2 (9.7, 32.8)

tPA: 1-day: 16.0 (-4.1, 36.2) 2-day: 10.4 (-6.3, 27.2) 3-day: 8.8 (-2.8, 20.5) Fibrinogen: 1-day: 5.3 (1.5, 15.2) 2-day: 1.5 (-4.4, 7.5) 3-day: 3.3 (-1.1, 7.7) Heart Rate Variability SDNN: 1-day: -4.9 (-7.8, -2.1) 2-day: -4.0 (-6.6, -1.4) 3-day: -4.1 (-6.1, -2.2)

r-MSSD: 1-day: -4.8 (-12.3, 2.7) 2-day: -2.2 (-9.0, 4.7) 3-day: -4.0 (-9.0, 0.9)

LF: 1-day: -6.1 (-10.1, -2.1) 2-day: -3.0 (-7.2, 1.2) 3-day: -4.3 (-7.0, -1.6)

HF: 1-day: -5.5 (-13.0, 2.1) 2-day: -2.7 (-9.5, 4.1) 3-day: -2.0 (-7.2, 3.2)



### December 2009 E-4

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ebelt et al. (2005, 056907 ) Period of Study: Summer of 1998

Location: Vancouver, Canada Outcome: CVD Age Groups : Range from 54-86 yr mean age= 74 yr Study Design: Extended analysis of a repeated-measures panel study

N: 16 persons with COPD Statistical Analyses: Earlier analysis expanded by developing mixed-effect regression models and by evaluating additional exposure indicators Dose-response Investigated? No Statistical Package : SAS V8 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Ambient PM 10 : 17 ± 6 Exposure to ambient PM 10 : 10.3 ± 4.6 Range (Min, Max): Ambient PM 10-2.5 : 7



# - 36 Exposure to ambient PM 10-2.5 : 1.5



# - 23.8 Monitoring Stations : 5 Copollutant (correlation): Ambient concentrations and exposure to ambient PM were highly correlated for each respective metric: r ≥ 0.71

PM 10-2.5 : r ≥ 0.72

PM 2.5 : r ≥ 0.92 Note: Total personal fine particle exposure (T) were dominated by exposures to non ambient particles which were not correlated with ambient fine particle exposure (A) or ambient concentrations (C). Results for each of these metrics are listed.

Effect estimates and 95% CI for IQR range increases in exposure Increment: C10: IQR = 7 μg/m 3 SBP (mm Hg): -2.2 (-4.78-0.38) DBP (mm Hg): -0.78 (-2.65-1.09) Ln-SVE (bph): 0. 16 (-0.07-0.40) HR (bpm): 1.02 (-0.79-2.82) SDNN (ms): -2.14 (-6.94-2.65) R-MSSD (ms): -2.24 (-4.27-0.21) Increment: A10: IQR = 6.5μg/m 3 SBP (mm Hg): -2.81 (-5.67-0.05) DBP (mm Hg): -0.59 (-2.79-1.62) Ln-SVE (bph): 0.27 (0.03-0.52) HR (bpm): 0.86 (-1.61-3.33) SDNN (ms): -3.91 (-9.73-1.91) R-MSSD (ms): -0.81 (-4.94-3.31)

Reference: Folino et al. (2009, 191902 ) Period of Study: Jun 2006-May 2007

Location: Padua, Italy Outcome: HRV & Inflammatory Markers Age Groups: 45-65 yr Study Design: Panel

N: 39 patients w/ myocardial infarction Statistical Analyses: Linear Regression Model, ANOVA

Covariates: Temperature, relativehumidity, atmospheric pressure, betablocker, aspirin, or nitrate consumption, smoking habit Dose-response Investigated? No Statistical Package: Stata Lags Considered: NR Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Summer: 46.4 (16.1) Winter: 73.0 (30.9) Spring: 38.3 (15.4) Monitoring Stations: NR Copollutant: PM 2.5 , PM 0.25 Co-pollutant Correlation: NR PM Increment: 1 μg/m 3 Beta (SE), p-value: SDNN: 0.115 (0 .093), 0.218 SDANN: 0.138 (0.103), 0.182 RMSSD: 0.049 (0.034), 0.146 pH: 0.002 (0.001), 0.033 LTB4: 0.427 (0.0279), 0.126 eNO: 0.000 (0.002), 0.851 PTX3: -0.003 (0.001), 0.033 C-reactive protein: -0.006 (0.004), 0.161 CC16: -0.002 (0.002), 0.280 IL-8: 0.000 (0.003), 0.895

Reference: Forbes et al. (2009, 190351 ) Period of Study: 1994, 1998, 2003

Location: England Outcome: Inflammation markers Age Groups: 16+ yr Study Design: C ross-sectional

N: 25,000 white adults w/ fibrinogen measurements & 17,000 white adults w/ C-reactive protein measurements Statistical Analyses: Multilevel Linear Regression Models

Covariates: Age, sex, BMI, social class, region, cigarette smoking Dose-response Investigated? No Statistical Package: Stata Lags Considered: NR Pollutant: PM 10 Averaging Time: Yearly

1994 Median: 19.5 Range: 12.5-36.1 IQR: 3.7 1998 Median: 17.9 Range: 12.6-27.0 IQR: 2.7 2003 Median: 16.2 Range: 11.0-22.7 IQR: 2.6 Monitoring Stations: NR Copollutant: NO 2 , SO 2 , O 3 Co-pollutant Correlation: N/A PM Increment: 1 μg/m 3 Percent Change (Lower CI, Upper CI): Fibrinogen 1994 Crude: -0.068 (-0.367, 0.231) 1994 Adjusted: 0.080 (-0.164, 0.326) 1998 Crude: -0.592 (-0.902, -0.280) 1998 Adjusted: -0.388 (-0.727, -0.047) 2003 Crude: -0.339 (-0.696, 0.019) 2003 Adjusted: -0.069 (-0.458, 0.322) Combined: -0.077 (-0.254, 0.100) C-reactive protein 1998 Crude: -0.914 (-2.206, 0.395) 1998 Adjusted: -0.266 (-1.782, 1.274) 2003 Crude: 0.286 (-1.327, 1.925) 2003 Adjusted: 0.661(-1.068, 2.421) Combined: 0.140 (-1.003, 1.296)



### December 2009 E-5

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Kaufman (1987, 190960 ) Period of Study: Nov 2004-2005

Location: Isfahan, Iran Outcome: Inflammation Age Groups: 10-18 yr Study Design: Panel

N: 374 children Statistical Analyses: Linear Regression, Logistic Regression

Covariates: Age, gender, BMI, waist circumference, heal thy eating index, physical activity level Dose-response Investigated? No Statistical Package: SPSS Lags Considered: 0- to 7-day avg Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 122.08 (33.63) 0th: 11.00 25th: 86.50 50th: 153.0 75th: 191.00 Monitoring Stations: 3 Copollutant: O 3 , SO 2 , NO 2 , CO Co-pollutant Correlation: NR PM Increment: NR Beta (SE): CRP: 1.5 (0.2) Ox-LDL: 1.4 (0.1) MDA: 1.3 (0.1) CDE: 1.1 (0.1) HOMA-IR: 1.1 (0.3)

Reference: Liao et al. (2004, 056590 ) Period of Study: 1996-1998

Location: ARIC study cohort (Washington County, MD Forsyth County, NC and selected suburbs of Minneapolis, MN). The 4th quarter of the ARIC cohort was sampled exclusively from black residents of Jackson, MS. Outcome: 5-min HR, HRV indices (HF, LF, SDNN) Study Design: Cross-sectional Statistical Analyses: Linear regression Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 24.3 (11.5) Copollutant: O 3 CO SO 2 NO 2 PM Increment: SD Effect Estimate [Lower CI, Upper CI]: Estimate (SE) HF: -0.06 ms2 (0.018) SDNN: -1.03 ms (0.31) H: 0.32 beats/min (0.158)

Reference: Liao et al. (2005, 088677 ) Period of Study: 1987-1989 baseline health exam

Location: 3 centers in the U.S. (Forsyth County, NC suburbs of Minneapolis, MN black residents of Jackson, MS) Outcome: Fibrinogen, factor VIII coagulant activity (VIII-C), von Willebrand factor (vWF), white blood cell count (WBC), and serum albumin Age Groups: 45-64 yr Study Design: Cross-sectional

N: 10,208 participants (7705 for PM) Statistical Analyses: Multiple linear regression

Covariates: Age, sex, ethnicity-center, education, smoking, drinking status, BMI, history of chronic respiratory disease, humidity, season, cloud cover, and temperature Dose-response Investigated? Yes, examined higher-ordered terms for each pollutant Statistical Package: SAS v8.2 Pollutant: PM 10 Averaging Time: 24-h avg (1, 2, and 3 days prior to the exam) Mean (SD): 29.9 (29.9) Mean (SD) within Quartiles: Q1-3: 24.0 (6.96) Q4: 47.3 (10.11) Copollutant: CO, SO 2 , NO 2 , O 3 PM Increment: 1 SD (12.8 μg/m 3 )

Effect Estimate: Adjusted regression coefficient (SE): Fibrinogen (mg/dl): 0.163 (0.755) Factor VIII-C (%): Non-linear association: β (PM 10 ) = -5.30, p < 0.01 β (PM 10 )2 = 0.80, p < 0.05 vWF (%): Diabetics: 3.93 (1.80) Nondiabetics: -0.54 (0.58) Albumin (g/dl): CVD: -0.006 (0.003) Non-CVD: 0.029 (0.017) p < 0.05



### December 2009 E-6

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Liao et al. (2007, 180272 ) Period of Study: 1999-2004

Location: 24 U.S. states Outcome: Ectopy Age Groups: Women 50-79 yr Study Design: Panel

N: 57,422 Statistical Analyses: Logistic regression & random effects modeling

Covariates: Age, race, center, education, history of CVD/chronic lung disease, rel. humidity, temperature, smoking Dose-response Investigated? No Statistical Package: SAS, Stata Lags Considered: Lags 0-365 day ‡ Monitors used in model for spatial interpolation of daily PM values. Pollutant: PM 10 Averaging Time: Daily Mean (SD)*: All: 27.5 (12.1) No Ectopy: 27.5 (12.1) Any Ectopy: 27.5 (11.9) 5th, 95th percentile*: All: 12.2, 48.9 No Ectopy: 12.3, 48.8 Any Ectopy: 11.8, 49.3 Monitoring Stations: NR‡ Copollutant: PM 2.5 Co-pollutant Correlation: NR *Lag 1 PM Increment: 10 μg/m 3 Percent Change (Lower CI, Upper CI): All Ventricular Ectopy Lag 0: 1.01 (0.95, 1.07) Lag 1: 1.02 (0.96, 1.09) Lag 2: 0.99 (0.93, 1.06) Current Smoker Ventricular Ectopy Lag 0: 1.21 (0.96, 1.53) Lag 1: 1.32 (1.07, 1.65) Lag 2: 1.22 (0.95, 1.56) Nonsmoker Ventricular Ectopy Lag 0: 1 (0.93, 1.06) Lag 1: 1.01 (0.94, 1.07) Lag 2: 0.98 (0.92, 1.05) All Supraventricular Ectopy Lag 0: 1 (0.95, 1.06) Lag 1: 1 (0.95, 1.05) Lag 2: 0.99 (0.94, 1.04) All Ventricular or Supraventricular Ectopy Lag 0: 1 (0.95, 1.04) Lag 1: 1 (0.96, 1.04) Lag 2: 0.98 (0.94, 1.02)

Reference: Liu et al. (2007, 156705 ) Period of Study: May 2005-Jul 2005

Location: Windsor, Ontario, Canada Outcome: Heart rate, blood pressure, brachial arterial diameter, flow-mediated vasodilatation (FMD), plasma cytokines, and thiobarbituric acid reactive substances (TBARS) Age Groups: 18-65 yr Study Design: Panel

N: 24 nonsmoking subjects with type I or II diabetes over a 7 week period (2- 14 visits for subjects)

170 total vascular measurements and 134 total blood samples collected Statistical Analyses: Mixed effects regression models

Covariates: (Time-dependent covariates) Daily temperature, relative humidity, blood glucose level, also checked for confounding by ambient air pollutant concentrations (controlled for ambient PM 2.5 )

Season: No adjustment since testing was completed within a 7-wk period during early summer Dose-response Investigated? No Statistical Package: S-Plus Pollutant: PM 10 (personal) Averaging Time: Real-time monitor measured exposure during 24-h period prior to clinic measures Median (5th-95th percentile): 0-24 h: 25.5 (9.8-133.0) 0-6 h: 15.3 (5.3-83.2) 7-12 h: 17.0 (7.1-186.3) 13-18 h: 28.5 (11.4-167.0) 19-24 h: 30.5 (10.1-148.2) Monitoring Stations: Personal monitoring Copollutant (correlation): Ambient PM 2.5 (r = 0.34) PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: **p < 0.05 *p < 0.10. Regression coefficients (SE) End-diastolic basal diameter (μm): All subjects (n=24): -2.52 (3.27) subjects not taking vasoactive meds (n=17): -3.93 (3.66) subjects w/BMI ≤ 29kg/m2 (n=14): 8.85 (5.85) End-systolic basal diameter (μm): All subjects (n=24): -9.02 (3.58)** subjects not taking vasoactive meds (n=17): -10.59 (4.36)** subjects w/BMI ≤ 29kg/m2 (n=14): 3.85 (5.49) End-diastolic FMD (%): All subjects (n=24): 0.20 (0.08)** subjects not taking vasoactive meds (n=17): 0.23 (0.09)** subjects w/BMI ≤ 29kg/m2 (n=14): 0.12 (0.05)** End-systolic FMD (%): All subjects (n=24): 0.38 (0.18)** subjects not taking vasoactive meds (n=17): 0.51 (0.22)** subjects w/BMI ≤ 29kg/m2 (n=14): 0.18 (0.10)* Flow (cm/s): All subjects (n=24): -0.16 (0.19) subjects not taking vasoactive meds (n=17): -0.48 (0.21)** subjects w/BMI ≤ 29kg/m2 (n=14): -0.39 (0.23)* Heart rate (bpm): All subjects (n=24): 0.01 (0.11) subjects not taking vasoactive meds (n=17): -0.06 (0.12) subjects w/BMI ≤ 29kg/m2 (n=14): 0.15 (0.12) Diastolic blood pressure (mm Hg): All subjects (n=24): 0.19 (0.16) subjects not taking vasoactive meds



### December 2009 E-7

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) (n=17): 0.40 (0.18)** subjects w/BMI ≤ 29kg/m2 (n=14): 0.27 (0.21) Systolic blood pressure (mm Hg): All subjects (n=24): 0.17 (0.19) subjects not taking vasoactive meds (n=17): 0.43 (0.24)* subjects w/ BMI ≤ 29kg/m2 (n=14): 0.38 (0.24) CRP ( μ g/mL): All subjects (n=24): 0.11 (0.07) subjects not taking vasoactive meds (n=17): 0.10 (0.09) subjects w/ BMI ≤ 29kg/m2 (n=14): 0.02 (0.03) ET-1 (pg/mL): All subjects (n=24): 0.00 (0.00) subjects not taking vasoactive meds (n=17): 0.00 (0.00) subjects w/BMI ≤ 29kg/m2 (n=14): 0.00 (0.01) IL-6 (pg/mL): All subjects (n=24): 0.00 (0.05) subjects not taking vasoactive meds (n=17): 0.01 (0.05) subjects w/BMI ≤ 29kg/m2 (n=14): -0.00 (0.03)

TNFα (pg/mL): All subjects (n=24): 0.03 (0.05) subjects not taking vasoactive meds (n=17): 0.02 (0.05) subjects w/ BMI ≤ 29kg/m2 (n=14): 0.03 (0.08) TBARS (pmol/mL) All subjects (n=24): 16.12 (4.00)** subjects not taking vasoactive meds (n=17): 8.10 (9.18) subjects w/ BMI ≤ 29kg/m2 (n=14): - 0.28 (6.60) regression coefficients (SE) among subjects not taking vasoactive medications, with lag time End-diastolic basal diameter (μm): 0- 6 h: 29.91 (10.64)** 7-12 h: 0.72 (3.95) 13-18 h: -3.62 (2.80) 19-24 h: -0.57 (1.7) End-systolic basal diameter (μm): 0-6 h: 28.88 (11.22)** 7-12 h: -0.78 (4.58) 13-18 h: -7.70 (3.30)** 19-24 h: -2.87 (2.05) End-diastolic FMD (%): 0-6 h: -0.12 (0.10) 7-12 h: 0.04 (0.05) 13-18 h: 0.11 (0.03)** 19-24 h: 0.12 (0.04)** End-systolic FMD (%): 0-6 h: 0.36 (0.08)** 7-12 h: 0.48 (0.32) 13-18 h: 0.19 (0.06)** 19-24 h: 0.34 (0.13)** Flow (cm/s): 0-6 h: -0.34 (0.22) 7-12 h: -0.26 (0.27 13-18 h: -0.27 (0.15)* 19-24 h: -0.30 (0.11)** Heart rate (bpm): 0-6 h: 0.31 (0.13)** 7-12 h: 0.26 (0.12)**



### December 2009 E-8

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 13-18 h: 0.01 (0.09) 19-24 h: -0.08 (0.05) Diastolic blood pressure (mm Hg): 0- 6 h: -0.29 (0.12)** 7-12 h: 0.24 (0.12)** 13-18 h: 0.46 (0.17)** 19-24 h: 0.18 (0.14) Systolic blood pressure (mm Hg): 0- 6 h: -0.65 (0.18)** 7-12 h: 0.17 (0.19) 13-18 h: 0.86 (0.24)** 19-24 h: 0.11 (0.10) CRP ( μ g/mL): 0-6 h: 0.15 (0.13) 7-12 h: 0.15 (0.13) 13-18 h: 0.03 (0.06) 19-24 h: 0.04 (0.03) ET-1 (pg/mL): 0-6 h: 0.02 (0.00)** : 7-12 h: -0.00 (0.00) 13-18 h: -0.00 (0.00) 19-24 h: 0.00 (0.00) IL-6 (pg/mL): 0-6 h: 0.03 (0.06) 7-12 h: 0.00 (0.06) 13-18 h: 0.02 (0.03) 19-24 h: 0.00 (0.02)

TNF- α (pg/mL): 0-6 h: 0.01 (0.07) 7-12 h: 0.09 (0.04)** 13-18 h: 0.01 (0.04) 19-24 h: -0.00 (0.03) TBARS (pmol/mL): 0-6 h: -4.44 (6.72) 7-12 h: 11.94 (5.08)** 13-18 h: 5.06 (4.03) 19-24 h: 1.06 (4.64)

Note: Adding ambient PM 2.5 data as a covariate in the model yielded similar regression coefficients for personal PM 10 Reference: Lipsett et al. (2006, 088753 ) Period of Study: Feb-May 2000

Location: Coachella Valley, CA Outcome: HRV parameters: SDNN, SDANN, r-MSSD, LF, HF, total power, triangular index (TRII). Study Design: Panel study

N: 19 non-smoking adults with coronary artery disease Statistical Analysis: Mixed linear regression models with random effects parameters Pollutant: PM 10 Averaging Time: 2 h Mean (range): Indio: 23.2 (6.3-90.4) Palm Springs: 14 (4.7-52) Monitoring Stations: 2 Copollutant: O 3 PM Increment: SE*1000 Effect Estimate (change in HRV per unit increase in PM concentration): SDNN: -0.71 msec (SE = 0.268)

Notes: Weekly ambulatory 24 h ECG recordings (once per week for up to 12 wk), using Holter monitors, were made. Subjects’ residences were within 5 miles of 1 of 2 PM monitoring sites. Regressed HRV parameters against 18: 00-20: 00 mean particulate pollution.



### December 2009 E-9

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ljungman et al. (2008, 180266 ) Period of Study: Aug 2001-Dec 2006

Location: Gothenburg & Stockholm, Sweden Outcome: Ventricular Arrhythmia Age Groups: 28-85 yr Study Design: Case-crossover

N: 88 patients w/ implantable cardioverter defibrillators Statistical Analyses: C onditional logistic regression

Covariates: Temperature, humidity, pressure, ischemic heart disease, ejection fraction, heart disease, diabetes, use of beta-blockers, age, BMI, location at time of arrhythmia, distance from air pollution monitor Dose-response Investigated? No Statistical Package: Stata, S-plus Lags Considered: L ags 2-24 h Pollutant: PM 10 Averaging Time: Hourly Gothenburg, Stockholm

Median: 2h: 18.95, 14.62 24 h: 19.92, 15.23

Min: 2h: 0.00, 0.33 24 h: 2.13, 3.96

Max: 2h: 203.75, 159.79 24 h: 78.01, 90.50

IQR: 2h: 14.16, 11.59 24 h: 11.49, 9.59 Monitoring Stations: 2 Copollutant: PM 2.5 , NO 2 Co-pollutant Correlation 2 h NO 2 : 0.36 24 h NO 2 : 0.29 PM Increment: Interquartile Range Odds Ratio (Lower CI, Upper CI): 2 h: 1.31 (1.00, 1.72) 24 h: 1.24 (0.87, 1.76)

Notes: OR of ventricular arrhythmia for an IQR increase of air pollutants in different subgroups (Fig 2)

Reference: Ljungman et al. (2009, 191983 ) Period of Study: May 2003-Jul 2004

Location: Athens, Greece Helsinki, Finland Ausburg, Germany Barcelona, Spain Rome, Italy Stokholm, Sweeden Outcome: Interleukin-6 Response Age Groups: 35-80 yr Study Design: Panel

N: 955 male myocardial infarction survivors Statistical Analyses: Additive Mixed Models

Covariates: Age, sex, BMI, city, HDL/total cholesterol, smoking, alcohol intake, HbA1c, NT-proBNP, history of MI, heart failure, or diabetes, phlegm Dose-response Investigated? No Statistical Package: NR Lags Considered: 1 day Pollutant: PM 10 Averaging Time: 24 h

Mean: 31.6 25th: 21.1 75th: 38.4 Monitoring Stations: NR Copollutant: CO, NO 2 , PNC, PM 2.5 Co-pollutant Correlation PM 2.5 : 0.81 PM Increment: Interquartile Range (17.4 μg/m 3 ) Change of IL-6 (Low er CI, Upper CI), p-value: 0.0 (-1.3, 1.3), 1.0

Reference: Mar et al. (2005, 087566 ) Period of Study: 1999-2001

Location: Seattle, WA Outcome: Change in arterial O 2 saturation, heart rate, and blood pressure (SBP and DBP) Age Groups: >75 yr Study Design: Panel study

N: 88 elderly subjects Statistical Analysis: GEE Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Indoor: 12.6 (7.8) Outdoor: 14.5 (7.0) PM Increment: 10 μ g/m 3 Unit change in measure(95% CI): Among all subjects: Each increase in outdoor same day PM 10 was associated with: SBP: -0.10 mmHg (95% CI: -1.37, 1.18) DBP: -0.03 mmHg (95% CI: -0.79, 0.73) HR: -0.48 beats/min (95% CI: -1.03, 0.06) Each increase in indoor same day PM 2.5 was associated with: SBP: 0.92 mmHg (95% CI: -0.95, 2.78) DBP: 0.63 mmHg (95% CI: -0.29, 1.56) HR: 0.02 beats/min (95% CI: -0.54, 0.58)

Notes: Results by health status presented in Fig 1. Used 2 sessions that each were 10 consecutive days of measurement. Used personal, indoor, and outdoor measures of PM 2.5



### December 2009 E-10

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Metzger et al. (2007, 092856 ) Period of Study: Jan 1993-Dec 2002

Location: Atlanta, GA Outcome: Days with any event recorded by the ICD, days with ICD shocks/defibrillation and days with either cardiac pacing or defibrillation Study Design: Repeated measures

N: 884 subjects Statistical Analysis: Logistic regression with GEE to account for residual autocorrelation within subjects Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 28.0 (12.2)

Median: 26.4 Copollutant: O 3 , NO 2 , CO, SO 2 . Aug1998-Dec2002: Oxygenated hydrocarbons PM Increment: OR (95% CI): Outcome = Any event recorded by ICD OR = 1.00 (95% CI: 0.97, 1.03)

Reference: Min et al. (2008, 191901 ) Period of Study: Dec 2003-Jan 2004

Location: Taein Isalnd, South Korea Outcome: Heart Rate Variability Age Mean (SD): 44.3 (21.9) Study Design: Panel

N: 1.349 participants Statistical Analyses: Linear Regression

Covariates: A ge, sex, BMI, smoking Dose-response Investigated? No Statistical Package: SAS, R Lags Considered: 0-72 h Pollutant: PM 10 Averaging Time: 1 h Mean (SD): 33.244 (19.017)

Percentiles: 25th: 18.000 50th: 26.000 75th: 41.000 Range: 187.000. 16.000 Monitoring Stations: 1 Copollutant: NO 2 , SO 2 PM Increment: 1 SD (19 μ g/m 3 ) Percent Change: [Lower CI, Upper CI]:

SDNN 6-h avg: -4.34 (-7.99, -0.55)** 9-h avg: -5.48 (-9.61, -1.17)**h^ 12-h avg: -6.23 (-10.47, -1.79)*** 24-h-avg: -4.73 (-9.73, 0.56)- 48-h avg: -1.25 (-5.59, 3.29) 72-h avg: -0.85 (-5.35, 3.86)

LF 6-h avg: -10.32 (-18.05, -1.86)** 9-h avg: -13.79 (-22.26, -4.39)*** 12-h avg: -14.48 (-23.18, -4.80)*** 24-h-avg: -13.15 (-23.36, -1.57)** 48-h avg: -0.10 (-9.99, 10.87) 72-h avg: -7.61 (-17.04, 2.88)

HF 6-h avg: -1.07 (-10.43, 9.28) 9-h avg: -3.28 (-13.72, 8.43) 12-h avg: -4.06 (-14.77, 8.00) 24-h-avg: -1.22 (-13.96, 13.41) 48-h avg: -3.55 (-14.01, 8.18) 72-h avg: -3.88 (-14.64, 8.23)

Notes: Percent change in HRV for air pollution children, adults, and the elderly (Fig 2) Percent change in HRV for PM 10 exposure in all ages (Fig 3)



### December 2009 E-11

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Peters et al. (2009, 191992 ) Period of Study: May 2003-Jul 2004

Location: Helsinki, Finland Ausburg, Germany Barcelona, Spain Rome, Italy Stokholm, Sweeden Outcome: Plasma Fibrinogen Age Groups: 37-81 Study Design: Panel

N: 854 adults Statistical Analyses: Additive Mixed Models

Covariates: Age, sex, BMI, city, HDL/total cholesterol, smoking, HbA1c, NT-proBNP, history of arrhythmia, asthma, arthrosis, stroke, bronchitis, season, apparent temperature, relative humidity, weekday, hour of visit Dose-response Investigated? No Statistical Package: NR Lags Considered: 0- to 5-day avg Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 30.3

Min: 0

Max: 194 Monitoring Stations: NR Copollutant: PM 2.5 , PM 10-2.5 Co-pollutant Correlation: NR PM Increment: 13.5 μg/m 3 Change (Lower CI, Upper CI): Genotype 1 1 rs2070006: 1.22 (0.47, 1.96) rs2070011: 1.16 (0.41, 1.90) rs1800790: 0.27 (-0.36, 0.91) rs2227399: 0.27 (-0.36, 0.91) rs6056: 0.19 (-0.45, 0.83) rs4220: 0.19 (-0.45, 0.83) Haplotype in cluster 2: 0.09 (-0.53, 0.76) rs1800791: 0.18 (0.21, 1.40) Genotype 1 2 rs2070006: 0.5 (-0.19, 2.15) rs2070011: 0.42 (-0.28, 1.13) rs1800790: 1.28 (0.54, 2.01) rs2227399: 1.28 (0.55, 2.02) rs6056: 1.26 (0.49, 2.04) rs4220: 1.27 (0.49, 2.04) Haplotype in cluster 2: 1.17 (0.35, 1.99) rs1800791: 0.40 (-0.48, 1.28) Genotype 2 2 rs2070006: 0.11 (-1.94, 2.15) rs2070011: 0.08 (-2.08, 2.24) rs1800790: 2.15 (0.71, 3.60) s2227399: 2.18 (0.73, 3.63) s6056: 2.24 (0.72, 3.77) s4220: 2.25 (0.73, 3.78) Haplotype in cluster 2: 2.16 (0.61, 3.71) rs1800791: -0.13 (-1.84, 1.58)

Reference: Rosenlund et al. (2007, 114679 ) Period of Study: 1985-1996

Location: Stockholm County Outcome: Myocardial Infarction Age Groups: 15-79 yr Study Design: Case-control

N: 24,387 first event of myocardial infarction cases and 276,926 population based controls Statistical Analyses: Logistic Regression

Covariates: Age, sex, calendar yr, SES Dose-response Investigated? No Statistical Package: Stata Lags Considered: 5 yr Pollutant: PM 10 Averaging Time: 5 yr

Median: 2.4

5th-95th: 0.3-6.2

Median: 2.2

5th-95th: 0.3-6.0 Monitoring Stations: NR Copollutant: NO 2 , CO Co-pollutant Correlation: HNR PM Increment: 5th-95th percentile (5μg/m 3 ) Odds Ratio (Lower CI, Upper CI): All Subjects Controls: 1.0 All Cases: 1.04 (1.00, 1.09) Nonfatal Cases: 0.98 (0.963, 1.03) Fatal Cases: 1.16 (1.09, 1.24) In-hospital death: 1.05 (0.95, 1.17) Out-of-hospital death: 1.23 (1.14, 1.33) Subjects who did not move b/t population censuses Controls: 1.0 All Cases: 1.11 (1.02, 1.21) Nonfatal Cases: 1.05 (0.96, 1.15) Fatal Cases: 1.56 (1.28, 1.91) In-hospital death: 1.58 (1.13, 2.19) Out-of-hospital death: 1.56 (1.22, 1.98)



### December 2009 E-12

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ruckerl et al. (2007, 156931 ) Period of Study: May 2003-Jul 2004

Location: Athens, Augsburg, Barcelona, Helsinki, Rome, and Stockholm Outcome: Interleukin-6 (IL-6), fibrinogen, C-reactive protein (CRP) Age Groups: 35-80 yr Study Design: Repeated measures/ longitudinal

N: 1003 MI survivors Statistical Analyses: Mixed-effect models

Covariates: City-specific confounders (age, sex, BMI) long-term time trend and apparent temperature RH, time of day, day of week included if adjustment improved model fit

Season: Long-term time trend Dose-response Investigated? Used psplines to allow for nonparametric exposure-response functions Statistical Package: SAS v9.1 Pollutant: PM 10 Averaging Time: Hourly and 24 h (lag 0-4, mean of lags 0-4, mean of lags 0-1, mean of lags 2-3, means of lags 0-3) Mean (SD): Presented by city only

Percentiles: NR Range (Min, Max): NR Monitoring Stations: Central monitoring sites in each city Copollutant: SO 2 O 3 NO NO 2 PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: % change in mean blood markers per increase in IQR increase of air pollutant.

IL-6: Lag (IQR): % change in GM (95%CI) Lag 0 (17.4): -0.34 (-1.66, 0.99) Lag 1 (17.4): -0.69 (-1.95, 0.58) Lag 2 (17.4): -1.59 (-3.99, 0.88) 5-day avg (13.5): -0.87 (-2.28, 0.55) Fibrinogen: Lag (IQR): % change in AM (95%CI) Lag 0 (17.4): 0.06 (-0.43, 0.55) Lag 1 (17.4): 0.14 (-0.35, 0.63) Lag 2 (17.4): 0.24 (-0.24, 0.72) 5-day avg (13.5): 0.60 (0.10, 1.09)

CRP: Lag (IQR): % change in GM (95%CI) Lag 0 (17.4): -0.71 (-2.75, 1.37) Lag 1 (17.4): -0.63 (-2.61, 1.39) Lag 2 (17.4): -1.42 (-4.23, 1.47) 5-day avg (13.5): -1.35 (-3.45, 0.79)



### December 2009 E-13

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ruckerl et al. (2006, 088754 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome: C-reactive protein (CRP) serum amyloid A (SAA) E-selectin vWF intercellular adhesion molecule-1 (ICAM-1) fibrinogen Factor VII prothrombin fragment 1+2 D-dimer Age Groups: 50+ yr Study Design: Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear and logistic regression models

Covariates: Models adjusted for different factors based on health endpoint CRP: RH, temperature, trend, ID ICAM-1: temperature, trend, ID vWF: air pressure, RH, temperature, trend, ID FVII: air pressure, RH, temperature, trend, ID, weekday

Season: Time trend as covariate Dose-response Investigated? Sensitivity analyses examined nonlinear exposure-response functions Statistical Package: SAS v8.2 and S-Plus v6.0 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 20.0 (13.0)

Percentiles: 25th: 10.8 50th: 15.6 75th: 26.0 Range (Min, Max): 5.4, 74.5 Monitoring Stations: 1 site Copollutant: UFPs AP PM 2.5 PM 10 OC EC NO 2 CO PM Increment: IQR (15.2 5-day avg: 12.8) Effect Estimate [Lower CI, Upper CI]: Effects of air pollution on blood markers presented as OR (95%CI) for an increase in the blood marker above the 90th percentile per increase in IQR air pollutant.

CRP: Time before draw: 0-23 h: 1.2 (0.8, 1.9) 24-47 h: 2.0 (1.1, 3.6) 48-71 h: 2.2 (1.2, 3.8) 5-day mean: 2.0 (1.2, 3.7)

ICAM-1: Time before draw: 0-23 h: 1.3 (0.9, 1.8) 24-47 h: 3.1 (2.0, 4.8) 48-71 h: 3.4 (2.2, 5.2) 5-day mean: 3.4 (2.2, 5.3) Effects of air pollution on blood markers presented as % change from the mean/GM in the blood marker per increase in IQR air pollutant.

vWF: Time before draw: 0-23 h: 4.0 (-0.6, 8.5) 24-47 h: 6.0 (0.6, 11.5) 48-71 h: 1.1 (-4.9, 7.0) 5-day mean: 6.1 (-0.6, 12.8)

FVII: Time before draw: 0-23 h: -6.6 (-10.4--2.5) 24-47 h: -8.4 (-12.3--4.3) 48-71 h: -5.9 (-9.6, -2.0) 5-day mean: -8.0 (-12.4, -3.4)

Note: Summary of results presented in figures. SAA results indicate increases in association with PM (not as strong and consistent as with CRP)

No association observed between Eselectin and PM An increase in prothrombin fragment 1+2 was consistently observed, particularly with lag 4 Fibrinogen results revealed few significant associations, potentially due to chance

D-dimer results revealed null associations in linear and logistic analyses



### December 2009 E-14

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ruckerl et al. (2007, 091379 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome: Soluble CD40 ligand (sCD40L), platelets, leukocytes, erythrocytes, hemoglobin Age Groups: 50+ yr Study Design: Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear regression models

Covariates: Long-term time trend, weekday of the visit, temperature, RH, barometric pressure

Season: Time trend as covariate Dose-response Investigated? No Statistical Package: SAS v8.2 and S-Plus v6.0 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 20.0 (13.0)

Percentiles: 25th: 10.8 50th: 15.6 75th: 26.0 Range (Min, Max): 5.4, 74.5 Monitoring Stations: 1 site Copollutant: UFPs AP PM 2.5 PM 10 NO PM Increment: IQR (15.2 5-day avg: 12.8) Effect Estimate [Lower CI, Upper CI]: Effects of air pollution on blood markers presented as % change from the mean/GM in the blood marker per increase in IQR air pollutant. sCD40L, % change GM (pg/mL): lag0: 1.6 (-3.5, 7.0) lag 1: 1.1 (-5.4, 7.9) lag 2: -3.5 (-8.9, 2.2) lag 3: -1.4 (-6.0, 3.4) 5-day mean: -1.2 (-7.8, 5.8) Platelets, % change mean (103/ μ l): lag 0: -0.4 (-1.9, 1.0) lag 1: 0.4 (-1.4, 2.3) lag 2: 0.5 (-1.4, 2.3) lag 3: -0.1 (-1.6, 1.4) 5-day mean: 0.0 (2.1, 0.0) Leukocytes, % change in mean (103/ μ l): lag0: -1.1 (-2.8, 0.7) lag 1: -0.5 (-2.6, 1.5) lag 2: 0.1 (-2.1, 2.4) lag 3: -0.7 (-2.6, 1.2) 5-day mean: -1.1 (-3.6, 1.4) Erythrocytes, % change mean (106/ μ l): lag0: 0.0 (-0.4, 0.5) lag 1: -0.4 (-1.0, 0.1) lag 2: -0.7 (-1.2, -0.2) lag 3: -0.4 (-0.8, 0.0) 5-day mean: -0.6 (-1.2, -0.1) Hemoglobin, % change mean (g/dl): lag 0: -0.1 (-0.7, 0.6) lag 1: -0.4 (-1.2, 0.3) lag 2: -0.7 (-1.3, 0.0) lag 3: -0.3 (-0.9, 0.2) 5-day mean: -0.7 (-1.5, 0.1)

Reference: Steinvil et al. (2008, 188893 ) Period of Study: 2003-2006

Location: Tel-Aviv, Israel Outcome: Inflammation Age Groups: Mean (SD): 46 (12) yr Study Design: Panel

N: 3659 Statistical Analyses: Linear Regression

Covariates: Age, waist circumference, BMI, HDL, OLDL, triglycerides, diastolic & systolic BP, alcohol consumption, sports intensity, medications, smoking status, family history of CHD, temperature, humidity, precipitation, season, & yr Dose-response Investigated? No Statistical Package: SPSS Lags Considered: 0-7 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 64 (100.8) 25th: 33.1 50th: 43.0 75th: 60.7 Monitoring Stations: NR Copollutant: SO 2 , NO 2 , O 3 , CO Co-pollutant Correlation: SO 2 : 0.043 NO 2 : 0.082 O 3 : -0.113 CO: 0.075 PM Increment: Interquartile Range (27.6 μg/m 3 ) hs-CRP Relative % Change (Lower CI, Upper CI):

Men: Lag 0: -1 (-2, 1) Lag 1: 0 (-1, 1); Lag 2: -1 (-2, 1) Lag 3: -1 (-2, 0) Lag 4: 0 (-1, 1) Lag 5: 0 (-1, 2) Lag 6: 1 (0, 2) Lag 7: 1 (0, 1) 0-7 avg: -2 (-5, 1)

Women: Lag 0: 0 (-2, 2) Lag 1: 0 (-1, 2) Lag 2: 1 (0, 2) Lag 3: 0 (-1, 1) Lag 4: 0 (-1, 2) Lag 5: 0 (-1, 2) Lag 6: -1 (-3, 1) Lag 7: 0 (-2, 1) 0-7 avg: 1 (-2, 4) Fibrinogen Absolute % Change (Lower CI, Upper CI):

Men: Lag0: 0.7(0.0,1.5); Lag1: 0.4(-0.2, 0.9); Lag2: -0.1(-0.9, 0.6) Lag3: -0.1(-0.7, 0.6); Lag4: 0.0(-0.7, 0.7); Lag5: 0.1(-0.7, 1.0) Lag6: 0.6(-0.1, 1.3); Lag7: 0.4(0.0, 0.8);



### December 2009 E-15

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 0-7 avg: -0.4(-1.9, 1.0)

Women: Lag0: 0.3(-0.6, 1.2); Lag1: -0.1(-0.8, 0.7); Lag2: -0.3(-0.9, 0.3) Lag3: -0.1(-0.7, 0.5); Lag4: 0.2(-0.4, 0.9); Lag5: 0.2(-0.7, 1.2) Lag6: -0.3(-1.4, 0.8); Lag7: 0.7(-0.1, 1.5); 0-7 avg: 0.0(-1.5, 1.5) WBC Absolute Change (Lower CI, Upper CI):

Men: Lag0: 2 (-22, 27) Lag1: 3 (-14, 19) Lag2: 1 (-22, 24) Lag3: -7 (-28, 14) Lag4: -22 (-44, -1) Lag5: -20 (-46, 7) Lag6: -5 (-27, 16) Lag7: -4(-16, 9) 0-7avg: -11(-58, 36)

Women: Lag 0: 20 (-6, 46)

Reference: Su et al. (2006, 157022 ) Period of Study: Feb-Apr 2002

Location: Taipei, Taiwan Outcome: Total cholesterol, HDL,tryglycerides, LDL, hs-CRP, IL-6, TNFα , tPA, PAI-1, and fibrinogen Age Groups: 40-75 yr Study Design: Panel study

N: 49 subjects (31 males and 18 females) with coronary heart disease or multiple risk factors for CHD Statistical Analysis: Linear mixed effects regression Pollutant: PM 10 Averaging Time: 1 h (High pollution day = PM 10 from 08: 00-18: 00 >100) Copollutant: O 3 PM Increment: High vs.. Low pollution days Effect Estimate [Lower CI, Upper CI]: CHD patients (n = 23): P-value for paired t-test comparing health endpoint means on high and low pollution days hs-CRP: p = 0.568 IL-6: p = 0.856 TNF- α : p = 0.246 PAI-1: p = 0.008 tPA: p = 0.322 Fibrinogen: p = 0.189P-value for health endpoint in mixedeffects models PAI-1: p = 0.010 tPA: p = 0.329 Fibrinogen: p = 0.747 Patients with multiple CHD risk factors (n = 26): P-value for paired ttest comparing health endpoint means on high and low pollution days hs-CRP: p = 0.475 IL-6: p = 0.561 TNF- α : p = 0.572 PAI-1: p = 0.098 tPA: p = 0.260 Fibrinogen: p = 0.087P-value for health endpoint in mixedeffects models PAI-1: p = 0.891 tPA: p = 0.789 Fibrinogen: p = 0.923

Notes: Subjects had paired fasting blood samples taken during high and low air pollution days.



### December 2009 E-16

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Vedal et al., (2004, 055630 ) Period of Study: 1997-2000

Location: Vancouver, British Columbia Outcome: Implantable cardioverter defibrillator (ICD) discharge Age Groups: All Study Design: Time series (Retrospective, longitudinal panel study)

N: 50 ICD patients with 1+ discharges (40,328 person-days and 257 arrhythmia event days) Statistical Analyses: Multiple logistic regression with GEE

Covariates: Temperature, relative humidity, barometric pressure, rainfall, wind direction and speed

Season: Summer (May-Sep) and winter (Oct-Apr) Dose-response Investigated: No Statistical Package: NR Lags Considered: -3 day Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 12.9 (3.8-49.3) SD = 5.6 Monitoring Stations: 8 Copollutant (correlation): O 3 : r = 0.11 SO 2 : r = 0.70 NO 2 : r = 0.49 CO: r = 0.43

Other variables: Temp: r = 0.43 Humidity: r = -0.35 Baro Pressure: r = 0.26 Rain: r = -0.63 Wind: r = -0.53 PM Increment: 5.6 μg/m 3 (SD) Percent Change [CI]: Values NR

Notes : The author states that significant negative associations were found for ICD discharge with same-day lag, andalso for 3-day lag with more arrhythmiaprone patients. All other non-significant percent change estimates are shown in Fig 3 and 4.

Reference: Vedal et al. (2004, 055630 ) Period of Study: 1997-2000

Location: Vancouver, British Columbia, Canada Outcome: ICD discharges (arrhythmias)

N: 150 patients w/ICD, 4 yr Statistical Analysis: Logistic regression, GEE

Covariates: Temporal trends, temperature, relative humidity, wind speed, rain

Season: Summer, winter Dose-response Investigated? No Lags Considered: 0, 1, 2, and 3 days Pollutant: PM 10 Mean: 12.9 (SD = 5.6) Copollutant): O 3 , SO 2 , NO 2 , CO Increment: 1 SD Effect Estimates, e.g., % change in the rate of arrhythmia, were presented in Fig 3. No association with PM 10 was observed while SO 2 was associated with an increase in the rate of arrhythmia among 16 patients with at least 2 discharges per yr.



### December 2009 E-17

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Whitsel et al. (2009, 191980 ) Period of Study: 1993-2004

Location: U.S. Outcome: Heart Rate Variability Age Groups: 50-79 yr Study Design: Panel

N: 4,295 women Statistical Analyses: Random Effects Model

Covariates: Temperature, humidity Dose-response Investigated? No Statistical Package: SUDAAN Lags Considered: 0 Pollutant: PM 10 Averaging Time: 24 h

Amsterdam

Mean: 20.0 Min: 3.8 25th: 10.4 50th: 16.9 75th: 23.9 Max: 82.2

Erfurt

Mean: 23.1 Min: 4.5 25th: 10.5 50th: 16.3 75th: 27.4 Max: 118.1

Helsinki

Mean: 12.7 Min: 3.1 25th: 8.1 50th: 10.6 75th: 16.0 Max: 39.8 Monitoring Stations: 3 Copollutant: NR Co-pollutant Correlation: N/A PM Increment: 10 μg/m 3 Beta (Lower CI, Upper CI): Supine Position, Amsterdam Lag 0: -0.06 (-0.95, 0.84) Lag 1: 0.18 (-0.74, 1.10) Lag 2: 0.93 (0.01, 1.85) 5-day avg: 0.49 (-0.74, 1.72) Supine Position, Erfurt Lag 0: -0.36 (-0.83, 0.11) Lag 1: -0.40 (-0.91, 0.11) Lag 2: -0.68 (-1.20, -0.17) 5-day avg: -0.68 (-1.44, 0.09) Supine Position, Helsinki Lag 0: -0.44 (-2.27, 1.40) Lag 1: -0.17 (-1.69, 1.3.5) Lag 2: -1.14 (-2.51, 0.23) 5-day avg: -0.59 (-3.08, 1.90) Supine Position, Pooled Lag 0: -0.30 (-0.71, 0.11) Lag 1: -0.25 (-0.68, 0.18) Lag 2: -0.26 (-1.22, 0.70)* 5-day avg: -0.36 (-0.99, 0.27) Standing Position, Amsterdam Lag 0: -0.44 (-1.6, 0.72) Lag 1: -0.61 (-1.8, 0.59) Lag 2: 0.32 (-0.88, 1.51) 5-day avg: -0.55 (-2.15, 1.04) Standing Position, Erfurt Lag 0: -0.59 (-1.24, 0.06) Lag 1: -0.70 (-1.42, 0.03) Lag 2: -0.65 (-1.37, 0.07) 5-day avg: -0.68 (-1.74, 0.39) Standing Position, Helsinki Lag 0: 1.17 (-1.46, 3.80) Lag 1: 0.01 (-2.17, 2.19) Lag 2: -0.63 (-2.60, 1.34) 5-day avg: -1.96 (-5.51, 1.60) Standing Position, Pooled Lag 0: -0.48 (-1.03, 0.07) Lag 1: -0.62 (-1.21, -0.03) Lag 2: -0.41 (-1.00, 0.17) 5-day avg: -0.72 (-1.57, 0.14) *p < 0.1

Reference: Yeatts et al. (2007, 091266 ) Period of Study: 12-wk period b/t Sep 2003-Jul 2004

Location: Chapel Hill, NC Outcome: Heart Rate Variability Age Groups: 21-50 yr Study Design: Panel

N: 12 asthmatics Statistical Analyses: Linear Mixed Model

Covariates: Temperature, humidity, pressure Dose-response Investigated? No Statistical Package: SAS Lags Considered: 1 day Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 17.5 (7.8)

Min: 1.4

Max: 45.6 Monitoring Stations: 1 Copollutant: PM 2.5 , PM 10-2.5 Co-pollutant Correlation PM 2.5 = 0.90* PM 10-2.5 = 0.73* *p < 0.01 PM Increment: 1 μg/m 3 Beta, SE, p-value (Lower CI, Upper CI): NR

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-18

# Table E-2. Short-term exposure - cardiovascular morbidity studies: PM 10-2.5 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chuang et al. (2007, 091063 ) Period of Study: Nov 2002-Mar 2003

Location: Taipei, Taiwan Outcome: Heart Rate Variability Age Groups: 52-76 yr Study Design: Panel

N: 10 CHD & 16 Hypertensive Patients Statistical Analyses: Linear Mixed Effects Model

Covariates: Age, sex, BMI, time of day, temperature, humidity, pressure, HRV Dose-response Investigated? No Statistical Package: S-PLUS Lags Considered: 1- to 4-h ma Pollutant: PM 10-2.5 Averaging Time: 1 h among CHD, among hypertensive Mean (SD): 16.4 (10.7), 14.0 (11.1)

IQR: 14.8, 11.9

Min: 0.7, 0.3

Max: 59.6, 66.5 Monitoring Stations: 1 personal monitor each Copollutant: PM 1.0-2.5 , PM 0.3-1.0 Co-pollutant Correlation: NR PM Increment: Interquartile range Percent Change (Lower CI, Upper CI):

Cardiac Patients- SDNN 1h moving: -1.73 (-3.53, 0.08) 2h moving: -1.97 (-4.43, 0.49) 3h moving: -1.70 (-4.39, 0.89) 4h moving: -1.75 (-5.42, 1.92)

Cardiac Patients- r-MSSD 1h moving: -4.39 (-9.54, 0.03) 2h moving: -4.36 (-8.99, 0.27) 3h moving: -4.20 (-9.02, 0.61) 4h moving: -2.70 (-9.24, 3.84)

Cardiac Patients- LF 1h moving: -1.85 (-4.33, 0.62) 2h moving: -3.87 (-8.22, 0.47 3h moving: -2.98 (-6.65, 0.69) 4h moving: -3.11 (-8.22, 1.99)

Cardiac Patients- HF 1h moving: -4.46 (-9.23, 0.32) 2h moving: -4.41 (-9.55, 0.72) 3h moving: -3.80 (-9.12, 1.53) 4h moving: -3.39 (-10.62, 3.84)

Cardiac Patients- LF: HF ratio 1h moving: 8.45 (-3.48, 20.38) 2h moving: 1.66 (-15.22, 18.55) 3h moving: 11.69 (-7.27, 30.64) 4h moving: 8.18 (-17.22, 33.57) Hypertensive Patients- SDNN 1h moving: -2.64 (-3.93, 0.55 2h moving: -3.51 (-7.87, 0.85) 3h moving: -2.74 (-6.22, 0.74) 4h moving: -2.49 (-6.13, 1.15) Hypertensive Patients- r-MSSD 1h moving: -2.53 (-5.10, 0.04) 2h moving: -5.42 (-10.92, 0.09) 3h moving: -3.15 (-6.32, 0.03) 4h moving: -4.23 (-8.88, 0.42) Hypertensive Patients- LF 1h moving: -4.38 (-8.78, 0.03) 2h moving: -5.23 (-10.95, 0.05) 3h moving: -3.34 (-1.72, 0.04) 4h moving: -2.96 (-6.63, 0.71) Hypertensive Patients- HF 1h moving: -4.92 (-9.94, 0.10) 2h moving: -6.07 (-12.28, 0.13) 3h moving: -1.94 (-5.44, 1.55) 4h moving: -2.78 (-6.78, 1.21) Hypertensive Patients- LF: HF ratio 1h moving: 5.94 (-3.27, 15.15) 2h moving: 10.70 (-2.19, 23.59) 3h moving: -1.51 (-17.02, 14.00) 4h moving: 3.41 (-16.91, 23.74) *p < 0.05



### December 2009 E-19

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ebelt et al. (2005, 056907 ) Period of Study: Summer of 1998

Location: Vancouver, Canada Outcome: CVD Age Groups : range from 54-86 yr mean age= 74 yr Study Design: extended analysis of a repeated-measures panel study

N: 16 persons with COPD Statistical Analyses: Earlier analysis expanded by developing mixed-effect regression models and by evaluating additional exposure indicators Dose-response Investigated? No Statistical Package : SAS V8 Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (SD): Ambient PM 10-2.5 : 5.6 (3.0) Exposure to ambient PM 10-2.5 : 2.4 (1.7) Range (Min, Max): Ambient PM 10-2.5 : (-1.2-11.9) Exposure to ambient PM 10-2.5 : (-0.4-7.2) Monitoring Stations : 5 Copollutant (correlation): Ambient concentrations and exposure to ambient PM were highly correlated for each respective metric: r ≥ 0.71 Note: Total personal fine particle exposure (T) were dominated by exposures to non ambient particles which were not correlated with ambient fine particle exposure (A) or ambient concentrations (C). Results for each of these metrics are listed.

PM Increment: Increment: C10-2.5: IQR = 4.5 μg/m 3 SBP (mm Hg): -2.12 (-5.07-0.82) DBP (mm Hg): -0.92 (-3.37-0.36) Ln-SVE (bph): 0. 06 (-0.24-0.36) HR (bpm): 1.09 (-0.69-2.86) SDNN (ms): 2.64 (-2.85-8.13) R-MSSD (ms): -0.33 (-4.49-3.82) Increment: A10-2.5: IQR = 2.4 μg/m 3 SBP (mm Hg): -2.55 (-6.15-1.05) DBP (mm Hg): -0.75 (-3.50-2.01) Ln-SVE (bph): 0. 26 (-0.07-0.58) HR (bpm): 1.04 (-0.95-3.03) SDNN (ms): 0.68 (-3.07-4.42) R-MSSD (ms): 1.10 (-3.08-5.28)

Reference: Lipsett et al. (2006, 088753 ) Period of Study: Feb-May 2000

Location: Coachella Valley, CA Outcome: HRV parameters, specifically SDNN, SDANN, r-MSSD, LF, HF, total power, triangular index (TRII). Study Design: Panel study

N: 19 non-smoking adults with coronary artery disease Statistical Analysis: Mixed linear regression models with random effects parameters Pollutant: PM 10-2.5 Averaging Time: 2 h Monitoring Stations: 2 Copollutant: O 3 PM Increment: SE*1000 Effect Estimate (change in HRV per unit increase in PM concentration): SDNN: -0.72 msec (SE = 0.296)

Notes: PM 10-2.5 calculated by subtracting PM 2.5 concentration from PM 10 concentration. Weekly ambulatory 24-h ECG recordings (once per wk for up to 12 wk), using Holter monitors, were made. Subjects’ residences were within 5 mi of 1 of 2 PM monitoring sites. Regressed HRV parameters against 18: 00-20: 00 mean particulate pollution

Reference: Metzger et al. (2007, 092856 ) Period of Study: Aug 1998-Dec 2002

Location: Atlanta, GA Outcome: Days with any event recorded by the ICD, days with ICD shocks/defibrillation and days with either cardiac pacing or defibrillation Study Design: Repeated measures

N: 884 subjects between 1993 and 2002 Statistical Analysis: Logistic regression with GEE to account for residual autocorrelation within subjects Pollutant: PM 10-2.5 (n/cm 3 ) Averaging Time: 24 h Mean (SD): 9.6 (5.4)

Median: 8.7 Copollutant: O 3 , NO 2 , CO, SO 2 , oxygenated hydrocarbons PM Increment: OR (95% CI): OR = 1.03 (95% CI: 1.00, 1.07)

Reference: Pekkanen et al. (2002, 035050 ) Period of Study: Winter 1998-1999

Location: Helsinki, Finland Outcome : ST Segment Depression (>0.1mV) Study Design : Panel of ULTRA Study participants

N : 45 subjects, 342 biweekly submaximal exercise tests, 72 exercise induced ST Segment Depressions Statistical Analysis: Logistic regression / GAM Pollutant: PM 10-2.5 (n/cm 3 ) Averaging Time: 24 h

Median : 4.8

IQR : 5.5 Monitoring Stations : 1 Copollutant: NO 2 , CO, PM 2.5 , PM 1 , ACP, ultrafine PM Increment: IQR Effect Estimate(s): PM 10-2.5 : OR = 1.99 (0.70, 5.67), lag 2

Notes : The effect was strongest for ACP and PM 2.5 , which in 2 pollutant models appeared independent. Increases in NO 2 and CO were also associated with increased risk of ST segment depression, but not with coarse particles.

Reference: Timonen et al. (2006, 088747 ) Period of Study: 1998-1999

Location: Amsterdam, Netherlands Erfurt, Germany Helsinki, Finland Outcome: HRV measurements: [LF,HF, LFHFR, NN interval, SDNN, rMSSD] Study Design: Panel study

N: 131 elderly subjects with stable coronary heart disease Statistical Analysis: Linear mixed models Pollutant: PM 10-2.5 Means: Amsterdam: 15.3 Erfurt: 3.7 Helsinki: 6.7 Copollutant: NO 2 , CO PM Increment: 10 μg/m 3

Effect Estimate: SDNN 0.69ms (95% CI: -1.24, 2.63) HF: 2.9% (95% CI: -7.3, 13.1) LFHFR: -3.3 (95% CI: -12.7, 6.1)

Notes: Followed for 6 mo with biweekly clinic visits 2-day lag. ULTRA Study



### December 2009 E-20

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Yeatts et al. (2007, 091266 ) Period of Study: 12-wk period b/t Sep 2003-Jul 2004

Location: Chapel Hill, NC Outcome: Heart Rate Variability Age Groups: 21-50 yr Study Design: Panel

N: 12 asthmatics Statistical Analyses: Linear Mixed Model

Covariates: T emperature, humidity, pressure Dose-response Investigated? No Statistical Package: SAS Lags Considered: 1 day Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (SD): 5.3 (2.8)

Min: 0

Max: 14.6 Monitoring Stations: 1 Copollutant: PM 2.5 , PM 10 Co-pollutant Correlation: PM 2.5 = 0.46* PM 10 = NR *p < 0.01 PM Increment: 1 μg/m 3

.Beta, SE (Lower CI, Upper CI), pvalue

HRV Max Heart Rate: -1.95, 0.88 (-3.67, - 0.23), 0.03 ASDNN5: -0.77, 0.37 (-1.580, -0.04), 0.05 SDANN5: -3.76, 1.53 (-6.76, -0.76), 0.02 SDNN24HR(mesc): -3.36, 1.38 (-6.06, - 0.65), 0.02 rMSSD: -0.75, 0.53 (-1.79, 0.28), 0.16 pNN50_24hr: -0.50, 0.27 (-1.03, 0.03), 0.07 pNN50_7min: -1.88, 0.55 (-2.95, -0.81), 0.07 Low-frequency power: -0.19, 0.42 (- 1.01, 0.63), 0.65 Percent low frequency: 0.57, 1.08 (- 1.55, 2.69), 0.60 High-frequency power: -0.46, 0.17 (- 0.79, -0.14), 0.01 Percent high frequency: -2.14, 0.94 (- 3.98, -0.30), 0.03 Blood Lipids Triglycerides: 4.78, 2.02 (0.81, 8.74), 0.02 VLDL: 1.15, 0.44 (0.29, 2.02), 0.01 Total cholesterol: 0.78, 0.54 (-0.28, 1.84), 0.15 Hematologic Factors Circulating eosinophils: 0.16, 0.06 (0.04, 0.28), 0.01 Platelets: -1.71, 1.11 (-3.89, 0.47), 0.13 Circulating Proteins Plasminogen: -0.01, 0.01 (-0.02, 0.00), 0.08 Fibrenogen: -0.04, 0.02 (-0.08, 0.00), 0.07 Von Willibrand factor: -1.23, 0.66 (-2.53, 0.06), 0.07 Factor VII: -0.90, 0.85 (-2.58, 0.77), 0.29

1 All units expressed in μg/m 3 unless otherwise specified.



# Table E-3. Short-term exposure - cardiovascular morbidity studies: PM 2.5 

# (including PM components/sources).

Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Adar et al. (2007, 001458 ) Period of Study: Mar-Jun 2002

Location: St. Louis, Missouri Outcome: Heart rate variability: heartrate, standard deviation of all normal-tonormal intervals (SDNN), square root of the mean squared difference between adjacent normal-to-normal intervals (rMSSD), percentage of adjacent normal-to-normal intervals that differed by more than 50 ms (pNN50), high frequency power (HF in the range of 0.15-0.4Hz), low frequency power (LF, in the range of 0.04-0.15Hz), and the ratio of LF/HF Age Groups: ≥ 60 yr Study Design: Panel (4 planned repeated measures surrounding bus Pollutant: PM 2.5 ( μ g/m 3 ) Averaging Time: Measurements collected over 48 h period surrounding the bus trip (during which health endpoints were measured) used to calculate 5-, 30-, 60-min, 4-h, 24-h ma Median (IQR): All: 7.7 (6.8) Facility: 6.8 (5.1) Bus: 17.2 (10.3) Activity: 8.2 (16.1) Lunch: 11.2 (5.9) Monitoring Stations: 2 portable carts Copollutant: PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: % change (95%CI) in HRV per IQR in the 24-h ma of the microenvironmental pollutant (IQr = 4.5 μ g/m 3 ) Single-pollutant models: SDNN: -5.5 (-6.3, -4.8) rMSSD: -9.1 (-9.8, -8.4) pNN50 + 1: -12.2 (-13.3, -11.1). LF: - 10.8 (-12.3, -9.3) HF: -15.1 (-16.7, -13.7) LF/HF: 5.1 (3.9, 6.4) H: 1.0 (0.9, 1.2) Two-pollutant models (with particle



### December 2009 E-21

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) trips with a total of 158 person-trips, 35 participating in all 4 trips)

N: 44 participants Statistical Analyses: Generalized additive models

Covariates: Subject, weekday, time, apparent temperature, trip type, activity, medications, and autoregressive terms

Season: Limited data collection period Dose-response Investigated? No Statistical Package: SAS v8.02, R v2.0.1 PM 2.5 BC Fine particle counts coarse particle counts

Correlation notes: 24-h mean PM 2.5 ,BC, and fine particle count concentrations ranged from 0.80-0.98 r = 0.76-0.97 when limited to time spent on the bus r = 0.55-0.86 when comparing bus concentrations to 24-h ma r = -0.003-0.51 when comparing 5-min avg and 24-h ma

Poor correlations found between coarse particle count concentrations and all fine particulate measures during all times periods number count coarse): SDNN: -5.7 (-6.5, -4.9) rMSSD: -9.4(-10.1, -8.6) pNN50+1: -13.1(-14.3, -11.9). LF: -10.7(-12.4, -9.1) HF: -14.9(-16.5, -13.3); LF/HF: 4.9 (3.6, 6.2)’ H: 0.9 (0.7,1.1) Independent short- and medium-term associations with HRV across all time periods % change per IQR (95%CI) IQR 5-min means = 6.8 μ g/m 3 and 23: 55-h means = 4.2 μ g/m 3 SDNN: 5-min mean: -0.5 (-0.8, -0.1) 23: 55-h mean: -4.6 (-5.3, -4.0) rMSSD: 5-min mean: -0.9 (-1.3, -0.5) 23: 55-h mean: -7.5 (-8.1 to -6.8) pNN50 + 1 5-min mean: -1.1 (-1.7 to -0.5) 23: 55-h mean: -9.9 (-10.9 to -8.9). LF 5-min mean: 0.4 (-0.5, 1.2) 23: 55-h mean: -10.0 (-11.4 to -8.6) HF 5-min mean: -1.5 (-2.3 to -0.6) 23: 55-h mean: -12.9 (-14.2 to -11.5) LF/HF 5-min mean: 1.9 (1.3, 2.4) 23: 55-h mean: 3.2 (2.1, 4.3) H: 5-min mean: 0.1 (0.1, 0.2) 23: 55-h mean: 0.8 (0.7, 0.9) Independent associations of short-term avg (5-min means) of PM with HRV by bus and nonbus periods

IQR for bus = 10 μ g/m 3 ) and nonbus = 5.6 μ g/m 3 ) % change (95%CI) p-value of interaction SDNN Bus: -5.0 (-6.3 to -3.7) Nonbus: -0.5 (-0.9 to -0.2) p-value for interaction: <0.0001. rMSSD Bus: -4.8 (-6.2 to -3.5) Nonbus: -0.7 (-1.1 to -0.4. p-value for interaction: <0.0001 pNN50 + 1 Bus: -6.3 (-8.4 to -4.2) Nonbus: -0.8 (-1.4 to -0.3) p-value for interaction: <0.0001 LF: Bus: -7.0 (-9.8 to -4.1) Nonbus: 0.6 (-0.1, 1.4) p-value for interaction: <0.0001. HF: Bus: -10.7 (-13.5 to -7.9)’ Nonbus: -0.7 (-1.5, 0.04) p-value for interaction: <0.0001. LF/HF: Bus: 3.9 (1.7, 6.0) Nonbus: 1.4 (0.8, 1.9) p-value for interaction: 0.39. H: Bus: 0.7 (0.5, 1.0) Nonbus: -0.01 (-0.08, 0.1) p-value for interaction: <0.0001 Note: Exposure to health associations by all lag periods presented in Fig 2 (magnitude of associations increased with averaging period, with the largest associations consistently found for 24-h ma)



### December 2009 E-22

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Adar et al. (2007, 001458 ) Period of Study: Mar-Jun 2002

Location: St. Louis, Missouri Outcome: Heart rate variability: heartrate, standard deviation of all normal-tonormal intervals (SDNN), square root of the mean squared difference between adjacent normal-to-normal intervals (rMSSD), percentage of adjacent normal-to-normal intervals that differed by more than 50 ms (pNN50), high frequency power (HF in the range of 0.15-0.4Hz), low frequency power (LF, in the range of 0.04-0.15Hz), and the ratio of LF/HF Age Groups: ≥ 60 yr Study Design: Panel (4 planned repeated measures with a total of 158 person-trips 35 participating in all 4 trips)

N: 44 participants Statistical Analyses: Generalized additive models

Covariates: Subject, weekday, time, apparent temperature, trip type, activity, medications, and autoregressive terms

Season: Limited data collection period Dose-response Investigated? No Statistical Package: SAS v8.02, R v2.0.1 Pollutant: BC (ng/m 3 ) Averaging Time: Measurements collected over 48 h period surrounding the bus trip (during which health endpoints were measured) used to calculate 5-, 30-, 60-min, 4-h, 24-h ma Median (IQR): All: 330 (337) Facility: 285 (270) Bus: 2911 (2464) Activity: 482 (1168) Lunch: 434 (276) Monitoring Stations: 2 portable carts Copollutant: PM 2.5 BC Fine particle counts Coarse particle counts

Correlation notes: 24-h mean PM 2.5 , BC, and fine particle count concentrations ranged from 0.80 to 0.98

r = 0.76 to 0.97 when limited to time spent on the bus r = 0.55 to 0.86 when comparing bus concentrations to 24-h ma r = -0.003 to 0.51 when comparing 5-min avg and 24-h ma

Poor correlations found between coarse particle count concentrations and all fine particulate measures during all times periods PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: % change (95%CI) in HRV per IQR in the 24-h ma of the microenvironmental pollutant (IQr = 459 ng/m 3 ) Single-pollutant models SDNN: -5.3 (-6 .5 to -4.1) rMSSD: -10.7 (-11.9 to -9.5) pNN50 + 1: -13.2 (-15.0 to -11.4) LF: -11.3 (-13.7 to -8.8) HF: -18.8 (-21.1 to -16.5) LF/HF: 9.3 (7.2, 11.4) H: 1.0 (0.8, 1.3) Independent short- and medium-term associations with HRV across all time periods % change per IQR (95%CI) IQR 5-min means = 337 ng/m 3 and 23: 55-h means = 490 ng/m 3 ) SDNN: 5-min mean: -0.3 (-0.5 to -0.1) 23: 55-h mean: -4.7 (-5.9 to -3.5) rMSSD: 5-min mean: -0.3 (-0.5 to -0.1) 23: 55-h mean: -9.3 (-10.5 to -8.1) pNN50 + 1: 5-min mean: -0.3 (-0.6 to - 0.1) 23: 55-h mean: -10.5 (-12.3 to -8.7) LF: 5-min mean: -0.5 (-0.9 to -0.1) 23: 55-h mean: -9.8 (-12.4 to -7.2) HF: 5-min mean: -0.9 (-1.2 to -0.5) 23: 55-h mean: -15.4 (-17.8 to -12.9) LF/HF: 5-min mean: 0.3 (0.1, 0.6) 23: 55-h mean: 6.5 (4.5, 8.6) H: 5-min mean: 0.1 (0.1, 0.2) 23: 55-h mean: 0.4 (0.2, 0.7) Independent associations of short-term avg (5-min means) of PM with HRV by bus and nonbus periods

IQR for bus = 2.6 μ g/m 3 ) and nonbus = 0.27 μ g/m 3 ) % change (95%CI) p-value of interaction SDNN: Bus: -4.6 (-6.1 to -3.0)’ Nonbus: - 0.1 (-0.3, 0.1) p-value for interaction: <0.0001 rMSSD: Bus: -2.6 (-4.2 to -0.9): Nonbus: -0.3 (-0.5 to -0.1) p-value for interaction: 0.64 pNN50 + 1: Bus: -2.0 (-4.5, 0.5): Nonbus: -0.5 (-0.8 to -0.1) p-value for interaction: 0.34 LF: Bus: -6.0 (-9.3 to -2.5): Nonbus: -0.2 (-0.7, 0.3) p-value for interaction: 0.028 HF: Bus: -5.8 (-9.1 to -2.3) Nonbus: -0.9 (-1.4 to -0.4) p-value for interaction: 0.50 LF/HF: Bus: -0.8 (-3.1, 1.7) Nonbus: 0.8 (0.5, 1.1) p-value for interaction: <0.0001 H: Bus: -0.5 (-0.8 to -0.2) Nonbus: 0.3 (0.26, 0.34) p-value for interaction: <0.0001 Note: Exposure to health associations by all lag periods presented in Fig 2 (magnitude of associations increased with averaging period, with the largest associations consistently found for 24-h ma)

Reference: Auchincloss et al. (2008, 156234 ) Outcome: Blood pressure: Systolic (SBP), diastolic (DBP ), mean arterial Pollutant: PM 2.5 PM Increment: 10 μg/m 3 (approx. equivalent to difference between 90th



### December 2009 E-23

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Period of Study: Jul 2000-Aug 2002

Location: 6 U.S. communities (Baltimore City and Baltimore County, Maryland Chicago, Illinois Forsyth County, North Carolina Los Angeles, California Northern Manhattan and the Bronx, New York and St. Paul, Minnesota) Part of MESA (Multi-ethnic Study of Atherosclerosis) (MAP), pulse pressure (PP) Avg of 2nd and 3rd BP measurement used for analyses Age Groups: 45-84 yr Study Design: Cross-sectional (MultiEthnic Study of Atherosclerosis baseline examination)

N: 5,112 persons (free of clinically apparent cardiovascular disease) Statistical Analyses: Linear regression secondary analyses used log binomial models to fit a binary hypertension outcome

Covariates: Age, sex, race/ ethnicity, per capita family income, education, BMI, diabetes status, cigarette smoking status, exposure to ETS, high alcohol use, physical activity, BP medication use, meteorology variables, and copollutants Examined site as a potential confounder and effect modifier Heterogeneity of effects also examined by traffic-related exposures, age, sex, type 2 diabetes, hypertensive status, cigarette use, by levels of SO 2 and CO, and for weather variables

Season: Adjusted for temperature and barometric pressure to adjust for seasonality (because seasons vary by the study sites) Also performed sensitivity analyses adjusting for season to examine the potential for residual confounding not accounted for by weather variables Dose-response Investigated? Assessed nonlinear relationships-no evidence of strong threshold/nonlinear effects for PM 2.5 Statistical Package: NR Averaging Time: 5 exposure metrics constructed: prior day, avg of prior 2 days, prior 7 days, prior 30 days, and prior 60 days Mean (SD): Prior day: 17.0 (10.5) Prior 2 days: 16.8 (9.3) Prior 7 days: 17.0 (6.9) Prior 30 days: 16.8 (5.0) Prior 60 days: 16.7 (4.4)

Percentiles: NR Range (Min, Max): NR Monitoring Stations: Used monitor nearest the participant’s residence to calculate exposure metrics Copollutant: SO 2 NO 2 CO Traffic-related exposures (straight-line distance to a highway total road length around a residence) Correlations with PM2.5 averaged over prior 30 days: O 3 Cool: r = -0.67 Moderate: r = -0.30 Warm: r = 0.23

CO Cool: r = 0.20 Moderate: r = 0.71 Warm: r = 0.23

SO 2 Cool: r = 0.36 Moderate: r = -0.17 Warm: r = -0.11

NO 2 Cool: r = 0.55 Moderate: r = 0.66 Warm: 0.32 and 10th percentile for prior 30 day mean) Effect Estimate [Lower CI, Upper CI]: Adjusted mean difference (95% CI) in PP and SBP (mmHg) per 10 μg/m 3 increase in PM 2.5 (avgd for the prior 30 days)

Pulse Pressure (PM 2.5 avgd for prior 30 days) Adjustment variables: Person-level Covariates : 1.04 (0.25, 1.84), p = 0.010 Person-level cov., weather: 1.12 (0.28, 1.97), p = 0.009 Person-level cov., weather, gaseous copollutants: 2.66 (1.61, 3.71), p = 0.000 Person-level cov., study site: 0.93 (-0.04, 1.90), p = 0.060 Person-level cov., study site, weather: 1.11 (0.01, 2.22), p = 0.049 Person-level cov., study site, weather, gaseous copollutants: 1.34 (0.10, 2.59) , p = 0.035 Systolic Blood Pressure Adjustment variables: Person-level Covariates : 0.66 (-0.41, 1.74) , p = 0.226 Person-level cov., weather: 0.99 (-0.15, 2.13) , p = 0.089 Person-level cov., weather, gaseous copollutants: 2.8 (1.38, 4.22) , p = 0.000 Person-level cov., study site: 0.86 (-0.45, 2.17) , p = 0.200 Person-level cov., study site, weather: 1.32 (-0.18, 2.82) , p = 0.085 Person-level cov., study site, weather, gaseous copollutants: 1.52 (-0.16, 3.21) , p = 0.077 Additional results: Associations became stronger with longer averaging periods up to 30 days. For example: Adjusted (personal covariates and weather) mean differences in PP: Prior day: -0.38 (-0.76, 0.00) Prior 2 days: -0.22 (-0.65, 0.21) Prior 7 days: 0.52 (-0.08, 1.11) Prior 30 days: 1.12 (0.28, 1.97) Prior 60 days: 1.08 (0.11, 2.05) (Pattern held for additional adjustments and for SBP results therefore, only results for 30-day mean differences were presented) Additional results (not presented): None of DBP results were statistically significant Results for MAP were similar to SBP, though weaker and generally not significant

Effect modification: Associations between PM 2.5 and BP were stronger for persons taking medications, with hypertension, during warmer weather, in the presence of high NO 2 , residing ≤ 300m from a highway, and surrounded by a high density of roads (Fig 1) associations were not modified by age, sex, diabetes, cigarette smoking, study site, high levels of CO or SO 2 , season , nor residence ≤ 400m fro a highway



### December 2009 E-24

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Note: Supplementary material available on-line shows results for DBP and MAP, among others

Reference: Baccarelli et al. (2009, 188183 ) Period of Study: Nov 2000-Jun 2005

Location: Boston, Mass Outcome: Heart rate variability Age Groups: Elderly Study Design: Panel

N: 549 men Statistical Analyses: Mixed-effects model

Covariates: Age, past/current CHD, BMI, mean arterial pressure, fasting blood glucose, smoking, alcohol consumption, use of beta-blockers, CAchannel blockers, angiotensinconverting enzyme inhibitors, room temperature, season, apparent temperature

Season: No Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 2.5 Averaging Time: 48-h ma Geometric Mean (95%CI): All Visits: 10.5 (10.0, 10.9) Visits w/ Genotype Data: 10.4 (9.9, 11.0) Visits w/o Genotype Data: 10.5 (9.8, 11.4) Monitoring Stations: 1 Copollutant: NR

Correlation: N/A PM Increment: 10 μg/m 3 Percent Change [Lower CI, Upper CI], P: All Subjects w/ Genotype Data SDNN: -6.0 (-13.5, 2.0), 0.14 HF: -17.1 (-32.3, 1.6), 0.07 LF: -8.2 (-22.1, 8.2), 0.31 All Subjects SDNN: -7.1 (-13.2, -0.6), 0.03 HF: -18.7 (-31.1, -4.0), 0.01 LF: -11.8 (-23.2, -1.3), 0.08



### December 2009 E-25

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Barclay et al. (2007, 192229 ) Period of Study: Jan 2003-May 2005

Location: Aberdeen, Scotland Outcome: Haematological outcomes, Heart Rhythm outcomes, & Heart Rate Variability outcomes Age Groups: 70.4 (8.9) Study Design: Panel

N: 132 patients w/ chronic heart failure Statistical Analyses: Linear & Mixed Effects Regression Model

Covariates: Age, temperature, humidity, pressure Dose-response Investigated? No Statistical Package: NR Lags Considered: L ags 0-2 day Pollutant: PM 2.5 Averaging Time: Daily

Mean: 7.454

Min: 1.092

Max: 21.97 Monitoring Stations: 0 Copollutant: PM 10 , PNC, NO 2 Co-pollutant Correlation NO 2 city: 0.164 NO city: 0.048 PM 10 city: 0.476* NO 2 personal: 0.169 PNC DEOM: 0.115 PM 2.5 traffic: 0.522* PNC total: 0.367* PNC traffic: 0.234 *correlations based on 3-day avg concentrations

Notes: PM 2.5 values model predicted PM Increment: NR Beta (Lower CI, Upper CI): Haemoglobin: -0.509 (-1.560, 0.542) Mean corpuscular haemoglobin: 0.188 (- 0.481, 0.857) Platelets: 3.022 (0.403, 5.642) Haematocrit: -0.813 (-1.892, 0.267) White blood cells: -1.652 (-4.727, 1.424) C reactive protein: 4.924 (-13.022, 22.869) IL-6: -5.980 (-23.649, 11.690) von Willebrand factor: 1.363 (-6.561, 9.287) E-selectin: 2.136 (-2.946, 7.217) Fibrinogen: -5.579 (-10.403, -0.755)* Factor VII: 3.747 (-1.959, 9.452) day-dimer: 5.211 (-2.974, 13.397) All arrhythmias: -7.082 (-28.789, 14.626) Ventricular ectopic beats: -12.203 (- 39.021, 14.615) Ventricular couplets: -1.255 (-25.678, 23.168) Ventricular runs: -2.548 (-17.448, 12.351) Supraventricular ectopic beats: 4.898 (- 19.772, 29.568) Supraventricular couplets: 6.138 (- 16.242, 28.518) Supraventricular runs: -0.545 (-17.577, 16.487) Avg HR: 0.617 (-0.782, 2.016) 24 h SDNN: 3.645 (-0.227, 7.517) 24 h SDANN: 4.437 (0.030, 8.844)* 24 h RMSSD: 0.617 (-0.782, 2.016) 24 h PNN 50%: 11.247 (-6.228, 28.722) 24 h LF power: 4.439 (-6.823, 15.701) 24 h LF normalized: -5.659 (-11.815, 0.497) 24 h HF power: 3.800 (-10.863, 18.464) 24 h HF normalized: -6.597 (-13.724, 0.531) 24 h LF/HF ratio: 1.033 (-8.355, 10.414) *p < 0.05

Notes: Estimates also available for PM 2.5 traffic LF= low frequency HF= high frequency

Reference: Briet et al. (2007, 093049 ) Period of Study: NR

Location: Paris, France Outcome: Endothelial Function Age Groups: 20-40 yr Study Design: Panel

N: 40 white male nonsmokers Statistical Analyses: Multiple Robust Regrssion

Covariates: R53R/R53H genotype, diet, subject factor, visit, temperature Dose-response Investigated? No Statistical Package: NCSS Lags Considered: 0-5 days Pollutant: PM 2.5 Averaging Time: 24 h 5 day Mean (SD): 28 (6) Monitoring Stations: NR Co-pollutant: PM 10 , SO 2 , NO, NO 2 , CO Co-pollutant Correlation: N/A PM Increment: 1 SD Beta (Lower CI, Upper CI), P, R2: Flow-mediated brachial artery dilation: -0.32 (-1.10, 0.46), NS, 0.04 Reactive hyperemia: 15.68 (7.11, 23.30), <0.0001, 0.24 Changes in Endothelial function b/t visits: 1.98 (0.67, 3.259), 0.004, 0.44



### December 2009 E-26

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Cárdenas et al. (2008, 191900 ) Period of Study: NR

Location: Mexico City, Mexico Outcome: Heart Rate Variability Age Groups: 20-40 yr Study Design: Panel

N: 54 subjects Statistical Analyses: Linear GEE models

Covariates: L ocalization, supine position, gender, age, humidity, heart rate, orthostatic position, head-up tilt test result Dose-response Investigated? No Statistical Package: NR Lags Considered: NR Pollutant: PM 2.5 Averaging Time: NR 25th, 50th, 75th percentile: Indoor: 14.8, 28.3, 47.9 Outdoor: 6.4, 10.8, 16.8 Monitoring Stations: NR Co-pollutant: NR Co-pollutant Correlation: N/A PM Increment: NR Mean Difference (Lower CI, Upper CI), lag: Ln low frequency Indoors: -0.028 (-0.0423, -0.0138) Outdoors: -0.194 (-0.4509, 0.0627) Ln high frequency Indoors: -0.019 (-0.0338, -0.0044) Outdoors: -0.298 (-0.5553, -0.0401)

Ln LF/HF ratio Indoors: -0.017 (-0.0330, -0.0007) Outdoors: -0.278 (-0.5540, 0.0030)

Reference: Cavallari et al. (2007, 157425 ) Period of Study: 1999-2006

Location: Massachusetts Outcome: Heart Rate Variability Age Groups: 22-63 Study Design: Panel

N: 36 males Statistical Analyses: Mixed Effects Regression Model

Covariates: Age, smoking, heart rate at work Dose-response Investigated? No Statistical Package: SAS Lags Considered: Lags 0-14 h Pollutant: PM 2.5 Averaging Time: Hourly Mean (SD): 1.12 (0.76)

Min: 0.12

Max: 3.99 Monitoring Stations: NR Copollutant: NR Co-pollutant Correlation: N/A PM 1 mg Increment: m 3 Beta (Lower CI, Upper CI):

Model 1 Lag 1 h: -1.44 (-7.75, 4.87) Lag 2 h: -5.33 (-10.97, 0.31)* Lag 3 h: -6.86 (-11.91, -1.81)‡ Lag 4 h: -2.17 (-9.33, 4.99) Lag 5 h: -4.73 (-11.99, 2.53) Lag 6 h: -3.52 (-9.89, 2.84) Lag 7 h: -1.59 (-7.53, 4.35) Lag 8 h: -0.72 (-7.63, 6.20) Lag 9 h: -5.55 (-10.65, -0.45)‡ Lag 10 h: -3.66 (-8.85, 1.53) Lag 11 h: -8.60 (-17.45, 0.24)* Lag 12 h: -5.98 (-14.67, 2.70) Lag 13 h: -8.27 (-17.00, 0.46)* Lag 14 h: -4.19 (-12.71, 4.33)

Model 2 Lag 1 h: 4.10 (-0.39, 8.60)* Lag 2 h: -3.21, (-8.78, 2.37) Lag 3 h: -6.45 (-11.59, -1.31)‡ Lag 4 h: -0.01 (-6.96, 6.94) Lag 5 h: -2.03 (-8.27, 4.22) Lag 6 h: -1.99 (-8.46, 4.48) Lag 7 h: -0.34 (-6.22, 5.54) Lag 8 h: 0.72 (-6.35, 7.78) Lag 9 h: -5.26 (-10.62, 0.11)* Lag 10 h: -3.68 (-9.17, 1.80) Lag 11 h: -9.41 (-18.60, -0.23)‡ Lag 12 h: -6.45 (-15.62, 2.72) Lag 13 h: -7.33 (-16.55, 1.89) Lag 14 h: -4.75 (-13.81, 4.32) *p < 0.05, ‡p < 0.10

Notes: Model 1 adjusted for smoking status and age only. Model 2 adjusted for smoking status, age, and heart rate during work.



### December 2009 E-27

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chahine et al. (2007, 156327 ) Period of Study: Jan 2000-Jun 2005

Location: Boston, MA Outcome: Heart Rate Variability Age Groups: M ean 72.8(6.6) yr Study Design: Panel

N: 539 white males Statistical Analyses: Mixed Effects Model

Covariates: A ge, BMI, mean arterial pressure, fasting blood glucose, smoking, alcohol consumption, use of beta-blockers, calcium channel blockers, ACE inhibitors, room temperature, season, outdoor temperature Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0- to 2-day ma Pollutant: PM 2.5 Averaging Time: 1 h Mean (SD): 11.7 (7.8) Monitoring Stations: 1 Copollutant: PM 1.0 Co-pollutant Correlation: N/A PM Increment: 10 μg/m 3 Percent Change (Lower CI, Upper CI), p-value: log10 SDNN Total: -6.8 (-12.9, -0.2), 0.0436 GSTM1 wildtype: -2.0 (-11.3, 8.3), 0.6908 GSTM1 null: -10.5 (-18.2, -2.2), 0.0150 HMOX-1 <25 repeats: 7.4 (-8.7, 26.2), 0.3891 HMOX-1 ≥ 25 repeats: -8.5 (-14.8, -1.8), 0.0137 log10 HF Total: -17.3 (-30.0, -2.3), 0.0263 GSTM1 wildtype: -4.0 (-24.8, 22.6), 0.7442 GSTM1 null: -24.2 (-39.2, -5.5), 0.0139 HMOX-1 <25 repeats: 8.9 (-27.1, 62.8), 0.6759 HMOX-1 ≥ 25 repeats: -20.1 (-32.9, -5.0), 0.0115 log10 LF Total: -11.2 (-22.8, 2.2), 0.0986 GSTM1 wildtype: -0.6 (-19.0, 22.0), 0.9545 GSTM1 null: -17.0 (-31.0, -0.2), 0.0478 HMOX-1 <25 repeats: 14.0 (-18.6, 59.5), 0.4465 HMOX-1 ≥ 25 repeats: -14.0 (-25.7, -0.5), 0.0430

Reference: Chen and Schwartz (2008, 190106 ) Period of Study: 1989-1991

Location: U.S. Outcome: White Blood Cell count Age Groups: 20-89 yr Study Design: Panel

N: 2,978 participants Statistical Analyses: Mixed Effects Models

Covariates: A ge, sex, race, SES, smoking, alcohol consumption, MS abnormalities, indoor air pollutants, exercise Dose-response Investigated? No Statistical Package: Stata Lags Considered: NR Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 36.8 (13.0) Median(range) for Q1: 23.1(14.6-27.8) Q2: 31.2 (27.9-34.3) Q3: 38.8 (34.3-43.3) Q4: 53.7 (43.3-78.5) Monitoring Stations: NR Copollutant: NR Co-pollutant Correlation: N/A PM Increment: Quartile, 1yr avg (36.8 μg/m 3 ) Avg WBC count(SE) by PM quartile: Q1: 6760 (79) Q2: 6942 (99) Q3: 6895 (84) Q4: 7109 (61) Beta(Lower CI, Upper CI), p-value: Crude: 239 (58, 420), 0.01 Model 1: 145 (10, 281), 0.035 Model 2: 141 (6, 277), 0.041 Model 3: 138 (2, 273), 0.046 Model 1: Age, sex, race, SES, smoking, alcohol consumption, MS abnormalities. Model 2: Model 1 plus indoor air pollutants, exercise. Model 3: Clean areas (Q1) vs.. other more polluted

areas



### December 2009 E-28

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chuang et al. (Chuang et al., 2007, 091063 ) Period of Study: Between Apr-Jun 2004 or 2005

Location: Taipei, Taiwan Outcome: High-sensitivity C-reactive protein (hs-CRP) Fibrinogen, plasminogen activator fibrinogen inhibitor-1 (PAI-1), tissue-typeplasminogen activator (tPA), 8-hydroxy2’-deoxyguanosine (8-OHdG), and logtransformed HRV indices (SDNN = standard de viation of NN intervals, r-MSSD = square root of the mean of the sum of the squares of differences between adjacent NN intervals, LF = low frequency [0.04- 0.15Hz], and HF = high frequency[0.15- 0.40Hz]) Age Groups: 18-25 yr Study Design: Panel (cross-sectional)

N: 76 students Statistical Analyses: L inear mixedeffects models

Covariates: Age, sex, BMI, weekday, temperature of previous day, relative humidity

Season: Only 1 season of data collection Dose-response Investigated? No Statistical Package: NR Pollutant: PM 10 , nitrate, sulfate Averaging Time: Hourly data used to calculate avg over 1- to 3-day periods Mean (SD): 1-day avg: 31.8 (10.6) 2-day avg: 36.4 (12.6) 3-day avg: 36.5 (12.6) Range (Min, Max): 1-day avg: 16.2, 50.1 2-day avg: 15.0, 53.4 3-day avg: 12.7, 59.5 Monitoring Stations: 2 sites (each pollutant measured at 1 site only) Copollutant: PM 10 Sulfate Nitrate OC EC NO 2 CO SO 2 O 3 PM 2.5 Increment: IQR (1-day avg: 20.4 2-day avg: 25.2 3-day avg: 20.0) Effect Estimate [Lower CI, Upper CI]: % change in health endpoint per increase in IQR of PM 2.5 (1-3 day averaging period single pollutant models)

hs-CRP: 1-day: 90.2 (-10.2, 190.1) 2-day: 99.1 (-26.1, 224.3) 3-day: 100.4 (-2.9, 203.7)

8-OHdG: 1-day: -5.0 (-14.3, 4.4) 2-day: -5.5 (-15.6, 4.6) 3-day: -5.6 (-13.8, 2.6)

PAI-1: 1-day: 20.4 (17.3, 33.5) 2-day: 16.2 (1.9, 30.5) 3-day: 20.0 (18.5, 31.5)

tPA: 1-day: 12.0 (-2.4, 26.3) 2-day: 12.0 (-2.9, 26.9); 3-day: 12.0 (-2.7, 26.6) Fibrinogen: 1-day: 2.6 (-2.7, 7.8) 2-day: 1.5 (-4.1, 7.1); 3-day: 3.6 (-0.8, 8.1) Heart Rate Variability SDNN: 1-day: -4.0 (-6.1 to -1.9) 2-day: -2.5 (-4.6 to -0.4) 3-day: -3.0 (-5.0 to -1.1)

r-MSSD: 1-day: -3.0 (-8.7, 2.7) 2-day: -2.0 (-8.4, 4.4); 3-day: -3.6 (-8.8, 1.6)

LF: 1-day: -3.1 (-6.1 to -0.1) 2-day: -3.2 (-4.6, 0.1); 3-day: -3.4 (-6.1 to -0.6)

HF: 1-day: -3.7 (-9.4, 2.1) 2-day: -2.1 (-8.4, 4.3); 3-day: -4.0 (-9.3, 1.2)



### December 2009 E-29

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chuang et al. (2007, 091063 ) Period of Study: Between Apr-Jun 2004 or 2005

Location: Taipei, Taiwan Outcome: High-sensitivity C-reactive protein (hs-CRP) Fibrinogen, plasminogen activator fibrinogen inhibitor-1 (PAI-1), tissue-typeplasminogen activator (tPA), 8-hydroxy2’-deoxyguanosine (8-OHdG), and logtransformed HRV indices (SDNN = standard de viation of NN intervals, r-MSSD = square root of the mean of the sum of the squares of differences between adjacent NN intervals, LF = low frequency [0.04- 0.15Hz], and HF = high frequency[0.15- 0.40Hz]) Age Groups: 18-25 yr Study Design: Panel (cross-sectional)

N: 76 students Statistical Analyses: Linear mixedeffects models

Covariates: Age, sex, BMI, weekday, temperature of previous day, relative humidity

Season: Only 1 season of data collection Dose-response Investigated? No Statistical Package: NR Pollutant: Nitrate Averaging Time: Hourly data used to calculate avg over 1-3 day periods Mean (SD): 1-day avg: 4.5 (2.7) 2-day avg: 4.7 (2.4) 3-day avg: 4.4 (2.2) Range (Min, Max): 1-day avg: 0.7, 10.6 2-day avg: 0.7, 8.9 3-day avg: 0.8, 7.5 Monitoring Stations: 2 sites (each pollutant measured at 1 site only) Copollutant: PM 10 Sulfate PM 2.5 OC EC NO 2 CO SO 2 O 3 Nitrate Increment: IQR (1-day avg: 2.5 2-day avg: 4.0 3-day avg: 3.4) Effect Estimate [Lower CI, Upper CI]: % change in health endpoint per increase in IQR of nitrate (1-3 day averaging period single pollutant models) hs-CRP: 1-day: -2.1 (-21.9, 17.8) 2-day: -11.6 (-58.6, 35.5) 3-day: -18.7 (-69.9, 32.5) 8-OHdG: 1-day: 9.0 (4.0, 14.1) 2-day: 15.1 (5.9, 24.3) 3-day: 15.0 (4.9, 25.0) PAI-1: 1-day: 4.0 (-2.5, 10.4) 2-day: 11.6 (0.1, 23.1) 3-day: 16.9 (4.3, 29.4) tPA: 1-day: 2.0 (-6.2, 10.3) 2-day: 12.9 (-1.6, 27.5) 3-day: 10.0 (-5.8, 25.8) Fibrinogen: 1-day: 1.6 (-1.3, 4.5) 2-day: 1.3 (-3.9, 6.5) 3-day: 1.0 (-4.6, 6.6) Heart Rate Variability SDNN: 1-day: -1.5 (-2.6 to -0.3) 2-day: -2.6 (-4.7 to -0.5) 3-day: -3.0 (-5.3 to -0.7) r-MSSD: 1-day: -5.5 (-8.7 to -2.2) 2-day: -7.1 (-14.0 to -0.2) 3-day: -8.1 (-14.5 to -1.8) LF: 1-day: -1.0 (-1.6 to -0.5) 2-day: -2.0 (-5.6, 1.6) 3-day: -2.0 (-5.2, 1.2) HF: 1-day: -2.0 (-5.3, 14[potential typo, possibly 1.4]) 2-day: -4.9 (-10.9, 0.9) 3-day: -6.9 (-13.4 to -0.3)



### December 2009 E-30

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chuang et al. (2007, 091063 ) Period of Study: Between Apr-Jun 2004 or 2005

Location: Taipei, Taiwan Outcome: High-sensitivity C-reactive protein (hs-CRP) Fibrinogen, plasminogen activator fibrinogen inhibitor-1 (PAI-1), tissue-typeplasminogen activator (tPA), 8-hydroxy2’-deoxyguanosine (8-OHdG), and logtransformed HRV indices (SDNN = standard de viation of NN intervals, r-MSSD = square root of the mean of the sum of the squares of differences between adjacent NN intervals, LF = low frequency [0.04- 0.15Hz], and HF = high frequency[0.15- 0.40Hz]) Age Groups: 18-25 yr Study Design: Panel (cross-sectional)

N: 76 students Statistical Analyses: Linear mixedeffects models

Covariates: Age, sex, BMI, weekday, temperature of previous day, relative humidity

Season: Only 1 season of data collection Dose-response Investigated? No Statistical Package: NR Pollutant: Sulfate Averaging Time: Hourly data used to calculate avg over 1- to 3-day periods Mean (SD): 1-day avg: 4.1 (3.6) 2-day avg: 4.1 (3.7) 3-day avg: 3.9 (3.5) Range (Min, Max): 1-day avg: 0.4, 10.9 2-day avg: 0.4, 11.9 3-day avg: 0.4, 11.5 Monitoring Stations: 2 sites (each pollutant measured at 1 site only) Copollutant: PM 10 PM 2.5 Nitrate OC EC NO 2 CO SO 2 O 3 Sulfate Increment: IQR (1-day avg: 3.9 2-day avg: 4.3 3-day avg: 3.8) Effect Estimate [Lower CI, Upper CI]: % change in health endpoint per increase in IQR of sulfate (1-3 day averaging period single pollutant models)

hs-CRP: 1-day: 80.0 (9.8, 150.2) 2-day: 87.1 (14.9, 159.4) 3-day: 71.1 (13.0, 129.2)

8-OHdG: 1-day: 1.0 (0.3, 1.3) 2-day: -0.4 (-5.4, 4.7) 3-day: -0.3 (-4.3, 3.7)

PAI-1: 1-day: 12.0 (5.4, 18.7) 2-day: 13.3 (6.6, 19.9) 3-day: 11.2 (5.7, 16.6)

tPA: 1-day: 2.0 (-4.6, 8.7) 2-day: 3.8 (-2.8, 10.3) 3-day: 3.0 (-2.3, 8.2) Fibrinogen: 1-day: 2.9 (0.2, 5.5) 2-day: 2.8 (0.1, 5.5) 3-day: 2.2 (0.4, 4.7) Heart Rate Variability SDNN: 1-day: -3.1 (-4.1 to -2.1) 2-day: -4.1 (-5.2 to -3.1) 3-day: -2.0 (-2.9 to -1.2)

r-MSSD: 1-day: -5.0 (-8.0 to -2.0) 2-day: -6.0 (-8.9 to -2.9) 3-day: -5.7 (-8.2 to -3.2)

LF: 1-day: -3.4 (-4.9 to -1.8) 2-day: -3.0 (-4.5 to -1.5) 3-day: -3.0 (-4.3 to -1.7)

HF: 1-day: -3.5 (-6.5 to -0.4) 2-day: -3.9 (-7.0 to -0.8) 3-day: -3.0 (-5.5 to -0.5)



### December 2009 E-31

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chuang et al. (2007, 098629 ) Period of Study: NR

Location: Boston, MA Outcome: ST Segment Depression Age Groups: 43-75 yr Study Design: Panel

N: 48 coronary artery disease patients Statistical Analyses: Linear & Mixed Logistic Regression models

Covariates: Participant, day of week, order of visit, visit date, hour of day, hourly temperature Dose-response Investigated? No Statistical Package: R Lags Considered: Lags 1-72 h Pollutant: PM 2.5 Averaging Time: Hourly 25th, 50th, 75th percentile: 12-h avg: 6.18, 8.91, 13.18 24-h avg: 6.38, 9.20, 13.31

Max: 12-h avg: 37.13 24-h avg: 40.38 Monitoring Stations: 1 Co-pollutant: BC, CO, O 3 , NO 2 , SO 2 Co-pollutant Correlation BC: 0.56 O 3 : 0.20 NO 2 : 0.38 SO 2 : 0.25 PM Increment: Interquartile Increase Change (Lower CI, Upper CI):

12-h mean PM 2.5 : -0.022 (-0.032, -0.012) PM 2.5 + NO 2 : -0.023 (-0.034, -0.012) PM 2.5 + SO 2 : -0.009 (-0.02, 0.001) PM 2.5 + BC: -0.011 (-0.023, 0.001)

24-h mean PM 2.5 : -0.026 (-0.037, -0.015) PM 2.5 + NO 2 : -0.017 (-0.029, 0.004) PM 2.5 + SO 2 : -0.014 (-0.025, -0.002) PM 2.5 + BC: -0.012 (-0.026, 0.003) Relative Risk (Lower CI, Upper CI):

12-h mean PM 2.5 : 1.02 (0.86, 1.21) PM 2.5 + NO 2 : 0.99 (0.82, 1.21) PM 2.5 + SO 2 : 0.87 (0.71, 1.05) PM 2.5 + BC: 0.92 (0.74, 1.14)

24-h mean PM 2.5 : 1.22 (0.99, 1.50) PM 2.5 + NO 2 : 1.00 (0.80, 1.25) PM 2.5 + SO 2 : 1.04 (0.83, 1.30) PM 2.5 + BC: 0.87 (0.65, 1.17) Mean (Lower CI, Upper CI): 12-h mean Myocardial Infarction: -0.042 (-0.057, - 0.026) No Myocardial Infarction: -0.012 (-0.023, 0.00) p- for interaction: 0.002 Visit 1: -0.102 (-0.12, -0.085) Visits 2-4: 0.006 (-0.005, 0.017) p- for interaction: <0.001 Diabetic: -0.097 (-0.119, -0.074) Non-diabetic: -0.009 (-0.019, 0.002) p- for interaction: <0.001 Diurnal daytime pattern: -0.032 (-0.043, - 0.021) Diurnal nighttime pattern: -0.006 (-0.018, 0.006) p- for interaction: <0.001 24-h mean Myocardial Infarction: -0.027 (-0.043, - 0.012) No Myocardial Infarction: -0.025 (-0.038, 0.011) p- for interaction: 0.787 Visit 1: -0.127 (-0.148, -0.105) Visits 2-4: 0.001 (-0.011, 0.013) p- for interaction: <0.001 Diabetic: -0.118 (-0.144, -0.091) Non-diabetic: -0.13 (-0.024, -0.002) p- for interaction: <0.001 Diurnal daytime pattern: -0.031 (-0.043, - 0.020) Diurnal nighttime pattern: -0.018 (-0.030, -0.005) p- for interaction: 0.233 Notes: The effects of PM on half-h St segment levels (Fig 1)



### December 2009 E-32

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Dales et al. (2007, 155743 ) Period of Study: NR

Location: Ottawa, Canada Outcome: Vascular Reactivity Age Groups: 18-50 yr Study Design: Panel

N: 39 volunteers Statistical Analyses: Mixed Effects Model

Covariates: Temperature, humidity, wind speed, time of day testing was done, site Dose-response Investigated? No Statistical Package: S-PLUS Lags Considered: NR Pollutant: PM 2.5 Averaging Time: 2 h Mean (SD): Downtown: 40 (20) Tunney’s Pasture: 10 (10) p-value 0.000 Monitoring Stations: NR Copollutant: PM1.0 Co-pollutant Correlation N/A PM Increment: Interquartile Range (27.02 μg/m 3 ) Beta (SE), p-value: Flow mediated vasodilation (%): -0.016 (0.0072) p=0.03 Heart Rate (beats/min): 0.081 (0.135) p=0.55 Diastolic blood pressure (mmHg): 0.088 (0.088) p=0.32 Systolic blood pressure (mmHg): -0.108 (0.006) p=0.48

Reference: de Hartog et al. (2009, 191904 ) Period of Study: 1998-1999

Location: Amsterdam, The Netherlands Erfurt, Germany and Helsinki, Finland Outcome: Heart Rate Variability Age Groups: 50+ Study Design: Panel

N: 122 coronary heart disease patients Statistical Analyses: Linear Regression

Covariates: Time trend, temperature, humidity, pressure Dose-response Investigated? No Statistical Package: SAS Lags Considered: Lags 0-3 days Pollutant: PM 2.5 Averaging Time: Daily p25, p50, p75. p95: Amsterdam: 10.4, 16.7, 23.9, 47.0 Erfurt: 10.8, 16.3, 26.7, 62.3 Helsinki: 8.3, 10.6, 15.9, 25.8 Monitoring Stations: NR Copollutant: PM <0.1, PM0.1-1.0, NO 2 , SO 2 Co-pollutant Correlation NR

Note: Correlations are provided for source-specific PM 2.5 & elements PM Increment: 1 μg/m 3 Beta (Lower CI, Upper CI):

SDNN Local traffic: -0.12 (-0.36, 0.12) Long-range transport: -0.04 (-0.14, 0.06) Oil combustion: -0.29 (-1.04, 0.45) Industry: 0.03 (-0.12, 0.19) Crustal: 0.11 (-0.35, 0.56) Salt: -0.19 (-1.92, 1.55)

HF Local traffic: 0.43 (-0.91, 1.79) Long-range transport: 0.19 (-0.38, 0.77) Oil combustion: 1.05 (-2.70, 4.94) Industry: 0.62 (-0.34, 1.59) Crustal: 1.57 (-1.28, 4.50) Salt: -1.43 (-9.86, 7.78)

SDNN ABS: -0.52 (-1.39, 0.31) S: -0.51 (-1.36, 0.33) V: -0.66 (-1.73, 0.41) Zn: 0.12 (-0.55, 0.79) Ca: 0.27 (-0.58, 1.11) Cl: 0.14 (-0.39, 0.67) Fe: 0.15 (-1.00, 1.30) Cu: -0.08 (-0.74, 0.57)

SDNN ABS: 2.91 (-2.54, 8.67) S: 0.25 (-4.42, 5.14) V: 0.73 (-4.74, 6.53) Zn: 3.85 (-0.26, 8.13) Ca: 3.39 (-1.80, 8.86) Cl: 1.13 (-1.48, 3.81) Fe: 6.69 (0.11, 13.69) Cu: 3.00 (-0.85, 7.00)

Notes: Estimates provided are for all subjects at lag 1, estimates are also available at lags 0, 2, and 3, as well as for subjects w/o beta-blockers at lags 0-3.



### December 2009 E-33

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: DeMeo et al. (2004, 087346 ) Period of Study: Jul-Aug 1999

Location: Boston, MA Outcome: Oxygen saturation Age Groups : 60.4-89.2 yr Study Design: Cross-sectional study

N: 28 adult participants Statistical Analyses: GLM, Natural Spline Smoothing, Regression Analysis, Random-effects model

Covariates: Mean temperature, Dew point temperature, Barometric pressure, Medication use

Season : Summer Dose-response Investigated? No Statistical Package : S-PLUS, SAS Lags Considered: Hourly lags between 2 and 7 h Pollutant: PM 2.5 Averaging Time: 6 h, 12 h, 24 h, 48 h PM Increment: IQR (13.42 μg/m 3 ) increase 6 h: 13.42 μg/m 3 12 h: 10.81 μg/m 3 24 h: 10.26μg/m 3 48: 10.57 μg/m 3 Overall: 0.172% (-0.313, 0.031) decrease 6 h: -0.769% (-1.21 to -0.327) decrease B-blocker users: -0.062% (-0.248, 0.123) Rest: 6 h: -0.173 (-0.345 to -0.001) 12 h: -0.160 (-0.308 to -0.012) 24 h: -0.169 (-0.316 to -0.022) 48 h: -0.153 (-0.304, 0.002) Exercise: 6 h: -0.005 (-0.215, 0.205) 12 h: -0.014 (-0.196, 0.168) 24 h: 0.001 (-0.180, 0.182) 48 h: -0.011 (-0.196, 0.174) Post exercise Rest: 6 h: -0.173 (-0.332 to -0.014) 12 h: -0.128 (-0.266, 0.010) 4 h: -0.113 (-0.250, 0.023) 48 h: -0.157 (-295 to -0.019) Paced breathing: 6 h: -0.142 (-0.292, 0.007) 12 h: -0.139 (-0.269 to -0.010) 24 h: -0.121 (-0.248, 0.007) 48 h: -0.082 (0.211, 0.047) Summary over protocol 6 h: -0.131 (-0.247 to -0.015) 12 h: -0.120 (-0.221, 0.020) 24 h: -0.112 (-0.212 to -0.013) Notes: Fig of the variation in oxygen saturation during the first rest period vs.. individual hourly lag measurements for PM 2.5 Reference: Diez-Roux et al. (2006, 156400 ) Period of Study: Baseline data collected Jun 2000-Aug 2002

Location: USA 6 field centers: Baltimore, MD Chicago, IL Forsyth Co, NC Los Angeles, CA New York, NY St. Paul, MN Outcome: C-reactive protein (CRP) assessed continuously and as a dichotomous variable (cutpoint, 3 mg/L) interleukin-6 (IL-6) Age Groups: 45-84 yr Study Design: Cross-sectional

N: 5634 persons Statistical Analyses: Linear regression & logistic regression

Covariates: Age, sex, race/ethnicity, general health status, BMI, diabetes, cigarette status, secondhand smoke, physical activity, arthritis flare in last 2 wk, medications, infections in last 2 wk (also ran models including site, copollutants, and weather)

Season: Examined seasonal patterns in the residuals of fully adjusted models stratified by season Dose-response Investigated? No Statistical Package: NR Pollutant: PM 2.5 Averaging Time: Prior day, prior 2 days, prior wk, prior 30 days, and prior 60 days Mean (SD): Presented in Fig 1 by site

Percentiles: Presented in Fig 1 by site Range: NR Monitoring Stations: NR Long-term exposure to PM estimated based on residential history reported retrospectively All addresses geocoded

Ambient AP obtained from U.S. EPA Copollutant: SO 2 NO 2 CO O 3 PM Increment: 10 μ g/m 3 Effect Estimate [Lower CI, Upper CI]: Adjusted (all personal-level covariates) relative difference in CRP (mg/L) per 10 μ g/m 3 increase in PM 2.5 Prior day: 0.99 (0.96, 1.01) Prior 2 days: 0.99 (0.96, 1.01) Prior 7 days: 1.00 (0.96, 1.04) Prior 30 days: 1.03 (0.98, 1.10) Prior 60 days: 1.04 (0.97, 1.11)

Odds Ratios of CRP of ≥ 3 mg/L per 10 μ g/m 3 increase in PM 2.5 (adjusted for all personal-level covariates) Prior day: 0.98 (0.92, 1.04) Prior 2 days: 0.99 (0.93, 1.06) Prior 7 days: 1.05 (0.96, 1.15) Prior 30 days: 1.12 (0.98, 1.29) Prior 60 days: 1.12 (0.96, 1.32)



### December 2009 E-34

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Dubowsky et al. (2006, 088750 ) Period of Study: Mar-Jun 2002

Location: St. Louis, Missouri Outcome: White blood cells (WBC), C-reactive protein (CRP), interleukin-6 (IL-6) Age Groups: ≥ 60 yr Study Design: Panel (4 planned repeated measures n = 35 participated in 4 trips)

N: 44 participants Statistical Analyses: Linear mixed models

Covariates: Sex, obesity, diabetes, smoking history, time-varying parameters (apparent temperature, h, day, trip, residence, mold, pollen, illness, and juice intake), medication and vitamin consumption (day of blood draw)

Season: Limited data collection period Dose-response Investigated? No Statistical Package: SAS v8.02 Pollutant: PM 2.5 (ambient) Averaging Time: Hourly data used to calculate avg concentrations over 1-7 days preceding the blood draw (ambient PM 2.5 )

Microenvironmental PM 2.5 measures were avgd over the 1-2 days preceding the blood draw Mean (SD) (1-day): 16 (6.0) Percentiles (1-day): 0: 6.5 25th: 12 75th: 22 100th: 28 Monitoring Stations: 1 ambient monitor Copollutant: PM 2.5 (ambient) BC (ambient) PM 2.5 (microenvironment) CO NO 2 SO 2 O 3 PM Increment: 6.1 μg/m 3 (5-day mean) Effect Estimate [Lower CI, Upper CI]:

Note: Most results presented in figures. Selected result in abstract text: % change in WBC per increase in IQR (5.4 μg/m 3 ) of PM 2.5 avgd over the previous week: 5.5 (0.1, 11) Associations (% changes and 95%CI) between 5-day mean ambient concentrations and markers of inflammation per increase (IQR) in pollutant. CRP: All participants: 14 (-5.4, 37) Among those with all 3 conditions (diabetes, obesity, and hypertension): 81 (21, 172) Among those with at least 2 of the conditions: 11 (-7.3, 33) IL-6: All participants: -2.1 (-13, 11) Among those with all 3 conditions (diabetes, obesity, and hypertension): 23 (-5.3, 59) Among those with at least 2 of the conditions: -3.1 (-14, 9.7) WBC (x109/L): All participants: 3.4 (-1.8, 8.9) Among those with all 3 conditions (diabetes, obesity, and hypertension): 0.4 (-8.8, 11) Among those with at least 2 of the conditions: 3.6 (-1.7, 9.1)

Reference: Dubowsky et al. (2006, 088750 ) Period of Study: Mar-Jun 2002

Location: St. Louis, Missouri Outcome: White blood cells (WBC), C-reactive protein (CRP), interleukin-6 (IL-6) Age Groups: ≥ 60 yr Study Design: Panel (4 planned repeated measures n = 35 participated in 4 trips)

N: 44 participants Statistical Analyses: Linear mixed models

Covariates: Sex, obesity, diabetes, smoking history, time-varying parameters (apparent temperature, h, day, trip, residence, mold, pollen, illness, and juice intake), medication and vitamin consumption (day of blood draw)

Season: Limited data collection period Dose-response Investigated? No Statistical Package: SAS v8.02 Pollutant: BC (ng/m 3 ) (ambient) Averaging Time: Hourly data used to calculate avg concentrations over 1-7 days preceding the blood draw (ambient PM)

microenvironmental PM 2.5 measures were avgd over the 1-2 days preceding the blood draw Mean (SD) (1-day): 900 (280) Percentiles (1-day): 0: 290 25th: 730 75th: 1,100 100th: 1,400 Monitoring Stations: 1 ambient monitor Copollutant: PM 2.5 (ambient) BC (ambient) PM 2.5 (microenvironment) CO NO 2 SO 2 O 3 PM Increment: 230 ng/m 3 (5-day mean) Effect Estimate [Lower CI, Upper CI]:

Note: Most results presented in figures. Associations (% changes and 95%CI) between 5-day mean ambient concentrations and markers of inflammation per increase (IQR) in pollutant. CRP: All participants: 13 (-0.34, 28) Among those with all 3 conditions (diabetes, obesity, and hypertension): 49 (16, 90) Among those with at least 2 of the conditions: 9.0 (-3.8, 24) IL-6: All participants: -0.8 (-8.9, 8.0) Among those with all 3 conditions (diabetes, obesity, and hypertension): 15 (-2.2, 35) Among those with at least 2 of the conditions: -2.7 (-11, 6.2) WBC (x109/L): All participants: 1.3 (-2.1, 4.8) Among those with all 3 conditions (diabetes, obesity, and hypertension): 0.05 (-5.9, 6.3) Among those with at least 2 of the conditions: 1.5 (-2.0, 5.1)



### December 2009 E-35

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ebelt et al. (2005, 056907 ) Period of Study: Summer of 1998

Location: Vancouver, Canada Outcome: CVD Age Groups : Range from 54-86 yr mean age= 74 yr Study Design: E xtended analysis of a repeated-measures panel study

N: 16 persons with COPD Statistical Analyses: Earlier analysis expanded by developing mixed-effect regression models and by evaluating additional exposure indicators Dose-response Investigated? No Statistical Package : SAS V8 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Ambient PM 2.5 : 11.4 ± 4.6 Exposure to ambient PM 2.5 : 7.9 ± 3.7 Range (Min, Max): Ambient PM 2.5 : 4.2-28.7 Exposure to ambient PM 2.5 : 0.9-21.3 Monitoring Stations : 5 Copollutant (correlation): Ambient concentrations and exposure to ambient PM were highly correlated for each respective metric: r ≥ 0.71 PM Increment:

Increment: C2.5: IQR = 5.8 SBP (mm Hg): -1.70 (-3.48-0.08) DBP (mm Hg): -0.58 (-2.02-0.85) Ln-SVE (bph): 0.20 (0.00-0.40) HR (bpm): 0.93 (-0.90-2.75) SDNN (ms): -4.37 (-9.40-0.65) R-MSSD (ms): -2.79 (-6.16-0.57) Increment: NS_C2.5: IQR = 4.2 SBP (mm Hg): -1.52 (-2.94- -0.09) DBP (mm Hg): -0.77 (-1.87-0.32) Ln-SVE (bph): 0.19 (-0.01-0.38) HR (bpm): 1.03 (-0.43-2.48) SDNN (ms): -3.83 (-7.77-0.11) R-MSSD (ms): -2.90 (-5.55- -0.25) Increment: S_C2.5: IQR = 1.5 SBP (mm Hg): -1.10 (-3.48-1.28) DBP (mm Hg): 0.76 (-1.15-2.68) Ln-SVE (bph): 0.09 (-0.05-0.23) HR (bpm): -0.42 (-2.28-1.44) SDNN (ms): -3.14 (-9.73-3.45) R-MSSD (ms): 0.24 (-5.14-5.63)

Increment: A2.5: IQR = 4.4 SBP (mm Hg): -1.90 (-3.66- -0.14) DBP (mm Hg): -0.33 (-1.72-1.06) Ln-SVE (bph): 0.20 (0.02-0.37) HR (bpm): 0.57 (-1.34-2.47) SDNN (ms): -3.91 (-8.79-0.97) R-MSSD (ms): -1.05 (-4.79-2.17) Increment: NS_A2.5: IQR = 3.4 SBP (mm Hg): -1.70 (-3.27- -0.14) DBP (mm Hg): -0.51 (-1.71-0.70) Ln-SVE (bph): 0.20 (0.02-0.37) HR (bpm): 0.69 (-0.96-2.35) SDNN (ms): -4.18 (-8.51-0.15) R-MSSD (ms): -1.40 (-4.40-1.60) Increment: S_T2.5: IQR = 0.9 SBP (mm Hg): -1.55 (-3.35-0.26) DBP (mm Hg): 0.49 (-0.91-1.90) Ln-SVE (bph): 0.08 (-0.14-0.19) HR (bpm): -0.24 (-1.75-1.26) SDNN (ms): -0.68 (-4.74-3.38) R-MSSD (ms): 0.91 (-3.51-5.33)

Increment: T2.5: IQR = 10.1 SBP (mm Hg): -1.26 (-2.60-0.08) DBP (mm Hg): 0.34 (-1.26-1.94) Ln-SVE (bph): 0.01 (-0.10-0.11) HR (bpm): -0.23 (-1.09-0.63) SDNN (ms): -2.11 (-4.90-0.68) R-MSSD (ms): -0.83 (-3.60-1.94)

Increment: N2.5: IQR = 8.9 SBP (mm Hg): -0.81 (-2.15-0.53) DBP (mm Hg): 0.40 (-1.19-1.98) Ln-SVE (bph): -0.04 (-0.18-0.10) HR (bpm): -0.35 (-0.85-0.14) SDNN (ms): -1.10 (-3.10-0.90) R-MSSD (ms): -0.54 (-2.54-1.46)

Note: Total personal fine particle exposure (T) were dominated by exposures to non ambient particles which were not correlated with ambient fine particle exposure (A) or ambient concentrations (C). Results for each of these metrics are listed.



### December 2009 E-36

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Fan et al. (2008, 191979 ) Period of Study: Feb-May 2005

Location: Paterson, New Jersey Outcome: Cardiopulmonary Health (FEV, FVC, PEF, SDNN, HR) Age Groups: 61.2 (13.7) Study Design: Panel

N: 11 Statistical Analyses: Mixed Effects models, Linear Regression models

Covariates: Temperature, humidity Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0 Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): |

∆ PM 2.5 avg Morning: 35.2 (25.9) Afternoon: 24.1 (22.1)

∆ PM 2.5 peak Morning: 71.3 (56.1) Afternoon: 64.3 (43.5) Range:

∆ PM 2.5 avg Morning: 1.1 - 87 Afternoon: 1.2 - 98

∆ PM 2.5 peak Morning: 4.0 - 278 Afternoon: 3.0 - 150 Monitoring Stations: NR Copollutant: NR Co-pollutant Correlation: N/A PM Increment: 10 μg/m 3 Beta (SE), p-value:

∆ SDNN Morning, ∆ PM 2.5 avg 15min: -14.5 (6.9), 0.06 2h: -18.9 (4.2), 0.0002 4h: -2.5 (8.6), 0.78 Morning, ∆ PM 2.5 peak 15min: -9.2 (11.2), 0.43 2h: -5.1 (13.8), 0.72 4h: -7.4 (12.0), 0.55 Afternoon, ∆ PM 2.5 avg 15min: -2.4 (7.6), 0.77 2h: -20.2 (10.8), 0.10 4h: -0.7 (11.2), 0.95 Afternoon, ∆ PM 2.5 peak 15min: 0.6 (8.9), 0.95 2h: 19.2 (14.6), 0.23 4h: -6.8 (14.1), 0.64

∆ HR Morning, ∆ PM 2.5 avg 15min: 1.2 (3.1), 0.71 2h: -5.5 (2.9), 0.08 4h: -3.1 (4.6), 0.51 Morning, ∆ PM 2.5 peak 15min: 0.8 (4.4), 0.86 2h: -7.2 (4.2), 0.11 4h: -7.1 (6.3), 0.28 Afternoon, ∆ PM 2.5 avg 15min: -2.0 (4.0), 0.62 2h: 0.9 (5.4), 0.87 4h: 8.2 (5.2), 0.14 Afternoon, ∆ PM 2.5 peak 15min: -5.6 (5.3), 0.31 2h: 3.1 (8.1), 0.71 4h: 11.1 (8.1), 0.20

∆ FEV 1 Morning, ∆ PM 2.5 avg: 0.02 (0.04), 0.68 Morning, ∆ PM 2.5 peak: -0.13 (0.08), 0.16

∆ FVC Morning, ∆ PM 2.5 avg: -0.10 (0.09), 0.31 Morning, ∆ PM 2.5 peak: -0.12 (0.17), 0.51

∆ PEF Morning, ∆ PM 2.5 avg: -0.54 (0.62), 0.42 Morning, ∆ PM 2.5 peak: -1.46 (1.12), 0.24

Notes: Estimates relative to increases in the avg and peak PM 2.5 concentrations

Reference: Folino et al. (2009, 191902 ) Period of Study: Jun 2006-May 2007

Location: Padua, Italy Outcome: HRV & Inflammatory Markers Age Groups: 45-65 yr Study Design: Panel

N: 39 patients w/ myocardial infarction Statistical Analyses: Linear Regression Model, ANOVA

Covariates: Temperature, relativehumidity, atmospheric pressure, betablocker, aspirin, or nitrate consumption, smoking habit Dose-response Investigated? No Statistical Package: Stata Lags Considered: NR Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Summer: 33.9 (12.7) Winter: 62.1 (27.9) Spring: 30.8 (14.0) Monitoring Stations: NR Copollutant: PM 10 , PM 0.25 Co-pollutant Correlation: NR PM Increment: 1 μg/m 3 Beta (SE), p-value: SDNN: 0.109 (0.115), 0.345 SDANN: 0.127 (0.126), 0.314 RMSSD: 0.045 (0.040), 0.256 pH: 0.002 (0.001), 0.041 LTB4: 0.590 (0.324), 0.069 eNO: -0.002 (0.003), 0.503 PTX3: -0.004 (0.002), 0.013 C-reactive protein: -0.008 (0.005), 0.115 CC16: -0.002 (0.002), 0.410 IL-8: 0.000 (0.003), 0.989



### December 2009 E-37

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Folino et al. (2009, 191902 ) Period of Study: Jun 2006-May 2007

Location: Padua, Italy Outcome: HRV & Inflammatory Markers Age Groups: 45-65 yr Study Design: Panel

N: 39 patients w/ myocardial infarction Statistical Analyses: Linear Regression Model, ANOVA

Covariates: Temperature, relativehumidity, atmospheric pressure, betablocker, aspirin, or nitrate consumption, smoking habit Dose-response Investigated? No Statistical Package: Stata Lags Considered: NR Pollutant: PM 0.25 Averaging Time: 24 h Mean (SD): Summer: 17.6 (7.5) Winter: 30.5 (17.4) Spring: 18.8 (10.8) Monitoring Stations: NR Copollutant: PM 10 , PM 2.5 Co-pollutant Correlation: NR PM Increment: 1 μg/m 3 Beta (SE), p-value: SDNN: 0.214 (0.204), 0.295 SDANN: 0.214 (0.214), 0.316 RMSSD: 0.081 (0.077), 0.291 pH: 0.005 (0.002), 0.004 LTB4: 0.835 (0.533), 0.117 eNO: -0.006 (0.005), 0.182 PTX3: -0.006 (0.003), 0.071 C-reactive protein: -0.011 (0.007), 0.104 CC16: 0.001 (0.004), 0.890 IL-8: -0.004 (0.006), 0.527

Reference: Goldberg et al. (2008, 180380 ) Period of Study: Jul 2002-Oct 2003

Location: Montreal, Canada Outcome: Oxygen saturation & pulse rate Age Groups: 50-85 yr Study Design: Panel

N: 31 Statistical Analyses: Mixed Random Effects Model

Covariates: Body temperature, consumption of salt, intake of fluids, being ill the day before, ambient temperature, relative humidity, barometric pressure Dose-response Investigated? No Statistical Package: Splus Lags Considered: lags 1 day; 0- to 2-day avg Pollutant: PM 2.5 Averaging Time: D aily

IQR: 7.3 Monitoring Stations: 8 Co-pollutant: CO, NO 2 , SO 2 , O 3 Co-pollutant Correlation CO: 0.72 NO 2 : 0.62 PM Increment: Interquartile Range (7.3 μg/m 3 ) Mean Difference (Lower CI, Upper CI), lag: Oxygen Saturation Unadjusted: -0.087 (-0.143, -0.031), lag 0 Unadjusted: -0.058 (-0.114, -0.002), lag 1 Unadjusted: -0.083 (-0.155, -0.010), lag 0-2-day avg Adjusted: -0.056 (-0.117, 0.005), lag 0 Adjusted: -0.019 (-0.079, 0.041), lag 1 Adjusted: -0.039 (-0.118, 0.039), lag 0- 2-day avg

Pulse Rate Unadjusted: 0.226 (-0.037, 0.489), lag 0 Unadjusted: 0.288 (0.022, 0.554), lag 1 Unadjusted: 0.420 (0.067, 0.772), lag 0- 2-day avg Adjusted: 0.158 (-0.136, 0.451), lag 0 Adjusted: 0.246 (-0.040, 0.531), lag 1 Adjusted: 0.353 (-0.034, 0.740), lag 0- 2-day avg



### December 2009 E-38

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Goldberg et al. (2008, 180380 ) Period of Study: Jul 2002-Oct 2003

Location: Montreal, Canada Outcome: Shortness of Breath & General health Age Groups: 50-85 yr Study Design: Panel

N: 31 Statistical Analyses: Mixed Random Effects Model

Covariates: Body temperature, consumption of salt, intake of fluids, being ill the day before, ambient temperature, relative humidity, barometric pressure Dose-response Investigated? No Statistical Package: Splus Lags Considered: lags 0-4 days; 0- to 2-day avg Pollutant: PM 2.5 Averaging Time: Daily

Mean: 9.5

Median: 7.0

Min: 0.8

Max: 50.2

IQR: 7.3 Monitoring Stations: 8 Co-pollutant: CO, NO 2 , SO 2 , O 3 Co-pollutant Correlation CO: 0.66 NO 2 : 0.54 O 3 : 0.32 SO 2 : 0.50 PM Increment: Interquartile Range (7.3 μg/m 3 ) Mean Difference (Lower CI, Upper CI), lag:

General Health Unadjusted: -0.317 (-0.699, 0.064), lag 0 Unadjusted: -0.284 (-0.670, 0.103), lag 1 Unadjusted: -0.048 (-0.427, 0.332), lag 2 Unadjusted: -0.241 (-0.620, 0.139), lag 3 Unadjusted: -0.010 (-0.390, 0.370), lag 4 Unadjusted: -0.482 (-1.053, 0.090), lag 0-2-day avg Adjusted: -0.125 (-0.545, 0.295), lag 0 Adjusted: -0.167 (-0.568, 0.234), lag 1 Adjusted: -0.081 (-0.464, 0.302), lag 2 Adjusted: -0.222 (-0.602, 0.157), lag 3 Adjusted: 0.016 (-0.364, 0.396), lag 4 Adjusted: -0.281 (-0.886, 0.325), lag 0-2-day avg Shortness of breath at night Unadjusted: -0.421 (-0.847, 0.006), lag 0 Unadjusted: -0.278 (-0.711, 0.155), lag 1 Unadjusted: -0.100 (-0.526, 0.327), lag 2 Unadjusted: -0.220 (-0.645, 0.206), lag 3 Unadjusted: -0.206 (-0.632, 0.220), lag 4 Unadjusted: -0.555 (-1.172, 0.063), lag 0-2-day avg Adjusted: -0.171 (-0.639, 0.297), lag 0 Adjusted: -0.130 (-0.579, 0.319), lag 1 Adjusted: -0.127 (-0.553, 0.299), lag 2 Adjusted: -0.192 (-0.616, 0.231), lag 3 Adjusted: -0.171 (-0.594, 0.253), lag 4 Adjusted: -0.301 (-0.952, 0.350), lag 0-2-day avg

Reference: Ibald-Mulli et al. (2004, 087415 ) Period of Study: W inter 1998-1999

Location: Helsinki, Finland Erfurt, Germany Amsterdam, the Netherlands Outcome: Blood Pressure & Heart Rate Age Groups: 40-84 Study Design: Panel

N: 131 adults w/ CHD Statistical Analyses: Linear Regression

Covariates: T rend, day of week, temperature, barometric pressure, relative humidity, medication use Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-2, 5-day avg Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Downtown: 40 (20) Tunney’s Pasture: 10 (10) p-value 0.000 Monitoring Stations: NR Copollutant: PM 1.0 Co-pollutant Correlation: N/A PM Increment: Interquartile Range (27.02 μg/m 3 ) Beta (SE), p-value: Flow mediated vasodilation (%): -0.016 (0.0072) p=0.03 Heart Rate (beats/min): 0.081 (0.135) p=0.55 Diastolic blood pressure (mmHg): 0.088 (0.088) p=0.32 Systolic blood pressure (mmHg): -0.108 (0.006) p=0.48

Reference: Langrish et al. (2009, 191908 ) Period of Study: Aug 2008

Location: Beijing, China Outcome: Cardiovascular Effects Age Groups: Median 28 yr Study Design: Panel

N: 15 Statistical Analyses: NR

Covariates: NR Dose-response Investigated? No Statistical Package: NR Lags Considered: NR Pollutant: PM 2.5 Averaging Time: NR

Mean: W/o mask: 86 W/ mask: 140 Monitoring Stations: NR Co-pollutant: CO, SO 2 , NO 2 Co-pollutant Correlation: N/A PM Increment: NR Mean (Lower CI, Upper CI): W/o Mask (Day) SBP: 100 (104, 116) DBP: 73 (69, 76) MAP: 85 (81, 88) Heart Rate: 79 (74, 84) Avg NN interval: 829 (789, 869) pNN50: 15.9 (10.7, 21.0) RMSSD: 35.1 (29.2, 41.0) SDNN: 61.2 (54.9, 67.5) Triangular index: 12.9 (11.9, 13.9) LF power: 816 (628, 1004) HF power: 460 (325, 595) LFn: 62.8 (56.7, 68.9) HFn: 29.2 (25.5, 32.8) HF/LF ratio: 0.738 (0.507, 0.970) W/ Mask (Day) SBP: 109 (104, 114) DBP: 73 (70-76) MAP: 85 (81, 89)



### December 2009 E-39

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Heart Rate: 78 (73, 82) Avg NN interval: 850 (805, 896) pNN50: 17.9 (14.2, 21.6) RMSSD: 37.1 (32.2, 42.0) SDNN: 65.5 (59.0, 72.2)* Triangular index: 13.8 (13.0, 14.5) LF power: 919 (717, 1122)* HF power: 485 (400, 569) LFn: 64.5 (60.6, 68.4) HFn: 30.0 (27.0, 33.1) HF/LF ratio: 0.680 (0.519, 0.842) W/o Mask (During Walk) SBP: 121 (115, 127) DBP: 81 (75-87) MAP: 94 (89, 99) Heart Rate: 88 (82, 94) Avg NN interval: 594 (562, 627) pNN50: 3.3 (0.8, 5.7) RMSSD: 17.2 (13.4, 21.0) SDNN: 45.8 (36.8, 54.8) Triangular index: 10.7 (9.1, 12.4) LF power: 313 (170, 455) HF power: 76.5 (33.6, 120.0) LFn: 68.2 (60.9, 75.5) HFn: 16.1 (11.9, 20.3) HF/LF ratio: 0.259 (0.173, 0.344) W/ Mask (During Walk) SBP: 114 (108, 120) DBP: 79 (74, 83) MAP: 90 (86, 94) Heart Rate: 91 (85, 97) Avg NN interval: 613 (571, 655) pNN50: 2.1 (-0.1, -4.4) RMSSD: 20.0 (15.5, 24.6) SDNN: 54.8 (42.5, 67.0) Triangular index: 11.4 (9.4, 13.3) W/ Mask (During Walk) LF power: 414 (233, 595) HF power: 116.8 (52.6, 181.0) LFn: 67.9 (61.9, 73.9) HFn: 16.0 (12.5, 19.4) HF/LF ratio: 0.247 (0.180, 0.314) Mean (SD): W/o Mask (After Walk) Headache: 2.53 (5.55) Dizziness: 1.07 (2.22) Tiredness: 8.47 (12.14) Sickness: 1.07 (2.22) Cough: 1.80 (4.80) Difficulty Breathing: 0.67 (0.90) Eye irritation: 1.40 (3.60) Throat irritation: 1.47 (4.07) Nose irritation: 1.53 (3.78) Unpleasant Smell: 0.93 (1.22) Bad taste: 0.73 (0.96) Difficulty walking: 12.53 (13.24) Perception of Pollution: 19.80 (18.37) W/ Mask (After Walk) Headache: 0.73 (1.03) Dizziness: 0.80 (1.57 Tiredness: 7.40 (9.37) Sickness: 0.87 (1.51) Cough: 1.00 (1.73) Difficulty Breathing: 3.80 (8.10) Eye irritation: 1.67 (3.27) Throat irritation: 1.07 (2.63) Nose irritation: 1.07 (1.91) Unpleasant Smell: 0.60 (0.91) Bad taste: 0.60 (1.18) Difficulty walking: 15.13 (11.51) Perception of Pollution: 11.60 (10.44) *p < 0.05 Notes: Estimates also available for 24 h, night, before walk, and 24 h after walk.



### December 2009 E-40

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lanki et al. (2006, 088412 ) Period of Study: Fall 1998-spring 1999

Location: Helsinki, Finland Outcome: ST segment depressions (2 endpoints: >0.1mV regardless of the direction of the ST slope and >0.1mV with horizontal or downward slope [stricter criteria]) Age Groups: Mean = 68.2 (6.5) yr Study Design: Panel

N: 45 elderly nonsmoking persons with stable coronary heart disease 342 total exercise tests for analyses Statistical Analyses: Generalized additive models with penalized splines (logistic regression) principal components analysis and linear regression of 13 measured elements used to apportion PM 2.5 mass between different sources

Covariates: Subject, linear terms for time trend, temperature, relative humidity, penalized spline for change in heart rate during the exercise test

Season: NR Dose-response Investigated? No Statistical Package: S-plus 2000 and R Pollutant: PM 2.5 (Analyses conducted for source specific PM 2.5 ) Averaging Time: Daily filter samples

Mean: Crustal: 0.6 Long-range transported: 6.4 Oil combustion: 1.6 Salt: 0.9 Local traffic: 2.9 Total: 12.8

Percentiles: Crustal 25: 0.0 50: 0.4 75: 1.1; Max: 5.3 Long-range transported 25: 2.2 50: 5.5 75: 9.8; Max: 26.5

Oil combustion 25: 0.6 50: 1.3 75: 2.3; Max: 12.2

Salt 25: 0.3 50: 0.8 75: 1.2; Max: 5.9

Local traffic 25: 1.7 50: 2.5 75: 3.4; Max: 12.0

Total 25: 8.3 50: 10.6 75: 15.9; Max: 39.8 Monitoring Stations: 1 monitor Copollutant (correlation):

Correlations with PM 2.5 : Crustal: r = -0.01 Long-range transported: r = 0.82

Oil combustion: r = 0.35

Salt: r = 0.19

Local traffic: r = 0.26 PM Increment: 1 μg/m 3 Effect Estimate [Lower CI, Upper CI]:Adjusted ORs between daily sourcespecific PM 2.5 concentrations and ST-segment depressions. ST-segment depression defined as >0.1 mV (n = 62)

Crustal Lag 0: 0.80 (0.47, 1.36) Lag 1: 0.66 (0.40, 1.10) Lag 2: 1.18 (0.68, 2.06) Lag 3: 1.87 (0.85, 4.09) Long-range transport Lag 0: 0.94 (0.84, 1.05) Lag 1: 1.00 (0.92, 1.08) Lag 2: 1.11 (1.02, 1.20) Lag 3: 1.06 (0.95, 1.18)

Oil combustion Lag 0: 0.87 (0.57, 1.32) Lag 1: 1.04 (0.75, 1.45) Lag 2: 1.10 (0.83, 1.46) Lag 3: 1.12 (0.79, 1.58)

Salt Lag0: 1.03 (0.57, 1.85) Lag1: 0.72 (0.37, 1.40) Lag2: 0.66 (0.31, 1.40) Lag3: 1.55 (0.83, 2.89)

Local traffic Lag 0: 0.91 (0.69, 1.21) Lag 1: 1.22 (0.88, 1.69) Lag 2: 1.53 (1.19, 1.97) Lag 3: 0.98 (0.78, 1.23) ST-segment depression defined as >0.1 mV with horizontal or downward slope (n = 46)

Crustal Lag0: 0.76 (0.42, 1.35) Lag1: 0.41 (0.22, 0.79) Lag2: 1.17 (0.65, 2.09) Lag3: 1.60 (0.72, 3.59) Long-range transport Lag 0: 0.98 (0.86, 1.10) Lag 1: 1.03 (0.95, 1.12) Lag 2: 1.11 (1.02, 1.21) Lag 3: 1.02 (0.95, 1.10)

Oil combustion Lag 0: 0.95 (0.61, 1.49) Lag 1: 1.13 (0.76, 1.68) Lag 2: 1.33 (0.98, 1.80) Lag 3: 1.29 (0.90, 1.86)

Salt Lag 0: 1.15 (0.56, 2.38) Lag 1: 0.90 (0.44, 1.81) Lag 2: 1.39 (0.63, 3.08) Lag 3: 1.93 (1.00, 3.72)

Local traffic Lag 0: 0.89 (0.64, 1.23) Lag 1: 1.21 (0.86, 1.71) Lag 2: 1.37 (1.03, 1.83) Lag 3: 1.03 (0.80, 1.32) Adjusted ORs for the association of indicator elements of PM 2.5 sources and ST-segment depressions in multipollutant models (models include all 5 indicator elements). ST-segment depression defined as >0.1 mV (n = 62) Si (Crustal) Lag0: 0.73 (0.39, 1.38)



### December 2009 E-41

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Lag1: 0.48 (0.25, 0.93) Lag2: 0.78 (0.35, 1.71) Lag3: 1.95 (0.69, 5.48) S (Long-range transport) Lag0: 0.70 (0.25, 1.95) Lag1: 0.58 (0.23, 1.47) Lag2: 1.08 (0.44, 2.63) Lag3: 1.60 (0.73, 3.48) Ni (Oil combustion) Lag0: 0.78 (0.30, 2.04) Lag1: 1.20 (0.58, 2.46) Lag2: 1.15 (0.61, 2.18) Lag3: 1.02 (0.41, 2.54) Cl (Salt) Lag0: 1.03 (0.79, 1.34) Lag1: 0.88 (0.56, 1.38) Lag2: 1.02 (0.62, 1.69) Lag3: 1.27 (0.85, 1.91) ABS (Local traffic) Lag0: 0.92 (0.36, 2.37) Lag1: 1.83 (0.73, 4.59) Lag2: 4.46 (1.69, 11.79) Lag3: 0.92 (0.40, 2.12) ST-segment depression defined as >0.1 mV with horizontal or downward slope (n = 46) Si (Crustal) Lag0: 0.67 (0.33, 1.36) Lag1: 0.34 (0.15, 0.81) Lag2: 0.81 (0.33, 2.00) Lag3: 1.90 (0.64, 5.65) S (Long-range transport) Lag0: 0.84 (0.29, 2.47) Lag1: 0.89 (0.34, 2.32) Lag2: 1.36 (0.54, 3.45) Lag3: 1.12 (0.53, 2.40) Ni (Oil combustion) Lag0: 1.10 (0.36, 3.37) Lag1: 1.16 (0.45, 2.96) Lag2: 1.64 (0.84, 3.20) Lag3: 1.63 (0.64, 4.14) Cl (Salt) Lag0: 1.13 (0.80, 1.62) Lag1: 0.99 (0.58, 1.68) Lag2: 1.55 (0.87, 2.76) Lag3: 1.45 (0.94, 2.25) ABS (Local traffic) Lag0: 0.74 (0.25, 2.23) Lag1: 1.76 (0.62, 5.00) Lag2: 4.86 (1.55, 15.26) Lag3: 0.97 (0.39, 2.41)



### December 2009 E-42

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lanki et al. (2008, 191984 ) Period of Study: Jan 1999-Apr 1999

Location: Helsinki, Finland Outcome: ST Segment Depressions >0.1 mV Age Groups: 50+ Study Design: Panel

N: 41 elderly people w/ CHD Statistical Analyses: Logistic Regression Model

Covariates: Long-term time trend, temperature, humidity, change in heart rate following exercise test Dose-response Investigated? No Statistical Package: R Lags Considered: lags 0-24 h Pollutant: PM 2.5 Averaging Time: Hourly 25th, 50th, 75th, Max:

Personal PM 2.5 1h: 6.9, 11.2, 15.8, 41.5 4h: 5.9, 10.0, 14.6, 41.3 8h: 5.0, 7.9, 13.0, 34.9 12h: 5.2, 7.8, 12.1, 28.8 22h: 6.6, 9.3, 13.0, 30.2

Outdoor PM 2.5 1h: 8.9, 12.9, 17.8, 42.9 4h: 8.8, 12.5, 17.6, 40.8 8h: 8.3, 12.1, 17.2, 39.2 12h: 8.3, 11.9, 17.0, 37.0 24 h: 9.0, 12.5, 17.7, 30.5 Monitoring Stations: 1 Co-pollutant: PM<0.1 Co-pollutant Correlation Personal & Outdoor PM 2.5 1 h & 1 h: 0.70 4 h & 4 h: 0.54 8 h & 8 h: 0.60 12 h & 12 h: 0.50 22 h & 24 h: 0.80

Notes: 1-22 h pollutant averaging times.Correlations also available for personalpersonal and outdoor-outdoor. PM Increment: 10 μg/m 3 Odds Ratio (Lower CI, Upper CI):

Personal PM 2.5 1-h avg: 3.26 (1.07, 9.99)* 4-h avg: 2.42 (0.75, 7.83) 8-h avg: 1.57 (0.49, 5.09) 12-h avg: 1.96 (0.44, 8.64) 22-h avg: 2.06 (0.30, 14.10)

Outdoor PM 2.5 1-h avg: 1.77 (0.87, 3.58) 4-h avg: 2.47 (1.05, 5.85)* 8-h avg: 1.83 (0.80, 4.20) 12-h avg: 1.90 (0.77, 4.65) 24-h avg: 1.60 (0.59, 4.39) *p < 0.05

Reference: Liao et al. (2007, 180272 ) Period of Study: 1999-2004

Location: 24 U.S. States Outcome: Ectopy Age Groups: women 50-79 yr Study Design: Panel

N: 57,422 Statistical Analyses: logistic regression & random effects modeling

Covariates: Age, race, center, education, history of CVD/chronic lung disease, rel. humidity, temperature, smoking Dose-response Investigated? No Statistical Package: SAS, Stata Lags Considered: lags 0-365 days Pollutant: PM 2.5 Averaging Time: Daily Mean (SD)*: All: 13.8 (79) No Ectopy: 13.8 (7.9) Any Ectopy: 13.8 (7.6) 5th, 95th percentile*: All: 5, 29.1 No Ectopy: 5, 29.2 Any Ectopy: 5.06, 28.5 Monitoring Stations: NR‡ Copollutant: PM 10 Co-pollutant Correlation: NR *Lag 1 ‡Monitors used in model for spatial interpolation of daily PM values. PM Increment: 10 μg/m 3 Percent Change (Lower CI, Upper CI): All Ventricular Ectopy Lag 0: 1.01 (0.91, 1.13) Lag 1: 1.07 (0.96, 1.20) Lag 2: 1.09 (0.98, 1.21) Current Smoker Ventricular Ectopy Lag 0: 1.52 (1.04, 2.24) Lag 1: 2 (1.32, 3.03) Lag 2: 1.59 (0.99, 2.55) Nonsmoker Ventricular Ectopy Lag 0: 0.99 (0.89, 1.11) Lag 1: 1.05 (0.94, 1.17) Lag 2: 1.08 (0.97, 1.21) All Supraventricular Ectopy Lag 0: 1.04 (0.96, 1.13) Lag 1: 1.01 (0.93, 1.10) Lag 2: 0.96 (0.87, 1.05) All Ventricular or Supraventricular Ectopy Lag 0: 1.03 (0.96, 1.11) Lag 1: 1.04 (0.97, 1.11) Lag 2: 1 (0.94, 1.07)

Reference: Lipsett et al. (2006, 088753 ) Period of Study: Feb-May 2000

Location: Coachella Valley, CA Outcome: HRV parameters, specifically SDNN, SDANN, r-MSSD, LF, HF, total power, triangular index (TRII). Study Design: Panel study

N: 19 non-smoking adults with coronary artery disease Statistical Analysis: Mixed linear regression models with random effects parameters Pollutant: PM 2.5 Averaging Time: 2 h Mean (range) Indio: 23.2 (6.3-90.4) Palm Springs: 14 (4.7-52) Monitoring Stations: 2 Copollutant: O 3 PM Increment: SE*100 Effect Estimate (change in HRV per unit increase in PM concentration): SDNN: -0.37 msec (SE = 1.01)

Notes: Weekly ambulatory 24 h ECG recordings (once per week for up to 12 wk), using Holter monitors, were made. Subjects’ residences were within 5 mi of 1 of 2 PM monitoring sites. Decreased HRV was associated with PM 2.5 , but these effects were not statistically significant. Regressed HRV parameters against 18: 00-20: 00 mean particulate pollution.



### December 2009 E-43

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ljungman et al. (2008, 180266 ) Period of Study: Aug 2001-Dec 2006

Location: Stockholm, Sweden Outcome: Ventricular Arrhythmia Age Groups: 28-85 yr Study Design: C ase-crossover

N: 88 patients w/ implantable cardioverter defibrillators Statistical Analyses: Conditional logistic regression

Covariates: Temperature, humidity, pressure, ischemic heart disease, ejection fraction, heart disease, diabetes, use of beta-blockers, age, BMI, location at time of arrhythmia, distance from air pollution monitor Dose-response Investigated? No Statistical Package: Stata, S-plus Lags Considered: lags 2-24 h Pollutant: PM 2.5 Averaging Time: Hourly

Median: 2 h: 9.17 24 h: 9.49

Min: 2 h: 0.15 24 h: 2.97

Max: 2 h: 99.25 24 h: 47.07

IQR: 2 h: 6.69 24 h: 5.27 Monitoring Stations: 1 Copollutant: PM 10 , NO 2 Co-pollutant Correlation: NR PM Increment: Interquartile Range Odds Ratio (Lower CI, Upper CI): 2 h: 1.23 (0.84, 1.80) 24 h: 1.28 (0.90, 1.84)

Notes: OR of ventricular arrhythmia for an IQR increase of air pollutants in different subgroups (Fig 2)

Reference: Ljungman et al. (2009, 191983 ) Period of Study: May 2003-Jul 2004

Location: Athens, Greece Helsinki, Finland Ausburg, Germany Barcelona, Spain Rome, Italy Stokholm, Sweeden Outcome: Interleukin-6 Response Age Groups: 35-80 yr Study Design: Panel

N: 955 male myocardial infarction survivors Statistical Analyses: Additive Mixed Models

Covariates: Age, sex, BMI, city, HDL/total cholesterol, smoking, alcohol intake, HbA1c, NT-proBNP, history of MI, heart failure, or diabetes, phlegm Dose-response Investigated? No Statistical Package: NR Lags Considered: 1 day Pollutant: PM 2.5 Averaging Time: 24 h

Mean: 17.7 25th: 10.9 75th: 21.9 Monitoring Stations: NR Copollutant: CO, NO 2 , PNC, PM 2.5 Co-pollutant Correlation: PM 10 : 0.81 PM Increment: Interquartile Range (11.0 μg/m 3 ) Change of IL-6 (Low er CI, Upper CI), p-value: 0.6 (-0.8, 2.0), 0.40

Reference: Luttman-Gibson et al. (2006, 089794 ) Period of Study: Jun-Dec 2000

Location: Steubenville, OH Outcome: Heart rate variability Age Groups: Study Design: Panel study

N: 32 participants Statistical Analysis: Linear mixed models Pollutant: PM 2.5 Averaging Time: 1 h 24 h Mean (IQR)

PM 2.5 : 20.0 (15.2) Sulfate: 6.9 (5.1) EC: 1.1 (0.6) Copollutant: NO 2 , SO 2 , O 3 PM Increment: IQR Percent change (95% CI): Each 13.4 μg/m 3 increase in 24 h mean PM 2.5 concentration was associated with: SDNN: -4.0% (95% CI: -7.0% to -0.9%) r-MSSD: -6.5% (95% CI: -12.1% to -0.6%) HF: -11.4% (95% CI: -21.5% to -0.1%) Each 5.1 μg/m 3 increase in sulfates on the previous day was associated with: SDNN: -3.3% (95% CI: -6.0% to -0.5%) r-MSSD: -5.6% (95% CI: -10.7%, 0.2%) HF: -10.3% (95% CI: -19.5% to -0.1%)

Notes: The authors conclude that increases in both traffic related particles and sulfates may adversely effect autonomic function.



### December 2009 E-44

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Mar et al. (2005, 087566 ) Period of Study: 1999-2001

Location: Seattle, WA Outcome: Change in arterial O 2 saturation, heart rate, and blood pressure (SBP and DBP) Age Groups: >75 yr Study Design: Panel study

N: 88 elderly subjects Statistical Analysis: GEE Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Personal: 9.3(8.4) Indoor: 7.4 (4.8) Outdoor: 9.0 (4.6) PM Increment: 10 μ g/m 3 Unit change in measure (95% CI): Among all subjects: Each increase in outdoor same day PM 2.5 was associated with: SBP: -0.81 mmHg (95% CI: -2.34, 0.73) DBP: -0.46 mmHg (95% CI: -1.49 to 0.57) H: -0.75 beats/min (95% CI: -1.42 to -0.07) Each increase in indoor same day PM 2.5 was associated with: SBP: 0.92 mmHg (95% CI: -2.04 to 3.87) DBP: 0.38 mmHg (95% CI: -1.43 to 2.20) H: 0.22 beats/min (95% CI: -0.71 to 1.16) Each increase in personal same day PM 2.5 was associated with: SBP: 0.37 mmHg (95% CI: -0.93 to 1.67) DBP: -0.20 mmHg (95% CI: -0.85 to 0.46) H: 0.44 beats/min (95% CI: 0.04 to 0.84)

Notes: Results by health status presented in Fig 1

Used 2 sessions that each were 10 consecutive days of measurements Used personal, indoor, and outdoor measures of PM 2.5 Reference: Metzger et al. (2007, 092856 ) Period of Study: Aug 1998-Dec 2002

Location: Atlanta, GA Outcome: Days with any event recorded by the ICD, days with ICD shocks/defibrillation and days with either cardiac pacing or defibrillation Study Design: Repeated measures

N: 884 subjects between 1993 and 2002 Statistical Analysis: Logistic regression with GEE to account for residual autocorrelation within subjects Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): PM 2.5 : 17.8 (8.6) PM 2.5 sulfates: 5.0 (3.4) PM 2.5 EC: 1.7 (1.2) PM 2.5 OC: 4.4 (2.4) PM 2.5 water-soluble metals: 0.029 (0.024)

Percentiles: PM 2.5 : Median: 16.2 PM 2.5 sulfates: Median: 4.1 PM 2.5 EC: Median: 1.4 PM 2.5 OC: Median: 3.9 PM 2.5 water-soluble metals: Median: 0.022 Copollutant: O 3 NO 2 CO SO 2 Oxygenated hydrocarbons PM Increment: OR (95% CI): Outcome = Any event recorded by ICD

PM 2.5 OR = 1.00 (95% CI: 0.95, 1.04) PM 2.5 EC OR = 1.01 (95% CI: 0.98, 1.05) PM 2.5 OC OR = 1.01 (95% CI: 0.98, 1.03) PM 2.5 Sulfates OR = 0.99 (95% CI: 0.93, 1.06) PM 2.5 Water soluble metals OR = 0.95 (95% CI: 0.90, 1.00

Reference: O'Neill et al. (2007, 091362 ) Period of Study: May 1998-Dec 2002

Location: Boston, MA Outcome: Soluble intercellular adhesion molecule 1 (ICAM-1)

Vascular cell adhesion molecule 1 (VCAM-1) von Willebrand factor (vWF) Age Groups: Mean (SD): 56.6 (10.6) Study Design: Cross-sectional

N: 92 participants (type 2 diabetic patients) Pollutant: PM 2.5 Averaging Time: 24 h (lagged ma of days 0 to 1, 2, 3, 4, and 5) Mean (SD): 11.4 (5.9) Descriptive statistics represent entire study period

Percentiles: IQR range: 7.6 Range (Min, Max): 0.07, 33.7) PM Increment: IQR (specific to lag period) Effect Estimate [Lower CI, Upper CI]: % change per IQR of PM 2.5 ICAM-1 - All subjects Lag 0: 2.87 (-4.63, 10.95) 2 dma: 2.25 (-5.15, 10.22) 3 dma: 1.48 (-5.63, 9.11) 4 dma: 1.80 (-4.98, 9.07) 5 dma: 1.51 (-5.30, 8.80) 6 dma: 2.12 (-4.23, 8.89)



### December 2009 E-45

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Statistical Analyses: l inear regression

Covariates: Apparent temperature, season, age, race, sex, glycosylated hemoglobin, cholesterol, smoking history, BMI Dose-response Investigated? No Statistical Package: NR Monitoring Stations: 1 site Copollutant: PM 2.5 BC SO 4 2– Subjects not known to be taking statins Lag 0: 5.47 (-3.74, 15.57) 2 dma: 5.70 (-3.70, 16.01) 3 dma: 4.57 (-4.31, 14.27) 4 dma: 4.57 (-4.27, 14.23) 5 dma: 3.80 (-4.84, 13.22) 6 dma: 3.79 (-4.49, 12.80) Subjects who report smoking in the past (but not within 6 mo) Lag 0: 0.9 (-9.56, 12.66) 2 dma: 0.40 (-12.08, 14.65) 3 dma: 1.34 (-9.23, 13.14) 4 dma: 2.29 (-6.84, 12.30) 5 dma: 1.09 (-8.30, 11.44) 6 dma: 3.08 (-6.30, 13.40); Subjects who did not report smoking in the past Lag 0: 0.46 (-8.23, 9.97) 2 dma: 1.37 (-7.96, 11.65) 3 dma: -0.96 (-10.01, 9.00) 4 dma: -1.34 (-10.35, 8.58) 5 dma: -0.87 (-10.17, 9.40) 6 dma: -1.78 (-10.64, 7.94)

VCAM-1 - All subjects Lag 0: 6.88 (-2.88, 17.62) 2 dma: 8.18 (-1.43, 18.72) 3 dma: 6.92 (-1.66, 16.25) 4 dma: 6.46 (-1.16, 14.66) 5 dma: 8.57 (0.05, 17.80) 6 dma: 11.76 (3.48, 20.70) Subjects not known to be taking statins Lag 0: 10.26 (-0.64, 22.35) 2 dma: 15.02 (3.76, 27.49) 3 dma: 14.59 (3.94, 26.34) 4 dma: 15.15 (4.54, 26.84) 5 dma: 16.16 (5.77, 27.58) 6 dma: 17.66 (7.77, 28.45) Subjects who report smoking in the past (but not within 6 mo) Lag 0: 13.2 (-1.30, 29.72) 2 dma: 18.4 (0.69, 39.33) 3 dma: 15.7 (1.19, 32.30) 4 dma: 13.1 (0.88, 26.78) 5 dma: 13.2 (0.49, 27.58) 6 dma: 16.2 (3.76, 30.10) Subjects who did not report smoking in the past Lag 0: -3.12 (-12.41, 7.17) 2 dma: -0.34 (-10.57, 11.05) 3 dma: -1.09 (-11.15, 10.12) 4 dma: -0.81 (-10.91, 10.43) 5 dma: 2.07 (-8.59, 13.96) 6 dma: 4.89 (-5.56, 16.50)

vWF - All subjects Lag 0: 15.16 (-9.79, 47.01) 2 dma: 12.57 (-9.19, 39.55) 3 dma: 25.14 (-9.87, 73.74) 4 dma: 23.42 (-9.47, 68.25) 5 dma: 17.92 (-10.22, 54.87) 6 dma: 20.48 (-8.82, 59.22) Subjects not known to be taking statins Lag 0: 7.40 (-19.82, 43.88) 2 dma: 7.10 (-19.09, 41.76) 3 dma: 10.78 (-17.92, 49.52) 4 dma: 11.61 (-16.64, 49.42) 5 dma: 9.15 (-20.32, 49.53) 6 dma: 7.91 (-20.70, 46.85) Subjects who report smoking in the



### December 2009 E-46

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) past (but not within 6 mo) Lag 0: 19.23 (-24.29, 87.77) 2 dma: 19.92 (-29.65,104.41) 3 dma: 29.54 (-17.24, 102.76) 4 dma: 41.98 (-6.95, 116.63) 5 dma: 44.05 (-1.23, 110.07) 6 dma: 50.39 (9.35, 106.82) Subjects who did not report smoking in the past Lag 0: -14.21 (-53.20, 57.24) 2 dma: -20.66 (-63.14, 70.77) 3 dma: -28.89 (-68.43, 60.19) 4 dma: -23.51 (-55.11, 30.34) 5 dma: -29.18 (-60.08, 25.66) 6 dma: -30.68 (-55.95, 9.08)

Reference: O'Neill et al. (2007, 091362 ) Period of Study: May 1998-Dec 2002

Location: Boston, MA Outcome: Soluble intercellular adhesion molecule 1 (ICAM-1)

Vascular cell adhesion molecule 1 (VCAM-1) von Willebrand factor (vWF) Age Groups: Mean (SD): 56.6 (10.6) Study Design: Cross-sectional

N: 92 participants (type 2 diabetic patients) Statistical Analyses: Linear regression

Covariates: Apparent temperature, season, age, race, sex, glycosylated hemoglobin, cholesterol, smoking history, BMI Dose-response Investigated? No Statistical Package: NR Pollutant: BC Averaging Time: 24 h (lagged ma of days 0 to 1, 2, 3, 4, and 5) Mean (SD): 1.1 (0.8) descriptive statistics represent entire study period

Percentiles: IQR range: 0.8 Range (Min, Max): 0.2, 5.8 Monitoring Stations: 1 site Copollutant: PM 2.5 BC SO 4 2– PM Increment: IQR (specific to lag period) Effect Estimate [Lower CI, Upper CI]: % change per IQR of BC

ICAM-1- - All subjects Lag 0: 5.09 (-2.37, 13.11) 2 dma: 3.97 (-10.24, 20.42) 3 dma: 5.10 (-10.17, 22.96) 4 dma: 8.38 (-6.46, 25.56) 5 dma: 10.09 (-7.36, 30.83) 6 dma: 10.58 (-5.34, 29.18) Subjects not known to be taking statins Lag 0: 5.77 (-3.92, 16.44) 2 dma: 2.39 (-7.65, 13.52) 3 dma: 0.84 (-8.16, 10.73) 4 dma: 1.67 (-6.71, 10.80) 5 dma: 1.55 (-6.46, 10.24) 6 dma: 2.20 (-6.47, 11.68) Subjects who report smoking in the past (but not within 6 mo) Lag 0: 5.84 (0.87, 11.05) 2 dma: 5.08 (-2.34, 13.07) 3 dma: 4.44 (-2.70, 12.11) 4 dma: 5.02 (-1.78, 12.29) 5 dma: 5.89 (-2.14, 14.58) 6 dma: 6.73 (-1.54, 15.70) Subjects who did not report smoking in the past Lag 0: 6.04 (0.87, 11.48) 2 dma: 6.54 (-1.64, 15.39) 3 dma: 5.86 (-1.90, 14.22) 4 dma: 6.11 (-1.18, 13.94) 5 dma: 6.89 (-1.42, 15.89) 6 dma: 7.86 (-1.35, 17.94)

VCAM-1 - All subjects Lag 0: 9.26 (2.98, 15.91) 2 dma: 10.18 (1.93, 19.10) 3 dma: 15.45 (2.70, 29.78) 4 dma: 17.97 (3.63, 34.30) 5 dma: 23.83 (8.41, 41.44) 6 dma: 27.51 (11.96, 45.21) Subjects not known to be taking statins Lag 0: 9.19 (3.23, 15.49) 2 dma: 14.64 (5.02, 25.14) 3 dma: 14.39 (5.30, 24.28) 4 dma: 14.19 (5.71, 23.36) 5 dma: 19.11 (9.44, 29.65) 6 dma: 22.60 (11.79, 34.45) Subjects who report smoking in the past (but not within 6 mo) Lag 0: 12.4 (2.77, 22.92) 2 dma: 28.5 (8.38, 52.24) 3 dma: 25.14 (3.50, 51.30) 4 dma: 23.1 (2.70, 47.58)



### December 2009 E-47

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 5 dma: 32.0 (7.29, 62.30) 6 dma: 31.8 (9.74, 58.26) Subjects who did not report smoking in the past Lag 0: 5.15 (-5.63, 17.17) 2 dma: 2.09 (-9.07 ,14.61) 3 dma: 3.90 (-6.38, 15.31) 4 dma: 4.92 (-4.63, 15.43) 5 dma: 7.89 (-1.31, 17.95) 6 dma: 10.97 (0.98, 21.96)

vWF- All subjects Lag 0: 7.96 (-4.34, 21.84) 2 dma: 14.87 (-2.85, 35.82) 3 dma: 15.34 (-3.22, 37.45) 4 dma: 15.47 (-7.60, 44.31) 5 dma: 19.50 (-8.89, 56.74) 6 dma: 20.53 (-9.80, 61.05) Subjects not known to be taking statins Lag 0: 3.23 (-8.91, 17.00) 2 dma: 9.82 (-8.39, 31.66) 3 dma: 17.79 (-16.03, 65.21) 4 dma: 13.14 (-18.71, 57.47) 5 dma: 16.14 (-20.43, 69.52) 6 dma: 13.25 (-22.09, 64.62) Subjects who report smoking in the past (but not within 6 mo) Lag 0: 7.63 (-17.01, 39.58) 2 dma: 37.64 (-7.18, 104.10) 3 dma: 75.41 (6.16, 189.85) 4 dma: 72.05 (-3.34, 206.22) 5 dma: 73.14 (6.94, 180.32) 6 dma: 71.23 (14.00, 157.19) Subjects who did not report smoking in the past Lag 0: 10.22 (-23.14, 58.04) 2 dma: 17.07 (-18.86, 68.91) 3 dma: 6.56 (-42.75, 98.36) 4 dma: -9.20 (-65.79, 140.99) 5 dma: -23.86 (-71.05, 100.29) 6 dma: -48.69 (-77.75, 18.29)

Reference: O'Neill et al. (2005, 088423 ) Period of Study: Baseline period: May 1998-Jan 2000 Time trial: 2000-2002

Location: Boston, MA Outcome: Changes in vascular reactivity, specifically percent change in brachial artery diameter (flow-mediated and nitroglycerin-mediated)

N: 270 patients with diabetes or at risk of diabetes, who participated in non-air pollution related studies at the Joselyn Diabetes Center in Boston Statistical Analysis: Linear regression Pollutant: PM 2.5 Mean (SD): 11.5 (6.4) Range: 1.1-40.0 Monitoring Stations: 1 Copollutant: Sulfates BC Ultrafine particle counts PM Increment: IQR (value not given) Percent change (95% CI): PM 2.5 6-day

ma Nitroglycerin-mediated reactivity: -7.6% (95% CI: 12.8% to -2.1%)

Notes: PM 2.5 was positively associated with nitroglycerin-mediated reactivity an association was also reported with ultrafine particles. Effect estimates were larger in type II than type I diabetes. BC and sulfate increases were associated with decreased flow-mediated reactivity among those with diabetes. Although the largest associations were with the 6-day ma, similar patterns and quantitatively similar results appear in the other lags.



### December 2009 E-48

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: O'Neill et al. (2007, 091362 ) Period of Study: May 1998-Dec 2002

Location: Boston, MA Outcome: soluble intercellular adhesion molecule 1 (ICAM-1)

vascular cell adhesion molecule 1 (VCAM-1) von Willebrand factor (vWF) Mean Age: 56.6 (10.6) Study Design: Cross-sectional

N: 92 participants (type 2 diabetic patients) Statistical Analyses: Linear regression

Covariates: Apparent temperature, season, age, race, sex, glycosylated hemoglobin, cholesterol, smoking history, BMI Dose-response Investigated? No Statistical Package: NR Pollutant: SO 4 2– Averaging Time: 24 h (lagged ma of days 0 to 1, 2, 3, 4, and 5) Mean (SD): 3.0 (2.0) descriptive statistics represent entire study period

Percentiles: IQR range: 2.2 Range (Min, Max): 0.5, 9.6) Monitoring Stations: 1 site Copollutant: PM 2.5 , BC, SO 4 2– PM Increment: IQR (specific to lag period) Effect Estimate [Lower CI, Upper CI]: % change per IQR of PM 2.5 ICAM-1 All subjects Lag 0: 5.30 (-2.60, 13.83) 2 dma: 4.02 (-3.26, 11.85) 3 dma: 4.03 (-5.34, 14.34) 4 dma: -0.79 (-7.30, 6.18) 5 dma: 1.06 (-7.10, 9.93) 6 dma: 3.15 (-5.66, 12.78) Subjects not known to be taking statins Lag 0: 10.14 (0.44, 20.77) 2 dma: 9.39 (-1.28, 21.20) 3 dma: 10.93 (-2.23, 25.85) 4 dma: -0.24 (-9.66, 10.16) 5 dma: 4.03 (-8.66, 18.47) 6 dma: 5.66 (-7.52, 20.72) Subjects who report smoking in the past (but not within 6 mo) Lag 0: -4.00 (-24.79, 22.52) 2 dma: -4.82 (-18.01, 10.48) 3 dma: -7.19 (-23.66, 12.83) 4 dma: -9.8 (-27.96, 12.97) 5 dma: -10.4 (-29.92, 14.44) 6 dma: -6.8 (-25.72, 17.03) Subjects who did not report smoking in the past Lag 0: 6.67 (-4.34, 18.94) 2 dma: 5.65 (-4.67, 17.10) 3 dma: 10.21 (-5.83, 28.99) 4 dma: 0.80 (-9.94, 12.83) 5 dma: 2.80 (-10.85, 18.54) 6 dma: 5.15 (-7.78, 19.89)

VCAM-1 All subjects Lag 0: -0.04 (-3.75, 3.80) 2 dma: 0.94 (-4.79, 7.01) 3 dma: -0.87 (-3.50, 1.82) 4 dma: 0.13 (-2.02, 2.34) 5 dma: -0.47 (-2.67, 1.78) 6 dma: -0.46 (-1.99, 1.09) Subjects not known to be taking statins Lag 0: -1.34 (-11.23, 9.66) 2 dma: -0.19 (-11.13, 12.09) 3 dma: -2.84 (-13.90, 9.64) 4 dma: 4.28 (-6.18, 15.90) 5 dma: -0.26 (-13.44, 14.93) 6 dma: -3.44 (-16.51, 11.67) Subjects who report smoking in the past (but not within 6 mo) Lag 0: 0.07 (-23.40, 30.73) 2 dma: -5.62 (-20.77, 12.43) 3 dma: -26.92 (-33.31 to -19.91) 4 dma: -3.06 (-28.01,30.56) 5 dma: -6.42 (-30.75, 26.47) 6 dma: -6.46 (-28.55, 22.47) Subjects who did not report smoking in the past Lag 0: -3.28 (-12.66, 7.12) 2 dma: -3.17 (-11.75, 6.23) 3 dma: -9.67 (-22.07, 4.70) 4 dma: -5.51 (-14.28, 4.15) 5 dma: -12.17 (-22.05 to -1.05) 6 dma: -11.77 (-20.95 to -1.52)

vWF (sulfate measures not available)



### December 2009 E-49

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Park et al. (2008, 156845 ) Period of Study: Jan 1995-Jun 2005

Location: Greater Boston area, MA Outcome: Total homocysteine (tHcy) Mean Age: 73.6 ± 6.9 yr Study Design: Cross-sectional and longitudinal analyses performed

N: 960 men Statistical Analyses: Generalizedadditive models (also hierarchical mixedeffects regression models to assess repeated measures of tHcy)

Covariates: Model 1: season, age, longterm trend, apparent temperature Model 2: further adjustment for BMI, systolic blood pressure, smoking status,pack yr of cigarettes, alcohol consumption Model 3: further adjustment for serum creatinine, plasma folate, vitamin B6, and vitamin B12 Dose-response Investigated? Modeled continuous covariates as penalized splines to determine if association with tHcy was linear Statistical Package: R software Pollutant: PM 2.5 Averaging Time: 24 h (ma up to 7 days prior to blood collection) Mean (SD): 12.0 (6.6)

Median: 10.6 Range (Min, Max): 2.0, 62.0 Monitoring Stations: 1 site Copollutant: PM 2.5 BC (r = 0.51) OC (r = 0.51) SO 4 2– (r = 0.85) PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: Estimated % change in tHcy per IQR increase in pollutant. Lag model Concurrent day. IQR: 7.66 Model 1: 1.32 (-0.83, 3.52) Model 2: 1.55 (-0.77, 3.91) Model 3: 1.57 (-0.38, 3.56) 1-day previous. IQR: 6.91 Model 1: -1.43 (-3.51, 0.69) Model 2: -1.41 (-3.53, 0.76) Model 3: -1.28 (-3.12, 0.60) 2-day ma. IQR: 6.47 Model 1: 0.04 (-2.13, 2.26) Model 2: -0.07 (-2.26, 2.17) Model 3: 0.25 (-1.69, 2.22) 3-day ma. IQR: 5.83 Model 1: -0.64 (-2.92, 1.69) Model 2: -0.74 (-3.04, 1.61) Model 3: -0.59 (-2.63, 1.49) 4-day ma. IQR: 5.21 Model 1: -0.63 (-2.94, 1.72) Model 2: -0.86 (-3.19, 1.52) Model 3: -0.73 (-2.78, 1.37) 5-day ma. IQR: 4.68 Model 1: -0.51 (-2.79, 1.83) Model 2: -0.82 (-3.13, 1.54) Model 3: -0.84 (-2.85, 1.22) 6-day ma. IQR: 4.50 Model 1: -0.91 (-3.32, 1.56) Model 2: -1.32 (-3.76, 1.17) Model 3: -1.44 (-3.58, 0.74) 7-day ma. IQR: 4.20 Model 1: -0.84 (-3.27, 1.64) Model 2: -1.19 (-3.64, 1.33) Model 3: -1.69 (-3.84, 0.51) Stratified analyses: No significant difference in effect of PM 2.5 among those with high and low levels of vitamins



### December 2009 E-50

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Park et al. (2008, 156845 ) Period of Study: Jan 1995-Jun 2005

Location: Greater Boston area, MA Outcome: Total homocysteine (tHcy) Mean Age: 73.6 ± 6.9 yr Study Design: cross-sectional and longitudinal analyses performed

N: 960 men Statistical Analyses: Generalizedadditive models (also hierarchical mixedeffects regression models to assess repeated measures of tHcy)

Covariates: Model 1: season, age, longterm trend, apparent temperature Model 2: further adjustment for BMI, systolic blood pressure, smoking status, pack yr of cigarettes, alcohol consumption Model 3: further adjustment for serum creatinine, plasma folate, vitamin B6, and vitamin B12 Dose-response Investigated? Modeled continuous covariates as penalized splines to determine if association with tHcy was linear Statistical Package: R software Pollutant: BC Averaging Time: 24 h (ma up to 7 days prior to blood collection) Mean (SD): 0.99 (0.56)

Median: 0.87 Range (Min, Max): 0.07, 3.7 Monitoring Stations: 1 site Copollutant (correlation): PM 2.5 (r = 0.51) BC OC (r = 0.0.51) SO 4 2– (r = 0.50) PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: Estimated % change in tHcy per IQR increase in pollutant. Lag model Concurrent day. IQR: 0.66 Model 1: 2.64 (-0.12, 5.48) Model 2: 2.62 (-0.17, 5.48) Model 3: 3.13 (0.76, 5.55) 1-day previous. IQR: 0.66 Model 1: 1.46 (-0.98, 3.96) Model 2: 1.32 (-1.14, 3.85) Model 3: 0.95 (-1.12, 3.05) 2-day ma. IQR: 0.60 Model 1: 2.75 (-0.18, 5.76) Model 2: 2.63 (-0.33, 5.67) Model 3: 2.59 (0.10, 5.14) 3-day ma. IQR: 0.57 Model 1: 2.95 (-0.44, 6.46) Model 2: 2.97 (-0.46, 6.51) Model 3: 3.12 (0.21, 6.11) 4-day ma. IQR: 0.52 Model 1: 3.94 (0.24, 7.78) Model 2: 3.76 (0.02, 7.64) Model 3: 3.00 (-0.13, 6.22) 5-day ma. IQR: 0.49 Model 1: 3.26 (-0.60, 7.27) Model 2: 2.64 (-1.23, 6.67) Model 3: 2.38 (-0.89, 5.77) 6-day ma IQR: 0.44 Model 1: 1.63 (-1.99, 5.38) Model 2: 1.03 (-2.62, 4.80) Model 3: 0.93 (-2.15, 4.11) 7-day ma. IQR: 0.44 Model 1: 1.38 (-2.45, 5.36) Model 2: 0.69 (-3.16, 4.70) Model 3: 0.45 (-2.81, 3.83) % change in tHcy per IQR increase in BC, 24-h avg Among those with low folate: 5.31 (2.26, 8.42) Among those with low B12: 5.06 (2.03, 8.17) nearly null associations among those with high levels



### December 2009 E-51

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Park et al. (2008, 156845 ) Period of Study: Jan 1995-Jun 2005

Location: Greater Boston area, MA Outcome: Total homocysteine (tHcy) Mean Age: 73.6 ± 6.9 yr Study Design: Cross-sectional and longitudinal analyses performed

N: 960 men Statistical Analyses: Generalizedadditive models (also hierarchical mixedeffects regression models to assess repeated measures of tHcy)

Covariates: Model 1: season, age, longterm trend, apparent temperatureModel 2: further adjustment for BMI, systolic blood pressure, smoking status,pack yr of cigarettes, alcohol consumption Model 3: further adjustment for serum creatinine, plasma folate, vitamin B6, and vitamin B12 Dose-response Investigated? Modeled continuous covariates as penalized splines to determine if association with tHcy was linear Statistical Package: R software Pollutant: OC Averaging Time: 24 h (ma up to 7 days prior to blood collection) Mean (SD): 3.5 (1.8)

Median: 3.1 Range (Min, Max): 0.29, 11.8 Monitoring Stations: 1 site Copollutant (correlation): PM 2.5 (r = 0.51) BC (r = 0.51) OC SO 4 2– (r = 0.41) PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: Estimated % change in tHcy per IQR increase in pollutant. Lag model Concurrent day. IQR: NA Model 1: NA Model 2: NA Model 3: NA 1-day previous. IQR: 2.00 Model 1: 2.12 (-0.98, 5.31) Model 2: 1.69 (-1.51, 5.00) Model 3: 1.87 (-0.81, 4.62) 2-day ma. IQR: 1.93 Model 1: -0.39 (-3.67, 3.01) Model 2: -0.88 (-4.26, 2.61) Model 3: 1.05 (-1.86, 4.06) 3-day ma. IQR: 1.68 Model 1: 0.53 (-2.66, 3.83) Model 2: 0.14 (-3.15, 3.54) Model 3: 1.32 (-1.44, 4.16) 4-day ma. IQR: 1.64 Model 1: 1.57 (-1.89, 5.15) Model 2: 1.42 (-2.14, 5.12) Model 3: 1.89 (-1.15, 5.03) 5-day ma, IQR: 1.60 Model 1: 2.27 (-1.49, 6.16) Model 2: 2.11 (-1.77, 6.15) Model 3: 2.12 (-1.29, 5.65) 6-day ma. IQR: 1.43 Model 1: 2.83 (-0.74, 6.52) Model 2: 2.78 (-0.90, 6.60) Model 3: 2.53 (-0.59, 5.74) 7-day ma. IQR: 1.23 Model 1: 2.75 (-0.41, 6.02) Model 2: 2.55 (-0.71, 5.92) Model 3: 2.55 (-0.21, 5.39) % change in tHcy per IQR increase in OC, 7-day avg. Among those with low B12: 5.23 (1.59, 9.01) Nearly null associations among those with high levels



### December 2009 E-52

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Park et al. (2005, 057331 ) Period of Study: Nov 2000-Oct 2003

Location: Greater Boston area, MA Outcome: Change in HRV (SDNN, HF, LF, LFHFR) Mean age: 72.7 yr Study Design: Cross-sectional

N: 497 adult males living in the Greater Boston, MA area Pollutant: PM 2.5 Averaging Time: 4 h 24 h 48 h Mean (SD): 11.4 (8.0) Range: 6.45-62.9 Copollutant: O 3 , Particle number count, BC, NO 2 , SO 2 , CO PM Increment: 8 μ g/m 3 Percent change (95% CI): 48h mean PM 2.5 : 20.8% decrease in HF (95% CI: 4.6%, 34.2%) 18.6% increase in LFHFR (4.1%, 35.2%).

Notes: Subjects were monitored during a 4-min rest period between 8 a.m. and 1 p.m. Modifying effects of hypertension,IHD, diabetes, and use of cardiac/antihypertensive medications also examined. Linear regression analyses. This subject group is from the VA Normative Aging Study. The 4-h averaging period was most strongly associated with HRV indices. The PM effect was robust in models including O 3

. The HRV change per IQR increase in PM 2.5 were larger in subjects with hypertension (n = 335) IHD (n = 142), and diabetes (n = 72). In addition, those who did not use calcium-channel blockers had a greater decline in LF associated with each IQR increase in PM 2.5 than did those who did use calcium channel blockers. IQR increases in 48h mean BC concentration were also associated with adverse changes in HRV, suggesting traffic pollution may be particularly toxic.

Reference: Park et al. (2006, 091245 ) Period of Study: Nov 2000-Dec 2004

Location: Greater Boston area, MA Outcome: Change in HF Study Design: Cross-sectional N: Statistical Analysis: Linear regression models Pollutant: PM 2.5 Averaging Time: 48 h Mean (SD): PM 2.5 : 11.7 (7.8) Sulfates: 3.3 (3.3) BC: 0.92 (0.46) Copollutant: O 3 PM Increment: 10 μ g/m 3 Percent change (95% CI): Wild-type HFE genotype: 31.7% (95% CI: 10.3, 48.1) Among those with either of the 2 HFE variants, there was no association between 48h PM 2.5 and HF (shown in a graph, ~10% non-significant increase).

Notes: Normative Aging Study. Examining association between PM and HF among those with and without the wild-type HFE genotype.

Reference: Pekkanen et al. (2002, 035050 ) Period of Study: Winter 1998-1999

Location: Helsinki, Finland Outcome : ST-Segment Depression (>0.1mV) Study Design : Panel of ULTRA Study participants

N : 45 Subjects, n = 342 biweekly submaximal exercise tests, 72 exercise induced ST Segment Depressions Statistical Analysis: Logistic regression / GAM Pollutant: PM 2.5 Averaging Time: 24 h Median: 10.6 IQR: 7.9

Pollutant: PM1 Median: 7.0 IQR: 5.6

Pollutant: ACP (100 to 1000nm) (n/cm 3 ) Median: 1200 IQR: 760 Copollutant: NO 2 , CO, PM 10-2.5 , ultrafine PM Increment: IQR Effect Estimate(s): ACP: OR = 3.29 (1.57, 6.92), lag 2

PM 1 : OR = 4.56 (1.73, 12.03), lag 2 PM 2.5 : OR = 2.84 (1.42, 5.66), lag 2

Notes : The effect was strongest for ACP and PM 2.5 , which in 2 pollutant models appeared independent. Increases in NO 2 and CO were also associated with increased risk of ST-segment depression, but not with coarse particles.



### December 2009 E-53

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Park et al. (2008, 156845 ) Period of Study: Jan 1995-Jun 2005

Location: Greater Boston area, MA Outcome: Total homocysteine (tHcy) Mean Age: 73.6 ± 6.9 yr Study Design: Cross-sectional and longitudinal analyses performed

N: 960 men Statistical Analyses: Generalizedadditive models (also hierarchical mixedeffects regression models to assess repeated measures of tHcy)

Covariates: Model 1: season, age, longterm trend, apparent temperature Model 2: further adjustment for BMI, systolic blood pressure, smoking status,pack yr of cigarettes, alcohol consumption Model 3: further adjustment for serum creatinine, plasma folate, vitamin B6, and vitamin B12 Dose-response Investigated? Modeled continuous covariates as penalized splines to determine if association with tHcy was linear Statistical Package: R software Pollutant: SO 4 2– Averaging Time: 24 h (ma up to 7 days prior to blood collection) Mean (SD): 3.2 (3.0)

Median: 2.4 Range (Min, Max): 0.39, 29.0 Monitoring Stations: 1 site Copollutant (correlation): PM 2.5 (r = 0.85) BC (r = 0.50) OC (r = 0.41) SO 4 2– PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: Estimated % change in tHcy per IQR increase in pollutant. Lag model Concurrent day: IQR: NA Model 1: NA Model 2: NA Model 3: NA 1-day previous: IQR: 2.61 Model 1: 0.91 (-0.77, 2.62) Model 2: 0.99 (-0.94, 2.95) Model 3: 0.91 (-0.72, 2.57) 2-day ma: IQR: 2.10 Model 1: -0.25 (-2.07, 1.60) Model 2: -0.29 (-2.35, 1.82) Model 3: 0.05 (-1.74, 1.86) 3-day ma: IQR: 1.73 Model 1: -0.15 (-1.97, 1.69) Model 2: -0.17 (-2.23, 1.93) Model 3: -0.01 (-1.78, 1.80) 4-day ma: IQR: 1.64 Model 1: -0.69 (-2.74, 1.41) Model 2: -0.60 (-2.95, 1.81) Model 3: -0.58 (-2.63, 1.51) 5-day ma: IQR: 1.60 Model 1: -1.14 (-3.53, 1.30) Model 2: -0.90 (-3.64, 1.92) Model 3: -1.09 (-3.48, 1.36) 6-day ma; ’ IQR: 1.40 Model 1: 0.00 (-2.39, 2.44) Model 2: 0.36 (-2.36, 3.16) Model 3: 0.41 (-2.01, 2.89) 7-day ma IQR: 1.30 Model 1: -0.16 (-2.51, 2.24) Model 2: 0.30 (-2.37, 3.04) Model 3: 0.07 (-2.25, 2.43) Stratified analyses: No significant difference in effect of SO 4 2– among those with high and low levels of vitamins

Reference: Peters et al. (2005, 095747 ) Also Peters et al. (2005, 156859 ) Period of Study: Feb 1999-Jul 2001

Location: Augsburg, Germany Outcome: Myocardial infarction Study Design: Case-crossover

N: 691 myocardial infarction patients Statistical Analysis: Conditional logistic regression Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: 1 h: Median = 14.5 IQR: 9.1 24-h: Median = 14.9 IQR: 7.7 Copollutant: NO 2 , SO 2 , CO Effect Estimate: 2-h lag: OR = 0.93 95% CI: 0,83, 1.04 24-h mean, 2-day lag: OR = 1.18 95% CI: 1.03, 1.34

Notes: Examined triggering for MI at various lags before MI onset (up to 6 h before MI, up to 5 days before MI). PM 2.5 levels 2 days before MI onset were associated with increased risk of MI, but not on the concurrent day, or lags 1, 3, 4, or 5. These findings are consistent with the prior Boston MI study for a 1- to 2-day lagged effect of PM 2.5

.



### December 2009 E-54

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Pope et al. (2004, 055238 ) Period of Study: Winter 1999-2000 (in Wasatch Front, UT). Summer 2000 (in Hawthorne, UT). Winter 2000-2001 (in Bountiful, UT and Lindon, UT)

Location: Utah: Wasatch Front, Hawthorne, Bountiful, and Lindon Outcome: Change in autonomic function (measured by changes in HRV), C-reactive protein (CRP), blood cell counts, platelets, and blood viscosity associated with short-term changes in PM 2.5 Age Groups: Elderly (specific age range not given) Study Design: Panel study

N: 88 elderly subjects Statistical Analysis: Linear regression

Season: Winter, summer Dose-response Investigated? No Pollutant: PM 2.5 (TEOM) Averaging Time: 24 h Mean (SD): 18.9 (13.4) Copollutant: None PM Increment: 100 μg/m 3

Effect Estimate: Each 100 μ g/m 3 increase associated with: -35 (SE = 8) msec decline in SDNN 0.81 (SE 0.17) mg/dL increase in CRP 0.31 (SE 9.34) k/μL increase in platelets 0.07 (SE 0.21) cP increase in blood viscosity

Notes: The study observed small but statistically significant adverse associations between daily mean PM 2.5 and HRV and C-reactive protein (CRP). The authors point out, however, that most of the variability in the temporal deviation of these physiological endpoints was not explained by PM 2.5

. These observations therefore suggest that PM 2.5 may be 1 of multiple factors that influence HRV and CRP.

Reference: Pope et al. (2006, 091246 ) Period of Study: 1994-2004

Location: Wasatch Front, Utah Outcome: Acute ischemic heart disease Study Design: Case-crossover study (time-stratified control selection) N: Statistical Analysis: Conditional logistic regression Pollutant: PM 2.5 (FRM) Averaging Time: 24 h Mean (SD): Site 1: 10.1 Site 2: 10.8 Site 3: 11.3 Monitoring Stations: 3 Copollutant: PM 10 (FRM) measured at 4 monitoring sites PM Increment: 10 μg/m 3

Effect Estimate: For same-day increase in PM 2.5 : OR = 1.045 95% CI: 1.011, 1.080

Notes: Case-crossover study (timestratified control selection) triggering of acute ischemic heart disease by ambient PM 2.5 concentrations on the same and previous 3 days. PM 2.5 measured at 3 sites and estimated for missing days. Effect estimates were larger for those with angiographically demonstrated coronary artery disease.

Reference: Pope et al. (2004, 055238 ) Period of Study: 1999-2001

Location: Wasatch Front, Utah Outcome: Heart rate variability (HRV) C-reactive protein (CRP) Blood cell counts, whole blood viscosity Age Groups: 54-89 yr Study Design: Panel study

N: 88 participants Statistical Analyses: Linear regression

Covariates: Subject-specific fixed effects Interactive spline smooths for temp, RH (partial control for H)

Season: Temperature as covariate Dose-response Investigated? Yes, also assessed PM by including cubic smoothing splines with 3 df Statistical Package: SAS Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 23.7 (20.2) Range (Min, Max): 1.7, 74.0 Monitoring Stations: NR Copollutant: None PM Increment: 100 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Regression coefficients (SE) for associations with concurrent day pollutant: Mean H: -4.49 (1.73) SDNN: -34.94 (8.32) SDANN: -18.98 (8.67) r-MSSD: -42.25 (10.90) CRP: 0.81 (0.18) Whole blood viscosity: 0.07 (0.21) WBC: -0.07 (0.38) Granulocytes: 0.02 (0.37) Lymphocytes: -0.07 (0.14) Monocytes: 0.12 (0.04) Basophils: -0.01 (0.01) Eosinophils: -0.01 (0.02) RBC: 0.03 (0.06) Platelets: 0.31 (9.34)

Reference: Rich et al. (2005, 079620 ) Period of Study: Jul 1995-Jul 2002

Location: Eastern Massachusetts, USA Outcome: Confirmed ventricular arrhythmias Study Design: Case-crossover (timestratified control selection)

N: 203 patients with implantable cardioverter defibrillators Statistical Analysis: Conditional logistic regression Pollutant: PM 2.5 (TEOM) Averaging Time: 1-h avg 24-h avg Median (IQR): 1-h avg: Median = 9.2 μg/m 3 24-h avg: Median = 9.8 μg/m 3 IQr = 7.8 Copollutant: O 3 , BC, CO, NO 2 , SO 2 PM Increment: 7.8 μg/m 3

Effect Estimate: For mean PM 2.5 in the 24 h before ventricular arrhythmia: OR = 1.19 95% CI: 1.02, 1.38

Notes: 794 ventricular arrhythmias among 84 subjects. Lag h: 0-2, 0-6, 0-23, 0-47



### December 2009 E-55

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Rich et al. (2006, 088427 ) Period of Study: Jul 1995-Jul 2002

Location: Eastern Massachusetts, USA Outcome: Confirmed episodes of paroxysmal atrial fibrillation Study Design: Case-crossover (timestratified control selection)

N: 203 patients with implantable cardioverter defibrillators Statistical Analysis: Conditional logistic regression Pollutant: PM 2.5 (TEOM) Averaging Time: 1-h avg 24-h avg Median (IQR): 1-h avg: Median = 9.2 μg/m 3 24-h avg: Median = 9.8 μg/m 3 IQr = 7.8 Copollutant: O 3 , BC, CO, NO 2 , SO 2 PM Increment: 9.4 μg/m 3

Effect Estimate: 0-h lag: OR 1.41 (0.82, 2.42)

Notes: 91 paroxysmal atrial fibrillation (PAF) episodes among 29 subjects. Lag h: 0, 0-23 Positive, but not significant increases in the relative odds of PAF associated with PM 2.5 concentrations in the same h and 24-h before PAF episode onset. Authors note reduced statistical power for PM 2.5 analyses due to missing data.

Reference: Rich et al. (2006, 088427 ) Period of Study: Jul 1995-Jul 2002

Location: Eastern Massachusetts, USA Outcome: Confirmed episodes of paroxysmal atrial fibrillation Study Design: Case-crossover (timestratified control selection)

N: 203 patients with implantable cardioverter defibrillators Statistical Analysis: Conditional logistic regression Pollutant: BC Averaging Time: 1-h avg, 24-h avg Median (IQR): IQR: 0.91μg/m 3 Copollutant: O 3 , PM 2.5 , CO, NO 2 , SO 2 PM Increment: 0.91μg/m 3 (IQR)

Effect Estimate: 0- to 23-h lag period: OR 1.46 (95% CI: 0.67, 3.17)

Notes: 91 paroxysmal atrial fibrillation (PAF) episodes among 29 subjects. Lag h: 0, 0-23 Positive, but not significant increases in the relative odds of PAF associated with BC concentrations in the same h and 24 h before PAF episode onset. Authors note reduced statistical power for BC analyses due to missing data.

Reference: Rich et al. (2006, 089814 ) Period of Study: May 2001-Dec 2002

Location: St. Louis, MO metropolitan

area Outcome: Confirmed ventricular arrhythmia Study Design: Case-crossover design (time-stratified control selection) Dose-response Investigated? No Pollutant: PM 2.5 (CAMM) Averaging Time: 24 h Median (IQR): 16.2 μg/m 3 (IQr = 9.7) Copollutant: NO 2 , SO 2 , CO, O 3 , EC, OC PM Increment: 9.7 μg/m 3 (IQR)

Effect Estimate: OR (PM 2.5 ) = 0.95 (95% CI: 0.72, 1.27) OR (SO 2 ) = OR = 1.24 (95% CI: 1.07, 1.44)

Notes: 139 confirmed ventricular arrhythmia episodes among 56 subjects. Lags: 0-2h, 0-6h, 0-11h, 0-23h, 0-47h

Authors did not find increased relative odds of VA associated with each IQR increase in 24-h mean PM 2.5 , but did find non-significantly increased relative odds of VA associated with 24-h EC. Shorter and longer lag times’ relative odds estimates provided no evidence of immediate ventricular arrhythmic effects of air pollution.

Reference: Rich et al. (2004, 055631 ) Period of Study: Feb-Dec 2000

Location: Vancouver, British Columbia, Canada Outcome: ICD discharges (as a proxy for VT/VF) Age Groups: 15-85 yr Study Design: Case-crossover design (ambidirectional control selection ± 7 days)

N: 34 patients with implantable cardioverter defibrillators Statistical Analysis: Conditional logistic regression Dose-response Investigated? No Pollutant: PM 2.5 (Partisol) Averaging Time: 1 h Mean (SD), IQR: Mean: : 8.2 μg/m 3 (SD = 10.7)

IQr = 5.2 Copollutant: O 3 , EC, OC, SO 4 2– , CO, NO 2 , SO 2 , PM 10 PM 10 : Mean: : 13.3 μg/m 3 (SD = 4.9) IQr = 7.4 PM Increment: Effect Estimate: Odds ratios were less than 1.0 at all lags (0, 1, 2, 3) for PM 2.5

. No consistent association between any of the air pollutants and implantable cardioverter defibrillators discharges.

Notes: Same study as Vedal et al. (2004, 055630 ), except Rich (2004) used data from a shorter time period so as to estimate relative odds of ICD discharge associated with acute increases in more pollutants than Vedal (2004, 055630 ).



### December 2009 E-56

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Rich et al. (2008, 156910 ) Period of Study: NR

Location: New Jersey Outcome: Pulmonary Artery and Right Ventricular Pressures Age Groups: 25-68 Study Design: Panel

N: 11 subjects Statistical Analyses: Repeated Measures

Covariates: Long-term trends, calendar month, weekday, apparent temperature Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-6d Pollutant: PM 2.5 Averaging Time : 24 h Mean (SD): NR Monitoring Stations: NR Copollutant: NR Co-pollutant Correlation: N/A PM Increment: 11.62μg/m 3 Change (Lower CI, Upper CI), p-value: ePAD: 0.19 (0.05, 0.33), 0.01 RV diastolic pressure: 0.23 (0.11, 0.34), <0.001 RV systolic pressure: 0.12 (-0.07, 0.31), 0.23 MPAP: 0.12 (-0.05, 0.28), 0.16/

Reference: Riediker et al. (2004, 091261 ) Period of Study: Fall 2001

Location: Wake County, North Carolina Outcome: Heart rate variability (measured 10 h after shift): mean cycle length of normal R-R intervals (MCL), the standard deviation of normal R-R intervals (SDNN), and percentage of normal R-R interval differences greater than 50 msec (PNN50), low frequency (0.04-0.15Hz), high frequency (0.15- 0.40Hz), the ratio of low to high frequency. Blood analysis (me asured 15 h after shift) : Uric acid, blood urea nitrogen, gamma glutamyl transpeptidase, white blood cell count, red blood cell count, hematocrit, hemoglobin, mean red blood cell volume (MCV), neutronphils (countand %), lymphocytes (count and %), Creactive protein, plasminogen, plasminogen activator inhibitor type 1,von Willebrand factor (vWF), endovthzelin-1, protein C, and interleukin-6 Age Groups: 23-30 yr Study Design: Panel

N: 9 healthy male troopers, repeated measures (36 person-days) Statistical Analyses: Mixed effects regression models (principal factor analysis for classification of exposure)

Covariates: Potential confounders: temperature, relative humidity, number of law-enforcement activities during the shift and the avg speed during the shiftControlling had no effect on effect estimates for “crustal” and “speed-change” factors However, confounder inclusion in the “speed change” and blood urea nitrogen and vWF reduced the effect estimate and the CI included zero

Season: Only 1 season included Dose-response Investigated? No Statistical Package: S-Plus 6.1 Pollutant: In-vehicle PM 2.5 components identified with factor analysis (crustal material, wear of steel automotive components, gasoline combustion, speed-changing traffic with engine emissions and brake wear Averaging Time: Exposure assessed during 3 p.m. to 12 a.m. work shifts

Mean: PM 2.5 mass = 23.0 μg/m 3 Monitoring Stations: Per vehicle Copollutant (correlation): Correlation to PM 2.5 Mass Benzene: r = 0.50 Aldehydes: r = 0.34 CO: r = 0.52 Aluminum: r = 0.58 Silicon: r = 0.66 Sulfur: r = 0.58 Calcium: r = 0.37 Titanium: r = 0.41 Chromium: r = 0.51 Iron: r = 0.71 Copper: r = 0.16 Selenium: r = 0.38 Tungsten: r = 0.37 PM2.Lightscatter: r = 0.71 PM Increment: 1 SD change in source factor

Effect Estimate: % change in the health outcome per 1 SD change in the “speed change” factor

MCL: 7% HRV: 16% supraventricular ectopic beats: 39% % Neutrophils: 7% % lymphocytes: -10% red blood cell volume MCV: 1% vWF: 9% blood urea nitrogen: 7% protein C: -11% % change in the health outcome per 1 SD change in the “crustal” factor MCL: 3% serum uric acid concentrations: 5%

Note: Results (including CIs) are reported in figures 2 & 3.



### December 2009 E-57

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Riojas-Rodriguez et al. (2006, 156913 ) Period of Study: Dec 2001-Apr 2002

Location: Mexico City metropolitan area Outcome: Heart rate variability (5- minute periods) Study Design: Panel study

N: 30 patients from the outpatient clinic of the National Institute of Cardiology of Mexico, where each subject had existing ischemic heart disease. Statistical Analysis: Mixed models Pollutant: PM 2.5 (nephelometry) Averaging Time: 5 min Mean (SD), Range: 46.8 μg/m 3 (SD = 1.82) Range: 0-483 μg/m 3 Copollutant: CO PM Increment: 10 μg/m 3

Effect Estimate: Each 20 μg/m 3 increase in 5 min PM 2.5 was associated with a: -0.008 decrease in the ln(HF)(95% CI: -0.015, 0.0004

Notes: Population of subjects with known ischemic heart disease (25 men and 5 women who had at least 1 prior MI [not in last 6 mo]) Each 10 μg/m 3 increase in 5-min mean PM 2.5 was associated with nonsignificantly decreased HF, and with similar, but smaller changes in LF and VLF.

Reference: Romieu et al. (2005, 086297 ) Period of Study: 2000-2001

Location: Mexico City, Mexico Outcome: Heart rate variability (HF, LF, VLF, PNN50, SDNN, r-MSSD) Age Groups: >60 yr of age Study Design: Double blind randomized controlled trial

N: 50 elderly residents of a Mexico City nursing home Pollutant: PM 2.5 Averaging Time: 24 h Copollutant: O 3 , NO 2 , SO 2 , PM 10 PM Increment: 8 μg/m 3

Effect Estimate: In the group receiving the fish oil supplement, each 8 μg/m 3 change in 24-h mean total exposure PM 2.5 was associated with a: a) 54% reduction (95% CI: -72% to -24%) in HF(log transformed) in the presupplementation phase b) 7% reduction (95% CI: -20%, 7%) in the supplementation phase. Changes in other HRV parameters were also smaller in the supplementation phase. In the group receiving soy oil supplementation, the % reduction in HF was also smaller in the supplementation phase, but the differences were smaller and not statistically significant.

Notes: Study of the effect of omega-3- fatty acid supplementation (2 g/day of fish oil vs.. 2 g/day of soy oil) to mitigate the effect of ambient PM 2.5 on HRV. Subjects had no cardiac arrhythmias,cardiac pacemakers, allergies to omega3 fatty acids or fish, treatment with oral anticoagulants, or history of bleeding diathesis. PM 2.5 was measured and estimated indoors, outdoors, and with regards to total exposure (the same as Holguin et al. (2003)).



### December 2009 E-58

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Romieu et al. (2008, 156922 ) Period of Study: Sep 2001-Apr 2002

Location: Mexico City, Mexico Outcome: Copper/zinc superoxide dismutase activity (Cu/Zn SOD) Lipoperoxidation (LPO) Reduced glutathione (GSH) Age Groups: 60-96 yr Study Design: Intervention (randomly assigned fish oil or soy oil)

N: 52 participants Statistical Analyses: Linear mixed models

Covariates: Time Dose-response Investigated? Assessed possible nonlinearity using generalized additive mixed models with p-splines Statistical Package: STATA v8.2 and SAS v9.1 Pollutant: PM 2.5 (indoor) Averaging Time: 24 h (same day) Mean (SD): 38.7 (14.7)

Percentiles: 25th: 30.62 50th: 35.11 75th: 41.10 Range (Min, Max): 14.8, 70.9 Monitoring Stations: Indoor measured inside nursing home Copollutant: O 3 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Regression coefficient (SE p-value): Cu/Zn SOD: -0.05 (0.02 0.001) LPO (square root transformed): 0.08 (0.09 0.381) GSH (log-transformed quadratic term for PM): -0.05 (0.01 0.002) Regression coefficient (SE p-value) by supplementation groups (same transformations as above): Cu/Zn SOD Soy Oil: -0.06 (0.02, <0.001) Fish Oil: * 0.04 (0.02, 0.009)

LPO Soy Oil: -0.02 (0.14, 0.904) Fish Oil: * 0.16 (0.07, 0.024)

GSH Soy Oil: -0.03 (0.04, 0.406) Fish Oil: -0.09 (0.04, 0.017)

*Quadratic term for PM

Reference: Ruckerl et al. (2007, 156931 ) Period of Study: May 2003-Jul 2004

Location: Athens, Augsburg, Barcelona, Helsinki, Rome, and Stockholm Outcome: Interleukin-6 (IL-6), fibrinogen, C-reactive protein (CRP) Age Groups: 35-80 yr Study Design: Repeated measures / longitudinal

N: 1003 MI survivors Statistical Analyses: Mixed-effect models

Covariates: City-specific confounders (age, sex, BMI) Long-term time trend and apparent temperature RH, time of day, day of week included if adjustment improved model fit

Season: Long-term time trend Dose-response Investigated? Used psplines to allow for nonparametric exposure-response functions Statistical Package: SAS v9.1 Pollutant: PM 2.5 Averaging Time: Hourly and 24-h (lag 0-4, mean of lags 0-4, mean of lags 0-1, mean of lags 2-3, means of lags 0-3) Mean (SD): Presented by city only Monitoring Stations: Central monitoring sites in each city Copollutant: SO 2 O 3 NO NO 2 PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: % change in mean blood markers per increase in IQR of air pollutant.

IL-6 Lag (IQR): % change in GM (95%CI) Lag 0 (11.0): 0.46 (-0.89, 1.83) Lag 1 (11.0): -0.39 (-1.69, 0.93) Lag 2 (11.0): -0.23 (-1.53, 1.07) 5-day avg (8.6): 0.05 (-1.37, 1.50) Fibrinogen Lag (IQR): % change in AM (95%CI) Lag 0 (11.0): 0.05 (-0.48, 0.58) Lag 1 (11.0): 0.17 (-0.35, 0.69) Lag 2 (11.0): 0.20 (-0.32, 0.71) 5-day avg (8.6): 0.38 (-0.21, 0.96)

CRP Lag (IQR): % change in GM (95%CI) Lag 0 (11.0): 0.11 (-1.95, 2.21) Lag 1 (11.0): -0.06 (-1.98, 1.90) Lag 2 (11.0): 0.11 (-1.80, 2.06) 5-day avg (8.6): -0.13 (-2.15, 1.92)



### December 2009 E-59

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ruckerl et al. (2006, 088754 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome: C-reactive protein (CRP) serum amyloid A (SAA) E-selectin von Willebrand Factor (vWF)intercellular adhesion molecule-1 (ICAM1) fibrinogen Factor VII prothrombin fragment 1+2 D-dimer Age Groups: 50+ Study Design: Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear and logistic regression models

Covariates: Models adjusted for different factors based on health endpoint CRP: RH, temperature, trend, ID ICAM-1: temperature, trend, ID vWF: air pressure, RH, temperature, trend, ID FVII: air pressure, RH, temperature, trend, ID, weekday

Season: Time trend as covariate Dose-response Investigated? Sensitivity analyses examined nonlinear exposure-response functions Statistical Package: SAS v8.2 and SPlus v6.0 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 20.0 (15.0)

Percentiles: 25th: 9.7 50th: 14.9 75th: 26.1 Range (Min, Max): 2.6, 83.7 Monitoring Stations: 1 site Copollutant: UFPs AP PM 2.5 PM 10 OC EC NO 2 CO PM Increment: IQR (16.4 5-day avg: 12.2) Effect Estimate [Lower CI, Upper CI]: Effects of air pollution on blood markers presented as OR (95%CI) for an increase in the blood marker above the 90th percentile per increase in IQR air pollutant.

CRP Time before draw: 0 to 23 h: 1.1 (0.7, 1.8) 24-47 h: 1.5 (0.9, 2.5) 48-71 h: 1.2 (0.8, 1.9) 5-day mean: 1.4 (0.9, 2.3)

ICAM-1 Time before draw: 0-23 h: 0.7 (0.4, 0.9) 24-47 h: 1.3 (0.8, 1.8) 48-71 h: 1.8 (1.2, 2.7) 5-day mean: 1.1 (0.8, 1.5) Effects of air pollution on blood markers presented as % change from the mean/GM in the blood marker per increase in IQR air pollutant.

vWF Time before draw: 0-23 h: 3.9 (-0.3, 8.1) 24-47 h: 3.1 (-1.6, 7.8) 48-71 h: 3.6 (-1.1, 8.3) 5-day mean: 5.6 (0.5, 10.8)

FVII Time before draw: 0-23 h: -2.5 (-6.2 to 1.4) 24-47 h: -2.8 (-6.1 to 0.6) 48-71 h: -2.3 (-5.0 to 0.6) 5-day mean: -3.5 (-6.4 to -0.4)

Note: Summary of results presented in figures. SAA results indicate increase in association with PM (not as strong and consistent as with CRP)

No association observed between Eselectin and PM An increase in prothrombin fragment 1+2 was consistently observed, particularly with lag 4 Fibrinogen results revealed few significant associations, potentially due to chance

D-dimer results revealed null associations in linear and logistic analyses



### December 2009 E-60

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ruckerl et al. (2006, 088754 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome: C-reactive protein (CRP) serum amyloid A (SAA) E-selectin von Willebrand Factor (vWF) intercellular adhesion molecule-1 (ICAM-1) fibrinogen Factor VII prothrombin fragment 1+2 D-dimer Age Groups: 50+ yr Study Design: Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear and logistic regression models

Covariates: Models adjusted for different factors based on health endpoint CRP: RH, temperature, trend, ID ICAM-1: temperature, trend, ID vWF: air pressure, RH, temperature, trend, ID FVII: air pressure, RH, temperature, trend, ID, weekday

Season: Time trend as covariate Dose-response Investigated? Sensitivity analyses examined nonlinear exposure-response functions Statistical Package: SAS v8.2 and SPlus v6.0 Pollutant: EC Averaging Time: 24 h Mean (SD): 2.6 (2.4)

Percentiles: 25th: 1.0 50th: 1.8 75th: 3.2 Range (Min, Max): 0.2, 12.4 Monitoring Stations: 1 site Copollutant: UFPs AP PM 2.5 PM 10 OC EC NO 2 CO PM Increment: IQR (2.3 5-day avg: 1.8) Effect Estimate [Lower CI, Upper CI]: Effects of air pollution on blood markers presented as OR (95%CI) for an increase in the blood marker above the 90th percentile per increase in IQR air pollutant.

CRP Time before draw: 0-23 h: 1.2 (0.7, 2.0) 24-47 h: 1.3 (0.7, 2.4) 48-71 h: 1.6 (0.9, 2.7) 5-day mean: 1.2 (0.7, 2.1)

ICAM-1 Time before draw: 0-23 h: 1.0 (0.7, 1.6) 24-47 h: 2.6 (1.7, 3.8) 48-71 h: 4.0 (2.5, 6.1) 5-day mean: 2.2 (1.4, 3.3) Effects of air pollution on blood markers presented as % change from the mean/GM in the blood marker per increase in IQR air pollutant.

vWF Time before draw: 0-23 h: 5.0 (0.0, 10.1) 24-47 h: 7.6 (1.4, 13.7) 48-71 h: 1.1 (-5.2, 7.4) 5-day mean: 5.7 (-0.5, 12.0)

FVII Time before draw: 0-23 h: -5.7 (-10.5 to - 0.7) 24-47 h: -6.9 (-11.2 to -2.3) 48-71 h: -4.2 (-8.4, 0.2) 5-day mean: -6.0 (-10.5 to -1.2)

Note: Summary of results presented in figures. SAA results indicate increase in association with PM (not as strong and consistent as with CRP)

No association observed between E-selectin and PM An increase in prothrombin fragment 1+2 was consistently observed, particularly with lag 4 Fibrinogen results revealed few significant associations, potentially due to chance

D-dimer results revealed null associations in linear and logistic analyses



### December 2009 E-61

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ruckerl et al. (2006, 088754 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome (ICD9 and ICD10): C-reactive protein (CRP) Serum amyloid A (SAA) E-selectin von Willebrand Factor (vWF)intercellular adhesion molecule-1 (ICAM1) Fibrinogen Factor VII Prothrombin fragment 1+2 D-dimer Age Groups: 50+ yr Study Design: Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear and logistic regression models

Covariates: Models adjusted for different factors based on health endpoint CRP: RH, temperature, trend, ID ICAM-1: temperature, trend, ID vWF: air pressure, RH, temperature, trend, ID FVII: air pressure, RH, temperature, trend, ID, weekday

Season: Time trend as covariate Dose-response Investigated? Sensitivity analyses examined nonlinear exposure-response functions Statistical Package: SAS v8.2 and SPlus v6.0 Pollutant: OC Averaging Time: 24 h Mean (SD): 1.5 (0.6)

Percentiles: 25th: 1.1 50th: 1.4 75th: 1.8 Range (Min, Max): 0.3, 3.4 Monitoring Stations: 1 site Copollutant: UFPs AP PM 2.5 PM 10 OC EC NO 2 CO PM Increment: IQR (0.7 5-day avg: 0.5) Effect Estimate [Lower CI, Upper CI]: Effects of air pollution on blood markers presented as OR (95%CI) for an increase in the blood marker above the 90th percentile per increase in IQR air pollutant.

CRP Time before draw: 0-23 h: 1.2 (0.7, 1.9) 24-47 h: 1.3 (0.8, 2.1) 48-71 h: 1.4 (0.8, 2.4) 5-day mean: 1.2 (0.7, 1.8)

ICAM-1 Time before draw: 0-23 h: 0.9 (0.6, 1.3) 24-47 h: 2.0 (1.3, 3.2) 48-71 h: 3.0 (1.8, 4.8) 5-day mean: 1.3 (0.8, 2.0) Effects of air pollution on blood markers presented as % change from the mean/GM in the blood marker per increase in IQR air pollutant.

vWF Time before draw: 0-23 h: 5.5 (0.2, 10.8) 24-47 h: 8.0 (2.1, 13.9) 48-71 h: 3.5 (-2.6, 9.6) 5-day mean: 7.4 (2.0, 12.8)

FVII Time before draw: 0-23 h: -6.1 (-10.6 to - 1.4) 24-47 h: -7.2 (-11.4 to -2.8) 48-71 h: -3.8 (-8.2, 0.9) 5-day mean: -5.6 (-9.8 to -1.1)

Note: Summary of results presented in figures. SAA results indicate increase in association with PM (not as strong and consistent as with CRP)

No association observed between Eselectin and PM An increase in prothrombin fragment 1+2 was consistently observed, particularly with lag 4 Fibrinogen results revealed few significant associations, potentially due to chance

D-dimer results revealed null associations in linear and logistic analyses



### December 2009 E-62

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ruckerl et al. (2007, 091379 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome: Soluble CD40 ligand (sCD40L), platelets, leukocytes, erythrocytes, hemoglobin Age Groups: 50+ yr Study Design: Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear regression models

Covariates: Long-term time trend, weekday of the visit, temperature, RH, barometric pressure

Season: Time trend as covariate Dose-response Investigated? No Statistical Package: SAS v8.2 and SPlus v6.0 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 20.0 (15.0)

Percentiles: 25th: 9.7 50th: 14.9 75th: 26.1 Range (Min, Max): 2.6, 83.7 Monitoring Stations: 1 site Copollutants: UFPs AP PM 2.5 PM 10 NO PM Increment: IQR (16.4 5-day avg: 12.2) Effect Estimate [Lower CI, Upper CI]: Effects of air pollution on blood markers presented as % change from the mean/GM in the blood marker per increase in IQR air pollutant. sCD40L, % change GM (pg/mL) lag0: 1.5 (-4.0, 7.3) Lag1: 0.2 (-5.4, 6.2) Lag2: -2.6 (-8.0, 3.1) Lag3: 0.5 (-3.9, 5.0) 5-day mean: 0.2 (-5.4, 6.2) Platelets, % change mean (103/ μ l) Lag0: -0.6 (-1.9, 0.7) Lag1: 0.1 (-1.3, 1.5) Lag2: 0.5 (-0.9, 1.9) Lag3: 0.2 (-1.1, 1.5) 5-day mean: -0.4 (-1.9, 1.2) Leukocytes, % change in mean (103/ μ l) Lag0: -1.6 (-3.2, 0.0) Lag1: -0.4 (-2.2, 1.4) Lag2: -0.2 (-2.1, 1.7) Lag3: -0.8 (-2.4, 0.7) 5-day mean: -1.6 (-3.5, 0.3) Erythrocytes, % change mean (106/ μ l) Lag0: -0.1 (-0.5, 0.3) Lag1: -0.3 (-0.7, 0.2) Lag2: -0.4 (-0.8, 0.0) Lag3: -0.2 (-0.5, 0.1) 5-day mean: -0.4 (-0.8, 0.0) Hemoglobin, % change mean (g/dl) Lag0: 0.0 (-0.6, 0.5) Lag1: -0.2 (-0.8, 0.3) Lag2: -0.5 (-1.1, 0.0) Lag3: -0.2 (-0.7, 0.2) 5-day mean: -0.5 (-1.0, 0.1)

Reference: Sarnat et al. (2006, 090489 ) Period of Study: Summer and fall 2000

Location: Steubenville, OH Outcome: Supraventricular ectopy (SVE) or ventricular ectopy (VE)

N: 32 nonsmoking older adults Statistical Analysis: Logistic mixed effects regression

Season: Summer and fall Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: 5 days Median (IQR): PM 2.5 : Median: 19.0 μg/m 3

IQr = 10.0

Sulfate: Median: 6.1. IQR: 4.2

EC: Median: 0.9. IQR: 0.5 Copollutants: O 3 , NO 2 , SO 2 PM Increment: IQR

Effect Estimate: PM 2.5 : SVE: OR = 1.42 (95% CI: 0.99, 2.04) VE: OR = 1.02 (95% CI: 0.63-1.65)

Sulfate: SVE: OR = 1.70 (95% CI: 1.12, 2.57) VE: OR = 1.08 (95% CI: 0.65, 1.80) EC: SVE: OR = 1.15 (95% CI: 0.73, 1.81) VE: OR = 1.00 (95% CI: 0.57, 1.75)

Notes: Longitudinal study of 32 nonsmoking older adults who had ECG measurements made every week for 24 wk. PM measured within 1 mile of subjects’ residences, and central site pollutant measurements were also made.



### December 2009 E-63

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Schneider et al. (2008, 191985 ) Period of Study: Nov 2004-Dec 2005

Location: Chapel Hill, NC Outcome: Endothelial Function Parameters Age Groups: 48-80 yr Study Design: Panel

N: 22 diabetics Statistical Analyses: Mixed Models

Covariates: Season, day of the week, temperature, relative humidity, barometric pressure Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-4 days; 5-day ma Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): 13.6 (7.0)

Min: 2.0

Max: 38.9 Monitoring Stations: 2 Copollutant: NR PM Increment: 10 μg/m 3 Percent Change: (Lower CI, Upper CI), lag: FMD: ^l -17.3 (-34.6, 0.0), lag 0 -4.4 (-24.6, 15.8), lag 1 -18.6 (-44.8, 7.6), lag 2 1.6 (-23.6, 26.9), lag 3 18.4 (-3.5, 40.3), lag 4 -19.4 (-62.6, 23.8), 5-day ma

NTGMD: 2.5 (-9.0, 13.9), lag 0 -13.6 (-24.5, -2.6), lag 1* -10.2 (-23.5, 3.0), lag 2 -8.0 (-22.4, 6.4), lag 3 3.6 (-7.9, 15.0), lag 4 -19.4 (-44.3, 5.5), 5-day ma

LAEI: 0.4 (-4.2, 5.0), lag 0 -0.3 (-6.0, 5.4), lag 1 2.5 (-4.3, 9.4), lag 2 -7.3 (-13.5, -1.1), lag 3* -2.3 (-8.0, 3.3), lag 4 -4.6 (-15.3, 6.1), 5-day ma

SAEI: -3.0 (-13.0, 7.0), lag 0 -17.0 (-27.5, -6.4), lag 1** -9.7 (-23.5, 4.2), lag 2 -15.1 (-29.3, -0.9)*, lag 3 -2.1 (-14.0, 9.7), lag 4 -25.4 (-45.4, -5.3), 5-day ma*

SVR: -1.6 (-3.7, 0.4), lag 0 1.6 (-0.9, 4.1), lag 1 3.5 (0.5, 6.5), lag 2 2.4 (-0.5, 5.3), lag 3 3.2 (0.7, 5.6), lag 4* 4.5 (-0.3, 9.2), 5-day ma *p < 0.05, ** p < 0.01

Notes: Percent change (95% CI) per 10 μg/m 3 PM 2.5 by GSTM1 genotype (Fig 3)

Reference: Schwartz et al. (2005, 074317 ) Period of Study: 12 wk during the summer of 1999

Location: Boston, MA Outcome: Heart rate variability (HRV), (SDNN, r-MSSD, PNN50, LFHFR) Age Groups: 61-89 yr Study Design: Panel study

N: 28 elderly subjects Statistical Analysis: Mixed models. To examine heterogeneity of effects, hierarchical modeling was used.

Season: Summer Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: 1 h, 24 h

Median: 24-h: 10 μ g/m 3 Monitoring Stations: 1 Copollutant: BC, O 3 , CO, SO 2 , NO 2 PM Increment: IQR (not given)

Effect Estimate: 24 h: 2.6 ms decrease in SDNN (95% CI: 0.8 to -6.0) 10.1 ms decrease in r-MSSD (95% CI: - 2.8 to -16.9). 1 h: 3.4 ms decrease in SDNN (95% CI: 0.6 to -7.3) 7.4 ms decrease in r-MSSD (95% CI: 1.6 to -15.5).

Notes: Various log-transformed HRV parameters were measured for 30 minutes once a week. The random effects model indicated that the negative effect of BC on HRV was not restricted to a few subjects. Same study population as Gold et al. (2005). Boston Elders Study For each pollutant/averaging time, similarly sized changes were observed for PNN50 (%) and LFHFR.



### December 2009 E-64

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Schwartz et al. (2005, 074317 ) Period of Study: 12 wk during the summer of 1999

Location: Boston, MA Outcome: Heart rate variability (HRV), (SDNN, r-MSSD, PNN50, LFHFR) Age Groups: 61-89 yr Study Design: Panel study

N: 28 elderly subjects Statistical Analysis: Mixed models. To examine heterogeneity of effects, hierarchical modeling was used.

Season: Summer Dose-response Investigated? No Pollutant: BC Averaging Time: 24 h

Median: 1.0 μ g/m 3 Monitoring Stations: 1 Copollutant: PM 2.5 , O 3 , CO, SO 2 , NO 2 PM Increment: IQR

Effect Estimate: 5.1 ms decrease in SDNN (-1.5 to -8.6) 10.1 ms decrease in r-MSSD (-2.4 to - 17.2).

Notes: Various log-transformed HRV parameters were measured for 30 minutes once a week. The random effects model indicated that the negative effect of BC on HRV was not restricted to a few subjects. Same study population as Gold et al. (2005). Boston Elders Study. Subjects with a prior MI experienced greater declines in BC associated HRV. For each pollutant/averaging time, similarly sized changes were observed for PNN50 (%) and LFHFR.

Reference: Schwartz et al. (2005, 074317 ) Period of Study: 2000

Location: Boston, Massachusetts Outcome: HF (high frequency component of heart rate variability) Study Design: Cross-sectional

N: 497 subjects Statistical Analysis: Linear regression, controlling for covariates Pollutant: PM 2.5 Averaging Time: 48 h Mean (SD): 11.4 μg/m 3 (8.0) Copollutant: None PM Increment: 10 μg/m 3

Effect Estimate: 34% decrease in HF (95% CI: -9% to -52%) in subjects without the GSTM1 allele. In subjects with the allele, no effect was noted. Similar findings for obese subjects and those with high neutrophil counts.

Notes: Study population: Normative Aging Study.

Effects of PM 2.5 appear to be mediated by ROS.

Reference: Sorensen et al. (2005, 089428 ) Period of Study: Nov 1999-Aug 2000

Location: Copenhagen, Denmark Outcome: 7-Hydro-8-Oxo-2’- Deoxyguanosine (8-oxodG) (measured in lymphocytes and urine) Age Groups: 20-33 yr Study Design: Panel (repeated measures)

N: 49 students living and studying in central Copenhagen 50 students examined each season (66 subjects total 32 participated in each season total of 98 measurements) Statistical Analyses: Mixed models repeated measures

Covariates: PM 2.5 , season, subject (random factor) Dose-response Investigated? No Statistical Package: SAS v8e Pollutant: PM 2.5 Averaging Time: 48 h Mean (SD): Fall: 20.7

Summer: 12.6

Percentiles: IQR Fall: 13.1-27.7

IQR summer: 9.4-24.3 Range (Min, Max): NR Monitoring Stations: NA (personal assessment) Copollutant (correlation): Spearman correlations with PM 2.5 mass: chromium (r = 0.22) copper (r = 0.33) iron (r = 0.29) vanadium (p>0.5) nickel (p>0.5) platinum (p>0.5) PM Increment: see below Effect Estimate [Lower CI, Upper CI]: Association between 8-oxodG in lymphocytes and personal exposure to transition metals in PM 2.5

. % increase in 8-oxodG per increase in metal concentration indicated Vanadium: 1.9% per 1 μ g/L (0.6, 3.3) Chromium: 2.2% per 1 μ g/L (0.8, 3.5) Platinum: 6.1% per 1 ng/L (-0.6, 13.2) Nickel: 0.8% per 10 μ g/L (-2.1, 3.7) Copper: -0.8% per 10 μ g/L (-2.7, 1.0) Iron: 0.6% per 10 μ g/L (-1.4, 2.6)

Note: PM 2.5 mass was independently associated with 8-oxodG in 5 of 6 transition metal models (p < 0.02 in models with vanadium, chromium, nickel, copper, and iron p = 0.07 in platinum model). No transition metals were associated with 8- oxodG measured in urine



### December 2009 E-65

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sorensen et al. (2003, 042700 ) Period of Study: Nov 1999-Aug 2000

Location: Copenhagen, Denmark Outcome: RBC count, hemoglobin, platelet count, fi brinogen, PLAAS (2- aminoadipic semialdehyde in plasma proteins), HBGGS ( γ -glutamyl semialdehyde in hemoglobin), HBAAS (2-aminoadipic semialdehyde in hemoglobin), MDA (malondialdehyde) Age Groups: 20-33 yr Study Design: Panel (repeated measures)

N: 50 students living and studying in central Copenhagen 50 students examined each season (68 subjects total 31 participated in each season total of 195 measurements) Statistical Analyses: Mixed model repeated-measures analysis

Covariates: Season, avg outdoor temperature, and sex

Season: Repeated measures 4 times (once per season) Dose-response Investigated? No Statistical Package: SAS v8e Pollutant: PM 2.5 (personal) Averaging Time: 48 h

Median: 16.1 μ g/m 3

Percentiles: Q25-Q75: 10.0-24.5 Copollutant: Urban background PM 2.5 Personal PM 2.5 PM Increment: 1 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Relationship between exposure and biomarkers Estimate (p-value): Platelet count (x 106/g protein): 0.0008 (0.37) Fibrinogen (nmol/g protein): 0.0006 (0.69) PLAAS (pmol/mg protein): 0.0016 (0.061) HBGGS (pmol/mg protein): 0.0001 (0.94) HBAAS (pmol/mg protein): 0.0006 (0.64) Increase (95%CI) in biomarkers per 10 μ g/ m 3 increase in PM 2.5 RBC Men: 0% (-1.6, 1.6) Women: 2.3% (0.5, 4.1) Hemoglobin Men: 0.0% (-1.7, 1.5) Women: 2.6% (0.8, 4.5)

Reference: Sorensen et al. (2003, 042700 ) Period of Study: Nov 1999-Aug 2000

Location: Copenhagen, Denmark Outcome: RBC count, hemoglobin, platelet count, fi brinogen, PLAAS (2- aminoadipic semialdehyde in plasma proteins), HBGGS ( γ -glutamyl semialdehyde in hemoglobin), HBAAS (2- aminoadipic semialdehyde in hemoglobin), MDA (malondialdehyde) Age Groups: 20-33 yr Study Design: Panel (repeated measures)

N: 50 students living and studying in central Copenhagen 50 students examined each season (68 subjects total 31 participated in each season total of 195 measurements) Statistical Analyses: Mixed model repeated-measures analysis

Covariates: S eason, avg outdoor temperature, and sex

Season: Repeated measures 4 times (once per season) Dose-response Investigated? No Statistical Package: SAS v8e Pollutant: Personal exposure to black carbon (10-6/m) Averaging Time: 48 h

Median: 8.1

Percentiles: Q25-Q75: 5.0-13.2 Copollutant: Urban background PM 2.5 Personal PM 2.5 PM Increment: 10-6/m Effect Estimate [Lower CI, Upper CI]: Relationship between exposure and biomarkers Estimate (p-value): RBC count (x 109/g protein): 0.0003 (0.75) Hemoglobin ( μ mol/g protein): 0.0004 (0.65) Platelet count (x 106/g protein): 0.0009 (0.51) Fibrinogen (nmol/g protein): -0.0027 (0.29) PLAAS (pmol/mg protein): 0.0041 (0.0009) HBGGS (pmol/mg protein): 0.0024 (0.25) HBAAS (pmol/mg protein): 0.0022 (0.20) MDA (pmol/mg protein): 0.0018 (0.30)



### December 2009 E-66

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sorensen et al. (2003, 042700 ) Period of Study: Nov 1999-Aug 2000

Location: Copenhagen, Denmark Outcome: RBC count, hemoglobin, platelet count, fi brinogen, PLAAS (2- aminoadipic semialdehyde in plasma proteins), HBGGS ( γ -glutamyl semialdehyde in hemoglobin), HBAAS (2-aminoadipic semialdehyde in hemoglobin), MDA (malondialdehyde) Age Groups: 20-33 yr Study Design: Panel (repeated measures)

N: 50 students living and studying in central Copenhagen 50 students examined each season (68 subjects total 31 participated in each season total of 195 measurements) Statistical Analyses: Mixed model repeated-measures analysis

Covariates: S eason, avg outdoor temperature, and sex

Season: Repeated measures 4 times (once per season) Dose-response Investigated? No Statistical Package: SAS v8e Pollutant: PM 2.5 (urban background concentration) Averaging Time: 48 h

Median: 9.2 μ g/m 3

Percentiles: Q25-Q75: 5.3-14.8 Copollutant: Urban background PM 2.5 Personal carbon black PM Increment: 1 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Relationship between exposure and biomarkers Estimate (p-value): RBC count (x 109/g protein): 0.0008 (0.36) Hemoglobin ( μ mol/g protein): 0.0005 (0.53) Platelet count (x 106/g protein): -0.0008 (0.49) Fibrinogen (nmol/g protein): 0.0004 (0.84) PLAAS (pmol/mg protein): 0.0004 (0.76) HBGGS (pmol/mg protein): -0.0020 (0.39) HBAAS (pmol/mg protein): -0.0021 (0.29) MDA (pmol/mg protein): 0.0012 (0.52)

Reference: Sullivan et al. (2007, 100083 ) Period of Study: Feb 2000-Mar 2002

Location: Seattle, Washington, USA Outcome: Blood CRP, fibrinogen, Ddimer Age Groups: >55 yr of age Study Design: Panel study

N: 47 elderly subjects Pollutant: PM 2.5 Averaging Time: 24 h Median (IQR): 7.7 μg/m 3 (6.4) Monitoring Stations: 1 Copollutant: Indoor PM 2.5 PM Increment: 10 μg/m 3

Effect Estimate: Among those with CVD, PM 2.5 1 day earlier: CRP: 1.25 (95% CI: 0.97, 1.58) Fibrinogen: 1.01 (95% CI: 0.97, 1.05) D-dimer: 1.04 (95% CI: 0.93, 1.15) With COPD: CRP: 0.69 (95% CI: 0.34, 1.42) Fibrinogen: 1.05 (95% CI: 0.97, 1.13) D-dimer: 1.10 (95% CI: 0.95, 1.28) Healthy: CRP: 1.01 (95% CI: 0.85, 1.19) Fibrinogen: 0.88 (95% CI: 0.81, 0.95) D-dimer: 1.10 (95% CI: 0.75, 1.58)

Notes: Out of 47 subjects, n = 23 with CVD and n = 24 (n = 16 COPD and 8 healthy) without CVD. Blood markers were measured on 2-3 morning over a 5-10 day period, and outdoor PM 2.5 was measured at a central monitoring site. These findings are not consistent with and effect of fine PM on markers of inflammation and thrombosis in the elderly.



### December 2009 E-67

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sullivan et al. (2005, 109418 ) Period of Study: Feb 2000-Mar 2002

Location: Seattle, Washington, USA Outcome: Heart rate variability (H, LF, HF, r-MSSD, SDNN) Study Design: Panel study

N: 34 elderly subjects with (n = 21) and without (n = 13) CVD. Statistical Analysis: Linear mixed effects regression Pollutant: PM 2.5 Averaging Time: 1 h Median (IQR): 10.7 (7.6) Copollutant: CO, NO 2 PM Increment: 10 μg/m 3

Effect Estimate: 1 h: With CVD: HF: (3% increase, 95% CI: -19, 32) Without CVD: HF(5% decrease, 95% CI: -34, 36) Similarly, no association was found for 4-h or 24-h mean PM 2.5 concentrations.

Notes: 285 daily 20 min HRV measures were made in the homes of study subjects over a 10-day period.



### December 2009 E-68

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sullivan et al. (2005, 109418 ) Period of Study: Feb 2000-Mar 2002

Location: Seattle area, WA Outcome (ICD9 and ICD10): Highsensitivity C-reactive protein (hs-CRP) fibrinogen

D-dimer Endothelin-1 (ET-1) Interleukin-6 (IL-6 Interleukin-6 receptor (IL-6r)

Tumor necrosis factor- α (TNF-8- α ) Tumor necrosis factor-receptors (p55, p75) Monocyte chemoattractant protein-1 (MCP-1) Age Groups: ≥ 55 yr Study Design: Panel (repeated measures)

N: 47 participants with (23) and without (10 COPD and 8 healthy) CVD Statistical Analyses: Mixed models

Covariates: Age, gender, medication use, meteorological variables (temperature and RH) Dose-response Investigated? No Statistical Package: SAS v8.02 Pollutant: PM 2.5 Averaging Time: 24 h (0-day and 1-day lags) Mean (SD): NR Percentiles: For all subject-days: 25th: 5.2 50th: 7.7 75th: 11.5 90th: 19.9 Range (Min, Max): 1.3, 33.9 Monitoring Stations: NA, measured at participant’s residence Copollutant: None PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Multiplicative change in mean outcome associated with 10 μg/m 3 increase in PM Among those with different disease status. CRP Fold-rise (95%CI) CV 0-day lag: 1.21 (0.86, 1.70) CV 1-day lag: 1.25 (0.97, 1.58); COPD 0-day lag: 0.93 (0.48, 1.80) COPD 1-day lag: 0.69 (0.33, 1.46) Healthy 0-day lag: 0.98 (0.88, 1.08) Healthy 1-day lag: 1.01 (0.84 1.21) Fibrinogen Fold- rise (95%CI) CV 0-day lag: 1.02 (0.98, 1.06) CV 1-day lag: 1.0 (0.97, 1.03); COPD 0-day lag: 1.0 (0.91, 1.09) COPD 1-day lag: 1.08 (0.99, 1.17) Healthy 0-day lag: 0.94 (0.87, 1.01) Healthy 1-day lag: 0.99 (0.88, 1.17)

D-dimer Fold- rise (95%CI) CV 0-day lag: 1.02 (0.88, 1.17) CV 1-day lag: 1.03 (0.93, 1.15); COPD 0-day lag: 1.04 (0.93, 1.16) COPD 1-day lag: 1.09 (0.94, 1.27) Healthy 0-day lag: 0.95 (0.79, 1.14) Healthy 1-day lag: 0.97 (0.71, 1.31) Among those with cardiovascular disease MCP-1 Fold-rise (95%CI) 0-day lag: 1.3 (1.1, 1.7) 1-day lag: 1.0 (0.9, 1.3) ET-1 Fold-rise (95%CI) 0-day lag: 1.1 (0.8, 1.2) 1-day lag: 1.1 (0.9, 1.2)

Note: TNF- α and IL-6 measures were below the limit of detection of assays

Reference: Timonen et al. (2006, 088747 ) Period of Study: 1998-1999

Location: Amsterdam, Netherlands Erfurt, Germany Helsinki, Finland Outcome: Heart variability (HRV) measurements: [LF, HF, LFHFR, NN interval, SDNN, r-MSSD] Study Design: Panel study

N: 131 elderly subjects with stable coronary heart disease Statistical Analysis: Linear mixed models Pollutant: PM 2.5 Means:

Amsterdam: 20.0

Erfurt: 23.3

Helsinki: 12.7 Copollutant: NO 2 , CO PM Increment: 10 μg/m 3

Effect Estimate: SDNN -0.33ms (95% CI: -1.05, 0.38) HF: -0.3% (95% CI: -10.6, 5.4) LFHFR: -1.4 (95% CI: -5.9, 8.7)

Notes: Followed for 6 mo with biweekly clinic visits 2-day lag. ULTRA Study



### December 2009 E-69

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Vallejo et al. (2006, 157081 ) Period of Study: Apr-Aug 2002

Location: Mexico City metropolitan area Outcome: Heart rate variability measures (SDNN, pNN50) Age Groups: Mean age 27 yr Study Design: Panel study

N: 40 young healthy participants (nonsmokers, no meds or history of CVD, respiratory, neurological, or endocrine disease) Statistical Analysis: Linear mixed effects models Pollutant: PM 2.5 (pDR nephelometric method-DataRAM) Copollutant: None PM Increment: 30 μg/m 3 Effect Estimate: pNN50: 0 h lag: -0.01% (95% CI: -0.03, 0.01) 1 h: -0.01% (95% CI: -0.04, 0.02) 2 h: -0.05% (95% CI: -0.09, 0.00) 3 h: -0.07% (95% CI: -0.13 to -0.02) 4 h: -0.08% (95% CI: -0.14 to -0.01) 5 h: -0.06% (95% CI: -0.13, 0.02) 6 h: -0.05% (95% CI: -0.13, 0.04) SDNN: 0 h: 0.00% (95% CI: 0.00, 0.01) 1 h: 0.00% (95% CI: -0.01, 0.01) 2 h: 0.00% (95% CI: -0.02, 0.01) 3 h: -0.01% (95% CI: -0.02, 0.00) 4 h: -0.01% (95% CI: -0.02, 0.01) 5 h: -0.01% (95% CI: -0.02, 0.01) 6 h: 0.00% (95% CI: -0.02, 0.02) Notes: Subjects underwent 13 h of ECG monitoring and personal PM 2.5 measurement. HRV measures were regressed against different lags of PM 2.5 concentration.

Reference: Van Hee et al. (2009, 192110 ) Period of Study: Jul 2000-Aug 2002

Location: Baltimore, Maryland Chicago, Illinois Winston-Salem, North Carolina

St. Paul

Minnesota New York, New York Los Angeles, California Outcome: Left Ventricular Mass Index and Ejection Fraction Age Groups: 45-84 yr Study Design: C ross-sectional

N: 3,827 participants Statistical Analyses: Linear Regression Models

Covariates: A ge, race, income, sex, education, medication use, LDL, HDL, physical activity, alcohol consumption, smoking, diabetes, systolic BP, diastolic BP Dose-response Investigated? No Statistical Package: Stata Lags Considered: NR Pollutant: PM 2.5 Averaging Time: NR Mean (SD): Fig only Monitoring Stations: N/A Interpolation used Copollutant: NR Co-pollutant Correlation: N/A PM Increment: 10 μg/m 3Difference (Lower CI, Upper CI), pvalue:

Left Ventricular Mass Index Unadjusted: -6.0 (-7.8, -4.2), <0.0001 All covariates except center, BP: -6.1 (- 7.8, -4.4), <0.0001 All covariates except BP: 3.7 (-6.0, 13.4), 0.46 Full model: 4.6 (-4.7, 13.9), 0.33 Full model plus center/race interaction: 3.8 (-6.1, 13.7), 0.45 Left Ventricular Ejection Fraction Unadjusted: 3.0 (2.2, 3.8), <0.0001 All covariates except center, BP: 1.4 (0.5, 2.2), 0.001 All covariates except BP: -1.1(-5.8, 3.7), 0.66 Full model: -1.3 (-6.0, 3.5), 0.60 Full model plus center/race interaction: - 3.0 (-8.0, 2.0), 0.24

Reference: Wellenius et al. (2007, 092830 ) Period of Study: Feb 2002-Mar 2003

Location: Boston, Massachusetts, USA Outcome: Circulating levels of B-type natriuretic peptide (BNP Measured in whole blood at 0, 6, 12 wk) Study Design: Panel study

N: 28 subjects (each with chronic stable HF and impaired systolic function) Statistical Analysis: Linear mixed effects models Pollutant: PM 2.5 Copollutant: NO 2 , SO 2 , O 3 , CO, BC PM Increment: 10 μg/m 3

Effect Estimate: Same day PM 2.5 : 0.8% increase in BNP (95% CI: -16.4, 21.5)

Notes: The study found no association between any pollutant and measures of BNP at any lag. Further, the within subject coefficient of variation was large suggesting the magnitude of effected air pollutant health effects are small in relation to within subject variability in BNP.



### December 2009 E-70

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Wellenius et al. (2007, 092830 ) Period of Study: Feb 2002-Mar 2003

Location: Boston, Massachusetts Outcome (ICD9 and ICD10): B-type natriuretic peptide (BNP) (natural-log transformed) Age Groups: 33-88 yr Study Design: Panel (blood collected at 0, 6, and 12 wk)

N: 28 patients with chronic stable heart failure and impaired systolic function Statistical Analyses: Linear mixedeffects models

Covariates: Temperature, dew point, mean dew point over the past 3 days,calendar month of blood draw, measurement occasion, treatment assignment, measurement occasion by treatment assignment interaction

Season: Adjusted for calendar month Dose-response Investigated? No Statistical Package: SAS v9.1 Pollutant: PM 2.5 Averaging Time: Daily (assessed lags of 0-3 days) Mean (SD): 10.9 (8.4)

Percentiles: 50th: 8.0 μg/m 3 Range (Min, Max): 0.7-50.9 μg/m 3 Monitoring Stations: 1 monitor Copollutant (correlation): CO (r = 0.35)

NO 2 (r = 0.31)

SO 2 (r = 0.18)

O 3 (r = 0.35) BC(r = 0.68) PM Increment: IQr = 8.1 μg/m 3 Effect Estimate [Lower CI, Upper CI]: % change in BNP per IQR increase in PM 2.5 Lag0: 1.5 (-18.7, 19.2) Lag1: 2.1 (-20.0, 30.3) Lag2: 1.3 (12.3, 17.1) Lag3: 5.6 (-16.8, 34.0)

Note: No significant associations observed between any pollutant and BNP levels at any lags (presented in Fig 2)

Reference: Wheeler et al. (2006, 088453 ) Period of Study: Fall 1999 and spring 2000

Location: Atlanta, GA Outcome: Heart rate variability Age Groups: 49-76 yr

N: 18 subjects with COPD and 12 subjects with a recent MI Statistical Analysis: Linear-mixed effect model

Season: Fall and spring Pollutant: PM 2.5 Averaging Time:

1 h

4 h

24 h

Mean: 24-h: 17.8 μg/m 3 Copollutant: O 3 , CO, SO 2 , NO 2 PM Increment: 11.65 μg/m 3 (IQR) in 4 h PM 2.5 Effect Estimate: Among COPD patients: 8.3% increase in SDNN (95% CI: 1.7, 15.3) Among MI patients: 2.9% decrease in SDNN (95% CI: -7.8, 2.3) Results for 1-h and 24-h averaging times were similar.

Notes: Data was collected on 7 days in the fall of 1999 or spring of 2000. Effects were modified by medication use, baseline pulmonary function, and health status.



### December 2009 E-71

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### Effect Estimates (95% CI)

Reference: Yeatts et al. (2007, 091266 ) Period of Study: 12-wk period b/t Sep 2003-Jul 2004

Location: Chapel Hill, NC Outcome: Heart Rate Variability Age Groups: 21-50 yr Study Design: Panel

N: 12 asthmatics Statistical Analyses: Linear Mixed Model

Covariates: Temperature, humidity, pressure Dose-response Investigated? No Statistical Package: SAS Lags Considered: 1 day Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 12.5 (6.0)

Min: 0.6

Max: 37.1 Monitoring Stations: 1 Copollutant: PM 10-2.5 , PM 10 Co-pollutant Correlation:

PM 10-2.5 = 0.46*

PM 10 = NR *p < 0.01 PM Increment: 1 μg/m 3Beta, SE (Lower CI, Upper CI), pvalue:

HRV Max Heart Rate: 0.40, 0.43 (-0.45, 1.24), 0.36 ASDNN5: -0.07, 0.15 (-0.37, 0.22), 0.63 SDANN5: 1.66, 0.65 (0.39, 2.93), 0.02 SDNN24HR(mesc): 1.16, 0.58 (0.02, 2.29), 0.06 rMSSD: 0.53, 0.20 (0.14, 0.91), 0.01 pNN50_24hr: -0.06, 0.11 (-0.27, 0.15), 0.58 pNN50_7min: 0.47, 0.42 (-0.35, 1.29), 0.27 Low-frequency power: -0.23, 0.14 (-0.51, 0.05), 0.11 Percent low frequency: -0.78, 0.41 (- 1.59, 0.03), 0.07 High-frequency power: 0.14, 0.07 (-0.01, 0.28), 0.07 Percent high frequency: 0.64, 0.36 (- 0.07, 1.34), 0.09 Blood Lipids Triglycerides: -0.63, 0.84 (-2.29, 1.02), 0.46 VLDL: -0.17, 0.22 (-0.61, 0.26), 0.44 Total cholesterol: -0.06, 0.22 (-0.49, 0.36), 0.77 Hematologic Factor Circulating eosinophils: -0.02, 0.00 (- 0.02, -0.02), 0.27 Platelets: -0.01, 0.45 (-0.88, 0.86), 0.98 Circulating Proteins Plasminogen: 0.00, 0.00 (-0.01, 0.00), 0.82 Fibrenogen: 0.00, 0.01 (-0.01, 0.02), 0.59 Von Willibrand factor: -0.31, 0.29 (-0.87, 0.25), 0.28 Factor VII: -0.65, 0.33 (-1.29, -0.01), 0.05



### December 2009 E-72

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Yue et al. (2007, 097968 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome: QT interval and T-wave amplitude for ECG recordings, and vWF, CRP from blood samples Study Design: Panel study

N: 56 patients (male CAD patients with 12 clinical visits) Statistical Analysis: Linear and logistic regression models Dose-response Investigated? No Pollutant: PM 2.5 , PNC (n/cm 3 ) Averaging Time: Mean: Mass concentrations of PNC (0.1-2.84 n/cm 3 ) Monitoring Stations: 1 Copollutant: None PM Increment: . IQR

Effect Estimate: Each IQR increase in 0-23 h mean traffic particle concentration was associated with: QT interval: 0.6% (95% CI: -0.3, 1.4) T wave amplitude: -1.6% (95% CI: -3.3, 0.1) vWF: 3.2% (95% CI: -0.5, 7.0) CRP: (OR = 1.5 95% CI 1.0-2.3)

Each IQR increase in 0-23 h mean combustion-generated particle concentration was associated with: QT interval: 0.1%(-0.3, 0.6) T wave amplitude: -0.2% (-1.2, 0.7) vWF: 2.8% (0.8, 4.8) CRP (OR = 1.0 0.8, 1.2)

Notes: Five sources of particles wereidentified (airborne soil, local trafficrelated ultrafine particles, combustiongenerated aerosols, diesel traffic-related particles, and secondary aerosols).

Reference: Yue et al. (2007, 097968 ) Period of Study: Oct 12, 2000-Apr 27, 2001

Location: Erfurt, Germany Outcome: QT interval, T wave amplitude, von Willebrand factor (vWF), C-reactive protein (CRP above 90th percentile compared to below) Age Groups: >50 yr Study Design: Panel (12 visits 625 observations for repolarization parameters and 578 observations for inflammatory markers)

N: 57 male coronary artery disease patients Statistical Analyses: Linear and logistic fixed-effects regression models (generalized additive models)

Covariates: Trend, weekday, and meteorological variables (temperature, relative humidity, barometric pressure) Dose-response Investigated? No Statistical Package: SAS v9.1 and SPlus v6.0 Pollutant: Five particle source factors (airborne soil, local traffic-related ultrafine particles, combustion-generated aerosols, diesel traffic-related particles, and secondary aerosols); see below for size fractions (factor scores) Averaging Time: Used daily factor scores in analyses Mean (SD): Factor 1: particles from airborne soil (1.0-2.8 μm): 2390 (1696) Factor 2: ultrafine particles from local traffic (0.01-0.1 μm): 9931 (5858) Factor 3: secondary aerosols from local fuel combustion (0.1-0.5 μm): 3770 (6129) Factor 4: particles from traffic (0.01- 0.5 μm): 6865 (5689) Factor 5: secondary aerosols from multiple sources (0.2-1.0 μm): 4732 (3890) Median: Factor 1: 2053 Factor 2: 8531 Factor 3: 1348 Factor 4: 5045 Factor 5: 3752 IQR (5-day avg): Factor 1: 1110 Factor 2: 5749 Factor 3: 4124 Factor 4: 5000 Factor 5: 3393 Range (Min, Max): Factor 1: 284, 12960 Factor 2: 866, 26632 Factor 3: 139, 39097 Factor 4: 283, 27605 Factor 5: 67, 20129 Monitoring Stations: 1 monitor PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: QT interval, % change (95%CI) Factor 1: 0-5 h: -0.1 (-0.6, 0.6) 6-11 h: -0.5 (-1.1, 0.2) 12-17 h: 0.1 (-0.4, 0.4) 18-23 h: -0.2 (-0.7, 0.2) 0-23 h: -0.2 (-0.9, 0.4) 1 day: -0.1 (-0.7, 0.6) 2 day: -0.3 (-0.9, 0.4) 3 day: -0.7 (-1.4, 0.1) 4 day: -0.2 (-0.9, 0.5) 0-4 day avg: -0.7 (-1.8, 0.3) Factor 2: 0-5 h: 0.2 (-0.4, 0.8) 6-11h: 0.8 (-0.0, 1.7) 12-17 h: 0.6 (-0.2, 1.4) 18-23 h: 0.5 (-0.4, 1.4) 0-23 h: 0.9 (-0.1, 2.0) 1 day: 1.5 (0.3, 2.7) 2 day: -0.4 (-1.7, 1.0) 3 day: 0.5 (-0.9, 1.9) 4 day: 0.1 (-1.2, 1.4) 0-4 day avg: 1.6 (-0.1, 3.3) Factor 3: 0-5 h: 0.1 (-0.3, 0.5) 6-11 h: 0.2 (-0.3, 0.6) 12-17 h: 0.2 (-0.3, 0.6) 18-23 h: 0.1 (-0.3, 0.4) 0-23 h: 0.1 (-0.3, 0.6) 1 day: 0.1 (-0.3, 0.4) 2 day: -0.1 (-0.4, 0.3) 3 day: -0.2 (-0.5, 0.2) 4 day: -0.1 (-0.5, 0.2) 0-4 day avg: -0.1 (-0.7, 0.6) Factor 4: 0-5 h: 0.2 (-0.4, 0.8) 6-11 h: 0.8 (0.0, 1.6) 12-17 h: 0.5 (-0.2, 1.3) 18-23 h: 0.5 (-0.2, 1.2) 0-23 h: 0.6 (-0.3, 1.4) 1 day: -0.4 (-1.5, 0.7) 2 day: -0.9 (-2.0, 0.1) 3 day: -0.5 (-1.4, 0.5)



### December 2009 E-73

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Copollutant: NA 4 day: -0.5 (-1.3, 0.2) 0-4 day avg: -0.3 (-1.7, 1.1) Factor 5 : n0-5 h: 1.0 (-0.1, 2.1) 6-11 h: 0.9 (-0.2, 2.0) 12-17 h: 0.3 (-0.7, 1.4) 18-23 h: -0.1 (-1.2, 1.0) 0-23h: 0.7 (-0.6, 1.9) 1 day: 0.1 (-1.1, 1.3) 2 day: -0.2 (-1.5, 1.1) 3 day: -0.6 (-1.9, 0.8) 4 day: -0.9 (-2.0, 0.2) 0-4 day avg: -0.4 (-1.9, 1.2) T wave amplitude, % change (95%CI) Factor 1 : 0-5 h: -0.3 (-1.5, 0.9) 6-11 h: -0.6 (-1.9, 0.7) 12-17 h: 0.1 (-0.8, 0.9) 18-23 h: -0.6 (-1.5, 0.4) 0-23 h: -0.5 (-1.8, 0.9) 1 day: 0.4 (-0.9, 1.7) 2 day: 1.2 (-0.3, 2.7) 3 day: 0.2 (-1.2, 1.7) 4 day: -0.2 (-1.3, 1.0) 0-4 day avg: 0.8 (-1.1, 2.6) Factor 2 : 0-5 h: -1.7 (-3.0 to -0.4) 6-11 h: -2.6 (-4.5 to -0.6) 12-17 h: -1.0 (-2.6, 0.7) 18-23 h: -1.1 (-2.8, 0.7) 0-23 h: -3.1 (-5.3 to -0.9) 1 day: -0.3 (-2.9, 2.2) 2 day: -1.2 (-4.1, 1.7) 3 day: -0.5 (-3.2, 2.1) 4 day: -3.4 (-9.9, 3.1) 0-4 day avg: -1.5 (-4.4, 1.5) Factor 3 : 0-5 h: -0.3 (-1.1, 0.6) 6-11 h: -0.1 (-0.9, 0.9) 12-17 h: 0.1 (-0.9, 1.0) 18-23 h: -0.4 (-1.2, 0.4) 0-23 h: -0.2 (-1.2, 0.7) 1 day: 0.1 (-0.7, 0.8) 2 day: -0.1 (-0.7, 0.7) 3 day: 0.4 (-0.3, 1.1) 4 day: 0.1 (-0.7, 0.7) 0-4 day avg: 0.3 (-0.9, 1.5) Factor 4 : 0-5 h: -1.5 (-2.8 to -0.2) 6-11 h: -1.3 (-3.0, 0.3) 12-17 h: -1.1 (-2.7, 0.4) 18-23 h: -0.9 (-2.4, 0.6) 0-23 h: -1.6 (-3.3, 0.1) 1 day: -1.2 (-3.3, 0.9) 2 day: -1.0 (-3.2, 1.2) 3 day: 0.2 (-1.5, 1.9) 4 day: 0.5 (-1.0, 2.0) 0-4 day avg: -1.7 (-4.1, 0.7) Factor 5 : 0-5 h: -1.6 (-3.6, 0.4) 6-11 h: -0.1 (-2.1, 2.0) 12-17 h: -0.2 (-2.2, 1.8) 18-23 h: -1.8 (-3.8, 0.2) 0-23 h: -1.2 (-3.4, 1.0) 1 day: -1.8 (-4.2, 0.6) 2 day: -0.7 (-3.5, 2.1) 3 day: 0.8 (-1.5, 3.2) 4 day: 0.5 (-1.5, 2.5) 0-4 day avg: -1.4 (-4.0, 1.2) vWF, % change (95%CI)Factor 1: 0-5 h: 1.1 (-1.5, 3.6) 6-11 h: 1.6 (-1.2, 4.5) 12-17 h: 0.4 (-1.4, 2.1) 18-23 h: 1.4 (-0.6, 3.5) 0-23 h: 1.6 (-1.3, 4.4) 1 day: -1.0 (-3.9, 1.9) 2 day: -1.8 (-4.8, 1.2)



### December 2009 E-74

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 3 day: -2.5 (-5.8, 0.9) 4 day: 0.5 (-2.9, 3.9) 0-4 day avg: -2.5 (-7.1, 2.2) Factor 2 : 0-5 h: 0.4 (-2.4, 3.2) 6-11 h: -0.4 (-4.3, 3.4) 12-17 h: 2.1 (-1.4, 5.7) 18-23 h: 2.3 (-1.4, 5.9) 0-23 h: 1.9 (-2.8, 6.6) 1 day: 2.8 (-2.8, 8.3) 2 day: 5.1 (-0.8, 11.1) 3 day: 11.4 (5.3, 17.6) 4 day: 6.6 (0.0, 13.1) 0-4 day avg: 11.4 (3.7, 19.1) Factor 3 : 0-5 h: 1.8 (0.1, 3.6) 6-11 h: 1.7 (-0.3, 3.7) 12-17 h: 2.2 (0.3, 4.2) 18-23 h: 2.8 (1.1, 4.5) 0-23 h: 2.8 (0.8, 4.8) 1 day: 2.7 (1.0, 4.4) 2 day: 3.4 (1.8, 5.0) 3 day: 2.3 (0.8, 3.8) 4 day: 1.4 (-0.2, 2.9) 0-4 day avg: 4.8 (2.0, 7.6) Factor 4 : 0-5h: 1.5 (-1.4, 4.3) 6-11h: 2.0 (-1.7, 5.6) 12-17h: 2.6 (-0.8, 5.9) 18-23h: 3.5 (0.4, 6.6) 0-23h: 3.2 (-0.5, 7.0) 1 day: 5.4 (0.6, 10.2) 2 day: 4.5 (-0.6, 9.5) 3 day: 3.8 (-0.6, 8.1) 4 day: 3.0 (-0.6, 6.6) 0-4d avg: 11.3 (5.0, 17.6) Factor 5 : 0-5 h: 1.9 (-2.8, 6.6) 6-11 h: 3.2 (-1.6, 8.0) 12-17 h: 2.4 (-2.3, 7.1) 18-23 h: 1.6 (-3.1, 6.2) 0-23 h: 2.9 (-2.5, 8.2) 1 day: -2.2 (-7.6, 3.2) 2 day: -1.3 (-7.4, 4.9) 3 day: 1.1 (-4.8, 7.1) 4 day: 1.3 (-4.2, 6.7) 0-4 day avg: 3.3 (-4.1, 10.6) CRP, Odds Ratio (95%CI) Factor 1 0-5 h: 0.9 (0.7, 1.1) 6-11 h: 1.4 (1.1, 1.8) 12-17 h: 1.2 (1.0, 1.4) 18-23 h: 1.0 (0.8, 1.3) 0-23 h: 1.1 (0.9, 1.5) 1 day: 1.4 (1.1, 1.8) 2 day: 1.3 (1.0, 1.7) 3 day: 1.0 (0.7, 1.4) 4 day: 1.1 (0.9, 1.5) 0-4 day avg: 1.6 (1.1, 2.2) Factor 2 0-5h: 0.8 (0.6, 1.0) 6-11h: 1.0 (0.7, 1.4) 12-17h: 1.1 (0.8, 1.5) 18-23h: 1.0 (0.8, 1.4) 0-23h: 0.9 (0.6, 1.4) 1 day: 0.9 (0.6, 1.5) 2 day: 2.1 (1.3, 3.3) 3 day: 1.9 (1.0, 3.6) 4 day: 1.4 (0.8, 2.3) 0-4d avg: 1.4 (0.8, 2.6) Factor 3 0-5 h: 1.0 (0.8, 1.1) 6-11 h: 0.9 (0.8, 1.1) 12-17 h: 1.0 (0.9, 1.2) 18-23 h: 1.0 (0.8, 1.2) 0-23 h: 1.0 (0.8, 1.2) 1 day: 1.1 (1.0, 1.3)



### December 2009 E-75

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 2 day: 1.0 (0.9, 1.2) 3 day: 1.2 (1.1, 1.4) 4 day: 1.1 (1.0, 1.3) 0-4 dY avg: 1.2 (1.0, 1.5) Factor 4 0-5 h: 0.8 (0.6, 1.1) 6-11 h: 0.8 (0.6, 1.1) 12-17 h: 1.3 (1.0, 1.8) 18-23 h: 1.1 (0.8, 1.5) 0-23 h: 1.0 (0.7, 1.4) 1 day: 1.5 (1.0, 2.3) 2 day: 2.0 (1.3, 3.2) 3 day: 1.5 (0.9, 2.3) 4 day: 1.3 (0.9, 1.8) 0-4 day avg: 1.7 (1.0, 2.9) Factor 5 0-5 h: 0.7 (0.5, 1.1) 6-11 h: 1.4 (0.9, 2.1) 12-17 h: 1.9 (1.3, 2.8) 18-23 h: 1.4 (1.0, 2.0) 0-23 h: 1.4 (0.9, 2.2) 1 day: 1.6 (1.0, 2.6) 2 day: 1.6 (0.9, 2.6) 3 day: 2.3 (1.3, 4.1) 4 day: 1.6 (0.9, 2.8) 0-4 day avg: 2.1 (1.2, 3.8) Reference: Zanobetti et al. (2004, 087489 ) Period of Study: 1999-2001

Location: Boston, Massachusetts, USA Outcome: Blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial blood pressure) Age Groups: Elderly Study Design: Panel study

N: 62 elderly subjects with n = 631 repeated visits for cardiac rehabilitation Statistical Analysis: Linear mixed effects models Pollutant: PM 2.5 Averaging Time: 24 h Median (10th-90th percentile) Median: 8.8 μg/m 3

10th-90th: 13.4 Monitoring Stations: 1 Copollutant: SO 2 , O 3 , CO, NO 2 , BC 120-h avg

Median: 0.651

10th-90th: 0.376 PM Increment: . 10.4 μg/m 3 for 5-day mean, 13.9 μg/m 3 for 2-day mean

Effect Estimate: Each 10.4 μg/m 3 increase in 5-day mean PM 2.5 concentration was associated with: Systolic BP: 2.8mmHg (95% CI: 0.1, 5.5) Diastolic BP: 2.7mmHg (95% CI: 1.2, 4.3) Mean arterial BP: 2.7mmHg (95% CI: 1.0, 4.5) Each 13.9 μg/m 3 increase in 2-day mean PM 2.5 , during exercise in person with H.70bpm Diastolic: 7.0mmHg (95% CI: 2.3, 12.1) Mean arterial BP: 4.7mmHg (95% CI: 0.5, 9.1)



### December 2009 E-76

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zeka et al. (2006, 157177 ) Period of Study: Nov 2000-Dec 2004

Location: Greater Boston area (Massachusetts) Outcome: White blood cells (WBC), Creactive protein (CRP), sediment rate, fibrinogen Age Groups: Mean age (SD) = 73.0 (6.7) Study Design: Cross-sectional

N: 710 subjects Statistical Analyses: Linear regression

Covariates: Age, BMI, season (also assessed potential for confounding by temperature, RH, barometric pressure, hypertensive or cardiac medications, hypertension, smoking, alcohol, and fasting glucose levels) Dose-response Investigated? No Pollutant: BC Averaging Time: Hourly (PN, BC, PM 2.5 ) and 24-h (SO 4 2– ) measurements used to create 48-h, 1-wk, and 4-wk ma Mean (SD): 0.77 (0.63)

Percentiles: 50th: 0.61

75th: 1.00

90th: 1.51 Monitoring Stations: 2 sites

Units: ng/m 3 Copollutant (correlation): PM 2.5 (r = 0.52)

BC PN (r = 0.30)

SO 4 2– (r = 0.30) PM Increment: 1 SD increase Effect Estimate [Lower CI, Upper CI]: % increase (95%CI) in biomarker per 1 SD increase in pollutant. Fibrinogen 48 h: 0.84 (-0.63, 2.31) 1 wk: 0.60 (-0.95, 2.15) 4 wk: 1.78 (0.19, 3.36) CRP 48 h: 4.51 (-2.03, 11.06) 1 wk: 1.07 (-5.55, 7.68) 4 wk: 5.41 (-1.00, 11.81) Sediment rate 48 h: -4.56 (-25.55, 16.43) 1 wk: 1.98 (-18.15, 22.11) 4 wk: 21.65 (1.48, 41.82) WBC count 48 h: -0.63 (-2.45, 1.19) 1 wk: -0.13 (-1.87, 1.60) 4 wk: -0.55 (-2.36, 1.26) Note: No statistically significant difference was reported for any category of effect modifiers (age, obesity, medications, homozygous for the deletion of GSTM1-null, hypertension) However, results suggested almost all the effect of BC on sediment rate was among the younger group (<78 yr)

There was a 4-fold difference for the association between BC and CRP in the presence of obesity Also evidence for effect modification by obesity of the association between BC and sediment rate There was a suggestive greater effect of BC on CRP among GSTM1-null subjects (9.73% [1.48, 17.98]) vs.. GSTM1- present subjects (-2.97% [-14.05, 8.10] for concentrations 4-wk prior) A stronger effect of BC on sediment rate was seen among non-users of statins (36.01% [13.88, 58.13]) vs.. users (-12.29% [39.13, 14.55])

Reference: Zeka et al. (2006, 157177 ) Period of Study: Nov 2000-Dec 2004

Location: Greater Boston area (Massachusetts) Outcome: White blood cells (WBC), Creactive protein (CRP), sediment rate, fibrinogen Age Groups: Mean age (SD) = 73.0 (6.7) Study Design: Cross-sectional

N: 710 subjects Statistical Analyses: Linear regression

Covariates: Age, BMI, season (also assessed potential for confounding by temperature, RH, barometric pressure, hypertensive or cardiac medications, hypertension, smoking, alcohol, and fasting glucose levels) Dose-response Investigated? No Pollutant: SO 4 2– Averaging Time: Hourly (PN, BC, PM 2.5 ) and 24-h (SO 4 2– ) measurements used to create 48-h, 1-wk, and 4-wk ma Mean (SD): 2.29 (1.62)

Percentiles: 50th: 1.84

75th: 2.81

90th: 4.10 Monitoring Stations: 2 sites Copollutant (correlation): PM 2.5 (r = 0.50) BC (r = 0.30) PN (r = -0.15)

SO 4 2– PM Increment: 1 SD increase Effect Estimate [Lower CI, Upper CI]: % increase (95%CI) in biomarker per 1 SD increase in pollutant. Fibrinogen: 48 h: 0.60 (-1.23, 2.42) 1 wk: 0.03 (-1.93, 1.99) 4 wk: 1.12 (-0.52, 2.77) CRP: 48 h: 1.57 (-7.13, 10.27) 1 wk: 0.21 (-8.27, 8.69) 4 wk: 5.29 (-1.91, 12.49) Sediment rate: 48 h: 4.05 (-23.26, 31.36) 1 wk: -5.87 (-32.39, 20.64) 4 wk: -1.60 (-25.24, 22.04) WBC count: 48 h: -0.12 (-2.35, 2.11) 1 wk: -0.48 (-2.87, 1.90) 4 wk: 0.75 (-1.30, 2.80) Note: No statistically significant difference was reported for any category of effect modifiers (age, obesity, medications, homozygous for the deletion of GSTM1-null, hypertension)



### December 2009 E-77

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zeka et al. (2006, 157177 ) Period of Study: Nov 2000-Dec 2004

Location: Greater Boston area (Massachusetts) Outcome (ICD9 and ICD10): White blood cells (WBC), C-reactive protein (CRP), sediment rate, fibrinogen Age Groups: Mean age (SD) = 73.0 (6.7) Study Design: Cross-sectional

N: 710 subjects Statistical Analyses: Linear regression

Covariates: Age, BMI, season (also assessed potential for confounding by temperature, RH, barometric pressure, hypertensive or cardiac medications, hypertension, smoking, alcohol, and fasting glucose levels) Dose-response Investigated? No Statistical Package: NR Pollutant: PM 2.5 Averaging Time: Hourly (PN, BC, PM 2.5 ) and 24-h (SO 4 2– ) measurements used to create 48-h, 1-wk, and 4-wk ma Mean (SD): 11.16 (7.95)

Percentiles: 50th: 9.39

75th: 14.57

90th: 21.48 Monitoring Stations: 2 sites Copollutant (correlation): PM 2.5 BC (r = 0.52) PN (r = -0.02)

SO 4 2– (r = 0.50) PM Increment: 1 SD increase Effect Estimate [Lower CI, Upper CI]: % increase (95%CI) in biomarker per 1 SD increase in pollutant. Fibrinogen: 48 h: -0.18 (-1.93, 1.57) 1 wk: -1.39 (-3.46, 0.67) 4 wk: 1.14 (-0.60, 2.88) CRP: 48 h: -4.88 (-13.29, 3.53) 1 wk: -1.37 (-10.44, 7.71) 4 wk: 4.36 (-3.25, 11.96) Sediment rate: 48 h: -16.91 (-43.66, 9.84) 1 wk: -18.89 (-47.48, 9.70) 4 wk: 24.93 (0.68, 49.18) WBC count: 48 h: -3.18 (-5.39 to -0.97) 1 wk: -0.51 (-3.02, 2.00) 4 wk: -0.03 (-2.17, 2.10) Note: No statistically significant difference was reported for any category of effect modifiers (age, obesity, medications, homozygous for the deletion of GSTM1-null, hypertension)

Reference: Zhang et al. (2009, 191970 ) Period of Study: 1999-2003

Location: U.S. Outcome: Myocardial Ischemia Age Groups: 52-90 Study Design: Panel

N: 55,529 Statistical Analyses: Logistic & Linear Regression

Covariates: A ge, race/ethnicity, education, exam site, BMI, current smoking status, history of CHD, diabetes, hypertension, SBP, chronic lung disease, or hypercholesterolemia, day of week, time of day, temperature, dew point, pressure, season Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-5-day Pollutant: PM 2.5 Averaging Time: NR Mean (SD): Lag 0: 14.1 (8) Lag 1: 13.8 (8) Lag 2: 13.8 (8) Lag 3: 13.8 (8) Lag 4: 13.9 (8) Lag 5: 14.1 (8) Lag 0-2: 13.9 (7) Monitoring Stations: NR‡ Co-pollutant: NR ‡ Monitors used in model for spatial interpolation of daily PM values. PM Increment: 10 μg/m 3 Odds Ratio (Lower CI, Upper CI), lag:

Minnesota Codes* MC4: 1.04 (0.97, 1.10), lag 0-2 MC4: 1.04 (0.98, 1.11), lag 3-5 MC5: 1.05 (1.00, 1.09), lag 0-2 MC5: 1.04 (1.00, 1.08), lag 3-5 MC 4 or 5: 1.04 (1.00, 1.09), lag 0-2 MC 4 or 5: 1.03 (0.99, 1.07), lag 3-5 Change (Lower CI, Upper CI), lag: ST-segment amplitude Lead I: -0.07 (-0.36, 0.21), lag 0-2 Lead I: 0.18 (-0.10, 0.46), lag 3-5 Lead II: -0.12 (-0.47, 0.23), lag 0-2 Lead II: 0.16 (-0.18, 0.50), lag 3-5 Lead aVL: -0.01 (-0.25, 0.23), lag 0-2 Lead aVL: 0.11 (-0.12, 0.34 ), lag 3-5 Lead V1: -0.02 (-0.39, 0.35), lag 0-2 Lead V1: -0.22 (-0.58, 0.14), lag 3-5 Lead V2: 0.07 (-0.57, 0.70), lag 0-2 Lead V2: -0.01 (-0.61, 0.62), lag 3-5 Lead V3: -0.11 (-0.68, 0.47), lag 0-2 Lead V3: -0.02 (-0.58, 0.54), lag 3-5 Lead V4: -0.0.3 (-0.51, 0.45), lag 0-2 Lead V4: 0.24 (-0.23, 0.71), lag 3-5 Lead V5: -0.01 (-0.41, 0.39), lag 0-2 Lead V5: 0.35 (-0.04, 0.74), lag 3-5 Lead V6: 0.02 (-0.30, 0.33), lag 0-2 Lead V6: 0.35 (0.04, 0.65), lag 3-5 T-wave amplitude Lead I: -1.60 (-3.07, -0.13), lag 0-2 Lead I: -0.31 (-1.73, 1.11), lag 3-5 Lead II: -0.54 (-1.99, 0.92), lag 0-2 Lead II: 0.71 (-0.70, 2.13), lag 3-5 Lead aVL: -1.21 (-2.50, 0.10), lag 0-2 Lead aVL: -0.55 (-1.18, 0.71), lag 3-5 Lead V1: 1.45 (-0.16, 3.06), lag 0-2 Lead V1: 0.03 (-1.53, 1.59), lag 3-5 Lead V2: -0.18 (-2.96, 2.60), lag 0-2 Lead V2: 0.57 (-2.12, 3.27), lag 3-5 Lead V3: -2.33 (-5.15, 0.49), lag 0-2 Lead V3: -0.13 (-2.87, 2.60), lag 3-5 Lead V4: -2.03 (-4.69, 0.63), lag 0-2 Lead V4: 0.64 (-1.94, 3.22), lag 3-5 Lead V5: -1.92 (-4.22, 0.38), lag 0-2 Lead V5: 0.55 (-1.69, 2.78), lag 3-5 Lead V6: -0.63 (-2.36, 1.10), lag 0-2 Lead V6: 0.82 (-0.86, 2.49), lag 3-5 QRS/T angles and heart rate (change)



### December 2009 E-78

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

QRS/T angle-spatial (°): 0.19 (-0.21, 0.59), lag 0-2 QRS/T angle-spatial (°): -0.20 (-0.59, 0.19), lag 3-5 QRS/T angle-frontal (°): 0.13 (-0.24, 0.50), lag 0-2 QRS/T angle-frontal (°): 0.35 (-0.01, 0.71), lag 3-5 Heart Rate (beats/min): 0.16 (0.02, 0.30), lag 0-2 Heart Rate (beats/min): 0.04 (-0.10, 0.18), lag 3-5 *Any ST abnormality (MC 4.1-4.4) Any T abnormality (MC 5.1-5.4)

1 All units expressed in μg/m 3 unless otherwise specified.



# Table E-4. Short-term exposur e-cardiovascular morbidity stud ies: Other size fractions.

Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Adar et al. (2007, 001458 ) Period of Study: Mar-Jun 2002

Location: St. Louis, Missouri Outcome: Heart rate variability: heartrate, standard deviation of all normal-tonormal intervals (SDNN), square root of the mean squared difference between adjacent normal-to-normal intervals (rMSSD), percentage of adjacent normal-to-normal intervals that differed by more than 50 ms (pNN50), high frequency power (HF in the range of 0.15-0.4Hz), low frequency power (LF, in the range of 0.04-0.15Hz), and the ratio of LF/HF Age Groups: ≥ 60 yr Study Design: Panel (4 planned repeated measures with a total of 158 person-trips 35 participating in all 4 trips)

N: 44 participants Statistical Analyses: Generalized additive models

Covariates: Subject, weekday, time, apparent temperature, trip type, activity, medications, and autoregressive terms

Season: Limited data collection period Dose-response Investigated? No Statistical Package: SAS v8.02, R v2.0.1 Pollutant: Particle count fine (PC fine) (particles/cm 3 ) Averaging Time: Measurements collected over 48-h period surrounding the bus trip (during which health endpoints were measured) used to calculate 5-, 30-, 60-min, 4-h, 24-h ma Median (IQR): All: 42 (57) Facility: 36 (45) Bus: 105 (96) Activity: 50 (133) Lunch: 69 (48) Monitoring Stations: 2 portable carts Copollutant: PM 2.5 BC Fine particle counts Coarse particle counts

Correlation notes: 24-h mean PM 2.5 , BC, and fine particle count concentrations ranged from 0.80 to 0.98

r = 0.76 to 0.97 when limited to time spent on the bus r = 0.55 to 0.86 when comparing bus concentrations to 24-h ma r = -0.003 to 0.51 when comparing 5- min avg and 24-h ma. Poor correlations found between coarse particle count concentrations and all fine particulate measures during all times periods PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: % change (95%CI) in HRV per IQR in the 24-h ma of the microenvironmental pollutant (IQr = 39 pt/cm 3 ) Single-pollutant models SDNN: -5.1 (-5 .8 to -4.4) rMSSD: -8.0 (-8.7 to -7.2) pNN50 + 1: -10.2 (-11.3 to -9.0) LF: -9.9 (-11.4 to -8.4) HF: -13.7 (-15.1 to -12.2) LF/HF: 4.3 (3.1, 5.5) H: 0.9 (0.8, 1.1)

Note: Exposure to health associations by all lag periods presented in Fig 2 (magnitude of associations increased with averaging period, with the largest associations consistently found for 24-h ma)



### December 2009 E-79

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Adar et al. (Adar et al., 2007, 001458 ) Period of Study: Mar-Jun 2002

Location: St. Louis, Missouri Outcome: Heart rate variability: heartrate, standard deviation of all normal-tonormal intervals (SDNN), square root of the mean squared difference between adjacent normal-to-normal intervals (rMSSD), percentage of adjacent normal-to-normal intervals that differed by more than 50 ms (pNN50), high frequency power (HF in the range of 0.15-0.4Hz), low frequency power (LF, in the range of 0.04-0.15Hz), and the ratio of LF/HF Age Groups: ≥ 60 yr Study Design: Panel (4 planned repeated measures with a total of 158 person-trips 35 participating in all 4 trips)

N: 44 participants Statistical Analyses: Generalized additive models

Covariates: Subject, weekday, time, apparent temperature, trip type, activity, medications, and autoregressive terms

Season: Limited data collection period Dose-response Investigated? No Statistical Package: SAS v8.02, R v2.0.1 Pollutant: Particle count coarse (PT coarse) (pt/cm 3 ) Averaging Time: Measurements collected over 48-h period surrounding the bus trip (during which health endpoints were measured) used to calculate 5-, 30-, 60-min, 4-h, and 24-h

ma Median (IQR): All: 0.02 (0.11) Facility: 0.01 (0.04) Bus: 0.16 (0.13) Activity: 0.29 (0.26) Lunch: 0.16 (0.36) Monitoring Stations: 2 portable carts Copollutant: PM 2.5 BC Fine particle counts Coarse particle counts Correlation notes: 24-h mean PM 2.5 , BC, and fine particle count concentrations ranged from 0.80 to 0.98

r = 0.76 to 0.97 when limited to time spent on the bus r = 0.55 to 0.86 when comparing bus concentrations to 24-h ma r = -0.003 to 0.51 when comparing 5- min avg and 24-h ma. Poor correlations found between coarse particle count concentrations and all fine particulate measures during all times periods PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: % change (95%CI) in HRV per IQR in the 24-h ma of the microenvironmental pollutant (IQr = 0.066 pt/cm 3 ) Single-pollutant models SDNN: 2.4 (1.3, 3.6) rMSSD: 3.9 (2.6, 5.1) pNN50 + 1: 2.9 (1.0, 4.9) LF: 6.4 (3.7, 9.1) HF: 10.2 (7.4, 13.1) LF/HF: -3.3 (-5.0 to -1.6) H: -1.1 (-1.3 to -0.8) Two-pollutant models (with PM 2.5 ): SDNN: -0.7 (-1.9, 0.6) rMSSD: -1.3 (-2.6 to -0.05) pNN50 + 1: -4.3 (-6.3 to -2.4) LF: 0.2 (-2.5, 3.0) HF: 1.3 (-1.5, 4.1) LF/HF: -0.9 (-2.7, 1.0) H: -0.6 (-0.9 to -0.4)

Note: Exposure to health associations by all lag periods presented in Fig 2 (magnitude of associations increased with averaging period, with the largest associations consistently found for 24-h ma)

Reference: Delfino et al. (2008, 156390 ) Period of Study: 2005-2006

Location: Los Angeles, California, air basin Outcome: C-reactive protein (CRP) Fibrinogen, tumor necrosis factor- α (TNF- α ) and its soluble receptor-II (TNF-RII) Interleukin-6 (IL-6) and its soluble receptor (IL-6sR)

Fibrin D-dimer Soluble platelet selectin (sP-selectin)

Soluble vascular cell adhesion molecule-1 (sVCAM-1)

Intracellular adhesion molecule-1 (sICAM-1) and myeloperoxidase (MPO) Erythrocyte lysates for glutathione peroxidase-1 (GPx-1) Copper-zinc superoxide dismutase (cu, Zn-SOD) Age Groups: ≥ 65 yr Study Design: Panel (biomarkers measured weekly 12 times)

N: 29 participants (nonsmoking with history of coronary artery disease) Statistical Analyses: Mixed models

Covariates: temperature (infectious illnesses were excluded by excluding weeks with such observations)

Season: Collected 6 wk of data during warm period and 6 wk of data during Pollutant: PM (multiple size fractions and components) Averaging Time: 24-h avg preceding the blood draw (lag 0) and cumulative avg up to 5 days preceding the draw Outdoor hourly PM: EC: Mean (SD): 1.61 (0.62) Median: 1.56 IQR: 0.92 Min, Max: 0.24, 3.94 OC: Mean (SD): 5.94 (2.11) Median: 5.58 IQR: 2.79 Min-Max: 2.51, 13.60 BC: Mean (SD): 2.00 (0.77) Median: 1.89 IQR: 0.96 Min-Max: 0.58, 5.11 OCpri: Mean (SD): 3.37 (1.21) Median: 3.21 IQR: 1.63 Min-Max: 0.99, 7.11 Secondary OC: Mean (SD): 2.49 (1.50) Median: 2.10 IQR: 1.86 Min-Max: 0, 8.10 PN (p/cm 3 ): Mean (SD): 16,043 (5886) Median: 13,968 IQR: 7,386 Min-Max: 6837, 31263 Indoor hourly PM EC: Mean (SD): 1.31 (0.52) Median: 1.30 IQR: 0.70 Min-Max: 0.19, 2.89 PM Increment: IQR Effect Estimate [Lower CI, Upper CI]:

Note: Nearly all results presented in figures

Results: The authors found significant positive associations for CRP, IL-6, sTNF-RII, and sP-selectin with outdoorand/or indoor concentrations of quasiultrafine PM ≤ 0.25 μ m in diameter, EC, OCpri, BC, PN, CO, and nitrogen dioxide from the current-day and multiday avg. There were consistent positive but largely nonsignificant coefficients for TNF- α , sVCAM-1, and sICAM-1, but not fibrinogen, IL-6sR, or D-dimer. The authors found inverseassociations for erythrocyte Cu, ZnSOD with these pollutants and other PM size fractions (0.25-2.5 and 2.5-10 μ m). Inverse associations of GPx-1 and MPO with pollutants were largely nonsignificant. Indoor associations were often stronger for estimated indoor EC, OCpri, and PN of outdoor origin than for uncharacterized indoor measurements. There was no evidence for positive associations with SOA.



### December 2009 E-80

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) cool period Dose-response Investigated? No Statistical Package: NR EC of outdoor origin: Mean (SD): 1.11 (0.39) Median: 1.06 IQR: 0.51 Min-Max: 0.41, 2.97 OC: Mean (SD): 5.69 (1.51) Median: 5.60 IQR: 1.96 Min-Max: 2.34, 10.79 OCpri of outdoor origin: Mean (SD): 2.18 (0.82) Median: 2.15 IQR: 1.07 Min-Max: 0.32, 5.21 Secondary OC of outdoor origin: Mean (SD): 2.08 (1.26) Median: 1.75 IQR: 1.45 Min-Max: 0, 6.87 PN (particles/cm 3 ): Mean (SD): 14,494 (6770) Median: 12,341 IQR: 7,337 Min-Max: 1016, 43027 PN of outdoor origin (p/cm 3 ): Mean (SD): 10,108 (3108) Median: 9,580 IQR: 3,684 Min-Max: 1016, 17700 Outdoor PM mass PM0.25: Mean (SD): 9.47 (2.97) Median: 9.4 IQR: 4.2 Min-Max: 3.31, 18.75 PM0.25-2.5: Mean (SD): 13.53 (10.67) Median: 11.7 IQR: 11.5 Min-Max: 1.29, 66.77 PM 10-2.5 : Mean (SD): 10.04 (4.07) Median: 9.9 IQR: 5.9 Min-Max: 1.76, 22.38 Indoor PM mass PM0.25: Mean (SD): 10.45 (6.77) Median: 9.5 IQR: 4.5 Min-Max: 1.42, 69.86 PM0.25-2.5 (μg/m 3 ): Mean (SD): 7.36 (4.57) Median: 6.5 IQR: 5.7 Min-Max: 0.77, 30.86 PM 10-2.5 : Mean (SD): 4.12 (4.76) Median: 2.8 IQR: 3.5 Min-Max: 0.12, 37.63 Copollutant: Outdoor hourly gases (NO 2 , CO, O 3 ) and indoor hourly gases (NO 2 , CO)

Reference: Pekkanen et al. (2002, 035050 ) Period of Study: Winter 1998-1999

Location: Helsinki, Finland Outcome : ST Segment Depression (>0.1mV) Study Design : Panel of ULTRA Study participants

N : 45 Subjects, n = 342 biweekly submaximal exercise tests, 72 exercise induced ST Segment Depressions Statistical Analysis: Logistic regression / GAM Pollutant: Ultrafine NC0.01-0.1 μm (n/cm 3 ) Averaging Time: 24 h

Median : 14,890

IQR : 9830 Monitoring Stations : 1 Copollutant: NO 2 , CO, PM 2.5 , PM 10-2.5 , PM 1 , ACP PM Increment: IQR Effect Estimate(s): NC0.01-0.1: OR = 3.14 (1.56, 6.32), lag 2

Notes : The effect was strongest for ACP and PM 2.5 , which in 2 pollutant models appeared independent. Increases in NO 2 and CO were also associated with increased risk of ST segment depression, but not with coarse particles.



### December 2009 E-81

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Peters et al. (2005, 095747 ) Also Peters et al, 2005 (2005, 156859 ) Period of Study: Feb 1999-Jul 2001

Location: Augsburg, Germany Outcome: Myocardial infarction Study Design: Case-crossover

N: 691 myocardial infarction patients Statistical Analysis: Conditional logistic regression Dose-response investigated (yes/no)? No Pollutant: Ultrafine (TNC) (n/cm 3 ) Averaging Time: 1 h: Median = 10,001

IQR: 7919 24 h: Median = 10,934

IQR: 6276 Copollutant: NO 2 , SO 2 , CO PM Increment: Effect Estimate: 2-h lag: OR = 0.95 95% CI: 0.84, 1.06 24-h mean, 2-day lag: OR = 1.04 95% CI: 0.90, 1.20

Notes: Examined triggering for MI at various lags before MI onset (up to 6 h before MI, up to 5 days before MI). No statistically significant increases in lagged ultrafine particle concentration were found.

Reference: Ruckerl et al. (2006, 088754 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome (ICD9 and ICD10): C-reactive protein (CRP) Serum amyloid A (SAA)

E-selectin von Willebrand Factor (vWF)

Intercellular adhesion molecule-1 (ICAM-1) Fibrinogen

Factor VII Prothrombin fragment 1+2

D-dimer Age Groups: 50+ yr Study Design: Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear and logistic regression models

Covariates: Models adjusted for different factors based on health endpoint CRP: RH, temperature, trend, ID ICAM-1: temperature, trend, ID vWF: air pressure, RH, temperature, trend, ID FVII: air pressure, RH, temperature, trend, ID, weekday

Season: Time trend as covariate Dose-response Investigated? Sensitivity analyses examined nonlinear exposure-response functions Statistical Package: SAS v8.2 and SPlus v6.0 Pollutant: AP (n/cm 3 ) Averaging Time: 24 h Mean (SD): 1593 (1034)

Percentiles:

25: 821

50: 1238

75: 2120 Range (Min, Max): 328, 4908 Unit (i.e. μg/m 3 ): n/cm 3 Monitoring Stations: 1 site Copollutant: UFPs

AP

PM 2.5 PM 10 OC

EC

NO 2 CO PM Increment: IQR (1299 5-day avg: 1127) Effect Estimate [Lower CI, Upper CI]: Effects of air pollution on blood markers presented as OR (95%CI) for an increase in the blood marker above the 90th percentile per increase in IQR air pollutant. CRP Time before draw: 0 to 23 h: 0.7 (0.5, 1.2) 24 to 47 h: 1.5 (0.9, 2.6) 48 to 71 h: 3.2 (1.7, 6.0) 5-day mean: 1.5 (0.8, 3.0) ICAM-1 Time before draw: 0 to 23 h: 0.6 (0.4, 0.9) 24 to 47 h: 1.8 (1.2, 2.8) 48 to 71 h: 1.6 (1.0, 2.5) 5-day mean: 0.9 (0.6, 1.5) Effects of air pollution on blood markers presented as % change from the mean/GM in the blood marker per increase in IQR air pollutant. vWF Time before draw: 0 to 23 h: 4.8 (0.2, 9.3) 24 to 47 h: 5.9 (0.4, 11.5) 48 to 71 h: 7.0 (0.7, 13.4) 5-day mean: 13.5 (6.3, 20.6) FVII Time before draw: 0 to 23 h: 0.0 (-2.9, 3.0) 24 to 47 h: -2.9 (-6.1, 0.4) 48 to 71 h: -3.6 (-6.8 to -0.3) 5-day mean: -4.1 (-7.9 to -0.3) Note: Summary of results presented in figures.

SAA results indicate increase in association with PM (not as strong and consistent as with CRP)

No association observed between Eselectin and PM An increase in prothrombin fragment 1+2 was consistently observed, particularly with lag 4 Fibrinogen results revealed few significant associations, potentially due to chance

D-dimer results revealed null associations in linear and logistic analyses



### December 2009 E-82

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ruckerl et al. (2006, 088754 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome: Soluble CD40 ligand (sCD40L), platelets, leukocytes, erythrocytes, hemoglobin Age Groups: 50+ yr Study Design : Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear regression models

Covariates: Long-term time trend, weekday of the visit, temperature, RH, barometric pressure

Season: Time trend as covariate Dose-response Investigated? No Statistical Package: SAS v8.2 and SPlus v6.0 Pollutant: AP (n/cm 3 ) Averaging Time: 24 h Mean (SD): 1593 (1034)

Percentiles: 25th: 821

50th: 1238

75th: 2120 Range (Min, Max): 328, 4908 Monitoring Stations: 1 site Copollutant: UFPs

AP

PM 2.5 PM 10 NO PM Increment: IQR (1299 5-day avg: 1127) Effect Estimate [Lower CI, Upper CI]: Effects of air pollution on blood markers presented as % change from the mean/GM in the blood marker per increase in IQR air pollutant. sCD40L, % change GM (pg/mL) lag0: 6.9 (0.5, 13.8) lag1: -1.1 (-8.0, 6.4) lag2: -4.9 (-11.9, 2.7) lag3: -3.8 (-10.3, 3.2) 5-day mean: -1.3 (-9.9, 8.1) Platelets, % change mean (103/ μ l) lag0: -1.0 (-2.5, 0.5) lag1: -0.4 (-2.1, 1.6) lag2: 0.8 (-1.0, 2.4) lag3: 0.0 (-1.8, 1.7) 5-day mean: -0.9 (-3.0, 1.3) Leukocytes, % change in mean (103/ μ l) lag0: -1.9 (-3.8 to -0.1) lag1: -0.6 (-2.9, 1.6) lag2: -0.6 (-3.2, 2.0) lag3: -2.3 (-4.6, 0.1) 5-day mean: -2.7 (-5.5, 0.1) Erythrocytes, % change mean (106/ μ l) lag0: -0.1 (-0.5, 0.3) lag1: -0.4 (-0.9, 0.2) lag2: -0.4 (-0.9, 0.2) lag3: -0.4 (-0.6, 0.3) 5-day mean: -0.4 (-1.0, 0.2) Hemoglobin, % change mean (g/dl) lag0: -0.2 (-0.7, 0.4) lag1: -0.3 (-1.0, 0.4) lag2: -0.1 (-0.9, 0.7) lag3: -0.1 (-0.8, 0.6) 5-day mean: -0.2 (-1.1, 0.6) Reference: Ruckerl et al. (2007, 156931 ) Period of Study: May 2003-Jul 2004

Location: Athens, Augsburg, Barcelona, Helsinki, Rome, and Stockholm Outcome: Interleukin-6 (IL-6), fibrinogen, C-reactive protein (CRP) Age Groups: 35-80 yr Study Design: Repeated measures / longitudinal

N: 1003 MI survivors Statistical Analyses: Mixed-effect models

Covariates: City-specific confounders (age, sex, BMI) Long-term time trend and apparent temperature RH, time of day, day of week included if adjustment improved model fit

Season: Long-term time trend Dose-response Investigated? Used psplines to allow for nonparametric exposure-response functions Statistical Package: SAS v9.1 Pollutant: UFP (n/cm 3 ) Averaging Time: Hourly and 24 h (lag 0-4, mean of lags 0-4, mean of lags 0-1, mean of lags2-3, means of lags 0-3) Mean (SD): Presented by city only

Percentiles: NR Range (Min, Max): NR Monitoring Stations: Central monitoring sites in each city Copollutant: SO 2 O 3 NO

NO 2 PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: % change in mean blood markers per increase in IQR of air pollutant. IL-6 Lag (IQR): % change in GM (95%CI) Lag 0 (11852): 1.88 (-0.16, 3.97) Lag 1 (11852): -0.67 (-2.56, 1.25) Lag 2 (11852): -2.12 (-4.03 to -0.17) 5-day avg (11003): -0.93 (-3.37, 1.56)

Fibrinogen Lag (IQR): % change in AM (95%CI) Lag 0 (11852): 0.40 (-0.40, 1.19) Lag 1 (11852): 0.11 (-0.69, 0.91) Lag 2 (11852): 0.09 (-0.71, 0.90) 5-day avg (11003): 0.50 (-2.20, 3.20)

CRP Lag (IQR): % change in GM (95%CI) Lag 0 (11852): 1.33 (-3.05, 5.90) Lag 1 (11852): -1.52 (-4.39, 1.45) Lag 2 (11852): -1.63 (-6.70, 3.71) 5-day avg (11003): -0.08 (-3.78, 3.75)



### December 2009 E-83

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Pekkanen et al. (2002, 035050 ) Period of Study: Winter 1998-1999

Location: Helsinki, Finland Outcome : ST Segment Depression (>0.1mV) Age Groups: Study Design : Panel of ULTRA Study participants

N : 45 Subjects, n = 342 biweekly submaximal exercise tests, 72 exercise induced ST Segment Depressions Statistical Analysis: Logistic regression / GAM Pollutant: Ultrafine NC0.01-0.1 μm (n/cm 3 ) Averaging Time: 24 h

Median : 14,890

IQR : 9830 Monitoring Stations : 1 Copollutant: NO 2 , CO, PM 2.5 , PM 10-2.5 , PM 1 , ACP PM Increment: IQR Effect Estimate(s): NC0.01-0.1: OR = 3.14 (1.56, 6.32), lag 2

Notes : The effect was strongest for ACP and PM 2.5 , which in 2 pollutant models appeared independent. Increases in NO 2 and CO were also associated with increased risk of ST segment depression, but not with coarse particles.

Reference: Peters et al. (2005, 095747 ) Also Peters et al, 2005 (2005, 156859 ) Period of Study: Feb 1999-Jul 2001

Location: Augsburg, Germany Outcome: Myocardial infarction Study Design: Case-crossover

N: 691 myocardial infarction patients Statistical Analysis: Conditional logistic regression Dose-response Investigated? No Pollutant: Ultrafine (TNC) (n/cm 3 ) Averaging Time: 1 h: Median = 10,001

IQR: 7919 24-h: Median = 10,934

IQR: 6276 Copollutant: NO 2 , SO 2 , CO PM Increment: Effect Estimate: 2-h lag: OR = 0.95 95% CI: 0.84, 1.06 24-h mean, 2-day lag: OR = 1.04 95% CI: 0.90, 1.20

Notes: Examined triggering for MI at various lags before MI onset (up to 6 h before MI, up to 5 days before MI). No statistically significant increases in lagged ultrafine particle concentration were found.

Reference: Ruckerl et al. (2007, 091379 ) Period of Study: Oct 2000-Apr 2001

Location: Erfurt, Germany Outcome (ICD9 and ICD10): Soluble CD40 ligand (sCD40L), platelets, leukocytes, erythrocytes, hemoglobin Age Groups: 50+ yr Study Design : Panel (12 repeated measures at 2-wk intervals)

N: 57 male subjects with coronary disease Statistical Analyses: Fixed effects linear regression models

Covariates: Long-term time trend, weekday of the visit, temperature, RH, barometric pressure

Season: Time trend as covariate Dose-response Investigated? No Statistical Package: SAS v8.2 and SPlus v6.0 Pollutant: UFP Averaging Time: 24 h Mean (SD): 12,602 (6455)

Percentiles: 25th: 7326 50th: 11,444 75th: 17,332 Range (Min, Max): 328, 4908 Monitoring Stations: 1 site Copollutant:

AP

PM 2.5 PM 10 NO PM Increment: IQR (10,005 5-day avg: 6,821) Effect Estimate [Lower CI, Upper CI]: sCD40L, % change GM (pg/mL) lag 0: 7.1 (0.1, 14.5) lag 1: 0.3 (-6.6, 8.6) lag 2: 0.6 (-5.9, 8.6) lag 3: -8.5 (-15.8, -0.5) 5-day mean: -0.7 (-7.6, 6.8) Platelets, % change mean (103/ μ l) lag 0: -1.8 (-3.4, -0.2) lag 1: -1.1 (-2.9, 0.6) lag 2: 1.0 (-2.9, 0.8) lag 3: -2.4(4.5, -0.3) 5-day mean: -2.2 (-4.0, -0.3) Leukocytes, [103/ μ l] lag 0: -2.4 (-4.5, -0.2) lag 1: -2.1 (-4.4, 0.2) lag 2: -0.2 (-2.4, 2.8) lag 3: -1.5 (-4.4, 1.4) 5-day mean: -1.6 (-4.1, 0.8)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-84

# E.1.2. Cardiovascular Emergency Depart ment Visits and Hospital Admissions

Table E-5. Short-term expos ure-cardiovascular: ED/HA PM 10



### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Anderson et al. (2003, 054820 ) Period of Study: 1992-1994

Location: London, U.K. Outcome: Ischemic Heart Disease Age Groups: 0-15, 15-64, 65-74, 75+ Study Design: Time series

N: NR Statistical Analyses: NR

Covariates: NR Dose-response Investigated? No Statistical Package: NR Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): NR Monitoring Stations: NR Copollutant: NR PM Increment: 10th-90th percentile % Change in Daily IHD Admissions by Age [CI]: 0-15 yr: NR 15-64 yr: 2.6 [0.3,5] 65-74 yr: 2.5 [0.1,4.9] 75+ yr: 2.2 [0.2,4.6]

Notes: RRs are presented in graph form showing little change with increasing age (PM increment of 10 μg/m 3 ). This article is primarily a systematic literature review of other studies.

Reference: Andersen et al. (2008, 189651 ) Period of Study: May 2001-Dec 2004

Location: Copenhagen, Denmark Outcome (ICD-10): CVD, including angina pectoris (I20), myocardial infarction (I21-22), other acute ischemic heart diseases (I24), chronic ischemic heart disease (I25), pulmonary embolism (I26), cardiac arrest (I46), cardiac arrhythmias (I48-48), and heart failure (I50). Age Groups: > 65 yr (CVD and RD), 5-18 yr (asthma) Study Design: Time series

N: NR Statistical Analyses: Poisson GAM

Covariates: Temperature, dew-point temperature, long-term trend, seasonality, influenza, day of the week, public holidays.

Season: NR Dose-response Investigated: No Statistical Package: R (gam procedure, mgcv package) Lags Considered: Lag 0 -5 days, 4- day pollutant avg (lag 0 -3) for CVD. Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 24(14)

Median: 21

IQR: 16-28 99th percentile): 72 Monitoring Stations: 1 Copollutant (correlation): NCtot: r = 0.39 NC100: r = 0.28 NCa12: r = 0.02 NCa23: r = -0.12 NCa57: r = 0.45 NCa212: r = 0.63 PM 2.5 : r = 0.80 CO: r = 0.37 NO 2 : r = 0.35 NO X : r = 0.32 NO X curbside: r = 0.18 O 3 : r = -0.21 Other variables: Temperature: r = 0.12 Relative humidity: r = 0.05 PM Increment: 13 μ g/m 3 (IQR) Relative risk (RR) Estimate [CI]: CVD hospital admissions (4-day avg, lag 0 -3), age 65+: One-pollutant model: 1.03 [1.01-1.05] Adj for NCtot: 1.04 [1.02-1.06] Adj for NCa212: 1.05 [1.01-1.09] RD hospital admissions (5-day avg, lag 0 -4), age 65+: One-pollutant model: 1.06 [1.02-1.09] Adj for NCtot: 1.05 [1.01-1.10] Adj for NCa212: 1.04 [0.98-1.11] Asthma hospital admissions (6-day avg lag 0-5), age 5 - 18: One-pollutant model: 1.02 [0.93-1.12] Adj for NCtot: 1.01 [0.91-1.12] Adj for NCa212: 0.94 [0.81-1.09] Estimates for individual day lags reported only in Fig form (see notes):

Notes: Fig 2: Relative risks and 95% confidence intervals per IQR in single day concentration (0- to 5-day lag). Summary of Fig 2: CVD: Positive, marginally or statistically significant associations at Lag 0-Lag 2.



### December 2009 E-85

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Anderson et al. (2007, 156214 ) Period of Study: January 1999



# - December 2004

Location: Copenhagen, Denmark Outcome (ICD10): Hospital Admission, CVD, including angina pectoris (I20), myocardial infarction (I21-22), other acute ischemic heart diseases (I24), chronic ischaemic heart disease (I25), pulmonary embolism (I26), cardiac arrest (I46), cardiac arrhythmias (I48-48), and heart failure (I50). Age Groups Analyzed: Age >65 Study Design: Time series N: 2192 days, 9 Hospitals Statistical Analyses: Principal Component Analysis and Constrained Physical Receptor Model (COPREM), Poisson regression, GAM,

Covariates: Season, day of the wk, public holidays, influenza epidemics and meteorology

Season: All yr Dose-response Investigated? No Statistical package: R, gam/mgcv package Lags Considered: 0-6 days Pollutant: Source specific PM 10 components Averaging Time: 24 h Mean (SD): Percentiles: 25th: 16 50th (Median): NR

75th: 30 Monitoring Stations: 1 Copollutant (correlation): PM 10 : Biomass: r = 0.53 Secondary: r = 0.73 Oil: r = 0.57 Crustal: r = 0.37 Sea salt: r = 0.04 Vehicle: r = 0.02 Notes: Correlations between source specific PM 10 components presented in paper PM Increment: IQR

RR Estimate Respiratory disease (age >65) Single pollutant model:

PM 10 : 1.027 (1.013, 1.042), IQR=14

PM 10 (other 5 sources): 1.045 (1.016, 1.074), IQR=13 Biomass: 1.040 (0.009, 1.072), IQR=5.4 Secondary: 1.050 (1.021, 1.081), IQR=6.1 Oil: 1.035 (1.006, 1.065), IQR=2.8 Crustal: 1.054 (1.028, 1.081), IQR=1.8 Sea salt: 0.98 (0.947, 1.017), IQR=2.2 Vehicle: 0.989 (0.949, 1.032), IQR=0.6

Notes: 2 pollutant model results for PM 10 with source specific components and gases also presented in manuscript.

Reference: Baccarelli et al. (2007, 091310 ) Period of Study: Jan 1995-Aug 2005

Location: Lombardia region, Italy Outcome (ICD9 and ICD10): Fasting and postmethionine-load total homocysteine (tHcy) Age Groups: 11-84 yr Study Design: Cross-sectional/Panel

N: 1,213 participants Statistical Analyses: Generalized additive models

Covariates: age, sex, BMI, smoking, alcohol, hormone use, temperature, day of the yr, and long-term trends

Season: Adjusted for long-term trends to account for season Dose-response Investigated? No Statistical Package: R software v2.2.1 Pollutant: PM 10 (some TSP measures used to predict PM 10 ) Averaging Time: Hourly concentrations used to calculate 24-h ma and 7-day

ma Mean (SD): NR

Percentiles: 25th: 20.1

50th: 34.1

75th: 52.6 Range (Min, Max): Max: 390.0 Monitoring Stations: 53 sites Copollutant: CO NO 2 SO 2 O 3 PM Increment: IQR Effect Estimate [Lower CI, Upper CI]: Estimates (%) per 32.5 μg/m 3 increase in 24-h ma of PM 10 Homocysteine, fasting: 0.4 (-2.4, 3.3) Homocysteine, postmethionine-load: (-1.5, 3.7) Estimates (%) per 25.7m 3 increase in 7- day ma of PM 10 Homocysteine, fasting: 1.0 (-1.9, 3.9) Homocysteine, postmethionine-load: 2.0 (-0.6, 4.7) Estimates of effect (%) on fasting homocysteine per IQR increase in 24-h PM 10 levels Among smokers: 6.2 (0.0, 12.7) Among non-smokers: -1.6 (-5.5, 2.5) Estimates of effect (%) on postmethionine-load homocysteine per IQR increase in 24-h PM 10 levels Among smokers: 6.0 (0.5, 11.8) Among non-smokers: -0.1 (-3.6, 3.5)



### December 2009 E-86

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ballester et al. (2006, 088746 ) Period of Study: 1995-1999

Location: 5 Spanish cities: Granada, Huelva, Madrid, Seville, Zaragoza Outcome (ICD-9): All cardiovascular disease (390-459), including all heart diseases (410-414, 427, 428) Age Groups: All ages Study Design: Time series

N: NR Statistical Analyses: Poisson GAMs

Covariates: Dily temp, barometric pressure relative humidity Daily influenza incidence, day of the week, holidays, unusual events (ex. medical strikes), seasonal variation, trend Dose-response Investigated: No Statistical Package: S-Plus GAM function Lags Considered: lag 0-3 days, lag 0-1 avg Pollutant: PM 10 Averaging Time: 24 h Mean (10-90th percentile): overall mean NR. City specific means Granada: 43.2 (24.8, 62.6) Huelva: 38.6 (23.1, 57.3) Madrid: 35.7 (21.4, 54.4) Seville: 41.9 (27.3, 57.6) Zaragoza: 32.8 (17.3, 50.3) Monitoring Stations: At least three stations/city (15+) Copollutant (correlation): Summary of the correlation coefficients between each pair of pollutants within cities: BS: r = 0.48

TSP: N/A

NO 2 : from r = 0.13 to r = 0.62 (median r = 0.40)

SO 2 : from r = 0.20 to r = 0.51 (median r = 0.46)

CO: from r = 0.34 to r = 0.45 (median r = 0.37)

O 3 : from r = -0.07 to r = 0.16 (median r = 0.11) PM Increment: 10 μg/m 3 Relative risk [CI]: Relative risks are expressed only in the form of figures (see notes). Percentage change in risk [CI]: All cardiovascular diseases (avg of lags 0 - 1): 0.91% [0.35, 1.47] Heart disease (avg of lags 0 -1) 1.56% [0.82, 2.31] Notes: Relative risks for the single pollutant models are expressed in Fig 2. Fig 2: Time sequence of the combined association between PM 10 and hospital admissions for all CVD (A) and heart disease (B). Summary of results: Significant, positive association of PM 10 with both overall CVD and heart disease hospitalizations at Lag 0 and Lag 1. Relative risks for 2 pollutant models are expressed in Fig 3: Fig 3: Combined estimates of the association between hospital admissions for heart diseases and air pollutants (avg of lags 0-1 Adjusted for CO, NO 2 , O 3 , or SO 2 ) Summary of results: Significant, positive association remains after adjusting for pollutants.



### December 2009 E-87

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bell et al. (2008, 091268 ) Period of Study: 1995-2002

Location: Taipei, Taiwan Outcome (ICD-9): Hospital admissions for ischemic heart disease (410 , 411, 414), cerebrovascular disease (430-437). Age Groups: All Study Design: Time series

N: 6,909 hospital admissions for ischaemic heart diseases, 11,466 for cerebrovascular disease. Statistical Analyses: Poisson regression

Covariates: Day of the week, time, apparent temperature, long-term trends, seasonality

Season: All Dose-response Investigated: No Statistical Package: NR Lags Considered: lags 0-3 days, avg of lags 0-3 Pollutant: PM 10 Averaging Time: 24 h Mean (range IQR): 49.1 (12.7-215.5 27.6) Monitoring Stations: Taipei area: 13 monitors Taipei City: 5 monitors

Monitors with correlations of 0.75 + for PM 10 : 12 monitors Copollutant: NR PM Increment: 28 μg/m 3 (near IQR) Percentage increase estimate [95% CI]: Ischemic heart disease: Taipei area (13 monitors): L0: 1.91 (-1.25, 5.17) L1: 0.39 (-2.73, 3.61) L2: 1.80 (-1.33, 5.04) L3: 2.01 (-1.14, 5.26) L03: 2.91 (-1.52, 7.55) Taipei City (5 monitors): L0: 2.08 (-1.04, 5.30) L1: 0.43 (-2.64, 3.60) L2: 2.17 (-0.92, 5.36) L3: 2.16 (-0.94, 5.36) L03: 3.40 (-1.19, 8.20) Monitors with > = 0.75 between monitor correlations (12 monitors): L0: 1.82 (-1.29, 5.03) L1: 0.35 (-2.72, 3.52) L2: 1.93 (-1.15, 5.10) L3: 1.93 (-1.16, 5.12) L03: 2.86 (-1.63, 7.54) Cerebrovascular disease: Taipei area (13 monitors): L0: -1.41 (-3.80, 1.04) L1: -1.95 (4.31, 0.48) L2: 0.77 (-1.62, 3.23) L3: 2.64 (0.21, 5.12) L03: 0.01 (-3.33, 3.47) Taipei City (5 monitors): L0: -1.27 (-3.64, 1.16) L1: -2.13 (-4.47, 0.27) L2: 0.85 (-1.52, 3.28) L3: 2.52 (0.13, 4.97) L03: -0.07 (-3.53, 3.51) Monitors with > = 0.75 between monitor correlations (12 monitors): L0: -1.34 (-3.70, 1.07) L1: -1.98 (-4.31, 0.40) L2: 0.80 (-1.56, 3.22) L3: 2.61 (0.22, 5.05) L03: -0.02 (-3.40, 3.49) Reference: Chan et al. (2007, 147787 ) Period of Study: Apr 1997-Dec 2002

Location: Boston, MA Outcome: Cerebrovascular Emergency Admissions Age Groups: 50+ yr Study Design: Tme series Statistical Analyses: GAM Poisosn Regression

Covariates: Yr, mo, day of wk, temperature, dew point Dose-response Investigated? No Statistical Package: NR Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 50.2 (22.1)

Min: 16.0

Max: 325.4

IQR: 25.4 Monitoring Stations: 16 Copollutant: O 3 , CO, SO 2 , NO 2 , PM 2.5 Co-pollutant Correlation:

O 3 : 0.43

CO: 0.47

SO 2 : 0.59

NO 2 : 0.64

PM 2.5 : 0.61 PM Increment: Interquartile Range (25.4 μg/m 3 ) Percent Change (Lower CI, Upper CI), p-value: Cerebrovascular Disease Lag 0: 1.001 (0.969, 1.033) Lag 1: 0.999 (0.9787, 1.020) Lag 2: 1.023 (0.989, 1.057) Lag 3: 1.030 (1.011, 1.049) Lag 3 + O 3 : 1.018 (0.987, 1.049) Lag 3 + CO: 1.019 (0.988, 1.050) Lag 3 + O 3 + CO: 1.015 (0.985, 1.045)

Stroke Lag 0: 0.969 (0.897, 1.041) Lag 1: 0.992 (0.918, 1.066) Lag 2: 1.004 (0.993, 1.015) Lag 3: 1.009 (0.988, 1.030)

Ischaemic stroke Lag 0: 0.984 (0.932, 1.036) Lag 1: 0.993 (0.939, 1.047) Lag 2: 0.989 (0.927, 1.041) Lag 3: 1.042 (0.981, 1.103)

Haemorrhagic stroke Lag 0: 0.966 (0.884, 1.048) Lag 1: 0.990 (0.908, 1.072) Lag 2: 1.002 (0.920, 1.084) Lag 3: 0.974 (0.902, 1.046)



### December 2009 E-88

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chan et al. (2008, 093297 ) Period of Study: 1995-2002

Location: Taipei Metropolitan area, Taiwan Outcome (ICD-9): Emergency visits for ischaemic heart diseases (410-411, 414), cerebrovascular diseases (430-437), and COPD (493, 496) Age Groups: All Study Design: Time series

N: NR Statistical Analyses: Poisson regression models

Covariates: Yr, mo, day of wk, temperature, dew point temperature, PM 2.5 , NO 2 Season: All Dose-response Investigated: No Statistical Package: SAS version 8.0 Lags Considered: 0- to 7-day lags Pollutant: PM 10 Averaging Time: 24 h Mean (SD): High dust events: Pre-dust periods: 45.5 (17.6) Asian dust events: 122.7 (24.4) Low dust events: Pre-dust periods: 59.4 (31.0) Asian dust events: 61.1 (17.8) Monitoring Stations: 1 Copollutant: NR PM Increment: 25.4 μg/m 3 (IQR) OR [95% CI]: In environmental conditions without dust storms (results only shown for best-fitting model) Lag 3 days: 1.023 (1.003, 1.041)

Reference: Chang et al. (2007, 147621 ) Period of Study: 1997-2001

Location: Taipei, Taiwan Outcome: CVD HA Age Groups: NR Study Design: Case-crossover Statistical Analyses: Conditional Logistic Regression

Covariates: T emperature, humidity Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-2 days Pollutant: PM 10 Averaging Time: 24 h

Mean: 48.32

Min: 14.44

25th: 32.65

50th: 42.80

75th: 57.16

Max: 234.91 Monitoring Stations: 6 Copollutant: O 3 , CO, SO 2 , NO 2 Co-pollutant Correlation: NR PM Increment: Interquartile Range (24.51 μg/m 3 ) Odds Ratio (Lower CI, Upper CI):

≥ 20°C PM 10 : 1.085 (1.061, 1.110) PM 10 + SO 2 : 1.131 (1.103, 1.161) PM 10 + NO : 10.977 (0.950, 1.006) 2 PM 10 + CO: 1.025 (0.999, 1.052) PM 10 + O 3 : 1.064 (1.039, 1.090)

<20°C PM 10 : 1.142 (1.105, 1.180) PM 10 + SO : 1.235 (1.184, 1.288) 2 PM 10 + NO 2 : 1.148 (1.103, 1.194) PM 10 + CO: 1.165 (1.121, 1.212) PM 10 + O 3 : 1.142 (1.105, 1.180)

Reference: D'Ippoliti et al. (2003, 074311 ) Period of Study: Jan 1995-Jun 1997

Location: Rome, Italy Outcome: Myocardial Infarction HA Age Groups: 18+ yr Study Design: Case-crossover Statistical Analyses: Conditional Logistic Regression

Covariates: Temperature, humidity Dose-response Investigated? No Statistical Package: NR Lags Considered: 0-4 days Pollutant: TSP Averaging Time: 24 h Mean (SD): 66.9 (19.7)

25th: 54.7

50th: 66.4

75th: 78.4

IQR: 23.7 Monitoring Stations: 3 Copollutant: CO, SO 2 , NO 2 Co-pollutant Correlation: CO: 0.35 SO 2 : 0.29 NO 2 : 0.38 PM Increment: Quartiles Odds Ratio (Lower CI, Upper CI): Lag 0-2-day avg QI: 1.0 (ref) QII: 1.048 (0.957, 1.148) QIII: 1.105 (1.007, 1.214) QIV: 1.132 (1.023, 1.253)

Various Lags Lag 0: 1.023 (1.004, 1.042) Lag 1: 1.015 (0.996, 1.034) Lag 2: 1.017 (0.999, 1.035) Lag 3: 0.989 (0.974, 1.003) Lag 4: 1.001 (0.987, 1.016)



### December 2009 E-89

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Fung et al., (2005, 093262 ) Period of Study: Nov 1995-Dec 2000

Location: London, Ontario Outcome (ICD-9): Cardiovascular diseases (410-414, 427-428) Age Groups: <65 yr, 65+ yr Study Design: Time series

N: 12,947 CVD admissions Statistical Analyses: GAM with locally weighted regression smoothers (LOESS)

Covariates: Maximum and minimum temp, humidity, day of the week, seasonal cycles, secular trends

Season: NR Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: Current to 3-day

mean Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 38.0 (5-248)

SD = 23.5 Monitoring Stations: 4 Copollutant (correlation): NO 2 : r = 0.30

SO 2 : r = 0.24

CO: r = 0.21

O 3 : r = 0.53

COH: r = 0.29 PM Increment: 26 μg/m 3 % Change in Daily Admission [CI]: Age <65 Current day mean: 2.6 [-2.3,7.7] 2-day mean: -1.2 [-7.2,5.1] 3-day mean: -3 [-9.6,4] Age 65+ Current day mean: 0.9 [-2.3,4.2] 2-day mean: -0.9 [-4.8,3.2] 3-day mean: -0.1 [-4.4,4.5]

Reference: Hanigan et al. (2008, 156518 ) Period of Study: 1996-2005 (Apr-Nov of each yr)

Location: Darwin, Australia Outcome: Daily emergency hospital admissions for total cardiovascular (ICD-9: 390-459 ICD-10: I00-I99), ischemic heart disease (ICD-9: 410-414 ICD-10: I20-I25). Age Groups: All Study Design: Time series

N: 8,279 hospital admissions Statistical Analyses: Poisson generalized linear models

Covariates: Indigenous status, time in days, temperature, relative humidity, day of the week, influenza epidemics, change between ICD editions, holidays, yrly population

Season: Apr-Nov (corresponding to the dry season) Dose-response Investigated? No Statistical Package: R version 2.3.1 Lags Considered: 0-3 Pollutant: PM 10 Averaging Time: 24 h Mean (SD range): 21.2 (8.2 55.2) Monitoring Stations: N/A (see notes) Copollutant: NR PM Increment: 10 μg/m 3 Percent change [95% CI]: Overall CVD: Lag 0 (indigenous): -3.78 [-13.4, 6.91] Lag 0 (non-indigenous): -3.43 [-9.00, 2.49]

All unstratified associations either negative or zero and not statistically significant. All other results of stratified analysis (by indigenous status) reported in a Fig (see notes).

Notes: Fig 3: Associations between hospitalizations for non-indigenous and indigenous people with estimated ambient PM 10 . Summary: Confidence intervals were wide, but indigenous people generally had stronger associations with PM 10 than nonindigenous people. Daily PM 10 exposure levels were estimated for the population of the city from visibility data using a previously validated models.



### December 2009 E-90

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hanigan et al. (2008, 156518 ) Period of Study: 1996-2005 (Apr-Nov of each yr)

Location: Darwin, Australia Outcome: Cardiorespiratory Disease HA (ICD 9: 390-519 ICD 10: I00-99 & J00-99) Age Groups: NR Study Design: Time series

N: 8279 events Statistical Analyses: poisson regression

Covariates: Indigenous status, time in days, temperature, relative humidity, day of the week, influenza epidemics, change between ICD editions, holidays, yearly population Dose-response Investigated? No Statistical Package: R Lags Considered: lags 0-3 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 21.2 (8.2) Range: 55.2 Monitoring Stations: 2 (monitored & modeled) Copollutant: NR Co-pollutant Correlation: N/A PM Increment: 10 μg/m 3 Percent Change (Lower CI, Upper CI), lag: Tot. Cardiovascular, Indigenous: -3.43 (- 9.00, 2.49), lag 0 Tot Cardiovascular, Non-Indigenous: - 3.78 (-13.4, 6.91), lag 0 *Fig 3. percent change in hospital admissions per 10 μg/m 3 increase in PM 10

Reference: Henrotin et al. (2007, 093270 ) Period of Study: Mar 1994-Dec 2004

Location: Dijon, France Outcome: Ischemic and hemorrhagic strokes Age Groups: All Study Design: Bi-directional casecrossover

N: 1487 (ischemic) and 220 (hemorrhagic) stroke patients Statistical Analyses: Conditional logistic regression

Covariates: Temperature, relative humidity, influenza epidemics, holidays

Season: NR Dose-response Investigated? Yes Statistical Package: STATA software v. 8.2 Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 21.1 (2-103)

SD = 11.3 Monitoring Stations: 1 Copollutant: NR PM Increment: 10 μg/m 3 OR Estimate [CI]: Ischemic stroke Same-day lag: 1.009 [0.930,1.094] 1-day lag: 1.011 [0.998,1.094] 2-day lag: 0.960 [0.889,1.036] 3-day lag: 0.990 [0.919,1.066] Hemorrhagic stroke Same-day lag: 0.901 [0.730,1.111] 1-day lag: 1.014 [0.828,1.241] 2-day lag: 1.100 [0.903,1.339] 3-day lag: 0.991 [0.881,1.212]

Notes: Ischemic stroke ORs were also categorized into male and female, yielding similar results (none were significant for any lag days).

Reference: Issever et al. (2005, 097736 ) Period of Study: Jan 1997-Dec 2001

Location: Istanbul, Turkey Outcome: Acute coronary syndrome (ACS) Age Groups: All Study Design: Time series

N: 2889 ACS admissions Statistical Analyses: Multiple stepwise regression, Pearson correlation

Covariates: Humidity, temperature, pressure Season: NR Dose-response Investigated? No Pollutant: PM 10 Averaging Time: 24 h

Mean: NR Monitoring Stations: 1 Copollutant (correlation): ACS: r = 0.37 (p = 0.003) ACS controlled for temp: r = 0.29 (p = 0.02) PM Increment: NR RR Estimate [CI]: NR

Notes: This study focused more on the seasonal change in acute coronary syndrome admissions.



### December 2009 E-91

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Jalaludin et al. (2006, 189416 ) Period of Study: Jan 1997-Dec 2001

Location: Sydney, Australia Outcome (ICD-9): Cardiovascular disease (390-459), cardiac disease (390-429), ischemic heart disease (410-413) and cerebrovascular disease or stroke (430-438) Age Groups: 65+ yr Study Design: Time series

N: NR Statistical Analyses: GAM, GLM

Covariates: Temperature, humidity

Season: Warm (Nov-Apr) and cool (May-Oct) Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 0-3 Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 16.8 (3.8-103.9)

SD = 7.2 Monitoring Stations: 14 Copollutant (correlation):

Warm BSP: r = 0.82 PM 2.5 : r = 0.89 O 3 : r = 0.59 NO 2 : r = 0.44; CO: r = 0.31 SO 2 : r = 0.37

Cool BSP: r = 0.75 PM 2.5 : r = 0.88 O 3 : r = 0.22 NO 2 : r = 0.67 CO: r = 0.48 SO 2 : r = 0.46

Other variables: Warm Temp: r = 0.36 Rel humidity: r = -0.25

Cool Temp: r = 0.13 Rel humidity: r = 0.05 PM Increment: 7.8 μg/m 3 (IQR) Percent Change Estimate [CI]: All CVD Same-day lag: 0.72 [-0.14,1.60] Avg 0-1 day lag: 0.25 [-0.61,1.12] Cool (same-day lag): 1.34 [0.08,2.61] Warm (same-day lag): 0.33 [-0.83,1.50] Cardiac disease Same-day lag: 1.15 [0.14,2.18] Avg 0-1 day lag: 0.97 [-0.07,2.02] Cool (same-day lag): 1.35 [-0.16,2.89] Warm (same-day lag): 1.12 [-0.23,2.48] Ischemic heart disease Same-day lag: 0.59 [-0.95,2.17] Avg 0-1 day lag: 0.61 [-0.95,2.20] Cool (same-day lag): 0.33 [-2.00,2.72] Warm (same-day lag): 0.79 [-1.23,2.85] Stroke Same-day lag: -1.66 [-3.48,0.20] Avg 0-1 day lag: -2.05 [-3.88,-0.20] Cool (same-day lag): 0.46 [-2.17,3.17] Warm (same-day lag): -3.49 [-5.97,- 0.95] Notes: All other lag-day ORs were provided, yet none were significant. Percent change in ED attendance was also reported graphically (Fig 1-5).

Reference: Johnston et al. (2007, 155882 ) Period of Study: 2000, 2004, 2005 (Apr-Nov of each yr)

Location: Darwin, Australia Outcome (ICD-10): All cardiovascular conditions (I00-I99), including ischemic heart disease (I20-I25). Age Groups: All Study Design: Case-crossover

N: 2466 emergency admissions Statistical Analyses: Conditional logistic regression

Covariates: Weekly influenza rates, temperature, humidity, days with rainfall >5mm, public holidays, school holiday periods (for respiratory conditions only)

Season: Apr-Nov (dry season) Dose-response Investigated? No Statistical Package: NR Lags Considered: 0-3 Pollutant: PM 10 Averaging Time: 24 h

Median: 17.4

IQR: 13.6-22.3

10-90th Percentile: 10.3-27.7 Range: 1.1-70.0 Monitoring Stations: 1 Copollutant: NR PM Increment: 10 μg/m 3 OR Estimate [95% CI]: All respiratory conditions: Ischemic heart disease: Lag 0: 0.82 [0.68-0.98] Lag 0 (non-indigenous): 0.75 [0.61-0.93] Lag 3 (indigenous): 1.71 [1.14-2.55]

Notes: Fig 5: OR and 95% CI for hospital admissions for cardiovascular conditions. Summary: Negative associations inoverall study population and in nonindigenous people. Positive associations in Indigenous people at Lag 1, Lag 2, and Lag 3. Fig 6: OR and 95% CI for hospital admissions for ischaemic heart disease. Summary: Negative associations inoverall study population and nonindigenous people. Positive association in indigenous people.



### December 2009 E-92

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Koken et al. (2003, 049466 ) Period of Study: Jul and Aug, 1993-1997

Location: Denver, Colorado Outcome (ICD-9): Acute myocardial infarction (410.00-410.92), pulmonary heart disease (416.0-416.9), cardiac dysrhythmias (427.0-427.9), congestive heart failure (428.0) Age Groups: 65+ yr Study Design: Time series

N: 298 days Statistical Analyses: GLM, GEE

Covariates: Maximum temp and dew point temp

Season: NR Dose-response Investigated: Yes Statistical Package: SAS (PROC GENMOD) Lags Considered: 0-4 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 24.2 (7.0-51.6)

SD = 6.25 Monitoring Stations: 3 Copollutant (correlation): NO 2 : r = 0.56

SO 2 : r = 0.36

O 3 : r = 0.03

CO: r = 0.25

Other variables: Max temp: r = 0.38 Dew point temp: r = -0.24 PM Increment: 8.0 μg/m 3 (IQR) Percent Change Estimate [CI]: No PM data reported

Reference: Lanki et al., (2006, 089788 ) Period of Study: 1992-2000

Location: Augsburg, Barcelona, Helsinki, Rome, and Stockholm Outcome (ICD-9): Acute myocardial infarction (410 ICD-10: I21, I22) Age Groups: 35+ yr, <75 yr, 75+ yr Study Design: Time series

N: 26,854 hospitalizations Statistical Analyses: GAM

Covariates: Temperature, barometric pressure Season: Warm (Apr-Sep) and cold (Oct-Mar) Dose-response Investigated: No Statistical Package: R package mgcv 0.9-5 Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Median: Augsburg: 43.5 Barcelona: 57.4 Helsinki: 21.0 Rome: 48.5 Stockholm: 12.5 Copollutant (correlation):

Augsburg PNC: r = 0.53 CO: r = 0.56 NO 2 : r = 0.64 O 3 : r = 0.43

Barcelona: PNC: r = 0.38 CO: r = 0.44 NO : r = 0.48

2 O 3 : r = 0.01

Helsinki: PNC: r = 0.45 CO: r = 0.21 NO 2 : r = 0.40 O 3 : r = 0.40

Rome: PNC: r = 0.32 CO: r = 0.41 NO 2 : r = 0.29 O 3 : r = 0.59

Stockholm: PNC: r = 0.06 CO: r = 0.41 NO : r = 0.29

2 O 3 : r = 0.59 PM Increment: 10 μg/m 3 Pooled Rate Ratio [CI]: All 5 cities (35+ yr) Same-day lag: 1.003 [0.995,1.011] 1-day lag: 1.001 [0.990,1.011] 2-day lag: 1.002 [0.994,1.010] 3-day lag: 1.002 [0.991,1.013] 3 cities with hospital discharge register (35+ yr) Same-day lag: 1.003 [0.994,1.012] 1-day lag: 0.997 [0.988,1.006] 2-day lag: 1.003 [0.995,1.012] 3-day lag: 1.003 [0.986,1.020] Warm season (35+ yr) Same-day lag: 1.006 [0.990,1.022] 1-day lag: 1.000 [0.985,1.016] 2-day lag: 1.005 [0.990,1.020] 3-day lag: 1.010 [0.995,1.025] Cold season (35+ yr) Same-day lag: 1.001 [0.991,1.012] 1-day lag: 0.998 [0.987,1.009] 2-day lag: 1.001 [0.991,1.012] 3-day lag: 0.991 [0.981,1.002] Age >75 Non-fatal Same-day lag: 1.012 [0.995,1.029] 1-day lag: 1.000 [0.983,1.017] 2-day lag: 0.999 [0.982,1.017] 3-day lag: 1.001 [0.984,1.018] Fatal Same-day lag: 1.009 [0.985,1.034] 1-day lag: 0.998 [0.974,1.023] 2-day lag: 1.003 [0.978,1.028] 3-day lag: 1.018 [0.975,1.063] Notes: Pooled rate ratios were also provided for groups <75 yielding similar results to the overall 3-city data.



### December 2009 E-93

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lee et al. (2003, 095552 ) Period of Study: Dec 1997-Dec 1999

Location: Seoul, Korea Outcome (ICD-10): Angina pectoris (I20), acute/subsequent myocardial infarction (I21-I23), other acute ischemic heart diseases (I24) Age Groups: All ages, 64+ yr Study Design: Time series

N: 822 days Statistical Analyses: GAM with LOESS, Pearson correlation

Covariates: Temperature, relative humidity, day of the week

Season: Summer (Jun-Aug) and winter Dose-response Investigated: Yes Statistical Package: NR Lags Considered: 0-6 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 64.0 (31.8) Monitoring Stations: 27 Copollutant (correlation): All yr SO 2 : r = 0.59 NO 2 : r = 0.74 O 3 : r = 0.11 CO: r = 0.60 Temp: r = -0.07 Humidity: r = 0.02 Summer SO 2 : r = 0.61 NO 2 : r = 0.73 O 3 : r = 0.64 CO: r = 0.55 Temp: r = -0.01 Humidity: r = -0.11 PM Increment: 40.4 μg/m 3 (IQR) RR Estimate [CI]: All yr All ages: 0.99 [0.96,1.01] 64+ yr: 1.05 [1.01,1.10] Summer All ages: 1.03 [0.97,1.09] 64+ yr: 1.09 [1.00,1.19] Two-pollutant model CO (1 ppm IQI): 1.04 [0.98,1.11] O 3 (21.7 ppb IQI): 1.07 [1.03,1.11] NO 2 (14.6 ppb IQI): 1.09 [1.02,1.16] SO 2 (4.4 ppb): 0.98 [0.94,1.03]

Reference: Lee et al. (2008, 192076 ) Period of Study: 1996-2005

Location: Taipei, Taiwan Outcome: Congestive Heart Failure HA (ICD 9: 428) Age Groups: NR Study Design: Case-crossover

N: 18593 events Statistical Analyses: conditional logistic regression

Covariates: Temperature, humidity Dose-response Investigated? No Statistical Package: SAS Lags Considered: Lags 0-2 Pollutant: PM 10 Averaging Time: 24 h

Mean: 49.94

Min: 11.33

25th: 33.37

50th: 45.05

75th: 60.82

Max: 234.92 Monitoring Stations: 6 Copollutant: SO 2 , CO, NO 2 , O 3 Co-pollutant Correlation SO 2 : 0.52 CO: 0.67 NO : 0.35

2 O 3 : 0.39 PM Increment: Interquartile Range (27.45 μg/m 3 ) Odds Ratio (Lower CI, Upper CI): W/ Hypertension: 1.23 (1.15, 1.32) W/o Hypertension: 1.20 (1.15, 1.25) W/ Diabetes: 1.20 (1.12, 1.40) W/o Diabetes: 1.21 (1.15, 1.26) W/ Dysrhythmia: 1.17 (1.08, 1.27) W/o Dysrhythmia: 1.22 (1.17, 1.27) W/ COPD: 1.21 (1.07, 1.36) W/o COPD: 1.21 (1.16, 1.25)

Reference: Larrieu et al. (2007, 093031 ) Period of Study: 1998-2003

Location: 8 French urban area: Bordeaux, Le Havre, Lille, Lyon, Marseille, Paris, Rouen, and Toulouse Outcome (ICD-10): Hospital admissions for cardiovascular disease (I00-I99), cardiac disease (I00-I52), ischemic heart disease (I20-I25), and stroke (cerebrovascular disease: I60-64 and transient ischemic attack: G45-G46). Age Groups: All, and 65 + Study Design: Time series N: Statistical Analyses: generalized additive Poisson regression

Covariates: Temperature, holidays, influenza epidemic periods, long-term trend, season, day of the week,

Season: NR Dose-response Investigated: No Statistical Package: R 2.2.1 Lags Considered: 0 –to 1-day lag (mean) Pollutant: PM 10 Averaging Time: 24 h

Mean: Bordeaux: 21.0

Le Havre: 21.7

Lille: 22.1 Lyon: 24.6

Marseille: 28.9

Paris: 23.1

Rouen: 21.2

Toulouse: 21.8 Monitoring Stations: 32 Copollutant: NR PM Increment: 10 μg/m 3 ERR [95% CI]: CVD: All ages: 0.7 [0.1, 1.2] 65+ yr: 1.1 [0.5, 1.7] Cardiac diseases: All ages: 0.8 [0.2, 1.4] 65+ yr: 1.5 [0.7, 2.2] Ischemic heart diseases: All ages: 1.9 [0.8, 3.0] 65+ yr: 2.9 [1.5, 4.3] Strokes: All ages: 0.2 [-1.6, 1.9] 65+ yr: 0.8 [-0.9, 2.5]



### December 2009 E-94

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Le Tertre et al. (2002, 023746 ) Period of Study: 1990-1997

Location: Barcelona, Birmingham, London, Milan, the Netherlands, Paris, Rome, and Stockholm Outcome (ICD-9): Cardiac diseases (390-429), ischemic heart disease (410- 413), and stroke (430-438) Age Groups: <65 yr, 65+ yr Study Design: Time series

N: NR Statistical Analyses: GAM

Covariates: Long term trend, season, days of the week, holidays, influenza epidemics, temperature, and humidity

Season: NR Dose-response Investigated: No Statistical Package: S-Plus Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Barcelona: 55.7 (18.4) Birmingham: 24.8 (13.1) London: 28.4 (12.3) Milan: 51.5 (22.7) Netherlands: 39.5 (19.9) Paris: 22.7 (10.8) Rome: 52.5 (12.9) Stockholm: 15.5 (7.2) Monitoring Stations: 1-12 Copollutant: NR PM Increment: 10 μg/m 3 Pooled Percent Increase [CI]: Cardiac (all ages) Fixed: 0.5 [0.3,0.7] Random: 0.5 [0.2,0.8] Cardiac (over 65) Fixed: 0.7 [0.4,1.0] Random: 0.7 [0.4,1.0] IHD (<65) Fixed: 0.3 [-0.1,0.6] Random: 0.3 [-0.2,0.7] IHD (over 65) Fixed: 0.6 [0.3,0.8]; Random: 0.8 [0.3,1.2] Stroke (over 65) Fixed: 0.0 [-0.3,0.3]; Random: 0.0 [- 0.3,0.3] Deaths: Cardiac: 0.5 [0.2,0.8]; Cardiac (65+): 0.7 [0.4,1.0] IHD (65+): 0.8 [0.3,1.2]

Notes: Estimated percentage increases are also provided by city for cardiac admissions and ischemic heart disease in Fig 1-3.

Reference: Mann et al. (2002, 036723 ) Period of Study: 1988-1995

Location: South Coast Air Basin, California Outcome (ICD-9): Ischemic heart disease (410-414), secondary congestive heart failure (sCHF) (428), and secondary arrhythmia (sARR) (426, 427) Age Groups: All, 40-59 yr, >60 yr Study Design: Time series

N: 54,863 IHD admissions Statistical Analyses: GAM

Covariates: Temperature, day of the week, relative humidity

Season: NR Dose-response Investigated: No Statistical Package: S-Plus Lags Considered: 0-5 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 43.7 (0.22-251)

SD = 27.7 Monitoring Stations: 20 Copollutant (correlation): Region 1: CO: r = 0.28 O 3 : r = 0.20 NO 2 : r = 0.36 Region 2: CO: r = 0.15 O 3 : r = 0.57 NO : r = 0.53

2 Region 3: CO: r = 0.36 O : r = 0.30

3 NO 2 : r = 0.46 Region 4: CO: r = 0.27 O 3 : r = 0.33 NO 2 : r = 0.50 Region 5: CO: r = 0.40 O 3 : r = 0.43 NO : r = 0.53

2 Region 6: CO: r = 0.33 O : r = 0.20

3 NO 2 : r = 0.42 Region 7: CO: r = 0.28 O 3 : r = 0.48 NO 2 : r = 0.60 PM Increment: 10 μg/m 3 Percent Change in IHD Admissions [CI]: Secondary ARR Same-day lag: 0.59 [-0.71,1.91] 1-day lag: 0.46 [-0.86,1.80] 2-day lag: -0.04 [-1.37,1.31] Secondary CHF Same-day lag: -0.62 [-1.77,0.55] 1-day lag: -0.45 [-1.60,0.71] 2-day lag: -0.36 [-1.52,0.82] No secondary diagnosis Same-day lag: -0.25 [-1.23,0.75] 1-day lag: 0.04 [-0.97,1.06] 2-day lag: 0.18 [-0.82,1.20] All IHD admissions: 0.19 [-0.576,0.955] MI admissions: -0.10 [-1.33,1.12] Other acute IHD admissions: 0.36 [- 0.87,1.60]



### December 2009 E-95

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Metzger et al. (2004, 044222 ) Period of Study: Aug 1993-Aug 2000

Location: Atlanta Metropolitan area (Georgia) Outcome (ICD-9): Emergency visits for ischemic heart disease (410-414), cardiac dysrhythmias (427), cardiac arrest (427.5), congestive heart failure (428), peripheral vascular and cerebrovascular disease (433-437, 440, 443-444, 451-453), atherosclerosis (440), and stroke (436). Age Groups: All Study Design: Time series

N: 4,407,535 emergency department visits Statistical Analyses: Poisson generalized linear modeling

Covariates: Day of the wk, hospital entry and exit indicator variables, federally observed holidays, temporal trends, temperature, dew point temperature

Season: All Dose-response Investigated: No Statistical Package: SAS Lags Considered: 3-day ma, lags 0 -7 Pollutant: PM 10 Averaging Time: 24 h Median (10% - 90% range): 26.3 (13.2, 44.7) Monitoring Stations: NR Copollutant (correlation): O 3 : r = 0.59 NO 2 : r = 0.49 CO: r = 0.47 SO 2 : r = 0.20 PM 2.5 : r = 0.84 PM 10-2.5 : r = 0.59 UFP: r = -0.13 PM 2.5 water-sol metals: r = 0.74 PM 2.5 sulfates: r = 0.74 PM 2.5 acidity: r = 0.68 PM 2.5 OC: r = 0.69 PM 2.5 EC: r = 0.56 oxygenated hydrocarbon: r = 0.58

Other variables: Temperature: r = 0.58 Dew point: r = 0.44 PM Increment: 10 μg/m 3 (approximately 1 SD) RR [95% CI]: For 3-day ma: All CVD: 1.009 [0.998, 1.019] Dysrhythmia: 1.008 [0.989, 1.029] Congestive heart failure: 0.992 [0.968-1.016]

Ischemic heart disease: 1.011 [0.992-1.030] Peripheral vascular and cerebrovascular disease: 1.020 [0.999-1.043]

Notes: Results for Lags 0-7 expressed in figures Fig 1: RR (95% CI) for single-day lag models for the association of ER visits for CVD with daily ambient PM 10

. Summary: Statistically significant association at Lag 0. Positive but not statistically significant association at Lag 1. Negative, statistically significant association at Lag 7, and negative associations at Lag 2 through Lag 6.

Reference: Middleton et al. (2008, 156760 ) Period of Study: 1995-1998, 2000-2004

Location: Nicosia, Cyprus Outcome: Hospital admissions for all cardiovascular disease (ICD-10: I00-I52). Age Groups: All, also stratified by age (<15 vs.. >15 yr) Study Design: Time series Statistical Analyses: Generalized additive Poisson models

Covariates: Seasonality, day of the week, long- and short-term trend, temperature, relative humidity Dose-response Investigated: No Statistical Package: STATA SE 9.0, R 2.2.0 Lags Considered: Lag 0 -2 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD median 5% - 95% range): Cold: 57.6 (52.5

50.8

20.0-103.0 5.0-1370.6) Warm: 53.4 (50.5

30.7

32.0-77.6 18.4-933.5) Monitoring Stations: 2 Copollutant: NR PM Increment: 10 μg/m 3 , and across quartiles of increasing levels of PM 10 Percentage increase estimate [CI]: All age/sex groups (Lag 0): All admissions: 0.85 (0.55, 1.15) Cardiovascular: 1.18 (-0.01, 2.37) Nicosia residents (Lag 0): Cardiovascular: 0.73 (-0.62, 2.09) Males (Lag 0): All admissions: 0.96 (0.54, 1.39) Cardiovascular: 1.27 (-0.15, 2.72) Females (Lag 0): All admissions: 0.74 (0.31, 1.18) Cardiovascular: 0.99 (-1.11, 3.14) Aged <15 yr (Lag 0): All admissions: 0.47 (-0.13, 1.08) Aged >15 yr (Lag 0): All admissions: 0.98 (0.63, 1.33)



### December 2009 E-96

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Peel et al. (2007, 090442 ) Period of Study: Jan 1993-Aug 2000

Location: Atlanta, GA Outcome (ICD-9): Ischemic heart disease (410-414), dysrhythmia (427), congestive heart failure (428), peripheral vascular and cerebrovascular disease (433-437, 440, 443, 444, 451-453) Age Groups: All Study Design: Case-crossover

N: 4,407,535 ED visits Statistical Analyses: Conditional logistic regression

Covariates: Avg temp and dew point temp

Season: NR Dose-response Investigated: No Statistical Package: SAS v. 9.1 Lags Considered: 0-2 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Daily levels: 27.9 (12.3) Diff in case and control-day avg: 9.1 (7.5) Monitoring Stations: 1 Copollutant: NR PM Increment: 10 μg/m 3 OR Estimate [CI]: All CVD: 1.010 [1.000,1.020] IHD: 1.009 [0.991,1.027] Dysrhythmia: 1.011 [0.991, 1.031] Peripheral/Cerebrovascular disease: 1.017 [0.996,1.039] CHF: 1.001 [0.978,1.024] With comorbid hypertension IHD: 1.003 [0.973,1.034] Dysrhythmia: 1.037 [0.988,1.089] Peripheral/Cerebrovascular disease: 1.024 [0.990,1.060] CHF: 1.041 [0.999,1.084] No comorbid hypertension IHD: 1.013 [0.991,1.036] Dysrhythmia: 1.006 [0.985,1.028] Peripheral/Cerebrovascular disease: 1.013 [0.987,1.040] CHF: 0.982 [0.955,1.010] With comorbid diabetes IHD: 1.022 [0.979,1.067] Dysrhythmia: 1.049 [0.968,1.137] Peripheral/Cerebrovascular disease: 1.016 [0.965,1.069] CHF: 1.029 [0.982,1.078] No comorbid diabetes IHD: 1.006 [0.987,1.026] Dysrhythmia: 1.009 [0.989,1.029] Peripheral/Cerebrovascular disease: 1.018 [0.995,1.042] CHF: 0.992 [0.966,1.019] With comorbid COPD IHD: 0.981 [0.921,1.044] Dysrhythmia: 0.984 [0.889,1.088] Peripheral/Cerebrovascular disease: 1.086 [0.998,1.181] CHF: 1.010 [0.954,1.069] No comorbid COPD IHD: 1.012 [0.993,1.031] Dysrhythmia: 1.012 [0.992,1.032] Peripheral/Cerebrovascular disease: 1.013 [0.991,1.035] CHF: 0.999 [0.974,1.025] Reference: Pope et al., (2006, 091246 ) Period of Study: 1994-2004

Location: Wasatch Front area, Utah Outcome: Myocardial infarction or unstable angina (ICD codes not reported) Age Groups: All Study Design: Case-crossover

N: 12,865 patients who underwent coronary arteriography Statistical Analyses: Conditional logistic regression

Covariates: Temperature and dew point temperature

Season: NR Dose-response Investigated: No Statistical Package: NR Lags Considered: 0- to 3-day lag, 2- to 4-day lagged ma Pollutant: PM 10 Averaging Time: 24 h Mean (SD maximum): Ogden: 28.5 (16.5 163) SLC Hawthorne: 27.7 (17.4 162) Provo/Orem, Lindom: 32.7 (21.1 240) SLC AMC: 35.9 (20.4 161) SLC North: 45.1 (25.1 199) Monitoring Stations: 5 Copollutant: NR PM Increment: 10 μg/m 3 Percent increase in risk [95% CI]: Results summarized in Fig (see notes).

Notes: Fig 1: Percent increase in risk (and 95% CI) of acute coronary events associated with 10 μg/m 3 of PM 10 for different lag structures. Summary of Fig 1: Positive, statistically significant or marginally significant associations between association seen for Lag 0, Lag 1 and 2-, 3-, and 4-day ma. Non-statistically significant associations



### December 2009 E-97

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Santos et al. (2008, 192004 ) Period of Study: Jan 1998-Aug 1999

Location: Sao Paulo, Bazil Outcome: Cardiac Arrhythmia ER Visits (ICD 10: I45-I49) Age Groups: 17+ yr Study Design: Time series

N: 3251 ER visits Statistical Analyses: Poisson

Covariates: Temperature, humidity, seasonality Dose-response Investigated? Yes Statistical Package: S-Plus Lags Considered: Lags 0-13 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 48.64 (20.34)

Min: 18.68

Max: 137.76 Monitoring Stations: 14 Copollutant: SO 2 , CO, NO 2 , O 3 Co-pollutant Correlation: SO 2 : 0.675* CO: 0.580* NO 2 : 0.781* O 3 : 0.438* *p < 0.01 PM Increment: Interquartile Range (22.2 μg/m 3 ) Percent Increase (Lower CI, Upper CI): PM 10 + NO 2 ,CO: -5.6 (-12.7, 2.1) PM 10 + CO: -1.1 (-7.0, 5.1) PM 10 + NO 2 : -2.4 (-9.4, 5.1) Fig 1. PM 10 effects, reported as percent increase, on arrhythmia ER visits caused by interquartile range increases, lags 0-6. Fig 2. Relative risks and 95% CI for arrhythmia ER visits according to the division of air pollutant daily concentrations in quintiles.

Reference: Tolbert et al. (2007, 090316 ) Period of Study: 1993-2004

Location: Atlanta Metropolitan area, Georgia Outcome (ICD-9): Combined CVD group, including: Ischemic heart disease (410-414), cardiac dysrhythmias (427), congestive heart failure (428), and peripheral vascular and cardiovascular disease (433-437, 440, 443-445, and 451-453). Age Groups: All Study Design: Time series

N: 10,234,490 ER visits (283,360 and 1,072,429 visits included in the CVD and RD groups, respectively) Statistical Analyses: Poisson generalized linear models

Covariates: Long-term temporal trends, season (for RD outcome), temperature, dew point, days of week, federal holidays, hospital entry and exit

Season: All Dose-response Investigated: No Statistical Package: SAS version 9.1 Lags Considered: 3-day ma (lag 0-2) Pollutant: PM 10 Averaging Time: 24 h Mean (median IQR, range, 10th-90th percentiles): 26.6 (24.8

17.5-33.8

0.5-98.4 12.3-42.8) Monitoring Stations: NR Copollutant (correlation): O : r = 0.59

3 NO : r = 0.53

2 CO: r = 0.51 SO : r = 0.21

2 Coarse PM: r = 0.67 PM 2.5 : r = 0.84 PM 2.5 SO : r = 0.69 4 PM 2.5 EC: r = 0.61 PM 2.5 OC: r = 0.65 PM 2.5 TC: r = 0.67 PM water-sol metals: r = 0.73

2.5 OHC: r = 0.53 PM Increment: 16.30 μg/m 3 (IQR) Risk ratio [95% CI]: Single pollutant models: CVD: 1.008 (0.997-1.020)

Reference: Tsai et al. (2003, 080133 ) Period of Study: 1997-2000

Location: Kaohsiung, Taiwan Outcome (ICD-9): Cerebrovascular diseases (430-438), subarachnoid hemorrhagic stroke (430), primary intracerebral hemorrhage (431-432), ischemic stroke (433-435), and others (436-438) Age Groups: All Study Design: Case-crossover

N: 23,179 admissions Statistical Analyses: Conditional logistic regression

Covariates: Temperature and humidity

Season: NR Dose-response Investigated: No Statistical Package: SAS Lags Considered: Cumulative 0-2 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 78.82 (20.50-217.33) Monitoring Stations: 6 Copollutant: NR PM Increment: 66.33 μg/m 3 (IQR) OR Estimate [CI]: Two-pollutant model (all stroke admissions) Primary intracerebral hemorrhage (PIH) Adj for SO 2 : 1.55 [1.31,1.83] Adj for NO 2 : 1.28 [1.01,1.61]; Adj for CO: 1.45 [1.20,1.74] Adj for O 3 : 1.56 [1.27,1.91] Ischemic stroke (IS) Adj for SO 2 : 1.46 [1.32,1.61] Adj for NO 2 : 1.16 [1.01,1.34] Adj for CO: 1.35 [1.21,1.51] Adj for O 3 : 1.51 [1.34,1.71] Single-pollutant model Temp >20oC PIH: 1.54 [1.31,1.81] IS: 1.46 [1.32,1.61] Temp <20oC PIH: 0.82 [0.48,1.40] IS: 0.97 [0.65,1.44]



### December 2009 E-98

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ulirsch et al. (2007, 091332 ) Period of Study: Nov 1994-Mar 2000

Location: Pocatello, Idaho and Chubbuck, Idaho Outcome (ICD-9): CVD (390-429). Age Groups: 65 + Study Design: Time series

N: 39,347 admissions/visits Statistical Analyses: Log-linear generalized linear models

Covariates: Time, temperature, relative humidity, influenza, day of the week

Season: All, and separate analyses were performed for the all-age group for cool months (Oct-Mar) vs.. warm months (Apr-Sep). Dose-response Investigated: No Statistical Package: S-plus version 6.1 Lags Considered: 0- to 4-day lags, and mean of days 0 -4 Pollutant: PM 10 Averaging Time: 24 h Mean (range 10th - 90th percentiles): 24.2 (3.0-183.0 10.5-40.7) Monitoring Stations: 4 Copollutant (correlation): NO 2 : r = 0.47

Other variables: Correlation for PM 10 between monitors: r = 0.42-0.87 PM Increment: 50 μg/m 3 , and 24.3 μg/m 3 (mean increase in PM 10 ) Mean percent of change (% change in the mean number of daily admissions and visits) [95% CI]: For 24.3 μg/m 3 increase in PM10: All-age RD/CVD: 3.7 [1.3, 6.3] All-age CVD (Lag 0): -0.02 [-5.9, 6.3] All-age CVD (Lag 1): 1.9 [-4.1, 8.4] All-age CVD (Lag 2): -3.1 [-9.1, 3.4] All-age CVD (Lag 3): 0.5 [-5.6, 6.9] All-age CVD (Lag 4): -1.7 [-4.3, 0.9] Lag 0-4 days: -0.5 [-8.0, 7.6] For 50 μg/m3 increase in PM10 (single pollutant models, CIs not given): All-age respiratory disease: 8.4 All-age RD/CVD: 7.9 18-64 yr RD: 7.2 All-age CVD (Lag 3): 1.0 All-age CVD (Lag 4): -3.6 All-age CVD (Lag 0 -4): -1.1 Notes: Included urgent care visits as well as emergency department visits and hospital admissions.

Reference: Yang et al. (2007, 092847 ) Period of Study: 1996-2005

Location: Taipei, Taiwan Outcome: Congestive Heart Failure HA (ICD 9: 428) Age Groups: NR Study Design: case-crossover

N: 24,240 events Statistical Analyses: Poisson

Covariates: Temperature, humidity Dose-response Investigated? No Statistical Package: SAS Lags Considered: lags 0-3 Pollutant: PM 10 Averaging Time: 24 h

Mean: 49.47

Min: 14.42

25th: 33.08

50th: 44.71

75th: 60.10

Max: 234.91 Monitoring Stations: 6 Copollutant: NR Co-pollutant Correlation: N/A PM Increment: Interquartile Range (27.02 μg/m 3 ) Odds Ratio (Lower CI, Upper CI): Temp ≥ 20°C PM 10 : 1.15 (1.10-1.21)* PM 10 + SO 2 : 1.23 (1.17, 1.30)* PM 10 + NO 2 : 1.03 (0.97, 1.10) PM 10 + CO 2 : 1.09 (1.03, 1.15)* PM 10 + O 3 : 1.10 (1.04, 1.15)* Temp <20°C PM 10 : 0.99 (0.93, 1.05) PM 10 + SO 2 : 0.96 (0.89, 1.03) PM 10 + NO 2 : 0.97 (0.90, 1.04) PM 10 + CO 2 : 0.96 (0.90, 1.03) PM 10 + O 3 : 1.00 (0.94, 1.05) *p < 0.05

Reference: Yang et al. (2007, 092847 ) Period of Study: 1996-2001

Location: Taipei, Taiwan Outcome: Congestive Heart Failure HA Age Groups: NR Study Design: case-crossover

N: NR Statistical Analyses: Poisson

Covariates: NR Dose-response Investigated? No Statistical Package: SAS Lags Considered: Lags 0-3 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Index days: 111.68 (38.32) Comparison days: 55.43 (24.66) Monitoring Stations: 7 Copollutant: NR Co-pollutant Correlation: N/A PM Increment: Index (>125 μg/m 3 ) vs.. Comparison ( ≤ 125 μg/m 3 ) Relative Risk (Lower CI, Upper CI), lag: 0.915 (0.805, 1.041), lag 0 1.114 (0.993, 1.250), lag 1 0.983 (0.873, 1.106), lag 2 0.974 (0.870, 1.090), lag 3



### December 2009 E-99

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Villeneuve et al. (2006, 090191 ) Period of Study: Apr 1992-Mar 2002

Location: Edmonton, Canada Outcome (ICD-9): Stroke (430-438), including ischemic stroke (434-436), hemorrhagic stroke (430,432), and transient ischemic attacks (TIA) (435). Age Groups: 65+ yr Study Design: Case-crossover N: 12,422 visits Statistical Analyses: Conditional logistic regression

Covariates: Temperature and relative humidity

Season: summer (Apr-Sep), winter (Oct-Mar) Dose-response Investigated: No Statistical Package: SAS (PHREG) Lags Considered: 0, 1, and 3 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): All yr: 24.2 (14.8) Summer: 25.9 (16.4) Winter: 22.6 (12.9) Monitoring Stations: 3 Copollutant (correlation): All yr SO 2 : r = 0.19 NO 2 : r = 0.34; CO: r = 0.30 O 3 -mean: r = 0.07; O 3 -max: r = 0.22 PM 2.5 : r = 0.79

Summer SO 2 : r = 0.18 NO 2 : r = 0.57; CO: r = 0.38 O 3 -mean: r = 0.20; O 3 -max: r = 0.40 PM 2.5 : r = 0.85

Winter SO 2 : r = 0.27 NO 2 : r = 0.48; CO: r = 0.53 O 3 -mean: r = -0.26; O 3 -max: r = -0.09 PM 2.5 : r = 0.70 PM Increment: μg/m 3 (IQR) All yr: 16.0 Summer: 17.5 Winter: 16.0 Adjusted OR Estimate [CI]: Acute ischemic stroke All yr Same-day lag: 0.98 [0.94,1.03] 1-day lag: 1.00 [0.96,1.05] 3-day lag: 0.99 [.93,1.05]

summer Same-day lag: 0.93 [0.87,1.00] 1-day lag: 1.01 [0.94,1.08] 3-day lag: 0.96 [0.88,1.04] Winter Same-day lag: 1.04 [0.97,1.11] 1-day lag: 1.00 [0.94,1.06]; 3-day lag: 1.05 [0.95,1.15] Hemorrhagic stroke All yr Same-day lag: 1.01 [0.90,1.12] 1-day lag: 1.03 [0.93,1.15] 3-day lag: 1.13 [0.98,1.30]

summer Same-day lag: 1.02 [0.88,1.20] 1-day lag: 1.07 [0.91,1.26] 3-day lag: 1.20 [0.98,1.46] Winter Same-day lag: 1.05 [0.90,1.22] 1-day lag: 1.04 [0.91,1.19] 3-day lag: 1.11 [0.90,1.37] Transient cerebral ischemic attack All yr Same-day lag: 0.96 [0.90,1.02] 1-day lag: 0.99 [0.94,1.05] 3-day lag: 0.94 [0.87,1.01]

summer Same-day lag: 0.97 [0.89,1.09] 1-day lag: 0.99 [0.91,1.08] 3-day lag: 0.94 [0.84,1.04] Winter Same-day lag: 0.95 [0.87,1.04] 1-day lag: 0.99 [0.92,1.07] 3-day lag: 0.93 [0.83,1.05] Notes: Adjusted ORs are provided for an IQR increase in the 3-day mean in Fig 1-4 for single and two-pollutant models.



### December 2009 E-100

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: von Klot et al. (2005, 088070 ) Period of Study: 1992-2001

Location: Augsburg, Germany Barcelona, Spain Helsinki, Finland Rome, Italy Stockholm, Sweden Outcome (ICD-9): Acute myocardial infarction (410 ICD-10: I21-I22), angina pectoris (411, 413 ICD-10: I20, I24), dysrhythmia (427 ICD-10: I46.0, 46.9, I47-I49, R00.1, R00.8), heart failure (428 ICD-10: 150) Age Groups: 35+ yr Study Design: Cohort N: 22,006 MI survivors Statistical Analyses: GAM, Spearman correlation

Covariates: Temperature, dew point temp, avg barometric pressure, relative humidity

Season: NR Dose-response Investigated: No Statistical Package: R Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (5th-95th percentile): Augsburg: 44.7 (16.8-81.4) Barcelona: 52.2 (25.3-89.2) Helsinki: 25.3 (9.5-57.6) Rome: 51.1 (23.3-89.4) Stockholm: 14.6 (6.4-30.0) Monitoring Stations: NR Copollutant (correlation): Augsburg PNC: r = 0.52 CO: r = 0.57; NO 2 : r = 0.64 O 3 : r = -0.32

Barcelona PNC: r = 0.29 CO: r = 0.39; NO 2 : r = 0.36 O 3 : r = -0.14

Helsinki PNC: r = 0.46 CO: r = 0.21; NO 2 : r = 0.40 O 3 : r = 0.02

Rome PNC: r = 0.33 CO: r = 0.31; NO 2 : r = 0.48 O 3 : r = -0.22

Stockholm PNC: r = 0.06 CO: r = 0.38; NO 2 : r = 0.29 O 3 : r = 0.15 PM Increment: 10 μg/m 3 Pooled RR Estimate [CI]:

All cardiac admissions: 1.021 [1.005,1.048] Myocardial infarction: 1.026 [0.995,1.058] Angina pectoris: 1.008 [0.986,1.032]

Notes: Rate ratios for 0-3 day lags are provided in graphical form (Fig 1). Same-day levels were significantly associated with cardiac readmissions.

Reference: Wellenius et al. (2005, 087483 ) Period of Study: Jan 1987-Nov 1999

Location: Pittsburgh, Pennsylvania Outcome (ICD-9): Congestive heart failure (428.0-428.1) Age Groups: 65+ yr Study Design: Case-crossover N: 55,019 patients Statistical Analyses: Conditional logistic regression, Pearson’s pairwise correlation

Covariates: Temperature, barometric pressure, dew point

Season: NR Dose-response Investigated: No Statistical Package: SAS Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (5th-95th percentile): 31.06 (8.89-70.49)

SD = 20.10 Monitoring Stations: 17 Copollutant (correlation): CO: r = 0.57

NO 2 : r = 0.64

O 3 : r = 0.29

SO 2 : r = 0.51 PM Increment: 24 μg/m 3 (IQR) Percent Increase [CI]: Single-pollutant: 3.07 [1.59,4.57] Adj. for CO: -1.10 [-3.02,0.86] Adj. for NO 2 : 0.52 [-1.46,2.53] Adj. for O 3 : 2.80 [1.29,4.33] Adj. for SO 2 : 2.18 [0.37,4.02] Percent Increase (with 10 μg/m 3 increment) 1.27 [0.66,1.88]



### December 2009 E-101

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Wellenius et al. (2005, 088685 ) Period of Study: Jan 1986-Nov 1999

Location: Birmingham, Chicago, Cleveland, Detroit, Minneapolis, New Haven, Pittsburgh, Salt Lake City, Seattle Outcome (ICD-NR): Ischemic stroke and hemorrhagic stroke Age Groups: 65+ yr Study Design: Case-crossover (timestratified) N: 115,503 hospital admissions Statistical Analyses: Conditional logistic regression

Covariates: Temperature and humidity

Season: NR Dose-response Investigated: No Statistical Package: SAS (v.9) and Rstatistical package Lags Considered: 0-2 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 32.69 (19.75) Monitoring Stations: NR (data obtained from the U.S. EPA) Copollutant (correlation): CO: r = 0.43

NO 2 : r = 0.53

SO 2 : r = 0.39 Other variables: Temp: r = 0.22 PM Increment: 22.96 μg/m 3 (IQR)Percent Increase [CI]: Ischemic (sameday lag): 1.03 [0.04,2.04] Hemorrhagic: -0.58 [-5.48,4.58]

Notes: Percent increase in rate for ischemic and hemorrhagic stroke are provided for each city in graphical form (Fig A and B).

Reference: Wellenius et al.,(2006, 088748 ) Period of Study: Jan 1986-Nov 1999

Location: Birmingham, Chicago, Cleveland, Detroit, Minneapolis, New Haven, Pittsburgh, Salt Lake City, Seattle Outcome (ICD-9): Congestive heart failure (428) Age Groups: 65+ yr Study Design: Case-crossover (timestratified) N: 292,918 admissions Statistical Analyses: Conditional logistic regression

Covariates: Temperature and barometric pressure

Season: NR Dose-response Investigated: No Statistical Package: SAS (v.9) and Rstatistical package Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h

Median: Overall: 28.3 Birmingham: 33.0 Chicago: 31.5

Cleveland: 34.5

Detroit: 29.5 Minneapolis: 24.0

New Haven: 22.

Seattle: 25.8 Monitoring Stations: NR (data obtained from the U.S. EPA) Copollutant: NR PM Increment: 10 μg/m 3 Percent Increase [CI]: Same-day lag: 0.72 [0.35,1.10] p-value = 0.0002

Notes: City-specific percent increases are graphed in Fig 1 for same-day lag showing a significant association in Chicago, Detroit, Seattle, and the summary values.

Percent increase in admission rate s are provided for lag 0-3 days in Fig 2 where same-day lag showed a significant association.

Reference: Yang et al. (2004, 094376 ) Period of Study: 1997-2000

Location: Kaohsiung, Taiwan Outcome (ICD-9): Cardiovascular diseases (410-429) Age Groups: All Study Design: Case-crossover N: 29,661 admissions Statistical Analyses: Conditional logistic regression

Covariates: Temperature and humidity

Season: NR Dose-response Investigated: No Statistical Package: SAS Lags Considered: Cumulative 0-2 days Pollutant: PM 10 Averaging Time: 24 h Median (min-max): 78.82 (20.50- 217.33) Monitoring Stations: 6 Copollutant: NR PM Increment: 66.33 μg/m 3 (IQR) OR Estimate [CI]: Temp >25oC: 1.439 [1.316,1.573] Temp <25oC: 1.568 [1.433,1.715] Adj for SO 2 Temp >25oC: 1.460 [1.333,1.599] Temp <25oC: 1.543 [1.404,1.696] Adj for NO 2 Temp >25oC: 1.306 [1.154,1.478] Temp <25oC: 0.912 [0.809,1.028] Adj for CO Temp >25oC: 1.260 [1.144,1.388] Temp <25oC: 1.259 [1.128,1.406] Adj for O 3 Temp >25oC: 1.086 [0.967,1.220] Temp <25oC: 1.703 [1.541,1.883]



### December 2009 E-102

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Yang et al. (2008, 157160 ) Period of Study: 1996-2004

Location: Taipei, Taiwan Outcome (ICD-9): Congestive heart failure (428) Age Groups: All Study Design: Case-crossover N: 24,240 CHF hospital admissions Statistical Analyses: Conditional logistic regression

Covariates: temperature, humidity

Season: All Dose-response Investigated: No Statistical Package: SAS Lags Considered: Cumulative lag 0-2 days Pollutant: PM 10 Averaging Time: 24 h Mean (median, range, IQR): 49.47 (44.71, 14.42-234.91, 33.08-44.71) Monitoring Stations: 6 Copollutant: NR PM Increment: 27.02 μg/m 3 (IQR) OR [95% CI]: Single pollutant models: >20 °C: 1.15 [1.10-1.21] <20 °C: 0.99 [0.93-1.05] Adjusted for SO 2 : ≥ 20 °C: 1.23 [1.17-1.30] <20 °C: 0.96 [0.89-1.03] Adjusted for NO 2 : ≥ 20 °C: 1.03 [0.97-1.10] <20 °C: 0.97 [0.90-1.04] Adjusted for CO: ≥ 20 °C: 1.09 [1.03-1.15] <20 °C: 0.96 [0.90-1.03] Adjusted for O 3 : ≥ 20 °C: 1.10 [1.04-1.15] <20 °C: 1.00 [0.94-1.05]

Reference: Zanobetti and Schwartz (2002, 034821 ) Period of Study: 1988-1994

Location: Cook county (Chicago), Illinois Wayne county (Detroit), Michigan Allegheny county (Pittsburgh), Pennsylvania and King county (Seattle), Washington Outcome (ICD-9): Cardiovascular disease (390-429) with/without diabetes (250) Age Groups: 65-74 and 75+ yr with diabetes, 65-74 and 75+ yr without diabetes Study Design: Time series

N: NR Statistical Analyses: GAM, metaregression

Covariates: Temperature, prior day’s temperature, relative humidity, barometric pressure, day of the week

Season: NR Dose-response Investigated: No Pollutant: PM 10 Averaging Time: 24 h Median (25-75th percentile): Chicago: 33 (23-46) Detroit: 32 (21-49) Pittsburgh: 30 (19-47) Seattle: 27 (18-39) Monitoring Stations: NR (obtained from USEPA Aerometric Information Retrieval System) Copollutant: NR PM Increment: 10 μg/m 3 Percent Change [CI]: All 4 cities <75 (w/ diabetes): 1.6 [1.2,2.0] 75+ (w/ diabetes): 2.0 [1.6,2.4] <75 (w/o diabetes): 0.9 [0.6,1.1] 75+ (w/o diabetes): 1.3 [1.0,1.5] Chicago <75 (w/ diabetes): 1.9 [1.1,2.7] 75+ (w/ diabetes): 2.0 [1.1,3.0] <75 (w/o diabetes): 0.7 [0.2,1.2] 75+ (w/o diabetes): 1.2 [0.8,1.7]

Detroit <75 (w/ diabetes): 1.3 [0.5,2.2] 75+ (w/ diabetes): 2.1 [1.0,3.1] <75 (w/o diabetes): 1.2 [0.7,1.7] 75+ (w/o diabetes): 1.2 [0.7,1.6]

Pittsburgh <75 (w/ diabetes): 1.8 [0.9,2.7] 75+ (w/ diabetes): 0.9 [-0.2,2.0] <75 (w/o diabetes): 0.6 [0.1,1.2] 75+ (w/o diabetes): 1.6 [1.2,2.1]

Seattle <75 (w/ diabetes): 1.9 [0.1,3.7] 75+ (w/ diabetes): 2.7 [0.7,4.8] <75 (w/o diabetes): 0.8 [0.0,1.6] 75+ (w/o diabetes): 0.9 [0.2,1.6] Notes : Overall percent increases were also provided for each city, yielding similar results.



### December 2009 E-103

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zanobetti and Schwartz (2005, 088069 ) Period of Study: 1985-1999 Location: 21 U.S. cities (Birmingham, Alabama Boulder, Colorado Canton, Ohio Chicago, Illinois Cincinnati, Ohio Cleveland, Ohio Colorado Springs, Colorado Detroit, Michigan Honolulu, Hawaii Houston, Texas Minneapolis-St. Paul, Minnesota Nashville, Tennessee New Haven, Connecticut Pittsburgh, Pennsylvania Provo-Orem, Utah Salt Lake City, Utah Seattle, Washington Steubenville, Ohio Youngstown, Ohio) Outcome (ICD-9): Myocardial infarction (410) Age Groups: >65 yr Study Design: Case-crossover N: 302,453 admissions Statistical Analyses: Conditional logistic regression

Covariates: Temperature

Season: NR Dose-response Investigated: Yes Statistical Package: SAS (PROC PHREG) Lags Considered: 0-2 days Pollutant: PM 10 Averaging Time: 24 h

Median: Ranged from 15.5-34.1Avg across all cities = 27 Monitoring Stations: 1+ (data obtained from USEPA’s Aerometric Information Retrieval System) Copollutant: NR PM Increment: 10 μg/m 3 Percent Increase [CI]: MI only: 0.65 [0.3,1] Previous COPD admission: 1.3 [- 0.1,2.8] Secondary pneumonia diagnosis: 1.4 [- 0.8,3.6]

Notes : Fig 1 presents percent change in MI per lag day, showing same-day lag to be significant. Fig 2 showspercent change with/without other comorbidities.

1 All units expressed in μg/m 3 unless otherwise specified.



# Table E-6. Short-term expos ure-cardiovascular-ED/HA - PM 10-2.5 

# .

Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Halonen et al. (2009, 180379 ) Period of Study: 1998-2004

Location: Helsinki, Finland Outcome: Cardiovascular Hospitalizations & Mortality (ICD 10: I00-99) Age Groups: 65+ yr Study Design: Time series

N: NR Statistical Analyses: Poisson, GAM

Covariates: Temperature, humidity, influenza epidemics, high pollen episodes, holidays Dose-response Investigated? No Statistical Package: R Lags Considered: lags 0-3 days; 5-day (0-4) mean Pollutant: PM 10-2.5 Averaging Time: Daily Mean (SD): NR

Min: 0.0 25th percentile: 4.9 50th percentile: 7.5 75th percentile: 12.1

Max: 101.4 Monitoring Stations: NR Copollutant: PM<0.03, PM0.03-0.1, PM<0.1, PM<0.10.29, PM 2.5 , CO, NO 2 Co-pollutant Correlation

PM<0.03: 0.14

PM0.03-0.1: 0.28

PM<0.1: 0.24

PM<0.10.29: 0.20

PM 2.5 : 0.25 PM Increment: Interquartile Range Percent Change (Lower CI, Upper CI): All Cardiovascular Morality Lag 0: -0.01 (-1.52, 1.53) Lag 1: -0.26 (-1.69, 1.18) Lag 2: -0.61 (-2.03, 0.83) Lag 3: -0.57 (-1.98, 0.85) 5-day mean: -0.70 (-2.56, 1.20) Coronary Heart Disease HA Lag 0: 1.12 (-0.28, 2.55) Lag 1: -0.38 (-1.68, 0.94) Lag 2: 0.01 (-1.33, 1.37) Lag 3: -0.53 (-1.82, 0.78) 5-day mean: 0.23 (-0.29, 0.75)

Stroke HA Lag 0: -1.33 (-3.26, 0.63) Lag 1: -1.90 (-3.82, 0.07) ‡ Lag 2: -1.09 (-3.04, 0.89) Lag 3: -0.51 (-2.40, 1.43) 5-day mean: -2.21 (-4.75, 0.39)

Arrhythmia HA Lag 0: 0.57 (-1.33, 2.49) Lag 1: -0.65 (-2.55, 1.29) Lag 2: 0.02 (-1.93, 2.00) Lag 3: -1.34 (-3.26, 0.62) 5-day mean: -1.11 (-3.68, 1.53) *p < 0.05, ‡p < 0.10



### December 2009 E-104

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Host et al. (2008, 155852 )(Host et al., 2008, 155852 ) Period of Study: 2000-2003

Location: Six French cities: Le Havre, Lille, Marseille, Paris, Rouen, and Toulouse Outcome (ICD-10): Daily hospitalizations for all cardiovascular (I00-I99), cardiac (I00-I52), and ischemic heart diseases (I20-I25). Age Groups: For cardiovascular diseases: All ages, and restricted to ≥ 65 yr Study Design: Time series N: NR (Total population of cities: approximately 10 million) Statistical Analyses: Poisson regression

Covariates: Seasons, days of the week, holidays, influenza epidemics, pollen counts, temperature, and temporal trends Dose-response Investigated: No Statistical Package: MGCV package in R software (R 2.1.1) Lags Considered: Avg of 0-1 days Pollutant: PM 10-2.5 Averaging Time: 24 h Mean μg/m3 (5th -95th percentile): Le Havre: 7.3 (2.5-14.0) Lille: 7.9 (2.2-13.7) Marseille: 11.0 (4.5-21.0) Paris: 8.3 (3.2-15.9) Rouen: 7.0 (3.0-12.5) Toulouse: 7.7 (3.0-15.0) Monitoring Stations: 13 total: 1 in Toulouse

4 in Paris

2 each in other cities Copollutant (correlation): PM 2.5 : Overall: r>0.6 Ranged between r = 0.28 and r = 0.73 across the six cities. PM Increment: 10 μg/m 3 , and an 18.8 μg/m 3 increase (corresponding to an increase in pollutant levels between the lowest of the 5th percentiles and the highest of the 95th percentiles of the cities’ distributions) ERR (excess relative risk) Estimate [CI]: For all cardiovascular diseases (10 μg/m 3 increase): All ages: 0.5% [- 1.2, 2.3]

≥ 65 yr: 1.0% [-1.0, 3.0]

For all cardiovascular diseases (18 μg/m 3 increase): All ages: 1.0% [- 2.3, 4.3]

≥ 65 yr: 1.9% [-2.0, 5.9] For cardiac diseases (10 μg/m 3 increase): All ages: 0.1% [-1.9, 2.1]

≥ 65 yr: 1.6% [-0.8, 4.1] For cardiac diseases (18.8 μg/m 3 increase): All ages: 0.1% [-3.6, 4.0]

≥ 65 yr: 3.1% [-1.5, 7.9] For ischemic heart diseases (10 μg/m 3 increase): All ages: 2.8% [-0.8, 6.6]

≥ 65 yr: 6.4% [1.6, 11.4] For ischemic heart diseases (18 μg/m 3 increase): All ages: 5.4% [-1.5, 12.8]

≥ 65 yr: 12.4 [3.1, 22.6]

Reference: Metzger et al. (2004, 044222 ) Period of Study: Aug 1998-Aug 2000

Location: Atlanta Metropolitan area (Georgia) Outcome (ICD-9): Emergency visits for ischemic heart disease (410-414), cardiac dysrhythmias (427), cardiac arrest (427.5), congestive heart failure (428), peripheral vascular and cerebrovascular disease (433-437, 440, 443-444, 451-453), atherosclerosis (440), and stroke (436). Age Groups: All Study Design: Time series N: 4,407,535 emergency department visits between 1993-2000 (data not reported for 1998 - 2000) Statistical Analyses: Poisson generalized linear modeling

Covariates: Day of the wk, hospital entry and exit indicator variables, federally observed holidays, temporal trends, temperature, dew point temperature

Season: All Dose-response Investigated: No Statistical Package: SAS Lags Considered: 3-day ma; lags 0 -7 Pollutant: PM 10 -2.5 Averaging Time: 24 h Median μg/m3 (10% - 90% range): 9.1 (4.4, 16.2) Monitoring Stations: 1 Copollutant (correlation): PM 10 : r = 0.59 O : r = 0.35

3 NO 2 : r = 0.46 CO: r = 0.32 SO 2 : r = 0.21 PM 2.5 : r = 0.43 UFP: r = 0.13 PM water

2.5 soluble metals: r = 0.47 PM 2.5 sulfates: r = 0.26 PM 2.5 acidity: r = 0.23 PM 2.5 OC: r = 0.51 PM 2.5 EC: r = 0.48 PM oxygenated hydrocarbon: r = 0.31

2.5 Other variables: Temperature: r = 0.20 Dew point: r = 0.00 PM Increment: 5 μg/m 3 (approximately 1 SD) RR [95% CI]: For 3 day ma: All CVD: 1.012 [0.985, 1.040] Dysrhythmia: 1.021 [0.974, 1.070] Congestive heart failure: 1.020 [0.964-1.079]

Ischemic heart disease: 0.994 [0.946-1.045] Peripheral vascular and cerebrovascular disease: 1.022 [0.972-1.074]] Results for Lags 0-7 expressed in figures (see notes).

Notes : Fig 1: RR (95% CI) for singleday lag models for the association of ER visits for CVD with daily ambient PM 10-2.5

. Summary of Fig 1 results: Positive association at Lag 0.



### December 2009 E-105

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Peng et al. (2008, 156850 ) Period of Study: Jan 1999-Dec 2005

Location: 108 U.S. counties in the following states: Alabama, Arizona, California, Colorado, Connecticut, District of Columbia, Florida, Georgia, Idaho, Illinois, I ndiana, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Utah, Virginia, Washington, West Virginia, Wisconsin Outcome (ICD-9): Emergency hospitalizations for: Cardiovascular disease, including heart failure (428), heart rhythm disturbances (426-427), cerebrovascular events (430-438), ischemic heart disease (410-414, 429), and peripheral vascular disease (440-448). Age Groups: 65 + yr, 65-74, 75+ Study Design: Time series N: approximately 12 million Medicare enrollees (3.7 million CVD and 1.4 million RD admissions) Statistical Analyses: Two-stage Bayesian hierarchical models: Overdispersed Poisson models for county-specific data. Bayesian hierarchical models to obtain national avg estimate

Covariates: Day of the wk, age-specific intercept, temperature, dew point temperature, calendar time, indicator for age of 75 yr or older. Some models were adjusted for PM 2.5

. Dose-response Investigated: No Statistical Package: R version 2.6.2 Lags Considered: 0-2 days Pollutant: PM 10-2.5 Averaging Time: 24 h Mean μg/m3 (IQR ): All counties assessed: 9.8 (6.9-15.0) Counties in Eastern U.S.: 9.1 (6.6-13.1)

Counties in Western U.S.: 15.4 (10.3-21.8) Monitoring Stations: At least 1 pair of co-located monitors (physically located in the same place) for PM 10 and PM 2.5 per county Copollutant (correlation): PM 2.5 : r = 0.12

PM 10 : r = 0.75 Other variables: Median within-county correlations between monitors: r = 0.60 PM Increment: 10 μg/m 3 Percentage change [95% CI]: CVD: Lag 0 (unadjusted for PM 2.5 ): 0.36 [0.05, 0.68] Lag 0 (adjusted for PM 2.5 ): 0.25 [-0.11, 0.60]

Notes : Effect estimates for PM 10-2.5 (0-2 day lags) are showing in Fig 2-5. Fig 2: Percentage change in emergency hospital admissions for CVD per 10 μg/m 3 increase in PM (single pollutant model and model adjusted for PM 2.5 concentration) Fig 4: Percentage change in emergency hospital admissions rate for CVD and RD per a 10 μg/m 3 increase in PM 10-2.5 (0-2 day lags, Eastern vs.. Western USA) Fig 5: County-specific log relative risks of emergency hospital admissions for CVD per 10 μg/m 3 increase in PM 10-2.5 at Lag 0 (unadjusted for PM 2.5 and plotted vs.. percentage of urbanicity) No significant associations between PM 10-2.5 and cause-specific cardiovascular disease.

Reference: Tolbert et al. (2007, 090316 ) Period of Study: Aug 1998-Dec 2004

Location: Atlanta Metropolitan area, Georgia Outcome (ICD-9): Combined CVD group, including: Ischemic heart disease (410-414), cardiac dysrhythmias (427), congestive heart failure (428), and peripheral vascular and cardiovascular disease (433-437, 440, 443-445, and 451-453) Age Groups: All Study Design: Time series

N: NR for 1998-2004. For 1993-2004: 10,234,490 ER visits (283,360 visits). Statistical Analyses: Poisson generalized linear models

Covariates: Long-term temporal trends, temperature, dew point, days of week, federal holidays, hospital entry and exit

Season: All Dose-response Investigated: No Statistical Package: SAS version 9.1 Lags Considered: 3-day ma (lag 0-2) Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (μg/m3) (median IQR, range, 10th-90th percentiles): 9.0 (8.2

5.6-11.5

0.5-50.3 3.6-15.1) Monitoring Stations: 1 Copollutant (correlation): PM : r = 0.67

10 O 3 : r = 0.36 NO 2 : r = 0.48 CO: r = 0.38SO 2 : r = 0.16 PM 2.5 : r = 0.47 PM 2.5 SO 4 : r = 0.32 PM 2.5 EC: r = 0.49 PM 2.5 OC: r = 0.49 PM 2.5 TC: r = 0.51 PM water-sol metals: r = 0.50

2.5 OHC: r = 0.41 PM Increment: 5.89 μg/m 3 (IQR) Risk ratio [95% CI]: CVD: 1.004 (0.990-1.019)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-106

# Table E-7. Short-term exposur e – cardiovascular: ED/HA PM 2.5 

# (including PM components/sources)

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Andersen et al. (2008, 189651 ) Period of Study: May 2001-Dec 2004

Location: Copenhagen, Denmark Outcome (ICD-10): CVD, including angina pectoris (I20), myocardial infarction (I21-22), other acute ischemic heart diseases (I24), chronic ischaemic heart disease (I25), pulmonary embolism (I26), cardiac arrest (I46), cardiac arrhythmias (I48-48), and heart failure (I50). RD, including chronic bronchitis (J41-42), emphysema (J43), other chronic obstructive pulmonary disease (J44), asthma (J45), and status asthmaticus (J46). Pediatric hospital admissions for asthma (J45) and status asthmaticus (J46). Age Groups: > 65 yr (CVD and RD), 5-18 yr (asthma) Study Design: Time series

N: NR Statistical Analyses: Poisson GAM

Covariates: Temperature, dew-point temperature, long-term trend, seasonality, influenza, day of the week, public holidays, school holidays (only for 5-18 yr olds), pollen (only for pediatric asthma outcome)

Season: NR Dose-response Investigated: No Statistical Package: R statistical software (gam procedure, mgcv package) Lags Considered: Lag 0-5 days, 4-day pollutant avg (lag 0-3) for CVD, 5-day avg (lag 0-4) for RD, and a 6-day avg (lag 0-5) for asthma. Pollutant: PM 2.5 Averaging Time: 24 h Mean μ gm 3 (SD): 10(5) Median: 9 IQR: 7-12 99th percentile): 28 Monitoring Stations: 1 Copollutant (correlation): NCtot: r = 0.40 NC100: r = 0.29 NCa12: r = 0.07 Nca23: r = -0.25 NCa57: r = 0.51 NCa212: r = 0.82 PM 10 : r = 0.80 CO: r = 0.46 NO 2 : r = 0.42 NO X : r = 0.40 curbside: r = 0.28 O : r = -0.20

3 Other variables: Temperature: r = -0.01 Relative humidity: r = 0.21 PM Increment: 5 μ g/m 3 (IQR) Relative risk (RR) Estimate [CI]: CVD hospital admissions (4-day avg, lag 0 - 3), age 65+: One-pollutant model: 1.03 [1.01-1.06] Adj for NCtot: 1.03 [1.01-1.06] RD hospital admissions (5-day avg, lag 0 -4), age 65+: One-pollutant model: 1.00 [0.95-1.00] Adj for NCtot: 1.00 [0.95-1.06] Asthma hospital admissions (6-day avg lag 0-5), age 5 - 18: One-pollutant model: 1.15 [1.00-1.32] Adj for NCtot: 1.13 [0.98-1.32] Estimates for individual day lags reported only in Fig form (see notes):

Notes : Fig 2: Relative risks and 95% confidence intervals per IQR in single day concentration (0-5 day lag). Summary: CVD: Marginally significant association at Lag 0. RD: No statistically or marginally significant associations. Positive associations at Lag 4-5.Asthma: Wide confidence intervals make interpretation difficult. Positive associations at Lag 1, 2, 3.



### December 2009 E-107

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ballester et al. (2006, 088746 ) Period of Study: 1995-1999

Location: 6 Spanish cities: Barcelona, Bilbao, Pamplona, Valencia, Vigo, Zaragoza Outcome (ICD-9): The number of daily emergency admissions with primary diagnosis for all cardiovascular disease (390-459) and heart diseases (410-414, 427, 428) Age Groups: All ages Study Design: Time series

N: NR Statistical Analyses: Poisson GAMs

Covariates: D aily temperature, barometric pressure, and relative humidity Daily influenza incidence, day of the week, holidays, unusual events (ex. medical strikes), seasonal variation, trend of the series

Season: NR Dose-response Investigated: No Statistical Package: S-Plus GAM function Lags Considered: 0-3 days, 0- to 1-day avg Pollutant: Black smoke (BS) Averaging Time: 24 h Mean μg/m3 (10-90th percentile): Overall mean NR. City specific means Barcelona: 35.0 (19.4, 53.0) Bilbao: 18.5 (8.8, 31.0) Pamplona: 7.4 (2.3, 13.0) Valencia: 40.3 (20.3, 66.4) Vigo: 79.4 (43.9, 122.3) Zaragoza: 40.4 (23.8, 61.3) Monitoring Stations: NR (at least 3 stations per city) Copollutant (correlation): Summary of the correlation coefficients between each pair of pollutants within cities: PM 10 : r = 0.48 TSP: from r = 0.16 to r = 0.69 (median r = 0.43) NO 2 : from r = 0.23 to r = 0.69 (median r = 0.48) SO 2 : from r = 0.09 to r = 0.59 (median r = 0.24) CO: from r = 0.62 to r = 0.69 (median r = 0.69) O 3 : from r = -0.43 to r = -0.06 (median r = -0.16) PM Increment: 10 μg/m 3 Relative risk [CI]: Relative risks are expressed only in the form of figures (see notes). Percentage change in risk [CI]: All cardiovascular diseases (avg of lags 0 - 1) 0.24% [-0.18, 0.67] Heart disease (avg of lags 0 -1) 0.71% [0.13, 1.29]

Notes : Relative risks for the single pollutant models are expressed in Fig 2. Fig 2: Time sequence of the combined association between BS and hospital admissions for all CVD (A) and heart disease (B). Summary: Significant, positive association of TSP with both overall CVD and heart disease hospitalizations at Lag 0. Relative risks for 2 pollutant models are expressed in Fig 3: Combined estimates of the association between hospital admissions for heart diseases and air pollutants (avg of lags 0-1 Adjusted for CO, NO 2 , O 3 , or SO 2 ). Summary: Significant, positive association remains after adjusting for NO 2 , O 3 , and SO 2 . Association remains positive but becomes marginally significant after adjusting for CO.

Reference: Ballester et al. (2006, 088746 ) Period of Study: 1993-1999

Location: 7 Spanish cities: Barcelona, Bilbao, Cartagena, Castellon, Gijon, Oviedo, Valencia Outcome (ICD-9): The number of daily emergency admissions with primary diagnosis for all cardiovascular disease (390-459) and heart diseases (410-414, 427, 428) Age Groups: All ages Study Design: Time series

N: NR Statistical Analyses: Poisson GAMs

Covariates: Daily temperature, barometric pressure, and relative humidity Daily influenza incidence, day of the week, holidays, unusual events (ex. medical strikes), seasonal variation, trend of the series

Season: NR Dose-response Investigated: No Statistical Package: S-Plus GAM function Lags Considered: 0-3 days, 0- to 1-day avg Pollutant: TSP Averaging Time: 24 h Mean μg/m3 (10-90th percentile): Overall mean NR. City specific means Barcelona: 51.8 (29.4, 78.8) Bilbao: 58.3 (30.3, 92.3) Cartagena: 54.9 (32.5, 79.9) Castellon: 60.4 (32.0, 92.1) Gijon: 77.4 (47.4, 118.3) Oviedo: 76.0 (48.3, 111.8) Valencia: 61.0 (44.1, 80.7) Monitoring Stations: NR (at least three stations per city) Copollutant (correlation): Summary of the correlation coefficients between each pair of pollutants within cities: BS: from r = 0.16 to r = 0.69 (median r = 0.43) PM 10 : NA NO 2 : from r = -0.13 to r = 0.65 (median r = 0.48) SO : from r = 0.06 to r = 0.69

2 (median r = 0.31) CO: from r = 0.06 to r = 0.59 (median r = 0.47) O 3 : from r = -0.27 to r = 0.07 (median r = -0.03) PM Increment: 10 μg/m 3 Relative risk [CI]: Relative risks are expressed only in the form of figures (see notes). Percentage change in risk [CI]: All cardiovascular diseases: 0.07% [-0.23, 0.36] Heart disease 0.45% [0.04, 0.86]

Notes : Relative risks for the single pollutant models are expressed in Fig 2. Fig 2: Time sequence of the combined association between TSP and hospital admissions for all CVD (A) and heart disease (B). Summary of results: Positive, marginally significant association of TSP with overall CVD at Lag 0. Positive, statistically significant relation between TSP and heart disease hospitalizations at Lag 0. Relative risks for 2 pollutant models are expressed in Fig 3: Fig 3: Combined estimates of the association between hospital admissions for heart diseases and air pollutants (avg of lags 0-1 adjusted for CO, NO 2 , O 3 , or SO 2 ). Summary of results: Small positive significant or marginally significant associations between TSP and general CVD and heart disease hospitalizations remain constant after adjustment for CO, NO 2 , O 3 , or SO 2

.



### December 2009 E-108

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bell et al. (2008, 091268 ) Period of Study: 1995-2002

Location: Taipei, Taiwan Outcome (ICD-9): Hospital admissions for ischemic heart disease (410, 411, 414), cerebrovascular disease (430-437), asthma (493), and pneumonia (486). Age Groups: All Study Design: Time series

N : 6,909 hospital admissions for ischaemic heart diseases, 11,466 for cerebrovascular disease, 19,966 for pneumonia, and 10,231 for asthma Statistical Analyses: Poisson regression

Covariates: Day of the week, time, apparent temperature, long-term trends, seasonality

Season: All Dose-response Investigated: No Statistical Package: NR Lags Considered: lags 0-3 days, mean of lags 0-3 Pollutant: PM 2.5 Averaging Time: 24 h Mean μg/m3 (range IQR) : 31.6 (0.50-355.0 20.2) Monitoring Stations: 2 Copollutant (correlation): NR PM Increment: 20 μg/m 3 (near IQR) Percentage increase estimate [95% CI]: Ischemic heart disease: L0: 3.48 (-0.39, 7.51) L1: 3.55 (-0.30, 7.56) L2: 3.32 (-0.50, 7.29) L3: 2.80 (-1.04, 6.79) L03: 8.38 (2.28, 14.84) Cerebrovascular disease: L0: -2.22 (- 50.2, 0.67) L1: -1.30 (-4.08, 1.55) L2: 0.24 (-2.49, 3.040 L3: 1.21 (-1.41, 3.90) L03: -1.45 (-5.58, 2.87) Asthma: L0: 0.46 (-2.41, 3.42) L1: -1.36 (-4.33, 1.71) L2: -0.83 (-3.67, 2.10) L3: -0.78 (-3.63, 2.16) L03: -1.75 (-6.21, 2.92) Pneumonia: L0: 0.06 (-2.74, 2.94) L1: 0.34 (-2.446, 3.20) L2: -0.59 (-3.38, 2.29) L3: -0.44 (-3.22, 2.41) L03: -0.61 (-4.87, 3.85) Reference: Bell et al. (2008, 091268 ) Period of Study: 1999-2005

Location: 202 U.S. counties Outcome (ICD-9): Heart failure (428), heart rhythm disturbances (426-427), cerebrovascular events (430-438), ischemic heart disease (410-414, 429), peripheral vascular disease (440-449), COPD (490-492), respiratory tract infections (464 - 466, 480 - 487) Age Groups: 65+ Study Design: Time series

N: NR Statistical Analyses: Two-stage Bayesian hierarchical model to find national avgFirst stage: Poisson regression (countyspecific)

Covariates: Day of the week, temperature, dew point temperature, temporal trends, indicator for persons 75+ yr, population size

Season: All, Jun-Aug (Summer), Sep-Nov (Fall), Dec-Feb (Winter), Mar-May (Spring) Dose-response Investigated: No Statistical Package: NR Lags Considered: 0- to 2-day lags Pollutant: PM 2.5 Averaging Time: 24 h Mean (μg/m3): Descriptive information presented in Fig S2 (boxplots):

IQR: 8.7 μg/m 3 Monitoring Stations: NR Copollutant (correlation): NR PM Increment: 10 μg/m 3 Percent increase [95% PI]:

Cardiovascular admissions: Lag 0 (all seasons): 0.80 [0.59-1.01] Lag 0 (winter, national): 1.49 [1.09-1.89] Lag 0 (winter, northeast): 2.01 [1.39-2.63] Lag 0 (winter, southeast): 1.06 [-0.07-2.21] Lag 0 (winter, northwest): 0.85 [-4.11-6.07] Lag 0 (winter, southwest): 0.76 [-0.25-1.79] Lag 0 (spring, national): 0.91 [0.47-1.35] Lag 0 (spring, northeast) 0.95 [0.32-1.58] Lag 0 (spring, southeast): 0.75 [-0.26-1.78] Lag 0 (spring, northwest): -0.07 [-12.40-13.98] Lag 0 (spring, southwest): 1.78 [-0.87-4.51] Lag 0 (summer, national): 0.18 [-0.23-0.58] Lag 0 (summer, northeast): 0.55 [0.08-1.02] Lag 0 (summer, southeast): -0.67 [-1.60-0.26] Lag 0 (summer, northwest): -1.55 [-15.22-14.31] Lag 0 (summer, southwest): -1.20 [-4.90-2.65] Lag 0 (fall, national): 0.68 [0.29-1.07] Lag 0 (fall, northeast): 1.03 [0.48-1.58] Lag 0 (fall, southeast): 0.17 [-0.72-1.07] Lag 0 (fall, northwest): -0.67 [-6.96-6.05] Lag 0 (fall, southwest): 0.30 [-0.98-1.59] Lag 1 (all seasons): 0.07 [-0.12-0.26] Lag 1 (winter): 0.56 [0.16-0.96] Lag 1 (spring): -0.10 [-0.58-0.39] Lag 1 (summer): -0.16 [-0.54-0.22] Lag 1 (fall): 0.04 [-0.28-0.35] Lag2 (all seasons): [0.06 [-0.12-0.23] Lag 2 (winter): 0.27 [-0.12-0.65] Lag 2 (spring): 0.19 [-0.23-0.60]



### December 2009 E-109

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Lag 2 (summer): -0.12 [-0.50-0.26] Lag 2 (fall): 0.02 [-0.30-0.34] Respiratory admissions: Lag 0 (all seasons): 0.22 [-0.12-0.56] Lag 0 (winter, national): 1.05 [0.29-1.82] Lag 0 (winter, northeast): 1.76 [0.60-2.93] Lag 0 (winter, southeast): 0.59 [-1.35-2.58] Lag 0 (winter, northwest): -0.07 [-6.74-7.08] Lag 0 (winter, southwest): 0.03 [-1.25-1.34] Lag 0 (spring, national): 0.31 [-0.47-1.11] Lag 0 (spring, northeast): 0.34 [-0.66-1.34] Lag 0 (spring, southeast): -0.06 [-1.77-1.68] Lag 0 (spring, northwest): -8.52 [-25.62-12.51] Lag 0 (spring, southwest): 1.87 [-2.00-5.90] Lag 0 (summer, national): -0.62 [-1.33-0.09] Lag 0 (summer, northeast): -0.8 [-1.65-0.07] Lag 0 (summer, southeast): -0.15 [-1.88-1.61] Lag 0 (summer, northwest): 0.25 [-21.46-27.96] Lag 0 (summer, southwest): 0.64 [-5.38-7.04] Lag 0 (fall, national): 0.02 [-0.63-0.67] Lag 0 (fall, northeast): -0.01 [-0.87-0.85] Lag 0 (fall, southeast): -0.58 [-2.06-0.91] Lag 0 (fall, northwest): -1.38 [-11.84-10.32] Lag 0 (fall, southwest): 1.77 [-0.73-4.33] Lag 1 (all seasons): 0.05 [-0.29-0.39] Lag 1 (winter): 0.50 [-0.27-1.27] Lag 1 (spring): -0.24 [-1.01-0.53] Lag 1 (summer): 0.28 [-0.39-0.95] Lag 1 (fall): 0.15 [-0.49-0.79 Lag 2 (all seasons): 0.41 [0.09-0.74] Lag 2 (winter, national): 0.72 [0.01-1.43] Lag 2 (winter, northeast): 0.79 [-0.21-1.80] Lag 2 (winter, southeast): 0.4 [-1.45, 2.27] Lag 2 (winter, northwest): -0.06 [-6.52-6.85] Lag 2 (winter, southwest): 1.2 [-0.10-2.52] Lag 2 (spring, national): 0.35 [-0.29-0.99] Lag 2 (spring, northeast): 0.04 [-0.88-0.97] Lag 2 (spring, southeast): 0.75 [-0.82-2.34] Lag 2 (spring, northwest): 2.29 [-14.26-22.03] Lag 2 (spring, southwest): 1.05 [-2.18-4.39] Lag 2 (summer, national): 0.57 [-0.07-1.23] Lag 2 (summer, northeast): 0.77 [-0.01-1.56] |Lag 2 (summer, southeast): -0.52 [-2.07-1.06] Lag 2 (summer, northwest): 0.74 [-18.73-24.86] Lag 2 (summer, southwest): 2.41 [-2.61-7.69] Lag 2 (fall, national): 0.39 [-0.22-1.01] Lag 2 (fall, northeast): 0.12 [-0.82-1.07] Lag 2 (fall, southeast): 0.14 [-1.29-1.59]



### December 2009 E-110

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Lag 2 (fall, northwest): -0.74 [-10.08-9.58] Lag 2 (fall, southwest): 0.97[-1.36-3.36] Reference: Bell et al. (2009, 191007 ) Period of Study: 1999-2005

Location: 168 U.S. Counties Outcome: CVD hospital admissions Study Design: Retrospective Cohort

Covariates: Socio-economic conditions, long term temperature Statistical Analysis: Bayesian hierarchical model Age Groups: ≥ 65 yr Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD) Unit: NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 20% of the population acquiring air conditioning Percent Change (95% CI) in community-specific PM health effect estimates for CVD hospital admissions Any AC, including window units Yearly health effect: -4.3 (-72.7 to 4.2) Summer health effect: -148 (-327 to 31.1) Winter health effect: -80.0 (-182 to 22.0)

Central AC Yearly health effect: -42.5(-63.4-21.6) Summer health effect: -79.5 (-143 to 15.7) Winter health effect: -41.9 (-124 to 40.0) Reference: Bell et al. (2009, 191997 ) Period of Study: 1999-2005

Location: U.S. Outcome: Cardiovascular HA Age Groups: 65+ Study Design: time series

N: NR Statistical Analyses: Bayesian Hierarchical Regression

Covariates: time trend, day of week, seasonality, dew point, temperature Statistical Package: NR Lags Considered: 0-2 Pollutant: PM 2.5 Averaging Time: Daily Mean: EC: 0.715 Ni: 0.002 V: 0.003 Min: EC: 0.309 Ni: 0.003 V: 0.001 Max: EC: 1.73 Ni: 0.021 V: 0.010 Interquartile Range: EC: 0.245 Ni: 0.001 V: 0.001 Interquartile Range of Percents: EC: 1.7 Ni: 0.01 V: 0.01 Monitoring Stations: NR Copollutant: Al, NH4+, As, Ca, Cl, Cu, EC, OMC, Fe, Pb, Mg. Ni, NO 3 -, K, Si, Na+, SO 4 =, Ti, V, Zn Co-pollutant Correlation: Ni, V: 0.48 V, EC: 0.33 Ni, EC: 0.30 Note: Pollutant concentrations available for all fractions of PM 2.5 PM Increment: Interquartile Range in the fraction of PM 2.5 Percent Increase in PM Health Effect (Lower CI, Upper CI), lag EC: 25.8 (4.4, 47.2), lag 0 EC + Ni: 14.0 (-7.6, 35.5), lag 0 EC + V: 14.9 (-7.8, 37.6), lag 0 EC+ V, HS education: 15.0 (3.3, 26.8), lag 0 EC+ V, median income: 15.8 (4.1, 27.5), lag 0 EC+ V, racial composition: 14.2 (2.8, 25.6), lag 0 EC+ V, percent living in urban area: 14.7 (3.1, 26.3), lag 0 EC+ V, population: 13.6 (2.2, 25.0), lag 0 EC + Ni, V: 11.9 (-10.4, 43.2), lag 0 Ni: 19.0 (9.9, 28.2), lag 0 Ni + EC: 17.3 (7.7, 26.9), lag 0 Ni + V: 15.5 (4.1, 26.9), lag 0 Ni + EC, V: 14.9 (3.4, 26.4), lag 0 V: 27.5 (10.6, 44.4), lag 0 V + EC: 23.1 (4.9, 41.4), lag 0 V+ Ni: 10.9 (-9.6, 31.5), lag 0 V + EC, Ni: 8.1 (-13.3, 29.5), lag 0 EC: 11.8 (-69.2, 92.8), lag 1 EC: 21.0 (-46.6, 88.6), lag 2 Ni: 20.6 (-15.5, 56.7), lag 1 Ni: -2.3 (-32.5, 27.9), lag 2 V: 34.0 (-31.2, 99.1), lag 1 V: 8.0 (-46.8, 62.7), lag 2 Percent HS education: -17.4 (-46.8, 11.9), lag 0 Median income: 21.3 (-20.0, 62.5), lag 0 Percent black: 26.9 (-15.8, 69.6), lag 0 Percent living in urban area: 34.4 (- 29.0, 97.8), lag0 Population: -4.3 (-13.3, 4.8), lag 0 Notes: Interquartile ranges in percent HS education, median income, percent black, percent living in urban area, and population are 5.2 %, $9,223, 17.3%, 11.0%, and 549,283 respectively.



### December 2009 E-111

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chan et al. (2007, 147787 ) Period of Study: Apr 1997-Dec 2002

Location: Boston, MA Outcome: Cerebrovascular Emergency Admissions Age Groups: 50+ yr Study Design: Time series Statistical Analyses: GAM Poisosn Regression

Covariates: Yr, mo, day of wk, temperature, dew point Dose-response Investigated? No Statistical Package: NR Lags Considered: 0-3 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 31.5 (16.0)

Min: 15.6

Max: 200.6

IQR: 19.7 Monitoring Stations: 16 Copollutant: O 3 , CO, SO 2 , NO 2 , PM 10 Co-pollutant Correlation O 3 : 0.33 CO: 0.44 SO 2 : 0.51 NO 2 : 0.50 PM 10 : 0.61 PM Increment: Interquartile Range (19.7 μg/m 3 ) Percent Change (Lower CI, Upper CI), p-value: Cerebrovascular Disease Lag 0: 1.006 (0.993, 1.019) Lag 1: 1.002 (0.990, 1.014) Lag 2: 1.015 (0.978, 1.052) Lag 3: 1.021 (1.005, 1.037) Lag 3 + O 3 : 1.009 (0.987, 1.031) Lag 3 + CO: 1.014 (0.993, 1.035) Lag 3 + O 3 + CO: 1.009 (0.987, 1.031)

Stroke Lag 0: 0.931 (0.831, 1.031) Lag 1: 0.936 (0.845, 1.027) Lag 2: 0.931 (0.820, 1.042) Lag 3: 0.991 (0.969, 1.013)

Ischaemic stroke Lag 0: 0.981 (0.907, 1.055) Lag 1: 0.994 (0.920, 1.078) Lag 2: 0.960 (0.885, 1.035) Lag 3: 1.059 (0.984, 1.134)

Haemorrhagic stroke Lag 0: 0.870 (0.740, 1.010) Lag 1: 0.882 (0.761, 1.003) Lag 2: 0.909 (0.810, 1.008) Lag 3: 0.921 (0.830, 1.012) Reference: Chan et al. (2008, 093297 ) Period of Study: 1995-2002

Location: Taipei Metropolitan area, Taiwan Outcome (ICD-9): Emergency visits for ischaemic heart diseases (410-411, 414), cerebrovascular diseases (430- 437), and COPD (493, 496) Age Groups: All Study Design: Time series

N: NR Statistical Analyses: Poisson regression

Covariates: Yr, mo, day of wk, temperature, dewpoint temperature, PM 10 , NO 2 Season: All Dose-response Investigated: No Statistical Package: SAS version 8.0 Lags Considered: 0- to 7-day lags Pollutant: PM 2.5 Averaging Time: 24 h Mean μg/m3 (SD): NR Monitoring Stations: 1 Copollutant (correlation): NR PM Increment: 19.7 μg/m 3 (IQR) OR [95% CI]: In environmental conditions without dust storms (results only given for best-fitting model) Lag 6 days: 1.024 (1.004, 1.044)

Reference: Delfino et al, (2008, 156390 ) Period of Study: October 2001



# - 2003



# - November 2003

Location: Southern California Outcome: Cardiovascular hospital admissions Study Design: Time series Statistical Analysis: Poisson regression with GEE Age Groups: All Pollutant: PM 2.5 Averaging Time: Hourly Mean (SD) Unit by county: Los Angeles Before Fires: 27.2 (12.4) μg/m 3 During Fires: 54.1 (21.0) μg/m 3 After Fires: 15.9 (5.5) μg/m 3 Orange Before Fires: 23.2 (9.6) μg/m 3 During Fires: 64.3 (26.5) μg/m 3 After Fires: 15.5 (10.2) μg/m 3 Riverside Before Fires: 32.7 (14.7) μg/m 3 During Fires: 42.1 (25.5) μg/m 3 After Fires: 16.9 (10.2) μg/m 3 San Bernadino Before Fires: 35.7 (16.6) μg/m 3 During Fires: 45.3 (28.7) μg/m 3 After Fires: 18.5 (8.3) μg/m 3 San Diego Before Fires: 18.5 (6.7) μg/m 3 Increment: 10 μg/m 3 Relative Rate (Min CI, Max CI) All Cardiovascular All Periods: 0.996 (0.989-1.003) Pre-Wildfire: 0.992 (0.976-1.009) Wildfire: 1.008 (0.999-1.018), p = 0.104 Post-Wildfire: 0.991 (0.964-1.019), p = 0.955

Ischaemic Heart Disease All Periods: 0.991 (0.980-1.003) Pre-Wildfire: 0.990 (0.963-1.017) Wildfire: 0.117 (0.990-1.024), p = 0.313 Post-Wildfire: 0.989 (0.950-1.030), p = 0.976 Congestive Heart Failure All Periods: 0.989 (0.974-1.004) Pre-Wildfire: 0.978 (0.942-1.015) Wildfire: 1.016 (0.933-1.039), p = 0.096 Post-Wildfire: 0.969 (0.914-1.027), p = 0.791



### December 2009 E-112

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) During Fires: 76.1 (66.6) μg/m 3 After Fires: 14.2 (7.2) μg/m 3 Ventura Before Fires: 18.4 (8.3) μg/m 3 During Fires: 50.1 (50.5) μg/m 3 After Fires: 12.9 (4.3) μg/m 3 Copollutant (correlation): NR Cardiac Dysrhythmia All Periods: 0.980 (0.962-0.998) Pre-Wildfire: 0.979 (0.935-1.025) Wildfire: 0.989 (0.961-1.017), p = 0.721 Post-Wildfire: 0.976 (0.912-1.044), p = 0.934

Cerebrovascular Disease and Stroke All Periods: 1.019 (1.004-1.035) Pre-Wildfire: 1.015 (0.980-1.052) Wildfire: 1.016 (0.997-1.036), p = 0.971 Post-Wildfire: 1.044 (0.987-1.104), p = 0.379 Relative Rate (Min CI, Max CI) in relation to pre-wildfire period (1) All Cardiovascular: Wildfire, unadjusted for PM 2.5 : 0.958 (0.920-0.997) Wildfire, adjusted for PM 2.5 : 0.947 (0.902-0.994) Post-wildfire, unadjusted for PM 2.5 : 1.061 (1.006-1.119) Post-wildfire, adjusted for PM 2.5 : 1.053 (0.994-1.114) Ischaemic Heart Disease: Wildfire, unadjusted for PM 2.5 : 0.913 (0.852- 0.978) Wildfire, adjusted for PM 2.5 : 0.905 (0.832-0.985) Post-wildfire, unadjusted for PM 2.5 : 1.029 (0.943-1.123) Post-wildfire, adjusted for PM 2.5 : 1.029 (0.936-1.131) Congestive Heart Failure: Wildfire, unadjusted for PM 2.5 : 0.981 (0.817- 0.972) Wildfire, adjusted for PM 2.5 : 0.911 (0.819-1.014) Post-wildfire, unadjusted for PM 2.5 : 1.113 (0.997-1.242) Post-wildfire, adjusted for PM 2.5 : 1.105 (0.982-1.244) Cardiac Dysrhythmia: Wildfire, unadjusted for PM 2.5 : 0.968 (0.874- 1.072) Wildfire, adjusted for PM 2.5 : 0.964 (0.851-1.093) Post-wildfire, unadjusted for PM 2.5 : 1.089 (0.949-1.251) Post-wildfire, adjusted for PM 2.5 : 1.057 (0.914-1.223) Cerebrovascular Disease and Stroke: Wildfire, unadjusted for PM 2.5 : 1.066 (0.981-1.159) Wildfire, adjusted for PM 2.5 : 1.017 (0.922-1.123) Post-wildfire, unadjusted for PM 2.5 : 1.013 (0.907-1.132) Post-wildfire, adjusted for PM 2.5 : 1.013 (0.902-1.138) Reference: Dominici et al. (2006, 088398 ) Period of Study: 1999-2002

Location: 204 U.S. counties, located in: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Georgia, Hawaii, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Outcome (ICD-9): Daily counts of hospital admissions for primary diagnosis of heart failure (428), heart rhythm disturbances (426-427), cerebrovascular events (430-438), ischemic heart disease (410-414, 429), peripheral vascular disease (440-448), chronic obstructive pulmonary disease (490-492), and respiratory tract infections (464-466, 480-487). Age Groups: >65 yr Study Design: Time series

N: 11.5 million Medicare enrollees Statistical Analyses: Bayesian 2-stage Pollutant: PM 2.5 Averaging Time: 24 h Mean (μg/m 3 ) (IQR): 13.4 (11.3-15.2) Monitoring Stations: NR Copollutant (correlation): NR Other variables: Median of pairwise correlations among PM 2.5 monitors within the same county for 2000: r = 0.91 (IQR: 0.81-0.95) PM Increment: 10 μg/m 3 (Results in figures; see notes) Percent increase in risk [95% PI]: Cerebrovascular disease (Lag 0): Age 65+: 0.81 [0.30, 1.32] Age 65-74: 0.91 [0.01, 1.82] Age 75+: 0.80 [0.21, 1.38] Peripheral vascular disease (Lag 0): Age 65+: 0.86 [-0.06, 1.79] Age 65-74: 1.21 [-0.26, 2.67] Age 75+: 0.86 [-0.39, 2.11] Ischemic heart disease (Lag 2): Age 65+: 0.44 [0.02, 0.86] Age 65-74: 0.37 [-0.22, 0.96] Age 75+: 0.52 [-0.01, 1.04]



### December 2009 E-113

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Utah, Virginia, Washington, West Virginia, Wisconsin hierarchical models.First stage: Poisson regression (countyspecific) Second stage: Bayesian hierarchical models, to produce a national avg estimate

Covariates: Day of the week, seasonality, temperature, dew point temperature, long-term trends

Season: NR Dose-response Investigated : No Statistical Package: R statistical software version 2.2.0 Lags Considered: 0-2 days, avg of days 0-2 Heart rhythm disturbances (Lag 0): Age 65+: 0.57 [-0.01, 1.15] Age 65-74: 0.46 [-0.63, 1.54] Age 75+: 0.72 [0.02, 1.42] Heart failure (Lag 0): Age 65+: 1.28 [0.78, 1.78] Age 65-74: 1.21 [0.35, 2.07] Age 75+: 1.36 [0.78, 1.94] COPD (Lag 0): Age 65 +: 0.91 [0.91, 1.64] Age 65-74: 0.42 [-0.64, 1.48] Age 75+: 1.47 [0.54, 2.40] Respiratory tract infection: Age 65+: 0.92 [0.41, 1.43] Age 65-74: 0.93 [0.04, 1.82] Age 75+: 0.92 [0.32, 1.53] Annual reduction in admissions attributable to a 10 μg/m 3 reduction in daily PM 2.5 level (95% PI): Cerebrovascular disease: Annual number of admissions: 226,641

Annual reduction in admissions: 1836 [680, 2992] Peripheral vascular disease: Annual number of admissions: 70,061 Annual reduction in admissions: 602 [- 42, 1254]

Ischemic heart disease: Annual number of admissions: 346,082

Annual reduction in admissions: 1523 [69, 2976] Heart rhythm disturbances: Annual number of admissions: 169,627 Annual reduction in admissions: 967 [- 17, 1951]

Heart failure: Annual number of admissions: 246,598

Annual reduction in admissions: 3156 [1923, 4389]

COPD: Annual number of admissions: 108,812

Annual reduction in admissions: 990 [196, 1785] Respiratory tract infections: Annual number of admissions: 226,620

Annual reduction in admissions: 2085 [929, 3241]

Notes : Fig 2: Point estimates and 95% posterior intervals of the % change in admissions rates per 10 μg/m 3 (national avg relative rates) for single lag (0, 1, and 2 days) and distributed lag models for 0 to 2 days (total) for all outcomes. Summary: Positive significant or marginally significant associations between PM 2.5 and cerebrovascular disease at Lag 0 Peripheral vascular disease at Lags 0 and 2 Ischemic heart disease at Lag 2 Heart rhythm disturbances at Lag 0



### December 2009 E-114

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Heart failure at Lag 0, Lag 2, and Lags 0 -2 COPD at Lag 0, Lag 1, and Lags 0-2 and respiratory tract infections at Lag 2 and Lags 0-2. Fig 3: Point estimates and 95% posterior intervals of the % change in admission rates per 10 μg/m 3 (regional relative rates). Summary: For cardiovascular diseases, all estimates in the Midwestern, Northeastern, and Southern regions were positive, while estimates in the other regions (South, West, Central, Northwest) were close to 0. For respiratory disease, there were larger effects in the Central, Southeastern, Southern, and Western regions than in the other regions. Fig 4: Point estimates and 95% posterior intervals of the % change in admission per 10 μg/m 3 (Eastern vs.. Western regions): Summary: All estimates for cardiovascular outcomes were positive in the U.S. Eastern region but not in the U.S. Western region. The estimates for respiratory tract infections were larger in the Western region than in the Eastern region. The estimates for CCPD were positive in the both regions.

Reference: Halonen et al. (2009, 180379 ) Period of Study: 1998-2004

Location: Helsinki, Finland Outcome: Cardiovascular Hospitalizations & Mortality (ICD 10: I00-99) Age Groups: 65+ yr Study Design: Time series

N: NR Statistical Analyses: Poisson, GAM

Covariates: Temperature, humidity, influenza epidemics, high pollen episodes, holidays Dose-response Investigated? No Statistical Package: R Lags Considered: lags 0-3 days; 5-day (0-4) mean Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): NR

Min: 1.1 25th percentile: 5.5 50th percentile: 9.5 75th percentile: 11.7

Max: 69.5 Monitoring Stations: NR Copollutant: PM<0.03, PM0.03-0.1, PM<0.1, PM<0.10.29, PM 10-2.5 , CO, NO 2 Co-pollutant Correlation PM<0.03: 0.14 PM0.03-0.1: 0.48 PM<0.1: 0.35 PM<0.10.29: 0.88 PM 10-2.5 : 0.25 PM Increment: Interquartile Range Percent Change (Lower CI, Upper CI): All Cardiovascular Morality Lag 0: 0.73 (-0.66, 2.13) Lag 1: 0.74 (-0.63, 2.13) Lag 2: 0.74 (-0.62, 2.11) Lag 3: 0.06 (-1.29, 1.43) 5-day mean: 0.87 (-0.94, 2.70) Coronary Heart Disease HA Lag 0: -0.17 (-1.5.0, 1.18) Lag 1: -0.03 (-1.31, 1.26) Lag 2: -0.63 (-1.87, 0.62) Lag 3: 0.48 (-0.78, 1.76) 5-day mean: 0.80 (-0.94, 2.58) Stroke HA Lag 0: -0.99 (-2.78, 0.84) Lag 1: 0.02 (-1.74, 1.82) Lag 2: -1.38 (-3.13, 0.40) Lag 3: -0.17 (-1.92, 1.61) 5-day mean: -0.78 (-3.10, 1.60) Arrhythmia HA Lag 0: 0.82 (-1.03, 2.68) Lag 1: 0.18 (-1.58, 1.97) Lag 2: -0.09 (-1.82, 1.67) Lag 3: -0.48 (-2.22, 1.29) 5-day mean: 0.16 (-2.16, 2.54) *p < 0.05, ‡p < 0.10



### December 2009 E-115

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Host et al. (2008, 155852 ) Period of Study: 2000-2003

Location: Six French cities: Le Havre, Lille, Marseille, Paris, Rouen, and Toulouse Outcome (ICD-10): Daily hospitalizations for all cardiovascular (I00-I99), cardiac (I00-I52), and ischemic heart diseases (I20-I25), all respiratory diseases (J00-J99), respiratory infections (J10-J22). Age Groups: For cardiovascular diseases: All ages, and restricted to ≥ 65 yr. For all respiratory diseases: 0-14 yr, 15-64 yr, and ≥ 65 yr. For respiratory infections: All ages Study Design: Time series

N: NR (Total population of cities: approximately 10 million) Statistical Analyses: Poisson regression

Covariates: Seasons, days of the wk, holidays, influenza epidemics, pollen counts, temperature, and temporal trends

Season: NR Dose-response Investigated: No Statistical Package: MGCV package in R software (R 2.1.1) Lags Considered: Avg of 0-1 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (5th -95th percentile): Le Havre: 13.8 (6.0-30.5) Lille: 15.9 (6.9-26.3) Marseille: 18.8 (8.0-33.0) Paris: 14.7 (6.5-28.8) Rouen: 14.4 (7.5-28.0) Toulouse: 13.8 (6.0-25.0) Monitoring Stations: 13 total: 1 in Toulouse

4 in Paris

2 each in other cities Copollutant (correlation): PM 10-2.5 : Overall: r > 0.6 Ranged between r = 0.28 and

r = 0.73 across the six cities. PM Increment: 10 μg/m 3 increase, and a 27 μg/m 3 increase (corresponding to the difference between the lowest of the 5th percentiles and the highest of the 95th percentiles of the cities’ distributions) ERR (excess relative risk) Estimate [CI]: For all cardiovascular diseases (10 μg/m 3 increase): All ages: 0.9% [0.1, 1.8]

≥ 65 yr: 1.9% [0.9, 3.0] For all cardiovascular diseases (27 μg/m 3 increase): All ages: 2.5% [0.2, 4.9]

≥ 65 yr: 5.3% [2.6, 8.2] For ischemic heart diseases (27 μg/m 3 increase): All ages: 5.2% [-0.6, 11.3]

≥ 65 yr: 12.7% [6.3, 19.5] For cardiac diseases (10 μg/m 3 increase): All ages: 0.9% [-0.1, 2.0]

≥ 65 yr: 2.4% [1.2, 3.7] For cardiac diseases (27 μg/m 3 increase): All ages: 2.5% [-0.3, 5.4]

≥ 65 yr: 6.8% [3.3, 10.3] For ischemic heart diseases (10 μg/m 3 increase): All ages: 1.9 % [-0.2, 4.0]

≥ 65 yr: 4.5% [2.3, 6.8] For all respiratory diseases (10 μg/m 3 increase): 0-14 yr: 0.4% [-1.2, 2.0] 15-64 yr: 0.8% [-0.7, 2.3];

≥ 65 yr: 0.5% [-2.0, 3.0] For all respiratory diseases (27 μg/m 3 increase): 0-14 yr: 1.1% [-3.1, 5.5] 15-64 yr: 2.2% [-1.8, 6.4];

≥ 65 yr: 1.3% [-5.3, 8.2] For respiratory infections (10 μg/m 3 increase): All ages: 2.5% [0.1, 4.8] For respiratory infections (27 μg/m 3 increase): All ages: 7.0% [0.7, 13.6]



### December 2009 E-116

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Jalaludin et al. (2006, 189416 ) Period of Study: Jan 1997-Dec 2001

Location: Sydney, Australia Outcome (ICD-9): Cardiovascular disease (390-459), cardiac disease (390-429), ischemic heart disease (410- 413) and cerebrovascular disease or stroke (430-438) Age Groups: 65+ yr Study Design: Time series

N: NR Statistical Analyses: GAM, GLM

Covariates: Temperature, humidity

Season: Warm (Nov-Apr) and cool (May-Oct) Dose-response Investigated: No Statistical Package: S-Plus Lags Considered: 0-3 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (min-max): 9.5 (2.4-82.1)

SD = 5.1 Monitoring Stations: 14 Copollutant (correlation): Warm BSP: r = 0.93 PM 10 : r = 0.89 O 3 : r = 0.57 NO 2 : r = 0.45 CO: r = 0.35 SO 2 : r = 0.27 Cool BSP: r = 0.90 PM 10 : r = 0.88 O 3 : r = 0.05 NO 2 : r = 0.68 CO: r = 0.60 SO 2 : r = 0.46

Other variables: Warm Temp: r = 0.24 Rel humidity: r = -0.15 Cool Temp: r = -0.04 Rel humidity: r = 0.20 PM Increment: 4.8 μg/m 3 (IQR) Percent Change Estimate [CI]: All CVD Same-day lag: 1.26 [0.56,1.96] Avg 0-1 day lag: 0.85 [0.18,1.52] Cool (same-day lag): 2.23 [0.98,3.50] Warm (same-day lag): 0.73 [-0.05,1.52] Cardiac disease Same-day lag: 1.55 [0.74,2.38] Avg 0-1 day lag: 1.33 [0.54,2.13] Cool (same-day lag): 2.37 [0.87,3.89] Warm (same-day lag): 1.13 [0.22,2.04] Ischemic heart disease Same-day lag: 1.17 [-0.08,2.44] Avg 0-1 day lag: 1.24 [0.04,2.45] Cool (same-day lag): 0.57 [-1.74,2.94] Warm (same-day lag): 1.31 [-0.04,2.68] Stroke Same-day lag: -0.89 [-2.41,0.65] Avg 0-1 day lag: -1.08 [-2.54,0.41] Cool (same-day lag): 1.45 [-1.17,4.15] Warm (same-day lag): -2.19 [-4.00,-0.36] Notes : All other lag-day ORs were provided, yet none were significant. Percent change in ED attendance was also reported graphically (Fig 1-5).

Reference: Jalaludin et al. (2006, 189416 ) Period of Study: Jan 1997-Dec 2001

Location: Sydney, Australia Outcome (ICD-9): Cardiovascular disease (390-459), cardiac disease (390-429), ischemic heart disease (410- 413) and cerebrovascular disease or stroke (430-438) Age Groups: 65+ yr Study Design: Time series

N: NR Statistical Analyses: GAM, GLM

Covariates: Temperature, humidity

Season: Warm (Nov-Apr) and cool (May-Oct) Dose-response Investigated: No Statistical Package: S-Plus Lags Considered: 0-3 days Pollutant: BS,P Averaging Time: 24 h Mean/104/m (min-max): 0.26 (0.04-3.37)

SD = 0.22 Monitoring Stations: 14 Copollutant (correlation): Warm PM 2.5 : r = 0.93 PM : r = 0.82

10 O 3 : r = 0.48 NO 2 : r = 0.35 CO: r = 0.33 SO 2 : r = 0.21

Cool PM 2.5 : r = 0.90 PM 10 : r = 0.75 O : r = -0.08

3 NO 2 : r = 0.59 CO: r = 0.62 SO 2 : r = 0.48

Other variables: Warm Temp: r = 0.23 Rel humidity: r = -0.04

Cool Temp: r = -0.09 Rel humidity: r = 0.36 PM Increment: 0.18/ 104/m (IQR) Percent Change Estimate [CI]: All CVD Same-day lag: 1.05 [0.44,1.66] Avg 0-1 day lag: 0.79 [0.20,1.38]; Cool (same-day lag): 2.38 [1.15,3.62] Warm (same-day lag): 0.45 [-0.18,1.09]

Cardiac disease Same-day lag: 1.34 [0.63,2.05] Avg 0-1 day lag: 1.13 [0.44,1.82]; Cool (same-day lag): 2.50 [1.04,3.98] Warm (same-day lag): 0.80 [0.07,1.54]

Ischemic heart disease Same-day lag: 0.91 [-0.17,2.02] Avg 0-1 day lag: 0.90 [-0.14,1.95]; Cool (same-day lag): 0.52 [-1.74,2.83] Warm (same-day lag): 0.93 [-0.15,2.03]

Stroke Same-day lag: -0.93 [-2.27,0.42] Avg 0-1 day lag: -0.82 [-2.11,0.49]; Cool (same-day lag): 1.38 [-1.19,4.01]; Warm (same-day lag): -1.85 [-3.31,-0.36] Notes : All other lag-day ORs were provided, yet none were significant. Percent change in ED attendance was also reported graphically (Fig 1-5).



### December 2009 E-117

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lisabeth et al. (2008, 155939 ) Period of Study: 2001-2005

Location: Nueces County, Texas Outcome: Ischemic stroke and transient ischemic attacks (ICD codes not reported). Age Groups: 45+ yr Study Design: Time series

N: 3,508 stroke/TIAs (2,350 strokes, and 1,158 TIAs) Statistical Analyses: Poisson regression

Covariates: Temperature, day of week, temporal trends

Season: All, but looked at potential effect modification by season (Summer: Jun-Sep; Non-summer: Oct-May) Dose-response Investigated: No Statistical Package: S-plus 7.0 Lags Considered: Lags 0-5 days, and avg lag effect (0-5 days) Pollutant: PM 2.5 Averaging Time: 24 h Median μg/m3 (IQR): 7.0 (4.8-10.0) Monitoring Stations: 6 Copollutant (correlation): NR PM Increment: 5.1 μg/m 3 (IQR) RR Estimate [CI]: Lag 0: 1.03 (0.99, 1.07) Lag 1: 1.03 (1.00-1.07) All other lags and avg (lag 0-5) were not statistically or marginally significant. Adjusted for O 3 : Lag 0: 1.03 (0.99, 1.07) Lag 1: 1.03 (0.99-1.06) All other lags and avg (lag 0-5) were not statistically or marginally significant.

Notes : Fig 3: % change in stroke/TIA risk associated with an IQR increase in PM 2.5

Reference: Metzger et al. (2004, 044222 ) Period of Study: Aug 1998-Aug 2000

Location: Atlanta Metropolitan area (Georgia) Outcome (ICD-9): Emergency visits for ischemic heart disease (410-414), cardiac dysrhythmias (427), cardiac arrest (427.5), congestive heart failure (428), peripheral vascular and cerebrovascular disease (433-437, 440, 443-444, 451-453), atherosclerosis (440), and stroke (436). Age Groups: All Study Design: Time series

N: 4,407,535 emergency department visits for 1993-2000 (data not reported for 1998-2000) Statistical Analyses: Poisson generalized linear modeling

Covariates: Day of the wk, hospital entry and exit indicator variables, federally observed holidays, temporal trends, temperature, dew point temperature

Season: All Dose-response Investigated: No Statistical Package: SAS Lags Considered: 3-day ma, lags 0 -7 Pollutant: PM 2.5 Averaging Time: 24 h Median μg/m3 (10%-90% range): PM 2.5 : 17.8 (8.9, 32.3) PM 2.5 water soluble metals: 0.021 (0.006-0.061) PM 2.5 acidity: 4.5 (1.9-1.07) PM OC: 0.010

2.5 (-0.001-0.045) PM 2.5 EC: 4.1 (2.2-7.1) Monitoring Stations: 1 Copollutant (correlation): PM 10 : r = 0.84 O : r = 0.65

3 NO 2 : r = 0.46 CO: r = 0.44 SO 2 : r = 0.17 PM 10-2.5 : r = .43 UFP: r = -0.16 PM 2.5 water-sol metals: r = 0.70 PM 2.5 sulfates: r = 0.77 PM 2.5 acidity: r = 0.58 PM 2.5 OC: r = 0.51 PM 2.5 EC: r = 0.48 oxygenated hydrocarbon: r = 31

Other variables: Temperature: r = 0.20 Dew point: r = 0.00 PM Increment: Approximately 1 SD increase: PM 2.5 : 10 μg/m 3

PM 2.5 water-sol metals: 0.03 μg/m 3 PM 2.5 sulfates: 5 μg/m 3 PM 2.5 acidity: 0.02 μequ/m 3 PM 2.5 OC: 2 μg/m 3 PM 2.5 EC: 1 μg/m 3 RR [95% CI]: PM 2.5 (3-day ma): All CVD: 1.033 [1.010, 1.056] Dysrhythmia: 1.015 [0.976, 1.055] Congestive heart failure: 1.055 [1.006-1.105]

Ischemic heart disease: 1.023 [0.983-1.064]

Peripheral vascular and cerebrovascular disease: 1.050 [1.008-1.093]

PM 2.5 water soluble metals (3-day ma): All CVD: 1.027[0.998, 1.056] Dysrhythmia: 1.031 [0.982, 1.082] Congestive heart failure: 1.040 [0.981-1.103]

Ischemic heart disease: 1.000 [0.951-1.051]

Peripheral vascular and cerebrovascular disease: 1.043 [0.991-1.098]

PM 2.5 sulfates (3-day ma): All CVD: 1.003 [0.968, 1.039] Dysrhythmia: 0.986 [0.926, 1.048] Congestive heart failure: 1.009 [0.938-1.085]

Ischemic heart disease: 0.997 [0.936-1.062]

Peripheral vascular and cerebrovascular disease: 1.025 [0.964-1.090]

PM 2.5 acidity (3-day ma):



### December 2009 E-118

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) All CVD: 0.994 [0.966, 1.022] Dysrhythmia: 0.991 [0.942, 1.043] Congestive heart failure: 0.989 [0.930-1.052]

Ischemic heart disease: 0.992 [0.944-1.043]

Peripheral vascular and cerebrovascular disease: 1.004 [0.955-1.056]

PM 2.5 OC (3-day ma) : All CVD: 1.026 [1.006, 1.046] Dysrhythmia: 1.008 [0.975, 1.044] Congestive heart failure: 1.048 [1.007-1.091]

Ischemic heart disease: 1.028 [0.994-1.064]

Peripheral vascular and cerebrovascular disease: 1.026 [0.990-1.062] hydrocarbons simultaneously.

PM 2.5 OC (3-day ma): All CVD: 1.020 [1.005, 1.036] Dysrhythmia: 1.011 [0.985, 1.037] Congestive heart failure: 1.035 [1.003-1.068]

Ischemic heart disease: 1.019 [0.992-1.046]

Peripheral vascular and cerebrovascular disease: 1.021 [0.994-1.049] Results for Lags 0-7 expressed in figures (see notes). Notes : Fig 1: RR (95% CI) for singleday lag models for the association of ER visits for CVD with daily ambient PM 2.5 and associated components. Summary of Fig 1 results: Statistically significant positive associations at Lag 0 and Lag 1 for PM 2.5 , at Lag 0 for PM 2.5 water soluble metals (inverse association at Lag 7), at Lag 0, Lag 1, and Lag 3 for organic and EC (inverse association at Lag 7). Fig 2: RR (95%) of multipollutant models for the association of ER visits for CVD with daily ambient air quality measurements. Summary of Fig 2 results: Positive association after adjustment for NO 2 , CO, and oxygenated hydrocarbons, but attenuated when adjusted for total carbon and null when adjusted for NO 2 , CO, total carbon, and oxygenated



### December 2009 E-119

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Peng et al. (2008, 156850 ) Period of Study: Jan 1999-Dec 2005

Location: 108 U.S. counties in the following states: Alabama, Arizona, California, Colorado, Connecticut, District of Columbia, Florida, Georgia, Idaho, Illinois, I ndiana, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Utah, Virginia, Washington, West Virginia, Wisconsin Outcome (ICD-9): Emergency hospitalizations for: Cardiovascular disease, including heart failure (428), heart rhythm disturbances (426-427), cerebrovascular events (430-438), ischemic heart disease (410-414, 429), and peripheral vascular disease (440-448). Respiratory disease, including COPD (490-492) and respiratory tract infections (464-466, 480-487) Age Groups: 65 + yr, 65-74, ,75 + Study Design: Time series

N: ~12 million Medicare enrollees (3.7 million CVD and 1.4 million RD admissions) Statistical Analyses: Two-stage Bayesian hierarchical models: Overdispersed Poisson models for county-specific data Bayesian hierarchical models to obtain national avg estimate

Covariates: Day of the week, agespecific intercept, temperature, dew point temperature, calendar time, indicator for age of 75 yr or older. Some models were adjusted for PM 10-2.5

. Season: NR Dose-response Investigated: No Statistical Package: R version 2.6.2 Lags Considered: 0-2 days Pollutant: PM 2.5 Averaging Time: 24 h Mean μg/m3 (IQR): All counties assessed: 13.5 (11.1-15.8)

Counties in Eastern U.S.: 13.8 (12.3-15.8)

Counties in Western U.S.: 11.1 (10.1-14.3) Monitoring Stations: At least 1 pair of co-located monitors (physically located in the same place) for PM 10 and PM 2.5 per county Other variables: Median within-county correlations between monitors: r = 0.92 PM Increment: 10 μg/m 3 Percentage change [95% CI]: CVD and RD (unadjusted for PM 10 -25): Lag 0: 0.71 [0.45, 0.96] Lag 2: 0.44 [0.06, 0.82] Most values NR (see note)

Notes : Effect estimates for PM 10-2.5 (0-2 day lags) are showing in Fig 2-5. Fig 2: Percentage change in emergency hospital admissions for CVD per 10 μg/m 3 increase in PM 2.5 (single pollutant model and model adjusted for PM 10-2.5 concentration) Fig 3: Percentage change in emergency hospital admissions for RD per 10 μg/m 3 increase in PM 2.5 (single pollutant model and model adjusted for PM 10-2.5 concentration) No significant associations between PM 2.5 and cause-specific cardiovascular disease.

Reference: Peters et al. (2005, 156859 ) Period of Study: Feb 1999-Jul 31, 2001

Location: Germany: City of Augsburg,County Augsburg, and County AichachFriedlberg Outcome: Transmural or nontransmural acute MI Age Groups: NR Study Design: Case-crossover and time series

N: 851 MI survivors Statistical Analyses: Conditional logistic regression for case-crossover element. Poisson regression for time series element.

Covariates: Case-crossover: Season, temperature, day of the week, time series: trend, season, influenza, weather, and day of the week

Season: All Dose-response Investigated: No Statistical Package: SAS, version 8.2 Poisson: R, version 1.7.1 Lags Considered: Lags 0-6 h, 0-5 days Poisson: Single lagged days, 5-day, 15-day, 30-day, and 45-day ma Pollutant: PM 2.5 Averaging Time: 1 h and 24 h Mean μg/m3 (range IQR/ median IQR): 1-h avg: 16.3 (-6.9-355.2 10.7-19.8 14.5) 24-h avg: 16.3 (6.1-58.5 11.6-19.3 14.9) Monitoring Stations: 1 Copollutant (correlation): 24-h avg: TNC: r = 0.37 TSP: r = 0.89 PM : r= 0.92

10 CO: r = 0.57 NO 2 : r = 0.67 NO: r = 0.59 SO 2 : r = 0.58 O 3 : r = -0.24 1hr avg: TNC: r = 0.42 CO: r = 0.52 NO : r = 0.58

2 NO: r = 0.50 SO 2 : r = 0.48 O : r = -0.35

3 Other variables: 24-h avg: Temperature: r = 0.05 1-h avg: Temperature: r = -0.01 PM Increment: 1-h avg: 9.1 μg/m 3 (IQR) 24-h avg: 7.7 μg/m 3 (IQR) OR [95% CI]: Case-Crossover (control selection method (unidirectional with three control periods):

1-h avg: Lag 0: 0.98 (0.88, 1.10) Lag 1: 0.97 (0.87, 1.09) Lag 2: 0.93 (0.83, 1.04) Lag 3: 0.98 (0.88, 1.09) Lag 4: 0.96 (0.86, 1.07) Lag 5: 0.94 (0.84, 1.05) Lag 6: 0.90 (0.80, 1.01).

24-h avg: Lag 0: 0.95 (0.83, 1.080) Lag 1: 1.10 (0.96, 1.25) Lag 2: 1.18 (1.03, 1.34) Lag 3: 1.07 (0.94, 1.22) Lag 4: 0.94 (0.83, 1.07) Lag 5: 0.90 (0.79, 1.02) Case-Crossover (control selection method: bidirectional with 16 control periods): 24-h avg: Lag 0: 1.03 (0.94, 1.12) Lag 1: 1.07 (0.98, 1.16) Lag 2: 1.08 (0.99, 1.17) Lag 3: 1.01 (0.92, 1.10) Lag 4: 0.96 (0.88, 1.04) Lag 5: 0.93 (0.85, 1.02) Lag 0 -4 (IQR = 5.8): 1.03 (0.94, 1.14) Unidirectional: Model 1 (unadjusted): 1.175 (1.033, 1.337) Model 2 (adjusted for day of week using indicator variables): 1.179 (1.035,



### December 2009 E-120

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 1.343)Model 3 (adjusted for temperaturequadratic, linear air pressure): 1.170 (1.028, 1.333)Model 4 (adjusted for temperaturequadratic, linear air pressure, day of week): 1.176 (1.031, 1.341) Model 5 (temperature-quadratic, airpressure-quadratic, relative humidityquadratic, day of week using indicator variables): 1.170 (1.026, 1.336) Model 6 (temperature-penalized spline, 4.4 df, linear air pressure, day of week using indicator variables): 1.175 (1.030, 1.340 Model 7 (temperature-penalized spline, 4.4 df, linear air pressure, relative humidity-penalized spline, 7.8 df, day of week using indicator variables: 1.177 (1.030, 1.344) Bidirectional (16 control periods): Model 1 (unadjusted): 1.077 (0.988, 1.174) Model 2 (adjusted for day of the week using indicator variables): 1.078 (0.988, 1.175)Model 3 (adjusted for temperaturequadratic, linear air pressure): 1.060 (0.970, 1.160)Model 4 (adjusted for temperaturequadratic, linear air pressure, day of the week): 1.060 (0.969, 1.160)

Model 5(temperature-quadratic, air pressurequadratic, relative humidity-quadratic, day of the week using indicator variables): 1.065 (0.973, 1.166) Model 6 (temperature-penalized spline, 4.4 df, linear air pressure, day of the week using indicator variables): 1.068 (0.976, 1.168) Model 7 (temperature-penalized spline, 4.4 df, linear air pressure, relative humidity-penalized spline, 7.8 df, day of the week using indicator variables: 1.077 (0.983, 1.179) Bidirectional (4 control periods): Model 1 (unadjusted): NR Model 2 (adjusted for day of the week by design): 1.049 (0.964, 1.141)Model 3 (adjusted for temperaturequadratic, linear air pressure): NRModel 4 (adjusted for temperaturequadratic, linear air pressure, day of the week): 1.032 (0.944, 1.128) Model 5 (temperature-quadratic, airpressure-quadratic, relative humidityquadratic, day of the week by design): 1.033 (0.945, 1.130) Model 6 (temperature-penalized spline, 4.4 df, linear air pressure, day of the week by design): 1.036 (0.947, 1.132) Model 7 (temperature-penalized spline, 4.4 df, linear air pressure, relative



### December 2009 E-121

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) humidity-penalized spline, 7.8 df, day of the week by design): 1.039 (0.950, 1.136) Stratified: Model 1 (unadjusted): NR Model 2 (adjusted for day of week by design): 1.059 (0.972, 1.154)Model 3 (adjusted for temperaturequadratic, linear air pressure): NRModel 4 (adjusted for temperaturequadratic, linear air pressure, day of week): 1.047 (0.957, 1.145) Model 5 (temperature-quadratic, airpressure-quadratic, relative humidityquadratic, day of week by design): 1.045 (0.954, 1.144) Model 6 (temperature-penalized spline, 4.4 df, linear air pressure, day of week by design): 1.054 (0.964, 1.153odel 7 (temperature-penalized spline, 4.4 df, linear air pressure, relative humidity-penalized spline, 7.8 df, day of week by design): 1.056 (0.965, 1.156) RR (95% CI): Time series (24 h avg): Lag 0: 0.97 (0.89, 1.07) Lag 1: 1.04 (0.96, 1.13) Lag 2: 1.07 (0.98, 1.15) Lag 3: 1.03 (0.95, 1.11) Lag 4: 0.98 (0.90, 1.07) Lag 5: 0.98 (0.90, 1.06) Lag 0-4: 1.03 (0.94, 1.12) Lag 0-14: 1.03 (0.95, 1.13) Lag 0-29: 1.09 (1.01, 1.18) Lag 0-44: 1.08 (1.00, 1.17) Time series (OR [95% CI]): Model 1 (unadjusted): 1.059 (0.981, 1.142) Model 2 (adjusted for day of week using indicator variables): 1.056 (0.979, 1.140)Model 3 (adjusted for temperaturequadratic, linear air pressure): 1.062 (0.982, 1.148)Model 4 (adjusted for temperaturequadratic, linear air pressure, day of week): 1.059 (0.979, 1.146) Model 5 (temperature-quadratic, airpressure-quadratic, relative humidityquadratic, day of week using indicator variables): 1.063 (0.981, 1.151) Model 6 (temperature-penalized spline, 4.4 df, linear air pressure, day of week using indicator variables): 1.065 (0.985, 1.153) Model 7 (temperature-penalized spline, 4.4 df, linear air pressure, relative humidity-penalized spline, 7.8 df, day of week using indicator variables: 1.069 (0.988, 1.157)



### December 2009 E-122

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Pope et al.(2006, 091246 ) Period of Study: 1994-2004

Location: Wasatch Front area, Utah Outcome: Myocardial infarction or unstable angina (ICD codes not reported) Age Groups: All, <65, 65+ Study Design: Case-crossover

N: 12,865 patients who underwent coronary arteriography Statistical Analyses: Conditional logistic regression

Covariates: Temperature and dew point temperature

Season: NR Dose-response Investigated: No Statistical Package: NR Lags Considered: 0- to 3-day lag, 2- to 4-day lagged ma Pollutant: PM 2.5 Averaging Time: 24 h Mean (μg/m3) (SD maximum): Ogden: 10.8 (10.6 108) SLC Hawthorne: 11.3 (11.9 94) Provo/Orem, Lindom: 10.1 (9.8 82) Monitoring Stations: 3 Copollutant (correlation): NR PM Increment: 10 μg/m 3 Percent increase in risk [95% CI]: Same-day increase in PM 2.5 (Lag 0): Index MI and unstable angina: 4.81 [0.98-8.79] Subsequent MI: 3.23 [-3.87, 10.85] All acute coronary events: 4.46 [1.07-7.97] All acute coronary events excluding observations using imputed PM 2.5 data: 4.24 [0.33-8.31] Stable presentation: -2.57 [-5.39, 0.34] Remaining results summarized in figures (see notes).

Notes : Fig 1: Percent increase in risk (and 95% CI) of acute coronary events associated with 10 μg/m 3 of PM 2.5 for different lag structures. Summary of Fig 1: Positive, statistically significant association seen for Lag 0, Lag 1 and 2, 3, and 4 day ma. Positive but non-statistically significant associations seen for Lags 2 and 3. Fig 2: Percent increase in risk (and 95% CI) of acute coronary events associated with 10 μg/m 3 of PM 2.5 stratified by various characteristics.

Reference: Pope et al. (2008, 191969 ) Period of Study: 1994-2006

Location: Ogden, Salt Lake City, & Provo/Orem, Utah Outcome: Heart Failure Hospitalizations Age Groups: NR Study Design: Case-crossover

N: 2,618 Statistical Analyses: Conditional Logistic Regression

Covariates: Age, sex, length of stay, temperature, pressure, clearing index,day of the week, seasonality, and longterm trends

Season: Adjusted for long-term trends to account for season Dose-response Investigated? No Statistical Package: NR Lags Considered: 0- to 28-day ma. Pollutant: PM 2.5 Averaging Time: NR Mean (SD): Ogden: 10.6(9.9) SLC, Hawthorne: 11.1 (11.2) Provo/Orem, Lindon: 10.1 (9.3)

Max: Ogden: 108 SLC, Hawthorne: 94 Provo/Orem, Lindon: 82 Monitoring Stations: NR Copollutant: PM 10 PM Increment: 10 μg/m 3 Percent Increase: (Lower CI, Upper CI): All HF Admissions All: 13.1 (1.3, 26.2)* Men: 13.4 (-1.7, 30.7)‡ Women: 12.7 (-5.1, 33.9) Age <65 yr: 3.5 (-13.5, 23.8) Age ≥ 65 yr: 19.6 (4.0, 37.5)* Length of stay 0-2 days: 24.4 (-0.8, 56.0) ‡ Length of stay 3-7 days: 10.8 (-4.6, 28.7) Length of stay 8+ days: 6.5 (-15.9, 34.8) First HF Admissions: 2.1 (-11.3, 17.5) Subsequent HF Admits: 32.4 (10.7, 58.4) †

All HF Admissions All: 32.4 (10.7, 58.4) † Men: 29.2 (2.7, 62.6)* Women: 41.5 (5.4, 89.9)* Age <65 yr: -3.1 (-26.5, 27.8) Age ≥ 65 yr: 64.1 (28.6, 109) † Length of stay 0-2 days: 68.9 (12.5, 154)* Length of stay 3-7 days: 35.7 (5.9, 73.9)* Length of stay 8+ days: 2.6 (-28.5, 47.1) *p < 0.05, † p < 0.01, ‡p < 0.10



### December 2009 E-123

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sarnat et al. (2008, 097972 ) Period of Study: Nov 1998-Dec 2002

Location: Atlanta (Georgia) metropolitan area Outcome (ICD-9): Cardiovascular disease ED visits: Ischemic heart disease (410-414), cardiac dysrhythmias (427), congestive heart failure (428), and peripheral vascular and cerebrovascular disease (433-437, 440, 443-444, 451-453) Age Groups: All Study Design: Time series

N: >4.5 million emer gency department visits Statistical Analyses: Poisson generalized linear models

Covariates: Day of the week, holidays, hospital, long-term trends, temperature, dew point temperature

Season: All, warm season (Apr 15-Oct 14), and cool season (Oct 15-Apr 14). Dose-response Investigated: No Statistical Package: NR Lags Considered: 0-day lag Pollutant: PM 2.5 Averaging Time: 24 h

Mean (μg/m3) (median 10th-90th percentile): Total PM 2.5 : Cool season: 15.8 (14.3 7.5-25.5). Warm season: 18.2 (17.0 9.1-29.0)

PM 2.5 EC: Cool: 1.7 (1.4 0.6-3.3). Warm: 1.4 (1.3 0.6-2.5)

PM 2.5 Zn (ng/m 3 ): Cool: 15.7 (11.7 4.6-30.2) Warm: 10.9 (8.5 3.3-20.2)

PM 2.5 K (ng/m 3 ): Cool: 63.0 (53.9 24.3-114.2) Warm: 52.7 (43.3 23.2-93.5)

PM 2.5 Si (ng/m 3 ): Cool: 67.7 (54.1 24.3-123.5). Warm: 110.9 (89.0 32.9-186.3)

PM 2.5 SO 4 2– : Cool: 3.4 (0.6 1.5-5.8). Warm: 6.0 (5.2 2.3-10.8)

PM 2.5 NO 3 -: Cool: 1.4 (1.2 0.5-2.6). Warm: 0.7 (2.9 0.3-1.2)

PM 2.5 Se (ng/m 3 ): Cool: 1.4 (1.1 0.4-3.0). Warm: 1.2 (0.9 0.4-2.7)

PM 2.5 OC: Cool: 4.6 (3.9 1.9-8.0) Warm: 4.0 (3.7 2.1-6.4) Monitoring Stations: 1 Copollutants: NR PM Increment: IQR (specific values not given) Risk ratio [95% CI]: CVD (Lag 0): All seasons: Total PM 2.5 : 1.022 [1.007, 1.038]

PM 2.5 EC: 1.02 [1.013-1.037]

PM 2.5 zinc: 1.013 [1.005-1.022]

PM 2.5 potassium: 1.030 [1.018-1.042]

PM 2.5 silicon: 1.008 [1.00-1.016]

PM 2.5 sulfate: 1.007 [0.994-1.019]

PM 2.5 nitrate: 1.002 [0.990-1.014]

PM 2.5 selenium: 1.002 [0.991-1.012]

PM 2.5 OC: 1.024 [1.013-1.035]

Cool season: Total PM 2.5 : 1.028 [1.012-1.044]

PM 2.5 EC: 1.029 [1.015-1.044]

PM 2.5 Zinc: 1.012 [1.002-1.022]

PM 2.5 K: 1.037 [1.021-1.054]

PM 2.5 Si: 1.022 [1.002-1.043]

PM 2.5 sulfate: 1.014 [0.991-1.037]

PM 2.5 nitrate: 1.006 [0.993-1.019]

PM 2.5 Se: 1.012 [0.997-1.027]

PM 2.5 OC: 1.027 [1.013-1.040]

Warm season: Total PM 2.5 : 1.006 [0.990-1.022]

PM 2.5 EC: 1.021 [1.000-1.043]

PM 2.5 Zinc: 1.017 [1.002-1.033]

PM 2.5 K: 1.024 [1.007-1.041]

PM 2.5 Si: 1.005 [0.996-1.014]

PM 2.5 sulfate: 1.001 [0.988-1.015]

PM 2.5 nitrate: 1.000 [0.969-1.033]

PM 2.5 Se: 0.996 [0.981-1.011]

PM 2.5 OC: 1.027 [1.004-1.051]



### December 2009 E-124

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Schreuder et al. (2006, 097959 ) Period of Study: Sep 1995-May 2002

Location: Spokane, WA Outcome: Cardiac HA Age Groups: NR Study Design: Time series Statistical Analyses: GAM Poisosn Regression

Covariates: Season, temperature, relative humidity, day of week Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 0-1 day Pollutant: PM 2.5 (ng/m 3 ) Averaging Time: 24 h

Arithmetic Mean: 10,580

Geometric Mean: 8,790

Min: 930

Max: 43,230

IQR: Entire period: 7.7 μg/m 3 Heating season: 10.1μg/m 3 Non-heating season: 5.5μg/m 3 Monitoring Stations: NR Copollutant: NR Co-pollutant Correlation: NR PM Increment: Interquartile Range Relative Risk (Lower CI, Upper CI): Entire Period, Lag 0: 1.008 (0.985, 1.032) Entire Period, Lag 1: 1.000 (0.978, 1.023) Heating Season, Lag 1: 1.015 (0.968, 1.063) Non-Heating Season, Lag 1: 0.995 (0.969, 1.021)



### December 2009 E-125

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sullivan et al. (2005, 109418 ) Period of Study: 1988-1994

Location: King County, Washington Outcome: Acute MI Age Groups: All, <50, 50-59, 70+ Study Design: Case-crossover

N: 5793 cases of acute MI (5793 case days and 20,134 referent exposure days from these case individuals) Statistical Analyses: Conditional logistic regression

Covariates: Relative humidity, temperature, season, day of week

Season: All, and also conducted stratified analysis by season of event (heating season: Nov-Feb nonheating season: Mar-Oct) Dose-response Investigated: No Statistical Package: SAS version 8.0 and SPSS version 10 Lags Considered: Lag 1 and Lag 2 for 24-h avg Pollutant: PM 2.5 Averaging Time: 1 h, 2 h, 4 h, and 24 h Summary of PM 2.5 1 h before MI onset: Mean (μg/m3) (median IQR, 90th percentile range): 12.8 (8.6

5.3-15.9

27.3 2.0-147) Monitoring Stations: 3 Copollutant (correlation): 1-h avg: PM 10 : r = 0.78

CO: r = 0.47

SO 2 : r = 0.16 PM Increment: 10 μg/m 3 Odds ratio [95% CI]: 1-h Averaging Time: 1.01 [0.98, 1.05] 2-h Averaging Time: 1.01 [0.97, 1.05] 4-h Averaging Time: 1.02 [0.98, 1.04] 24-h Averaging Time: 1.02 [0.98, 1.07]

Association between PM 2.5 (24 h) lagged 1 or 2 days non-significant (data not shown) Season (1-h avg): Heating: 1.01 [0.98-1.05] Nonheating: 0.99 [0.91-1.09] Age (1-h avg): <50 yr: 1.04 [0.95, 1.14] 50-60 yr: 0.99 [0.94, 1.05] 70+ yr: 1.03 [0.98, 1.08] Age (24-h avg): <50 yr: 1.07 [0.98, 1.19] 50-69 yr: 0.99 [0.93, 1.06] 70+ yr: 1.04 [0.99, 1.11] Sex (1-h avg): Men: 1.02 [0.98, 1.06] Women: 1.00 [0.95, 1.06] Sex (24-h avg): Men: 1.03 [0.99, 1.08] Women: 1.00 [0.94, 1.07] Race (1-h avg): White: 1.01 [0.97, 1.04] Nonwhite: 1.06 [0.97, 1.17] Race (24-h avg): White: 1.01 [0.97, 1.06] Nonwhite: 1.10 [0.99, 1.23] Smoking status (1-h avg): Current: 0.99 [0.93, 1.06] Nonsmoker: 1.03 [0.97, 1.08] Smoking status (24-h avg): Current: 0.99 [0.95, 1.14] Nonsmoker: 1.03 [0.98, 1.09] Survivor of MI * (1-h avg): Yes: 1.02 [0.98, 1.06]; No: 0.96 [0.86, 1.08] Survivor of MI * (24-h avg): Yes: 1.03 [0.98, 1.07]; No: 0.97 [0.85, 1.10] Previous congestive heart failure (1 h avg): Yes: 1.06 [0.97, 1.16]; No: 1.00 [0.97, 1.04] Previous congestive heart failure (24-h avg): Yes: 1.08 [0.97, 1.2]; No: 1.00 [0.97, 1.04] Previous MI (1-h avg): Yes: 1.03 [0.97, 1.1]; No: 1.01 [0.96, 1.06] Previous MI (24-h avg): Yes: 1.04 [0.97, 1.17]; No: 1.02 [0.98, 1.08] Hypertension (1-h avg): Yes: 1.02 [0.97, 1.07]; No: 1.01 [0.96, 1.06] Hypertension (24-h avg): Yes: 1.02 [0.97, 1.07]; No: 1.02 [0.97, 1.08] Diabetes mellitus (1-h avg): Yes: 1.06 [0.98, 1.14]; No: 1.01 [0.97, 1.05] Diabetes mellitus (24-h avg): Yes: 1.04 [0.95, 1.14]; No: 1.01 [0.97, 1.06] *Compares those who survive hospitalization (yes) with those who died in hospital from complications of MI.



### December 2009 E-126

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Symons et al. (2006, 091258 ) Period of Study: Apr-Dec 2002

Location: Baltimore, Maryland Outcome: Congestive heart failure Age Groups: All Study Design: Case-crossover

N: 125 patients Statistical Analyses: Conditional logistic regression

Covariates: Temperature and humidity

Season: NR Dose-response Investigated: Yes Statistical Package: SAS and S-Plus Lags Considered: 0-3 days (single and cumulative) Pollutant: PM 2.5 Averaging Time: 8 h & 24 h Mean (min-max):

8 h 17.0 (0.1-111.9)

SD = 12.7

24 h 16.0 (3.5-69.2)

SD = 10.0 Monitoring Stations: 8 Copollutant (correlation): NR PM Increment: 9.2 μg/m 3 (IQR) RR Estimate [CI]: 8 h (participant’s onset period) Same-day lag: 0.87 [0.69,1.09] 1-day lag: 0.96 [0.78,1.18] 2-day lag: 1.09 [0.91,1.30] 3-day lag: 0.99 [0.79,1.23] Cumulative 1-day lag: 0.89 [0.67,1.16] Cumulative 2-day lag: 0.99 [0.74,1.33] Cumulative 3-day lag: 0.98 [0.70,1.36]

24 h avg Same-day lag: 0.81 [0.65,1.01] 1-day lag: 0.90 [0.74,1.11] 2-day lag: 0.85 [0.68,1.07] 3-day lag: 0.86 [0.70,1.05] Cumulative 1-day lag: 0.82 [0.64,1.04] Cumulative 2-day lag: 0.76 [0.57,1.01] Cumulative 3-day lag: 0.70 [0.51,0.97] Notes : β coefficients presented in Fig 5

Reference: Tolbert et al. (2007, 090316 ) Period of Study: Aug 1998-Dec 2004

Location: Atlanta Metropolitan area, Georgia Outcome (ICD-9): Combined CVD group, including: Ischemic heart disease (410-414), cardiac dysrhythmias (427), congestive heart failure (428), and peripheral vascular and cardiovascular disease (433-437, 440, 443-445, and 451-453) Age Groups: All Study Design: Time series

N: NR for 1998-2004. For 1993-2004: 10,234,490 ER visits (283,360 and 1,072,429 visits included in the CVD and RD groups, respectively) Statistical Analyses: Poisson generalized linear models

Covariates: Long-term temporal trends, season (for RD outcome), temperature, dew point, days of week, federal holidays, hospital entry and exit

Season: All Dose-response Investigated: No Statistical Package: SAS version 9.1 Lags Considered: 3-day ma(lag 0 -2) Pollutant: PM 2.5 Averaging Time: 24 h Mean (μg/m3) (median IQR, range, 10th -90th percentiles): PM 2.5 : 17.1 (15.6 11.0-21.9 0.8-65.8 7.9-28.8).

PM 2.5 sulfate: 4.9 (3.9 2.4-6.2 0.5-21.9 1.7-9.5).

PM OC: 4.4 (3.8

2.5 2.7-5.3 0.4-25.9 2.1-7.2).

PM 2.5 EC: 1.6 (1.3 0.9-2.0 0.1-11.9 0.6-3.0).

PM 2.5 water-soluble metals: 0.030 (0.023 0.014-0.039 0.003-0.202 0.009-0.059) Monitoring Stations: 1 Copollutant (correlation): Between PM 2.5 and: PM : r = 0.84

10 O 3 : r = 0.62 NO 2 : r = 0.47 CO: r = 0.47 SO 2 : r = 0.17 PM 10-2.5 : r = 0.47 PM 2.5 SO : r = 0.76 4 PM 2.5 EC: r = 0.65 PM 2.5 OC: r = 0.70 PM 2.5 TC: r = 0.71 PM 2.5 water-sol metals: r = 0.69 OHC: r = 0.50

Between PM 2.5 SO 4 and: PM 10 : r = 0.69 O 3 : r = 0.56 NO : r = 0.14

2 CO: r = 0.14 SO 2 : r = 0.09 PM 10- : r = 0.32 2.5 PM 2.5 : r = 0.76 PM 2.5 EC: r = 0.32 PM 2.5 OC: r = 0.33 PM Increment: PM 2.5 : 10.96 μg/m 3 (IQR) PM 2.5 sulfate: 3.82 μg/m 3 (IQR) PM 2.5 total carbon: 3.63 μg/m 3 (IQR) PM 2.5 OC: 2.61 μg/m 3 (IQR) PM 2.5 EC: 1.15 μg/m 3 (IQR) PM 2.5 water-soluble metals: 0.03 μg/m 3 (IQR) Risk ratio [95% CI] (single pollutant models): PM 2.5 : CVD: 1.005 [0.993-1.017] PM 2.5 sulfate: CVD: 0.999 [0.987-1.011] PM total carbon:

2.5 CVD: 1.016 [1.005-1.026] PM 2.5 OC: CVD: 1.015 [1.005-1.026] PM 2.5 EC: CVD: 1.015 [1.005-1.025] PM water-soluble metals:

2.5 CVD: 1.009 [0.997-1.021] Notes : Results of selected multipollutant models for cardiovascular disease are presented in Fig 1. Fig 1: PM 2.5 total carbon adjusted for CO, NO 2 , or NO 2 +CO Summary of results: PM 2.5 total carbon continued to have a positive, statistically significant association with CVD after adjustment for NO 2 but not after adjustment



### December 2009 E-127

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

PM 2.5 TC: r = 0.34 PM 2.5 water-sol metals: r = 0.65 OHC: r = 0.47

Between PM 2.5 EC and: PM 10 : r = 0.61 O 3 : r = 0.40 NO 2 : r = 0.64 CO: r = 0.66 SO 2 : r = 0.22 PM 10-2.5 : r = 0.49 PM 2.5 : r = 0.65PM 2.5 SO 4 : r = 0.32 PM 2.5 OC: r = 0.82 PM 2.5 TC: r = 0.91 PM 2.5 water-sol metals: r = 0.52 OHC: r = 0.35

Between PM 2.5 OC and: PM 10 : r = 0.65 O 3 : r = 0.54 NO 2 : r = 0.62 CO: r = 0.59 SO 2 : r = 0.17 PM 10-2.5 : r = 0.49 PM 2.5 : r = 0.70 PM 2.5 SO 4 : r = 0.33 PM 2.5 EC: r = 0.82 PM 2.5 TC: r = 0.98 PM 2.5 water-sol metals: r = 0.49 OHC: r = 0.37

Between PM 2.5 total carbon and: PM 10 : r = 0.67 O 3 : r = 0.52 NO 2 : r = 0.65 CO: r = 0.63 SO 2 : r = 0.19 PM 10-2.5 : r = 0.51 PM 2.5 : r = 0.71 PM 2.5 SO 4 : r = 0.34 PM 2.5 EC: r = 0.91 PM 2.5 OC: r = 0.98 PM 2.5 water-sol metals: r = 0.52 OHC: r = 0.38

Between PM 2.5 water-soluble metals and: PM 10 : r = 0.73 O 3 : r = 0.43 NO 2 : r = 0.32 CO: r = 0.35 SO 2 : r = 0.06 PM 10-2.5 : r = 0.50 PM 2.5 : r = 0.69 PM 2.5 SO 4 : r = 0.65 PM 2.5 EC: r = 0.52 PM 2.5 OC: r = 0.49 PM 2.5 TC: r = 0.52



### December 2009 E-128

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Villeneuve et al. (2006, 090191 ) Period of Study: Apr 1992-Mar 2002

Location: Edmonton, Canada Outcome (ICD-9): Stroke (430-438), including ischemic stroke (434-436), hemorrhagic stroke (430,432), and transient ischemic attacks (TIA) (435). Age Groups: 65+ yr Study Design: Case-crossover

N: 12,422 visits Statistical Analyses: Conditional logistic regression

Covariates: Temperature and relative humidity

Season: Summer (Apr-Sep), winter (Oct-Mar) Dose-response Investigated: No Statistical Package: SAS (PHREG) Lags Considered: 0, 1, and 3 days Pollutant: PM 2.5 Averaging Time: 24 h Mean μg/m3 (SD): All yr: 8.5 (6.2) Summer: 8.7 (7.1) Winter: 8.3 (5.2) Monitoring Stations: 3 Copollutant (correlation): All yr SO 2 : r = 0.22 NO 2 : r = 0.41 CO: r = 0.43 O 3 -mean: r = -0.07 O 3 -max: r = 0.07 PM 10 : r = 0.79

Summer SO 2 : r = 0.20 NO 2 : r = 0.52 CO: r = 0.42 O 3 -mean: r = 0.11 O 3 -max: r = 0.34 PM 10 : r = 0.85

Winter SO 2 : r = 0.28 NO 2 : r = 0.57 CO: r = 0.71 O 3 -mean: r = -0.45 O 3 -max: r = -0.35 PM 10 : r = 0.70 PM Increment: μg/m 3 (IQR) All yr: 6.3 Summer: 6.5 Winter: 6.0 Adjusted OR Estimate [CI]: Acute ischemic stroke All yr: Same-day lag: 1.00 [0.96,1.04] 1-day lag: 1.00 [0.96,1.05] 3-day lag: 1.01 [0.96,1.06] Summer: Same-day lag: 0.96 [0.90,1.03] 1-day lag: 1.01 [0.94,1.07] 3-day lag: 0.98 [0.89 [1.07] Winter: Same-day lag: 1.04 [0.99,1.10] 1-day lag: 1.01 [0.96,1.07] 3-day lag: 1.05 [0.98,1.13]

Hemorrhagic stroke All yr: Same-day lag: 0.99 [0.90,1.08] 1-day lag: 1.07 [0.98,1.16] 3-day lag: 1.05 [0.93,1.19] Summer: Same-day lag: 0.99 [0.86,1.15] 1-day lag: 1.12 [0.97,1.30] 3-day lag: 1.08 [0.88,1.31] Winter: Same-day lag: 1.04 [0.92,1.18] 1-day lag: 1.08 [0.97,1.20] 3-day lag: 1.11 [0.94,1.31]

Transient cerebral ischemic attack All yr: Same-day lag: 0.98 [0.93,1.03] 1-day lag: 0.99 [0.95,1.04] 3-day lag: 0.96 [0.90,1.03] Summer: Same-day lag: 1.00 [0.92,1.08] 1-day lag: 1.03 [0.95,1.12] 3-day lag: 0.98 [0.88,1.09] Winter: Same-day lag: 0.97 [0.90,1.05] 1-day lag: 0.97 [0.91,1.04] 3-day lag: 0.94 [0.86,1.03] Notes : Adjusted ORs are provided for an IQR increase in the 3-day mean in Fig 1-4 for single and two-pollutant models.

Reference: Zanobetti and Schwartz (2006, 090195 ) Period of Study: 1995-1999

Location: Boston Metropolitan area Outcome (ICD-9): Myocardial infarction (410) or pneumonia (480-487) Age Groups: 65+ yr Study Design: Case-crossover

N: 15,578 patients admitted for MI and 25,857 admitted for pneumonia Statistical Analyses: Conditional logistic regression

Covariates: Temperature, day of the week.

Season: All, and also tested for interaction by warm (Apr-Sep) vs.. cold

season Dose-response Investigated: No Statistical Package: SAS version 8.2 (PROC PHREG) Lags Considered: Lag 0 , and mean of lags 0 -1 Pollutant: PM 2.5 Averaging Time: 24 h Median (μg/m3) (IQR 5th-95th percentile): 11.1 (7.23-16.14 3.87-26.31) Monitoring Stations: 1 Copollutant (correlation):

BC: r = 0.66

NO 2 : r = 0.55

CO: r = 0.52

O 3 : r = 0.20

PM non-traffic: r = 0.74 PM Increment: Difference between the 90th and 10th percentile for PM 2.5 Myocardial infarction cohort (Lag 0): 17.17 μg/m 3 Myocardial infarction cohort (Lag 0-1): 16.32 μg/m 3 Pneumonia cohort (Lag 0): 17.14 μg/m 3 Pneumonia cohort (Lag 0): 16.32 μg/m 3 Percentage (%) increase in risk [95% CI]: Myocardial infarction cohort: Lag 0: 8.50 (1.89-14.43) Lag 0-1: 8.65 (1.22-15.38)

Pneumonia cohort: Lag 0: 6.48 (1.13-11.43) Lag 0-1: 5.56 (-0.45, 11.27) Notes : Assessed for effect modification by season. Results are reported in Fig 2. Summary of results: PM 2.5 is associated with pneumonia hospitalization in the cold season but not the hot season. PM 2.5 is associated with MI hospitalization in the hot season but not the cold season.



### December 2009 E-129

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zanobetti and Schwartz (2006, 090195 ) Period of Study: 1995-1999

Location: Boston Metropolitan area Outcome (ICD-9): Myocardial infarction (410) or pneumonia (480-487) Age Groups: 65 + yr Study Design: Case-crossover

N: 15,578 patients admitted for MI and 25,857 admitted for pneumonia Statistical Analyses: Conditional logistic regression

Covariates: T emperature, day of the week.

Season: All, and also assessed for interaction by hot (Apr-Sep) vs.. cold

season Dose-response Investigated: No Statistical Package: SAS Software Release 8.2 Lags Considered: Lag 0 , and mean of lags 0 -1 Pollutant: BC Averaging Time: 24 h Median (μg/m3) (IQR 5th-95th percentiles): 1.15 (0.74-1.72 0.42-2.83) Monitoring Stations: 1 Copollutant (correlation):

PM 2.5 : r = 0.66

NO 2 : r = 0.70

CO: r = 0.82

O 3 : r = -0.25

PM non-traffic: r = -0.01 PM Increment: Difference between the 90th and 10th percentile for BC Myocardial infarction cohort (Lag 0): 2.01 μg/m 3 Myocardial infarction cohort (Lag 0-1): 1.69 μg/m 3 Pneumonia cohort (Lag 0): 2.05 μg/m 3 Pneumonia cohort (Lag 0 -1): 1.69 μg/m 3 Percentage (%) increase in risk [95% CI]: Myocardial infarction cohort: Lag 0: 6.98 (-0.27-13.76) Lag 0-1: 8.34 (0.21-15.82)

Pneumonia cohort: |Lag 0: 10.76 (4.54-15.89) Lag 0-1: 11.71 (4.79, 17.36) Notes : Assessed for effect modification by season. Results are reported in Fig 2. Summary of results: PM 2 .BC is associated with pneumonia hospitalization in the cold season but not the hot season. BC had a stronger positive association with MI hospitalization in the cold season, but the confidence interval was wide.

1 All units expressed in μg/m 3 unless otherwise specified.



# Table E-8. Short-term exp osure-cardiovascular-ED/HA- other size fractions.

Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Andersen et al, (2008, 189651 ) Period of Study: May 2001-Dec 2004

Location: Copenhagen, Denmark Outcome (ICD-10): CVD, including angina pectoris (I20), myocardial infarction (I21-22), other acute ischemic heart diseases (I24), chronic ischaemic heart disease (I25), pulmonary embolism (I26), cardiac arrest (I46), cardiac arrhythmias (I48-48), and heart failure (I50). RD, including chronic bronchitis (J41-42), emphysema (J43), other chronic obstructive pulmonary disease (J44), asthma (J45), and status asthmaticus (J46). Pediatric hospital admissions for asthma (J45) and status asthmaticus (J46). Age Groups: >65 yr (CVD and RD), 5-18 yr (asthma) Study Design: Time series

N: NR Statistical Analyses: Poisson GAM

Covariates: Temperature, dew-point temperature, long-term trend, seasonality, influenza, day of the week, public holidays, school holidays (only for 5-18 yr olds), pollen (only for pediatric asthma outcome)

Season: NR Pollutant: Total number concentration of ultrafine and accumulation mode particles (NCtot) (particles/cm 3 ) Averaging Time: 24 h

NCtotal Mean (SD): 8,116 (3502 ) Median: 7,358 IQR: 5,738-9,645 99 th Percentile: 19,895

NCa12 Mean (SD): 493 (315) Median: 463 IQR: 308-650 99 th Percentile: 1,263

NCa23 Mean (SD): 2,253 (1,364) Median: 2,057 IQR: 1,280-3,066 99 th Percentile: 6,096

NCa57 Mean (SD): 5,104 (2,687) Median: 4,562 IQR: 3,248-6,274 99 th Percentile: 14,410

NCa100 Mean (SD): 6,847 (2,846) Median: 6,243 IQR: 4,959-8,218 99 th Percentile: 16,189

NCa212 PM Increment: IQR increase in pollutant level: Nctot: 3907 particles/cm 3 (IQR) N ca12 : 342 particles/cm 3 (IQR) N ca23 : 1786 particles/cm 3 (IQR) N ca57 : 3026 particles/cm 3 (IQR) N C100 : 3259 particles/cm 3 (IQR) N ca212 : 495 particles/cm 3 (IQR) Relative risk (RR) Estimate [CI]: CVD hospital admissions (4-day avg, lag 0 - 3), age 65+ One-pollutant model (NCtot): 1.00 [0.99-1.02] Adj for PM 10 : 0.98 [0.96-1.01] Adj for PM 2.5 : 0.99 [0.95-1.03] Adj for CO: 0.99 [0.97-1.02] Adj for NO 2 : 1.01 [0.98-1.03] Adj for O 3 : 1.01 [0.96-1.06] One-pollutant model (NC100): 1.00 [0.98-1.02] One pollutant model (Nca12): 0.99 [.97-1.01] Adj for other size fractions: 0.99 [0.97-1.02] One pollutant model (Nca23): 0.99 [0.96-1.01] Adj for other size fractions: 0.99 [0.96-1.02] One pollutant model (NCa57): 1.01 [0.98-1.02] Adj for other size fractions: 0.99 [0.97-1.02] One pollutant model (Nca212): 1.02 [1.00-1.04]



### December 2009 E-130

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Dose-response Investigated: No Statistical Package: R statistical software (gam procedure, mgcv package) Lags Considered: Lag 0 -5 days, 4- day pollutant avg (lag 0 -3) for CVD, 5- day avg (lag 0-4) for RD, and a 6-day avg (lag 0-5) for asthma. Mean (SD): 392 (441) Median: 246 IQR: 89-584 99 th Percentile: 2,248 *NC, number concentration tot, total (all particles 6-700 in diameter) a12, size mode with mean diameter of 12 nm a23, size mode with median diameter of 23 nm a57, size mode with median diameter of 57 nm a212 size mode with median diameter of 212 nm NC100 = a12+a23+0.797*a57+0.084*a 212. Monitoring Stations: 1 Copollutant (correlation): Correlation of NCtot with: PM 10 : r = 0.39 PM 2.5 : r = 0.40 NO 2 : r = 0.68 : r = 0.66 NC 100 : r = 0.98 NC a12 : r = 0.31 NC a23 : r = 0.57 NC a57 : r = 0.87 NC a212 : r = 0.29 CO: r = 0.54 NO X curbside: r = 0.36 O 3 : r = -0.12

Other variables: Temperature: r = -0.06 Relative humidity: r = -0.04 Adj for other size fractions: 1.02 [1.00-1.05] Adj for PM 10 : 0.98 [0.95-1.01] RD hospital admissions (5-day avg, lag 0 -4), age 65+: One-pollutant model: 1.04 [1.00-1.07] Adj for PM 10 : 1.00 [0.96-1.05] Adj for PM 2.5 : 0.97 [0.89-1.05] Adj for CO: 1.03 [0.98-1.07] Adj for NO 2 : 1.00 [0.95-1.05] Adj for O 3 : 0.95 [0.87-1.04] One pollutant model (NC100): 1.03 [0.99-1.07] One pollutant model (Nca12): 1.01 [0.98-1.05] Adj for other size fractions: 1.01 [0.97-1.05] One pollutant model (Nca23): 0.99 [0.94-1.03] Adj for other size fractions: 0.98 [0.94-1.03] One pollutant model (Nca57): 1.04 [1.00-1.08] Adj for other size fractions: 1.02 [0.97-1.06] One pollutant model (Nca212): 1.04 [1.01-1.08] Adj for other size fractions: 1.03 [0.99-1.07] Adj for PM 10 : 1.01 [0.96-1.07] Asthma hospital admissions (6-day avg lag 0-5), age 5-18: One-pollutant model: 1.07 [0.98-1.17] Adj for PM 10 : 1.03 [0.92-1.15] Adj for PM 2.5 : 1.04 [0.85-1.28] Adj for CO: 1.09 [0.99-1.21] Adj for NO 2 : 1.07 [0.96-1.19] Adj for O 3 : 1.08 [0.87-1.35] One pollutant model (NC100): 1.06 [0.97-1.16] One pollutant model (Nca212): 1.08 [0.99-1.18] Adj for other size fractions: 1.07 [0.97-1.19] One pollutant model (Nca23): 1.09 [0.98-1.21] Adj for other size fractions: 1.08 [0.97-1.21] One pollutant model (Nca57): 1.02 [0.94-1.12] Adj for other size fractions: 0.93 [0.83-1.04] One pollutant model (Nca212): 1.08 [1.00-1.17] Adj for other size fractions: 1.12 [1.02-1.23] Adj for PM 10 : 1.10 [0.96-1.13] Notes : Fig 2: Relative risks and 95% confidence intervals per IQR in single day concentration (0-5 day lag). Summary of Fig 2: CVD: Positive, marginally or statistically significant associations at Lag 2 (Nctot, Nca57, Nca212), Lag 3 (Nca212), and Lag 1 (Nca212). RD: Positive, statistically or marginally significant associations at Lag 4 (Nctot, Nca57, NCa212) and Lag 5 (Nctot, Nca57, Nca212), and to a lesser extent Lag 2 (Nctot, Nca212) and Lag 3 (Nctot, Nca212). Asthma: Wide confidence intervals make interpretation difficult. Positive, significant association for Nca212 at Lag 1.



### December 2009 E-131

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Lanki et al. (2006, 089788 ) Period of Study: 1992-2000

Location: Augsburg, Barcelona, Helsinki, Rome, and Stockholm Outcome (ICD-9): Acute myocardial infarction (410 ICD-10: I21, I22) Age Groups: 35+ yr, <75 yr, 75+ yr Study Design: Time series

N: 26,854 hospitalizations Statistical Analyses: GAM

Covariates: Temperature, barometric pressure Season: Warm (Apr-Sep) and cold (Oct-Mar) Dose-response Investigated: No Statistical Package: R package mgcv 0.9-5 Lags Considered: 0-3 days Pollutant: UFP ( PNC) Averaging Time: 24 h Median particles/cm3: Augsburg: 12,400 Barcelona: 76,300 Helsinki: 13,600 Rome: 46,000 Stockholm: 11,800 Copollutant (correlation): Augsburg PM 10 : r = 0.53 CO: r = 0.63 NO 2 : r = 0.65 O 3 : r = 0.26

Barcelona: PM 10 : r = 0.38 CO: r = 0.80 NO 2 : r = 0.49 O 3 : r = -0.35

Helsinki: PM 10 : r = 0.45 CO: r = 0.48 NO 2 : r = 0.82 O 3 : r = 0.01

Rome: PM 10 : r = 0.32 CO: r = 0.83 NO 2 : r = 0.68 O 3 : r = 0.03

Stockholm: PM 10 : r = 0.06 CO: r = 0.56 NO 2 : r = 0.83 O 3 : r = -0.01 PM Increment: 10,000 particles/cm 3 Pooled Rate Ratio [CI]: All 5 cities (35+ yr) Same-day lag: 1.005 [0.996,1.015] 1-day lag: 0.997 [0.982,1.012] 2-day lag: 0.999 [0.990,1.008] 3-day lag: 0.998 [0.979,1.017] 3 cities with hospital discharge register (35+ yr) Same-day lag: 1.013 [1.000,1.026] 1-day lag: 0.995 [0.953,1.039] 2-day lag: 1.001 [0.989,1.014] 3-day lag: 1.009 [0.974,1.046] Warm season (35+ yr) Same-day lag: 1.009 [0.972,1.048] 1-day lag: 1.023 [0.988,1.060]; 2-day lag: 1.050 [1.016,1.085] 3-day lag: 1.022 [0.987,1.058] Cold season (35+ yr) Same-day lag: 1.014 [1.001,1.028] 1-day lag: 1.001 [0.956,1.048] 2-day lag: 1.001 [0.989,1.014] 3-day lag: 1.009 [0.971,1.049] Age >75Non-fatal Same-day lag: 1.032 [1.008,1.056] 1-day lag: 1.009 [0.985,1.032] 2-day lag: 0.989 [0.966,1.013] 3-day lag: 1.009 [0.969,1.051]

Fatal Same-day lag: 1.016 [0.978,1.055] 1-day lag: 1.001 [0.966,1.038] 2-day lag: 1.005 [0.969,1.041] 3-day lag: 0.984 [0.948,1.021] Notes : Rate ratios for PNC are given for 0-5 lag days in graph form (Fig 1) for each city. Pooled rate ratios were also provided for groups <75 yielding similar results to the overall 3-city data.

Reference: Metzger et al. (2004, 044222 ) Period of Study: Aug 1998-Aug 2000

Location: Atlanta Metropolitan area (Georgia) Outcome (ICD-9): Emergency visits for ischemic heart disease (410-414), cardiac dysrhythmias (427), cardiac arrest (427.5), congestive heart failure (428), peripheral vascular and cerebrovascular disease (433-437, 440, 443-444, 451-453), atherosclerosis (440), and stroke (436). Age Groups: All Study Design: Time series

N: 4,407,535 emergency department visits between 1993-2000 (data not reported for 1998-2000) Statistical Analyses: Poisson generalized linear modeling

Covariates: Day of the week, hospital entry and exit indicator variables, federally observed holidays, temporal trends, temperature, dew point temperature

Season: All Dose-response Investigated: No Statistical Package: SAS Lags Considered: 3-day ma, lags 0-7 Pollutant: UFP (10-100 nm particle count) (no/cm 3 ) Averaging Time: 24 h Median (10%-90% range): 25,900 (11,500-74,600) Monitoring Stations: 1 Copollutant (correlation): PM : r = -0.13

10 O 3 : r = -0.13 NO 2 : r = 0.26 CO: r = 0.10 SO 2 : r = 0.24 PM 2.5 : r = -0.16 PM 2.5 water soluble metals: r = -0.27 PM 2.5 sulfates: r = -0.31; PM 2.5 acidity: r = -0.39; PM 2.5 OC: r = 0.08; PM 2.5 EC: r = 0.08; PM 2.5 oxygenated hydrocarbon: r = 0.05

Other variables: Temperature: r = -0.33 Dew point: r = -0.41 PM Increment: 30,000 no/cm 3 (approximately 1 SD)3 RR [95% CI]: For 3 day ma: All CVD: 0.985 [0.965, 1.005] Dysrhythmia: 0.972 [0.937, 1.008] Congestive heart failure: 0.983 [0.943-1.025]

Ischemic heart disease: 0.989 [0.953-1.026] Peripheral vascular and cerebrovascular disease: 0.998 [0.960-1.039] Results for Lags 0-7 expressed in figures (see notes).

Notes : Fig 1: RR (95% CI) for singleday lag models for the association of ER visits for CVD with daily ambient UFP. Summary of Fig 1 results: Null or negative associations.



### December 2009 E-132

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: von Klot et al. (2005, 088070 ) Period of Study: 1992-2001

Location: Augsburg, Germany Barcelona, Spain Helsinki, Finland Rome, Italy Stockholm, Sweden Outcome (ICD-9): Acute myocardial infarction (410 ICD-10: I21-I22), angina pectoris (411, 413 ICD-10: I20, I24), dysrhythmia (427 ICD-10: I46.0, 46.9, I47-I49, R00.1, R00.8), heart failure (428 ICD-10: 150) Age Groups: 35+ yr Study Design: Cohort

N: 22,006 MI survivors Statistical Analyses: GAM, Spearman correlation

Covariates: Temperature, dew point temp, avg barometric pressure, relative humidity

Season: NR Dose-response Investigated: No Statistical Package: R-software with “mgcv” package Lags Considered: 0-3 days Pollutant : UFP (PNC) Averaging Time: 24 h Mean particle/cm3 (5th-95th percentile): Augsburg: Barcelona: Helsinki: Rome: Stockholm: Monitoring Stations : NR Copollutant (correlation): Augsburg PM 10 : r = 0.52 CO: r = 0.63 NO 2 : r = 0.64 O 3 : r =-0.32

Barcelona PM 10 : r = 0.29 CO: r = 0.71; NO 2 : r = 0.44 O 3 : r =-0.55

Helsinki PM 10 : r = 0.46 CO: r = 0.47; NO 2 : r = 0.83 O 3 : r =-0.16

Rome PM 10 : r = 0.33 CO: r = 0.80; NO 2 : r = 0.71 O 3 : r =-0.47

Stockholm PM 10 : r = 0.06 CO: r = 0.54; NO 2 : r = 0.80 O 3 : r =-0.17 PM Increment: 10,000 particles/cm 3 Pooled RR Estimate [CI]:

All cardiac admissions: 1.026 [1.005,1.048] Myocardial infarction: 1.039 [0.998.1.082] Angina pectoris: 1.020 [0.992,1.048]

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-133

# E.2. Short-Term Exposure and Respiratory Outcomes

E.2.1. Respiratory Morbidity Studies

Table E-9. Short-term exposure-respiratory mo rbidity outcomes -PM 10 

# .

Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Aekplakorn, et al. (2003, 089908 ) Period of Study : 107 days, from Oct 1997-Jan 1998

Location : Mae Mo district, Lampang Province, North Thailand Outcome : Upper respiratory symptoms, lower respiratory symptoms, cough Age Groups : 6-14 yr old Study Design : Logistic regression

N: 98 asthmatic school children, 98 non-asthmatic school children Statistical Analyses: GEE, stratified analysis, PROC GENMOD

Covariates: Temperature and relative humidity

Season : Winter Dose-response Investigated? No Statistical Package : SAS v 8.1 Pollutant : PM 10 Averaging Time: Daily Mean (SD):

Sob Pad station: 31.92

Sob Mo station: 33.64

Hua Fai station: 37.45 Range (Min, Max): Sob Pad: 6.63, 153.25 Sob Mo: 4.23, 121.80 Hua Fai: 6.98, 113.30 Monitoring Stations : 3 Copollutant: PM 2.5 , SO 2 PM Increment: 10 μg/m 3 Odds Ratios [Lower CI, Upper CI] lag: Asthmatics: URS: 1.03 (0.99, 1.07) lag 0 LRS: 1.04 (0.99, 1.09) lag 0 Cough: 1.04 (1.00, 1.07) lag 0 Non-Asthmatics: URS: 1.04 (0.99, 1.08) lag 0 LRS: 1.0 (0.93, 1.07) lag 0 Cough: 0.99 (0.94, 1.05) lag 0 PM + SO

10 2 Asthmatics: URS: 1.03 (0.99, 1.07) lag 0 LRS: 1.03 (0.98, 1.09) lag 0 Cough: 1.04 (1.00, 1.08) lag 0 Non-Asthmatics: URS: 1.04 (0.99, 1.08) lag 0 LRS: 1.0 (0.93, 1.07) lag 0 Cough: 0.99 (0.95, 1.05) lag 0



### December 2009 E-134

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Andersen et al. (2008, 189651 ) Period of Study: Dec 1998-Dec 2004

Location: Copenhagen, Denmark Outcome: Daily symptoms (prospective daily recording of symptoms via diary) Age Groups: 0-3 yr Study Design: Panel study of children with genetic susceptibility to asthma (mothers had asthma)

N: 205 children (living within a 15km radius of the central monitor during the first 3 yr of life) born between Aug 2, 1998 and Dec 12, 2001 Statistical Analyses: Logistic regression model (GEE)

Covariates: T emperature, season, gender, age, exposure to smoking, and paternal history of asthma Effect modification: gender, medication use, and paternal history of asthma Statistical Package: SAS v9.1 Lag: 0,1,2,3,4,2-4 Pollutant: PM 10 Mean: 25.1

SD: 16.7

Percentiles:

25th: 15.7

75th: 30.2

IQR: 14.5 Copollutant (correlation): PM 2.5 (r = 0.79)

Number concentration of ultrafine particles, UFP (r = 0.37)

NO 2 (r = 0.43)

NO X (r = 0.40) CO (r = 0.45)

O 3 (r = -0.32) Temp (r = 0.25) PM Increment: IQR (14.5 μ g/m 3 ) increase Odds Ratios (95%CI) for incident wheezing symptoms Age 0-1 L0: 1.05 (0.88, 1.25) L1: 1.00 (0.82, 1.22) L2: 1.01 (0.83, 1.23) L3: 1.20 (0.98, 1.46) L4: 1.23 (1.02, 1.48) L2-4: 1.21 (0.99, 1.48)

Age 1-2 L0: 1.00 (0.86, 1.15) L1: 1.02 (0.87, 1.19) L2: 1.05 (0.93, 1.19) L3: 0.96 (0.84, 1.09) L4: 1.04 (0.90, 1.21) L2-4: 1.03 (0.88, 1.22)

Age 2-3 L0: 0.87 (0.72, 1.06) L1: 0.95 (0.78, 1.15) L2: 0.99 (0.82, 1.17) L3: 1.03 (0.84, 1.25) L4: 0.89 (0.74, 1.09) L2-4: 0.94 (0.74, 1.19) Age 0-3 L0: 0.97 (0.87, 1.08) L1: 0.99 (0.89, 1.10) L2: 1.01 (0.92, 1.12) L3: 1.03 (0.93, 1.14) L4: 1.04 (0.94, 1.15) L2-4: 1.04 (0.92, 1.17) Two pollutant models (lag 2-4) 1-pollutant model: 1.21 (0.99, 1.48) 2-pollutant (adj for NO 2 ): 1.13 (0.88, 1.45) 2-pollutant (adj for ): 1.16 (0.90, 1.48) 2-pollutant (adj for CO): 1.23 (0.96, 1.57) 110 children living within 5km radius from monitor (sensitivity analysis): Age 0-1: 1.32 (0.95, 1.82) Age 1-2: 1.20 (0.87, 1.67) Age 2-3: 0.78 (0.52, 1.16) Age 0-3: 1.11 (0.88, 1.39)



### December 2009 E-135

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Boezen et al. (2005, 087396 ) Period of Study: Two consecutive winters (winter 1993-winter 1995)

Location: R ural (Meppel, Nunspeet) and urban (Amsterdam) areas in the Netherlands Outcome: FEV 1 , airway hyperresponsiveness (AHR), serum total IgE and daily data on lower respiratory symptoms (LRS), upper respiratory symptoms (URS), cough and morning and evening peak expiratory flow Age Groups: 50-70 yr Study Design: Case-control study

N: 327 patients Statistical Analyses: Logistic regression

Covariates: daily minimum temperature, linear, quadratic and cubic time trend, weekend/holidays, and influenza incidence for the rural and urban areas and two winters separately

Season : winter Dose-response Investigated? No Lags Considered: 0, 1, 2, and 5-day

mean Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Winter 93/94 Urban: 41.5 Winter 93/94 Rural: 44.1 Winter 94/95 Urban: 31.1 Winter 94/95 Rural: 26.6 Percentiles: 50th(Median): Winter 93/94 Urban: 34.6 Winter 93/94 Rural: 30.4 Winter 94/95 Urban: 28.9 Winter 94/95 Rural: 23.7 Range (Min, Max): 93/94 Urban: (12.1-112.7) 93/94 Rural: (7.9-242.2) 94/95 Urban: (8.8-89.9) 94/95 Rural: (7.1-96.9) Copollutant: SO 2 NO 2 BS PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]:AHR-/IgEUpper Respiratory Symptoms Lag 0: OR = 0.99 (0.97-1.01) Lag 1: OR = 1.01 (0.99-1.03) Lag 2: OR = 1.00 (0.96-1.02) 5-day mean: OR = 1.00 (0.96-1.04) Cough Lag 0: OR = 1.00 (0.99-1.02) Lag 1: OR = 0.99 (0.98-1.01) Lag 2: OR = 1.00 (0.98-1.01) 5-day mean: OR = 0.98 (0.95-1.01) >10% fall in morning peak expiratory flow Lag 1: OR = 1.01 (0.98-1.04) Lag 2: OR = 0.97 (0.94-1.00) 5-day mean: OR = 0.97 (0.92-1.02) AHR-/IgE+ Upper Respiratory Symptoms Lag 0: OR = 1.01 (0.99-1.03) Lag 1: OR = 1.02 (1.00-1.04) Lag 2: OR = 1.01 (0.99-1.03) 5-day mean: OR = 1.08 (1.04-1.11) Cough Lag 0: OR = 1.01 (0.99-1.03) Lag 1: OR = 0.99 (0.98-1.01) Lag 2: OR = 1.00 (0.98-1.02) 5-day mean: OR = 1.01 (0.97-1.05) >10% fall in morning peak expiratory flow Lag 1: OR = 0.99 (0.97-1.02) Lag 2: OR = 0.99 (0.97-1.02) 5-day mean: OR = 0.97 (0.93-1.01)AHR+/IgEUpper Respiratory Symptoms Lag 0: OR = 0.99 (0.95-1.03) Lag 1: OR = 1.01 (0.97-1.05) Lag 2: OR = 0.99 (0.96-1.03) 5-day mean: OR = 0.98 (0.91-1.06) Cough Lag 0: OR = 1.00 (0.97-1.02) Lag 1: OR = 1.01 (0.98-1.03) Lag 2: OR = 0.99 (0.96-1.02) 5-day mean: OR = 1.02 (0.96-1.08) >10% fall in morning peak expiratory flow Lag 1: OR = 0.99 (0.95-1.03) Lag 2: OR = 0.99 (0.95-1.03) 5-day mean: OR = 0.99 (0.93-1.06) AHR+/IgE+ Upper Respiratory Symptoms Lag 0: OR = 1.01 (0.98-1.04) Lag 1: OR = 1.03 (1.00-1.05) Lag 2: OR = 1.02 (0.99-1.05) 5-day mean: OR = 1.06 (1.00-1.11) Cough Lag 0: OR = 1.03 (1.01-1.06) Lag 1: OR = 1.00 (0.98-1.02) Lag 2: OR = 0.99 (0.97-1.01) 5-day mean: OR = 0.99 (0.95-1.04) Lag 2: OR = 0.99 (0.96-1.03) 5-day mean: OR = 0.99 (0.92-1.05) >10% fall in morning peak expiratory flow Lag 1: OR = 1.04 (1.00-1.07) Lag 2: OR = 1.03 (0.99-1.06) 5-day mean: OR = 1.05 (0.99-1.11) Reference: Boezen et al. (1999, 040410 ) Periods of Study: 3 Winters (1992-1995)

Location: Urban and rural areas of the Netherlands Outcome: Respiratory symptoms Lower respiratory symptoms (wheeze, attacks of wheezing, shortness of breath) Upper respiratory symptoms (sore throat, runny or blocked nose) Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Winter 1992-93 Urban: 54.8 Rural: 44.7 Winter 1993-94 Increment: 100 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag: OR for respiratory symptoms and exposure to PM 10 in children with BHR and high serum total IgE Lower Respiratory Symptoms 1.32 (1.07, 1.63) 0



### December 2009 E-136

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Bronchial hyperresponsiveness (BHR) Study Design: Time-series Statistical Analyses: Logistic regression (PROC model) Age Groups: 7-11 Urban: 41.5 3 Rural: 44.1 Winter 1994-95 Urban: 31.1 Rural: 26.6 Range (Min, Max): Winter 1992-93 Urban: (4.7, 145.6) Rural: (4.8, 103.8) Winter 1993-94 Urban: (12.1, 112.7) Rural: (7.9, 242.2) Winter 1994-95 Urban: (8.8, 89.9) Rural: (7.1, 96.9)

Copollutants: BS SO 2 NO 2 1.36 (1.13, 1.64) 1 1.36 (1.13, 1.65) 2 2.39 (1.71, 3.35) 0-5 avg. Upper Respiratory Symptoms 1.13 (0.97, 1.32) 0 1.00 (0.87, 1.16) 1 0.96 (0.84, 1.11) 2 0.91 (0.70, 1.18) 0-5 avg >10% morning peak expiratory flow (PEF) decrease 1.10 (0.92, 1.33) 0 1.08 (0.90, 1.28) 1 1.03 (0.87, 1.23) 2 1.10 (0.83, 1.46) 0-5 avg >10% evening peak expiratory flow (PEF) increase 1.37 (1.16, 1.63) 0 1.09 (0.92, 1.29) 1 1.16 (0.98. 1.36) 2 1.35 (1.04, 1.77) 0-5 avg. OR for respiratory symptoms and exposure to PM 10 in children without BHR and low serum total IgE Lower Respiratory Symptoms 1.08 (0.75, 1.57) 0 1.04 (0.70, 1.53) 1 0.98 (0.69, 1.39) 2 1.15 (0.61, 2.15) 0-5 avg. Upper Respiratory Symptoms 1.12 (0.99, 1.28) 0 1.01 (0.89, 1.15) 1 1.01 (0.89, 1.15) 2 0.93 (0.67, 1.28) 0-5 avg >10% morning PEF decrease 1.07 (0.93, 1.23) 0 0.86 (0.75, 0.99) 1 0.97 (0.85, 1.11) 2 0.99 (0.79, 1.23) 0-5 avg >10% evening PEF decrease 1.13 (0.98, 1.30) 0 1.05 (0.91, 1.21) 1 0.99 (0.87, 1.14) 2 0.94 (0.75, 1.17) 0-5 avg OR for respiratory symptoms and exposure to PM 10 in children with BHR and low serum total IgE Lower Respiratory Symptoms 0.77 (0.48, 1.24) 0 1.34 (0.94, 1.93) 1 1.24 (0.86, 1.81) 2 1.92 (0.84, 4.41) 0-5 avg Upper Respiratory Symptoms 1.13 (0.92, 1.40) 0 0.98 (0.79, 1.22) 1 0.97 (0.79, 1.20) 2 0.83 (0.54, 1.25) 0-5 avg >10% morning PEF decrease 1.04 (0.78, 1.38) 0 0.86 (0.66, 1.12) 1 0.91 (0.71, 1.17) 2 0.78 (0.51, 1.20) 0-5 avg >10% evening PEF decrease 1.07 (0.82, 1.41) 0 0.98 (0.76, 1.26) 1 0.93 (0.73, 1.19) 2 0.83 (0.55, 1.26) 0-5 avg OR for respiratory symptoms and exposure to PM 10 in children without BHR and high serum total IgE Lower Respiratory Symptoms 1.04 (0.80, 1.35) 0 1.21 (0.98, 1.51) 1 1.18 (0.96, 1.45) 2 1.35 (0.89, 2.04) 0-5 avg Upper Respiratory Symptoms 1.01 (0.85, 1.20) 0 0.95 (0.81, 1.12) 1 0.93 (0.80, 1.09) 2



### December 2009 E-137

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) 0.93 (0.69, 1.25) 0-5 avg >10% morning PEF decrease 0.97 (0.80, 1.17) 0 1.09 (0.91, 1.30) 1 1.02 (0.85, 1.21) 2 0.95 (0.71, 1.28) 0-5 avg >10% evening PEF decrease 1.02 (0.85, 1.22) 0 1.06 (0.90, 1.25) 1 1.08 (0.93, 1.27) 2 1.04 (0.80, 1.34) 0-5 avg. Reference: Chattopadhyay et al. (2007, 147471 ) Period of Study: NR

Location: Three different points in Kolkata, India: North, South, and Central Outcome: pulmonary function tests (respiratory impairments) Age Groups: All ages Study Design: Cross-sectional

N: 505 people studied for PFT total population of Kolkata not given Statistical Analyses: Frequencies

Covariates: Meteorologic data (i.e. temperature, wind direction, wind speed, and humidity) Dose-response Investigated? No Pollutant: PM 10 Averaging Time: 8 h Mean (SD):

North Kolkata: 535.9

Central Kolkata: 1114.5

South Kolkata: 909.2 Monitoring Stations: 1 Copollutant:

PM<10-3.3

PM<3.3-0.4 PM Increment: NR Respiratory impairments (SD): North Kolkata Male (n = 137) Restrictive: 4 (2.92) Obstructive: 5 (3.64) Combined Res. And Obs.: 6 (4.37) Total: 15 (10.95) Female (n = 152) Restrictive: 3 (1.97) Obstructive: 5 (3.28) Combined Res. And Obs.: N/A Total: 8 (5.26) Total (n = 289) Restrictive: 7 (2.42) Obstructive: 10 (3.46) Combined Res. And Obs: 6 (2.07) Total: 23 (7.96)

Central Kolkata Male (n = 44) Restrictive: 6 (13.63) Obstructive: 1 (2.27) Combined Res. And Obs.: 1 (2.27) Total: 8 (18.18) Female (n = 50) Restrictive: 3 (6.00) Obstructive: 2 (4.00) Combined Res. And Obs.: N/A Total: 5 (10.00) Total (n = 94) Restrictive: 9 (9.57) Obstructive: 3 (3.19) Combined Res. And Obs.: 1 (1.06) Total: 13 (13.82)

South Kolkata Male (n = 52) Restrictive: 1 (1.92) Obstructive: 2 (3.84) Combined Res. And Obs.: 3 (5.76) Total: 6 (11.53) Female (n = 70) Restrictive: 2 (2.85) Obstructive: 1 (1.42) Combined Res. And Obs.: N/A Total: 3 (4.28) Total (n = 122) Restrictive: 3 (2.45) Obstructive: 3 (2.45) Combined Res. And Obs.: 3 (2.45) Total: 9 (7.37)



### December 2009 E-138

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Dales et al. (2006, 090744 ) Period of Study: Jan 1986-Dec 2000

Location: 11 Canadian Cities: Calgary, Edmonton, Halifax, London, Hamilton, Ottawa, St. John, Toronto, Vancouver, Windsor, Winnipeg Health Outcome: Respiratory Illness: Asphyxia (799) Respiratory failure (799.1) Dyspnea and respiratory abnormalities (786) Respiratory distress syndrome (769) Unspecified birth asphyxia in live-born infant (768.9) Other respiratory problems after birth (770.8) Pneumonia (486) Study Design: Time-series Statistical Analyses: Poisson Age Groups: 0-27 days Pollutant: PM 10 Averaging Time: 24-h avg Copollutants (correlation): O 3 : r = -0.29 to 0.41 NO 2 : r = -0.26 to 0.69 SO 2 : r = -0.09 to 0.61 CO: r = -0.13 to 0.71 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) Lag: In respiratory illness and exposure to PM 10 in neonates

PM 10 alone: 2.13 (-0.50, 4.76) Multipollutant model PM 10 : 1.45 (-1.90, 4.80) PM 10 , O 3 : 2.67 (0.98, 4.39) PM 10 , NO 2 : 2.48 (1.18, 3.80) PM 10 , SO 2 : 1.41 (0.35, 2.47) PM 10 , CO: 1.30 (0.13, 2.49)

Reference: de Hartog et al. (2003, 001061 ) Period of Study: Winter of 1998-1999 Amsterdam, from Nov 1998 to Jun 1999 Erfurt, from Oct 1998 to Apr 1999 Helsinki, from Nov 1998 to Apr 1999

Location: Amsterdam, the Netherlands; Erfurt, Germany; Helsinki, Finland Outcome: Respiratory symptoms Age Groups: ≥ 50 yr Study Design: Panel

N: 131 subjects with history of coronary heart disease Statistical Analyses: Logistic regression

Covariates: Ambient temperature, relative humidity, atmospheric pressure, incidence of influenza-like illness

Season: Winter Dose-response Investigated? No Statistical Package: S-PLUS 2000 Lags Considered: 0-, 1-, 2-, 3-, and 5-day avg Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Amsterdam: 36.5 Erfurt: 27.1 Helsinki: 19.6 Range (Min, Max): Amsterdam: (13.6-112.0) Erfurt: (5.2-104.2) Helsinki: (6.4-67.4) Monitoring Stations: 1

Copollutant: PM 2.5 N C0.01-0.1 CO NO 2 SO 2 ‘There was a tendency toward positive associations between avoidance of activities and both particulate air pollution (PM 10 ) and gases, but none of the associations were statistically significant....In both incidence analyses and prevalence analyses, odds ratios for PM 10 were generally similar to the corresponding odds ratios for PM 2.5 , but were somewhat less significant.’

Reference: Delfino et al. (1998, 051406 ) Period of Study: Aug-Oct 1995

Location: Alpine, CA Outcome: asthma symptom severity Age Groups: 9-17 Study Design: Panel Study

N: 24 non-smoking pediatric asthmatics Statistical Analyses: GEE

Covariates: Day of week, temperature, humidity, wind speed Statistical Package: SAS Lags Considered: 0-5, 0, 0-4 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 31 (8)

90th: 42 Range (Min, Max): 16, 54 Copollutant (correlation):

O 3 (r = 0.32) PM Increment: 42 μg/m 3 (90th percentile increase) Asthma symptoms: Everyone: 1.47 (0.90, 2.39) lag 0 Everyone: 1.73 (1.03, 2.89) lag 0-4 Less symptomatic: 2.47 (1.23-4.95) lag 0 Less symptomatic: 4.03 (1.22, 13.33) lag 0-4 More symptomatic: 1.50 (0.80, 2.80) lag 0 More symptomatic: 1.95 (1.12, 3.43) lag 0-4 PM 10 + O 3 Asthma symptoms: 1.31 (0.84, 2.06) lag 0 1.65 (1.03, 2.66) lag 0-4 Less symptomatic: 2.08 (1.12-3.83) lag 0 Less symptomatic: 3.35 (1.06, 10.51) lag 0-4 More symptomatic: 1.40 (0.77, 2.53) lag 0 More symptomatic: 1.87 (1.11, 3.13) lag 0-4



### December 2009 E-139

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Delfino et al. (2002, 093740 ) Period of Study: Mar-Apr 1996

Location: Alpine, California (a semi-rural area) Outcome: Asthma symptoms that interfere with daily activities Age Groups: 9-19 yr Study Design: Daily panel study

N: 22 asthmatic children Statistical Analyses: GEE

Covariates: Temperature, relative humidity, day-of-week trends, linear time trend across the 61 days, and upper or lower respiratory infection

Season: “Early spring season” of Mar-Apr Dose-response Investigated? Yes Statistical Package: SAS, version 8 Lags Considered: 0-, 1-, 2-, 3-, 4-, 5-, and 3-day ma Pollutant: PM 10 Averaging Time: 1 h max Mean (SD) : 38(15) Percentiles: 90th: 63 Range (Min, Max): (12-69) Averaging Time: 8 h max Mean (SD): 28(12) Percentiles: 90th: 46 Range (Min, Max): (8-57) Averaging Time: 24 h Mean (SD): 20(9) Percentiles: 90th: 32 Range (Min, Max): (7-42) Copollutant (correlation): 1 h max PM 10 8 h max PM 10 : r = 0.93 24 h PM 10 : r = 0.84 1 h max O 3 : r = 0.68 8 h max O 3 : r = 0.95 1 h max NO 2 : r = 0.49 8 h max NO 2 : r = 0.55 8 h max PM 10 : 1 h max PM 10 : r = 0.93 24 h PM 10 : r = 0.95 1 h max O 3 : r = 0.72 8 h max O 3 : r = 0.65 1 h max NO 2 : r = 0.48 8 h max NO 2 : r = 0.55 24 h PM 10 : 1 h max PM 10 : r = 0.84 8 h max PM 10 : r = 0.95 1 h max O 3 : r = 0.74 8 h max O 3 : r = 0.71 1 h max NO 2 : r = 0.37 8 h max NO 2 : r = 0.44 PM Increment: 90th percentile increase Effect Estimate [Lower CI, Upper CI]: ORs for risk of asthma symptoms in those who report a respiratory infection compared to those who do not have a respiratory infection 1 h max PM 10 lag 0: 4.88 (1.31-18.2) 8 h max PM 10 lag 0: 6.78 (1.38-33.3) 24 h mean PM 10 lag 0: 4.68 (0.71-30.7) 3-day ma 1 h max PM 10 : 11.1 (1.10-112) 3-day ma 8 h max PM 10 : 10.1 (1.42- 72.0) 3-day ma 24 h PM 10 : 2.67 (0.60-11.8) Effect modification by anti-inflammatory medication use on the relationship of asthma symptoms in children 1 h max PM 10 lag 0: 1.41 (0.87-2.30) On medication: 0.96 (0.25-3.69) Not on medication: 1.92 (1.22-3.02)

8 h max PM 10 lag 0: 1.19 (0.74-1.94) On medication: 0.75 (0.18-3.04) Not on medication: 1.68 (0.91-3.09)

24 h mean PM 10 lag 0: 1.08 (0.73-1.61) On medication: 0.80 (0.24-2.69) Not on medication: 1.35 (0.82-2.22) 3-day ma 1 h max PM 10 : 1.45 (0.76- 2.76) On medication: 1.01 (0.14-7.02) Not on medication: 1.92 (0.99-3.71) 3-day ma 8 h max PM 10 : 1.32 (0.76- 2.29) On medication: 0.82 (0.17-3.94) Not on medication: 1.89 (1.10-3.24) 3-day ma 24 h PM 10 : 1.22 (0.84-1.77) On medication: 0.75 (0.26-2.14) Not on medication: 1.75 (1.15-2.68) Dose-response results are found in Fig 2 and not quantitatively reported elsewhere.

Reference: Delfino et al. (2003, 090941 ) Period of Study: Nov 1999-Jan 2000

Location: Huntington Park, Los Angeles Outcome: Asthma severity scale Peak Expiratory Flow Rate (PEF) Age Groups: Ages 10 to 16 Study Design: Longitudinal study panel

N: 22 children Statistical Analyses: Regression analysis (GEE, GLM) multivariate regression models

Covariates: Day of the week, Maximum Temperature, Respiratory Infections

Season: Winter Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0, 1 Pollutant: PM 10 Mean (SD): 59.9 (24.7) Range (Min, Max): 20-126

IQR: 37

90th: 86.0 Monitoring Stations: 1 Copollutant (correlation):

8-h max NO 2 = 0.38

8-h max O 3 = -0.16

8-h max CO = 0.50

8-h max SO 2 = 0.73 PM Increment: IQR 37.0 μg/m 3 OR Estimate [Lower CI, Upper CI] lag: Lag 0 Symptom Scores >1: 1.45 (1.11, 1.90) Symptom Scores >2: NR Lag 1 Symptom Scores >1: 1.07 (0.64, 1.77) Symptom Scores >2: NR



### December 2009 E-140

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Delfino et al. (2004, 056897 ) Period of Study: Sep-Oct 1999 Apr-Jun 2000

Location: Alpine, California Outcome: FEV 1 Age Groups: 9-19 yr old Study Design: Panel study

N: 24 children Statistical Analyses: GLM

Akaike’s information criterion and Bayesian information criterion

Covariates: Day of week, Personal temperature and relative humidity, time of FEV 1 maneuver (morning, afternoon, or evening), Season (fall 1999 or spring 2000)

As-needed medication use Presence or absence of upper or lower respiratory infections

Season: Spring, Fall Dose-response Investigated? No Statistical Package: SAS Lags Considered: Lag 0-4 Pollutant: PM 10 Averaging Time: 4 h, 8 h, 12 h, 24 h Personal Monitor 1-h max personal PM last 24-h Mean (SD): 151.0 (12.03) 90th: 292.4 Range (Min, Max): (9.1, 996.8) Mean personal PM last 24-h Mean (SD): 37.9 (19.9) 90th: 65.1 Range (Min, Max): (3.9, 113.8) Central outdoor stationary-site PM 1-h Maximum TEOM PM 10 last 24-h Mean (SD): 54.4 (13.8) 90th: 71.0 Range (Min, Max): (24.4, 95.4) Mean TEOM PM 10 last 24-h Mean (SD): 29.7 (8.6) 90th: 40.9 Range (Min, Max): (12.9, 50.7) 24-h mean PM 10 Mean (SD): 23.6 (9.1) 90th: 34.6 Range (Min, Max): (3.2, 48.0) Copollutant (correlation): 8-h max personal PM 8-h max O 3 = 0.03 8-h Max NO 2 = 0.26 24-h Mean Personal PM = 0.94 8-h Max TEOM PM 10 = 0.38 24-h Mean TEOM PM 10 = 0.40 24-h Central HI PM 10 = 0.37 24-h Central HI PM 2.5 = 0.38 24-h Outdoor HI PM 10 = 0.32 24-h Outdoor HI PM 2.5 = 0.39 24-h Indoor HI PM 10 = 0.23 24-h Indoor HI PM 2.5 = 0.37 24-h mean personal PM 8-h max O 3 = 0.01 8-h Max NO 2 = 0.27 8-h Max Personal PM = 0.94 8-h Max TEOM PM 10 = 0.36 24-h Mean TEOM PM 10 = 0.39 24-h Central HI PM 10 = 0.36 24-h Central HI PM 2.5 = 0.43 24-h Outdoor HI PM 10 = 0.34 24-h Outdoor HI PM 2.5 = 0.44 24-h Indoor HI PM 10 = 0.29 24-h Indoor HI PM 2.5 = 0.46 24-h Mean TEOM PM 10 8-h max O 3 = 0.41 8-h Max NO 2 = 0.58 8-h Max Personal PM = 0.40 24-h Mean Personal PM = 0.39 8-h Max TEOM PM 10 = 0.92 24-h Central HI PM 10 = 0.86 24-h Central HI PM 2.5 = 0.78 24-h Outdoor HI PM 10 = 0.79 24-h Outdoor HI PM 2.5 = 0.78 24-h Indoor HI PM 10 = 0.36 24-h Indoor HI PM 2.5 = 0.59 Results presented graphically: Percent predicted FEV 1 was inversely associated with personal exposure to fine particles.

- Inverse associations of FEV 1 with stationary-site indoor, outdoor and central-site gravimetric PM 2.5 and PM 10 , and with hourly TEOM PM 10



### December 2009 E-141

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Delfino et al. (2006, 090745 ) Period of Study: Region 1: Aug to Mid Dec 2003. Region 2: Jul through Nov 2004

Location: Region 1: Riverside, CA. Region 2: Whittier, CA Outcome: Fractional Concentration of Nitric Oxide in exhaled air (FENO) Age Groups: 9 through 18 Study Design: Longitudinal Panel Study

N: 45 children Statistical Analyses: Linear mixedeffects models Two-stage hierarchical model Empirical Variograms Fourth-order polynomial distributed lag mixed-effects model

Covariates: Personal temperature, Personal Rel. Humid., 10-day exposure run, Respiratory infections, Region ofstudy, Sex, Cumulative daily use of asneeded B-agonist inhalers Dose-response Investigated? No Lags Considered: Lag 0, Lag 1, 2-day

ma Pollutant: PM 10 Central Site Averaging Time: 24 h

Riverside Mean (SD): 70.82 (29.36) 50th(Median): 65.96 Range (Min, Max): (30.75,54.05) μg/m 3

Whittier Mean (SD): 35.73 (16.6) 50th(Median): 34.65 Range (Min, Max): (5.86, 105.46) μg/m 3 Monitoring Stations: 48 personal nephelometers, 2 central sites PM Increment: IQR increase (Riverside: 28.41 μg/m 3 , Whittier 21.87 μg/m 3 ) Coefficient [Lower CI, Upper CI] lag: Lag = 2-day ma Stratified by Medication Use Not Taking Anti-Inflamm. Medication Central 0.76 (-1.54, 3.07) Taking Anti-Inflamm. Medication Central 0.53 (-0.83, 1.90)

Inhaled Corticosteroids Central 1.28 (-0.01, 2.58)

Antileukotrienes +- inhaled corticosteroids Central -2.10 (-5.33, 1.12)

Notes : Fig of Estimated lag effect of hourly personal PM 2.5 on FENO. Fig of the Estimated lag effect of hourly personal PM 2.5 on FENO by use of medications. Fig of one- and two-pollutant models for change in FENO using 2-day Ma personal and central-site pollutant measurements.



### December 2009 E-142

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Desqueyroux et al. (2002, 026052 ) Period of Study: Nov 1995-Nov 1996

Location: Paris, France Outcome: Asthma attacks Age Groups: Adults. Study Design: Panel study

N: 60 moderate to severe adult asthmatics Statistical Analyses: Marginal logistic regression

Covariates: FEV 1 , smoking, allergy, oral steroid treatment, mean daily temperature, relative humidity, pollen counts, season, holiday period

Season: winter, summer Dose-response Investigated? No Statistical Package: SAS Lags Considered: 1, 2, 3, 4, 5, 3-5 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Summer: 23 (9) Winter: 28 (14) Range (Min, Max): Summer: 6, 63 Winter: 9, 84 Monitoring Stations: 7 Copollutant: SO 2 , NO 2 , O 3 PM Increment: 10 μg/m 3 OR Estimate [Lower CI, Upper CI] lag: 0.87 [0.71, 1.06] lag 1 0.93 [0.80, 1.08] lag 2 1.11 [0.98, 1.26] lag 3 1.17 [1.03, 1.33] lag 4 1.16 [1.01, 1.34] lag 5 1.21 [1.01, 1.34] lag 3-5

Vs seasons alone: Winter: 1.41 [1.16, 1.71] lag 3-5 Summer: 1.03 [0.72, 1.47] lag 3-5 Vs link to explanatory factors: No link: [1.71 [1.20, 2.43] lag 3-5 Link: 1.27 [1.06, 1.52] lag 3-5

Vs occurrence of infection: Without infection: 1.52 [1.16, 2.00] lag 3-5 With infection: 1.30 [1.03, 1.65] lag 3-5 Vs baseline pulmonary function: FEV 1 >/ = 68% predicted: 1.38 [1.06, 1.79] lag 3-5 FEV <68% predicted: 1.45 [1.11, 1.90] lag 3-5

Vs smoking habits: Nonsmokers: 1.53 [1.18, 1.98] lag 3-5 Current & ex-smokers: 1.18 [0.90, 1.54] lag 3-5

Vs allergy: Non-allergic: 1.29 [0.94, 1.77] lag 3-5 Allergic: 1.49 [1.17, 1.90] lag 3-5

Vs regular oral steroid treatment: No: 1.41 [1.15, 1.73] lag 3-5 Yes: 1.41 [0.88, 2.25] lag 3-5

Multipollutant model: PM 10 + NO 2 : 1.43 [1.16, 1.76] Lag 3-5 PM 10 + SO 2 : 1.51 [1.20, 1.90] Lag 3-5 PM 10 + O 3 : 1.09 [0.71, 1.67] Lag 3-5 Reference: Diette et al. (2007, 156399 ) Period of Study: Sep 2001



# - Dec 2003

Location: East Baltimore, MD Outcome: Asthma in the last 12 mo (493.x) Age Groups: 2 to 6 yr old Study Design: Prospective cohort

N: 150 with asthma

150 without asthma Statistical Analyses: Student’s two-tailed t-test Kruskal-Wallis test Pearson’s chi square Fisher’s exact test Covariates: Season of collection Dose-response Investigated? No Statistical Package: STATASE 8.0 Pollutant: PM 10 Averaging Time: 72 h 50th(Median): 43.7

IQR: (29-70) Notes : “Pollutant concentrations in the homes of asthmatic and control children who lived in the same home for their whole life were not different compared with those who had moved at least once.”



### December 2009 E-143

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Ebelt et al. (2005, 056907 ) Period of Study: Summer of 1998

Location: Vancouver, Canada Outcome: spirometry Age Groups: Range from 54-86 yr mean age = 74 yr Study Design: Extended analysis of a repeated-measures panel study

N: 16 persons with COPD Statistical Analyses: Earlier analysis expanded by developing mixed-effect regression models and by evaluating additional exposure indicators Dose-response Investigated? No Statistical Package: SAS V8 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Ambient PM 10 : 17 (6) Exposure to ambient PM 10 : 10.3 (4.6) Range (Min, Max): Ambient PM 10 : (7-36) Exposure to ambient PM 10 : (1.5-23.8) Monitoring Stations: 5 Copollutant (correlation): Ambient PM 10-2.5 : r = 0.69 Ambient PM 2.5: r = 0.78 Exposure to Ambient PM10: r = 0.71 PM Increment: Ambient PM 10 : 7 (IQR) Exposure to ambient PM 10 : 6.5 (IQR)

Notes : Effect estimates are presented in Fig 2 and Electronic Appendix Table 1 (only available with electronic version of article) and not provided quantitatively elsewhere.

Reference: Fischer et al. (2007, 156435 ) Period of Study: 7 wk (dates not specified)

Location: The Netherlands Outcome: Respiratory Symptoms, Sore throat, Runny nose, Cold, Sick at home Study Design: Prospective cohort

N: 68 Statistical Analyses: Linear regression model (PROC mixed) Age Groups: 10-11 Lag: 1-2 Statistical Package: SAS v 6.11 Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 56 μg/m 3 IQ (25th, 75th): (21, 187) μg/m 3 Copollutants: BS NO 2 CO NO Increment: 10 μg/m 3

% Increase in eNO and PM 10 and change in spirometric lung function lag eNO and PM10 only 6.5 (0.9, 12.4) 1 7.8 (-11.3, 31.0) 2 FVC mean (SEM) 0.4 (0.5) 1 0.6 (1.6) 2 FEV 1 mean (SEM) -0.3 (0.5) 1 -2.1 (1.9) 2 PEF mean (SEM) -2.8 (3.3) 1 7.1 (12.0) 2 MMEF mean (SEM) -0.5 (1.7) 1 -2.5 (5.9) 2 Reference: Forsberg et al. (1998, 051714 ) Period of Study: Jan 1994-March 1994

Location: Urban and rural areas of Umea, Sweden Outcome: Respiratory Symptoms, Shortness of breath Wheeze, Asthma attacks, Recent asthma, Dry cough, Doctor-diagnosed asthma, Recently treated for asthma, Early chest illness Study Design: Cohort panel Statistical Analyses: Logistic linear regression Age Groups: 6-12 Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Urban: 13.4 μg/m3 Rural: 11.5 μg/m3 Range (Min, Max): Urban: (0, 40.5) μg/m3 Rural: (1.6, 29.0) μg/m3 Copollutants (correlation): BS: r = 0.73 Increment: 10 μg/m 3 OR between prevalence of acute respiratory symptoms and PM 10 exposure for urban and rural children lag Urban children: Cough: 1.031 (0.957, 1.112) 0 0.997 (0.923, 1.077) 1 1.018 (0.940, 1.103): 2 1.094 (0.895, 1.338) 0-6 avg Phlegm: 0.998 (0.899, 1.108) 0 1.035 (0.928, 1.154) 1 1.121 (1.013, 1.240) 2 1.043 (0.822, 1.324) 0-6 avg Upper respiratory symptoms: 1.004 (0.949, 1.063) 0 0.975 (0.922, 1.031) 1 0.951 (0.895, 1.010) 2 0.849 (0.687, 1.050) 0-6 avg Lower respiratory symptoms: 0.984 (0.872, 1.110) 0 0.919 (0.812, 1.039) 1 0.894 (0.771, 1.036) 2 0.800 (0.617, 1.038) 0-6 avg Rural children (control) Cough: 0.997 (0.900, 1.105) 0 1.003 (0.906, 1.112) 1 0.997 (0.891, 1.116) 2 0.855 (0.655, 1.115) 0-6 avg Phlegm: 1.024 (0.880, 1.192) 0 0.995 (0.853, 1.160) 1 1.117 (0.956, 1.305) 2 1.041 (0.742, 1.459) 0-6 avg Upper respiratory symptoms: 1.093 (0.989, 1.208) 0 1.018 (0.918, 1.130) 1



### December 2009 E-144

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) 1.075 (0.962, 1.201) 2 1.052 (0.786, 1.407) 0-6 avg Lower respiratory symptoms: 1.022 (0.855, 1.180) 0 0.998 (0.855, 1.164) 1 1.000 (0.830, 1.206) 2 0.939 (0.703, 1.253) 0-6 avg OR between incidence of acute respiratory symptoms and PM 10 exposure in urban and rural children lag Urban Children: Cough: 1.114 (0.886, 1.401) 0 0.891 (0.703, 1.130) 1 0.766 (0.577, 1.017) 2 0.817 (0.523, 1.276) 0-6 avg Phlegm: 0.954 (0.664, 1.371) 0 1.056 (0.744, 1.501) 1 1.416 (0.969, 2.069) 2 0.808 (0.357, 1.827) 0-6 avg Upper respiratory symptoms: 1.155 (0.965, 1.383) 0 0.788 (0.629, 0.986) 1 0.886 (0.728, 1.077) 2 0.770 (0.549, 1.081) 0-6 avg Lower respiratory symptoms: 1.060 (0.828, 1.356) 0 0.763 (0.584, 0.996) 1 0.652 (0.493, 0.863) 2 0.519 (0.306, 0.882) 0-6 avg Rural Children: Cough: 1.052 (0.767, 1.444) 0 0.753 (0.547, 1.038) 1 0.840 (0.571, 1.235) 2 0.800 (0.409, 1.565) 0-6 avg Phlegm: 1.051 (0.731, 1.509) 0 1.010 (0.693, 1.472) 1 0.998 (0.652, 1.528) 2 0.797 (0.344, 1.847) 0-6 avg Upper respiratory symptoms: 1.044 (0.813, 1.341) 0 0.810 (0.612, 1.072) 1 0.800 (0.611, 1.048) 2 0.714 (0.417, 1.220) 0-6 avg Lower respiratory symptoms: 1.079 (0.756, 1.539) 0 0.888 (0.615, 1.281) 1 0.715 (0.472, 1.083) 2 0.822 (0.395, 1.711) 0-6 avg OR between prevalence of medication use and PM10 exposure in urban and rural children lag Bronchodilator use - Urban children: 0.998 (0.951, 1.048) 0 0.999 (0.952, 1.049) 1 1.006 (0.953, 1.062) 2 0.919 (0.775, 1.090) 0-6 avg Rural children: 0.970 (0.904, 1.040) 0 0.959 (0.893, 1.030) 1 1.008 (0.927, 1.095) 2 1.087 (0.914, 1.292) 0-6 avg OR between incidence of medication use and PM 10 exposure in urban and rural children lag Bronchodilator use - Urban children: 1.498 (0.899, 2.498) 0 1.049 (0.565, 1.947) 1 1.148 (0.674, 1.954) 2 1.787 (0.611, 5.227) 0-6 avg Rural children: 1.275 (0.702, 2.315) 0 0.924 (0.437, 1.956) 1



### December 2009 E-145

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) 1.005 (0.522, 1.936) 2 1.823 (0.534, 6.277) 0-6 avg Reference: Goncalves et al. (2005, 089884 ) Period of Study: Dec 1992-Mar 1993. Dec 1992-Mar 1994

Location: Sao Paulo Outcome: Respiratory morbidity/admissions Age Groups: Children <13 yr Study Design: Time series Statistical Analyses: Principal component analysis

Covariates: Daily mean temperature, daily mean water vapor density, solar radiation

Season: Summer Dose-response Investigated? No Statistical Package: NR Lags Considered: Lag 3 Pollutant: PM 10 Averaging Time: 24 h Copollutant: SO 2 , O 3 PCA coefficients: PC1, PC2, PC3:

Summer 1992/1993: PM 10 : 0.69, 0.45, 0.13 Solar Radiation: -0.04, 0.94 to -0.12 Mean Temperature: 0.62, 0.44 to -0.47 Mean Water Vapor Density: 0.73 to -0.46 to -0.26 SO 2 : 0.78 to -0.03, 0.33 O 3 : 0.18, 0.63, 0.37 Respiratory Mortality: 0.05 to -0.02, 0.81 Variations explained by Principal Component: PC1: 0.29 PC2: 0.27 PC3: 0.17

Summer 1993/1994: PM 10 : 0.38, 0.80 to -0.23 Solar Radiation: 0.02, 0.09 to -0.97 Mean Temperature: 0.71, 0.40 to -0.37 Mean Water Vapor Density: 0.88, 0.25, 0.09 SO 2 : 0.01, 0.92, 0.00 O 3 : 0.47 to -0.06 to -0.35 Respiratory Mortality: -0.73, 0.11, 0.08 Variations explained by Principal Component: PC1: 0.31 PC2: 0.25 PC3: 0.18

Notes : Association between respiratory morbidity and air pollution more likely during summer with smaller contrasts in synoptic weather condition (summer 1992/93) but respiratory morbidity more related to weather variables during summer with larger contrasts (summer 1993/94).

Reference: Gordian and Choudhury (2003, 054842 ) Period of Study: 1994-Dec 1996

Location: Anchorage, Alaska Outcome: Asthma medication among school children Age Groups: Elementary school children (kindergarten-6th grade) Study Design: Time series Statistical Analyses: Time series regression model

Covariates: Day of the week, month, time trend, temperature

Season: All seasons Dose-response Investigated? No Statistical Package: SAS Lags Considered: 1, 2, 7, 14, 21, 28 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 36.11 (30.46) Range (Min, Max): 2.96, 210.0 Monitoring Stations: 1 Model regression slope coefficient for PM 10 (estimated SE) lag: 7.25 (2.88) lag 21 RR: 1.075 (1.016, 1.138)

Notes : PM 10 coefficients for other lags were also statistically significant but not reported.



### December 2009 E-146

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Harre et al. (1997, 095726 ) Period of Study: Jun 994-Aug 1994

Location: Christchurch, New Zealand Outcome: Respiratory symptoms, Cough, Wheeze, Chest tightness, Shortness of breath, Change in sputum volume, Nose, throat, or eye irritation, PEFR Study Design: Prospective cohort Statistical Analyses: Poisson, log linear regression Age Groups: >55 Pollutant: PM 10 Averaging Time: 24-h avg Copollutants:

CO

SO 2 NO 2 Increment : 35.04 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Chest symptoms: 1.38 (1.07, 1.78) 1 Wheeze: 0.97 (0.75, 1.26) 1 Nebulizer Use: 0.71 (0.42, 1.18) 1 Inhaler Use: 0.94 (0.78, 1.13) 1

Reference: Hastings and Jardine (2002, 030344 ) Period of Study: 1997-1998

Location: Bosnia (U.S. military camps) Outcome: Weekly rates of upper respiratory disease (URD), reported by the medical treatment facility in each military camp Age Groups: U.S. soldiers Study Design: Ecologic (at level of military camp)

N: 5 camps Statistical Analyses: 1.Pearson correlations between weekly URD rates and weekly PM 10 (avg and max) 2.Kruskal Wallace test to compare URD rates in the 4 exposure quartiles 3. Mann Whitney test to compare dichotomized exposure groups (above and below 50th percentile) Dose-response Investigated? Yes Lags Considered: Weekly rates of URD disease were related to avg weekly PM levels in the same week Pollutant: PM 10 Mean (SD): PM 10 avg: 75.5 PM 10 max: 92.9

Percentiles: PM 10 max: 25th: 58.57 50th: 74.55 75th: 107.56 PM avg:

10 25th: 42.19 50th: 64.17 75th: 81.75 Range (Min, Max): PM 10 avg: 25.0, 338.7 PM 10 max: 25.0, 338.7 Monitoring Stations: At least 1 in each of the 5 camps PM max Quartiles (combining all camps): Q1: <58.7 μg/m 3 Q2: 60.1 to <75.54 μg/m 3 Q3: 78.56 to <107.56 μg/m 3 Q4: >107.56 μg/m 3 For dichotomous analysis cutoff = 74.55 μg/m 3 PM avg Quartiles (combining all camps): Q1: <42.19 μg/m3 Q2: 42.19 to 64.17 μg/m3 Q3: 64.17 to 81.75 μg/m3 Q4: >81.75 μg/m3 For dichotomous analysis cutoff = 64.17 μg/m 3

Pearson correlation coefficientsbetween URD rate and PM category [pvalue]: PM 10 max: quartiles of PM*URD rates All camps 0.203 [0.041] Blue Factory camp 0.277 [0.095] Comanche 0.165 [0.237] Demi 0.639 [0.123] McGovern 0.535 [0.177] Tuzla Main 0.107 [0.327]

PM 10 max: dichotomous PM*URD rates: All camps 0.283 [0.007] Blue Factory camp 0.038 [0.430] Comanche 0.282 [0.107] Demi 0.927 [0.012] McGovern 0.853 [0.033] Tuzla Main 0.155 [0.258]

PM 10 avg: quartiles of PM*URD rates: All camps 0.149 [0.101] Blue Factory camp 0.301 [0.077] Comanche 0.246 [0.141] Demi 0.437 [0.231] McGovern 0.853 [0.033] Tuzla Main 0.182 [0.222]

PM 10 avg: dichotomous PM*URD rates: All camps 0.060 [0.305] Blue Factory camp -0.075 [0.365] Comanche 0.143 [0.268] Demi N/A* McGovern N/A* Tuzla Main 0.123 [0.303]

Kruskal Wallace p-value comparing URD rates across exposure quartiles:

PM 10 max All camps 0.047 Blue Factory camp 0.321 Comanche 0.556 Demi 0.165 McGovern 0.202 Tuzla Main 0.554

PM 10 avg



### December 2009 E-147

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) All camps 0.672 Blue Factory camp 0.809 Comanche 0.658 Demi 0.564 McGovern 0.157 Tuzla Main 0.891

Mann-Whitney p-value comparing URD rates between upper and lower 50th percentile of PM:

PM 10 max All camps 0.034 Blue Factory camp 0.173 Comanche 0.314 Demi 0.083 McGovern 0.401 Tuzla Main 0.481

PM 10 avg All camps 0.824 Blue Factory camp 0.682 Comanche 0.508 Demi N/A* McGovern N/A* Tuzla Main 0.656 Notes : * There were no days that fell in the upper 50 percentile for PM avg in these camps -Rates of URD by PM quartiles for each camp presented in figures. Authors state, “Generally the avg URD rate increased with quartile of maximum exposure...the trend was not as clear for quartiles of PM 10 avg exposure”



### December 2009 E-148

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Hong et al. (2007, 091347 ) Period of Study: Mar 23-May 2004

Location: School on the Dukjeok Island near Incheon City, Korea Outcome: Peak expiratory flow rate (PEFR) Age Groups: 3rd to 6th grade (mean age = 9.6 yr) Study Design: Panel study

N: 43 schoolchildren Statistical Analyses: Mixed linear regression

Covariates: Age, sex, height, weight, asthma history, and passive smoking exposure at home Dose-response Investigated? No Lags Considered: 0, 1, 2, 3, 4, 5 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 35.30 (23.48) 50th (Median): 29.36 Range (Min, Max): (12.24-124.87) PM Component: Fe: mean = 0.208 (0.203) μg/m 3

Median = 0.112 Range (Min, Max): (0.061-0.806) Mn: mean = 0.008 (0.005) μg/m 3

Median = 0.007 Range (Min, Max): (0.000-0.019) Pb: mean = 0.051 (0.031) μg/m 3

Median = 0.051 Range (Min, Max): (0.011-0.155) Zn: mean = 0.021 (0.021) μg/m 3

Median = 0.013 Range (Min, Max): (0.006-0.112) Al: mean = 0.085 (0.100) μg/m 3

Median = 0.031 Range (Min, Max): (0.017-0.344) Copollutant: PM 2.5 Effect Estimate: Regression coefficients of morning and daily mean PEFR on PM 10 and metal components using linear mixed-effects regression Lag 1 (PM 10 ) Morning PEFR Crude: ß = -0.00, p = 0.99 Adjusted: ß = -0.04, p = 0.37 Mean PEFR Crude: ß = 0.00, p = 0.93 Adjusted: ß = -0.05, p = 0.12 Lag 1 (logFe) Morning PEFR Crude: ß = -1.26, p = 0.31 Adjusted: ß = -3.24, p = 0.13 Mean PEFR Crude: ß = -1.20, p = 0.20 Adjusted: ß = -2.37, p = 0.15 Lag 1 (logMn) Morning PEFR Crude: ß = -4.40, p < 0.01 Adjusted: ß = -9.82, p < 0.01 Mean PEFR Crude: ß = -4.05, p < 0.01 Adjusted: ß = -8.44, p < 0.01 Lag 1 (logPb) Morning PEFR Crude: ß = -6.79, p < 0.01 Adjusted: ß = -6.83, p < 0.01 Mean PEFR Crude: ß = -6.23, p < 0.01 Adjusted: ß = -6.37, p < 0.01 Lag 1 (logZn) Morning PEFR Crude: ß = -0.55, p = 0.71 Adjusted: ß = -0.98, p = 0.59 Mean PEFR Crude: ß = 1.33, p = 0.24 Adjusted: ß = 1.53, p = 0.28 Lag1 (logAl) Morning PEFR Crude: ß = -0.58, p = 0.57 Adjusted: ß = -2.22, p = 0.25 Mean PEFR Crude: ß = -0.59, p = 0.45 Adjusted: ß = -1.48, p = 0.32 Regression coefficients of morning and daily mean PEFR on metal components of PM 10 and GSTM1 and GSTT1 genotype using linear mixed-effects regression Lag 1 (logPb) Morning PEFR: ß = -7.26, p < 0.01 Mean PEFR: ß = -6.43, p < 0.01 GSTM1 Morning PEFR: ß = 21.19, p = 0.23 Mean PEFR: ß = 20.09, p = 0.25 Lag 1 (logMn) Morning PEFR: ß = -10.31, p < 0.01 Mean PEFR: ß = -8.66, p < 0.01 GSTM1 Morning PEFR: ß = 21.02, p = 0.23 Mean PEFR: ß = 19.84, p = 0.25 Lag 1 (logPb) Morning PEFR: ß = -7.26, p < 0.01 Mean PEFR: ß = -6.43, p < 0.01 GSTT1 Morning PEFR: ß = 2.07, p = 0.90 Mean PEFR: ß = -2.39, p < 0.88 Lag 1 (logMn) Morning PEFR: ß = -10.32, p < 0.01 Mean PEFR: ß = -8.67, p < 0.01 GSTT1 Morning PEFR: ß = 2.02, p = 0.90 Mean PEFR: ß = 2.33, p = 0.88



### December 2009 E-149

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Hwang et al. (2006, 088971 ) Period of Study: 2001

Location: Taiwan Outcome: Allergic rhinitis Study Design: Cross-sectional Statistical Analyses: Two-stage hierarchical models Age Groups: 6-15 yr Pollutant: PM 10 Averaging Time: 1-h avg Mean (SD): 55.58 (16.57) Range (Min, Max): (29.36, 99.58) Copollutants (correlation):

CO: r = 0.27

NO X : r = 0.34

O 3 : r = 0.28

SO 2 : r = 0.58 Increment: 10 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag: PM 10 alone: 1.00 (0.99, 1.02) , PM 10 : 0.99 (0.97, 1.00) CO, PM 10 : 1.00 (0.99, 1.01) O 3 , PM 10 : 1.00 (0.99, 1.02) Gender Male: 1.02 (0.99, 1.04) Female: 0.99 (0.97, 1.02) Parental atopy* Yes: 1.00 (0.98, 1.03) No: 1.01 (0.99, 1.03) Parental education <6 yr: 1.05 (0.96, 1.14) 6-8 yr: 1.03 (0.98, 1.07) 9-11 yr: 1.00 (0.98, 1.03) 12+ yr: 0.99 (0.97, 1.02) Environmental tobacco smoke Yes: 1.01 (0.99, 1.03) No: 1.00 (0.98, 1.03) Visible mold** Yes: 1.02 (0.99, 1.06) No: 1.00 (0.98, 1.02) * Parental atopy was a measure of genetic predisposition and was defined as the father or the mother of the index child ever having been diagnosed as having asthma, allergic rhinitis, or atopic

eczema. ** Visible mold found in the home.

Reference: Jalaludin et al. (2004, 056595 ) Period of Study: Feb 1994-Dec 1994

Location: Western and southwestern Sydney, Australia Outcome: Respiratory symptoms, Wheeze, Dry cough, Wet cough Study Design: Longitudinal study panel Statistical Analyses: Logistic regression model (GEE) Age Groups: 9-11 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 22.8 (13.8) IQ Range (25th,75th): (12.00, 122.8) Copollutants (correlation): O 3 : r = 0.13

NO 2 : r = 0.26 Increment: 10 μg/m 3 Odds Ratio (Lower CI, Upper CI) Lag Wheeze 1.01 (0.99, 1.03) 0 1.01 (0.97, 1.04) 1 0.99 (0.96, 1.03) 2 1.02 (0.98, 1.06) 0-2 avg 1.04 (0.99, 1.10) 0-5 avg Dry Cough 1.00 (0.98, 1.03) 0 1.00 (0.97, 1.03) 1 1.00 (0.97, 1.02) 2 1.00 (0.97, 1.03) 0-2 avg 1.03 (0.98, 1.08) 0-5 avg Wet Cough 1.01 (0.99, 1.04) 0 0.99 (0.97, 1.01) 1 1.00 (0.97, 1.03) 2 0.99 (0.96, 1.02) 0-2 avg 0.99 (0.94, 1.04) 0-5 avg Inhaled B2-agonist Use 0.99 (0.98, 1.01) 0 1.00 (0.98, 1.03) 1 0.99 (0.97, 1.01) 2 1.00 (0.97, 1.02) 0-2 avg 1.02 (0.98, 1.06) 0-5 avg Inhaled Corticosteroid Use 1.00 (0.99, 1.01) 0 1.00 (0.99, 1.02) 1 1.00 (0.99, 1.02) 2 1.00 (0.98, 1.02) 0-2 avg 1.00 (0.97, 1.02) 0-5 avg Doctor Visit for Asthma 1.11 (1.04, 1.19) 0 1.10 (1.02, 1.19) 1 1.15 (1.06, 1.24) 2 1.11 (1.03, 1.20) 0-2 avg 1.14 (0.98, 1.31) 0-5 avg OR for respiratory symptoms and PM10 exposure by different groups



### December 2009 E-150

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

All children Wheeze: 1.01 (0.99, 1.04) Dry Cough: 1.00 (0.97, 1.02) Wet Cough: 1.01 (0.98, 1.04) Inhaled B2-agonist Use: 1.00 (0.98, 1.02) Inhaled Corticosteroid Use: 0.99 (0.98, 1.01) Doctor Visit for asthma: 1.11 (1.03, 1.19) Group 1* Wheeze: 1.01 (0.98, 1.04) Dry Cough: 0.97 (0.94, 0.99) Wet Cough: 1.00 (0.97, 1.03) Inhaled B2-agonist use: 1.00 (0.98, 1.02) Inhaled Corticosteroid Use: 1.00 (0.98, 1.01) Doctor Visit for asthma: 1.09 (0.98, 1.21) Group 2** Wheeze: 1.01 (0.97, 1.05) Dry Cough: 1.02 (0.98, 1.06) Wet Cough: 1.01 (0.96, 1.06) Inhaled B2-agonist use: 0.99 (0.94, 1.05) Inhaled Corticosteroid Use: 0.99 (0.97, 1.01) Doctor Visit for asthma: 1.12 (1.02, 1.23) Group 3*** Wheeze: 1.08 (0.90, 1.31) Dry Cough: 1.01 (0.91, 1.11) Wet Cough: 1.02 (0.94, 1.11) Inhaled B2-agonist use: 0.98 (0.84, 1.11) Inhaled Corticosteroid Use: 1.27 (1.08, 1.49) Doctor Visit for asthma: NR *Group 1 consists of children with a history of wheeze in the past 12 mo, positive histamine challenge, and doctor diagnosed asthma. **Group 2 consists of children with a history of wheeze in the past 12 mo and doctor diagnosed asthma. ***Group 3 consists of children only with a history y of wheeze in the past 12 mo.



### December 2009 E-151

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Jansen, et al. (2005, 082236 ) Period of Study: 1987-2000

Location: Seattle, WA Outcome: FENO: fractional exhaled nitrogen oxide, Spirometry, Blood pressure, SaO 2 : oxygen saturation, Pulse rate Age Groups: 60-86 yr old Study Design: Short-term crosssectional case series

N: 16 subjects diagnosed with COPD, asthma, or both Statistical Analyses: Linear mixed effects model with random intercepts

Covariates: Age, relative humidity, temperature, medication use

Season: winter 2002-2003 Dose-response Investigated? No Statistical Package: STATA Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Fixed-site Monitor: 18.0 All Subjects (N = 16) Indoor, home: 11.93 Outdoor, home: 13.47 Personal: 23.34 Asthmatic Subjects (N = 7) Indoor, home: 12.54 Outdoor, home: 11.86 Personal: 26.88 COPD Subjects (N = 9) Indoor, home: 11.45 Outdoor, home: 14.76 Personal: 19.91 Range (Min, Max): Fixed-site Monitor 2.5, 51 IQR: All Subjects Indoor, home: 6.93 Outdoor, home: 9.53 Personal: 20.72 Asthmatic Subjects Indoor, home: 10.19 Outdoor, home: 8.77 Personal: 20.08 COPD Subjects Indoor, home: 4.56 Outdoor, home: 6.14 Personal: 19.94 PM Increment: 10 μ g/m 3 Slope [95% CI]: dependence of FENO concentration [ppb] on PM 10 Asthmatic Subjects Indoor, home: 3.81 [-0.86: 8.50] Outdoor, home: 5.87 [2.87: 8.88]* Personal: 0.66 [-0.56: 1.88] COPD Subjects Indoor, home: 2.19 [-3.48: 7.87] Outdoor, home: 4.45 [-1.11: 10.01] Personal: 0.17 [-1.61: 1.96] Results indicate that FENO may be a more sensitive biomarker of PM exposure than other traditional health endpoints.



### December 2009 E-152

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Johnston, et al. (2006, 091386 ) Period of Study: 7 mo (Apr 7-Nov 7, 2004)

Location: Darwin, Australia Outcome: Asthma symptoms Age Groups: All ages Study Design: Time-series

N: 251 people (130 adults, 121 children Statistical Analyses: Logistic regression model

Covariates: Minimum air temperature, doctor visits for influenza and the prevalence of asthma symptoms and, the fungal spore count and both onset of asthma symptoms and commencement of reliever medication

Season: “Dry season”-specific months NR, note Southern Hemisphere Dose-response Investigated? No Statistical Package: STATA8 Lags Considered: 0-5 days Pollutant: PM 10 Averaging Time: Daily Mean (SD): 20 (6.4) Range (Min, Max): 2.6-43.3 PM Component: Vegetation fire smoke (95%) and motor vehicle emissions (5%) Monitoring Stations: 1

Correlation: PM 2.5 : r = 0.90 PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] Symptoms attributable to asthma Overall:1.010 (0.98,1.04) Adults:1.027 (0.987,1.068) Children:0.930 (0.966, 1.060) Using preventer: 1.022 (0.985, 1.060)

Became symptomatic Overall: 1.240 (1.106,1.39) Adults: 1.277 (1.084,1.504) Children: 1.247 (1.058,1.468) Using preventer:1.317 (1.124,1.543)

Used Reliever Overall: 1.010 (0.99, 1.04) Adults: 1.026 (0.990, 1.063) Children: 1.006 (0.960,1.055) Using preventer:1.035 (1.004,1.060)

Commenced Reliever Overall: 1.132 (0.99, 1.29) Adults: 1.199 (0.994, 1.446) Children: 1.093 (0.906,1.319) Using preventer:1.194 (0.996, 1.432)

Commenced Oral Steroids Overall: 1.540 (1.01, 2.34) Adults: 1.752 (1.008, 3.045) Children: 1.292 (0.682, 2.448) Using preventer:1.430 (0.888, 2.304)

Asthma Attack Overall: 1.030 (0.95, 1.12) Adults: 1.08 (0.976, 1.202) Children: 0.861 (0.710, 1.044) Using preventer:1.051 (0.939,1.175)

Exercise induced asthma Overall: 0.980 (0.92, 1.05) Adults: 0.988 (0.902, 1.081) Children: 0.972 (0.844,1.119) Using preventer:1.026 (0.928,1.134)

Saw a health professional for asthma Overall: 1.030 (0.85, 1.26) Adults: 1.064 (0.794, 1.424) Children: 0.998 (0.749,1.328) Using preventer:0.924 (0.731, 1.169)

Missed school or work due to asthma Overall: 1.102 (0.941, 1.290) Adults: 1.135 (0.897, 1.435) Children: 1.073 (0.862,1.333) Using preventer:1.025 (0.857,1.228) Mean daily number of asthma symptoms Overall: 1.020 (1.001,1.031) Adults: 1.027 (1.005,1.049) Children: 1.016 (0.986,1.047) Using preventer:1.034 (1.011,1.058) Mean Daily number of applications of reliever Overall: 1.020 (1.00,1.030) Adults: 1.032 (1.008, 1.057) Children: 1.002 (0.969,1.034) Using preventer:1.022 (1.001,1.043)



### December 2009 E-153

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Just et al. (2002, 035429 ) Period of Study: Apr 1996-Jun 1996

Location: Paris, France Outcome: Incident and prevalent episodes of asthma attacks, nocturnal cough, wheeze, symptoms of irritation, respiratory infections, supplementary use of β 2-agonists, Z-transformed peak expiratory flow (PEF), daily PEF variability Age Groups: 7-15 yr old Study Design: Cohort

N: 82 children Statistical Analyses: Linear regression, logistic regression, GEE

Covariates: Effects of time trend, day of the week, weather, pollen levels

Season: Spring/summer Lags Considered: 0, 0-2 mean, 0-4

mean Pollutant: PM 10 Averaging Time: Daily Mean (SD): 23.5 (8.4) Range (Min, Max): 9.0, 44.0 Monitoring Stations: 5 Copollutant (correlation):

BS: 0.59

SO 2 : 0.70

NO 2 : 0.54

O 3 : 0.21 Temp: 0.04

Humid: -0.41 PM Increment: 10 μg/m 3 for binary responses data (results that use odds ratios [ORs]) Incident episodes of 1) Asthma a) lag 0: 1.06 (0.61, 1.83) b) 0-2 mean: 1.09 (0.48, 2.49) c) 0-4 mean: 1.07 (0.44, 2.65) 2) Nocturnal cough a) lag 0: 1.10 (0.88, 1.37) b) 0-2 mean: 1.03 (0.77, 1.37) c) 0-4 mean: 1.11 (0.86, 1.42) 3) Respiratory infections a) lag 0: 0.64 (0.35, 1.15) b) 0-2 mean: 0.74 (0.38, 1.43) c) 0-4 mean: 0.99 (0.58, 1.68) Prevalent episodes of 1) Asthma a) lag 0: 1.07 (0.72, 1.59) b) 0-2 mean: 1.18 (0.64, 2.17) c) 0-4 mean: 1.16 (0.63, 2.13) 2) Nocturnal cough a) lag 0: 1.05 (0.83, 1.34) b) 0-2 mean: 1.10 (0.81, 1.50) c) 0-4 mean: 1.09 (0.79, 1.52) 3) Respiratory infections a) lag 0: 1.17 (0.68, 2.03 ) b) 0-2 mean: 1.31 (0.51, 3.36) c) 0-4 mean: 1.71 (0.71, 4.12) 4) Eye irritation a) lag 0: 1.18 (1.01, 1.39) b) 0-2 mean: 1.28 (1.03, 1.59) c) 0-4 mean: 1.42 (1.12, 1.80) Analysis restricted to days with no steroid use: Incident episodes of 1) Eye irritation a) lag 0: 1.07 (0.66, 1.71) b) 0-2 mean: 0.83 (0.45, 1.53) c) 0-4 mean: 0.92 (0.46, 1.83) 2) Throat irritation a) lag 0: 1.33 (0.66, 2.69) b) 0-2 mean: 1.28 (0.58, 2.80) c) 0-4 mean: 1.06 (0.38, 2.95) 3) Nose irritation a) lag 0: 0.74 (0.48, 1.13) b) 0-2 mean: 0.76 (0.42, 1.36) c) 0-4 mean: 0.96 (0.53, 1.73) Prevalent episodes of 1) Eye irritation a) lag 0: 1.20 (0.88, 1.65) b) 0-2 mean: 1.71 (0.97, 3.01) c) 0-4 mean: 1.97 (1.03, 3.76) 2) Throat irritation a) lag 0: 1.23 (0.83, 1.82) b) 0-2 mean: 1.08 (0.68, 1.73) c) 0-4 mean: 0.91 (0.47, 1.73) 3) Nose irritation a) lag 0: 1.20 (0.91, 1.58) b) 0-2 mean: 1.09 (0.78, 1.52) c) 0-4 mean: 1.09 (0.73, 1.61) Notes: The authors noted that incident or prevalent wheeze was not correlated with levels of any type of pollutant. Also, they state no relationship was observed between PEF variables and levels of PM. The authors also note that in a multipollutant model assessing independent effects of PM and O 3 on prevalent episodes of eye irritation (mean 0-4), the PM parameter decreased and was not significant (p = 0.19).



### December 2009 E-154

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Kulkarni et al. (2006, 089257 ) Period of Study: Nov 2002-Dec 2003

Location: Leicester, United Kingdom Outcome: Lung function by spirometry: FVC, FEV 1 , FEV 1 : FVC, FEF 25-75 Age Groups: 8-15 yr Study Design: Cross-sectional

N: 114 children, 64 provided sputum for assessment of carbon content of macrophages. Statistical Analyses: Linear regressions, Spearman rank correlations. Mann-Whitney, Chi-square and unpaired t tests were used to compare results between asthmatic and non asthmatic children

Covariates: BMI, sex, exercise, traffic PM 10 Dose-response Investigated? Yes Statistical Package: SPSS Pollutant: Primary PM 10 (μg/m 3 ) concentration was modeled, and was considered a covariate for carbon content of macrophages. Carbon content of alveolar macrophages was the primary variable of interest. Averaging Time: 1 yr 50th(Median): Children without asthma, 1.21 Children with asthma, 1.81 Range (Min, Max): Children without asthma, 0.10, 2.17 Children with asthma, 0.17, 2.13 PM Component: Carbon content in alveolar macrophages Monitoring Stations: NR. Copollutant (correlation): Vs carbon content in macrophages (increment, coefficient range]) -1.0 μg/m 3 , 0.1 [0.01-0.18] PM Increment: 1.0 μg/m 3 % Change [Lower CI, Upper CI]: Single pollutant model: FEV 1 : -4.3 [-8.5, 0.2] p = 0.04 R2 = 0.06 Single pollutant model: FVC: -1.2 [-5.6, 3.2] p = 0.59 R2 = 0.005 Single pollutant model: FEF 25-75 : -8.6 [ -17.3, 0.1] p = 0.05 R2 = 0.06

2 pollutant model with Macrophage Carbon: FEV 1 : PM 10 -2.9 [-6.9, 1.2] p = 0.17 FVC: PM 10 0.1 [-4.4, 4.6] p = 0.96 FEF 25-75 : PM 10 -5.5 [-14.2, 3.1] p = 0.21

Reference: Kuo, et al. (2002, 036310 ) Period of Study: 1-yr period (yr not specified)

Location: Central Taiwan Outcome: Asthma (yes/no) Age Groups: 13-16 yr Study Design: Cohort

N: 12,926 total children 775 asthmatic children 8 junior high schools Statistical Analyses: Pearson correlation coefficients Logistic regression

Covariates: Gender, age, residential area, level of parental education, number cigarettes smoked by family members, incense burning in the home, frequency of physical activities Dose-response Investigated? No Statistical Package: SAS 6.12 Lags Considered: Monthly avg at each school Pollutant: PM 10 Averaging Time: 1 h Mean (SD):

School A: 59.7

School B: 65.3

School C: 84.3

School D: 59.2

School E: 75.3

School F: 60.2

School G: 54.1

School H: 69.0 Monitoring Stations: 8 (1 for each school) PM Increment: Dichotomized annual avg: <65.9 μg/m 3 ≥ 65.9 μg/m 3

OR Estimate [Lower CI, Upper CI] lag: Crude (outcome = asthma, yes/no) <65.9 μg/m 3 : 1 (ref) ≥ 65.9 μg/m 3 : 0.837 [NR] Adjusted (outcome = asthma, yes/no) <65.9 μg/m 3 : 1 (ref) ≥ 65.9 μg/m 3 : 0.947 [0.640, 1.401] Notes: Asthma prevalence was highest in urban areas and lowest in rural areas

Pearson correlation between annual PM levels at each school and asthma prevalence at each school: 0.214 (p > 0.05)

Reference: Lagorio et al. (2006, 089800 ) Period of Study: May 1999-Jun 1999 Jan 1999-Dec 1999

Location: Rome, Italy Outcome: Lung function of subjects (FVC and FEV 1 ) with COPD, Asthma Age Groups: COPD: 50 to 80 yr Asthma: 18 to 64 yr Study Design : Time series panel

N: COPD N = 11; Asthma N = 11 Statistical Analyses: Non-parametric Spearman correlation

GEE

Covariates: COPD and IHD: daily mean temperature, season variable (spring or winter), relative humidity, day of week Asthma: season variable, temperature, humidity, and β -2-agonist use

Season: Spring and winter Dose-response Investigated? Yes Statistical Package: STATA Lags Considered: 1-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Overall: 42.8 (21.8) Spring: 36.9 (10.8) Winter: 49.0 (28.1) Range (Min, Max): (7.9, 123)

PM Component: NR Monitoring Stations : Two fixed sites: (Villa Ada and Istituto superior di Sanita) Copollutant (correlation): NO 2 r = 0.45 O 3 r = -0.36 CO r = 0.55 SO 2 r = 0.21 PM 10-2.5 r = 0.61 PM 2.5 r = 0.93 PM Increment: 1 μg/m 3 They observed negative association between ambient PM 10 and respiratory function (FVC and FEV 1 ) in the COPD panel. The effect on FVC was seen at lag 24 h, 48 h, and 72 h. The effect on FEV 1 was evident at lag 72 h. There was no statistically significant effect of PM 10 on FVC and FEV 1 in the asthmatic and IHD panels. β Coefficient (SE) COPD FVC(%) 24 h -0.66 (0.30) 48-h -0.75 (0.35) 72-h -0.94 (0.47) FEV 1 (%) 24 h -0.37 (0.27) 48-h -0.58 (0.31) 72-h -0.87 (0.43) Asthma FVC(%) 24 h -0.12 (0.24) 48-h -0.09 (0.29) 72-h -0.08 (0.36) FEV 1 (%) 24 h -0.28 (0.28) 48-h -0.40 (0.34) 72-h -0.40 (0.43)



### December 2009 E-155

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Lee, et al. (2007, 093042 ) Period of Study: 2000-2001

Location: South-Western Seoul Metropolitan area, Seoul, South Korea Outcome: PEFR (peak expiratory flow rate), lower respiratory symptoms (cold, cough, wheeze) Age Groups: 61-89 yr (77.8 mean age) Study Design: Longitudinal panel survey

N: 61 adults Statistical Analyses: Logistic regression model

Covariates: Temperature (Celsius), relative humidity, age, season Dose-response Investigated? No Statistical Package: SAS 8.0 Lags Considered: 0-4 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD) : 71.40 (30.69)

Percentiles: 25th: 43.47 50th(Median): 74.92

75th: 87.54 Range (Min, Max): 26.23, 148.34 Monitoring Stations: 2 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI] lag: PEFR (peak expiratory flow rate) -0.39 (-0.63 to -0.14) 1 day relative odds of a lower respiratory symptom (cold, cough, wheeze) 1.015 (0.900,1.144) 1 day

Reference : Lewis, et al. (2005, 081079 ) Period of Study: Winter 2001-spring 2002

Location: Detroit, Michigan, USA Outcome : Poorer lung function (increased diurnal variability and decreased forced expiratory volume) Age Groups: 7-11 yr Study Design: longitudinal cohort study

N: 86 children Statistical Analyses: descriptive statistics and bivariate analyses of exposures, multivariable regression models that included interaction terms between exposure measures and CS use or, alternatively, presence of a URI, multivariate analog of linear regression.

Covariates: sex, home location, annual family income, presence of one or more smokers in household, race, season (entered as dummy variables), and parameters to account for intervention group effect.

Season: Winter 2001 (Feb 10-23), spring 2001 (May 5-18), summer 2001 (Jul 14-27), fall 2001 (Sep 22-Oct 5), winter 2002 (Jan 18-31), and spring 2002 (May 18-31). Dose-response Investigated? No Lags Considered: 1-2 days 3-5 days Pollutant: PM 10 Averaging Time: 2 wk Mean (SD): Eastside 23.0 (13.5) Southwest 28.2 (16.1) Range (Min, Max): 2.9, 70.9 PM Component: (“likely” in southwest site) carbon and diesel emissions Monitoring Stations: 2 Copollutant:

PM 2.5 0.93

O 3 Daily mean 0.59

O 3 8-h peak 0.57 PM Increment: 19.1 μg/m 3 Lung function among children reporting use of maintenance CSs Diurnal variability FEV 1 Lag 1: 1.53 [-0.85, 3.90] Lag 1: 2.94 [-1.07, 6.96] PM 10 + O 3 Lag 2: 5.32 [0.32, 10.33] Lag 2: 13.73 [8.23, 19.23] PM 10 + O 3 Lag 3-5: 1.46 [-2.21,5.13] Lag 3-5: 3.30 [0.58, 6.02] PM 10 + O 3 Lowest daily value FEV 1 Lag 1: -0.28 [-2.34, 1.77] Lag 1: -6.25 [-11.15 to -1.36] PM 10 + O 3 Lag 2: -2.21 [-3.97 to -0.46] Lag 2: -5.97 [-11.06 to -0.87] PM 10 + O 3 Lag 3-5: -2.58 [-7.65, 2.49] Lag 3-5: 1.98 [-0.38, 4.33] PM 10 + O 3 Lung function among children reporting presence of URI on day of lung function assessment Diurnal variability FEV 1 Lag 1: 3.51 [-4.52,11.55] Lag 1: 3.21 [-1.28,7.71] PM 10 + O 3 Lag 2: 1.12 [-4.62, 6.86] Lag 2: 5.40 [-0.82, 11.62] PM 10 + O 3 Lag 3-5: 3.90 [0.34, 7.47] Lag 3-5: 6.27 [0.07, 12.47] PM 10 + O 3 Lowest daily value FEV 1 Lag 1: -2.72 [-9.47, 4.03] Lag 1: -13.11 [-21.59 to -4.62] PM 10 + O 3 Lag 2: 0.24 [-5.10, 4.63] Lag 2: -3.32 [-6.83, 0.18] PM 10 + O 3 Lag 3-5: -4.48 [-8.36, 0.60] Lag 3-5: -3.17 [-5.82 to -0.51] PM 10 + O 3



### December 2009 E-156

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Mar et al. (2004, 057309 ) Period of Study: 1997-1999

Location: Spokane, Washington Outcome: Respiratory symptoms Age Groups: Adults: Ages 20-51 yr Children: Ages 7-12 yr Study Design: Time-series

N: 25 people Statistical Analyses: Logistic regression

Covariates: Temperature, relative humidity, day of-the-wk Statistical Package: STATA 6 Lags Considered: 0-2 days Pollutant: PM 10 Mean (SD): 1997: 24.5 (18.5) 1998: 20.6 (12.3) 1999: 16.8 (8.0) Monitoring Stations: 1 station Copollutant (correlation): PM 10 PM1: r = 0.48 PM 2.5 : r = 0.61 PM 10-2.5 : r = 0.93 PM Increment: 10 μg/m 3 OR Estimate [Lower CI, Upper CI] lag: Adult Respiratory symptoms: Wheeze: 1.01[0.93, 1.09] lag 0 0.98[0.91, 1.06] lag 1 0.99[0.92, 1.06] lag 2 Breath: 1.02[0.96, 1.08] lag 0 1.01[0.97, 1.06] lag 1 1.02[0.97, 1.06] lag 2 Cough: 0.96[0.88, 1.05] lag 0 0.97[0.90, 1.04] lag 1 0.98[0.92, 1.05] lag 2 Sputum: 1.01[0.92, 1.12] lag 0 0.99[0.91, 1.08] lag 1 1.00[0.93, 1.08] lag 2

Runny Nose: 0.98[0.93, 1.04] lag 0 0.97[0.93, 1.02] lag 1; 0.97[0.94, 1.01] lag 2

Eye Irritation: 0.97[0.87, 1.08] lag 0 0.97[0.88, 1.06] lag 1 0.97[0.91, 1.04] lag 2 Lower Symptoms: 0.96[0.91, 1.02] lag 0 0.95[0.89, 1.00] lag 1 0.95[0.90, 1.00] lag 2 Any Symptoms: 0.97[0.93, 1.02] lag 0 0.96[0.91, 1.00] lag 1 0.95[0.91, 0.99] lag 2 Children Respiratory symptoms : Wheeze: 0.92[0.71, 1.18] lag 0 0.89[0.64, 1.24] lag 1 0.95[0.69, 1.31] lag 2

Breath: 1.04[0.95, 1.15] lag 0 1.04[0.95, 1.15] lag 1 1.06[0.95, 1.19] lag 2 Cough: 1.09[1.02, 1.16] lag 0 1.08[1.02, 1.14] lag 1 1.10[1.02, 1.18] lag 2 Sputum: 1.08[0.98, 1.17] lag 0 1.07[0.98, 1.17] lag 1 1.07[0.98, 1.16] lag 2

Runny Nose: 1.08[1.00, 1.16] lag 0 1.08[1.02, 1.15] lag 1 1.08[1.02, 1.14] lag 2 Eye Irritation: 1.06[0.74, 1.51] lag 0 0.94[0.70, 1.26] lag 1 0.99[0.88, 1.12]lag 2 Lower Symptoms: 1.07[1.00, 1.14] lag 0 1.06[0.98, 1.15] lag 1 1.07[0.95, 1.19] lag 2 Any Symptoms: 1.07[1.02, 1.11] lag 0 1.09[1.03, 1.15] lag 1 1.10[1.03, 1.17] lag 2



### December 2009 E-157

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Mar et al. (2005, 087566 ) Period of Study: 1999-2001

Location: Seattle, Washington Outcome: Pulmonary function (arterial oxygen saturation) and cardiac function (heart rate and blood pressure) Study Design: Time series

N: 88 Statistical Analyses: Linear logistic regression Age Groups: >57 Pollutant: PM 10 Averaging Time: 24-h avg Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) Lag Indoor Systolic: 0.92 (-0.95, 2.78) 0 Diastolic: 0.63 (-0.29, 1.56) 0

Outdoor Systolic: -0.10 (-1.37, 1.18) 0 Diastolic: -0.03 (-0.79, 0.73) 0

Nephelometer Systolic: 0.35 (-0.91, 1.61) 0 Diastolic: -0.12 (-0.91, 0.67) 0

% Increase between heart rate and PM10 exposure for people >57 PM 10 Indoor: 0.02 (-0.54, 0.58) 0 Outdoor: -0.48 (-1.03, 0.06) 0 Nephelometer: -0.31 (-0.76, 0.14) 0 Reference: McCormack et al. (2009, 199833 ) Period of Study: Sep 2001-Apr 2004

Location: East Baltimore, Maryland Outcome: Asthma symptoms Study Design: Panel Statistical Analysis: Chi-square, Student t-test, Negative binomial regression models with GEE, Logistic regression with GEE Statistical Package: StataSE Age Groups: Asthmatic children aged 2-6 yr Pollutant: PM 10-2.5 , PM 2.5 Averaging Time: 3 days Mean (SD) Unit:

PM 10-2.5 : 17.4 ± 21.2 μg/m 3

PM 2.5 : 40.3 ± 35.4 μg/m 3 Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 Relative Risk (Min CI, Max CI) Lag Bivariate Models, PM 10-2.5 Cough, wheezing, chest tightness: 1.05 (0.99-1.10), p = 0.08 Slow down: 1.08 (1.03-1.13). p < 0.01 Symptoms with running: 1.03 (0.97-1.09). p = 0.39 Nocturnal symptoms: 1.06 (1.01-1.11), p = 0.03 Limited speech: 1.11 (1.05-1.18), p < 0.01 Rescue medication use: 1.06 (1.02-1.11), p < 0.01 Bivariate Models, PM 2.5 Cough, wheezing, chest tightness: 1.01 (0.98-1.05), p = 0.41 Slow down: 1.00 (0.97-1.04), p = 0.85 Symptoms with running: 1.04 (1.01-1.07), p = 0.14 Nocturnal symptoms: 1.02 (0.98-1.05), p = 0.37 Limited speech: 1.01 (0.95-1.07), p = 0.33 Rescue medication use: 1.03 (1.00-1.60), p = 0.06 Multivariate Models, PM 10-2.5 Cough, wheezing, chest tightness: 1 .06 (1.01-1.12), p = 0.02 Slow down: 1.08 (1.02-1.14), p = 0.01 Symptoms with running: 1.00 (0.94-1.08), p = 0.81 Nocturnal symptoms: 1.08 (1.01-1.14), p = 0.02 Limited speech: 1.11 (1.03-1.19), p < 0.01 Rescue medication use: 1.06 (1.01-1.10), p = 0.02 Multivariate Models, PM 2.5 Cough, wheezing, chest tightness: 1.03 (0.99-1.07), p = 0.18 Slow down: 1.04 (1.00-1.09), p = 0.06 Symptoms with running: 1.07 (1.02-1.11), p < 0.01 Nocturnal symptoms: 1.06 (1.01-1.10), p = 0.01 Limited speech: 1.07 (1.00-1.14), p = 0.04 Rescue medication use: 1.04 (1.01-1.08), p = 0.04



### December 2009 E-158

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Mortimer et al. (2008, 187280 ) Period of Study: 1989-2000

Location: Joaquin Valley, California Outcome: Respiratory Symptoms, Decreased lung function Study Design: Time series Statistical Analyses: Deletion/Substitution/ Addition algorithm (GEE) Logistic linear regression Age Groups: 6-11 Pollutant: PM 10 Averaging Time: 24-h avg Copollutants (correlation):

CO: r = 0.05

NO 2 : r = 0.30

O 3 : r = 0.39 Increment: NR β (SE):

FVC: PM 10 (age 0-3 yr): 0.0121 (0.0037)

FEV 1 : PM 10 (age 0-3 yr): 0.0102 (0.0034)

PEF: PM 10 (Mother smoked during pregnancy): -0.0102 (0.0039)

Reference: Mortimer et al. (2002, 030281 ) Period of Study: Jun-Aug 1993

Location: Eight urban areas of the U.S.: Bronx and East Harlem, NY Baltimore, MD Washington, DC Detroit, MI Cleveland, OH Chicago, IL and St. Louis, MO. Outcome: peak expiratory flow rate (PEFR) and symptoms Age Groups: 4-9 yr Study Design: Cohort study

N: 846 children with a history of asthma Statistical Analyses: Mixed linear models and GEE

Covariates: Day of study, previous 12- h mean temperature, urban area, diary number, rain in the past 24 h

Season: Summer Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0, 1, 2, 3, 4, 5, 6, 1- 5 avg, 1-4 avg, 0-4 avg, 0-3 avg Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 53 Monitoring Stations: NR Copollutant (correlation): 8-h avg O 3 : r = 0.51 PM Increment: 20 μg/m 3 Effect Estimate [Lower CI, Upper CI]: (RR estimates are odds ratios for incidence of morning asthma symptoms using the avg of lag 1-2) 3 urban areas (DE, CL, CH) Single pollutant: OR = 1.26 (1.00-1.59)

O 3 +PM 10 : OR = 1.25 (0.97-1.61)

O 3 +SO 2 +NO 2 +PM 10 : OR = 1.14 (0.80- 1.48)

Reference: Moshammer and Neuberger (2003, 041956 ) Period of Study: 2000-2001

Location: Linz, Austria Outcome: Lung Function: FVC, FEV 1 , MEF 25 , MEF 50 , MEF 75 , PEF, LQ Signal, PAS Signal Age Groups: Ages 7 to 10 Study Design: Case-crossover

N: 161 children

1898-2120 “half-h means” Statistical Analyses: Correlations Regression Analysis

Covariates: Morning, evening, night

Season: Spring, summer, winter, fall Dose-response Investigated? No Pollutant: PM 10 Averaging Time: 8 h Daily Means Mean (SD): 23.13 (20.08) Range (Min, Max): (NR, 190.79) Monitoring Stations: 1 Copollutant (correlation): LQ = 0.751

PAS = 0.406 Notes: “Acute effects of ‘active particle surface’ as measured by diffusion charging were found on pulmonary function (FVC, FEV 1 , MEF 50 ) of elementary school children and on asthma-like symptoms of children who had been classified as sensitive.”

Reference: Moshammer et al. (2006, 090771 ) Period of Study: 2000-2001

Location: Linz, Austria Outcome: Respiratory symptoms and decreased lung function Age Groups: Children ages 7-10 Study Design: Time-series

N: 163 children Statistical Analyses: GEE model

Covariates: Sex, age, height, weight Dose-response Investigated? NR Statistical Package: NR Lags Considered: 1 Pollutant: PM 10 Averaging Time: 8 h Mean (SD): Maximum 24 h: 76.39 Annual avg: 19.06 Percentiles: 8-h mean 25th: 14.39 8-h mean 50th(Median): 24.85 8-h mean 75th: 38.82 Monitoring Stations: 1 station Copollutant (correlation): PM 1 : r = 0.91 PM 2.5 : r = 0.93 NO 2 : r = 0.62 PM Increment: 10 μg/m 3 % change in Lung Function per 10 μg/m3 FEV: 0.11 FVC: 0.06 FEV 0.5 : -0.19 MEF 75 %: -0.30 MEF 50 %: -0.36 MEF 25 %: 0.41 PEF: 0.22 % change in Lung Function per IQR FEV: -0.27 FVC: -0.07 FEV .5 : -0.47 0 MEF 75 %: -0.74 MEF 50 %: -0.86 MEF %: 0.98 25 PEF: -0.54



### December 2009 E-159

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Neuberger et al. (2004, 093249 ) Period of Study: Sep 1999-Mar 2000

Location: Vienna, Austria Outcome: Ratio measure: Time to peak tidal expiratory flow divided by total expiration time (i.e., tidal lung function, a surrogate for bronchial obstruction) Age Groups: 3.0-5.9 yr (preschool children) Study Design: Longitudinal prospective cohort

N: 56 children Statistical Analyses: Mixed models linear regression, with autoregressive correlation structure

Covariates: Age, sex, respiratory rate, phase angle, temperature, kindergarten, parental education, observer (also in sensitivity analyses: height, weight, cold/sneeze on same day, heating with fossil fuels, hair cotinine, number of tidal slopes used to measure tidal lung function) Dose-response Investigated? No Statistical Package: SAS 8.0 Lags Considered: 0 Pollutant: PM 10 Averaging Time: 24 h Copollutant (correlation): PM 2.5 (r = 0.94) in Vienna PM Increment: Interquartile range (NR) Change in mean associated with an IQR increase in PM (p-value) lag -1.067 (0.241) lag 0

Reference: Neuberger et al. (2004, 093249 ) Period of Study: Oct. 2000-May 2001

Location: Linz, Austria Outcome: Forced oscillatory resistance (at zero Hz), FVC, FEV 1 , MEF 25 , MEF 50 , MEF 75 , PEF Age Groups: 7-10 yr Study Design: Longitudinal prospective cohort

N: 164 children Statistical Analyses: Mixed models linear regression with autoregressive correlation structure

Covariates: sex, time and individual

Season: Oct-May Dose-response Investigated? No Statistical Package: NR Lags Considered: 0-7 Pollutant: PM 10 Averaging Time: 24 h Monitoring Stations: 1 PM Increment: 1 μg/m 3

Notes: No significant associations between PM 10 and the metrics of lung function were reported. The authors state they only reported significant associations, so results are assumed to be null.

Reference : Odajima et al. (2008, 192005 ) Period of Study: Apr 2003-Mar 2004

Location: Fukuoka, Japan Outcome: PEF Study Design: Panel/Field Statistical Analysis: GEE Statistical Package: SAS

Covariates: Age, sex, growth index, temperature, NO 2 , O 3 Age Groups: Asthmatic children, 4-11 yr old Pollutant: PM 10 Averaging Time: 3 h Mean (SD) Unit: Warmer months, 5-8 am SPM: 40.7 μg/m 3 NO 2 : 15.2 ppb O 3 : 17.7 ppb

Warmer months, 7-10pm SPM: 41.5 μg/m 3 NO 2 : 20.0 ppb O 3 : 28.1 ppb

Colder months, 5-8am SPM: 32.6 μg/m 3 NO 2 : 20.5 ppb O 3 : 17.5 ppb Colder months, 7-10pm SPM: 34.7 μg/m 3 NO 2 : 28.0 ppb O 3 : 19.4 ppb Range (Min, Max): Increment: 10 μg/m 3 Relative Risk (Min CI, Max CI) LagApr-Sep, morning sample, multipollutant:: SPM, 5am-8am: -0.6 (-1.228, 0.028) SPM, 2am-5am: -0.78 (-1.399, -0.161) SPM, 11pm-2am: -0.612 (-1.180, - 0.045) SPM, 8pm-11am: -0.732 (-1.318, - 0.145) O 3 , 5am-8am: -0.575 (-1.569, 0.419) O 3 , 2am-5am: -0.052 (-0.997, 0.893) O 3 , 11pm-2am: -0.305 (-1.269, 0.658) O 3 , 8pm-11am: -0.416 (-1.283, 0.451) NO 2 , 5am-8am: -0.3 (-2.246, 1.645) NO 2 , 2am-5am: 0.265 (-1.354, 1.885) NO 2 , 11pm-2am: -0.187 (-1.447, 1.073) NO 2 , 8pm-11am: 0.432 (-0.689, 1.553) Single-pollutant model: SPM, 5am-8am: -0.67 (-1.236, -0.104) SPM, 2am-5am: -0.761 (-1.328, -0.194) SPM, 11pm-2am: -0.661 (-1.159, -



### December 2009 E-160

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) Warmer months, 5-8am SPM: (11.0, 126.0) NO 2 : (1.3, 44.7) O 3 : (0.3, 52.3)

Warmer months, 7-10pm SPM: (8.3, 191.3) NO 2 : (3.0, 51.3) O 3 : (1.3, 71.3)

Colder months, 5-8am SPM: (9.0, 160.0) NO 2 : (1.3, 44.0) O 3 : (0.6, 48.7) Colder months, 7-10pm SPM: (10.3, 131.0) NO 2 : (3.6, 49.0) O 3 : (1.0, 60.0) Copollutant (correlation): Warmer months (24-h mean): O 3 : r = 0.32 NO 2 : r = 0.30 Colder months (24-h mean): O 3 : r = -0.02 NO 2 : r = 0.45 0.163) SPM, 8pm-11am: -0.714 (-1.212, - 0.215)

Evening sample, multi-pollutant model SPM, 7pm-10pm: -0.449 (-1.071, 0.174) SPM, 4pm-7pm: -0.434 (-1.122, 0.254) SPM, 1pm-4pm: -0.415 (-1.015, 0.184) SPM, 10am-1pm: -0.522 (-1.199, 0.155) O 3 , 7pm-10pm: -0.22 (-1.171, 0.731) O 3 , 4pm-7pm: -0.118 (-0.809, 0.574) O 3 , 1pm-4pm: -1.086 (-0.888, 0.516) O 3 , 10am-1pm: -0.315 (-1.123, 0.493) NO 2 , 7pm-10pm: 0.296 (-0.806, 1.397) NO 2 , 4pm-7pm: 0.220 (-0.818, 1.258) NO 2 , 1pm-4pm: 0.438 (-0.568, 1.444) NO 2 , 10am-1pm: 0.536 (-0.546, 1.617) Single-pollutant model: SPM, 7pm-10pm: -0.449 (-0.956, 0.058) SPM, 4pm-7pm: -0.449 (-1.029, 0.131) SPM, 1pm-4pm: -0.414 (-0.943, 0.115) SPM, 10am-1pm: -0.486 (-1.051, 0.079)Oct-Mar, morning sample, multipollutant:: SPM, 5am-8am: 0.290 (-0.279, 0.859) SPM, 2am-5am: 0.431 (-0.173, 1.036) SPM, 11pm-2am: 0.304 (-0.311, 0.919) SPM, 8pm-11am: 0.010 (-0.523, 0.543) O 3 , 5am-8am: -0.415 (-1.568, 0.738) O 3 , 2am-5am: -0.046 (-1.245, 1.153) O 3 , 11pm-2am: 0.004 (-1.265, 1.273) O 3 , 8pm-11am: -0.470 (-2.017, 1.077) NO 2 , 5am-8am: -0.319 (-2.269, 1.631) NO 2 , 2am-5am: 0.262 (-1.777, 2.300) NO 2 , 11pm-2am: 0.609 (-1.132, 2.350) NO 2 , 8pm-11am: 0.155 (-1.545, 1.856) Single-pollutant model: SPM, 5am-8am: 0.308 (-0.189, 0.805) SPM, 2am-5am: 0.485 (-0.026, 0.996) SPM, 11pm-2am: 0.486 (-0.049, 1.022) SPM, 8pm-11am: 0.100 (-0.414, 0.613) Evening Sample, Multi-pollutant Model SPM, 7pm-10pm: 0.059 (-0.397, 0.515) SPM, 4pm-7pm: 0.360 (-0.093, 0.812) SPM, 1pm-4pm: 0.357 (-0.157, 0.871) SPM, 10am-1pm: 0.169 (-0.394, 0.731) O 3 , 7pm-10pm: -0.656 (-2.394, 1.083) O 3 , 4pm-7pm: 0.046 (-1.140, 1.232) O 3 , 1pm-4pm: 0.164 (-1.038, 1.365) O 3 , 10am-1pm: 0.665 (-0.613, 1.942) NO 2 , 7pm-10pm: -0.415 (-2.444, 1.613) NO 2 , 4pm-7pm: -0.144 (-1.490, 1.202) NO 2 , 1pm-4pm: -0.181 (-1.821, 1.459) NO 2 , 10am-1pm: 0.194 (-1.503, 1.890) Single-pollutant model : SPM, 7pm-10pm: 0.071 (-0.388, 0.529) SPM, 4pm-7pm: 0.318 (-0.123, 0.758) SPM, 1pm-4pm: 0.317 (-0.171, 0.804) SPM, 10am-1pm: 0.112 (-0.412, 0.636)



### December 2009 E-161

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Peacock et al. (2003, 042026 ) Period of Study: Nov 1996-Feb 1997

Location: Southern England Outcome: Reduced peak expiratory flow rate (PEFR) Age Groups: 7-13 yr Study Design: Time-series

N: 179 Statistical Analyses: GEE, multiple regression

Covariates: Day of the week, 24-h mean outside temperature.

Season: Winter Dose-response Investigated? No Statistical Package: STATA Lags Considered: Same day, lag 1, lag 2, 5-day ma Pollutant: PM 10 Averaging Time: Daily Mean (SD): Rural (nationally validated) 21.2 (11.3) Rural (locally validated) 18.7 (11.3) Urban 1 18.4 (9.8) Urban 2 22.7 (10.6)

Percentiles: 10th Rural (nationally validated) 11.0 Rural (locally validated) 9.0 Urban 1 10.5 Urban 2 12.5 90th Rural (nationally validated) 33.0 Rural (locally validated) 32.5 Urban 1 32.0 Urban 2 36.0 Range (Min, Max): Rural (nationally validated) 7.0, 82.0 Rural (locally validated) 6.6, 87.9 Urban 1 4.7, 62.8 Urban 2 6.7, 63.7 Monitoring Stations: 3

Copollutants: NO 2 O 3 SO 2 SO 4 2– Increment: 10 μg/m 3 Odds Ratio (Lower CI, Upper CI) Lag Change in PEFR Community -0.04 (-0.11, 0.03) 0 0.03 (-0.04, 0.05) 1 -0.01 (-0.07, 0.05) 2 -0.10 (-0.25, 0.05) 0-4 avg

Local -0.01 (-0.06, 0.03) 0 0.04 (0.01, 0.08) 1 0.01 (-0.04, 0.05) 2 0.04 (-0.05, 0.13) 0-4 avg

20% decrease in PEFR All children 1.012 (0.992, 1.031) 0 1.016 (0.995, 1.036) 1 1.013 (1.000, 1.025) 2 1.037 (0.992, 1.084) 0-4 avg Wheezy Children Only 1.016 (0.986, 1.047) 0 1.030 (1.001, 1.060) 1 1.018 (0.995, 1.041) 2 1.114 (1.057, 1.174) 0-4 avg

Reference: Peled, et al. (2005, 156015 ) Period of Study: 5-6 wk between MarJun 1999 and Sep-Dec 1999.

Location: Ashdod, Ashkelon and Sderot, Israel Outcome: Reduced peak expiratory flow (PEF) Age Groups: 7-10 yr Study Design: Nested cohort study

N: 285 Statistical Analyses: Time series analysis, generalized linear model, GEE, one-way ANOVA

Covariates: seasonal changes, meteorological conditions and personal physiological, clinical and socioeconomic measurements

Season: Spring, fall Dose-response Investigated? No Statistical Package: STATA Pollutant: PM 10 Averaging Time: Daily

Mean:

Ashkelon: 67.1

Sderot: 52.9

Ashdod: 31.0 PM Component: Local industrial emissions, desert dust, vehicle emissions and emissions from two electric power plants Monitoring Stations: 6 Copollutant: PM 2.5 PM Increment: 1 μg/m 3 β coefficient (SE) [95% CI]

Sderot:

PM 10 MAX: -0.34 (0.41) [-1.16, 0.46]

PM 10 MAX x sin( ω 2 day): 0.84 (0.22) [0.405, 1.28]

PM 10 MAX x cos ( ω 1 day): -1.61 (0.41) [-2.43, 0.79]

PM 10 MAX x sin ( ω 1 day): 0.44 (0.120) [-0.68-0.21] In Sderot, an interaction between PM 10 and the sequential day were significantly associated with PEF.

Reference: Pitard, et al. (2004, 087433 ) Period of Study: 732 days (Jul 1998-Jun 2000)

Location: City of Rouen, France Outcome: Respiratory drug sales Age Groups: 0-14, 15-64, 65-74, over 75 yr Study Design: Ecological time-series

N: 106,592 Statistical Analyses: Generalized additive model

Covariates: Days of the weeks, trend, seasonal variations, influenza epidemics, meteorological variables, holidays Dose-response Investigated? No Statistical Package: S-plus Lags Considered: 0 to 10 days Pollutant: PM 10 Averaging Time: Daily Mean (SD): 16.7 (13.3)

Percentiles:

25th: 8.00 50th(Median): 13.0

75th: 20 Range (Min, Max): 2.00, 126 Monitoring Stations: 2 Copollutant (correlation): SO 2 (0.39)

NO 2 (0.61) PM Increment: 10 μg/m 3

Percent increase in sales of antiasthmatics and bronchodilators (Lower CI, Upper CI) lag: 6.2 (2.4, 10.1) lag 10 days Percent increase in sales of cough and cold preparation for children under 15 yr of age (Lower CI, Upper CI) lag: 9.2 (5.9, 12.6) 10 days



### December 2009 E-162

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Preutthipan et al. (2004, 055598 ) Period of Study: 31 days (school days) from Jan



# - Feb 1999

Location: Mae Pra Fatima School, central Bangkok, Thailand Outcome: Decreases in peak expiratory flow rates (PEFR), respiratory symptoms including wheeze, shortness of breath, runny/stuffed nose, sneezing, cough, phlegm, and sore throat Age Groups: Third to ninth grade Study Design: Time- Series

N: 133 children (93 asthmatics, 40 nonasthmatics) Statistical Analyses: For continuousdata, an unpaired t-test or MannWhitney U test was used. For categorical data, the chi-square test or Fisher’s exact test was used. One-way analysis of covariance (ANCOVA) was used to compare avg daily reported respiratory symptoms, diurnal PEFR variability, and the pr evalence of PEFR decrements between groups of days.

Covariates: Age, sex, weight, height, parents smoking, person smoking in home, daily number of household cigarettes, air-conditioned bedroom, fuel used for cooking (charcoal, gas), distance from home to main road Dose-response Investigated? No Lags Considered: Up to 5 days Pollutant: PM 10 Averaging Time: Daily Mean (SD): 111.0 (39) Range (Min, Max): 46, 201 Monitoring Stations: 1 Copollutant:

SO 2 CO

O 3 PM Increment: Authors classified exposure according to High and Low PM 10 days: High = >120 μg/m 3 Low = <120 μg/m 3 Daily reported respiratory symptoms and diurnal PEFR variability as classified by concurrent days with high vs.. low PM 10 Mean % reporting (SEM) Asthmatics: High PM 10 Wheeze/shortness of breath = 21.3 (1.4) Runny/stuffed nose or sneezing = 42.3 (1.8) Cough = 59.9 (1.9) Phlegm = 60.5 (2.3) Sore throat = 23.7 (1.5) Any respiratory symptoms = 72.2 (3.2) Diurnal PEFR variability = 3.0 (0.4) Asthmatics: Low PM 10 Wheeze/shortness of breath = 19.3 (1.3) Runny/stuffed nose or sneezing = 35.8 (1.6) Cough = 59.1 (1.6) Phlegm = 58.6 (2.0) Sore throat = 21.0 (1.4) Any respiratory symptoms = 63.8 (2.8) Diurnal PEFR variability = 2.8 (0.3) Nonasthmatics: High PM 10 Wheeze/shortness of breath = 11.7 (1.4) Runny/stuffed nose or sneezing = 40.9 (2.5) Cough = 50.4 (2.6) Phlegm = 50.2 (2.5) Sore throat = 27.1 (1.7) Any respiratory symptoms = 67.8 (3.7) Diurnal PEFR variability = 2.4 (0.4) Nonasthmatics: Low PM 10 Wheeze/shortness of breath = 9.3 (1.2) Runny/stuffed nose or sneezing = 33.1 (2.2) Cough = 54.0 (2.2) Phlegm = 49.9 (2.2) Sore throat = 23.9 (1.5) Any respiratory symptoms = 56.4 (3.2) Diurnal PEFR variability = 2.1 (0.4) Notes: None of the daily reported respiratory symptoms had significant direct correlations with daily PM 10 levels, according to the authors.



### December 2009 E-163

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Rabinovitch et al. (2004, 096753 ) Periods of Study: Nov 1999-Mar 2000

Nov 2000-Mar 2001

Nov 2001-Mar 2002

Location: Denver, Colorado Outcome: Respiratory symptoms, Asthma symptoms (cough and wheeze), Upper respiratory symptoms Study Design: Time-series panel Statistical Analyses: Logistic linear regression Age Groups: 6-12 Pollutants: PM 10 Averaging Time: 24-h avg Mean (SD): 28.1 (13.2) Range (Min, Max): (6.0, 102.0) Copollutant:

CO

NO 2 SO 2 O 3 Increment: 1 μg/m 3 β (SE) AM: -0.010 (0.008) PM: -0.011 (0.010) Odds Ratio (Lower CI, Upper CI) Lag 1.016 (0.911, 1.133) 0-3 avg. OR for respiratory symptoms and PM 10 exposure for children age 6-12 Asthma exacerbation: 1.00 (0.75, 1.25) 0-3 avg Medication: 0.85 (0.75, 0.95) 0-3 avg Previous night’s symptoms: 1.10 (1.00, 1.20) 0-3 avg Current day’s symptoms: 1.00 (0.90, 1.10) 0-3 avg % Increase (Lower CI, Upper CI) Lag % Increase in FEV 1 or PEF and PM 10 exposure for children age 6-12 AM FEV 1 : -0.01 (-0.02, 0.01) 0-3 avg PM FEV 1 : -0.02 (-0.03, 0.02) 0-3 avg AM PEF: -0.025 (-0.035, 0.02) 0-3 avg PM PEF: 0.00 (-0.03, 0.03) 0-3 avg. Reference: Renzetti et al. (2009, 199834 ) Period of Study: Jun 2006-Jul 2006

Location: Pescara and Ovindoli, Italy Outcome: Airway inflammation and function Study Design: Panel

Covariates: NR Statistical Analysis: Student T-test, Pearson’s correlation coefficients Statistical Package: StatView Age Groups: Children, mean age 9.9 yr Pollutant: PM 10 Averaging Time: Daily Mean (SD) Unit: Urban: 56.9 ± 13.1 μg/m 3 Rural: 13.8 ± 5.6 μg/m 3 Copollutant (correlation): NR All results are presented in Fig format.



### December 2009 E-164

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Rojas-Martinez et al. (2007, 091064 ) Period of Study: 1996-1999

Location: Mexico City, Mexico Outcome: Lung function: FEV 1 , FVC, FEF 25-75% Age Groups: Children 8 yr old at time of cohort recruitment Study Design: School-based “dynamic” cohort study

N: 3170 children 14,545 observations Statistical Analyses: Three-level generalized linear mixed models with unstructured variance-covariance matrix

Covariates: Age, body mass index, height, height by age, weekday spent outdoors, environmental tobacco smoke, previous-day mean air pollutant concentration, time since first test Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-1 days Pollutant: PM 10 Averaging Time: 24 h, 6 mo Mean (SD): 24-h averaging Tlalnepantla: 66.7 (35.6) Xalostoc: 96.7 (49.4) Merced: 79.3 (40.8) Pedregal: 53.4 (31.9) Cerro de la Estrella: 69.6 (35.3) 6-mo averaging Mean: 75.6 Percentiles: 6-mo averaging 25th: 55.8 50th(Median): 67.5 75th: 92.2 Monitoring Stations: 5 sites for PM 10 , 10 for other pollutants Copollutant: O 3 NO 2 PM Increment: IQR

PM 10 , 6-LC: 36.4 GIRLS One-pollutant model FVC: -39 [-47: -31] FEV: -29 [-36: -21] FEF 25-75% : -17 [-36: 1] FEV 1 /FVC: 0.12 [0.07: 0.17] Two-pollutant model PM 10 , 6-LC & O 3 FVC: -30 [-39: -22] FEV: -24 [-31: -16] FEF 25-75% : -9 [-26: 9] FEV 1 /FVC: 0.10 [0.06: 0.15] PM 10 , 6-LC & NO 2 FVC: -21 [-30: -13] FEV: -17 [-25: -8] FEF 25-75% : -23 [-43: -4] FEV 1 /FVC: 0.07 [0.02: 0.13] Multipollutant model PM 10 , 6-LC, O 3 , & NO 2 FVC: -14 [-23: -5] FEV: -11 [-20: -3] FEF25-75%: -7 [-27: 12] FEV 1 /FVC: 0.08 [0.03: 0.13]

BOYS One-pollutant model FVC: -33 [-41: -25] FEV: -27 [-34: -19] FEF 25-75% : -18 [-34: -2] FEV 1 /FVC: 0.04 [-0.01: 0.09] Two-pollutant model PM 10 , 6-LC & O 3 FVC: -28 [-36: -19] FEV: -22 [-30: -15] FEF 25-75% : -10 [-27: 7] FEV 1 /FVC: 0.04 [-0.01: 0.09] PM 10 , 6-LC & NO 2 FVC: -16 [-26: -7] FEV: -19 [-27: -10] FEF 25-75% : -26 [-44: -9] FEV 1 /FVC: 0.005 [-0.06: 0.05] Multipollutant model PM 10 , 6-LC, O 3 , & NO 2 FVC: -12 [-22: -3] FEV: -15 [-23: -6] FEF 25-75% : -12 [-30: 6] FEV 1 /FVC: -0.002 [-0.06: 0.05] Long-term exposure to O 3 , PM 10 , and NO 2 is associated with decrements in FVC and FEV 1 growth in Mexico City schoolchildren. In a multipollutant model, PM 10 (-12%), O 3 (-9%), and NO 2 (-41%) each contribute independently and statistically significantly to diminished FVC growth. For FEV 1 , however, the multipollutant model indicates that only PM 10 (-15%) and NO 2 (-25%) each contribute independently and statistically significantly to diminished FEV 1 growth.



### December 2009 E-165

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Sahsuvaroglu et al. (2009, 190983 ) Period of Study: 1994-1995

Location: Hamilton, Canada Outcome: Asthma symptoms Study Design: Panel

Covariates: Neighborhood income, dwelling value, state of housing, deprivation index, smoking Statistical Analysis: Logistic regressions Statistical Package: SPSS

N: 6388 Age Groups: Children in grades 1 and 8 Pollutant: PM 10 Averaging Time: 3-yr avg Avg: All Subjects: 20.90 μg/m 3 Boys: 20.88 μg/m 3 Girls: 20.92 μg/m 3

Range: All Subjects: 26.98 Boys: 26.98 Girls: 20.10 Copollutant (correlation): NO X Theissen: 0.083 SO 2 Theissen: -0.021 O 3 Theissen: -0.251 NO 2 Kriged: 0.126 NO 2 LUR: 0.072 Increment: NR Odds Ratio (95%CI) for copollutant model PM10Spline and NO2LUR All Girls: 1.063 (0.969-1.666) Older Girls: 1.058 (0.918-1.219) Odds Ratio (95%CI) for copollutant model PM10Spline and NO2LUR, SO2Theissen and O3Theissen All Girls: 1.045 (0.943-1.158) Older Girls: 1.044 (0.891-1.225) Regression coefficients (95%CI) between non-allergic asthma and PM10Spline exposure All Children: 1.043 (0.996-1.092) Younger Children: 1.011 (0.929-1.100) Older Children: 1.073 (1.013-1.136) All Girls: 1.069 (0.999-1.144) All Boys: 1.024 (0.962-1.091) Younger Girls: 1.065 (0.943-1.203) Younger Boys: 0.962 (0.853-1.085) Older Girls: 1.072 (0.984-1.169) Older Boys: 1.075 (0.995-1.160) Reference: Sanchez-Carrillo et al. (2003, 098428 ) Period of Study: 1996-1997

Location: metropolitan Mexico City, Mexico Outcome: Upper respiratory symptom indicator (wet cough, sore throat, hoarseness, nose dryness, and head cold); Lower respiratory symptom indicator (dry cough, lack of air, and chest sounds); and Ocular symptom indicator (eye irritation, eye itch, eye burning, teary eyes, red eyes, and eye infection) Age Groups: All ages Study Design: Cohort

N: 151,418 interviews Statistical Analyses: Logistic regression models

Covariates: Sex, age, education, cigarette smoking, season, emergency episode mass media report, temperature, and relative humidity Dose-response Investigated? Yes Statistical Package: NR Lags Considered: 1 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Northeast: 132 (52) Northwest: 87 (46) Central: 85 (37) Southeast: 79 (35) Southwest: 55 (28) Range (Min, Max): Northeast: (34-269) Northwest: (10-275) Central: (9-319) Southeast: (14-225) Southwest: (12-264) Monitoring Stations : Up to 32 Copollutant (correlation): O 3 : r = 0.067 O 3 8: 00-18: 00 h: r = 0.075 SO 2 : r = 0.265 NO 2 : r = 0.265 Effect Estimate [Lower CI, Upper CI]: PM 10 quartiles: 10.04-52.62 (ref) 52.63-73.58 Upper respiratory indicator: 1.02 (0.99-1.06) Lower respiratory indicator: 1.04 (0.99-1.09) Ocular indicator: 0.99 (0.95-1.03) 73.59-101.91 Upper respiratory indicator: 1.07 (1.03-1.10) Lower respiratory indicator: 1.09 (1.04-1.14) Ocular indicator: 0.89 (0.86-0.92)101.92-318.80 Upper respiratory indicator: 0.93 (0.90-0.97) Lower respiratory indicator: 1.03 (0.98-1.08) Ocular indicator: 0.84 (0.81-0.87) Northeast - 2nd quartile Upper respiratory indicator: 0.354 (0.112-1.222) Lower respiratory indicator: 0.215 (0.040-1.160) Ocular indicator: 1.080 (0.915-1.274) 3rd quartile Upper respiratory indicator: 0.118 (0.039-0.356) Lower respiratory indicator: 0.126 (0.023-0.690) Ocular indicator: 1.228 (0.720-2.095) 4th quartile Upper respiratory indicator: 0.095 (0.034-0.267) Lower respiratory indicator: 0.119 (0.026-0.549) Ocular indicator: 0.878 (0.619-1.246) Northwest - 2nd quartile Upper respiratory indicator: 0.990 (0.898-1.090) Lower respiratory indicator: 1.246 (1.087-1.429) Ocular indicator: 1.218 (0.808-1.834) 3rd quartile Upper respiratory indicator: 1.133 (0.974-1.317) Lower respiratory indicator: 1.202 (1.044-1.385) Ocular indicator: 0.345 (0.125-0.951) 4th quartile Upper respiratory indicator:



### December 2009 E-166

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) 1.019 (0.904-1.149) Lower respiratory indicator: 1.344 (1.137-1.589) Ocular indicator: 1.949 (1.416-2.683) Central - 2nd quartile Upper respiratory indicator: 1.088 (1.002-1.183) Lower respiratory indicator: 1.046 (0.930-1.176) Ocular indicator: 1.220 (1.115-1.335) 3rd quartile Upper respiratory indicator: 1.054 (0.977-1.137) Lower respiratory indicator: 1.055 (0.948-1.175) Ocular indicator: 1.049 (0.965-1.142) 4th quartile Upper respiratory indicator: 0.899 (0.826-0.979) Lower respiratory indicator: 0.952 (0.845-1.073) Ocular indicator: 0.875 (0.796-0.963) Southeast - 2nd quartile Upper respiratory indicator: 0.778 (0.575-1.052) Lower respiratory indicator: 1.047 (0.916-1.196) Ocular indicator: 0.460 (0.299-0.708) 3rd quartile Upper respiratory indicator: 1.297 (1.127-1.491) Lower respiratory indicator: 1.391 (1.131-1.711) Ocular indicator: 0.474 (0.314-0.715) 4th quartile Upper respiratory indicator: 0.893 (0.812-0.983) Lower respiratory indicator: 0.937 (0.818-1.073) Ocular indicator: 0.314 (0.182-0.542) Southwest - 2nd quartile Upper respiratory indicator: 0.987 (0.913-1.066) Lower respiratory indicator: 2.181 (1.177-4.040) Ocular indicator: 1.026 (0.928-1.135) 3rd quartile Upper respiratory indicator: 0.673 (0.673-1.886) Lower respiratory indicator: 0.899 (0.790-1.024) Ocular indicator: 1.017 (0.862-1.200) 4th quartile Upper respiratory indicator: 0.524 (0.524-1.787) Lower respiratory indicator: 4.346 (0.917-20.606) Ocular indicator: 0.187 (0.090-0.387)



### December 2009 E-167

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Schildcrout et al. (2006, 089812 ) Period of Study: Nov 1993-Sep 1995

Location: Albuquerque, New Mexico Baltimore, Maryland Boston, Massachusetts Denver, Colorado San Diego, California Seattle, Washington St. Louis, Missouri Toronto, Ontario, Canada Outcome: Asthma Symptoms, Rescue Inhaler Uses Age Groups: 5-12 yr Study Design: Meta-analysis of CAMP

N: 990 children Statistical Analyses: “Working independence covariance structure” Logistic Regression Poisson Regression

“GEE Procedure”

Covariates: Season, age, raceethnicity, annual family income, day of the week Dose-response Investigated? Statistical Package: SAS 8.2

R Lags Considered: 0 day lag, 1 day lag, 2 day lag, 3-day moving sum Pollutant: PM 10 Averaging Time: 24-h avg Seattle: Daily Albuquerque: Daily Baltimore: 50% of study days measured Boston: 23% of study days measured Denver: 37% of study days measured San Diego: 24% of study days measured St. Louis: 19% of study days measured Toronto: 47% of study days measured Percentiles: 10th: 6.8-14.0 25th: 12.0-22.4 50th(Median): 17.7-32.4 75th: 26.2-42.7 90th: 32.5-53.9 Monitoring Stations: 1-12 Copollutant (correlation): NO 2 r = 0.26-0.64 SO 2 r = 0.31-0.65 O 3 r = 0.03-0.73 CO r = 0.24-0.88 PM Increment: 25 μg/m 3 One-pollutant model Asthma Symptoms: 1.02 [0.94, 1.11] 0 1.01 [0.97, 1.06] 1 1.02 [0.98, 1.07] 2 1.01 [0.98, 1.05] 3-day moving sum Rescue Inhaler Uses: [0.97, 1.05] 0 [0.97, 1.05] 1 1.00 [0.97, 1.03] 2 1.01 [0.98, 1.03] 3-day moving sum

Two-pollutant model Asthma Symptoms: CO-PM 10 1.08 [1.01, 1.15] 0 1.06 [0.99, 1.14] 1 1.08 [1.02, 1.14] 2 1.05 [1.01, 1.08] 3-day moving sum

NO 2 – PM 10 1.06 [0.99, 1.13] 0 1.04 [0.97, 1.11] 1 1.08 [1.02, 1.15] 2 1.04 [1.00, 1.07] 3-day moving sum

SO 2 -PM 10 1.05 [0.98, 1.13]; 0 1.04 [0.96, 1.14] 1 1.05 [0.98, 1.12] 2 1.04 [0.99, 1.08] 3-day moving sum

Rescue Inhaler Uses: CO-PM 10 1.06 [0.99, 1.13] 0 1.05 [0.99, 1.11] 1; 1.05 [1.01, 1.09] 2 1.03 [1.00, 1.07] 3-day moving sum NO 2 – PM 10 1.03 [0.97, 1.08] 0 1.03 [0.98, 1.08] 1 1.04 [1.00, 1.09] 2 1.02 [1.00, 1.05] 3-day moving sum

SO 2 -PM 10 1.01 [0.95, 1.07] 0 1.02 [0.97, 1.07] 1 1.03 [0.98, 1.09] 2 1.02 [0.98, 1.05] 3-day moving sum

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-168

# Table E-10. Short-term exposure - respiratory morbidity outcomes - PM 10-2.5 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Aekplakorn et al. (2003, 089908 ) Period of Study: 107 days, Oct 1997-Jan 1998

Location: Mae Mo district, Lampang Province, north Thailand Outcome: Upper respiratory symptoms, lower respiratory symptoms, cough Age Groups : 6-14 yr Study Design: Logistic regression

N: 98 asthmatic school children Statistical Analyses: Generalized Estimating Equations, stratified analysis, PROC GENMOD

Covariates: Temperature and relative humidity

Season : Winter Dose-response Investigated? No Statistical Package : SAS v 8.1 Pollutant: PM 10-2.5 Averaging Time: Daily Mean (SD): NR Range (Min, Max): NR Monitoring Stations : 3 Copollutant : PM 10 , SO 2 PM Increment: 10 μg/m 3

Odds Ratios [Lower CI, Upper CI] lag:

Asthmatics: URS: 1.04 (0.93, 1.17) lag 0 LRS: 1.09 (0.95, 1.26) lag 0 Cough: 1.08 (0.96, 1.21) lag 0

Non-Asthmatics: URS: 1.05 (0.99, 1.19) lag 0 LRS: 0.90 (0.72, 1.11) lag 0 Cough: 0.95 (0.81, 1.11) lag 0



### December 2009 E-169

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bourotte et al. (2007, 150040 ) Period of Study: May 2002-Jul 2002

Location: Sao Paulo, Brazil Outcome: Peak expiratory flow (PEF) Age Groups : Avg age 39.8 ± 12.3 yr Study Design: Cross-sectional

N: 33 patients Statistical Analyses: Linear mixedeffects model

Covariates: Gender, Age, BMI, Air Pollutants, Ambient temperature, Relative Humidity

Season: Winter Dose-response Investigated? No Statistical Package : S-plus Lags Considered: 2-day lag, 3-day lag Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 21.7 (12.9) μg/m 3 Range (Min, Max): (4.13, 62.0) Components: Na + K + Mg2 + Ca2 + FinfClNO 3 – SO 4 2– Monitoring Stations : 1 PM Increment: NR Effect [Lower CI, Upper CI] lag:

Morning PEF Na + concurrent day = -0.454 (-1.605, 0.697) Na + 2-day lag = -0.907 (-2.288, 0.474) Na + 3-day lag = -1.361 (-2.972, 0.251) K + concurrent day = 1.685 (-0.492, 3.862) K + 2-day lag = 1.838 (-1.272, 4.984) K + 3-day lag = 2.604 (-0.812, 6.025) Mg 2 + concurrent day = 2.265* (-0.427, 4.956) Mg 2 + 2-day lag = 1.271 (-1.869, 4.410) Mg 2 + 3-day lag = 0.939 (-2.425, 4.303) Ca 2 + concurrent day = 5.491* (2.558, 8.424) Ca 2 + 2-day lag = 6.358* (2.251, 10.465) Ca 2 + 3-day lag = 6.069 (1.962, 10.176) F inf

concurrent day = 1.572 (-0.792, 3.935) F inf

2-day lag = 1.630 (-1.679, 4.939) F in 3-day lag = 2.736* (-1.754, 7.226)

f Cl – concurrent day = -0.951 (-2.238, 0.336) Cl – 2-day lag = -1.871 (-3.242 to -0.4997) Cl – 3-day lag = -2.286* (-3.934 to -0.638)\ NO 3 – concurrent day = 4.195* (-0.063, 8.452) NO 3 – 2-day lag = 6.292* (2.034, 10.55) NO 3 – 3-day lag = 7.341* (3.083, 11.60) SO 4 2– concurrent day = 3.528 (-0.053, 7.110) SO 4 2– 2-day lag = 4.411* (0.829, 7.991)| SO 4 2– 3-day lag = 6.175* (2.593, 9.756)

Evening PEF Na + concurrent day = -0.680 (-1.831, 0.471) Na + 2-day lag = -1.90 (-3.316 to -0.494) Na + 3-day lag = -2.336* (-3.878 to -0.794) K + concurrent day = 0.613 (-1.564, 2.790) K + 2-day lag = 0.613 (-2.497, 3.723) K + 3-day lag = 0.000 (-3.421, 3.421)| Mg 2 + concurrent day = -0.718 (-3.522, 2.085) Mg 2 + 2-day lag = -1.933 (-5.073, 1.206) Mg 2 + 3-day lag = -3.591 (-7.056 to -0.126) Ca 2 + concurrent day = 2.312* (-1.208, 5.832) Ca 2 + 2-day lag = 2.023 (-2.084, 6.130) Ca 2 + 3-day lag = 0.578 (-3.530, 4.685) F inf

concurrent day = -1.281 (-3.644, 1.083) F inf

2-day lag = -2.503 (-5.930, 0.924) F in 3-day lag = -4.540 (-9.149, 0.068)

f Cl – concurrent day = -0.317 (-1.604, 0.970) Cl – 2-day lag = -1.268 (-2.556, 0.019) Cl – 3-day lag = -1.902 (-3.589 to -0.216) NO 3 – concurrent day = 3.146 (-1.112, 7.404) NO 3 – 2-day lag = 3.146 (-1.112, 7.404) NO 3 – 3-day lag = 1.049 (-3.209, 5.306) SO 4 2– concurrent day = 1.764 (-1.817, 5.346) SO 4 2– 2-day lag = 2.646 (-0.935, 6.228) SO 4 2– 3-day lag = 1.764 (-1.817, 5.346) Reference: Ebelt et al. (2005, 056907 ) Period of Study: Summer of 1998

Location: Vancouver, Canada Outcome: Spirometry Age Groups : Range from 54-86 yr Mean age= 74 yr Study Design: Extended analysis of a repeated-measures panel study

N: 16 persons with COPD Statistical Analyses: Earlier analysis expanded by developing mixed-effect regression models and by evaluating additional exposure indicators Dose-response Investigated? No Statistical Package : SAS V8 Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (SD): Ambient PM : 5.6 (3.0) 10-2.5 Exposure to ambient PM 10-2.5 : 2.4 (1.7) Range (Min, Max): Ambient PM : (-1.2-11.9) 10-2.5 Exposure to ambient PM 10-2.5 : (-0.4-7.2) Monitoring Stations : 5 Copollutant (correlation): Ambient PM 10 : r= 0.69 Ambient PM 2.5 : r= 0.15 Nonsulfate Ambient PM : r= 0.14

2.5 Exposure to Ambient PM 10-2.5 : r= 0.73 PM Increment: Ambient PM 10-2.5 : 4.5 (IQR) Exposure to ambient PM 10-2.5 : 2.4 (IQR)

Notes: Effect estimates are presented in Fig 2 and Electronic Appendix Table 1 (only available with electronic version of article) and not provided quantitatively elsewhere.



### December 2009 E-170

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lagorio et al.(2006, 089800 ) Period of Study: May 1999-June 1999 and Nov 1999-Dec 1999

Location: Rome, Italy Outcome: Lung function of subjects (FVC and FEV 1 ) with COPD, Asthma Age Groups : COPD 50-80 yr Asthma 18-64 yr Study Design: Time series

N: COPD N = 11; Asthma N = 11 Statistical Analyses: Non-parametric Spearman correlation GEE

Covariates: COPD: daily mean temperature, season variable (spring or winter), relative humidity, day of week Asthma: season variable, temperature, humidity, and -2-agonist use

Season: Spring and winter Dose-response Investigated? Yes Statistical Package : STATA Lags Considered: 1-3 days PM Size: PM 10-2.5 Averaging Time: 24 h Mean (SD): Overall: 15.6 (7.2) Spring: 18.7 (7.4) Winter: 12.3 (5.4) Range (Min, Max): (3.4, 39.6) PM Component: Cd: 0.46±0.40 ng/m 3 Cr: 1.9±1.7 ng/m 3 Fe: 283±167 ng/m 3 Ni: 4.8±6.5 ng/m 3 Pb: 30.6±19.0 ng/m 3 Pt: 5.0±8.6 pg/m 3 V: 1.8±1.4 ng/m 3 Zn: 45.8±33.1 ng/m 3 Monitoring Stations : Two fixed sites: (Villa Ada and Istituto superior di Sanita) Copollutant (correlation): NO 2 r = 0.51 O 3 r = 0.31 CO r = -0.09 SO 2 r = -0.16 PM 10 r = 0.61 PM 2.5 r = 0.34 PM Increment: 1 μg/m 3 They observed no statistically significant effect of PM 10-2.5 on FVC and FEV 1 on any of the panels (COPD, Asthma). β Coefficient (SE)

COPD FVC(%) 24 h -1.32 (1.06)^l 48-h -1.46 (1.31) 72-h -1.38 (1.53) FEV 1 (%) 24 h -0.59 (0.95) 48-h -1.01 (1.19) 72-h -0.90 (1.42)

Asthma FVC(%) 24 h -0.17 (0.75) 48-h -0.36 (0.91) 72-h -0.24 (1.07) FEV 1 (%) 24 h -0.67 (0.89) 48-h -1.19 (1.07) 72-h -0.51 (1.26)

Reference : Laurent et al. (2008, 156672 ) Period of Study: Dec 2003-Dec 2004

Location: Strasbourg, France Outcome: Sales of short acting β

agonists Study Design: Case-crossover

Covariates: NR Statistical Analysis: Conditional logistic regression Age Groups: 0-39 yr Pollutant: PM 10 Averaging Time: NR Mean (SD) Unit: 20.8 (10.2) μg/m 3 Range (Min, Max): NR Copollutant (correlation): NO 2 , O 3 , correlations NR Increment: 10 μg/m 3 Percent Increase in Short Acting β -agonists sold

Per increment increase in ambient PM 10 at lags 4-7, a 7.5% increase (95% CI: 4- 11.2%) was seen in SABA sales. All other results were given in Fig 1 and 2

Reference: Tang et al. (2007, 091269 ) Period of Study: Dec 2003-Feb 2005

Location: Sin-Chung City, Taipei County, Taiwan Outcome: Peak expiratory flow rate (PEFR) of asthmatic children Age Groups : 6-12 yr Study Design: Panel study

N: 30 children Statistical Analyses:

Linear mixed-effect models were used to estimate the effect of PM exposure on PEFR

Covariates: Gender, age, BMI, history of respiratory or atopic disease in family, SHS, acute asthmatic exacerbation in past 12 mo, ambient temperature and relative humidity, presence of indoor pollutants, and presence of outdoor pollutants, Dose-response Investigated? yes Statistical Package : S-Plus 2000 Lags Considered: 0-2 Pollutant: PM 10-2.5 Averaging Time: 1 h Mean (SD): Personal: 17.8 (19.6) Ambient: 17.0 (10.6) Range (Min, Max):

Personal: 0.3-195.7

Ambient: 0.1-80.2 Monitoring Stations : 1 PM Increment: 15.9 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Change in morning PEFR: -20.55 (-45.83, 4.73) lag 0 -39.05 (-104.16 , 26.06) lag 1 -39.56 (-79.56, 0.44) lag 2 -37.15 (-105.01, 30.7) 2-day mean -35.47 (-27.32, 56.38) 3-day mean Change in evening PEFR: -1.68 (-19.13, 15.78) lag 0 1.59 (-14.32, 17.5) lag 1 0.86 (-30.84, 32.57) lag 2 5.97 (-15.57, 27.5) 2-day mean 29.75 (-1.69, 61.18) 3-day mean



### December 2009 E-171

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Trenga et al., (2006, 155209 ) Period of Study: 1999-2002

Location: Seattle, WA Outcome : Lung function: FEV 1 , PEF, MMEF (maximal midexpiratory flow assessed only for children) Age Groups : Adults (56-89-yr-old) healthy & with COPD Asthmatic children 6-13-yr-old Study Design: Adult and pediatric panel study over 3 yr with 1 monitoring period (“session”) per yr

N: 57 adults (33 healthy, 24 with COPD) = 692 subject-days = 207 study-days17 asthmatic children = 319 subjectdays = 98 study-days Statistical Analyses: Mixed effects, longitudinal regression models, with the effects of pollutant decomposed into each subject’s a) overall meanb) Difference between their sessionspecific mean and overall mean c) Difference between their daily values and session-specific mean

Covariates: Gender, age, ventral site temperature and relative humidity, CO, NO 2 Season: NR Dose-response Investigated? No Statistical Package : SAS Lags Considered: 0-1 days Pollutant: PM 10-2.5 (coarse) Averaging Time: 24 h Percentiles: Subject-specific exposure PM 10 -PM 2.5 Outdoor 25th: 3.3 50th (Median): 4.7 75th: 6.9

Adults Outdoor 25th: 3.3 50th (Median): 5.0 75th: 7.1 Range (Min, Max): Subject-specific exposure

Children Outdoor (0.0, 25.3)

Adults Outdoor (0.0, 25.7) Monitoring Stations : 2 Also subject-specific local outdoors (i.e., at each home), indoor, and personal Copollutant (correlation):

CO

NO 2 PM 2.5 PM Increment: 10 μg/m 3

Adult Outdoor Home PM 10 -PM 2.5 FEV 1 Overall: Lag 0 -27.9 [-87.5: 31.8] Lag 1 47.1 [-5.1: 99.4] No-COPD: Lag 0 -49.2 [-22.3: 23.9] Lag 1 74.3 [6.8: 141.8] COPD: Lag 0 7.3 [-84.7: 99.4] Lag 1 11.5 [-65.4: 88.3] PEF Overall: Lag 0 5.3 [-5.1: 15.7] Lag 1 -2.5 [-11.6: 6.5] No-COPD: Lag 0 5.1 [-7.7: 17.8] Lag 1 -5.8 [-17.5: 5.9] COPD: Lag 0 5.7 [-10.3: 21.6] Lag 1 1.7 [-11.5: 14.9] Pediatric FEV 1 Outdoor Home PM 10 -PM 2.5 Overall Lag 0 -7.43 [-69.41: 54.55] Lag 1 -25.61 [-88.16: 36.94] No Anti-inflam. Medication Lag 0 -63.87 [-199.58: 71.84] Lag 1 -96.48 [-232.48: 39.52] Anti-inflam. Medication Lag 0 6.57 [-96.90: 110.04] Lag 1 -8.63 [-217.39: 200.14] PEF Outdoor Home PM 10 -PM 2.5 Overall Lag 0 4.53 [-6.60: 15.67] Lag 1 -3.35 [-14.31: 7.62] No Anti-inflam. Medication Lag 0 2.05 [-22.36: 26.45] Lag 1 -6.56 [-30.90: 17.78] Anti-inflam. Medication Lag 0 5.15 [-7.90: 18.19] Lag 1 -2.58 [-15.35: 10.19] MMEF Outdoor Home PM 10 -PM 2.5 Overall Lag 0 -0.01 [-7.29: 7.28] Lag 1 -2.07 [-9.25: 5.12] No Anti-inflam. Medication Lag 0-7.14 [-23.16: 8.87] Lag 1 -14.39 [-30.11: 1.32] Anti-inflam. Medication Lag 0 1.76 [-6.78: 10.30] Lag 1 0.89 [-7.56: 9.33]

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-172

# Table E-11. Short-term exposure - respiratory morbidity outcomes - PM 2.5 

# (including components/sources).

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Adamkiewicz et al. (2004, 087925 ) Period of Study: Aug-Dec 2000

Location: Steubenville, Ohio Outcome: FENO Age Groups : Ranged 53.5-90.6 yr Study Design: Prospective cohort

N: Total of 294 breaths from 29 subjects Statistical Analyses: Fixed effect models, ANOVA, GLM procedure

Covariates: Subject, week of study, day of the week, h of the day, ambient barometric pressure, temperature, and relative humidity Dose-response Investigated? No Statistical Package : SAS Lags Considered: Hourly lags, 0-48 h Pollutant: PM 2.5 Averaging Time: 1 h Mean (SD): 19.5 Percentiles: 25th: 7.6 75th: 25.5 Range (Min, Max): NR, 105.8 Monitoring Stations : 1 Averaging Time: 24 h Mean (SD): 19.7 Percentiles: 25th: 9.7 75th: 27.4 Range (Min, Max): NR, 57.8 Monitoring Stations : 1 Copollutant (correlation): Ambient NO Indoor NO NO 2 O

3 SO 2 PM Increment: 17.9 μg/m 3 Effect Estimate [Lower CI, Upper CI]: 1-h Single pollutant models: 0.36 (0.58-2.14)

PM Increment: 17.7 Effect Estimate [Lower CI, Upper CI]: 24-h ma: 1.45 (0.33-2.57) Multipollutant models for PM 2.5 , ambient NO and room NO and estimated change in FENO (ppb) for an IQR in pollutant measure Model 1 1.95 (0.47-3.43) Model 2 1.38 (0.26-2.51) Model 4 1.97 (0.48-3.46)

Notes: Association of FENO with PM 2.5 at different lags presented in Fig 1 are not presented quantitatively elsewhere.

Reference: Adar et al. (2007, 098635 ) Period of Study: Mar-Jun 2002

Location: St. Louis, MO Outcome: FENO Age Groups : 60+ Study Design: Panel Study

N: 44 non-smoking seniors Statistical Analyses: Mixed models containing random subject effects

Covariates: Day of week, trip type, FENO collection device, current illness, use of vitamins, antihistamines, statins, steroids, and asthma medications, temperature, pollen, mold, NO concentration in testing room Statistical Package : SAS Lags Considered: 0 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Pretrip: 14.8 Post-trip: 16.5

Percentiles: 25th (pretrip): 11.2 75th (pretrip): 20.1 25th (post-trip): 11.7 75th (post-trip): 21.6 Monitoring Stations : 1 Copollutant (correlation): BC CO NO 2 SO 2 O 3 PM Increment: 9.8 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Pre-trip % change: 21.9 (6.7, 39.4) Post-trip % change: -4.7 (-17.1, 9.6)

Reference: Aekplakorn et al. (2003, 089908 ) Period of Study: 107 days, from Oct 1997-Jan 1998

Location: Mae Mo district, Lampang Province, north Thailand Outcome: Upper respiratory symptoms, lower respiratory symptoms, cough Age Groups : 6-14 yr old Study Design: Logistic regression

N: 98 asthmatic school children Statistical Analyses: Generalized Estimating Equations, stratified analysis, PROC GENMOD

Covariates: Temperature and relative humidity

Season: Winter Dose-response Investigated? No Statistical Package : SAS v 8.1 Pollutant: PM 2.5 Averaging Time: Daily Mean (SD):

Sob Pad station: 24.77

Sob Mo station: 24.89

Hua Fai station: 26.27 Range (Min, Max): Sob Pad: 4.52, 24.77 Sob Mo: 3.13, 24.89 Hua Fai: 3.67, 26.27 Monitoring Stations : 3 Copollutant: PM 10 SO 2 PM Increment: 10 μg/m 3 Odds Ratios [Lower CI, Upper CI] lag: Asthmatics: URS: 1.04 (0.99, 1.09) lag 0 LRS: 1.05 (0.98, 1.2) lag 0 Cough: 1.05 (0.99, 1.10) lag 0 Non-Asthmatics: URS: 1.03 (0.96, 1.09) lag 0 LRS: 1.02 (0.93, 1.10) lag 0 Cough: 1.00 (0.93, 1.07) lag 0 PM + SO

10 2 Asthmatics: URS: 1.04 (0.99, 1.10) lag 0 LRS: 1.05 (0.98, 1.10) lag 0 Cough: 1.05 (0.99, 1.11) lag 0 Non-Asthmatics: URS: 1.03 (0.97, 1.09) lag 0 LRS: 1.02 (0.93, 1.11) lag 0 Cough: 1.00 (0.93, 1.07) lag 0



### December 2009 E-173

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Allen et al. (2008, 156208 ) Period of Study: 1999-2002 (additional PM composition data collected Dec 2000 and May 2001)

Location: Seattle, USA Outcome: Daily changes in exhaled nitric oxide (FENO) and 4 lung function measures, midexpiratory flow (MEF), peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV 1 ), and forced vital capacity (FVC) Age Groups: 6-13 yr Study Design: Panel study

N: 19 children with asthma Statistical Analyses: Linear mixed effects model with random intercept to test for within participant associations

Covariates: Temperature, relative humidity, BMI, age, and, in the case of FENO, ambient NO measured at a centrally located monitoring site

Models also included a term for withinparticipant, within-session effects, and a term for participant between-session effects

Effect modification : Decided a priori to include interaction term for PM 2.5 exposure and inhaled corticosteroids Pollutant: PM 2.5 Mean (SD): 11.23 (6.48) Range (Min, Max):

2.76-40.38

25th: 6.38

75th: 14.73 Copollutant (correlation):

Ambient LAC* r=0.83

Ambient LG**r=0.84

Personal PM 2.5 : r=0.34

Personal LAC: r=0.54 Ambient-generated PM 2.5 : r=0.87 Nonambient-generated PM 2.5 : r=-0.06 * LAC Light-absorbing carbon ** LG: Leroglucosan (a marker of wood smoke) Health effect estimates presented in graphic form (Fig 1). Summary from text is as follows: Personal LAC, personal PM 2.5 , and ambient-generated PM 2.5 were associated with (p < 0.05) and ambient PM 2.5 was marginally associated (p=0.09) with increased FENO. Neither of the ambient combustion markers (LAC, LG) nor nonambient-generated PM 2.5 was associated with FENO changes.

All of the ambient concentrations were associated with decrements in PEF and MEF while ambient-generated PM 2.5 was marginally associated (p < 0.10). Only ambient LG was associated with a decrease in FEV 1 and there were no associations between exposure metrics and FVC.

Reference: Barraza-Villarreal et al.(2008, 156254 ) Period of Study: Jun 2003-Jun 2005

Location: Mexico City Outcome: Respiratory Symptoms, Coughing, Wheezing, Airway inflammation, Asthma Study Design: Prospective cohort Statistical Analyses: Bivarate analysis Age Groups : 6-14 Pollutant: PM 2.5 Averaging Time: Maximum 8-h avg Mean (SD) unit: 28.9 (2.8) Range (Min, Max): (4.2, 102.8) Copollutants (correlation):

O 3 NO 2 Increment: 17.5 μg/m 3 % Increase (Lower CI, Upper CI) lag: Asthmatic children Inflammatory Marker: FENO: 1.08 (1.01, 1.16) 0 IL-8: 1.08 (0.98, 1.19) 0 ph_EBC: -0.03 (-0.09, 0.03) 0 Lung Function: FEV 1 : -16.0 (-31.0 to -0.13) 0-4 avg FVC: -23.0 (-42.0 to -5.21) 0-4 avg FEV25-75: -11.0 (-42.0, 20.3) 0-4 avg

Nonasthmatic children Inflammatory Marker: FENO: 0.89 (0.78, 1.01) 0 IL-8: 1.16 (1.00, 1.36) 0; ph_EBC: -0.05 (-0.14, 0.04) 0 Lung Function: FEV 1 : -21.0 (-42.3, 0.38) 0-4 avg FVC: -29.0 (-52.8 to -4.35) 0-4 avg FEV 25-75 : -20.0 (-69.0, 29.0) 0-4 avg

All children age 6-14 Respiratory Symptom: Cough: 1.11 (1.06, 1.17) Wheezing: 1.06 (0.99, 1.13)



### December 2009 E-174

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bennett et al. (2007, 156268 ) Period of Study: 1992-2005

Location: Melbourne, Australia Outcome: Adverse respiratory symptoms (wheeze, shortness of breath on waking, cough in the morning, phlegm in the morning, cough with phlegm in the morning, asthma attack) Age Groups : All ages with a mean of 37.2 yr Study Design: Cohort study

N: 1446 persons Statistical Analyses: Logistic regression models

Covariates: Age, gender, current smoking status, medication use (ß2- agonist and inhaled steroid), atopy Dose-response Investigated? No Statistical Package : STATA statistical software, version 9 (Statcorp, 2005) Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 6.8 Range (Min, Max): (1.8-73.3) Monitoring Stations : 1 PM Increment: 1 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Within-person (longitudinal effects) Wheeze: OR=1.08 (0.79-1.48) SOB on waking: OR=1.34 (0.84-2.16) Cough in the morning: OR=0.74 (0.47-1.15) Phlegm in the morning: OR=1.55 (0.95-2.53) Cough w/ phlegm morning: OR=1.28 (0.70-2.33) Asthma attack: OR=0.91 (0.55-1.49) Between-person (cross-sectional) effects Wheeze: OR=1.32 (0.82-2.10) SOB on waking: OR=1.29 (0.46-3.60) Cough in the morning: OR=0.21 (0.07-0.62) Phlegm in the morning: OR=0.49 (0.16-1.44) Cough w/ phlegm morning: OR=0.28 (0.08-0.97) Asthma attack: OR=0.52 (0.17-1.59)



### December 2009 E-175

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bourotte et al. (2007, 150040 ) Period of Study: May 2002-Jul 2002

Location: Sao Paulo, Brazil Outcome: Peak expiratory flow (PEF) Age Groups : Avg age 39.8 ± 12.3 yr Study Design: Cross-sectional

N: 33 patients Statistical Analyses: Linear mixed-effects model

Covariates: Gender, Age, BMI, Air Pollutants, Ambient temperature, Relative Humidity

Season: Winter Dose-response Investigated? No Statistical Package : S-plus Lags Considered: 2-day lag, 3-day lag Pollutant: PM 2.5 (Fine) Averaging Time: 24 h Mean (SD): 11.9 (5.12) Range (Min, Max): (2.82, 26.6) Components: K + Mg 2 + Ca 2 + F in f Cl – NO 3 – SO 4 2– Monitoring Stations : 1 PM Increment: NR Effect [Lower CI, Upper CI] lag: Morning PEF Na + concurrent day = -0.409 (-2.485, 1.667) Na + 2-day lag = -0.818 (-4.139, 2.503) Na + 3-day lag = -0.205 (-4.356, 3.974) K + concurrent day = -0.211 (-2.778, 2.357) K + 2-day lag = -0.843 (-4.695, 3.008) K + 3-day lag = 0.843 (-4.292, 5.978) Mg 2 + concurrent day = -1.750 (-5.302, 1.802) Mg 2 + 2-day lag = -5.016 (-10.79, 0.762) Mg 2 + 3-day lag = -3.850 (-10.15, 2.449) Ca 2 + concurrent day = 3.192* (-0.599, 6.943) Ca 2 + 2-day lag = 5.880 (1.105, 10.65) Ca 2 + 3-day lag = 7.560* (2.103, 13.02) F inf

concurrent day = 2.218* (-0.033, 4.470) F inf

2-day lag = 3.697* (1.446, 5.949) Fi 3-day lag =4.067* (1.065, 7.069)

nf Cl – concurrent day = -1.010 (-3.469, 1.450) Cl – 2-day lag = -1.615 (-5.714, 2.483) Cl – 3-day lag = -1.615 (-6.534, 3.303) NO 3 – concurrent day = 3.144 (0.409, 5.878) NO 3 – 2-day lag = 3.593 (0.858, 6.328) NO 3 – 3-day lag = 4.491 (1.756, 7.226) SO 4 2– concurrent day = 2.210 (-0.032, 4.272) SO 4 2– 2-day lag = 3.180 (1.028, 5.332) SO 4 2– 3-day lag = 3.180 (1.028, 5.332) Evening PEF Na + concurrent day = -1.636 (-3.712, 0.440) Na + 2-day lag = -0.205 (-3.256, 3.117) Na + 3-day lag = -1.023 (-5.174, 3.129) K + concurrent day = -1.897 (-4.465, 0.670) K + 2-day lag = -1.686 (-5.966, 2.592) K + 3-day lag = -1.054 (-6.189, 4.081) Mg 2 + concurrent day = -2.753 (-6.400, 0.894) Mg 2 + 2-day lag = -2.567 (-8.534, 3.401) Mg 2 + 3-day lag = -4.876 (-11.36, 1.612) Ca 2 + concurrent day = 2.184 (-1.567, 5.935) Ca 2 + 2-day lag = 5.040 (0.265, 9.815) Ca 2 + 3-day lag = 5.040 (-0.417, 10.50) F inf

f concurrent day = 1.479 (-0.773, 3.730) F inf

2-day lag = 1.819 (-0.403, 4.100) F in 3-day lag = 2.958 (-0.044, 5.960)

f Cl – concurrent day = -0.404 (-2.863, 2.055) Cl – 2-day lag = 0.000 (-4.099, 4.099) Cl – 3-day lag =0.202 (-4.716, 5.120) NO 3 – concurrent day = 1.796 (-0.939, 4.531) NO 3 – 2-day lag = 2.695 (-0.040, 5.430) NO 3 – 3-day lag = 3.144 (0.409, 5.878) SO 4 2– concurrent day = 2.120 (-0.032, 4.272) SO 4 2– 2-day lag = 2.120 (-0.032, 4.272) SO 4 2– 3-day lag =2.120 (-0.032, 4.272)



### December 2009 E-176

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: de Hartog et al. (2003, 001061 ) Period of Study: Winter of 1998-1999 (in Amsterdam, from Nov 1998-Jun 1999; in Erfurt, from Oct 1998-Apr 1999; and in Helsinki, from Nov 1998-Apr 1999.)

Location: Amsterdam, the Netherlands Erfurt, Germany and Helsinki, Finland Outcome: Respiratory symptoms Age Groups : ≥ 50 yr Study Design: C ohort

N: 131 subjects with history of coronary heart disease Statistical Analyses: Logistic regression

Covariates: Ambient temperature, relative humidity, atmospheric pressure, incidence of influenza-like illness

Season : Winter Dose-response Investigated? No Statistical Package : S-PLUS 2000 Lags Considered: 0-, 1-, 2-, 3-, and 5-day avg Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Amsterdam, the Netherlands: 20.0 Erfurt, Germany: 23.4 Helsinki, Finland: 12.8 Range (Min, Max): Amsterdam, the Netherlands: (3.8-82.2) Erfurt, Germany: (4.5-118.1) Helsinki, Finland: (3.1-39.8) Unit (i.e. μg/m 3 ): μg/m 3 Monitoring Stations : 1 Copollutant:

PM 10 NC0.01-0.1

CO

NO 2 SO 2 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Association of air pollution and incidence of symptoms in three panels of elderly subjects Lag 0 Chest pain w/ physical exertion: 1.04 (0.96-1.13) Shortness of breath: 1.04 (0.96-1.12) Awakened, breathing problems: NA Avoidance of activities: 1.04 (0.96-1.14) Phlegm: 1.03 (0.93-1.13) Lag 1 Chest pain w/ physical exertion: 1.01 (0.93-1.09) Shortness of breath: 1.06 (0.99-1.14) Awakened, breathing problems: 1.09 (1.00-1.20) Avoidance of activities: 1.03 (0.95-1.12) Phlegm: 1.10 (1.01-1.19) Lag 2 Chest pain w/ physical exertion: 0.98 (0.90-1.05) Shortness of breath: 1.05 (0.98-1.12) Awakened, breathing problems: 1.04 (0.95-1.14) Avoidance of activities: 1.05 (0.97-1.14) Phlegm: 1.08 (1.00-1.18) Lag 3 Chest pain w/ physical exertion: 1.00 (0.93-1.08) Shortness of breath: 1.08 (1.01-1.15) Awakened, breathing problems: 0.99 (0.91-1.08) Avoidance of activities: 1.06 (0.98-1.14) Phlegm: 1.10 (1.01-1.19) 5-day Chest pain w/ physical exertion: 1.02 (0.91-1.13) Shortness of breath: 1.12 (1.02-1.24) Awakened, breathing problems: 1.03 (0.90-1.18) Avoidance of activities: OR= 1.09 (0.97- 1.22) Phlegm: OR= 1.16 (1.03-1.32)



### December 2009 E-177

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Delfino et al. (2004, 056897 ) Period of Study: Sep-Oct 1999 Apr-Jun 2000

Location: Alpine, California Outcome : FEV 1 Age Groups : 9-19 yr old Study Design: Panel study

N: 24 children Statistical Analyses: GLM

Akaike’s information criterion and Bayesian information criterion

Covariates: Day of wk, personal temperature and relative humidity, time of FEV 1 maneuver (morning, afternoon, or evening), Season (fall 1999 or spring 2000), As-needed medication use, Presence or absence of upper or lower respiratory infections

Season: Spring, fall Dose-response Investigated? No Statistical Package : SAS Lags Considered: 0-4 Pollutant: PM 2.5 Averaging Time: 24-h avg 1-h max personal PM last 24 h Mean (SD): 151.0 (12.03) 90th: 292.4 Range (Min, Max): (9.1, 996.8) Mean personal PM last 24 h Mean (SD): 37.9 (19.9) 90th: 65.1 Range (Min, Max): 3.9, 113.8 Home stationary-site PM 24-h Mean indoor PM 2.5 Mean (SD): 12.1 (5.4) 90th: 20.2 Range (Min, Max): 2.8, 35.3 24-h Mean outdoor PM 2.5 Mean (SD): 11.0 (5.4) 90th: 18.4 Range (Min, Max): 1.8, 31.0 Central outdoor stationary-site PM 24-h Mean PM 2.5 Mean (SD): 10.3 (5.6) 90th: 18.4 Range (Min, Max): 1.7, 29.1 Copollutant (correlation): 24-h Central HI PM 2.5 8-h max O 3 = 0.24 8-h Max NO 2 = 0.73 8-h Max Personal PM = 0.38 24-h Mean Personal PM = 0.43 8-h Max TEOM PM 10 = 0.71 24-h Mean TEOM PM 10 = 0.78 24-h Central HI PM 10 = 0.90 24-h Outdoor HI PM 2.5 = 0.89 24-h Outdoor HI PM 10 = 0.72 24-h Indoor HI PM 10 = 0.40 24-h Indoor HI PM 2.5 = 0.73 Results presented graphically; % predicted FEV 1 was inversely associated with personal exposure to fine particles.

Inverse associations of FEV 1 with stationary-site indoor, outdoor and central-site gravimetric PM 2.5 and PM 10 , and with hourly TEOM PM 10



### December 2009 E-178

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Delfino et al. (2006, 090745 ) Period of Study: Region 1: Aug-Mid Dec 2003. Region 2: Jul-Nov 2004

Location: Region 1: Riverside, CA. Region 2: Whittier, CA Outcome: Fractional Concentration of Nitric Oxide in exhaled air (FENO) Age Groups : 9 through 18 Study Design: Longitudinal Panel Study

N: 45 children

Riverside children

32 Whittier children Statistical Analyses: Linear mixedeffects models Two-stage hierarchical model Empirical Variograms Fourth-order polynomial distributed lag mixed-effects model

Covariates: Personal temperature, Personal Rel. Humid., 10-day exposure run, Respiratory infections, Region ofstudy, Sex, Cumulative daily use of asneeded B-agonist inhalers Dose-response Investigated? No Lags Considered: 0, 1, 2, MA day Pollutant : PM 2.5 Personal Exposure Averaging Time: 24 h Riverside Mean (SD): 32.78 (21.84) 50th(Median): 28.14 Range (Min, Max): 7.27, 98.43 Whittier Mean (SD): 36.2 (25.46) 50th(Median): 29.07 Range (Min, Max): 7.55, 197.05 Personal Exposure Averaging Time: 1 h Riverside Mean (SD): 97.94 (70.29) 50th(Median): 83.7 Range (Min, Max): 14.9, 431.8

Whittier Mean (SD): 93.63 (75.19) 50th(Median): 71.95 Range (Min, Max): 5.8, 572.9 Personal Exposure Averaging Time: 8 h

Riverside Mean (SD): 47.21 (30.9) 50th(Median): 38.5 Range (Min, Max): 8.9, 132.1

Whittier Mean (SD): 51.75 (36.88) 50th(Median): 40.15 Range (Min, Max): 8.7, 254.1

Central Site Averaging Time: 24 h

Riverside Mean (SD): 36.63 (23.46) 50th(Median): 29.26 Range (Min, Max): (9.52, 87.22)

Whittier Mean (SD): 18 (12.14) 50th(Median): 16.3 Range (Min, Max): 2.7, 77.09 Monitoring Stations : 48 personal nephelometers 2 central sites Copollutant (correlation): Personal 24-h personal PM 2.5 1.00 24-h personal EC 0.18 24-h personal OC 0.15 24-h personal NO 2 0.33 24-h central PM 2.5 0.64 24-h central EC 0.12 24-h central OC 0.21 24-h central NO 2 0.22 Central 24-h personal PM 2.5 0.64 24-h personal EC 0.00 24-h personal OC -0.11 24-h personal NO 2 0.12 24-h central PM 2.5 1.00 24-h central EC 0.55 24-h central OC 0.66 24-h central NO 2 0.25 PM Increment: IQR increase (Riverside: 28.41 μg/m 3 , Whittier 21.87 μg/m 3 ) Coefficient [Lower CI, Upper CI] lag:

Mixed-model estimates of the association between personal and central-site air pollutant exposure and FENO Lag 0 Personal 0.42 (-0.15, 0.99) Central 0.03 (-0.68, 0.74)

Lag 1 Personal 0.51 (-0.10, 1.12) Central 0.44 (-0.28, 1.16)

2-day ma Personal 1.01 (0.14, 1.88) Central 0.52 (-0.43, 1.47) Stratified by Medication Use

Lag = 2-day ma Not Taking Anti-Inflamm. Medication Personal 1.11 (-1.39, 3.60) Central 0.44 (-1.65, 2.53) Taking Anti-Inflamm. Medication Personal 1.01 (0.19, 1.84) Central 0.55 (-0.47, 1.57) Inhaled Corticosteroids Personal 1.58 (0.72, 2.43) Central 1.16 (0.11, 2.20) Antileukotrienes +- inhaled corticosteroids Personal -0.89 (-2.73, 0.95) Central -0.75 (-2.83, 1.32) Notes: Fig of Estimated lag effect of hourly personal PM 2.5 on FENO. Fig of the Estimated lag effect of hourly personal PM 2.5 on FENO by use of medications. Fig of one- and two-pollutant models for change in FENO using 2-day Ma personal and central-site pollutant measurements.



### December 2009 E-179

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Delfino et al. (2006, 090745 ) Period of Study: Region 1: Aug-Mid Dec 2003. Region 2: Jul-Nov 2004

Location: Region 1: Riverside, CA. Region 2: Whittier, CA Outcome: Fractional Concentration of Nitric Oxide in exhaled air (FENO) Age Groups : 9 through 18 Study Design: Longitudinal Panel Study

N: 45 children Statistical Analyses: Linear mixedeffects models Two-stage hierarchical model Empirical Variograms Fourth-order polynomial distributed lag mixed-effects model

Covariates: Personal temperature, personal rel. humid., 10-day exposure run, respiratory infections, region ofstudy, sex, cumulative daily use of asneeded B-agonist inhalers Dose-response Investigated? No Lags Considered: Lag 0, Lag 1, 2-day

ma Pollutant: PM 2.5 PM Component: EC Personal Exposure Averaging Time: 24 h

Riverside Mean (SD): 0.42 (0.69) 50th(Median): 0.34 μg/m 3 Range (Min, Max): 0.01, 6.94

Whittier Mean (SD): 0.78 (1.42) 50th(Median): 0.47 Range (Min, Max): 0, 17.2

Central Site Averaging Time: 24 h

Riverside Mean (SD): 1.61 (0.78) 50th(Median): 1.35 Range (Min, Max): 0.52, 3.64

Whittier Mean (SD): 0.71 (0.43) 50th(Median): 0.63 Range (Min, Max): 0.14, 2.95 Monitoring Stations : 48 personal nephelometers,

2 central sites Copollutant (correlation): Personal 24-h personal PM 2.5 0.18 24-h personal EC 1.00 24-h personal OC 0.41 24-h personal NO 2 0.0.21 24-h central PM 2.5 0.00 24-h central EC 0.04 24-h central OC -0.01 24-h central NO 2 0.23 Central 24-h personal PM 2.5 0.12 24-h personal EC 0.04 24-h personal OC 0.03 24-h personal NO 2 0.19 24-h central PM 2.5 0.55 24-h central EC 1.00 24-h central OC 0.87 24-h central NO 2 0.70 PM Increment: IQR increase (Riverside: 28.41 μg/m 3 , Whittier 21.87 μg/m 3 ) Coefficient [Lower CI, Upper CI] lag: Mixed-model estimates of the association between personal and central-site air pollutant exposure and FENO

Lag 0 Personal 0.29 (0.10, 0.48) Central 0.10 (-0.65, 0.85)

Lag 1 Personal -0.01 (-0.23, 0.21) Central 0.99 (0.27, 1.71)

2-day ma Personal 0.72 (0.32, 1.12) Central 1.38 (0.15, 2.61) Stratified by Medication Use

Lag = 2-day ma Not Taking Anti-Inflamm. Medication Personal 0.84 (0.08, 1.60) Central 1.02 (-2.55, 4.60) Taking Anti-Inflamm. Medication Personal 0.71 (0.28, 1.15) Central 1.42 (0.25, 2.60) Inhaled Corticosteroids Personal 0.67 (0.28, 1.07) Central 1.28 (0.07, 2.49) Antileukotrienes +- inhaled corticosteroids Personal 0.03 (-3.29, 3.35) Central 1.15 (-1.58, 3.88) Notes: Fig of Estimated lag effect of hourly personal PM 2.5 on FENO. Fig of the estimated lag effect of hourly personal PM 2.5 on FENO by use of medications. Fig of one- and two-pollutant models for change in FENO using 2-day Ma personal and central-site pollutant measurements.



### December 2009 E-180

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Delfino et al. (2006, 090745 ) Period of Study: Region 1: Aug-Mid Dec 2003. Region 2: Jul through Nov 2004

Location: Region 1: Riverside, CA. Region 2: Whittier, CA Outcome: Fractional Concentration of Nitric Oxide in exhaled air (FENO) Age Groups : 9 through 18 Study Design: Longitudinal Panel Study

N: 45 children Statistical Analyses: Linear mixedeffects models Two-stage hierarchical model Empirical Variograms Fourth-order polynomial distributed lag mixed-effects model

Covariates: Personal temperature, personal rel. humid., 10-day exposure run, respiratory infections, region ofstudy, sex, cumulative daily use of asneeded B-agonist inhalers Dose-response Investigated? No Lags Considered: Lag 0, Lag 1, 2-day

ma Pollutant: PM 2.5 PM Component: OC Personal Exposure Averaging Time: 24 h

Riverside Mean (SD): 5.63 (2.59) 50th(Median): 4.98 Range (Min, Max): 1.94, 12.38

Whittier Mean (SD): 6.81 (3.45) 50th(Median): 6.43 Range (Min, Max): 2.18, 31.5

Central Site Averaging Time: 24 h

Riverside Mean (SD): 6.88 (1.86)

Percentiles: 50th

Median: 6.07 Range (Min, Max): 4.11, 11.62

Whittier Mean (SD): 3.93 (1.49) 50th(Median): 3.76 Range (Min, Max): 1.64, 8.82 Monitoring Stations : 48 personal nephelometers,

2 central sites Copollutant (correlation): Personal 24-h personal PM 2.5 0.15 24-h personal EC 0.41 24-h personal OC 1.00 24-h personal NO 2 0.20 24-h central PM 2.5 -0.11 24-h central EC 0.03 24-h central OC -0.02 24-h central NO 2 0.21 Central 24-h personal PM 2.5 0.21 24-h personal EC -0.01 24-h personal OC -0.02 24-h personal NO 2 0.17 24-h central PM 2.5 0.66 24-h central EC 0.87 24-h central OC 1.00 24-h central NO 2 0.62 PM Increment: IQR increase (Riverside: 28.41 μg/m 3 , Whittier 21.87 μg/m 3 )

Mixed-model estimates of the association between personal and central-site air pollutant exposure and FENO Lag 0 Personal 0.51 (-0.28, 1.30) Central 0.93 (-0.20, 2.06)

Lag 1 Personal 0.13 (-0.77, 1.03) Central0.51 (-0.64, 1.66)

2-day ma Personal 0.94 (-0.47, 2.35) Central 1.6 (-0.17, 3.37) Stratified by Medication Use

Lag = 2-day ma. Not Taking Anti-Inflamm. Medication Personal 0.88 (-1.62, 3.38) Central 0.36 (-4.07, 4.79) Taking Anti-Inflamm. Medication Personal 0.87 (-0.79, 2.53) Central 2.05 (0.24, 3.86) Inhaled Corticosteroids Personal 2.47 (0.30, 4.64) Central 1.96 (0.14, 3.78) Antileukotrienes +- inhaled corticosteroids Personal 0.52 (-1.99, 3.02) Central 1.29 (-2.58, 5.15) Notes: Fig of Estimated lag effect of hourly personal PM 2.5 on FENO. Fig of the Estimated lag effect of hourly personal PM 2.5 on FENO by use of medications. Fig of one- and two-pollutant models for change in FENO using 2-day Ma personal and central-site pollutant measurements



### December 2009 E-181

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Dubowsky et al. (2006, 088750 ) Period of Study: Mar 2002



# - Jun 2002

Location: St. Louis, Missouri Outcome: Chronic inflammation, Diabetes, Obesity, Hypertension, Cardiac Risk Study Design: Prospective Cohort Statistical Analyses: Poisson, LOESS Age Groups :

≥ 60 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD) unit: 16 (6.0) Range (Min, Max): 6.5, 28 Copollutants:

BC

CO

NO 2 SO 2 O 3 Increment: 5.4 μg/m 3 % Increase (Lower CI, Upper CI) Lag % increase in inflammatory response and exposure to PM 2.5 in people ≥ 60 Inflammatory Marker: IL-6: -8 (-16, 8) 1: -6 (-10, 5) 2: -5 (-11, 6) 3: -3 (-9, 6) 4: -4 (-12, 10) 5: -5 (-13, 8) 6: -6 (-14, 9) 7 CRP: -2 (-22, 15) 1: 3 (-8, 17) 2: 4 (-9, 20) 3: 9 (-4, 27) 4: 11 (-5, 35) 5: 8 (-9, 29) 6: 5 (-12, 26) 7 WBC: 0 (-2, 4) 1: 1 (-1, 2) 2: 2 (-1, 3) 3: 1 (-2, 5) 4: 3 (-1, 10) 5: 5 (0, 12) 6: 8 (0, 14) 7 % Increase in inflammatory responses and exposure to ambient PM 2.5 concentrations in people ≥ 60 Inflammatory Marker: CRP All conditions*: 14 (-5.4, 37) 0-5 avg 3 conditions met*: 81 (21, 172) 0-5 avg 2 conditions met*: 11 (-7.3, 33) 0-5 avg IL-6 All conditions*: -2.1 (-13, 11) 0-5 avg 3 conditions met*: 23 (-5.3, 59) 0-5 avg 2 conditions met*: -3.1 (-14, 9.7) 0-5 avg WBC All conditions*: 3.4 (-1.8, 8.9) 0-5 avg 3 conditions met*: 0.4 (-8.8, 11) 0-5 avg 2 conditions met*: 3.6 (-1.7, 9.1) 0-5 avg * All conditions met means model is adjusted for sex, obesity, diabetes, smoking history, ambient and microenvironmental apparent temperature, mold, pollen, trip, h, and vitamins.

Three conditions met means model is adjusted for three of the variables.

Two conditions met means model is adjusted for 2 of the variables.



### December 2009 E-182

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ebelt et al. (2005, 056907 ) Period of Study: Summer of 1998

Location: Vancouver, Canada Outcome: spirometry, Age Groups : range from 54-86 yr Mean age= 74 yr Study Design: extended analysis of a repeated-measures panel study

N: 16 persons with COPD Statistical Analyses: Earlier analysis expanded by developing mixed-effect regression models and by evaluating additional exposure indicators Dose-response Investigated? No Statistical Package : SAS V8 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Ambient PM 2.5 : 11.4 (4.6) Exposure to ambient PM 2.5 : 7.9 (3.7) Nonsulfate ambient PM 2.5 : 9.3 (3.7) Exposure to nonsulfate ambient PM 2.5 : 6.5 (3.0) Total exposure to PM 2.5 : 18.5 (14.9) Exposure to nonambient PM 2.5 : 10.6 (14.5) Range (Min, Max): Ambient PM 2.5 : (4.2-28.7) Exposure to ambient PM 2.5 : (0.9-21.3) Nonsulfate ambient PM 2.5 : (3.3-23.3) Exposure to nonsulfate ambient PM 2.5 : (0.7-16.9) Total exposure to PM 2.5 : (2.2-90.9) Exposure to nonambient PM 2.5 : (-2.6- 85.0) Monitoring Stations : 5 Copollutant (correlation): Ambient PM 10 : r= 0.78 Ambient PM 10-2.5 : r= 0.15 Ambient Sulfate- 0.82 Nonsufate Ambient PM 2.5 : r= 0.98 PM Increment: Ambient PM 2.5 : 5.8 (IQR) Exposure to ambient PM 2.5 : 4.4 (IQR)

Nonsulfate ambient PM 2.5 : 4.2 (IQR) Exposure to nonsulfate ambient PM 2.5 : 3.4 (IQR) Total exposure to PM 2.5 : 10.1 (IQR) Exposure to nonambient PM 2.5 : 8.9 (IQR)

Notes: Effect estimates are presented in Fig 2 and Electronic Appendix Table 1 (only available with electronic version of article) and not provided quantitatively elsewhere.

Reference: Ebelt et al. (2005, 056907 ) Period of Study: Summer of 1998

Location: Vancouver, Canada Outcome: spirometry Age Groups : Range from 54-86 yr Mean age= 74 yr Study Design: extended analysis of a repeated-measures panel study

N: 16 persons with COPD Statistical Analyses: Earlier analysis expanded by developing mixed-effect regression models and by evaluating additional exposure indicators Dose-response Investigated? No Statistical Package : SAS V8 Pollutant: Sulfate (SO 4 ) Averaging Time: 24 h Mean (SD): Ambient Sulfate: 2.0 (1.1) Exposure to Ambient Sulfate: 0.2 (4.7) Range (Min, Max): Ambient Sulfate: (0.4-5.4) Exposure to ambient Sulfate: (0.2-4.7) Monitoring Stations : 5 Copollutant (correlation): Ambient PM 2.5 : r= 0.82 Nonsulfate Ambient PM : r= 0.74 2.5 Exposure to Ambient Sulfate: r= 0.82 PM Increment: Ambient Sulfate: 1.5 (IQR) Exposure to Ambient Sulfate: 0.9 (IQR)

Notes: Effect estimates are presented in Fig 2 and Electronic Appendix Table 1 (only available with electronic version of article) and not provided quantitatively elsewhere.

Reference: Ferdinands et al. (2008, 156433 ) Period of Study: Aug 2004

Location: Atlanta, Georgia Outcome: Respiratory Symptoms, airway inflammation Study Design: Prospective cohort Statistical Analyses: Pearson Correlation Analysis Age Groups : 14-18 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD) unit: 27.2 (11.9) Range (Min, Max): 21.7, 34.7 Copollutants (correlation): O 3 : r= 0.8-0.9 The study presents results qualitatively not quantitatively.

Reference: Gent et al. (2003, 052885 ) Period of Study: Apr-Sep 2001

Location: Connecticut Springfield, MA Outcome: Respiratory symptoms including: Wheeze, persistent cough, chest tightness, shortness of breath Age Groups : Infants Study Design: 1-yr prospective cohort study

N: 1002 infants

17160 observations Statistical Analyses: Logistic regression analysis

GEEs

Tests for linear trend Test for goodness of fit

Hosmer-Lemeshow statistic for regression Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 13.1 (7.9) Percentiles : 20th: 6.9 40th: 9.0 50th(Median): 10.3 60th: 12.1 80th: 19.0 Range (Min, Max): 3.7, 44.2 Monitoring Stations : 4 sites Copollutant (correlation): Temperature: 0.58 PM Increment: 12 μg/m 3 same day 19 μg/m 3 previous day Model 5 (same day) Wheeze <6.9 = 1.00 6.9-8.9 = 0.95 (0.83, 1.10) 9.0-12.0 = 1.04 (0.89, 1.20) 12.1-18.9 = 1.05 (0.92, 1.20) ≥ 19.0 = 0.93 (0.78, 1.11) Persistent Cough <6.9 =1.00 6.9-8.9 = 0.95 (0.87, 1.04) 9.0-12.0 = 0.96 (0.87, 1.06) 12.1-18.9 = 1.00 (0.91, 1.09) ≥ 19.0 = 0.95 (0.83, 1.09) Chest Tightness <6.9 = 1.00 6.9-8.9 = 1.01 (0.86, 1.19) 9.0-12.0 = 1.06 (0.89, 1.26) 12.1-18.9 = 1.24 (1.06, 1.45) ≥ 19.0 = 1.05 (0.84, 1.33) Shortness of Breath <6.9 = 1.00 6.9-8.9 = 1.01 (0.87, 1.17) 9.0-12.0 = 1.03 (0.87, 1.22)



### December 2009 E-183

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Covariates: Temperature Dose-response Investigated? No Statistical Package : SAS Lags Considered: 1-day lag 12.1-18.9 = 1.07 (0.91, 1.25) ≥ 19.0 = 1.03 (0.83, 1.28) Bronchodilator <6.9 = 1.00 6.9-8.9 = 1.04 (0.99, 1.09) 9.0-12.0 = 1.02 (0.96, 1.08) 12.1-18.9 = 1.04 (0.99, 1.09) ≥ 19.0 = 1.02 (0.97, 1.08) Model 6 (previous day) Wheeze <6.9 = 1.00 6.9-8.9 = 1.06 (0.95, 1.20) 9.0-12.0 = 1.09 (0.94, 1.28) 12.1-18.9 = 1.03 (0.89, 1.19) ≥ 19.0 = 1.14 (0.97, 1.34) Persistent Cough <6.9 =1.00 6.9-8.9 = 1.04 (0.94, 1.14) 9.0-12.0 = 1.05 (0.94, 1.17) 12.1-18.9 = 1.03 (0.94, 1.14) ≥ 19.0 = 1.12 (1.02 1.24) Chest Tightness <6.9 = 1.00 6.9-8.9 = 1.03 (0.87, 1.23) 9.0-12.0 = 1.04 (0.85, 1.27) 12.1-18.9 = 1.00 (0.84, 1.19) ≥ 19.0 = 1.21 (1.00, 1.46) Shortness of Breath <6.9 = 1.00 6.9-8.9 = 1.00 (0.84, 1.19) 9.0-12.0 = 1.09 (0.90, 1.31) 12.1-18.9 = 1.09 (0.90, 1.31) ≥ 19.0 = 1.26 (1.02, 1.54) Bronchodilator <6.9 = 1.00 6.9-8.9 = 0.98 (0.94, 1.03) 9.0-12.0 = 0.99 (0.95, 1.03) 12.1-18.9 = 0.97 (0.94, 1.01) ≥ 19.0 = 0.99 (0.95, 1.04) PM 2.5 + O 3 : Medication Users: Same-day Wheeze <6.9 = 1.00 6.9-8.9 = 0.89 (0.75, 1.29) 9.0-12.0 = 1.02 (0.87, 1.19) 12.1-18.9 = 0.94 (0.77, 1.15) ≥ 19.0 = 0.83 (0.65, 1.06) Persistent Cough <6.9 = 1.00 6.9-8.9 = 0.95 (0.84, 1.06) 9.0-12.0 = 0.97 (0.86, 1.10) 12.1-18.9 = 0.94 (0.77, 1.15) ≥ 19.0 = 0.83 (0.65, 1.06) Chest Tightness <6.9 = 1.00 6.9-8.9 = 0.90 (0.74, 1.09) 9.0-12.0 = 0.97 (0.79, 1.18) 12.1-18.9 = 0.97 (0.76, 1.25) ≥ 19.0 = 0.76 (0.54, 1.05) Shortness of Breath <6.9 = 1.00 6.9-8.9 = 0.95 (0.80, 1.12) 9.0-12.0 = 1.00 (0.82, 1.21) 12.1-18.9 = 0.90 (0.73, 1.12) ≥ 19.0 = 0.87 (0.65, 1.17) Bronchodilator <6.9 = 1.00 6.9-8.9 = 1.03 (0.98, 1.08) 9.0-12.0 = 1.01 (0.96, 1.07) 12.1-18.9 = 1.02 (0.95, 1.08) ≥ 19.0 = 0.99 (0.91, 1.07) Previous Day Wheeze <6.9 = 1.00 6.9-8.9 = 1.03 (0.89, 1.18) 9.0-12.0 = 1.05 (0.88, 1.24) 12.1-18.9 = 0.98 (0.82, 1.17) ≥ 19.0 = 1.05 (0.85, 1.29) Persistent Cough <6.9 = 1.00 6.9-8.9 = 0.99 (0.89, 1.11) 9.0-12.0 = 0.98 (0.86, 1.10) 12.1-18.9 = 0.95 (0.83, 1.10) ≥ 19.0 = 1.00 (0.88, 1.15) Chest Tightness <6.9 = 1.00 6.9-8.9 = 0.89 (0.72, 1.10) 9.0-12.0 = 0.90 (0.70, 1.16) 12.1-18.9 = 0.81 (0.63, 1.03) ≥ 19.0 = 0.91 (0.71, 1.17) Shortness of Breath <6.9 = 1.00 6.9-8.9 = 0.96 (0.78, 1.18)



### December 2009 E-184

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 9.0-12.0 = 1.00 (0.81, 1.25) 12.1-18.9 = 0.96 (0.74, 1.24) ≥ 19.0 = 1.20 (0.94, 1.52) Bronchodilator <6.9 = 1.00 6.9-8.9 = 0.99 (0.94, 1.04) 9.0-12.0 = 0.97 (0.93, 1.02) 12.1-18.9 = 0.96 (0.91, 1.02) ≥ 19.0 = 0.97 (0.89, 1.04) PM 2.5 + O 3 : Non-users: Same-day Wheeze <6.9 = 1.00 6.9-8.9 = 0.92 (0.72, 1.17) 9.0-12.0 = 1.08 (0.85, 1.36) 12.1-18.9 = 0.94 (0.73, 1.22) ≥ 19.0 = 1.15 (0.75, 1.75) Persistent Cough <6.9 = 1.00 6.9-8.9 = 0.96 (0.83, 1.12) 9.0-12.0 = 1.02 (0.89, 1.18) 12.1-18.9 = 0.93 (0.78, 1.12) ≥ 19.0 = 1.07 (0.85, 1.34) Chest Tightness <6.9 = 1.00 6.9-8.9 = 0.84 (0.54, 1.31) 9.0-12.0 = 1.09 (0.74, 1.61) 12.1-18.9 = 0.78 (0.47, 1.30) ≥ 19.0 = 0.71 (0.36, 1.39) Shortness of Breath <6.9 = 1.00 6.9-8.9 = 0.61 (0.39, 0.95) 9.0-12.0 = 1.13 (0.85, 1.50) 12.1-18.9 = 0.72 (0.42, 1.23) ≥ 19.0 = 1.17 (0.72, 1.90) Bronchodilator Use: <6.9 = 1.00 6.9-8.9 = 0.95 (0.78, 1.15) 9.0-12.0 = 0.95 (0.78, 1.16) 12.1-18.9 = 0.85 (0.69, 1.06) ≥ 19.0 = 0.99 (0.76, 1.30) Previous-day Wheeze <6.9 = 1.00 6.9-8.9 = 1.01 (0.78, 1.31) 9.0-12.0 = 1.15 (0.88, 1.51) 12.1-18.9 = 1.08 (0.78, 1.51) ≥ 19.0 = 1.18 (0.71, 1.97) Persistent Cough <6.9 = 1.00 6.9-8.9 = 1.07 (0.94, 1.22) 9.0-12.0 = 1.13 (0.97, 1.32) 12.1-18.9 = 1.03 (0.87, 1.22) ≥ 19.0 = 1.14 (0.88, 1.46) Chest Tightness <6.9 = 1.00 6.9-8.9 = 1.44 (0.90, 2.30) 9.0-12.0 = 1.50 (0.97, 2.33) 12.1-18.9 = 1.56 (0.91, 2.66) ≥ 19.0 = 1.76 (0.83, 3.73) Shortness of Breath <6.9 = 1.00 6.9-8.9 = 0.99 (0.75, 1.30) 9.0-12.0 = 1.30 (0.88, 1.91) 12.1-18.9 = 0.84 (0.57, 1.24) ≥ 19.0 = 1.48 (0.94, 2.34) Bronchodilator Use <6.9 = 1.00 6.9-8.9 = 1.05 (0.85, 1.34) 9.0-12.0 = 1.28 (1.01, 1.62) 12.1-18.9 = 1.05 (0.80, 1.37) ≥ 19.0 = 1.19 (0.83, 1.71) Notes: Line graphs of daily levels of O 3 and PM 2.5 and daily temperature with daily prevalence of respiratory symptoms for users of asthma maintenance medication

Reference: Gent et al, (2009, 180399 ) Period of Study: 2000-2003

Location: New Haven County CT Outcome: Increased asthma symptoms and medication use Study Design: Panel

Covariates: Season, day of the week, date Statistical Analysis: Logistic regression Statistical Package: SAS Pollutant: PM 2.5 and components Averaging Time: Daily

Mean: (estimated sources, μg/m 3 )

Motor Vehicle: 6.6

Road Dust: 2.3

Sulfur: 5.5 Odds Ratio and p-value for sources and components of PM 2.5.

Lags are 0, 1 or 2 days, and the mean of days 0-2 (L02).

Source: Motor Vehicle EC, Increment = 1000 ng/m 3 Wheeze L0: 1.04, p = 0.04 L1: 1.01, p = 0.70



### December 2009 E-185

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Age Groups: Children aged 4-12 Biomass Burning: 0.9

Oil: 0.8

Sea Salt: 0.5 Range (Min, Max): NR Copollutant (correlation): NR L2: 1.00, p = 0.99 L02: 1.07, p = 0.06 Persistent Cough L0: 1.01, p = 0.42 L1: 1.01, p = 0.38 L2: 0.99, p = 0.44 L02: 1.03, p = 0.23 Shortness of Breath L0: 1.06, p = 0.001 L1: 1.01, p = 0.65 L2: 1.01, p = 0.63 L02: 1.12, p = 0.01 Chest Tightness L0: 1.03, p = 0.20 L1: 1.02, p = 0.24 L2: 1.01, p = 0.59 L02: 1.10, p = 0.04 Inhaler Use L0: 1.01, p = 0.15 L1: 1.00, p = 0.72 L2: 1.00, p = 0.75 L02: 1.02, p = 0.40 Zn, Increment = 10 ng/m 3 Wheeze L0: 1.00, p = 0.69 L1: 0.99, p = 0.54 L2: 1.00, p = 0.89 L02: 1.00, p = 0.98 Persistent Cough L0: 1.00, p = 0.60 L1: 1.00, p = 0.77 L2: 0.99, p = 0.24 L02: 1.00, p = 0.94 Shortness of Breath L0: 1.02, p = 0.001 L1: 1.00, p = 0.57 L2: 1.01, p = 0.49 L02: 1.04, p = 0.06 Chest Tightness L0: 1.00, p = 0.72 L1: 1.00, p = 0.96 L2: 1.01, p = 0.38 L02: 1.03, p = 0.13 Inhaler Use L0: 1.00, p = 0.41 L1: 1.00, p = 0.44 L2: 1.00, p = 0.52 L02: 1.01, p = 0.53 Pb, Increment = 5 ng/m 3 Wheeze L0: 1.02, p = 0.31 L1: 1.00, p = 0.91 L2: 1.01, p = 0.62 L02: 1.07, p = 0.13 Persistent Cough L0: 1.02, p = 0.25 L1: 1.00, p = 0.88 L2: 1.00, p = 0.87 L02: 1.05, p = 0.12 Shortness of Breath L0: 1.03, p = 0.11 L1: 0.98, p = 0.51 L2: 1.03, p = 0.05 L02: 1.12, p = 0.01 Chest Tightness L0: 1.02, p = 0.31 L1: 0.99, p = 0.79 L2: 1.03, p = 0.13 L02: 1.10, p = 0.02 Inhaler Use L0: 1.01, p = 0.06 L1: 0.98, p = 0.11 L2: 1.02, p = 0.04 L02: 1.04, p = 0.10 Cu, Increment = 5 ng/m 3 Wheeze



### December 2009 E-186

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) L0: 1.01, p = 0.59 L1: 0.99, p = 0.55 L2: 0.99, p = 0.82 L02: 1.02, p = 0.67 Persistent Cough L0: 1.02, p = 0.13 L1: 1.02, p = 0.21 L2: 0.98, p = 0.26 L02: 1.05, p = 0.04 Shortness of Breath L0: 1.06, p = 0.01 L1: 1.01, p = 0.74 L2: 0.96, p = 0.10 L02: 1.06, p = 0.21 Chest Tightness L0: 10.3, p = 0.23 L1: 1.02, p = 0.42 L2: 0.97, p = 0.17 L02: 1.04, p = 0.39 Inhaler Use L0: 1.01, p = 0.22 L1: 0.99, p = 0.37 L2: 1.00, p = 0.70 L02: 1.01, p = 0.46 Se, Increment = 1 ng/m 3 Wheeze L0: 1.00, p = 0.97 L1: 0.99, p = 0.52 L2: 1.00, p = 0.91 L02: 1.02, p = 0.71 Persistent Cough L0: 1.00, p = 0.84 L1: 0.99, p = 0.32 L2: 1.00, p = 0.93 L02: 0.98, p = 0.43 Shortness of Breath L0: 1.02, p = 0.40 L1: 0.97, p = 0.10 L2: 1.01, p = 0.55 L02: 1.02, p = 0.67 Chest Tightness L0: 1.00, p = 0.79 L1: 0.97, p = 0.13 L2: 1.01, p = 0.72 L02: 0.98, p = 0.61 Inhaler Use L0: 0.99, p = 0.20 L1: 1.01, p = 0.02 L2: 0.99, p = 0.32 L02: 0.99, p = 0.75 Source: Road Dust Si, Increment = 100 ng/m 3 Wheeze L0: 1.03, p = 0.03 L1: 1.00, p = 0.99 L2: 1.02, p = 0.26 L02: 1.07, p = 0.04 Persistent Cough L0: 1.02, p = 0.01 L1: 1.00, p = 0.78 L2: 1.01, p = 0.60 L02: 1.05, p = 0.02 Shortness of Breat1.04, p = 0.01h L0: 1.04, p = 0.01 L1: 1.01, p = 0.60 L2: 1.01, p = 0.63 L02: 1.08, p = 0.02 Chest Tightness L0: 1.02, p = 0.20 L1: 1.02, p = 0.17 L2: 1.00, p = 0.88 L02: 1.06, p = 0.10 Inhaler Use L0: 1.02, p = 0.004 L1: 0.99, p = 0.18 L2: 1.01, p = 0.45



### December 2009 E-187

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) L02: 1.03, p = 0.09 Fe, Increment = 100 ng/m 3 Wheeze L0: 1.04, p = 0.02 L1: 1.00, p = 0.80 L2: 1.00, p = 0.87 L02: 1.07, p = 0.05 Persistent Cough L0: 1.02, p = 0.06 L1: 1.01, p = 0.52 L2: 0.99, p = 0.52 L02: 1.04, p = 0.04 Shortness of Breath L0: 1.06, p = 0.002 L1: 1.01, p = 0.65 L2: 0.98, p = 0.27 L02: 1.08, p = 0.04 Chest Tightness L0: 1.01, p = 0.47 L1: 1.02, p = 0.22 L2: 0.98, p = 0.35 L02: 1.05, p = 0.21 Inhaler Use L0: 1.02, p = 0.004 L1: 0.99, p = 0.44 L2: 1.00, p = 0.91 L02: 1.03, p = 0.08 Al, Increment = 50 ng/m 3 Wheeze L0: 1.02, p = 0.17 L1: 1.01, p = 0.73 L2: 1.02, p = 0.30 L02: 1.07, p = 0.03 Persistent Cough L0: 1.03, p = 0.001 L1: 1.00, p = 0.96 L2: 1.00, p = 0.68 L02: 1.06, p = 0.01 Shortness of Breath L0: 1.05, p = 0.002 L1: 1.01, p = 0.63 L2: 1.01, p = 0.59 L02: 1.09, p = 0.004 Chest Tightness L0: 1.02, p = 0.21 L1: 1.02, p = 0.18 L2: 1.00, p = 0.94 L02: 1.07, p = 0.04 Inhaler Use L0: 1.02, p = 0.02 L1: 0.99, p = 0.27 L2: 1.01, p = 0.50 L02: 1.02, p = 0.11 Ca, Increment = 50 ng/m 3 Wheeze L0: 1.07, p = 0.02 L1: 1.00, p = 0.97 L2: 1.01, p = 0.74 L02: 1.14, p = 0.04 Persistent Cough L0: 1.05, p = 0.01 L1: 0.99, p = 0.64 L2: 1.00, p = 0.90 L02: 1.09, p = 0.03 Shortness of Breath L0: 1.10, p = 0.002 L1: 1.02, p = 0.66 L2: 1.00, p = 0.89 L02: 1.18, p = 0.01 Chest Tightness L0: 1.04, p = 0.26 L1: 1.03, p = 0.43 L2: 1.00, p = 0.93 L02: 1.14, p = 0.07 Inhaler Use L0: 1.04, p = 0.01



### December 2009 E-188

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) L1: 0.97, p = 0.06 L2: 1.01, p = 0.44 L02: 1.04, p = 0.17 Ba, Increment = 10 ng/m 3 Wheeze L0: 0.99, p = 0.57 L1: 1.00, p = 0.92 L2: 0.99, p = 0.48 L02: 0.99, p = 0.81 Persistent Cough L0: 1.00, p = 0.83 L1: 1.01, p = 0.38 L2: 0.99, p = 0.32 L02: 1.00, p = 0.81 Shortness of Breath L0: 1.04, p = 0.02 L1: 1.00, p = 0.96 L2: 0.96, p = 0.05 L02: 1.03, p = 0.38 Chest Tightness L0: 1.01, p = 0.63 L1: 1.00, p = 0.88 L2: 0.98, p = 0.30 L02: 1.02, p = 0.51 Inhaler Use L0: 1.01, p = 0.08 L1: 0.99, p = 0.19 L2: 1.00, p = 0.92 L02: 1.01, p = 0.36 Ti, Increment = 5 ng/m 3 Wheeze L0: 1.00, p = 0.59 L1: 0.99, p = 0.49 L2: 1.01, p = 0.34 L02: 1.01, p = 0.56 Persistent Cough L0: 1.00, p = 0.57 L1: 1.00, p = 0.55 L2: 1.00, p = 0.30 L02: 1.01, p = 0.29 Shortness of Breath L0: 1.01, p = 0.01 L1: 1.00, p = 0.56 L2: 1.00, p = 0.60 L02: 1.03, p = 0.05 Chest Tightness L0: 1.00, p = 0.34 L1: 1.00, p = 0.55 L2: 0.99, p = 0.49 L02: 1.01, p = 0.52 Inhaler Use L0: 1.00, p = 0.72 L1: 1.00, p = 0.30 L2: 1.00, p = 0.67 L02: 1.00, p = 0.66

Source: Sulfur S, Increment = 1000 ng/m 3 Wheeze L0: 0.98, p = 0.43 L1: 0.99, p = 0.62 L2: 1.02, p = 0.29 L02: 1.00, p = 0.99 Persistent Cough L0: 1.00, p = 0.84 L1: 1.00, p = 0.69 L2: 1.02, p = 0.21 L02: 1.02, p = 0.27 Shortness of Breath L0: 1.01, p = 0.63 L1: 0.99, p = 0.71 L2: 1.01, p = 0.55 L02: 1.01, p = 0.79 Chest Tightness L0: 0.99, p = 0.80 L1: 1.01, p = 0.62



### December 2009 E-189

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) L2: 1.01, p = 0.81 L02: 1.02, p = 0.68 Inhaler Use L0: 0.99, p = 0.13 L1: 1.00, p = 0.81 L2: 1.02, p = 0.04 L02: 1.00, p = 0.81 P, Increment = 50 ng/m 3 Wheeze L0: 0.98, p = 0.39 L1: 0.98, p = 0.48 L2: 1.02, p = 0.38 L02: 0.99, p = 0.89 Persistent Cough L0: 1.00, p = 0.75 L1: 0.99, p = 0.69 L2: 1.01, p = 0.38 L02: 1.03, p = 0.30 Shortness of Breath L0: 1.01, p = 0.61 L1: 0.99, p = 0.71 L2: 1.01, p = 0.67 L02: 1.01, p = 0.78 Chest Tightness L0: 1.00, p = 0.88 L1: 1.01, p = 0.72 L2: 1.00, p = 0.87 L02: 1.02, p = 0.67 Inhaler Use L0: 0.98, p = 0.15 L1: 1.00, p = 0.83 L2: 1.01, p = 0.11 L02: 1.00, p = 0.99 Source: Biomass Burning K, Increment = 50 ng/m 3 Wheeze L0: 0.98, p = 0.06 L1: 0.99, p = 0.43 L2: 1.00, p = 0.85 L02: 0.96, p = 0.04 Persistent Cough L0: 1.00, p = 0.64 L1: 1.00, p = 0.83 L2: 1.00, p = 0.46 L02: 1.00, p = 0.86 Shortness of Breath L0: 1.01, p = 0.01 L1: 0.98, p = 0.09 L2: 1.00, p = 0.38 L02: 1.00, p = 0.79 Chest Tightness L0: 1.00, p = 0.02 L1: 0.99, p = 0.24 L2: 0.98, p = 0.07 L02: 0.99, p = 0.67 Inhaler Use L0: 1.00, p = 0.68 L1: 0.99, p = 0.05 L2: 1.00, p = 0.59 L02: 0.99, p = 0.28

Source: Oil V, Increment = 10 ng/m 3 Wheeze L0: 0.99, p = 0.73 L1: 0.96, p = 0.03 L2: 0.99, p = 0.56 L02: 0.93, p = 0.04 Persistent Cough L0: 1.01, p = 0.56 L1: 0.99, p = 0.24 L2: 0.98, p = 0.01 L02: 0.96, p = 0.05 Shortness of Breath L0: 1.01, p = 0.46 L1: 0.98, p = 0.24



### December 2009 E-190

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) L2: 1.00, p = 0.83 L02: 0.98, p = 0.58 Chest Tightness L0: 0.99, p = 0.71 L1: 0.98, p = 0.32 L2: 0.98, p = 0.23 L02: 0.94, p = 0.12 Inhaler Use L0: 0.98, p = 0.12 L1: 1.00, p = 0.68 L2: 0.99, p = 0.22 L02: 0.96, p = 0.03 Ni, Increment = 5 ng/m 3 Wheeze L0: 1.01, p = 0.59 L1: 0.97, p = 0.09 L2: 1.00, p = 0.76 L02: 0.99, p = 0.72 Persistent Cough L0: 1.01, p = 0.21 L1: 0.99, p = 0.57 L2: 0.99, p = 0.23 L02: 1.00, p = 0.99 Shortness of Breath L0: 1.04, p = 0.05 L1: 0.98, p = 0.36 L2: 1.00, p = 0.81 L02: 1.04, p = 0.32 Chest Tightness L0: 1.01, p = 0.58 L1: 1.00, p = 0.89 L2: 0.98, p = 0.27 L02: 1.01, p = 0.84 Inhaler Use L0: 1.01, p = 0.48 L1: 1.00, p = 0.83 L2: 0.99, p = 0.51 L02: 1.01, p = 0.48

Source: Sea Salt Na, Increment = 100 ng/m 3 Wheeze L0: 0.98, p = 0.23 L1: 1.00, p = 0.80 L2: 1.00, p = 0.88 L02: 0.97, p = 0.29 Persistent Cough L0: 1.00, p = 0.58 L1: 0.99, p = 0.19 L2: 1.00, p = 0.61 L02: 0.98, p = 0.21 Shortness of Breath L0: 1.00, p = 0.94 L1: 0.99, p = 0.46 L2: 1.01, p = 0.63 L02: 0.99, p = 0.74 Chest Tightness L0: 0.99, p = 0.43 L1: 0.99, p = 0.75 L2: 1.00, p = 0.88 L02: 0.98, p = 0.61 Inhaler Use L0: 0.99, p = 0.35 L1: 1.00, p = 0.61 L2: 1.00, p = 0.85 L02: 0.99, p = 0.37 Cl, Increment = 10 ng/m 3 Wheeze L0: 1.00, p = 0.89 L1: 1.00, p = 0.88 L2: 1.00, p = 0.38 L02: 1.00, p = 0.81 Persistent Cough L0: 1.00, p = 0.31 L1: 1.00, p = 0.31 L2: 1.00, p = 0.51



### December 2009 E-191

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) L02: 1.00, p = 0.06 Shortness of Breath L0: 1.00, p = 0.89 L1: 1.00, p = 0.94 L2: 1.00, p = 0.70 L02: 1.00, p = 0.80 Chest Tightness L0: 1.00, p = 0.24 L1: 1.00, p = 0.28 L2: 1.00, p = 0.52 L02: 1.00, p = 0.65 Inhaler Use L0: 1.00, p = 0.69 L1: 1.00, p = 0.52 L2: 1.00, p = 0.51 L02: 1.00, p = 0.83 Odds Ratio (95%CI) from repeated measures logistic regression models of respiratory symptoms and daily source concentrations of PM 2.5 . Lag 0 Model Wheeze, p = 0.23 Motor Vehicle: 1.05 (0.99-1.10) Road Dust: 1.10 (1.01-1.19) Sulfur: 0.97 (0.94-1.00) Biomass Burning: 0.80 (0.66-0.98) Oil: 1.02 (0.86-1.20) Sea Salt: 0.96 (0.86-1.07) Persistent Cough, p < 0.001 Motor Vehicle: 1.02 (0.99-1.04) Road Dust: 1.06 (1.01-1.11) Sulfur: 1.00 (0.98-1.01) Biomass Burning: 0.97 (0.92-1.03) Oil: 1.02 (0.95-1.10) Sea Salt: 0.99 (0.92-1.07) Shortness of Breath, p < 0.001 Motor Vehicle: 1.06 (1.01-1.11) Road Dust: 1.12 (1.02-1.22) Sulfur: 0.98 (0.94-1.02) Biomass Burning: 1.05 (0.95-1.17) Oil: 1.07 (0.92-1.26) Sea Salt: 1.01 (0.92-1.12) Chest Tightness, p < 0.001 Motor Vehicle: 1.02 (0.97-1.08) Road Dust: 1.04 (0.95-1.15) Sulfur: 0.99 (0.94-1.03) Biomass Burning: 1.06 (0.95-1.18) Oil: 0.99 (0.82-1.18) Sea Salt: 0.95 (0.84-1.08)

Inhaler Use, p < 0.001 Motor Vehicle: 1.02 (1.00-1.05) Road Dust: 1.06 (1.02-1.11) Sulfur: 0.98 (0.97-1.00) Biomass Burning: 1.00 (0.96-1.03) Oil: 0.98 (0.91-1.05) Sea Salt: 0.99 (0.94-1.04)

Lag 02 Model Wheeze, p = 0.86 Motor Vehicle: 1.10 (1.01-1.19) Road Dust: 1.26 (1.05-1.51) Sulfur: 0.98 (0.92-1.04) Biomass Burning: 0.64 (0.46-0.88) Oil: 0.80 (0.56-1.08) Sea Salt: 0.91 (0.82-1.16) Persistent Cough, p < 0.001 Motor Vehicle: 1.03 (0.98-1.09) Road Dust: 1.16 (1.02-1.32) Sulfur: 1.01 (0.98-1.05) Biomass Burning: 0.93 (0.81-1.06) Oil: 0.84 (0.71-1.00) Sea Salt: 0.88 (0.77-1.01)



### December 2009 E-192

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Shortness of Breath, p = 0.006 Motor Vehicle: 1.12 (1.01-1.24) Road Dust: 1.28 (1.05-1.55) Sulfur: 0.97 (0.90-1.04) Biomass Burning: 0.78 (0.52-1.18) Oil: 0.94 (0.69-1.29) Sea Salt: 1.01 (0.79-1.29) Chest Tightness, p = 0.39 Motor Vehicle: 1.08 (0.98-1.20) Road Dust: 1.20 (0.97-1.49) Sulfur: 1.00 (0.92-1.08) Biomass Burning: 0.87 (0.62-1.22) Oil: 0.80 (0.58-1.10) Sea Salt: 0.95 (0.71-1.27)

Inhaler Use, p < 0.001 Motor Vehicle: 1.03 (0.98-1.08) Road Dust: 1.09 (1.00-1.19) Sulfur: 1.00 (0.97-1.03) Biomass Burning: 0.95 (0.87-1.04) Oil: 0.92 (0.81-1.05) Sea Salt: 0.97 (0.88-1.07) Odds Ratio (95%CI) from repeated measures logistic regression models of respiratory symptoms and daily source concentrations of PM 2.5 when copollutants are included.

Wheeze Motor Vehicle NO 2 : 1.03 (0.98-1.08) CO: 1.05 (0.99-1.11) SO 2 : 1.04 (0.99-1.09) O 3 : 1.06 (0.97-1.16) Road Dust NO 2 : 1.11 (1.02-1.20) CO: 1.10 (1.01-1.19) SO 2 : 1.10 (1.01-1.19) O 3 : 1.11 (1.01-1.23) Sulfur NO 2 : 0.96 (0.92-0.99) CO: 0.97 (0.94-1.01) SO 2 : 0.97 (0.93-1.00) O 3 : 0.95 (0.91-1.00) Biomass Burning NO 2 : 0.79 (0.65-0.98) CO: 0.80 (0.66-0.98) SO 2 : 0.79 (0.64-0.98) O 3 : 0.74 (0.57-0.97) Oil NO 2 : 1.02 (0.87-1.21) CO: 1.02 (0.86-1.20) SO 2 : 1.01 (0.86-1.19) O 3 : 0.92 (0.62-1.39) Sea Salt NO 2 : 0.96 (0.85-1.07) CO: 0.96 (0.86-1.08) SO 2 : 0.95 (0.85-1.07) O 3 : 1.01 (0.72-1.40)

Inhaler Use Motor Vehicle NO 2 : 1.02 (0.99-1.04) CO: 1.02 (0.99-1.05) SO 2 : 1.02 (0.99-1.04) O 3 : 1.02 (0.98-1.07) Road Dust NO 2 : 1.06 (1.02-1.10) CO: 1.06 (1.02-1.11) SO 2 : 1.06 (1.02-1.11) O 3 : 1.06 (1.00-1.13) Sulfur NO 2 : 0.98 (0.96-1.00) CO: 0.98 (0.96-1.00) SO 2 : 0.98 (0.96-1.00)



### December 2009 E-193

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

O 3 : 0.97 (0.95-1.00) Biomass Burning NO 2 : 1.00 (0.96-1.03) CO: 0.99 (0.96-1.03) SO 2 : 0.99 (0.96-1.03) O 3 : 0.99 (0.95-1.03) Oil NO 2 : 0.98 (0.91-1.05) CO: 0.97 (0.91-1.04) SO 2 : 0.97 (0.91-1.04) O 3 : 1.03 (0.88-1.22) Sea Salt NO 2 : 0.99 (0.94-1.04) CO: 0.99 (0.94-1.04) SO 2 : 0.99 (0.94-1.04) O 3 : 1.01 (0.88-1.15) Reference: Girardot et al. (2006, 088271 ) Period of Study: Aug 2002-Oct 2002 Jun 2003-Aug 2003

Location: Charlies Bunion Trail (portion of Appalachia Trail) Outcome: Pulmonary function/spirometry-FVC, FEV 1 , PEF, FVC/FEV 1 , FEF25-75 Age Groups : 18-82 yr Study Design: Cohort

N: 354 hikers Statistical Analyses: Multiple linear regression

Covariates: Age, h hiked, mean temperature, sex, smoking status, history of asthma or wheeze symptoms, carriage of backpack, whether reaching summit or not

Season: Fall 2002, Summer 2003 Dose-response Investigated? No Statistical Package : SAS Pollutant: PM 2.5 Averaging Time: 24 h

Mean:

Trail: 13.9 ± 8.2 Estimated personal: 15.0 ± 7.4 Range (Min, Max): Trail: 1.6 , 38.4 Estimated personal: 0.21, 41.9 Copollutant (correlation): O 3 (r=0.67, for estimated personal exposure) PM Increment: 1 μg/m 3 % Change ± CI p value Univariate: FVC: 0.023 ± 0.035 0.51 FEV : 0.015 ± 0.029 1 0.607 PEF: 0.185 ± 0.091 0.043 FVC/FEV 1 : 0.003 ± 0.023 0.905 FEF25-75%: 0.052 ± 0.093 0.578 Adjusted: FVC: 0.007 +/ 0.040 0.966 FEV : 0.003 ± 0.033 1 0.937 PEF: 0.258 ± 0.103 0.013 FVC/FEV 1 : - 0.011 ± 0.027 0.676 FEF25-75%: - 0.041 ± 0.109 0.707 Spirometry result for each quintile ± CI Quintile 1 (6.0 μg/m 3 ): FVC (L): Prehike: 4.32 ± 0.13 Posthike: 4.33 ± 0.12 FEV (L): Prehike: 3.39 ± 0.10 1 Posthike: 3.40 ± 0.10 FEV /FVC (%): Prehike: 78.66 ± 0.86 1 Posthike: 78.63 ± 0.81 FEF25-75% (L/sec): Prehike: 3.27 ± 0.14 Posthike: 3.26 ± 0.14 PEF (L/sec): Prehike: 7.91 +/ 0.22 Posthike: 7.58 ± 0.22 Quintile 2 (10.4 μg/m 3 ): FVC (L): Prehike: 4.30 ± 0.11 Posthike: 4.30 ± 0.11 FEV (L): Prehike: 3.42 ± 0.09 1 Posthike: 3.43 ± 0.09 FEV /FVC (%): Prehike: 79.37 ± 0.71 1 Posthike: 79.55 ± 0.69 FEF25-75% (L/sec): Prehike: 3.39 ± 0.14 Posthike: 3.38 ± 0.14 PEF (L/sec): Prehike: 8.37 +/ 0.23 Posthike: 8.26 ± 0.25 Quintile 3 (14.8 μg/m 3 ): FVC (L): Prehike: 4.34 ± 0.12 Posthike: 4.33 ± 0.12 FEV 1 (L): Prehike: 3.42 ± 0.10 Posthike: 3.40 ± 0.09 FEV 1 /FVC (%): Prehike: 79.20 ± 0.81 Posthike: 78.83 ± 0.80 FEF25-75% (L/sec): Prehike: 3.19 ± 0.13 Posthike: 3.21 ± 0.13 PEF (L/sec): Prehike: 8.12 +/ 0.25 Posthike: 7.89 ± 0.25 Quintile 4 (17.9 μg/m 3 ):



### December 2009 E-194

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) FVC (L): Prehike: 4.23 ± 0.11 Posthike: 4.23 ± 0.11 FEV 1 (L): Prehike: 3.36 ± 0.10 Posthike: 3.36 ± 0.10 FEV 1 /FVC (%): Prehike: 79.18 ± 0.81 Posthike: 79.26 ± 0.79 FEF25-75% (L/sec): Prehike: 3.34 ± 0.15 Posthike: 3.30 ± 0.15 PEF (L/sec): Prehike: 7.75 +/ 0.25 Posthike: 7.73 ± 0.26 Quintile 5 (25.6 μg/m 3 ): FVC (L): Prehike: 4.15 ± 0.11 Posthike: 4.18 ± 0.12 FEV 1 (L): Prehike: 3.31 ± 0.09 Posthike: 3.33 ± 0.10 FEV 1 /FVC (%): Prehike: 79.73 ± 0.66 Posthike: 79.55 ± 0.64 FEF25-75% (L/sec): Prehike: 3.22 ± 0.14 Posthike: 3.24 ± 0.14 PEF (L/sec): Prehike: 7.72 +/ 0.22 Posthike: 7.77 ± 0.23 Overall (15.0 μg/m 3 ): FVC (L): Prehike: 4.27 ± 0.05 Posthike: 4.27 ± 0.05 FEV 1 (L): Prehike: 3.38 ± 0.04 Posthike: 3.38 ± 0.04 FEV 1 /FVC (%): Prehike: 79.2 ± 0.34 Posthike: 79.2 ± 0.33 FEF25-75% (L/sec): Prehike: 3.28 ± 0.06 Posthike: 3.28 ± 0.06 PEF (L/sec): Prehike: 7.97 +/ 0.11 Posthike: 7.97 ± 0.11 Reference: Hertz-Picciotta et al. (2007, 135917 ) Period of Study: 1994-2003

Location: Teplice and Prachatice, Czech Republic Outcome: Lower respiratory illness-croup (J05, J04), acute bronchitis (J20), acute bronchiolitis (J21) Age Groups : Neonates followed for 2-4.5 yr Study Design: Cohort

N: 1133 children Statistical Analyses: Generalized linear longitudinal models

Covariates: District, mother’s age, mother’s education, mother or adult smoke, child’s sex, season, day of the week, fuel for heating and/or cooking, breastfeeding category, number of other children, temperature

Season: Winter, spring, summer and fall Dose-response Investigated? No Statistical Package : SUDAAN version 8 Lags Considered: 1-3, 1-7, 1-14, 1-30, 1-45 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): PAH: 22.3 (SD-16 for 3-day avg and 11 for 45-day avg) PM Increment: 25 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Birth-23 mo: 1.30 [1.08, 1.58] lag 1-30 2-4.5 yr: 1.23 [0.94, 1.62] lag 1-30 RR Estimate for categories of exposure [Lower CI, Upper CI] lag: Crude RR: Birth-23 mo: > 50 μg/m 3 : 2.26 [1.81, 2.82] lag 1-30 25-50 μg/m 3 : 1.48 [1.32, 1.65] lag 1-30 < 25 μg/m 3 : Referent 2-4.5 yr: > 50 μg/m 3 : 3.66 [2.07, 6.48] lag 1-30 25-50 μg/m 3 : 1.60 [1.41, 1.82] lag 1-30 < 25 μg/m 3 : Referent



### December 2009 E-195

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hertz- Picciotta et al. (2007, 135917 ) Period of Study: 1994-2003

Location: Teplice and Prachatice, Czech Republic Outcome: Lower respiratory illness-croup (J05, J04), acute bronchitis (J20), acute bronchiolitis (J21) Age Groups : Neonates followed for 2-4.5 yr Study Design: Cohort

N: 1133 children Statistical Analyses: Generalized linear longitudinal models

Covariates: District, mother’s age, mother’s education, mother or adult smoke, child’s sex, season, day of the week, fuel for heating and/or cooking, breastfeeding category, number of other children, temperature Dose-response Investigated? No Statistical Package : SUDAAN version 8 Lags Considered: 1-3, 1-7, 1-14, 1-30, 1-45 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD):

PAH: 52.5 ng/m 3 (SD-57 ng/m 3 for 3-day avg and 46 ng/m 3 for 45-day avg) PAH Increment: 100 ng/m 3 RR Estimate [Lower CI, Upper CI] lag: Birth-23 mos: 1.29 [1.07, 1.54] lag 1-30 2-4.5 yr: 1.56 [1.22, 2.00] lag 1-30 RR Estimate for categories of exposure [Lower CI, Upper CI] lag:

Crude RR: Birth-23 mos: > 100 ng/m 3 : 2.52 [2.22, 2.87] lag 1-30 40-100 ng/m 3 : 1.87 [1.65, 2.13] lag 1-30 < 40 ng/m 3 : Reference 2-4.5 yr: > 100 ng/m 3 : 2.26 [1.93, 2.65] lag 1-30 40-100 ng/m 3 : 1.40 [1.20, 1.64] lag 1-30 < 40 ng/m 3 : Reference

Reference: Hogervorst, et al. (2006, 156559 ) Period of Study: 2002

Location: Maastricht, the Netherlands (six schools selected) Outcome : Decreased lung function Age Groups : 8-13 yr Study Design: Multivariate linear regression (enter method) analysis

N: 342 children Statistical Analyses: ANOVA, chi square Covariates: Independent variables: Age, height, gender, smoking at home by parents, pets, use of ventilation hoods during cooking, presence of unvented geysers, tapestry in the home, indoor/outdoor time, education level of parents. Dependent variables: lung function indices Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): 19.0 (3.2) Monitoring Stations : 6 Copollutant:

PM 10 Total Suspended Particles (TSP) PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: FEV: 3.62 [0.50,7.63] lag NR FVC: 1.80 [-2.10, 5.80] lag NR FEF: 5.93 [-2.34, 14.89] lag NR

Reference: Holguin et al, (2007, 099000 ) Period of Study:

Location: Ciudad Juarez, Mexico Outcome: FeNO, FEV 1 Study Design: Panel

Covariates: sex, age, body mass index, day of week, season, yr of maternal and paternal education, passive smoking Statistical Analysis: linear and nonlinear mixed effects models Age Groups: 6-12 yr Pollutant: PM 2.5 Averaging Time: 48 h Mean (SD) Unit: 17.5 (8.9) μg/m 3 Range (Min, Max): NR Copollutant (correlation): NR Increment: NR Relative Risk (Min CI, Max CI) Lag Results not given in table form, but abstract states that no significant associations with PM 2.5 were observed.



### December 2009 E-196

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hong et al. (2007, 091347 ) Period of Study: Mar 23-May 2004

Location: School on the Dukjeok Island near Incheon City, Korea Outcome: Peak expiratory flow rate (PEFR) Age Groups : 3rd-6th grade (mean age=9.6 yr) Study Design: P anel study

N: 43 schoolchildren Statistical Analyses: Mixed linear regression

Covariates: age, sex, height, weight, asthma history, and passive smoking exposure at home Dose-response Investigated? No Lags Considered: 0, 1, 2, 3, 4, 5 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 20.27 (8.23) 50th(Median): 22.07 Range (Min, Max): 5.94-36.28 Copollutant: PM 10 Components of PM 10 (Fe, Mn, Pb, Zn, Al) Effect Estimate: Regression coefficients of morning and daily mean PEFR on PM 2.5 Lag 1 (PM 2.5 ) Morning PEFR Crude: ß= -0.14, p=0.12 Adjusted: ß= -0.54, p,0.01 Mean PEFR Crude: ß= -0.15, p=0.02 Adjusted: ß= -0.54, p,0.01 Regression coefficients of morning and daily mean PEFR on PM 2.5 and GSTM1 and GSTT1 genotype using linear mixed-effects regression Lag 1 (PM 2.5 ) Morning PEFR: ß= -0.57, p < 0.01 Mean PEFR: ß= -0.56, p < 0.01 GSTM1 Morning PEFR: ß= 20.04, p=0.25 Mean PEFR: ß= 18.75, p=0.28 GSTT1 Morning PEFR: ß= 2.31, p=0.89 Mean PEFR: ß= 1.75, p=0.91 Reference: Jansen, et al. (2005, 082236 ) Period of Study: 1987-2000

Location: Seattle, WA Outcome: FENO: fractional exhaled nitrogen oxide, Spirometry, Blood pressure, SaO 2 : oxygen saturation, Pulse rate Age Groups : 60-86-yr-old Study Design: Short-term crosssectional case series

N: 16 subjects diagnosed with COPD, asthma, or both Statistical Analyses: Linear mixed effects model with random intercepts

Covariates: Age, relative humidity, temperature, medication use

Season: W inter 2002-2003 Dose-response Investigated? No Statistical Package : STATA Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD):

Fixed-Site Monitor: 14.0 All Subjects (N=16) Indoor, home: 7.29 Outdoor, home: 10.47 Asthmatic Subjects (N=7) Indoor, home: 7.25 Outdoor, home: 8.99 COPD Subjects (N=9) Indoor, home: 7.33 Outdoor, home: 11.66 Range (Min, Max):

Fixed-Site Monitor: 1.3, 44 IQR All Subjects Indoor, home: 4.05 Outdoor, home: 8.87 Asthmatic Subjects Indoor, home: 5.72 Outdoor, home: 7.55 COPD Subjects Indoor, home: (3.18 Outdoor, home: 6.71 PM Increment: PM 2.5 : 10 μ g/m 3 Slope [95% CI]: dependence of FENO concentration [ppb] on PM 2.5 Asthmatic Subjects Indoor, home: 3.69 [-0.74: 8.12] Outdoor, home: 4.23 [1.33: 7.13]* Copd Subjects Indoor, home: -0.35 [-7.45: 6.75] Outdoor, home: 3.83 [-1.84: 9.49] Results indicate that FENO may be a more sensitive biomarker of PM exposure than other traditional health endpoints.



### December 2009 E-197

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Johnston, et al. (2006, 091386 ) Period of Study: 7 mo (Apr-Nov 2004)

Location: Darwin, Australia Outcome: Asthma symptoms Age Groups : All Ages Study Design: Time-series

N: 251 people (130 adults, 121 children Statistical Analyses: Logistic regression model

Covariates: Minimum air temperature, doctor visits for influenza and the prevalence of asthma symptoms and, the fungal spore count and both onset of asthma symptoms and commencement of reliever medication

Season: “Dry season”- note Southern Hemisphere Dose-response Investigated? No Statistical Package : STATA8 Lags Considered: 0-5 days Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): 11.1 (5.4) Range (Min, Max): 2.2, 36.5 PM Component: Vegetation fire smoke (95%) and motor vehicle emissions (5%) Monitoring Stations : 1 PM Increment: 5 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Symptoms attributable to asthma Overall: 1.000 (0.98,1.01) Adults: 1.000 (0.976,1.026) Children: 1.008 (0.980, 1.037) Using preventer: 1.013 (0.990, 1.037) Became symptomatic Overall: 1.150 (1.07,1.23) Adults: 1.165 (1.058,1.284) Children: 1.148 (1.042,1.264) Using preventer: 1.181 (1.076,1.296) Used Reliever Overall: 1.000 (0.98,1.02) Adults: 1.007 (0.980, 1.035) Children: 1.002 (0.972,1.034) Using preventer: 1.020 (1.000,1.042) Commenced Reliever Overall: 1.120 (1.03,1.210) Adults: 1.141 (1.021, 1.275) Children: 1.112 (0.994,1.243) Using preventer: 1.129 (1.013,1.257) Commenced Oral Steroids Overall: 1.310 (1.03,1.66) Adults: 1.601 (1.192, 2.150) Children: 0.995 (0.625,1.459) Using preventer: 1.350 (1.040,1.752) Asthma Attack Overall: 0.980 (0.94,1.04) Adults: 1.026 (0.962, 1.095) Children: 0.832 (0.731, 0.946) Using preventer: 1.002 (0.934,1.075) Exercise induced asthma Overall: 0.990 (0.95,1.03) Adults: 0.998 (0.943, 1.056) Children: 0.982 (0.899,1.071) Using preventer: 1.002 (0.942,1.067) Saw a health professional for asthma Overall: 1.030 (0.91,1.16) Adults: 1.079 (0.899, 1.296) Children: 1.003 (0.841,1.195) Using preventer: 0.980 (0.847,1.133) Missed school or work due to asthma Overall: 1.025 (0.9284,1.131) Adults: 1.077 (0.923, 1.247) Children: 1.000 (0.873,1.458) Using preventer: 1.005 (0.897,1.124) Mean daily number of asthma symptoms Overall: 1.003 (0.99,1.01) Adults: 0.998 (0.984, 1.012) Children: 1.004 (0.985,1.023) Using preventer: 1.013 (0.999,1.028) Mean Daily number of applications of reliever Overall: 1.002 (0.993,1.010) Adults: 1.001 (0.986, 1.016) Children: 1.000 (0.980,1.021) Using preventer: 1.005 (0.994,1.017)



### December 2009 E-198

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Koenig et al. (2003, 156653 ) Period of Study: Winter 2000-2001, Spring 2001

Location: Seattle, WA Outcome: Exhaled NO (eNO) Age Groups : 6-13 yr old Study Design: Cohort

N: 19 children Statistical Analyses: Linear mixedeffects regression

Covariates: Medication use, ambient NO reading for specific individual on specific day of session, mean ambient NO for subject during session, mean ambient NO for subject during all sessions

Season: Winter, Spring Dose-response Investigated? No Statistical Package : STATA Pollutant: PM 2.5 Averaging Time: 10 consecutive days Mean (SD): Outdoor: 13.3 (1.4) Indoor: 11.1 (4.9) Personal: 13.4 (3.2) Central-site: 10.1 (5.7) Range (Min, Max): Outdoor: Max: 40.4 Indoor: Max: 36.3 Personal: Max: 49.4 Central-site: NR Monitoring Stations : Outdoor: NR Indoor: NR Personal: NR Central-site: 3 Copollutant (correlation): Outdoor PM-central-site NO: 0.50For NO values < 100 ppb, outdoor PMcentral-site NO: 0.04 PM Increment: 10 μg/m 3 Results presented as change in eNO (95% CI) Among ICS* nonuser Personal monitor 4.48 (1.02, 7.93) Outdoor monitor 4.28 (1.38, 7.17) Indoor monitor 4.21 (1.02, 7.41) Central site 3.82 (1.22, 6.43) Among ICS* user Personal monitor -0.09 (-2.39, 2.21) Outdoor monitor 0.74 (-2.28, 3.76) Indoor monitor -1.11 (-5.08, 2.87) Central site 1.28 (-1.23, 3.79)

* ICS: Inhaled corticosteroid

Reference: Koenig et al. (2003, 156653 ) Period of Study: Winter 2000-2001, Spring 2001

Location: Seattle, WA Outcome : Increased exhaled nitric oxide (eNO) Age Groups : 6-13 yr of age Study Design: Combined recursive and predictive model

N: 19 children with asthma Statistical Analyses: Linear mixed effects model

Covariates: Residence type, air cleaner, avg outdoor temperature, avg daily rainfall

Season: Winter, Spring Dose-response Investigated? No Statistical Package : STATA 7.0 for health analyses, SAS 8.0 Pollutant: PM 2.5 Averaging Time: Daily Mean: Home indoor 9.5 Home outdoor 11.1 Recursive model Eag: 7.0 Recursive model Eig: 2.1 Predictive model Eag: 6.0 Predictive model Eig: 4.0 Combined model Eag: 6.4 Combined model Eig: 3.2 25th: Home indoor 5.7 Home outdoor 6.3 Recursive model Eag: 4.2 Recursive model Eig: 0.0 Predictive model Eag: 3.4 Predictive model Eig: 0.9 Combined model Eag: 3.7 Combined model Eig: 0.5 50th(Median): Home indoor 7.6 Home outdoor 9.5 Recursive model Eag: 5.9 Recursive model Eig: 1.2 Predictive model Eag: 5.0 Predictive model Eig: 2.2 Combined model Eag: 5.5 Combined model Eig: 1.7 75th : Home indoor 10.8 Home outdoor 14.6 Recursive model Eag: 9.2 Recursive model Eig: 2.3 Predictive model Eag: 7.5 Predictive model Eig: 4.9 Combined model Eag: 7.8 Combined model Eig: 4.2 Range (Min, Max): Home indoor 2.3, 36.3 Home outdoor 2.8, 40.4 Recursive Eag: 1.8,22.6 Recursive Eig: 0.0,17.2 Predictive Eag: 1.3,22.6 Predictive Eig: 0.0,33.0 Combined Eag: 1.3,22.6 Combined Eig: 0.0,33.0 Monitoring Stations : 19 personal environmental monitors PM Increment: 10- μ g/m 3 RR Estimate [Lower CI, Upper CI] lag: Eag= ambient-generated personal exposure Eig= indoor-generated personal exposure eNO= exhaled nitric oxide Recursive model with 8 children, Eag was marginally associated with increases in eNO [5.6 ppb [-0.6,11.9]. Eig was not associated with eNO (-0.19 ppb). For those combined estimates, only Eag was significantly associated with an increase in eNO: Eag: 5.0 ppb [0.3, 9.7] Eig: 3.3 ppb [1.1, 7.7]

Notes: Effects were seen only in children who were not using corticosteroid therapy



### December 2009 E-199

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Kongtip et al. (2006, 096920 ) Period of Study: Sep-Oct 2004

Location: Dindang district, Bangkok metropolitan, Thailand Outcome: respiratory and other Outcomes reported Age Groups : Age range 15-55 yr Study Design: Panel study

N: 77 street vendors Statistical Analyses: Binary logistic regression

Covariates: Gender, age, type of fuel used, working duration (months) Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 70.94

Percentiles: 50th(Median): 72.05 Range (Min, Max): 23.20-120.00 Monitoring Stations : 1 Copollutant (correlation):

SO 2 NO 2 O 3 VOCs

CO PM Increment: 1 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Model 1 Headache: 1.011 (0.999-1.022) Nose congestion: 1.006 (0.997-1.015) Sore throat: 1.000 (0.991-1.008) Cold: 1.006 (0.995-1.017) Cough: 0.989 (0.980-0.998) Phlegm: 0.998 (0.992-1.003) Chest tightness: 0.995 (0.955-1.036) Fever: 1.008 (0.993-1.024) Eye irritation: 1.022 (1.011-1.033) Dizziness: 1.027 (1.013-1.041) Weakness: 0.996 (0.983-1.008) Upper respiratory symptom: 1.001 (0.994-1.008) Lower respiratory symptom: 0.997 (0.992-1.002) Model 2 Headache: 1.004 (0.996-1.013) Nose congestion: 1.003 (0.996-1.010) Sore throat: 0.995 (0.989-1.001) Cold: 0.996 (0.988-1.004) Cough: 0.990 (0.983-0.996) Phlegm: 0.995 (0.991-0.999) Chest tightness: 0.997 (0.970-1.025) Fever: 1.010 (0.998-1.022) Eye irritation: 1.019 (1.010-1.028) Dizziness: 1.020 (1.009-1.032) Weakness: 1.003 (0.994-1.012) Upper respiratory symptom: 0.995 (0.990-1.000) Lower respiratory symptom: 0.995 (0.991-0.999)

Reference: Lagorio et al. (2006, 089800 ) Period of Study: May-Jun1999 and Nov-Dec 1999

Location: Rome, Italy Outcome: Lung function (FVC and FEV 1 ) of subjects with COPD, Asthma Age Groups : COPD 50-80 yr Asthma 18-64 yr Study Design: Time series

N: COPD = 11

Asthma = 11 Statistical Analyses: Non-parametric Spearman correlation

GEE

Covariates: COPD and IHD: daily mean temperature, season variable (spring or winter), relative humidity, day of week Asthma: season variable, temperature, humidity, and β -2-agonist use

Season : Spring and Winter Dose-response Investigated? Yes Statistical Package : STATA Lags Considered: 1-3 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Overall: 27.2 (19.4) Spring: 18.2 (5.0) Winter: 36.7 (24.1) Range (Min, Max): 4.5, 100 PM Component: Cd: 0.46±0.40 ng/m 3 Cr: 1.9±1.7 ng/m 3 Fe: 283±167 ng/m 3 Ni: 4.8±6.5 ng/m 3 Pb: 30.6±19.0 ng/m 3 Pt: 5.0±8.6 pg/m 3 V: 1.8±1.4 ng/m 3 Zn: 45.8±33.1 ng/m 3

Monitoring Stations : 2 fixed sites: (Villa Ada and Istituto superior di Sanita) Copollutant (correlation): NO 2 r = 0.43 O 3 r = -0.51 CO r = 0.67 SO 2 r = 0.34 PM 10-2.5 r = 0.34 PM 10 r = 0.93 PM Increment: 1 μg/m 3 They observed negative association between ambient PM 2.5 and respiratory function (FVC and FEV 1 ) in the COPD panel. The effect on FVC was seen at lag 24 h, 48 h, and 72 h. The effect on FEV 1 was evident at lag 72 h. There was no statistically significant effect of PM 2.5 on FVC and FEV 1 in the asthmatic and IHD panels. β Coefficient (SE) COPD FVC(%) 24 h -0.80 (0.36) 48-h -0.89 (0.41) 72-h -1.10 (0.55) FEV 1 (%) 24 h -0.47 (0.33) 48-h -0.69 (0.37) 72-h -1.06 (0.50) Asthma FVC(%) 24 h -0.14 (0.29) 48-h -0.07 (0.33) 72-h -0.06 (0.39) FEV 1 (%) 24 h -0.30 (0.34) 48-h -0.36 (0.39) 72-h -0.40 (0.46)



### December 2009 E-200

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lee et al. (2007, 093042 ) Period of Study: 2000-2001

Location: South-Western Seoul Metropolitan area, Seoul, South Korea Outcome: PEFR (peak expiratory flow rate), lower respiratory symptoms (cold, cough, wheeze) Age Groups : 61-89 yr of age (77.8 mean age) Study Design: longitudinal panel survey

N: 61 adults Statistical Analyses: SAS MIXED, logistic regression model

Covariates: Temperature (Celsius), relative humidity, age, Dose-response Investigated? No Statistical Package : SAS 8.0 Lags Considered: 0-4 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 51.15 (19.94)

Percentiles:

25th: 33.00 50th(Median): 53.20

75th: 87.54 Range (Min, Max): 17.94, 92.71 Monitoring Stations : 2 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI] lag: PEFR (peak expiratory flow rate) -0.54 (-0.89,-0.19) 1 day relative odds of a lower respiratory symptom (cold, cough, wheeze) 0.976 (0.849,1.121) 1 day

Reference: Lewis et al. (2005, 081079 ) Period of Study: Winter 2001-Spring 2002

Location: Detroit, Michigan, USA Outcome: Poorer lung function (increased diurnal variability and decreased forced expiratory volume) Age Groups : 7-11 yr old Study Design: Longitudinal cohort study

N: 86 children Statistical Analyses: D escriptive statistics and bivariate analyses of exposures, multivariable regression multivariate analog of linear regression.

Covariates: Sex, home location, annual family income, presence of one or more smokers in household, race, season (entered as dummy variables), and parameters to account for intervention group effect.

Season: Winter 2001 (Feb 10-23), Spring 2001 (May 5-18), Summer 2001 (Jul 14-27), Fall 2001 (Sep 22-Oct 5), Winter 2002 (Jan 18-31), and Spring 2002 (May 18-31)]. Dose-response Investigated? No Lags Considered: 1-2 days, 3-5 days Pollutant: PM 2.5 Averaging Time: 2 wk Mean (SD):

Eastside 15.7 (10.6)

Southwest 17.5 (12.2) Range (Min, Max): 1.0, 56.1 Monitoring Stations : 2 Copollutant (correlation):

PM 10 0.93

O 3 Daily mean 0.57

O 3 8-h peak 0.53 PM Increment: 12.5 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Lung function among children reporting use of maintenance CSs Diurnal variability FEV 1 Lag 1: 1.61 [-0.5,3.72] Lag 1: 0.99 [-5.64, 7.62] PM 2.5 + O 3 Lag 2: 2.96 [-1.74,7.66] Lag 2: 4.62 [-4.31, 13.54] PM 2.5 + O 3 Lag 3-5: 1.37 [-1.49,4.22] Lag 3-5: 2.70 [1.0, 4.40] PM 2.5 + O 3 Lowest daily value FEV 1 Lag 1: -2.23 [-6.99,2.53] Lag 1: 3.36 [-3.92, 10.63] PM 2.5 + O 3 Lag 2: -0.21 [-4.09,3.68] Lag 2: 0.88 [-8.69, 10.46] PM 2.5 + O 3 Lag 3-5: -0.76 [-5.00, 3.49] Lag 3-5: -2.78 [-4.87 to -0.70] PM 2.5 + O 3 Lung function among children reporting presence of URI on day of lung function assessment Diurnal variability FEV 1 Lag 1: 4.08 [-1.78, 9.94] Lag 1: 3.99 [-2.76, 10.74] PM 2.5 + O 3 Lag 2: 7.62 [-0.49, 15.73] Lag 2: 4.10 [-1.41, 9.60] PM 2.5 + O 3 Lag 3-5: 1.47 [-7.73, 10.67] Lag 3-5: 3.81 [-1.83, 9.45] PM 2.5 + O 3 Lowest daily value FEV 1 Lag 1: -1.21 [5.62,3.21] Lag 1: -0.74 [-4.14, 2.65] PM 2.5 + O 3 Lag 2: -0.10 [4.36,4.16] Lag 2: -1.67 [-5.09, 1.75] PM 5 + O 3 2. Lag 3-5: -2.88 [-5.46 to -0.30] Lag 3-5: -2.78 [-4.79 to -0.77] PM 2.5 + O 3



### December 2009 E-201

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Liu et al. (2009, 192003 ) Period of Study: 4 wk in 2005

Location: Windsor, Ontario, Canada Outcome: Decreased lung function Study Design: Panel Statistical Analysis: mixed-effects regression models Statistical Package: S-PLUS Age Groups: Asthmatic children, 9-14 yr Pollutant: PM 2.5 Averaging Time: 1, 2 & 3 days Mean (SD) Unit (1d): 6.5 μg/m 3 Range (Min, Max): 2.0-19.0 Copollutant (correlation):

SO 2 : 0.56

NO 2 : 0.71

O 3 : -0.41 Increment: 5.4 μg/m 3 Percent Change (Min CI, Max CI) Lag FEV 1 Same Day: -0.5 (-1.3-0.3) Lag 1 Day: -0.5 (-1.1-0.5) 2-Day Avg: -0.6 (-1.5-0.4) 3-Day Avg: -1.1 (-3.1-0.9) FEF 25%-75% Same Day: -1.9 (-3.5--0.3) Lag 1 Day: -1.2 (-2.8-0.3) 2-Day Avg: -2.0 (-3.8--0.2) 3-Day Avg: -3.3 (-7.2-0.8) FeNO Same Day: 5.3 (-3.6-15) Lag 1 Day: 1.7 (-6.3-15) 2-Day Avg: 4.3 (-5.4-15.1) 3-Day Avg: -17.3 (-33.5-2.9) TBARS Same Day: 16.9 (2.2-33.6) Lag 1 Day: 14.6 (0.8-30.4) 2-Day Avg: 22.0 (4.8-42.1) 3-Day Avg: 69.1 (20.1-138.2) 8-Isoprostane Same Day: 5.1 (-3.6-14.5) Lag 1 Day: -3.8 (-12.1-5.3) 2-Day Avg: 0.1 (-9.8-11.1) 3-Day Avg: 5.8 (-15.8-33.0)/



### December 2009 E-202

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Mar et al. (2004, 057309 ) Period of Study: 1997-1999

Location: Spokane, Washington Outcome: Respiratory Symptoms Age Groups : Adults: Ages 20-51 yr Children: Ages 7-12 yr

N: 25 people Statistical Analyses: Logistic regression

Covariates: Temperature, relative humidity, day of-the-wk Statistical Package : STATA 6 Lags Considered: 0-2 days Pollutant: PM 2.5 Mean (SD): 1997: 11.0 (5.9) 1998: 10.3 (5.4) 1999: 8.1 (3.8) Unit (i.e. μg/m 3 ): Monitoring Stations : 1 station Copollutant (correlation):

PM 2.5 PM 1 r = 0.92

PM 10 r = 0.61

PM 10-2.5 r = 0.28 PM Increment: 10 μg/m 3 OR Estimate [Lower CI, Upper CI] lag: Adult Respiratory symptoms: Wheeze: 1.04[0.86, 1.26] lag 0 1.00[0.83, 1.19] lag 1 0.99[0.84, 1.17] lag 2 Breath: 0.97[0.87, 1.08] lag 0 0.98[0.87, 1.10] lag 1 0.95[0.80, 1.13] lag 2 Cough : 0.86[0.62, 1.21] lag 0 0.87[0.63, 1.20] lag 1 0.89[0.66, 1.20] lag 2 Sputum : 0.94[0.63, 1.41] lag 0 0.90[0.62, 1.31] lag 1 0.92[0.66, 1.27] lag 2 Runny Nose: 0.98[0.83, 1.15] lag 0 0.95[0.82, 1.10] lag 1 0.93[0.80, 1.08] lag 2 Eye Irritation: 0.91[0.70, 1.20] lag 0 0.89[0.70, 1.13] lag 1 0.86[0.68, 1.08] lag 2 Lower Symptoms: 0.91[0.73, 1.13] lag 0 0.89[0.72, 1.10] lag 1 0.89[0.72, 1.10] lag 2 Any Symptoms: 0.92[0.80, 1.07] lag 0 0.89[0.76, 1.04] lag 1 0.89[0.75, 1.05] lag 2 Children Respiratory symptoms: Wheeze: 0.55[0.26, 1.19] lag 0 0.53[0.18, 1.58] lag 1 0.55[0.19, 1.64] lag 2 Breath: 1.13[0.86, 1.48] lag 0 1.12[0.86, 1.44] lag 1 1.10[0.82, 1.48] lag 2 Cough: 1.17[0.98, 1.40] lag 0 1.21[1.00, 1.47] lag 1 1.18[0.99, 1.42] lag 2 Sputum: 1.06[0.92, 1.22] lag 0 1.10[0.91, 1.34] lag 1 1.09[0.92, 1.30] lag 2 Runny Nose : 1.09[0.85, 1.39] lag 0 1.12[0.89, 1.41] lag 1 1.16[0.94, 1.42] lag 2 Eye Irritation: 0.93[0.53, 1.64] lag 0 0.75[0.45, 1.27] lag 1 0.77[0.65, 0.91] lag 2 Lower Symptoms: 1.18[1.00, 1.38] lag 0 1.21[1.00, 1.46] lag 1 1.17[0.96, 1.43] lag 2 Any Symptoms: 1.17[1.03, 1.34] lag 0 1.22[1.04, 1.43] lag 1 1.23[1.07, 1.42] lag 2



### December 2009 E-203

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Mar et al. (2005, 087566 ) Period of Study: 1999-2001

Location: Seattle, Washington Outcome: Pulmonary function (arterial oxygen saturation) and cardiac function (heart rate and blood pressure) Study Design: Time series Statistical Analyses: Linear logistic regression Age Groups : > 57 Pollutant: PM 2.5 Averaging Time: 24-h avg Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) Lag Personal: Systolic: 0.37 (-0.93, 1.67) 0 Diastolic: -0.20 (-0.85, 0.46) 0 Indoor: Systolic: 0.92 (-2.04, 3.87) 0 Diastolic: 0.38 (-1.43, 2.20) 0 Outdoor: Systolic: -0.81 (-2.34, 0.73) 0 Diastolic: -0.46 (-1.49, 0.57) 0 % Increase between heart rate and PM 2.5 exposure for people > 57 PM 2.5 : Personal: 0.44 (0.04, 0.84) 0 Indoor: 0.22 (-0.71, 1.16) 0 Outdoor: -0.75 (-1.42 to -0.07) 0 Reference: Mar et al. (2005, 088759 ) Period of Study: 1999-2002

Location: Seattle, Washington Outcome : Respiratory Symptoms Age Groups : 6-13 yr Study Design: Time-Series

N: 19 children Statistical Analyses: Polynomial distributed lag model, Poisson regression

Covariates: Age, ambient NO levels, temperature, relative humidity, modification of use of inhaled corticosteroids

Season: Winter, Spring Dose-response Investigated? No Statistical Package : STATA Lags Considered: 0-8 h Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Results presented in Fig 1. Monitoring Stations : 3 Stations PM Increment: 10 μg/m 3 Change in FE(NO) (exhaled NO concentration) with air pollution [Lower CI, Upper CI] lag: Medication use: No meds: 6.99[3.43, 10.55] lag 1-h Meds: -0.18[-3.33, 2.97] lag 1-h No meds: 6.30[2.64, 9.97] lag 4-h Meds: -0.77[-4.58, 3.04] lag 4-h No meds: 0.46[-1.18, 2.11] lag 8-h Meds: 0.40[-1.94, 2.74] lag 8-h

Reference: McCreanor et al. (2007, 092841 ) Period of Study: 2003-2005

Location: London, England Outcome : Decreased Lung Function Age Groups : Adults Study Design: Crossover study

N: 60 adults Statistical Analyses: Linear regression

Covariates: Temperature, relative humidity, age, sex, bod-mass index, and race or ethnic group Pollutant: PM 2.5 Averaging Time: 1 h Mean (SD): NR 50th(Median): Oxford St: 28.3 Hyde Park: 11.9 Range (Min, Max): Oxford St: (13.9, 76.1) Hyde Park: (3, 55.9) % changes in FEV and FVC are presented in Fig 1-3. Results are not presented quantitatively in text or tables. The authors did not find any significant differences in respiratory symptoms between the two locations. Also, there were no significant differences in sputum eosinophil counts or eosinophil cationic protein levels.

Reference: Moshammer and Neuberger (2003, 041956 ) Period of Study: 2000-2001

Location: Linz, Austria Outcome: Lung Function: FVC, FEV 1 , MEF 25 , MEF 50 , MEF 75 , PEF, LQ Signal, PAS Signal Age Groups : Ages 7-10 Study Design: Case-crossover

N: 161 children

1898-2120 “half-h means” Statistical Analyses: Correlations Regression Analysis

Covariates: Morning, evening, night

Season: Spring, Summer, Winter, Fall Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: 8 h means & daily

means Mean (SD): 14.61 (10.83) Range (Min, Max): (NR, 119.92) Monitoring Stations : 1 Copollutant (correlation):

LQ = 0.751

PAS = 0.354 Notes: “Acute effects of ‘active particle surface’ as measured by diffusion charging were found on pulmonary function (FVC, FEV 1 , MEF 50 ) of elementary school children and on asthma-like symptoms of children who had been classified as sensitive.”



### December 2009 E-204

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Moshammer et al. (2006, 090771 ) Period of Study: 2000-2001

Location: Linz, Austria Outcome : Respiratory symptoms and decreased lung function Age Groups : Children ages 7-10 Study Design: Time-series

N: 163 children Statistical Analyses: Generalized estimating equations model

Covariates: Sex, age, height, weight Dose-response Investigated? NR Statistical Package : NR Lags Considered: 1 Pollutant: PM 2.5 Averaging Time: 8 h Mean (SD):

Maximum 24 h: 76.39 Annual avg: 19.06

Percentiles: 8-h mean 25th: 8.64 8-h mean 50th(Median): 15.70

8-h mean 75th: 25.82 Monitoring Stations : 1 station Copollutant (correlation): PM 1 r = 0.95

PM 10 r = 0.93

NO 2 r = 0.54 PM Increment: 10 μg/m 3 % change in Lung Function per 10 μg/m3 FEV: 0.23 FVC: 0.08 FEV 0.5 : 0.33 MEF 75 %: -0.49 MEF 50 %: -0.58 MEF 25 %: -0.83 PEF: 0.41 % change in Lung Function per IQR FEV: -0.59 FVC: -0.2 FEV 0.5 : 0.85 MEF 75 %: -1.25 MEF 50 %: -1.48 MEF 25 %: -2.14 PEF: -1.06 Multiple pollutant model FEV: 0.10 FVC: 0.21 FEV 0.5 : 0.06 MEF 75 %: -0.15 MEF 50 %: 0.04 MEF 25 %: -0.21 PEF: -0.18 % change in Lung Function per IQR FEV: 0.27 FVC: 0.54 FEV 0.5 : 0.15 MEF 75 %: -0.39 MEF 50 %: 0.11 MEF 25 %: 0.54 PEF: 0.015: -0.47 Reference: Murata et al. (2007, 189159 ) Period of Study: Nov 2004

Location: Tokyo, Japan Outcome: Exhaled nitric oxide levels, (eNO), a marker of airway inflammation Age Groups : 5-10 yr Study Design: Cohort/Panel study

N: 19 schoolchildren* Statistical Analyses: Linear regression

Covariates: None

Season: Nov (fall) Dose-response Investigated? No Statistical Package : SAS Lags Considered: Lag h 1-24, 8-h ma, 7-h ma, 6-h ma, 24-h ma Pollutant: PM 2.5 Averaging Time: Hourly, 24 h Mean (SD): 39.0 (16.9) μg/m 3 (daily mean) Range (Min, Max): 10, 120 (range of hourly values) Monitoring Stations : 1, on the street where the children lived PM Increment: IQR 110 μg/m 3

 Mean [Lower CI, Upper CI] lag: 0.145 [0.62, 0.228] ppb eNO 8-h ma

Notes: Associations for lag h 1-24 presented in figures. Authors state “Individual hourly lag models showed a consistent association between the eNO value and PM 2.5 for exposure in the previous 24 h” “The trend on the graphs strongly suggest that fluctuations in eNO were affected by changes in air pollutants over at least the previous 8-h period”

PM 2.5 , black carbon, and NO X were all highly correlated (shown in figures), so effects are difficult to separate Pollutant concentrations peaked in the morning and evening h during traffic peaks



### December 2009 E-205

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Neuberger et al. (2004, 093249 ) Period of Study: Jun 1999-Jun 2000

Location: Austria (Vienna and a rural area near Linz) Outcome: Questionnaire derived asthma score, and a 1-5 point respiratory health rating by parent Age Groups : 7-10 yr Study Design: Cross-sectional survey

N: about 2000 children Statistical Analyses: mixed models linear regression-used factor analysis to develop the “asthma score”

Covariates: Pre-existing respiratory conditions, temperature, rainy days, # smokers in household, heavy traffic on residential street, gas stove or heating, molds, sex, age of child, allergies of child, asthma in other family members Dose-response Investigated? No Statistical Package : NR Lags Considered: 4-wk avg (preceding interview) Pollutant: PM 2.5 Averaging Time: 24 h Copollutant (correlation):

PM 10 (r=0.94) in Vienna PM Increment: 10 μg/m 3 Change in mean associated unit increase in PM (p-value) lag Respiratory Health score Vienna: 0.016 (p>0.05) lag 4 week avg Rural area: 0.022 (p < 0.05) lag 4 week avg Asthma score Vienna: 0.006 (p>0.05) lag 4 week avg Rural area: 0.004 (p>0.05) lag 4 week avg

Reference: Neuberger et al. (2004, 093249 ) Period of Study: Sep 1999-Mar 2000

Location: Vienna, Austria Outcome: Ratio measure: Time to peak tidal expiratory flow divided by total expiration time (i.e., tidal lung function, a surrogate for bronchial obstruction) Age Groups : 3.0-5.9 yr (preschool children) Study Design: Longitudinal prospective cohort

N: 56 children Statistical Analyses: mixed models linear regression, with autoregressive correlation structure

Covariates: Age, sex, respiratory rate, phase angle, temperature, kindergarten, parental education, observer (also in sensitivity analyses: height, weight, cold/sneeze on same day, heating with fossil fuels, hair cotinine, number of tidal slopes used to measure tidal lung function) Dose-response Investigated? No Statistical Package : SAS 8.0 Lags Considered: Lag 0 Pollutant: PM 2.5 Averaging Time: 24 h PM Component: T otal carbon

EC

OC Copollutant (correlation):

PM 10 (r=0.94) in Vienna PM Increment: Interquartile range (NR) Change in mean associated with an IQR increase in PM (p-value) lag

PM 2.5 mass: -0.987 (0.091) lag 0 Total carbon: -0.815 (0.041) lag 0 EC: -0.657 (0.126) lag 0 OC: -0.942 (0.025) lag 0

Reference: Neuberger et al. (2004, 093249 ) Period of Study: Oct. 2000-May 2001

Location: Linz, Austria Outcome : Forced oscillatory resistance (at zero Hz), FVC, FEV 1 , MEF 25 , MEF 50 , MEF 75 , PEF Age Groups : 7-10 yr Study Design: Longitudinal prospective cohort

N: 164 children Statistical Analyses: M ixed models linear regression with autoregressive correlation structure

Covariates: Sex, time and individual

Season: Oct-May Dose-response Investigated? No Statistical Package : NR Lags Considered: Lag 0-7 Pollutant: PM 2.5 Averaging Time: 24 h Monitoring Stations : 1 PM Increment: 1 μg/m 3

Notes: Authors report increased oscillatory resistance significantly associated with PM 2.5 (lag 0)



### December 2009 E-206

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: O'Connor et al. (2008, 156818 ) Period of Study: Aug 1998-Jul 2001

Location: Boston, the Bronx, Chicago, Dallas, New York, Seattle, Tucson Outcome: Pulmonary function and respiratory symptoms Age Groups : 5-12 yr Study Design: Inner-City Asthma Study (ICAS)-Panel/cohort study

N: 861 children Statistical Analyses: Mixed effects models Lags Considered: Lag 0-6, 0-4 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 14 Range (Min, Max): 5-35 (estimated from Fig) Copollutant (correlation):

NO 2 (r=0.59)

SO 2 (r=0.37) CO (r=0.44)

O 3 (r=-0.02) PM Increment: 13.2 μg/m 3 90th-10th percentile Change in pulmonary function lag

FEV 1 : -1.47 (-2.00 to -0.94) lag 0-4 PEFR: -1.10 (-1.65 to -0.56) lag 0-4 PM 2.5 +O 3 +NO 2 FEV 1 : -0.73 (-1.33 to -0.12) lag 0-4 PEFR: -0.25 (-0.88, 0.38) lag 0-4

Risk of Respiratory Symptoms lag Wheeze: 0.98 (0.88, 1.09) lag 0-4 Nighttime asthma: 1.11 (0.94, 1.30) lag 0-4 Slow play: 1.01 (0.89, 1.15) lag 0-4 Missed school: 1.33 (1.06, 1.66) lag 0-4 PM 2.5 +O 3 +NO 2 Wheeze: 0.92 (0.81, 1.05) lag 0-4 Nighttime asthma: 1.03 (0.86, 1.23) lag 0-4 Slow play: 0.92 (0.79, 1.06) lag 0-4 Missed school: 1.13 (0.87, 1.45) lag 0-4 Reference: Peacock et al. (2003, 042026 ) Period of Study: Nov 1996-Feb 1997

Location: northern Kent, UK Outcome: Reduced peak expiratory flow rate (PEFR) Age Groups : 7-13 yr of age Study Design: Time Series

N: 179 Statistical Analyses: generalized estimating equations

Covariates: Day of the week, 24-h mean outside temperature.

Season: Winter Dose-response Investigated? No Statistical Package : STATA Lags Considered: Same day, lag 1, lag 2, 5-day ma Pollutant: Sulfate (SO 4 2– ) Averaging Time: Daily avg Mean (SD): Urban 2 24 h avg: 1.3 (1.1)

Percentiles:

10th: Urban 2 0.5

90th: Urban 2 2.4 Range (Min, Max): Urban 2 0.3, 6.7 Monitoring Stations : 3 Sulfate (SO 4 2– ) Increment: 1.3 μg/m 3 Odds ratio [Lower CI, Upper CI] lag: 1.090 [0.898, 1.322] 5 days

Reference: Peled, et al. (2005, 156015 ) Period of Study: 5-6 wk between Mar-Jun 1999 and Sep-Dec 1999.

Location: Ashdod, Ashkelon and Sderot, Israel Outcome: Reduced peak expiratory flow (PEF) Age Groups : 7-10 yr Study Design: Nested cohort study

N: 285 Statistical Analyses: Time series analysis Generalized linear model, generalized estimating equations, one-way ANOVA, generalized linear model

Covariates: Seasonal changes, meteorological conditions and personal physiological, clinical and socioeconomic measurements

Season: Spring, Fall Dose-response Investigated? No Statistical Package : STATA Pollutant: PM 2.5 Averaging Time: Daily

Mean:

Ashkelon: 24.0

Sderot: 29.2

Ashdod: 23.9 PM Component: Local industrial emissions, desert dust, vehicle emissions and emissions from two electric power plants Monitoring Stations : 6 Copollutant: PM 10 PM Increment: 1 μg/m 3 β coefficient (SE) [95% CI]

Ashkelon:

PM 2.5 MAX: -0.144 (0.12) [-0.38-0.09]

Ashdod:

PM 2.5 MAX: -2.74 (0.61) [-3.95-1.53]

PM 2.5 MAX TMAX: 0.11 (0.02) [0.06- 0.16] In Ashdod, PM 2.5 and an interaction between PM 2.5 and temperature were significantly associated.



### December 2009 E-207

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Penttinen et al. (2006, 087988 ) Period of Study: Nov 1996-Apr 1997

Location: Helsinki, Finland Outcome: Decreased lung function and respiratory symptoms Age Groups : Adults, mean age 53 yr Study Design: Time Series

N: 78 people Statistical Analyses: Generalized least squares autoregressive model

Covariates: Temperature, relative humidity, day of study, day of study squared, binary dummy variable for weekends

Season: Winter, Spring Dose-response Investigated? NR Statistical Package : SAS version 6 Lags Considered: 0-3 Pollutant: PM 2.5 PM Component: Soil, heavy fuel oil, sea salt Averaging Time: 24 h Percentiles: 25th: Long range transport: 2.44 Local combustion: 1.75 Soil: 0.14 Heavy fuel oil: -0.13 Sea Salt: 0.22 Unidentifiable: -1.41 All sources: 6.47 50th(Median): Long range transport: 4.15 Local combustion: 2.41 Soil: 0.64 Heavy fuel oil: 0.10 Sea Salt: 0.27 Unidentifiable: 0.02 All sources: 8.37 75th: Long range transport: 7.33 Local combustion: 3.05 Soil: 1.46 Heavy fuel oil: 0.52 Sea Salt: 0.42 Unidentifiable: 0.74 All sources: 11.15 Range (Min, Max): Long range transport: (-0.89, 28.31) Local combustion: (0.83, 6.51) Soil: (-1.13, 6.43) Heavy fuel oil: (-0.67, 4.74) Sea Salt: (0.09, 0.98) Unidentifiable: (-4.40, 4.77) All sources: (4.11, 33.53) Monitoring Stations : 1 site PM Increment: 1.3 μg/m 3

PM 2.5 , long range: PEF Morning: 0.37[-0.59, 1.34] lag 0 -1.04[-1.88 to -0.19] lag 1 -0.82[-1.81, 0.16] lag 2 0.22[-0.64, 1.08] lag 3 -0.24[-1.12, 0.64] 5 day mean.

PEF Afternoon: 0.20[-0.67, 1.06] lag 0 -0.20[-1.24, 0.83] lag 1 -0.30[-1.14, 0.53] lag 2 0.45[-0.57, 1.47] lag 3 0.03[-0.79, 0.85] 5 day mean.

PEF Evening: -0.33[-1.30, 0.64] lag 0 -0.29[-1.13, 0.55] lag 1 -0.41[-1.46, 0.64] lag 2 0.39[-0.47, 1.24] lag 3 0.07[-0.81, 0.95] 5 day mean

PM 2.5 , local combustion: PEF Morning: -0.73[-1.69, 0.23] lag 0 -0.46[-1.24, 0.32] lag 1 -0.43[-1.49, 0.63] lag 2 0.34[-0.47, 1.15] lag 3 -0.25[-1.03, 0.53] 5 day mean.

PEF Afternoon: -0.21[-1.07, 0.65] lag 0 -0.81 [-1.77, 0.16] lag 1 -0.83[-1.74, 0.09] lag 2 0.20[-0.80, 1.20] lag 3 -0.87[-1.63 to -0.12] 5 day mean.

PEF Evening: -0.51[-1.48, 0.45] lag 0 -1.16[-1.93 to -0.39] lag 1 0.23[-1.35, 0.90] lag 2 0.56[-0.21, 1.32] lag 3 -1.14[-1.95 to -0.33] 5 day mean

PM 2.5 , soil: PEF Morning: 0.81[0.05, 1.57] lag 0 0.03 [-0.65, 0.71] lag 1 0.50[-0.34, 1.35] lag 2 -0.07[-0.74, 0.61] lag 3 0.39[-0.46, 1.23] 5 day mean.

PEF Afternoon: 1.05[0.38, 1.72] lag 0 0.40[-0.38, 1.19] lag 1 0.66 [0.03, 1.30] lag 2 -0.36[-1.12, 0.41] lag 3 0.55 [-0.21, 1.32] 5 day mean.

PEF Evening: 1.08[0.33, 1.84] lag 0 1.00[0.31, 1.68] lag 1 0.33[-0.56, 1.22] lag 2 -0.84 [-1.53 to -0.15]lag 3 0.90[0.08, 1.73] 5 day mean

PM 2.5 , oil: PEF Morning: -0.22[-1.00, 0.56] lag 0 -0.20[-1.24, 0.84] lag 1 0.66[-0.68, 2.00] lag 2 0.57 [-0.18, 1.32] lag 3 0.10[-0.61, 0.81] 5 day mean.

PEF Afternoon: -0.04[-0.75, 0.67] lag 0



### December 2009 E-208

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 0.29[-0.98, 1.55] lag 1 0.08 [-1.13, 1.28] lag 2 0.62[-0.31, 1.54] lag 3 0.07 [-0.64, 0.78] 5 day mean.

PEF Evening: 0.57[-0.23, 1.37] lag 0 0.12[-0.92, 1.15] lag 1 -0.97[-2.39, 0.45] lag 2 0.40[-0.31, 1.12] lag 3 0.43[-0.33, 1.19] 5 day mean

PM 2.5 , salt: PEF Morning: 0.76[-0.13, 1.65] lag 0 0.43 [-0.30, 1.16] lag 1 0.13[-0.75, 1.02] lag 2 0.38[-0.47, 1.23] lag 3 0.95[-0.18, 2.09] 5 day mean.

PEF Afternoon: 0.62[-0.18, 1.41] lag 0 0.80[-0.08, 1.69] lag 1 0.14[-0.62, 0.90] lag 2 0.16[-0.83, 1.15] lag 3 0.88 [-0.18, 1.94] 5 day mean.

PEF Evening: 1.09[0.19, 1.98] lag 0 0.63[-0.10, 1.35] lag 1 0.32[-0.62, 1.26] lag 2 -0.31[-1.16, 0.54] lag 3 0.88[-0.27, 2.02] 5 day mean

PM 2.5 , unidentified: PEF Morning: 0.38[-0.67, 1.43] lag 0 0.09[-0.83, 1.00] lag 1 0.22[-0.82, 1.26] lag 2 0.78 [-0.10, 1.66] lag 3 0.78[-0.14, 1.69] 5 day mean.

PEF Afternoon: 0.02[-0.92, 0.96] lag 0 0.65[-0.48, 1.77] lag 1 0.17[-0.71, 1.05] lag 2 0.69[-0.36, 1.75] lag 3 0.17 [-0.72, 1.06] 5 day mean.

PEF Evening: -0.11[-1.17, 0.95] lag 0 0.19[-0.72, 1.10] lag 1 0.86[-0.25, 1.96] lag 2 0.15[-0.70, 1.01] lag 3 -0.19[-1.15, 0.77] 5 day mean

PM 2.5 , local combustion : PEF morning: Cu: -0.25 [-1.25, 0.75] Zn: -0.45[-1.19, 0.29] Mn: 0.13[-0.83, 1.08] Fe: 0.08[-0.70, 0.85]. PEF afternoon: Cu: -0.37[-1.29, 0.55] Zn: -0.19[-0.87, 0.50] Mn: -0.48[-1.37, 0.42] Fe: 0.29[-0.45, 1.04]. PEF evening: Cu: -0.48[-1.47, 0.52] Zn: -0.17[-0.92, 0.57] Mn: 0.51[-0.44, 1.47] Fe: 0.34[-0.46, 1.14]

PM 2.5 , long range: PEF morning: S: 0.11[-0.886, 1.07] K: -0.10[-1.00, 0.80] Pb: -0.62[-1.37, 0.13]



### December 2009 E-209

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Br: -0.40 [-1.40, 0.60]. PEF afternoon: S: -0.05[-0.92, 0.81] K: 0.26[-0.56, 1.07] Pb: -0.12[-0.84, 0.60] Br: 0.15[-0.81, 1.12]. PEF evening: S: 0.08[-0.86, 1.02] K: 0.18[-0.70, 1.07]; Pb: -0.20[-0.97, 0.58] Br: 0.35[-0.71, 1.40]

PM 2.5 , soil: PEF morning: Si: 0.27[-0.43, 0.97] Al: 0.17 [-0.72, 1.05] Ca: 0.13[-1.08, 1.35]. PEF afternoon: Si: 0.39[-0.24, 1.01] Al: 0.49[-0.29, 1.27] Ca: 0.15[-0.92, 1.22] PEF evening: Si: 0.60[-0.06, 1.26] Al: 0.76[-0.08, 1.60] Ca: 0.90[-0.22, 2.03]

PM 2.5 , Oil combustion: PEF morning: V: -0.01[-0.87, 0.86] Ni: -0.09[-1.08, 0.90]. PEF afternoon: V: -0.48[-1.32, 0.35] Ni: 0.26[-0.72, 1.23]. PEF evening: V: 0.02[-00.88, 0.92] Ni: 0.50[-0.55, 1.55]

PM 2.5 , Sea salt: PEF morning: Na: 0.92[-0.34, 2.17] Cl: 0.93[0.08, 1.79] PEF afternoon: Na: 0.96[-0.24, 2.16] Cl: 0.57[-0.22, 1.36] PEF evening Na: 0.87[-0.40, 2.15] Cl: 0.65[-0.19, 1.49]



### December 2009 E-210

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Pino et al. (2004, 050220 ) Period of Study: Apr 1995-Oct 1996

Location: Santiago, Chile Outcome: Respiratory Symptoms, Wheezing bronchitis Study Design: Time-series Statistical Analyses: Bayesian hierarchical analysis, cubic spline Age Groups : 4 mo-2 yr old Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD) unit: 52.0 (31.6) Range (5th, 95th): 17.0, 114.0 Copollutants (correlation):

SO 2 : r= 0.73

NO 2 : r= 0.85 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: % increase in wheezing bronchitis and PM 2.5 exposure for infants 4 mo-2 yr old 4.75 (1.25, 8.25) 1 3.85 (0.45, 7.75) 2 2.25 (-1.00, 6.00) 3 1.75 (-2.20, 5.75) 4 4.00 (0.25, 8.00) 5 5.00 (1.00, 8.50) 6 7.00 (3.50, 11.00) 7 8.10 (4.00, 11.25) 8 9.00 (6.00, 12.00) 9 8.75 (5.75, 12.00) 10 1.50 (-3.50, 4.75) 11 0.25 (-3.75, 4.25) 12 0.00 (-4.00, 4.00) 13 1.00 (-3.50, 4.50) 14 1.50 (-3.50, 4.50) 15 OR for wheezing bronchitis and PM 2.5 exposure in infants 4 mo to 2 yr old according to family history of asthma Yes to family history of asthma 1.09 (1.00, 1.19) 1 1.10 (1.02, 1.20) 2 1.11 (1.02, 1.22) 3 No to family history of asthma 1.04 (1.00, 1.08) 1 1.02 (0.98, 1.06) 2 1.01 (0.96, 1.05) 3 Reference: Rabinovitch et al., (2006, 088031 ) Period of Study: 2001-2003 (two winters 2001-2002 and 2002-2003)

Location: Denver, CO Outcome : Bronchodilator doser activations (daily) and urinary leukotriene E4 (daily) Age Groups : Children 6-13 yr old Study Design: S chool-based cohort study

N: 73 children Statistical Analyses: Doser activation: Poisson regression with GEE with AR1 working covariance Urinary leukotriene E4: linear mixed model with spatial exponential covariance

Covariates: Temperature, pressure, humidity, time trend, Friday indicator, upper respiratory infection (URI), height (leukotriene E4 only).

Season: Winter Dose-response Investigated? NR Statistical Package : SAS Lags Considered: 0-2 days Pollutant: PM 2.5 Averaging Time: Morning (midnight to 11: 00 AM) mean Morning (midnight to 11: 00 AM) maximum 24-h mean Mean (SD): 24-h mean, TEOM Year 1, N: 55 days: 6.5 (3.2) Year 2, N: 128 days: 8.2 (3.7) 24-h mean, FRM Year 1, N: 55 days: 11.8 (7.2) Year 2, N: 122 days: 11.2 (5.5) Morning mean, TEOM Year 1, N: 71 days: 7.4 (4.7) Year 2, N: 127 days: 9.1 (5.0) Morning maximum, TEOM Year 1, N: 71 days: 15.5 (9.5) Year 2, N: 127 days: 18.4 (9.6)

Percentiles : 24-h mean, TEOM Year 1 25th: 4.4 50th(Median): 6.2 75th: 7.9 Year 2 25th: 55 50th(Median): 7.3 75th: 9.9 24-h mean, FRM Year 1 25th: 7.8 50th(Median): 10.1 75th: 14.1 Year 2 25th: 7.5 50th(Median): 9.3 75th: 13.3 Morning mean, TEOM Year 1 25th: 4.0 PM Increment: IQR (over current and previous day) Doser Activation Morning avg PM 2.5 TEOM Year 1: Pct Increase: 3.0 [-0.5: 6.6] p = 0.10 Year 2: Pct Increase: 2.7 [1.1: 4.4] p = 0.006 Aggregated yr: 2.2 [0.7: 3.6] p = 0.005 Morning max PM 2.5 TEOM Year 1 Pct Increase: 4.0 [0.5: 7.6] p = 0.02 Year 2 Pct Increase: 2.3 [0.7: 4.0] p = 0.009 Aggregated yr 2.6 [0.9: 4.2] p= 0.002 24-h PM 2.5 TEOM Lag 0: 0.4 [-0.7: 1.6] p-value = 0.45 Lag 1: 0.9 [-0.7: 2.4] p-value = 0.27 Lag 2: -0.4 [-1.7: 0.9] p-value = 0.59 Lag 0-2 Avg: 0.6 [-1.0: 2.2] p-value = 0.43 FRM Lag 0: 0.2 [-1.2: 1.6] p-value = 0.81 Lag 1: 0.9 [-0.9: 2.6] p-value = 0.31 Lag 2: -0.2 [-2.2: 1.8] p-value = 0.88 Lag 0-2 Avg: 1.2 [-0.6: 2.9] p-value = 0.20 Morning avg PM 2.5 TEOM URI not adjusted Mild/Moderate Asthmatics: 1.5 [-0.5: 3.4] p = 0.14 Severe Asthmatics: 3.7 [1.6: 5.8] p- = 0.0006 Difference between severity groups, p = 0.12 Aggregated severity group: 2.2 [0.7: 3.6] p= 0.005 URI adjusted Mild/Moderate Asthmatics: 1.0 [-1.9: 3.9]p= 0.50 Severe Asthmatics: 6.0 [1.8: 10.1] p = 0.006 Difference between severity groups,



### December 2009 E-211

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 50th(Median): 5.9 75th: 9.6 Year 2 25th: 5.2 50th (Median): 8.5 75th: 11.6 Morning maximum, TEOM Year 1 25th: 8 50th (Median): 13 75th: 20 Year 2 25th: 11 50th (Median): 16 75th: 23 Range (Min, Max): 24-h mean, TEOM Year 1 (2.1, 23.7) Year 2 (1.7, 20.5) 24-h mean, FRM Year 1 (4.3, 53.5) Year 2 (3.4, 26.3) Morning mean, TEOM Year 1 (1.4, 22.7) Year 2 (1.6, 30.2) Morning maximum, TEOM Year 1 (4, 42) Year 2 (4, 46) Monitoring Stations : 2 (1 TEOM and 1 Federal Reference Monitor [FRM]) p = 0.08 Aggregated severity groups: 2.7 [-0.1: 5.4] p= 0.06 Morning maximum PM 2.5 TEOM URI not adjusted Mild/Moderate Asthmatics: 1.9 [-0.2: 4.1] p= 0.07 Severe Asthmatics: 3.9 [1.1: 6.8] p = 0.006 Difference between severity groups, p = 0.29 Aggregated severity groups: 2.6 [0.9: 4.2] p= 0.002 URI adjusted Mild/Moderate Asthmatics: 1.6 [-2.2: 5.4] p = 0.41 Severe Asthmatics: 8.1 [2.9: 13.4] p = 0.003 Difference between severity groups, p = 0.03 Aggregated severity groups: 3.8 [0.2: 7.4] p = 0.04 Leukotriene E4 24-h PM 2.5 TEOM Lag 0: 3.3 [-0.7: 7.2] p = 0.09 Lag 1: -1.6[-5.7: 2.5] p = 0.40 Lag 2: 1.1 [-2.8: 5.1] p= 0.64 Lag 0-2 Avg: 2.3 [-4.0: 8.6] p = 0.45 FRM Lag 0: 2.7 [1.1: 6.5] p = 0.12 Lag 1: -0.8 [-4.9: 3.3] p = 0.65 Lag 2: -0.8 [-4.9: 3.3] p = 0.71 Lag 0-2 Avg: 2.6 [-2.3: 7.5] p = 0.27 Leukotriene E4 Morning avg PM 2.5 TEOM Height 25percentile: 8.9 [3.0: 14.7] p= 0.004 Height 50percentile: 5.9 [1.4: 10.4] p = 0.01 Height 75percentile: 1.9 [-3.4: 7.3] p = 0.47 Model w/o Height × Pollutant: 5.6 [1.0: 10.2] p = 0.02 Morning maximum PM 2.5 TEOM Height 25percentile: 8.3 [3.4: 13.2] p = 0.001 Height 50percentile: 6.1 [2.1: 10.2] p= 0.004 Height 75 percentile: 3.2 [-2.0: 8.4] p= 0.23 Model w/o Height × Pollutant: 6.2 [1.9: 10.5] p = 0.006 Reference: Rabinovitch et al. (2004, 096753 ) Periods of Study: Nov 1999-Mar 2000

Nov 2000-Mar 2001

Nov 2001-Mar 2002

Location: Denver, Colorado Outcome: Respiratory symptoms, Asthma symptoms (cough and wheeze), Upper respiratory symptoms Study Design: Time-series Statistical Analyses: Logistic linear regression, PROC Mixed, PROC Genmod Age Groups : 6-12 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): 10.8 (7.1) Range (Min, Max): (1.8, 53.5) Copollutant (correlation): CO NO 2 SO 2 O 3 PM Increment: 1 μg/m 3 β (SE) AM: -0.003 (0.009) PM: 0.004 (0.011) Odds Ratio (Lower CI, Upper CI) Lag 0.971 (0.843, 1.118) 0-3 avg.



### December 2009 E-212

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ranzi et al. (2004, 089500 ) Period of Study: Feb-May 1999

Location: Emilia-Romagmna, Italy (urban-industrial and rural area) Outcome: respiratory symptoms, PEF measurements, drug consumption and daily activity Age Groups : Children, mean age=(7.2- 7.9 yr) Study Design: Panel study

N: 120 children Statistical Analyses: Ecological analysis and Panel analysis

Covariates: Temperature, humidity, gender, medicinal use, symptomatic status of previous day Dose-response Investigated? No Statistical Package : NR Lags Considered: 0, 1, 2, 3, 0-3 ma Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD):

Urban= 53.07

Rural= 29.11 Monitoring Stations : 3 Copollutant (correlation):

TSP: r=0.613 Daily air pollution concentrations: r= 0.658 PM Increment: 10 μg/m 3

Effect Estimate: Urban-industrial panel Cough and Phlegm: RR=1.0044 (1.0011-1.0077)

Reference: Rodriguez et al. (2007, 092842 ) Period of Study: 1996-2003

Location: Perth, Australia Outcome: Body temperature, cough, runny/ blocked nose, wheeze/ rattle chest (daily) Age Groups : Children 0-5 yr old Study Design: hospital-based cohort study

N: 198-263 children Statistical Analyses: Logistic regression with GEE and AR (order not specified) working covariance

Covariates: temperature, humidity Dose-response Investigated? No Statistical Package : SAS Lags Considered: 0-5 days Pollutant: PM 2.5 Averaging Time: 1 h and 24 h Mean (SD): 1-h averaging, 20.767 24-h averaging, 8.534 Range (Min, Max): 1-h averaging (0.012: 93.433) 24-h averaging (0.004: 39.404) Monitoring Stations : 10 total, usually 3-5 sites for each pollutant Copollutant (correlation):

O 3 NO +

CO PM Increment: NR [Lower CI, Upper CI] lag: NR LAG: 0 day PM 2.5 , 1-h Body temperature: 1.004 [0.998: 1.011] Cough: 1.006 [1.000: 1.012] Wheeze/rattle chest: 1.004 [0.998: 1.010] Runny/blocked nose: 0.997 [0.983: 1.010] PM 2.5 , 24-h Body temperature: 1.005 [0.986: 1.024] Cough: 1.019 [0.999: 1.040] Wheeze/rattle chest: 0.990 [0.969: 1.012] Runny/blocked nose: 0.968 [0.926: 1.013] LAG: 5 days PM 2.5 , 1-h Body temperature: 1.005 [0.999: 1.040] Cough: 1.003 [0.995: 1.010] Wheeze/rattle chest: 1.005 [0.998: 10.12] Runny/blocked nose: 1.015 [1.000: 1.030] PM 2.5 , 24-h Body temperature: 1.020 [0.998: 1.011] Cough: 1.006 [0.984: 1.011] Wheeze/rattle chest: 1.018 [0.997: 1.040] Runny/blocked nose: 1.039 [0.990: 1.089] LAG: 0-5 days PM 2.5 , 1-h Body temperature: 1.000 [0.998: 1.002] Cough: 1.001 [0.999: 1.003] Wheeze/rattle chest: 1.002 [1.000: 1.004] Runny/blocked nose: 1.01 [0.997: 1.006] 1.02 PM 2.5 , 24-h Body temperature: 1.000 [0.994: 1.005] Cough: 1.004 [0.997: 1.011] Wheeze/rattle chest: 1.001 [0.995: 1.007] Runny/blocked nose: 0.998 [0.985: 1.011]



### December 2009 E-213

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sakai et al. (2004, 087435 ) Period of Study: Nov 1999-Mar 2001

Location: Diesel-powered ship from Tokyo, Japan to Showa Station on Ongul Island, Antarctica for 366 days (from Feb 1, 2000) and then heading back to Japan on Feb 1, 2001 Outcome: circulating leukocyte counts and serum inflammatory cytokine levels Age Groups : 24-57 yr, mean=36.1 ± 4.7 yr Study Design: Cohort

N: 39 members of 41st Japanese Antarctic Research Expedition (JARE-41) Statistical Analyses: ANOVA

Covariates: Smoking history, occupational pollutant exposure Dose-response Investigated? No Statistical Package : SPSS 11.5J Pollutant: PM 5.0-2.0 Averaging Time: 24 h Unit (i.e. μg/m3): particles/L PM Component: organic and inorganic substances, including microorganisms Copollutant (correlation):

PM 2.0-0.3 PM 10-5.0 Effect Estimate: Multiple regression analysis between inhaled factors in Antarctica Total leukocyte Cigarette smoking= 0.211, p < 0.001 Support staff= 0.139, p=0.024 Total PM= 0.168, p=0.004 Segmented PMN Cigarette smoking= 0.015, p=0.805 Support staff= 0.097, p=0.119 Total PM= 0.272, p < 0.001

Band-formed PMN Cigarette smoking= 0.035, p=0.543 Support staff= 0.010, p=0.864 Total PM= 0.470, p < 0.001 Monocyte Cigarette smoking= 0.081, p=0.187 Support staff= -0.019, p=0.759 Total PM= 0.328, p < 0.001

G-CSF Cigarette smoking= 0.131, p < 0.038 Support staff= 0.176, p=0.005 Total PM= 0.078, p=0.186

IL-6 Cigarette smoking= 0.182, p=0.004 Support staff= 0.076, p=0.228 Total PM= 0.158, p=0.008 Reference: Sakai et al. (2004, 087435 ) Period of Study: Nov 1999-Mar 28, 2001

Location: Diesel-powered ship from Tokyo, Japan to Showa Station on Ongul Island, Antarctica for 366 days (from Feb 1, 2000) and then heading back to Japan on Feb 1, 2001 Outcome: circulating leukocyte counts and serum inflammatory cytokine levels Age Groups : 24-57 yr, mean=36.1 ± 4.7 yr Study Design: cohort

N: 39 members of 41st JapaneseAntarctic Research Expedition (JARE41) Statistical Analyses: ANOVA

Covariates: Smoking history, occupational pollutant exposure Dose-response Investigated? No Statistical Package : SPSS 11.5J Pollutant: PM 10-5.0 Averaging Time: 24 h Unit (i.e. μg/m3): particles/L Monitoring Stations : NR Copollutant (correlation):

PM 2.0-0.3 PM 10-5.0 Effect Estimate : Multiple regression analysis between inhaled factors in Antarctica Total leukocyte Cigarette smoking= 0.211, p < 0.001 Support staff= 0.139, p=0.024 Total PM= 0.168, p=0.004 Segmented PMN Cigarette smoking= 0.015, p=0.805 Support staff= 0.097, p=0.119 Total PM= 0.272, p < 0.001

Band-formed PMN Cigarette smoking= 0.035, p=0.543 Support staff= 0.010, p=0.864 Total PM= 0.470, p < 0.001

Monocyte Cigarette smoking= 0.081, p=0.187 Support staff= -0.019, p=0.759 Total PM= 0.328, p < 0.001

G-CSF Cigarette smoking= 0.131, p < 0.038 Support staff= 0.176, p=0.005 Total PM= 0.078, p=0.186

IL-6 Cigarette smoking= 0.182, p=0.004 Support staff= 0.076, p=0.228 Total PM= 0.158, p=0.008



### December 2009 E-214

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Silkoff et al. (2005, 087471 ) Period of Study: Winter 1999-2000, Winter 2000-2001

Location: Denver, CO Outcome: Lung function: FEV 1 , PEF Age Groups : Adults (>40 yr-old) with COPD, as well as >10 pack-yr tobacco use, FEV 1 < 70%, FEV 1 /FVC < 60%, and no other lung disease Study Design: COPD patient panel study (2 independent panels One for each winter)

N: 34 subjects (16 1st winter, 18 second winter) Statistical Analyses: Mixed effects models with first-order, autoregressive, ma variance-covariance Binary outcomes (rescue medication use, total symptom score) assessed using Poisson regression with GEE andfirst-order, auto-regressive variancecovariance

Covariates: Temperature, relative humidity, barometric pressure analysis run separately for each winter

Season: Winter Dose-response Investigated? No Statistical Package : SAS Lags Considered: 0-2 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Winter 1999-2000: 9.0 (5.2) Winter 2000-2001: 14.3 (9.6) Percentiles: Winter 1999-2000 25th 5.4 50th(Median): 7.7 75th: 11.3 Winter 2000-2001 25th 7.6 50th(Median): 11.7 75th: 17.2 Range (Min, Max): Winter 1999-2000 (1.8, 36.6)

Winter 2000-2001 (3.4, 59.6) Monitoring Stations : multiple sites Copollutant (correlation):

CO

NO 2 PM 10 PM Increment: SD

Winter 1999-2000: 5.2

Winter 2000-2001: 9.6 Model results reported graphically only. No quantitative results reported. Direction of slope ( ± ) and statistical significance (SIG: yes; NS: no) inferred from graphs. Among subjects with severe COPD observed in Winter 1999-2000, statistically significant, but marginal, improvements in PEF associated with morning lag 0 PM 2.5

. There were no statistically significant associations between rescue medication use and symptom score with PM.

Reference: Sivacoumar et al. (2006, 111115 ) Period of Study: Apr 1998-May 1998; Sep 1998-Oct 1998

Location: Pammal, India Outcome: Respiratory symptoms, Decreased pulmonary function Study Design: Case-control Statistical Analyses: Poisson Age Groups : >18 Pollutant: PM 2.5 Averaging Time: 24-h avg The study does not present quantitative results of association.

Reference: Slaughter et al. (2003, 086294 ) Period of Study: 1994

Location: Seattle, WA Outcome: Asthma attacks, asthma severity, medication use Age Groups : 5.1-13.1 yr old Study Design: Cross-sectional study

N: 133 children Statistical Analyses: Ordinal Logistic Regression Poisson Modeling

Covariates: Temperature, Day of the Week, Seasonality Dose-response Investigated? No Statistical Package : STATA Lags Considered: 1-, 2-, 3-day lag Pollutant: PM 2.5 Averaging Time: Daily Avg

25th: 5.0 50th(Median): 7.3 3

75th: 11.3 Monitoring Stations : 3 Copollutant (correlation):

PM 10 = 0.75

CO = 0.82 PM Increment: 10 μg/m 3 increase RR Estimate [Lower CI, Upper CI] lag: Inhaler use: 1-day lag: 1.04 (0.98, 1.10) OR Estimate [Lower CI, Upper CI] lag: Asthma Attack: 1-day lag: 1.20 (1.05, 1.37) Previous day: 1.13 (1.03, 1.23) Medication Use Nontransition model: Previous Day: 1.08 (1.01, 1.15) Notes : Figures of estimated odds ratios for having a more serious asthma attack for short-term, within-subject increases in PM 2.5 , PM 10 , and CO. Transition models additionally control for the previous day’s severity. Figures of estimated relative risks for having inhaler use for short-term, within-subject increases in PM 2.5 , PM 10 , and CO. Transition models additionally control for the previous day’s severity.



### December 2009 E-215

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Strand et al. (2006, 089203 ) Period of Study: 2002-2004

Location: Denver, Colorado, United States Outcome: Reduced forced expiratory volume (FEV 1 ) Age Groups : 6-12 yr old Study Design: Mixed model analysis (using the default restricted maximum likelihood (REML) estimators)

N: 50 children Statistical Analyses: least squares regression, SAS “Output Delivery System” (ODS)

Season: Fall and Winter Dose-response Investigated? Yes Statistical Package : SAS Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): Outdoor: 12.699 (6.426) Indoor: 8.148 (4.348) Sulfate/PM 2.5 /outdoor: 0.079 (0.067) Sulfate/PM 2.5 /indoor: 0.074 (0.060) Range (Min, Max): Mean Personal: (0, 3.035) Outdoor: (0, 6.303) Indoor: (0, 2.759) PM Component: EC, sulfate, nitrate and ETS. Monitoring Stations : 2 fixed monitors and up to 10 personal monitors on a given day. Copollutant (correlation): Sulfate (0.63) PM Increment: 10 μg/m 3

Effects Estimate: Using the estimated slope for the validation study model [Lower CI, Upper CI] lag: 2.2 percent decrease in FEV 1 per 10 μg/m 3 increase in ambient PM 2.5 [0.0, 4.3 decrease] 1 day

Reference: Tang et al. (2007, 091269 ) Period of Study: Dec 2003-Feb 2005

Location: Sin-Chung City, Taipei County, Taiwan Outcome: Peak expiratory flow rate (PEFR) of asthmatic children Age Groups : 6-12 yr Study Design: Panel study

N: 30 children Statistical Analyses: Linear mixedeffect models were used to estimate the effect of PM exposure on PEFR

Covariates: Gender, age, BMI, history of respiratory or atopic disease in family, SHS, acute asthmatic exacerbation in past 12 mo, ambient temp and relative humidity, presence of indoor pollutants, and presence of outdoor pollutants, Dose-response Investigated? yes Statistical Package : S-Plus 2000 Lags Considered: 0-2 Pollutant: PM 2.5 Averaging Time: 1 h Mean (SD): Personal: 27.8 (25.3) Range (Min, Max):

Personal: 1.4-263.4 Monitoring Stations : 1 PM Increment: 24.5 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Change in morning PEFR: -6.00 (-29.85, 17.85) lag 0 -12.52 (-77.93, 52.9) lag 1 -24.87 (-71.49, 21.74) lag 2 -45.67 (-117.09, 25.74) 2-day mean -5.69 (-105.96, 94.59) 3-day mean Change in evening PEFR: 0.50 (-18.82, 19.82) lag 0 16.66 (-7.59, 40.9) lag 1 11.60 (-11.1, 34.31) lag 2 39.97 (7.1, 72.85) 2-day mean -3.32 (-66.14, 59.5) 3-day mean

Reference: Timonen et al. (2004, 087915 ) Period of Study: Oct 1998-Apr 1999

Location: Amsterdam, Netherlands Erfurt, Germany Helsinki, Finland Outcome: Urinary concentration of Clara cell protein CC16 of subjects with coronary heart disease Age Groups : 50+ Study Design: Longitudinal cohort study (panel)

N: 37 (Amsterdam) 47 (Erfurt) 47 (Helsinki) Statistical Analyses: The response of interest was log transformed, creatinine adjusted CC16. Mixed-effect model was used to investigate the association between CC16 and air pollutants.

Covariates: Subjects, long term time trend, temperature (lags 0-3), relative humidity (lags 0-3), barometric pressure (lags 0-3), and weekday of visit. Dose-response Investigated? yes Statistical Package : S-Plus and SAS Lags Considered: 0-3 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Amsterdam: 20.0 μg/m 3 Erfurt: 23.1 μg/m 3 Helsinki: 12.7 μg/m 3

Range (Min, Max): Amsterdam: 3.8-82.2 Erfurt: 4.5-118.1 Helsinki: 3.1-39.8 Monitoring Stations : 3 Copollutant (correlation): Spearman Correlation: NC 0.01-0.1: Amsterdam -0.15 Erfurt 0.62 Helsinki 0.14 NC0.1-1.0: Amsterdam 0.80 Erfurt 0.84 Helsinki 0.80 NO 2 : Amsterdam 0.49 Erfurt 0.82 Helsinki 0.35 CO: Amsterdam 0.58 Erfurt 0.77 Helsinki 0.40 PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Pooled estimate; 2.8 (-1.1-6.7) lag 0 2.9 (-0.6-6.5) lag 1 5.0 (-2.4-12.4) lag 2 1.6 (-4.7-7.9) lag 3 9.7 (-6.0-25.4) 5-day mean

CC16 was not associated to PM 2.5 in the pooled analysis but CC16 was significantly associated to PM 2.5 in Helsinki: 23.3 (6.3-40.3) lag 0 6.4 (-8.2-21.1) lag 1 20.2 (6.9-33.5) lag 2 17.6 (4.3-30.9) lag 3 38.8 (15.8-61.8) 5-day mean



### December 2009 E-216

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Trenga et al. (2006, 155209 ) Period of Study: 1999-2002

Location: Seattle, WA Outcome: Lung function: FEV 1 , PEF, MMEF (maximal midexpiratory flow assessed only for children) Age Groups : Adults (56-89-yr-old) healthy & with COPD Asthmatic children 6-13-yr-old Study Design: Adult and pediatric panel study over 3 yr with 1 monitoring period (“session”) per yr

N: 57 adults (33 healthy, 24 with COPD) = 692 subject-days = 207 study-days17 asthmatic children = 319 subjectdays = 98 study-days Statistical Analyses: Mixed effects, longitudinal regression models, with the effects of pollutant decomposed into each subject’s a) overall meanb) Difference between their sessionspecific mean and overall mean c) Difference between their daily values and session-specific mean

Covariates: G ender, age, ventral site temperature and relative humidity, CO, NO 2 Dose-response Investigated? No Statistical Package : SAS Lags Considered: 0-1 days Pollutant: PM 2.5 Averaging Time: 24 h Percentiles: Children Personal 25th: 8.1 50th(Median): 11.3 75th: 16.3 Indoor 25th: 5.7 50th(Median): 7.5 75th: 10.2 Local outdoor 25th: 6.4 50th(Median): 9.6 75th: 14.

Adults Personal 25th: 5.9 50th(Median): 8.5 75th: 12.4 Indoor 25th: 5.1 50th(Median): 7.6 75th: 10.8 Local outdoor 25th: 6 50th(Median): 8.6 75th: 13.1 Range (Min, Max): Children, Personal 1.0, 49.4 Indoor (2.2, 36.3) Local outdoor (2.8, 40.4) Adults, Personal 1.3, 66.6 Indoor(1.6, 65.3) Local outdoor (0.0, 41.5) Monitoring Stations : 2 also subject-specific local outdoors (i.e., at each home), indoor, and personal Copollutant (correlation): CO NO 2 PM 2.5 PM 10-2.5 (coarse) PM Increment: 10 μg/m 3

ADULT Personal PM 2.5 - FEV 1 Overall: Lag 0 -6.0 [-29.1: 17.2] Lag 1 12.0 [-12.9: 36.9] No-COPD: Lag 0 -4.6 [-31.0: 21.9] Lag 1 19.3 [-8.2: 46.7] COPD: Lag 0 -10.2 [-55.8: 35.4] Lag 1 -19.0 [-74.1: 36.2] PEF: Lag 0 1.5 [-2.2: 5.2] Lag 1 2.1 [-1.9: 6.1] No-COPD: Lag 0 3.4 [-0.9: 7.6] Lag 1 1.9 [-2.5: 6.3] COPD: Lag 0 -4.3 [-11.5: 3.0] Lag 1 2.6 [-6.3: 11.5] Indoor PM 2.5 - FEV 1 Overall: Lag 0 -12.8 [-44.5: 19.0] Lag 1 19.4 [-11.3: 50.1] No-COPD: Lag 0 -15.8 [-50.0: 18.4] Lag 1 28.4 [-4.6: 61.3] COPD: Lag 0 2.6 [-71.7: 76.8] Lag 1 -29.7 [-102.9: 43.5] PEF Overall: Lag 0 -0.5 [-5.6: 4.6] Lag 1 2.3 [-3.3: 7.8] No-COPD: Lag 0 0.1 [-5.4: 5.6] Lag 1 2.5 [-3.5: 8.4] COPD: Lag 0 -3.2 [-15.1: 8.7] Lag 1 1.1 [-12.0: 14.3] Outdoor Home PM 2.5 - FEV 1 Overall: Lag 0 -1.4 [-35.6: 32.7] Lag 1 -2.4 [-37.6: 32.7]. No-COPD: Lag 0 1.5 [-36.1: 39.2] Lag 1 10.7 [-26.9: 48.4] COPD: Lag 0 -8.9 [-62.2: 44.4] Lag 1 -45.2 [-102.6: 12.1] PEF Overall: Lag 0 2.3 [-3.3: 7.9] Lag 1 0.4 [-5.6: 6.4] No-COPD: Lag 0 4.0 [-2.2: 10.1] Lag 1 2.0 [-4.4: 8.4] COPD: Lag 0 -1.8 [-10.6: 6.9] Lag 1 -4.8 [-14.6: 4.9] Central Sites PM 2.5 - FEV 1 Overall: Lag 0 -35.5 [-70.0: -1.0] Lag 1 -40.4 [-71.1: -9.6]. No-COPD: Lag 0 -32.6 [-69.5: 4.3] Lag 1 -29.0 [-62.5: 4.5] COPD: Lag 0 -43.6 [-95.0: 7.8] Lag 1 -70.8 [-118.4: 23.1] PEF Overall: Lag 0 1.5 [-4.2: 7.1] Lag 1 -2.3 [-7.4: 2.9] No-COPD: Lag 0 2.5 [-3.5: 8.6] Lag 1 -0.5 [-6.1: 5.0] COPD: Lag 0 -1.5 [-9.9: 6.9] Lag 1 -7.1 [-15.0: 0.9] PEDIATRIC FEV 1 Personal PM 2.5 Overall: Lag 0 -13.08 [-38.26: 12.10] Lag 1 -16.12 [-42.61: 10.37]. No anti-inflammatory medication: Lag 0 -41.73 [-94.31: 10.84] Lag 1 -30.99 [-82.17: 20.19]. Anti-inflammatory medication: Lag 0 -4.61 [-34.49: 25.28] Lag 1 -10.87 [-45.01: 23.27] Indoor PM 2.5 Overall: Lag 0 -45.90 [-89.92: 1.88] Lag 1 -64.78 [-111.27: 18.28] No anti-inflammatory medication: Lag 0 -75.92 [-145.16: 6.67] Lag 1 -65.08 [-136.98: 6.82]. Anti-inflammatory medication: Lag 0 -28.50 [-94.72: 37.71]



### December 2009 E-217

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Lag 1 -64.60 -147.23: 18.04] Outdoor Home PM 2.5 Overall: Lag 0 -13.11 [-57.41: 31.19] Lag 1 -9.37 [-54.73: 36.00]. No anti-inflammatory medication: Lag 0 -24.42 [-81.22: 32.38] Lag 1 16.52 [-45.76: 78.80]. Anti-inflammatory medication: Lag 0 -3.59 [-75.88: 68.70] Lag 1-26.76 [-89.53: 36.01] Central Sites PM 2.5 . Overall: Lag 0 -12.32 [-53.21: 28.56] Lag 1 5.75 [-33.27: 44.76]. No anti-inflammatory medication: Lag 0 -33.59 [-89.99: 22.82] Lag 1 31.30 [-29.91: 92.51] Anti-inflammatory medication: Lag 0 -2.13 [-71.99: 67.73] Lag 1 -3.53 [-67.32: 60.27] PEF: Personal PM 2.5 Overall: Lag 0 0.31 [-4.02: 4.64] Lag 1 -2.19 [-6.49: 2.12] No anti-inflammatory medication: Lag 0 0.22 [-8.85: 9.29] Lag 1 -10.48 [-18.68: 2.28] Anti-inflammatory medication: Lag 0 0.34 [-4.67: 5.35] Lag 1 0.74 [-4.21: 5.69] Indoor PM 2.5 Overall: Lag 0 -8.68 [-16.64: -0.72] Lag 1 -9.22 [-17.51: -0.93] No anti-inflammatory medication: Lag 0 -13.34 [-25.90: -0.79] Lag 1 -17.13 [-29.86: 4.41]. Anti-inflammatory medication: Lag 0 -5.98 [-15.85: 3.89] Lag 1 -4.19 [-14.59: 6.20] Outdoor Home PM 2.5 Overall: Lag 0 -6.27 [-14.07: 1.53] Lag 1 -5.64 [-13.73: 2.44]. No anti-inflammatory medication: Lag 0 -7.52 [-17.56: 2.51] Lag 1 -6.92 [-18.03: 4.19]. Anti-inflammatory medication: Lag 0 -5.22 [-14.77: 4.34] Lag 1 -4.78 [-14.42: 4.86] Central Sites PM 2.5 Overall: Lag 0 -5.62 [-12.86: 1.62] Lag 1 -2.45 [-9.34: 4.43]. No anti-inflammatory medication: Lag 0 -6.32 [-16.31: 3.68] Lag 1 -0.83 [-11.60: 9.95] Anti-inflammatory medication: Lag 0 -5.29 [-13.42: 2.85] Lag 1 -3.04 [-10.76: 4.67] MMEF Personal PM 2.5 Overall: Lag 0 -0.99 [-3.96: 1.98] Lag 1 -1.08 [-4.05: 1.88]. No anti-inflammatory medication: Lag 0 -3.32 [-9.52: 2.88] Lag 1 -2.49 [-8.23: 3.25]. Anti-inflammatory medication: Lag 0 -0.31 [-3.77: 3.16] Lag 1 -0.59 [-4.06: 2.89] Indoor PM 2.5 Overall : Lag 0 -3.29 [-8.52: 1.94] Lag 1 -11.08 [-16.26: 5.90]

. Anti-inflammatory medication: Lag 0-12.65 [-20.74: -4.56]’ Lag 1 -



### December 2009 E-218

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 13.84 [-21.82: 5.85] Anti-inflammatory medication: Lag 0 2.14 [-4.17: 8.45] Lag 1 -9.33 [-15.89: -2.78] Outdoor Home PM 2.5 Overall : Lag 0 -4.13 [-9.28: 1.01] Lag 1 -0.73 [-6.02: 4.56] No anti-inflammatory medication: Lag 0 -8.23 [-14.77: 1.69] Lag 1 -1.19 [-8.45: 6.07] Anti-inflammatory medication: Lag 0 -0.68 [-6.87: 5.50] Lag 1 -0.42 [-6.72: 5.87] Central Sites PM 2.5 . Overall : Lag 0 -2.10 [-6.99: 2.79] Lag 1 -0.12 [-4.67: 4.42] No anti-inflammatory medication: Lag 0 -8.21 [-14.79: 1.62] Lag 1 -0.22 [-7.34: 6.90] Anti-inflammatory medication: Lag 0 0.82 [-4.48: 6.12]. Lag 1 -0.09 [-5.19: 5.01] Reference: Tang et al. (2007, 091269 ) Period of Study: Dec 2003-Feb 2005

Location: Sin-Chung City, Taipei County, Taiwan Outcome: Peak expiratory flow rate (PEFR) of asthmatic children Age Groups : 6-12 yr Study Design: Panel study

N: 30 children Statistical Analyses: Linear mixedeffect models were used to estimate the effect of PM exposure on PEFR

Covariates: Gender, age, BMI, history of respiratory or atopic disease in family, SHS, acute asthmatic exacerbation in past 12 mo, ambient temp and relative humidity, presence of indoor pollutants, and presence of outdoor pollutants, Dose-response Investigated? Yes Statistical Package : S-Plus 2000 Lags Considered: 0-2 Pollutant: PM 2.5-1 Averaging Time: 1 h Mean (SD): Personal: 6.2 (4.8) Range (Min, Max):

Personal: 0.3-86.8 Monitoring Stations : 1 No quantitative effects reported.

Reference: Tang et al. (2007, 091269 ) Period of Study: Dec 2003-Feb 2005

Location: Sin-Chung City, Taipei County, Taiwan Outcome: Peak expiratory flow rate (PEFR) of asthmatic children Age Groups : 6-12 yr Study Design: Panel study

N: 30 children Statistical Analyses: Linear mixedeffect models were used to estimate the effect of PM exposure on PEFR

Covariates: Gender, age, BMI, history of respiratory or atopic disease in family, SHS, acute asthmatic exacerbation in past 12 mo, ambient temp and relative humidity, presence of indoor pollutants, and presence of outdoor pollutants, Dose-response Investigated? yes Statistical Package : S-Plus 2000 Lags Considered: 0-2 Pollutant: PM1 Averaging Time: 1 h Mean (SD): Personal: 34.0 (28.9) Ambient: 31.4 (18.8) Range (Min, Max):

Personal: 1.8-284.6

Ambient: 0.1-128.4 Monitoring Stations : 1 PM Increment: 27.6 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Change in morning PEFR: -6.44 (-30.18, 17.29) lag 0 -12.26 (-77.6 , 53.09) lag 1 -4.38 (-54.79, 46.03) lag 2 -44.06 (-113.79, 25.67) 2-day mean -6.01 (-101.48, 89.46) 3-day mean Change in evening PEFR: 1.17 (-17.79, 20.13) lag 0 -4.98 (-27.77, 17.81) lag 1 11.30 (-11.55, 34.16) lag 2 41.74 (11.36, 72.13) 2-day mean 28.21 (-19.08, 75.5) 3-day mean



### December 2009 E-219

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Timonen et al. (2004, 087915 ) Period of Study: Oct 1998-Apr 1999

Location: Amsterdam, The Netherlands Erfurt, Germany Helsinki, Finland Outcome: Urinary concentration of Clara cell protein CC16 of subjects with coronary heart disease Age Groups : 50+ Study Design: Longitudinal cohort study (panel) N: N=37 (Amsterdam) N=47 (Erfurt) N=47 (Helsinki) Statistical Analyses: The response of interest was log transformed, creatinine adjusted CC16. Mixed-effect model was used to investigate the association between CC16 and air pollutants.

Covariates: Subjects, long term time trend, temperature (lags 0-3), relative humidity (lags 0-3), barometric pressure (lags 0-3), and weekday of visit. Dose-response Investigated? yes Statistical Package : S-Plus and SAS Lags Considered: 0-3 Pollutant: NC 0.01-0.1 Averaging Time: 24 h Mean (SD): Amsterdam: 17338 /cm 3 Erfurt: 21124 /cm 3 Helsinki: 17041 /cm 3

Range (Min, Max): Amsterdam: 5699-37195 Erfurt: 3867-96678 Helsinki: 2305-50306 Unit (i.e. μg/m 3 ): 1/cm 3

Monitoring Stations : 3 PM 2.5 : Amsterdam -0.15 Erfurt 0.62 Helsinki 0.14 NO 2 : Amsterdam 0.49 Erfurt 0.82 Helsinki 0.72 CO: Amsterdam 0.22 Erfurt 0.72 Helsinki 0.35 PM Increment: 10,000 /cm 3 RR Estimate [Lower CI, Upper CI] lag: Pooled estimate; 1.7 (-4.4-7.8) lag 0 -1.8 (-8.3-4.6) lag 1 1.5 (-5.6-8.6) lag 2 2.3 (-4.8-9.3) lag 3 1.8 (-9.4-13.0) 5-day mean

There was no association between NC 0.01-0.1 and CC16 in the pooled analysis.

Reference: Timonen et al. (2004, 087915 ) Period of Study: Oct 1998-Apr 1999

Location: Amsterdam, The Netherlands Erfurt, Germany Helsinki, Finland Outcome: Urinary concentration of Clara cell protein CC16 of subjects with coronary heart disease Age Groups : 50+ Study Design: Longitudinal cohort study (panel) N: N=37 (Amsterdam) N=47 (Erfurt) N=47 (Helsinki) Statistical Analyses: The response of interest was log transformed, creatinine adjusted CC16. Mixed-effect model was used to investigate the association between CC16 and air pollutants.

Covariates: Subjects, long term time trend, temperature (lags 0-3), relative humidity (lags 0-3), barometric pressure (lags 0-3), and weekday of visit. Dose-response Investigated? Yes Statistical Package : S-Plus and SAS Lags Considered: 0-3 Pollutant: NC10-0.1 Averaging Time: 24 h Mean (SD): Amsterdam: 2131 /cm 3 Erfurt: 1829 /cm 3 Helsinki: 1390 /cm 3

Range (Min, Max): Amsterdam: 413-6413 Erfurt: 303-6848 Helsinki: 344-3782 Unit (i.e. μg/m 3 ): 1/cm 3

Monitoring Stations : 3 Copollutant (correlation): Spearman Correlation: NC 0.1-0.01: Amsterdam 0.16 Erfurt 0.67 Helsinki 0.53 PM 2.5 : Amsterdam 0.80 Erfurt 0.84 Helsinki 0.80 NO :

2 Amsterdam 0.67 Erfurt 0.82 Helsinki 0.72 CO: Amsterdam 0.60 Erfurt 0.78 Helsinki 0.51 PM Increment: 1000 /cm 3 RR Estimate [Lower CI, Upper CI] lag: Pooled estimate; 4.3 (-1.4-10.0) lag 0 5.1 (-0.6-10.7) lag 1 4.5 (-0.5-9.6) lag 2 1.6 (-3.5-6.7) lag 3 13.1 (-4.3-30.5) 5-day mean

CC16 was not associated to NC 0.1-1.0 in the pooled analysis but CC16 was significantly associated to NC 0.1-1.0 in Helsinki: 15.5 (0.001-30.9) lag 0 10.8 (-4.2-25.8) lag 1 10.5 9-4.1-25.1) lag 2 17.4 (3.4-31.4) lag 3 43.2 (17.4-69.0) 5-day mean



### December 2009 E-220

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: von Klot et al. (2002, 034706 ) Period of Study: Sep 1996-Mar 1997 (winter)

Location: Erfurt, Germany Outcome: Asthma symptoms (wheezing, shortness of breath at rest, waking up with breathing problems, or coughing without having a cold) and Asthma medication (inhaled short-acting ß2- agonists, inhaled long-acting ß2- agonists, inhaled corticosteroids, cromolyn sodium, theophylline, oral corticosteroids, and N-acetylcysteine) Age Groups : Adults, mean=59.0 yr and range =37-77 yr Study Design: Panel study

N: 53 adult asthmatics Statistical Analyses: Logistic regression models

Covariates: Seasonal variation in medication use or symptom prevalence, meteorological factors (relative humidity, temperature), weekend, Christmas holidays

Season: W inter Dose-response Investigated? No Statistical Package : NR Lags Considered: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ma calculated from same day and preceding days Pollutant: MC0.5-0.1 Averaging Time: 10-min intervals Mean (SD): 24.8 Percentiles: 25th: 11.4 50th(Median): 19.6 75th: 33.1 Range (Min, Max): (2.4-108.3) Copollutant (correlation): PM 10-2.5 : r= 0.51 NC0.1-0.01: r= 0.45 NC0.5-0.1: r= 0.95 NC2.5-0.5: r= 0.92 MC2.5-0.01: r= 1.00 PM 10 : r= 0.91 NO 2 : r= 0.69 CO: r= 0.66 SO 2 : r= 0.60 NC Increment: 1 IQR Effect Estimate [Lower CI, Upper CI]: Association between the prevalence of inhaled ß2- agonist use and MC0.1-0.5 Same day, IQR= 21, OR= 0.98 (0.92-1.04) 5-day mean, IQR= 21 OR= 1.11 (1.02-1.20) 14-day mean IQR= 17, OR= 1.01 (0.93-1.10) Association between the prevalence of inhaled corticosteroid use and MC0.1-0.5 Same day, IQR= 2, OR= 1.09 (1.02-1.17) 5-day mean IQR= 21, OR= 1.28 (1.18-1.39) 14-day mean, IQR= 17, OR= 1.49 (1.38-1.61)

Association between the prevalence of wheezing and MC0.1-0.5 Same day, IQR= 21, OR= 1.01 (0.94-1.08) 5-day mean, IQR= 21, OR= 1.08 (0.99-1.17) 14-day mean, IQR= 17, OR= 1.05 (0.96-1.15)

Reference: von Klot et al. (2002, 034706 ) Period of Study: Sep 1996-Mar 1997 (winter)

Location: Erfurt, Germany Outcome: Asthma symptoms (wheezing, shortness of breath at rest, waking up with breathing problems, or coughing without having a cold) and Asthma medication (inhaled short-acting ß2- agonists, inhaled long-acting ß2- agonists, inhaled corticosteroids, cromolyn sodium, theophylline, oral corticosteroids, and N-acetylcysteine) Age Groups : Adults, mean=59.0 yr and range =37-77 yr Study Design: Panel study

N: 53 adult asthmatics Statistical Analyses: Logistic regression models

Covariates: Seasonal variation in medication use or symptom prevalence, meteorological factors (relative humidity, temperature), weekend, Christmas holidays

Season: Winter Dose-response Investigated? No Statistical Package : NR Lags Considered: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ma calculated from same day and preceding days Pollutant: MC2.5-0.01 Averaging Time: 10-min intervals Mean (SD): 30.3

Percentiles:

25th: 13.5 50th(Median): 24.6

75th: 41.3 Range (Min, Max): (3.6-133.8) Copollutant (correlation):

PM 10-2.5 : r= 0.52

NC 0.5-0.1 : r= 0.45

NC 2.5-0.5 : r= 0.94

MC 0.5-0.1 : r= 1.00

NC 0.1-0.01 : r= 0.45

PM 10 : r= 0.94

NO 2 : r= 0.68

CO: r= 0.65

SO 2 : r= 0.62 NC Increment: 1 IQR Effect Estimate [Lower CI, Upper CI]: Association between the prevalence of inhaled ß2- agonist use and MC0.01- 2.5 Same day, IQR= 28, OR= 0.96 (0.90- 1.04) 5-day mean, IQR= 26 , OR= 1.10 (1.01- 1.20) 14-day mean, IQR= 20, OR= 1.03 (0.95-1.12)



### December 2009 E-221

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: von Klot et al. (2002, 034706 ) Period of Study: Sep 1996-Mar 1997 (winter)

Location: Erfurt, Germany Outcome: Asthma symptoms (wheezing, shortness of breath at rest, waking up with breathing problems, or coughing without having a cold) and Asthma medication (inhaled short-acting ß2- agonists, inhaled long-acting ß2- agonists, inhaled corticosteroids, cromolyn sodium, theophylline, oral corticosteroids, and N-acetylcysteine) Age Groups : Adults, mean=59.0 yr and range =37-77 yr Study Design: Panel study

N: 53 adult asthmatics Statistical Analyses: Logistic regression models

Covariates: Seasonal variation in medication use or symptom prevalence, meteorological factors (relative humidity, temperature), weekend, Christmas holidays

Season: Winter Dose-response Investigated? No Statistical Package : NR Lags Considered: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ma calculated from same day and preceding days Pollutant: NC0.1-0.01 Averaging Time: 10-min intervals Mean (SD): 17,300 /cm 3

Percentiles:

25th: 9286 50th(Median): 16940

75th: 24484 Range (Min, Max): (3272-46195) Unit (i.e. μg/m 3 ): 1/cm 3 Copollutant (correlation):

PM 10-2.5 : r= 0.41

NC 0.5-0.1 : r= 0.55

NC 2.5-0.5 : r= 0.34

MC 0.5-0.1 : r= 0.45

MC 2.5-0.01 : r= 0.45

PM 10 : r= 0.51

NO 2 : r= 0.66

CO: r= 0.66

SO 2 : r= 0.36 NC Increment: 1 IQR Effect Estimate [Lower CI, Upper CI]: Association between the prevalence of inhaled ß2- agonist use and NC0.01-0.1 Same day, IQR= 15000, OR= 0.97 (0.90-1.04) 5-day mean, IQR= 10000, OR= 1.11 (1.01-1.21) 14-day mean, IQR= 7700, OR= 1.08 (0.96-1.21) Association between two pollutants, jointly in one model, and the Outcomes Inhaled short-acting ß2- agonist use NC0.1-0.01 OR= 1.07 (0.97-1.18) MC0.5-0.1: OR= 1.07 (0.98-1.18)

Inhaled corticosteroid use NC0.1-0.01 OR= 1.01 (0.87-1.18) MC0.5-0.1: OR= 1.53 (1.39-1.69)

Wheezing NC0.1-0.01 OR= 1.12 (1.01-1.24) MC0.5-0.1: OR= 1.02 (0.92-1.12)

Association between the prevalence of inhaled corticosteroid use and NC0.01- 0.1 Same day, IQR= 15000, OR= 1.07 (1.00-1.15) 5-day mean, IQR= 10000, OR= 1.22 (1.12-1.33) 14-day mean, IQR= 7700, OR= 1.45 (1.29-1.63) Association between the prevalence of wheezing and NC0.1-0.01 Same day, IQR= 15000, OR= 0.94 (0.86-1.01) 5-day mean, IQR= 10000, OR= 1.13 (1.03-1.24) 14-day mean, IQR= 7700, OR= 1.27 (1.13-1.43) Association between the prevalence of respiratory symptoms and NC0.1-0.01 Attack of shortness of breath and wheezing Same day, IQR= 15000, OR= 1.01 (0.91-1.12) 5-day mean, IQR= 10000, OR= 1.08 (0.96-1.21) 14-day mean, IQR= 7700, OR= 1.26 (1.08-1.48)

Walking up with breathing problems Same day, IQR= 15000, OR= 1.04 (0.96-1.13) 5-day mean, IQR= 10000, OR= 1.09 (0.99-1.19) 14-day mean, IQR= 7700, OR= 1.26 (1.13-1.41)

Shortness of breath Same day, IQR= 15000, OR= 0.98 (0.90-1.06) 5-day mean, IQR= 10000, OR= 1.09 (0.99-1.19) 14-day mean, IQR= 7700, OR= 1.24 (1.11-1.40)

Phlegm Same day, IQR= 15000, OR= 1.01 (0.94-1.09)



### December 2009 E-222

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 5-day mean, IQR= 10000, OR= 1.11 (1.02-1.21) 14-day mean, IQR= 7700, OR= 1.11 (0.99-1.25) Cough Same day, IQR= 15000, OR= 1.07 (0.98-1.16) 5-day mean, IQR= 10000, OR= 1.17 (1.07-1.28) 14-day mean, IQR= 7700, OR= 1.20 (1.06-1.35) Reference: von Klot et al. (2002, 034706 ) Period of Study: Sep 1996-Mar 1997 (winter)

Location: Erfurt, Germany Outcome: Asthma symptoms (wheezing, shortness of breath at rest, waking up with breathing problems, or coughing without having a cold) and Asthma medication (inhaled short-acting ß2- agonists, inhaled long-acting ß2- agonists, inhaled corticosteroids, cromolyn sodium, theophylline, oral corticosteroids, and N-acetylcysteine) Age Groups : Adults, mean=59.0 yr and range =37-77 yr Study Design: Panel study

N: 53 adult asthmatics Statistical Analyses: Logistic regression models

Covariates: Seasonal variation in medication use or symptom prevalence, meteorological factors (relative humidity, temperature), weekend, Christmas holidays

Season: Winter Dose-response Investigated? No Statistical Package : NR Lags Considered: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ma calculated from same day and preceding days Pollutant: NC0.5-0.1 Averaging Time: 10-min intervals Mean (SD): 2005 /cm 3

Percentiles:

25th: 958 50th(Median): 1610

75th: 2767 Range (Min, Max): (291-6700) Unit (i.e. μg/m 3 ): 1/cm 3 Copollutant (correlation):

PM 10-2.5 : r= 0.50

NC 0.1-0.01 : r= 0.55

NC 2.5-0.5 : r= 0.76

MC 0.5-0.1 : r= 0.95

MC 2.5-0.01 : r= 0.93

PM 10 : r= 0.85

NO 2 : r= 0.75

CO: r= 0.79

SO 2 : r= 0.51 NC Increment: 1 IQR Effect Estimate [Lower CI, Upper CI]: Association between the prevalence of inhaled ß2- agonist use and NC0.5-0.1 Same day, IQR= 1800, OR= 0.99 (0.92-1.05) 5-day mean, IQR= 1500, OR= 1.10 (1.03-1.19) 14-day mean, IQR= 1450, OR= 0.95 (0.86-1.05)

Association between the prevalence of inhaled corticosteroid use and NC0.5- 0.1 Same day, IQR= 1800, OR= 1.06 (0.99-1.14) 5-day mean, IQR= 1500, OR= 1.23 (1.14-1.32) 14-day mean, IQR= 1450, OR= 1.51 (1.37-1.67) Association between the prevalence of wheezing and NC0.5-0.1 Same day, IQR= 1800, OR= 1.00 (0.93-1.07) 5-day mean, IQR= 1500, OR= 1.08 (1.00-1.17) 14-day mean, IQR= 1450, OR= 1.11 (1.00-1.24)



### December 2009 E-223

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: von Klot et al. (2002, 034706 ) Period of Study: Sep 1996-Mar 1997 (winter)

Location: Erfurt, Germany Outcome: Asthma symptoms (wheezing, shortness of breath at rest, waking up with breathing problems, or coughing without having a cold) and Asthma medication (inhaled short-acting ß2- agonists, inhaled long-acting ß2- agonists, inhaled corticosteroids, cromolyn sodium, theophylline, oral corticosteroids, and N-acetylcysteine) Age Groups : Adults, mean=59.0 yr and range =37-77 yr Study Design: Panel study

N: 53 adult asthmatics Statistical Analyses: Logistic regression models

Covariates: Seasonal variation in medication use or symptom prevalence, meteorological factors (relative humidity, temperature), weekend, Christmas holidays

Season: Winter Dose-response Investigated? No Statistical Package : NR Lags Considered: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ma calculated from same day and preceding days Pollutant: NC2.5-0.5 Averaging Time: 10-min intervals Mean (SD): 21.4 /cm 3

Percentiles:

25th: 5.6 50th(Median): 13.0

75th: 31.6 Range (Min, Max): (0.9-127.6) Unit (i.e. μg/m 3 ): 1/cm 3 Copollutant (correlation):

PM 10-2.5 : r= 0.48

NC 0.1-0.01 : r= 0.34

NC 0.5-0.1 : r= 0.76

MC 0.5-0.1 : r= 0.92

MC 2.5-0.01 : r= 0.94

PM 10 : r= 0.88

NO 2 : r= 0.54

CO: r= 0.46

SO 2 : r= 0.66 NC Increment: 1 IQR Effect Estimate [Lower CI, Upper CI]: Association between the prevalence of inhaled ß2- agonist use and NC2.5-0.5 Same day, IQR= 26, OR= 0.99 (0.93- 1.05) 5-day mean, IQR= 22, OR= 1.09 (1.01- 1.17) 14-day mean, IQR= 17, OR= 1.08 (1.02-1.15) Association between the prevalence of inhaled corticosteroid use and NC2.5- 0.5 Same day, IQR= 26, OR= 1.13 (1.06- 1.21) 5-day mean, IQR= 22, OR= 1.28 (1.19- 1.37) 14-day mean, IQR= 17, OR= 1.44 (1.36-1.53) Association between the prevalence of wheezing and NC2.5-0.5 Same day, IQR= 26, OR= 1.03 (0.95- 1.10) 5-day mean, IQR= 22, OR= 1.05 (0.97- 1.13) 14-day mean, IQR= 17, OR= 1.03 (0.96-1.10)

Reference: von Klot et al. (2002, 034706 ) Period of Study: Sep 1996-Mar 1997 (winter)

Location: Erfurt, Germany Outcome: Asthma symptoms (wheezing, shortness of breath at rest, waking up with breathing problems, or coughing without having a cold) and Asthma medication (inhaled short-acting ß2- agonists, inhaled long-acting ß2- agonists, inhaled corticosteroids, cromolyn sodium, theophylline, oral corticosteroids, and N-acetylcysteine) Age Groups : Adults, mean=59.0 yr and range =37-77 yr Study Design: Panel study

N: 53 adult asthmatics Statistical Analyses: Logistic regression models

Covariates: Seasonal variation in medication use or symptom prevalence, meteorological factors (relative humidity, temperature), weekend, Christmas holidays

Season : Winter Dose-response Investigated? No Statistical Package : NR Lags Considered: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ma calculated from same day and preceding days Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (SD): 10.3

Percentiles:

25th: 2.9 50th(Median): 6.9

75th: 14.6 Range (Min, Max): (-8.7-64.3) Copollutant (correlation):

NC 0.1-0.01 : r= 0.41

NC 0.5-0.1 : r= 0.50

NC 2.5-0.5 : r= 0.48

MC 0.5-0.1 : r= 0.51

MC 2.5-0.01 : r= 0.52

PM 10 : r= 0.67

NO 2 : r= 0.45

CO: r= 0.42

SO 2 : r= 0.28 PM Increment: 1 IQR Effect Estimate [Lower CI, Upper CI]: Association between the prevalence of inhaled ß2- agonist use and PM 10-2.5 Same day, IQR= 12, OR= 1.01 (0.95- 1.06) 5-day mean, IQR= 11, OR= 1.01 (0.94- 1.09) 14-day mean, IQR= 6.7, OR= 0.92 (0.86-1.00) Association between the prevalence of inhaled corticosteroid use and PM 10-2.5 Same day, IQR= 12, OR= 1.03 (0.98- 1.08) 5-day mean, IQR= 11, OR= 1.12 (1.04- 1.20) 14-day mean, IQR= 6.7, OR= 1.27 (1.18-1.37) Association between the prevalence of wheezing and PM 10-2.5 Same day, IQR= 12, OR= 0.97 (0.91- 1.02) 5-day mean, IQR= 11, OR= 1.06 (0.98- 1.15) 14-day mean, IQR= 6.7, OR= 1.05 (0.96-1.15)

Reference: Ward et al. (2002, 025839 ) Period of Study: 1997 (two 8-wk periods)

Location: Birmingham and Sandwell, UK Outcome: Change in PEF (peak expiratory flow), self reported respiratory symptoms (same day cough, illness, short of breath, waking up at night with cough or wheeze, wheeze) Age Groups : 9 yr olds Study Design: Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Winter: 12.7 μg/m 3 Summer: 12.3 μg/m 3 Range (Min, Max): PM Increment: Winter: 12.3 μg/m 3 Summer: 6.3 μg/m 3 Mean (PEF l/min) [Lower CI, Upper CI] lag: Winter morning: 0.80 [-1.97, 3.67] lag 0 0.62 [-2.22, 3.54] lag 1



### December 2009 E-224

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Time-series Panel study

N: 162 children from 5 schools Statistical Analyses: Linear regression (PEF), Logistic regression (respiratory symptoms)

Covariates: Trend, temperature, schooldays (yes/no)

Season: Winter (Jan 13-Mar 10) Summer (May 19- Jul 14) Dose-response Investigated? No Statistical Package : Nr Lags Considered: Lag 0, lag 1, lag 2, lag 3, 7-day ma Winter: 4, 37 Summer: 5, 28 PM Component:

Total mass Monitoring Stations : 5 stations near the 5 schools Copollutant (correlation):

Winter:

PM 10 (r=0.93)

NO 2 (r=0.88)

O 3 (r=-0.83)

Summer:

HNO 3 (r=0.81) -0.86 [-4.32, 2.47] lag 2 -2.47 [-5.30, 0.36] lag 3 -4.07 [-10.60, 2.42] 7-day mean

Winter afternoon: 0.95 [-2.22, 4.23] lag 0 -0.99 [-4.69, 2.72] lag 1 -1.60 [-5.18, 2.01] lag 2 -3.45 [-6.53 to -0.25] lag 3 1.00 [-11.47, 13.56] 7-day mean Summer morning: -1.49 [-3.65, 0.67] lag 0 0.21 [-2.12, 2.55] lag 1 2.50 [0.28, 4.72] lag 2 3.41 [1.40, 5.44] lag 3 3.90 [-2.53, 10.33] 7-day mean

Summer afternoon: -0.49 [-2.43, 1.45] lag 0 -0.78 [-2.72, 1.16] lag 1 0.57 [-1.35, 2.49] lag 2 0.16 [-1.85, 2.17] lag 3 -0.08 [-5.43, 5.27] 7-day mean Winter morning in atopy/recent wheezing subgroup: -0.072 [-0.527, 0.383] lag 0 -0.271 [-0.701, 0.159] lag 1 0.127 [-0.354, 0.608] lag 2 0.055 [-0.391, 0.501] lag 3 Winter morning in no atopy or recent wheezing subgroup: 0.126 [-0.413 , 0.666] lag 0 0.193 [-0.340 , 0.728] lag 1 -0.170 [-0.788 , 0.447] lag 2 -0.314 [-0.846 , 0.216] lag 3 Winter morning in subgroup with parental atopy/recent wheezing: 0.187 [-0.008 , 0.382] lag 0 -0.006 [-0.207 , 0.195] lag 1 -0.011 [-0.226 , 0.204] lag 2 -0.037 [-0.228 , 0.154] lag 3 Winter morning in subgroup without parental atopy/recent wheezing: 0.026 [-0.341 , 0.395] lag 0 0.068 [-0.307 , 0.444] lag 1 -0.099 [-0.535 , 0.335] lag 2 -0.252 [-0.615 , 0.110] lag 3 RR Estimate [Lower CI, Upper CI] lag: Cough: Winter: 0.98 [0.80, 1.18] lag 0 0.95 [0.77, 1.17] lag 1 1.02 [0.83, 1.24] lag 2 1.01 [0.83, 1.23] lag 3 1.31 [0.82, 2.09] 7-day mean

Summer: 1.13 [1.04, 1.22] lag 0 1.04 [0.94, 1.13] lag 1 0.94 [0.87, 1.02] lag 2 0.89 [0.82, 0.96] lag 3 0.81 [0.62, 1.06] 7 day mean

Illness: Winter: 1.17 [1.05, 1.32] lag 0 1.07 [0.95, 1.23] lag 1 1.16 [1.01, 1.35] lag 2 1.01 [0.90, 1.16] lag 3 1.57 [1.15, 2.13] 7-day mean

Summer: 1.02 [0.91, 1.13] lag 0 1.00 [0.89, 1.13] lag 1 0.96 [0.85, 1.07] lag 2 0.97 [ 0.86, 1.09] lag 3 0.68 [0.41, 1.13] 7-day mean



### December 2009 E-225

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Shortness of breath: Winter: 1.07 [0.94, 1.24] lag 0 0.98 [0.84, 1.13] lag 1 0.96 [0.82, 1.13] lag2 0.91 [0.79, 1.07] lag 3 0.82 [0.58, 1.18] 7-day mean

Summer: 1.04 [0.90, 1.20] lag 0 1.08 [0.93, 1.25] lag 1 0.97 [0.84, 1.13] lag 2 0.93 [0.81, 1.08] lag 3 1.16 [0.76, 1.77] 7-day mean Wake at night with cough/wheeze: Winter: 1.10 [0.96, 1.26] lag 0 1.05 [0.90, 1.22] lag 1 0.98 [0.83, 1.13]; lag 2 0.94 [0.81, 1.09]; lag 3 0.93 [0.66, 1.32] 7-day mean

Summer: 0.93 [0.78, 1.10] lag 0 0.81 [0.67, 0.98] lag 1 0.91 [0.77, 1.09] lag 2 0.97 [0.83, 1.13] lag 3 1.04 [0.57, 1.90] 7-day mean

Wheeze: Winter: 0.98 [0.83, 1.16] lag 0 0.90 [0.75, 1.05] lag 1 1.00 [0.83, 1.20] lag 2 1.13 [0.95, 1.35] lag 3 1.02 [0.68, 1.57]; 7-day mean

Summer: 1.02 [0.88, 1.19] lag 0 0.98 [0.84, 1.16] lag 1 0.87 [0.74, 1.02] lag 2 0.85 [0.72, 0.99] lag 3 0.96 [0.51, 1.81] 7-day mean

Reference: Ward et al. (2002, 025839 ) Period of Study: 1997 (two 8-wk periods)

Location: Birmingham and Sandwell, UK Outcome: Change in PEF (peak expiratory flow), self reported respiratory symptoms (same day cough, illness, short of breath, waking up at night with cough or wheeze, wheeze) Age Groups : 9 yr olds Study Design: Time-series panel study

N: 162 children from 5 schools Statistical Analyses: Linear regression (PEF), Logistic regression (respiratory symptoms)

Covariates: Trend, temperature, schooldays (yes/no)

Season: Winter (Jan 13-Mar 10) Summer (May 19- Jul 14) Dose-response Investigated? No Statistical Package : Nr Lags Considered: Lag 0, lag 1, lag 2, lag 3, 7-day ma Pollutant: Sulfate Averaging Time: 24 h Mean (SD): Winter: 2.4 μg/m 3 Summer: 3.8 μg/m 3 Range (Min, Max): Winter: 0.8, 14.9 Summer: 1.1, 7.8 PM Component:

SO 4 Monitoring Stations : 2 stations PM Increment: Winter: 4.8 μg/m 3 Summer: 3.1 μg/m 3 Mean (PEF l/min) [Lower CI, Upper CI] lag Winter morning: -1.75 [-4.00, 0.50] lag 0 -0.91 [-3.44, 1.62] lag 1 -0.62 [-3.16, 1.91] lag 2 -1.82 [-4.27, 0.64] lag 3 -3.22 [-8.03, 1.58] 7-day mean

Winter afternoon: 0.99 [-1.58, 3.55] lag 0 0.79 [-2.42, 4.00] lag 1 -1.89 [-4.99, 1.21] lag 2 -1.73 [-4.69, 1.23] lag 3 -1.96 [-13.35, 9.42] 7-day mean Summer morning: -0.72 [-3.27, 1.82] lag 0 -1.69 [-4.28, 0.90] lag 1 1.35 [-1.27, 3.97] lag 2 3.38 [1.03, 5.72] lag 3 2.98 [-4.17, 10.13] 7-day mean

Summer afternoon: -0.32 [-2.81, 2.17] lag 0 0.84 [-1.63, 3.30] lag 1 -0.08 [-2.61, 2.44] lag 2 -0.25 [-2.69, 2.19]lag 3 -2.20 [-9.51, 5.12] 7-day mean Winter morning in atopy/recent wheezing subgroup: 0.200 [-0.755, 1.156] lag 0 -0.219 [-1.318, 0.881] lag 1 -0.431 [-1.526, 0.664]; lag 2 1.200 [0.095, 2.305] lag 3



### December 2009 E-226

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Winter morning in no atopy or recent wheezing subgroup: -0.613 [-1.714, 0.488] lag 0 -0.174 [-1.423, 1.075] lag 1 0.006 [-1.243, 1.253] lag 2 -1.080 [-2.308, 0.148] lag 3 Winter morning in subgroup with parental atopy/recent wheezing: 0.457 [0.003 , 0.910] lag 0 0.078 [-0.503, 0.660] lag 1 -0.102 [-0.656, 0.452] lag 2 0.002 [-0.609, 0.613] lag 3 Winter morning in subgroup without parental atopy/recent wheezing: -0.622 [-1.379, 0.136] lag 0 -0.272 [-1.147, 0.602] lag 1 -0.138 [-1.005, 0.728] lag 2 -0.496 [-1.359, 0.367] lag 3 RR Estimate [Lower CI, Upper CI] lag: Cough: Winter: 1.01 [0.84, 1.20] lag 0 1.02 [0.85, 1.24] lag 1 0.99 [0.82, 1.20] lag 2 0.86 [0.71, 1.05] lag 3 0.78 [0.53, 1.14] 7-day mean

Summer: 1.08 [0.98, 1.20] lag 0 1.03 [0.93, 1.15] lag 1 0.97 [0.88, 1.07] lag 2 0.90 [0.82, 0.99] lag 3 0.73 [0.54, 0.97] 7 day mean

Illness: Winter: 1.06 [0.96, 1.17] lag 0 1.15 [1.03, 1.28] lag 1 1.14 [1.00, 1.28] lag 2 1.04 [0.92, 1.18] lag 3 1.30 [1.00, 1.66] 7-day mean

Summer: 0.98 [0.86, 1.11] lag 0 0.97 [0.84, 1.12] lag 1 1.01 [0.88, 1.16] lag 2 0.95 [0.84, 1.09] lag 3 0.72 [0.46, 1.12] 7-day mean

Shortness of breath: Winter: 0.96 [0.85, 1.07] lag 0 0.98 [0.86, 1.12] lag 1 0.94 [0.82, 1.07] lag2 0.93 [0.81, 1.08] lag 3 0.80 [0.59, 1.07] 7-day mean

Summer: 0.95 [0.80, 1.14] lag 0 1.07 [0.89, 1.28] lag 1 1.04 [0.87, 1.24] lag 2 0.94 [0.80, 1.12] lag 3 |0.58 [0.33, 1.04] 7-day mean Wake at night with cough/wheeze: Winter: 0.97 [0.87, 1.08] lag 0 1.01 [0.89, 1.15] lag 1 1.00 [0.88, 1.14]; lag 2 0.93 [0.82, 1.07]; lag 3 0.79 [0.59, 1.05] 7-day mean

Summer: 0.95 [0.78, 1.16] lag 0 0.81 [0.67, 0.99] lag 1 0.93 [0.76, 1.13] lag 2 0.87 [0.72, 1.05] lag 3 0.77 [0.41, 1.48] 7-day mean

Wheeze: Winter: 1.00 [0.87, 1.15] lag 0 0.96 [0.82, 1.13] lag 1 0.88 [0.75, 1.04] lag 2 1.12 [0.95, 1.32] lag 3



### December 2009 E-227

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 0.83 [0.58, 1.20]; 7-day mean

Summer: 0.97 [0.80, 1.17] lag 0 .09 [0.89, 1.32] lag 1 1.00 [0.82, 1.22] lag 2 0.81 [0.69, 0.97] lag 3 1.30 [0.68, 2.50] 7-day mean

Reference: Ward et al. (2002, 025839 ) Period of Study: 1997 (two 8-week periods)

Location: Birmingham and Sandwell, UK Outcome: Change in PEF (peak expiratory flow), self reported respiratory symptoms (same day cough, illness, short of breath, waking up at night with cough or wheeze, wheeze) Age Groups : 9 yr olds Study Design: Time-series panel study

N: 162 children from 5 schools Statistical Analyses: Linear regression (PEF), Logistic regression (respiratory symptoms)

Covariates: Trend, temperature, schooldays (yes/no)

Season: Winter (Jan 13-Mar 10) Summer (May 19- Jul 14) Dose-response Investigated? No Statistical Package : Nr Lags Considered: Lag 0, lag 1, lag 2, lag 3, 7-day ma Pollutant: NO 3 Averaging Time: 24 h Mean (SD): Winter: 3.6 μg/m 3 Summer: 3.5 μg/m 3 Range (Min, Max): Winter: 0.1, 29.9 Summer: 0.7, 13.2 Monitoring Stations : 2 stations PM Increment: Winter: 6.7 μg/m 3 Summer: 3.7 μg/m 3 Mean (PEF l/min) [Lower CI, Upper CI] lag: Winter morning: -2.08 [-4.02 to -0.15] lag0 -0.64 [-2.87, 1.59] lag 1 0.71 [-1.69, 3.11] lag 2 -1.38 [-3.61, 0.84] lag 3 -0.92 [-5.32, 3.47] 7-day mean

Winter afternoon: 0.24 [-1.89, 2.38] lag0 -0.72 [-3.87, 2.43] lag 1 -1.37 [-5.11, 2.38] lag 2 -2.54 [-5.74, 0.66] lag 3 0.21 [-7.67, 8.11] 7-day mean Summer morning: -0.80 [-2.74, 1.15] lag 0 0.68 [-1.31, 2.67] lag1 1.42 [-0.73, 3.58] lag2 2.54 [0.48, 4.59] lag3 1.74 [-2.66, 6.13] 7-day mean

Summer afternoon: -0.72 [-2.47, 1.03] lag 0 -0.59 [-2.36, 1.18] lag 1 -0.33 [-2.11, 1.45] lag 2 0.66 [-1.26, 2.58] lag 3 0.47 [-3.36, 4.29] 7-day mean Winter morning in atopy/recent wheezing subgroup: -0.036 [-0.627 , 0.555] lag 0 0.142 [-0.573 , 0.857] lag 1 0.000 [-0.760, 0.759] lag 2 0.689 [-0.061, 1.439] lag 3 Winter morning in no atopy or recent wheezing subgroup : -0.434 [-1.116, 0.248] lag 0 -0.201 [-1.002 , 0.600] lag 1 0.154 [-0.703 , 1.010] lag 2 -0.605 [-1.422 , 0.210] lag 3 Winter morning in subgroup with parental atopy/recent wheezing : 0.228 [-0.054, 0.511] lag 0 0.476 [0.060, 0.892] lag 1 0.196 [-0.202, 0.594] lag 2 0.083 [-0.321, 0.487] lag 3 Winter morning in subgroup without parental atopy/recent wheezing: -0.482 [-0.952, -0.012] lag 0 -0.276 [-0.846, 0.294] lag 1 0.078 [-0.520, 0.675] lag 2 -0.298 [-0.864, 0.268] lag 3 RR Estimate [Lower CI, Upper CI] lag: Cough: Winter: 0.92 [0.80, 1.07] lag 0 0.91 [0.77, 1.07] lag 1 0.99 [0.83, 1.17] lag 2 0.87 [0.73, 1.03] lag 3 0.71 [0.52, 0.97] 7-day mean

Summer: 1.05 [0.97, 1.13] lag 0



### December 2009 E-228

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 1.01 [0.93, 1.10] lag 1 0.95 [0.88, 1.03] lag 2 0.89 [0.83, 0.96] lag 3 0.81 [0.68, 0.97] 7 day mean

Illness: Winter: 1.05 [0.97, 1.14] lag 0 1.11 [1.01, 1.22] lag 1 1.13 [1.01, 1.26] lag 2 1.13 [1.04, 1.26] lag 3 1.13 [0.92, 1.38] 7-day mean

Summer: 0.97 [0.87, 1.09] lag 0 0.98 [0.87, 1.10] lag 1 0.95 [0.85, 1.06] lag 2 0.94 [0.85, 1.05] lag 3 0.74 [0.54, 1.03] 7-day mean

Shortness of breath: Winter: 0.99 [0.90, 1.10] lag 0 1.01 [0.90, 1.13] lag 1 0.93 [0.82, 1.05] lag2 0.98 [0.86, 1.13] lag 3 0.85 [0.67, 1.08] 7-day mean

Summer: 1.04 [0.90, 1.18] lag 0 1.12 [0.98, 1.28] lag 1 1.04 [0.90, 1.20] lag 2 0.90 [0.79, 1.03] lag 3 1.06 [0.78, 1.43] 7-day mean Wake at night with cough/wheeze: Winter: 0.98 [0.89, 1.08] lag 0 1.05 [0.94, 1.16] lag 1 0.99 [0.88, 1.12]; lag 2 0.99 [0.87, 1.12]; lag 3 0.84 [0.67, 1.05] 7-day mean

Summer: 0.94 [0.80, 1.09] lag 0 0.86 [0.72, 1.01] lag 1 0.94 [0.79, 1.11] lag 2 0.92 [0.79, 1.07] lag 3 0.95 [0.62, 1.47] 7-day mean

Wheeze: Winter: 0.98 [0.87, 1.10] lag 0 1.00 [0.87, 1.14] lag 1 0.89 [0.77, 1.03] lag 2 1.11 [0.95, 1.30] lag 3 0.80 [0.61, 1.07] 7-day mean

Summer: 1.01 [0.87, 1.17] lag 0 0.96 [0.83, 1.11] lag 1 0.95 [0.82, 1.10] lag 2 0.87 [0.75, 1.01] lag 3 1.04 [0.67, 1.60] 7-day mean

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-229

# E.2.2. Respiratory Emergency Department Visits and Hospital Admissions

Table E-12. Short-term expos ure-respiratory-ED/HA-PM 10 

# .

Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Andersen et al. (2008, 189651 ) 1st page: 458 Period of Study: May 2001- Dec 2004

Location: Copenhagen, Denmark Hospital Admissions/ED visits Outcome (ICD-10):

RD , including chronic bronchitis (J41-42), emphysema (J43), other chronic obstructive pulmonary disease (J44), asthma (J45), and status asthmaticus (J46). Pediatric hospita l admissions for asthma (J45) and status asthmaticus (J46). Age Groups Analyzed: > 65 yr (RD combined), 5-18 yr (asthma) Study Design: Time series

N: NR Statistical Analyses: Poisson GAM

Covariates: temperature, dew-point temperature, long-term trend, seasonality, influenza, day of the week, public holidays, school holidays (only for 5-18 yr olds), pollen (only for pediatric asthma outcome)

Season: NR Dose-response Investigated: No Statistical package: R statistical software (gam procedure, mgcv package) Lags Considered: Lag 0 -5 days, 5-day avg (lag 0-4) for RD, and a 6-day avg (lag 0-5) for asthma. Pollutant: PM 10 (μg/m 3 ) Averaging Time: 24 h Mean (SD): 24(14)

Median: 21

IQR: 16-29 99th percentile: 72 Monitoring Stations: 1 Copollutant (correlation): NCtot: r = 0.39 NC100: r = 0.28 NCa12: r = 0.02 Nca23: r = -0.12 NCa57: r = 0.45 Nca212: r = 0.63 PM : r = 0.80

2.5 CO: r = 0.37 NO : r = 0.35

2 : r = 0.32 curbside: r = 0.18 O : r = -0.21

3 Other variables: Temperature: r = 0.12 Relative humidity: r = 0.05 PM Increment: 13 μ g/m 3 3 (IQR) Relative risk (RR) Estimate [CI]: RD hospital admissions (5 day avg, lag 0 -4), age 65+: One-pollutant model: 1.06 [1.02-1.09] Adj for NCtot: 1.05 [1.01-1.10] Adj for NCa212: 1.04 [0.98-1.11] Asthma hospital admissions (6-day avg lag 0-5), age 5 - 18: One-pollutant model: 1.02 [0.93-1.12] Adj for NCtot: 1.01 [0.91-1.12] Adj for NCa212: 0.94 [0.81-1.09] Estimates for individual day lags reported only in Fig form (see notes):

Notes: Fig 2: Relative risks and 95% confidence intervals per IQR in single day concentration (0-5 day lag). Summary of Fig 2: RD: Positive, statistically or marginally significant associations at Lag 2-5. Asthma: Wide confidence intervals make interpretation difficult. Positive associations at Lag 1, 2, 3, and 5.

Reference: Cheng et al. (2007, 093034 ) Period of Study: 1996-2004

Location: Kaohsiung, Taiwan Outcome (ICD-9: 480-486): Pneumonia Age Groups: NR Study Design: Case-crossover

N: 82,587 pneumonia hospital admissions Statistical Analyses: Conditional logistic regression

Covariates: Temperature and humidity on the same day

Season: NR Dose-response Investigated? No Statistical Package: SAS Lags Considered: Cumulative lag period up to 2 previous days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 77.01 (16.7-232)

Percentiles: 25%: 42.12

50%: 75.27

75%: 104.65 Monitoring Stations: 6 Copollutant: NR PM Increment: 62.53 μg/m 3 (IQR) OR Estimate [CI]: Single Pollutant Model: Temp>25oC: 1.21 [1.15,1.28] Temp < 25oC: 1.57 [1.50,1.65] Two-Pollutant Model: Temp>25oC Adj. for SO 2 : 1.21 [1.14,1.28] Adj. for NO 2 : 1.15 [1.07,1.24] Adj. for CO: 1.10 [1.03,1.17] Adj. for O 3 : 0.96 [0.89,1.03] Temp < 25oC Adj. for SO 2 : 1.56 [1.48,1.65] Adj. for NO 2 : 1.09 [1.02,1.16] Adj. for CO: 1.30 [1.22,1.39] Adj. for O 3 : 1.56 [1.48,1.65]



### December 2009 E-230

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chimonas and Gessner (2007, 093261 ) Period of Study: Jan 1999-Jun 2003

Location: Anchorage, Alaska Outcome (ICD-9): Asthma (493.0- 493.9); Lower respiratory illness-LRI (466.1, 466.0, 480-487, 490, 510-511); Inhaled quick-relief medication; Steroid medication Age Groups: <20 yr old Study Design: Time series

N: 42,667 admissions Statistical Analyses: GEE for multivariable modeling

Covariates: Season, serial correlation, yr, weekend, temperature, precipitation, and wind speed

Season: NR Dose-response Investigated? No Statistical Package: SPSS (dataset), SAS (analysis) Lags Considered: 1 day and 1 week Pollutant: PM 10 Averaging Time: 24 h and 1 wk Mean (min-max): Daily: 27.6 (2-421) Weekly: 25.3 (5.0-116.0) Monitoring Stations: NR Copollutant: Daily PM 2.5 ρ = 0.25 (p < 0.01) Weekly PM 2.5 ρ = 0.08 (p = 0.21) PM Increment: 10 μg/m 3 RR Estimate [CI]: Same Day Outpatient Asthma: 1.006 [1.001,1.013] Outpatient LRI: 1.001 [0.987,1.015] Inpatient Asthma: 1.003 [0.922,1.091] Inpatient LRI: 1.015 [0.978,1.053] Inhaled Steroid Prescriptions: 1.006 [0.996,1.011] Quick-relief Medication: 1.018 [1.006,1.030] Weekly (median increase) Outpatient Asthma: 1.021 [1.004,1.038] Outpatient LRI: 1.013 [0.978,1.049] Inpatient Asthma: 1.023 [0.948,1.104] Inpatient LRI: 1.025 [0.981,1.072] Inhaled Steroid Prescriptions: 0.989 [0.969,1.010] Quick-relief Medication: 1.057 [1.037,1.077]

Reference: Chiu et al. (2008, 191989 ) Period of Study: 1996-2001

Location: Taipei, Taiwan Outcome: Hospital admissions for COPD Study Design: Time-series

Covariates: Temperature, humidity, PM 10 and O 3 Statistical Analysis: Poisson regression Statistical Package: SAS Age Groups: All Pollutant: PM 10 Averaging Time: 24 h Mean (SD) Unit: Index Days: 111.68 ± 38.32 μg/m 3 Comparison Days: 55.43 ± 24.66 μg/m 3 Range (Min, Max): NR Copollutant (correlation): NR All results refer to “dust storm days” and can be found in Table 3

Reference: Chiu et al. (2009, 190249 ) Period of Study: 1996-2004

Location: Taipei, Taiwan Outcome: Hospital admissions for pneumonia (ICD-9 480-486) Study Design: Time-series

Covariates: Weather variables, day of the week, seasonality, long-term time trends Statistical Analysis: Conditional logistic regression Statistical Package: SAS Age Groups: All Pollutant: PM 10 Averaging Time: 24 h

Mean Unit: 49.47 μg/m 3 Range (Min, Max): 14.42, 234.91 Copollutant (correlation):

SO 2 : 0.50

NO 2 : 0.58

CO: 0.34

O 3 : 0.31 Increment: IQR Odds Ratio (95% CI) Temperature ≥ 23o C: 1.11 (1.08-1.14) Temperature < 23o C: 1.09 (1.07-1.11) Adjusted for SO 2 Temperature ≥ 23o C: 1.10 (1.08-1.13) Temperature < 23o C: 1.19 (1.17-1.22) Adjusted for NO 2 Temperature ≥ 23o C: 0.90 (0.88-0.93) Temperature < 23o C: 1.09 (1.07-1.12) Adjusted for CO Temperature ≥ 23o C: 1.03 (1.00-1.05) Temperature < 23o C: 1.07 (1.05-1.10) Adjusted for O 3 Temperature ≥ 23o C: 1.05 (1.03-1.08) Temperature < 23o C: 1.09 (1.07-1.11)



### December 2009 E-231

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Erbas et al. (2005, 073849 ) Period of Study: Jan 2000-Dec 2001

Location: Melbourne, Australia Hospital Admissions Outcome (ICD-10): Asthma (J45, J46) Age Groups: 1-15 yr Study Design: Time series

N: 8955 asthma cases Statistical Analyses: GAM, GEE (if autocorrelation was present in residuals)

Covariates: Temp and humidity

Season: NR Dose-response Investigated? No Statistical Package: NR Lags Considered: 0, 1, 2 days Pollutant: PM 10 Averaging Time: 1 h Mean (SD): Western: 2.99 (2.11) 10th percentile: 13.67 90th percentile: 48.00 Inner Melbourne: 4.54 (2.65) 10th percentile: 15.63 90th percentile: 59.73 South/Southeastern: 1.13 (1.18) 10th percentile: 12.00 90th percentile: 36.05 Eastern: 3.61 (2.39) 10th percentile: 16.00 90th percentile: 51.05 Combined: 30.07 (10.55-112.33) SD = 15.27 10th percentile: 16.00 90th percentile: 50.51 Monitoring Stations: Data obtained from an air quality simulation model (TAPM) by CSIRO Atmospheric Research Copollutant: NR PM Increment: Increase from 10th to 90th percentile RR Estimate [CI]: Same day lag

Western: NR Inner Melbourne: 1.17 [1.05,1.31] South/Southeastern: 1.14 [0.95,1.33] Eastern: 1.09 [1.01,1.18]

Notes: All other lags NR

Reference: Farhat et al. (2005, 089461 ) Period of Study: Aug 1996-Aug 1997

Location: São Paulo, Brazil Hospital Admissions and Emergency Room Visits Outcome (ICD-9): Lower respiratory tract diseases (466, 480-519) including pneumonia or bronchopneumonia (480- 486), asthma (493), bronchiolitis (466) Age Groups: <13 yr Study Design: Time series

N: 43,635 Statistical Analyses: GAM, Poisson regression, Pearson correlation

Covariates: Time, temperature, humidity, weekday

Season: NR Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 0-7 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 62.6 (25.5-186.3) SD = 26.6 IQr = 30 N = 396 Monitoring Stations: 13 Copollutant (correlation): SO 2 : r = 0.69 NO 2 : r = 0.83 O : r = 0.35

3 CO: r = 0.72 (all p < 0.05)

Additional correlations: Rel humidity: r = -0.55 Min temp: r = -0.44 (both p < 0.05) PM Increment: 30 μg/m 3 (IQR) RR Estimate [CI]: Lower respiratory tract disease 5-day ma Copollutant model: NO 2 : 2.1 [-7.1,11.3] SO 2 : 16.5 [10.5,22.6] O : 10.1 [5.0,15.2]

3 CO: 14.1 [8.1,20.2] Multipollutant model: 5.2 [-4.6,15.1] Pneumonia or bronchopneumonia 6-day ma Copollutant model: NO 2 : 14.8 [-3.8,33.4] SO 2 : 14.8 [-0.3,30.0]; O 3 : 16.2 [1.0,31.3] CO: 17.6 [0.4,34.8] Multipollutant model: 5.23 [-16.2,26.6] Asthma or bronchiolitis 2-day ma Copollutant model: NO 2 : -11.04 [-50.0,28.0] SO 2 : 15.8 [-7.8,39.3] O : 11.7 [-10.4, 33.9]

3 CO: 12.4 [-14.8,39.7] Multipollutant model: -15.5 [-61.2,30.2]



### December 2009 E-232

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Fung et al. (2006, 089789 ) Period of Study: June 1995-Mar 99

Location: Vancouver, Canada Hospital Admission/ED

Outcome: Respiratory diseases (460- 519) Age Groups: Age >65 Study Design: Time series

N: 26,275 individuals admitted Statistical Analyses: Poissonregression (spline 12 knots), casecrossover (controls +/7 days from case date), Dewanji and Moolgavkar (DM) method

Covariates: Long-term trends, day-ofthe-week effect, weather

Season: All yr Dose-response Investigated? No Statistical Package: SPlus, R Lags Considered: 0-7 days Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 13.31(6.13) μg/m 3 Range (Min, Max): (3.77, 52.17) Monitoring Stations: NR Copollutant (correlation): PM 10 :

PM 2.5 r = 0.80

PM 10-2.5 r = -0.11

CO r = 0.46

Coh r = 0.61

O 3 r = -0.08

NO 2 r = 0.54

SO 2 r = 0.61 PM Increment: : 7.9 μg/m 3 Rr Estimate (65+ Yr) Dm Method: 1.014[0.998,1.029] Lag 0 1.016[0.998,1.034] 3-day avg 0.988[0.970, 1.006] 5-day avg 0.983[0.963, 1.004] 7-day avg Time Series: 1.016[0.999, 1.033] Lag 0 1.015[0.996, 1.035] 3-day avg 1.009[0.987, 1.032] 5-day avg 1.009[0.983, 1.036] 7-day avg Case-Crossover: 1.017[0.998, 1.036] Lag 0 1.015[0.993, 1.037] 3-day avg 1.008[0.984, 1.033] 5-day avg 1.003[0.976, 1.031] 7-day avg Reference: Fung al. (2005, 093262 ) Period of Study: Nov 1995-Dec 2000

Location: London, Ontario Hospital Admissions Outcome (ICD-9): Asthma (493) and all other respiratory diseases (460-519) Age Groups: <65 yr 65+ yr Study Design: Time series

N: 5574 respiratory admissions Statistical Analyses: GAM with locally weighted regression smoothers (LOESS)

Covariates: Maximum and minimum temp, humidity, day of the week, seasonal cycles, secular trends

Season: NR Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: Current to 3-day

mean Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 38.0 (5-248)

SD = 23.5 Monitoring Stations: 4 Copollutant (correlation): NO 2 : r = 0.30

SO 2 : r = 0.24

CO: r = 0.21

O 3 : r = 0.53

COH: r = 0.29 PM Increment: 26 μg/m 3 % Change in Daily Admission [CI]: Age <65 Current day mean: -0.9 [-6.8,5.4] 2-day mean: -1.3 [-8.5,6.6] 3-day mean: 1.9 [-6.5,11] Age 65+ Current day mean: 3.3 [-1.7,8.6] 2-day mean: 5 [-1.5,11.9] 3-day mean: 1.2 [-6.1,9.1]



### December 2009 E-233

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Galán et al. (2003, 087408 ) Period of Study: 1995-1998

Location: Madrid, Spain Hospital Admissions Outcome (ICD): Asthma (493) Age Groups: All ages Study Design: Time series

N: 555,153 at-risk Statistical Analyses: GAM, autoregressive Poisson regression

Covariates: Temperature, relative humidity, pollen, yr, day of the week, public holiday

Season: NR Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 0, 1, 2, 3, and 4 day

s Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 32.1 (11.2-108.6) SD = 12.1 Monitoring Stations: 13 Copollutant (correlation): SO 2 : r = 0.581 NO 2 : r = 0.717 O 3 : r = -0.188

Other variables: O.europaea: r = -0.066 Plantago sp.: r = -0.202 Poaceae: r = -0.132 Urticaceae: r = -0.104 Temp: r = -0.122 Humidity: r = 0.119 PM Increment: 10 μg/m 3 RR Estimate [CI]: Single-pollutant Current-day lag: 1.011 (0.980-1.042) 1-day lag: 1.006 (0.976-1.037) 2-day lag: 1.008 (0.978-1.038) 3-day lag: 1.039 (1.010-1.068) 4-day lag: 1.027 (0.999-1.056) Adjustment for pollen (PM 10 3-day lag) O. europaea: 1.041 (1.011-1.071) Plantago sp.: 1.046 (1.017-1.076) Poaceae: 1.043 (1.015-1.073) Urticaceae: 1.038 (1.009-1.068) All four: 1.045 (1.016-1.074)

Reference: Hajat et al. (2002, 030358 ) Period of Study: Jan 1992-Dec 1994

Location: London, England Family Practice consultations

Outcome: Upper Resp Disease (excluding allergic rhinitis) (460-3), (465), (470-5), (478) Age Groups: 0-14, 15-64, >65 yr Study Design: Time series

N: 268,718-295,740 registered patients Statistical Analyses: Poisson regression, GAM, LOESS smoothers, default convergence criteria

Covariates: Long term trends, pollen counts, flu, meteorological variables

Season: All yr Dose-response Investigated? No Statistical Package: SPLUS Lags Considered: 2-3 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 28.5 (13.7) μg/m 3

Percentiles: 10th: 15.8

90th: 46.5 Monitoring Stations: 1 Copollutant: NR PM Increment: All Year: 18

Warm Season: 15

Cold Season: 20 % Change, Single Pollutant Models: All Year: Ages 0-14: 2.0[-0.2, 4.2] Lag 3 Ages 15-64: 5.7[2.9, 8.6] Lag 2 Ages >65: 10.2[5.3, 15.3] Lag 2 Warm Season: Ages 0-14: 1.1[-2.4, 4.8] Lag 3 Ages 15-64: 6.0[2.7, 9.4] Lag 2 Ages >65: 0.1[-7.7, 8.5] Lag 2 Cold Season: Ages 0-14: 2.7[-0.1, 5.5] Lag 3 Ages 15-64: 3.6[1.0, 6.4] Lag 2 Ages >65: 18.9[11.7, 26.7] Lag 2 % Change, 2 Pollutant Models: 0-14 Yr PM 10 w/ NO 2 : 3.8[1.6, 6.1] PM 10 w/ O 3 : 1.8[-0.4, 3.9] PM 10 w/ SO 2 : 2.0[-0.6, 4.6] 15-65 Yr PM 10 w/ NO 2 : 2.8[0.7, 4.9] PM 10 w/ O 3 : 4.8[2.6, 7.0] PM 10 w/ SO 2 : 4.8[2.2, 7.5] >65 Yr PM 10 w/ NO 2 : 4.6[0.5, 8.8] PM 10 w/ O 3 : 10.7[5.7, 16.0] PM 10 w/ SO 2 : 10.6[4.5, 17.1]



### December 2009 E-234

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hanigan et al. (2008, 156518 ) Period of Study: 1996-2005 (Apr-Nov of each yr)

Location: Darwin, Australia Outcome: Cardiorespiratory Disease HA (ICD 9: 390-519 ICD 10: I00-99 & J00-99) Age Groups: NR Study Design: Time series

N: 8279 events Statistical Analyses: Poisson regression

Covariates: Indigenous status, Dose-response Investigated? No Statistical Package: R Lags Considered: Lags 0-3 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 21.2 (8.2) Range: 55.2 Monitoring Stations: 2 (monitored & modeled) Copollutant: NR Co-pollutant Correlation

N/A PM Increment: 10 μg/m 3 Percent Change (Lower CI, Upper CI), lag: Total Respiratory: 4.81 (-1.04, 11.01), lag 0 Total Resp., Indigenous: 9.40 (1.04, 18.46), lag 0 Total Resp., Non-Indigenous: 3.14 (- 2.99, 9.66), lag Resp. Infection, Indigenous: 15.02 (3.73, 27.54), lag 3 Resp. Infection, Non-Indigenous: 0.67 (- 7.55, 9.61), lag 3 Asthma Indigenous: 16.27 (3.55, 40.17), lag 1 Asthma Non-Indigenous: 8.54 (-5.60, 24.80), lag 1 *Fig 3. percent change in hospital admissions per 10 μg/m 3 increase in PM 10 Reference: Hanigan et al. (2008, 156518 ) Period of Study: 1996-2005 (Apr-Nov of each yr)

Location: Darwin, Australia Hospital Admissions/ED visits Outcome (ICD-9 or ICD-10): Daily emergency hospital admissions for total respiratory (ICD-9: 460-519 ICD-10: J00-J99), asthma (ICD-9: 493 ICD-10: J45-J47), COPD (ICD-9: 490-492, 494-496 ICD-10: J40-J44, J47, J67), and respiratory infections (ICD-9: 461-466, 480-487, 514 ICD-10: J00-J22). Age Groups Analyzed: All Study Design: Time series

N: 8,279 hospital admissions Statistical Analyses: Poisson generalized linear models

Covariates: Indigenous status, time in days, temperature, relative humidity, day of the week, influenza epidemics, change between ICD editions, holidays, yrly population

Season: Apr-Nov (corresponding to the dry season) Dose-response Investigated? No Statistical package: R version 2.3.1 Lags Considered: Lag 0 -3 Pollutant: PM 10 Averaging Time: 24 h Mean (SD range) : 21.2 (8.2- 55.2) Monitoring Stations: N/A (see notes) Copollutant (correlation): NR PM Increment: 10 μg/m 3 Percent change [95% CI]: Overall respiratory disease: Lag 0: 4.81 [-1.04, 11.01] Lag 0 (indigenous people): 9.40 [1.04, 18.46] Lag 0 (non-indigenous people): 3.14 [-2.99, 9.66] In unstratified analyses, the subgroups of respiratory infections, asthma, and COPD all had positive associations with PM Lag 0.

10 Asthma: Lag 1 (indigenous people): 16.27 [-3.55, 40.17] Lag 1 (non-indigenous people): 8.54 [-5.60, 24.80] Respiratory infections: Lag 3 (indigenous people): 15.02 [3.73, 27.54] Lag 3 (non-indigenous people): 0.67 [-7.55, 9.61] Notes: Fig 3: Associations between hospitalizations for non-indigenous and indigenous people with estimated ambient PM 10

. Summary of Fig 3: Confidence intervals were wide, but indigenous people generally had stronger associations with PM 10 than nonindigenous people. Daily PM 10 exposure levels were estimated for the population of the city from visibility data using a previously validated models.



### December 2009 E-235

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hapcioglu et al. (2006, 093263 ) Period of Study: Jan 1997-Dec 2001

Location: Istanbul, Turkey Hospital Admissions Outcome (ICD-9): COPD (ICD: NR) Age Groups: NR Study Design: Time series

N: 1586 patients Statistical Analyses: Multiple stepwise regression, Pearson correlation

Covariates: Humidity, temperature, and pressure Season: Summer, fall, winter, spring Dose-response Investigated? No Statistical Package: SPSS Lags Considered: NR Pollutant: PM 10 Averaging Time: 1 mo Mean (SD): NR Monitoring Stations: 1 Copollutant: NR

Correlation with COPD:

r = 0.28 p = 0.03 Adj for temp: r = 0.16 p = 0.23 PM Increment: NR

Notes: RRs only provided for season, not PM

Reference: Hwang and Chan (2002, 023222 ) Period of Study: 1998

Location: Taiwan Clinic visits

Outcome: LRI 466, 480-486 (acute bronchitis, acute bronchiolitis, pneumonia) Age Groups: 0-14 yr, 15-64, 65+ yr Study Design: Cluster analysis of small study areas

N: 50 communities Statistical Analyses: GLM to model temporal patterns, hierarchical model to obtain estimates across 50 communities

Covariates: Day of week, temperature, dew point, summer/Winter

Season: All Dose-response Investigated? Yes Statistical Package: NR Lags Considered: 0-2 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 58.9 μg/m 3 (14.0) Range (Min, Max): 33.3, 83.1 μg/m 3 PM Component: Monitoring Stations: 59

Notes: Number Of stations estimated from fig. Copollutant: NR PM Increment: 10% Increase In PM 10 (5.9 μg/m 3 ) Percent Change: 0-14 0.5% (-0.1, 0.8] Lag0 [-0.3, 0.3] Lag1 0.3 [0.0, 0.6] Lag2 15-64 0.6 [0.2, 0.9] Lag0 0.2 [-0.1, 0.5] Lag1 0.3 [0.0, 0.6] Lag2 65+ 0.8 [0.4, 1.1] Lag0 0.3 [-0.1, 0.6] Lag1 0.5 [0.1, 0.8] Lag2 All Ages 0.5 [0.2, N0.8] Lag0 [-0.3, 0.3] Lag1 0.3 [0.0, 0.6] Lag2

Reference: Jaffe et al. (2003, 041957 ) Period of Study: July 1991-June 1996

Location: Cincinnati, Cleveland, Columbus, Ohio ED visits Outcome (ICD10): Asthma (493) Age Groups: Age 5-34 yr Study Design: Time-series

N: 4,416 recipients Statistical Analyses: Poisson regression, GAM

Covariates: City, day of week, wk, yr, minimum temperature, dispersion parameter

Season: Jun-Aug only Dose-response Investigated? Yes Statistical Package: NR Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Cincinnati: 43.0(16.4) Cleveland: 60.8(28.4) Columbus: 37.4(16.3) Range (Min, Max): Cincinnati: (16,90) Cleveland: (12,183) Columbus: (7,87) Monitoring Stations: 3 Copollutant (correlation): Cincinnati: PM 10 O 3 r = 0.42 NO 2 r = 0.36 SO 2 r = 0.31 Cleveland: PM 10 O 3 r = 0.42 NO 2 r = 0.34 SO 2 r = 0.29 Columbus: PM 10 O 3 r = 0.51 NO 2 r = Na SO 2 r = 0.42 PM Increment: 50 μg/m 3 % Change

Asthma Cincinnati: -22%[-49,-19] Lag 3 Cleveland: 12%[0,27] Lag 2 Columbus: 32%[-6,-85] Lag 3 Ar Estimate [Lower Ci, Upper Ci] Lag:

Asthma

Cincinnati: PM 10 : Nr

Cleveland: PM 10 : 1.32

Columbus: PM 10 : 3.62

Notes: Dose response was investigated by assessing the relationship between odds of ed visit by quintile of PM 10

. Results are displayed in Fig. “no consistent effects for all three cities were observed for PM 10 .” Rate ratios were also reported for each city.



### December 2009 E-236

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Jalaludin et al. (2004, 056595 ) Period of Study: Feb-Dec 1994

Location: Sydney, Australia Doctor Visits Outcome (ICD- NR): Respiratory symptoms (wheeze, dry cough, and wet cough), asthma medication use, and doctor visits for asthma Age Groups: Primary school children Study Design: Longitudinal cohort study

N: 125 children Statistical Analyses: GEE logistic regression models

Covariates: Temperature, humidity, daily pollen count, daily alternaria count, number of h spend outdoors, season

Season: Fall (Feb-Apr), winter (MayAug), spring/summer (Sep-Dec) Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-2 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 22.8 (13.8) Monitoring Stations: 4 Copollutant (correlation):

O 3 : r = 0.13

NO 2 : r = 0.26

Other variables: Temp: r = 0.04 Humidity: r = -0.29 Total pollen: r = 0.04

Alternaria: r = 0.04 PM Increment: IQR (μg/m 3 ) Same day: 12.0 1-day lag: 12.02 2-day lag: 12.25 2-day avg: 11.15 5-day avg: 10.23 OR Estimate [CI]:

Doctor Visits for Asthma Same day: 1.11 [1.04,1.19] 1-day lag: 1.10 [1.02,1.19] 2-day lag: 1.15 [1.06,1.24] 2-day avg: 1.11 [1.03,1.20] 5-day avg: 1.14 [0.98,1.31]

Prevalence of Doctor Visits for Asthma: Quartile 1: 0.50 (mean PM = 12.4) Quartile 2: 0.38 (mean PM = 17.2) Quartile 3: 0.65 (mean PM = 23.0) Quartile 4: 0.63 (mean PM = 38.3)

Notes: ORs and prevalence are also provided for wheeze, dry cough, wet cough, inhaled β 2-agonist use, and inhaled corticosteroid use. None were statistically significant.



### December 2009 E-237

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Johnston et al. (2007, 155882 ) Period of Study: 2000, 2004, 2005 (Apr-Nov of each yr)

Location: Darwin, Australia Hospital Admissions/ED visits Outcome (ICD-10): All respiratory conditions (J00-J99), including asthma (J45-46), COPD (J40-J44), and respiratory infections (J00-J22). Age Groups Analyzed: All Study Design: Case-crossover

N: 2466 emergency admissions Statistical Analyses: Conditional logistic regression

Covariates: Weekly influenza rates, temperature, humidity, days with rainfall >5mm, public holidays, school holiday periods (for respiratory conditions only)

Season: Apr-Nov (dry season) Dose-response Investigated? No Statistical package: NR Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h

Median: 17.4

IQR: 13.6-22.3

10-90th Percentile: 10.3-27.7 Range: 1.1-70.0 Monitoring Stations: 1 Copollutant (correlation): NR PM Increment: 10 μg/m 3 OR Estimate [95% CI]: All respiratory conditions: Lag 0: 1.08 [0.98-1.18] Lag 0 (indigenous): 1.17 [0.98-1.40]

COPD: Lag 0: 1.21 [1.0-1.47] Lag 0 (indigenous): 1.98 [1.10-3.59]

Asthma: Lag 0: 1.14 [0.90-1.44]

Asthma + COPD: Lag 0: 1.19 [1.03-1.38] Notes: Fig 1: Adjusted OR and 95% CI for hospital admissions for all respiratory conditions per 10 μg/m 3 rise in PM 10 for the same day and lags up to 3 days, overall and stratified by indigenous status. Summary of Fig 1 results: Marginally significant positive association at Lag 0 in overall study population. Larger marginally significant positive association among indigenous people. Fig 2 : OR and 95% CI for hospital admissions for COPD. Summary of Fig 2 results: Marginally significant positive associations at Lag 0 and Lag 1 in overall study population and among non-indigenous people. Large, statistically significant positive association at Lag 0 for indigenous people, with smaller, non-significant positive associations at Lag 1 and Lag2. Fig 3: OR and 95% CI for hospital admissions for asthma. Summary of Fig 3 results: Positive, non-significant (sometime marginally significant) associations at Lag 0, Lag 2, and Lag 3 for overall population and indigenous status strata. Fig 4: OR and 95% CI for hospital admissions for respiratory infections. Summary of Fig 4 results: Negative associations at Lag 2 and Lag 3 in all population strata.



### December 2009 E-238

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Kim et al. (2007, 092837 ) Period of Study: 2002

Location: Seoul, Korea Ed Visits Outcome (ICD10): Asthma (J45), (J46) Age Groups: All Ages Study Design: Cass-Crossover

N: 92,535 Visits Statistical Analyses: Conditional Logistic Regression, Relative Effect Modification (Rem)

Covariates: Time Trend, Season, Daily Mean Temperature, Relative Humidity, Air Pressure. Sep As Modifier Of Air Pollution Asthma Visit Association.

Season: All Year Dose-response Investigated? No Statistical Package: Nr Lags Considered: 0-2 days Pollutant: PM 10 Averaging Time: 8 h Mean (SD): Daily Concentration: 67.6 (39.0) μg/m 3 Relevant Exposure Term (Difference Between Concentration On Event Day And Mean Of Concentrations On Control Days): 26.0 (19.7)

Percentiles: 50th(Median): Daily Concentration: 61.9 Relevant Exposure Term: 21.6 Range (Min, Max): Daily Concentration: (4.9, 302.0) Relevant Exposure Term: (0.0, 143.1) Monitoring Stations: 3 Copollutant: Nr PM Increment: 47.4 μg/m 3 Rr Estimate For Asthma (Stratified By Sep): Individual Level Sep: Quintile 1-1.06[1.02, 1.09] Quintile 2-1.07[1.04, 1.10] Quintile 3-1.06[1.03, 1.10] Quintile 4-1.03[0.99, 1.07] Quintile 5-1.10[1.05, 1.14] Regional Level Sep: Quintile 1-1.04[0.99, 1.10] Quintile 2-1.03[1.00, 1.07] Quintile 3-1.05[1.03, 1.08] Quintile 4-1.06[1.02, 1.10] Quintile 5-1.09[1.06, 1.13] Total-1.06[1.04, 1.08], 3 D Ma

Notes: Relative Effect Modification (Rem) Estimates Presented In Paper.

Reference: Ko et al. (2007, 091639 ) Period of Study: Jan 2000-Dec 2004

Location: Hong Kong, China Ed Visits Outcome (ICD-9): COPD: chronic bronchitis (491), emphysema (492), chronic airway obstruction (496) Age Groups: All Ages Study Design: Time Series

N: 15 hospitals, 119,225 admissions Statistical Analyses: Poisson regression, gam with stringent convergence criteria, aphea2 protocol.

Covariates: Time trend, season, temperature, humidit y, other cyclical factors, day, day of wk, holidays

Season: All yr, interactions with season tested Dose-response Investigated? No Statistical Package: Splus 4.0 Lags Considered: 0-5 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 50.1(23.9) μg/m 3

Percentiles : 25th: 31.9 50th(Median): 44.5

75th: 64.1 Range (Min, Max): (13.6, 172.2) Monitoring Stations: 14 Stations Copollutant (correlation): PM 10 : SO 2 r = 0.436

NO 2 r = 0.229

O 3 r = 0.421

PM 2.5 r = 0.952 PM Increment: 10 μg/m 3

Rr Estimate

COPD: 1.003[1.000, 1.005] Lag 0 1.005[1.002, 1.007] Lag 1 1.010[1.007, 1.012] Lag 2 1.011[1.008, 1.013] Lag 3 1.008[1.006, 1.011] Lag 4 1.007[1.004, 1.009] Lag 5 1.005[1.002, 1.008] Lag 0-1 1.011[1.008, 1.014] Lag 0-2 1.016[1.013, 1.019] Lag 0-3 1.020[1.017, 1.024] Lag 0-4 1.024[1.021, 1.028] Lag 0-5



### December 2009 E-239

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ko et al. (2007, 091639 ) Period of Study: Jan 2000



# - Dec 2004

Location: Hong Kong, China Hospital Admission Outcome (ICD-9): Asthma (493) Age Groups: All, 0-14, 15-56, 65+ Study Design: Time series

N: 69,716 admissions, 15 hospitals Statistical Analyses: Poisson regression, with GAM with stringent convergence criteria.

Covariates: Time trend, season, temperature, humidity, other cyclical factors

Season: All yr, evaluated effect of season in analysis Dose-response Investigated? No Statistical Package: SPLUS 4.0 Lags Considered: 0-5 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 52.5(27.1) μg/m 3

Percentiles: 25th: 30.9 50th(Median): 47.1

75th: 68.8 Range (Min, Max): (13.4, 198.9) Monitoring Stations: 14 stations Copollutant (correlation): PM 10 : SO 2 r = 0.436 NO 2 r = 0.761 O 3 r = 0.600 PM 2.5 r = 0.956 PM Increment: 10.0 μg/m 3

RR Estimate: Asthma (Single-pollutant model): 1.006[1.003, 1.010] lag 0 1.005[1.002, 1.009] lag 1 1.005[1.002, 1.009] lag 2 1.008[1.005, 1.012] lag 3 1.006[1.002, 1.009] lag 4 1.006[0.999, 1.006] lag 5 1.008[1.004, 1.012]; lag 0-1 1.012[1.008, 1.016] lag 0-2 1.015[1.011, 1.019] lag 0-3 1.018[1.013, 1.022] lag 0-4 1.019[1.015, 1.024] lag 0-5 Asthma by age group 0-14: 1.023[1.015, 1.031] lag 0-5 14-65: 1.014[1.006, 1.022] lag 0-5 >65: 1.015[1.009, 1.022] lag 0-4 Asthma-Effect of season: 1.148[1.051, 1.245] lag 0-5

Reference: Kuo et al. (2002, 036310 ) Period of Study: 1 yr

Location: central Taiwan Hospital Admissions Outcome (ICD-NR): Asthma Age Groups: 13-16 yr Study Design: Cohort

N: 12,926 Statistical Analyses: Multiple logistic regression, Pearson correlation

Covariates: Sex, age, residential area, level of parents’ education, number of cigarettes smoked by smokers in the family, incense burning, frequency of physical activity

Season: NR Dose-response Investigated? No Statistical Package: SAS Lags Considered: NR Pollutant: PM 10 Averaging Time: 1 h Mean (min-max): NR Range: (54.1-84.3) Monitoring Stations: 8 Copollutant: Values NR

Notes: Author states that a positive correlation was found between NO 2 and PM 10 PM Increment: NR

OR Estimate:

PM 10 <65.9 μg/m 3 -referent

PM 10 >65.9 μg/m 3

Crude OR: 0.837 Adj OR: 0.947 95% CI: (0.640,1.401)

Reference: Langley-Turnbaugh et al. (2005, 093269 ) Period of Study: 2000-2001

Location: Portland, Bridgeton, and Presque Isle, Maine Hospital Admissions Outcome (ICD-9): Asthma (493xx) Age Groups: 0-18 yr, 19+ yr Study Design: Time series

N: NR Statistical Analyses: NR

Covariates: NR

Season: Winter, spring, summer, fall Dose-response Investigated? No Statistical Package: NR Lags Considered: NR

Notes: Hospital admissions were used to determine seasonality of asthma admissions so that PM components from those time periods could be analyzed Pollutant: PM 10 Averaging Time: NR Mean (min-max): NR Monitoring Stations: NR Copollutant: NR PM Increment: NR RR Estimate [CI]: NR

Notes: Portland filters contained more PM in the winter (Jan) and Bridgeton filters contained more PM in the spring (May) study analyzed metal components of PM 10 (Mn, Cu, Pb, As, V, Ni, Al) Clinical data shows a strong peak in fall and weaker peaks in Jan and May for asthma admissions



### December 2009 E-240

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lee et al. (2002, 034826 ) Period of Study: Dec 1997-Dec 1999

Location: Seoul, Korea Hospital Admissions Outcome (ICD10): Asthma, J45, J46, Age Groups: Children <15 yr Study Design: Time-Series

N: 822 days, 6,436 admissions Statistical Analyses: Poisson regression, GAM, LOESS smoothers.

Covariates: Days of the week, temperature, humidity

Season: All Dose-response Investigated? No Statistical Package: NR Lags Considered: 0-5, 0-1 ma for 1-2, 2-3, and 3-4 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 64.0 (31.8) μg/m 3

Percentiles: 25th: 40.5 μg/m 3 50th(Median): 59.1 μg/m 3

75th: 80.9 μg/m 3 Range (Min, Max): NR Monitoring Stations: 27 Notes: Copollutant (correlation): PM 10 -SO 2 : 0.585

PM 10 -NO 2 : 0.738

PM 10 -O 3 : 0.106

PM 10 -CO: 0.598 PM Increment: IQR: 40.4 μg/m 3

RR Estimate: Single Pollutant: 1.07 (1.04, 1.11) lag 1 Two pollutant models: +SO 2 : 1.05 (1.01, 1.09) lag 1 +NO 2 : 1.03 (0.99, 1.07) lag 1 +O 3 : 1.06 (1.03, 1.10) lag 1 +CO: 1.04 (1.00, 1.08) lag 1 Three pollutant models: +O 3 + CO: 1.02 (0.98, 1.06), lag 1 Four pollutant models: +O 3 + CO +SO 2 : 1.02 (0.98, 1.06), lag 1 Five pollutant model: 1.016 (0.975, 1.059) lag 1 Notes: Investigated the association between outdoor air pollution and asthma attacks in children <15 yr.

Reference: Lee et al. (2006, 090176 ) Period of Study: Jan 1997-Dec 2002

Location: Hong Kong, China Hospital Admission

Outcome: Asthma (493) Age Groups: <18 yr Study Design : Time series

N: 26,663 asthma admissions for asthma and 5821 admissions for influenza Statistical Analyses: Poisson regression, GAM

Covariates: Temperature, atmospheric pressure, relative humidity

Season: All Dose-response Investigated? No Statistical Package: SAS 8.02 Lags Considered: 0-5

Notes: Controls were admissions for influenza ICD9 487 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 56.1 (24.2)

Percentiles: 25th: 37.3 50th(Median): 51.1

75th: 70.7 Monitoring Stations: 10 Notes: Copollutant (correlation): PM 10 -PM 2.5 : 0.90

PM 10 -SO 2 : 0.39

PM 10 -NO 2 : 0.80

PM 10 -O 3 : 0.60 PM Increment: IQr = 33.4

Percent Increase: Single pollutant model: 4.97 [2.96, 7.03], lag 0 5.71 [3.78, 7.68], lag 1 6.40 [4.51, 8.32 ], lag 2 7.25 [5.38, 9.16 ], lag 3 7.45 [5.58, 9.35], lag 4 5.96 [4.11, 7.85 ], lag 5 Multipollutant model (SO 2 , CO, NO 2 , O 3 ) 3.67 [1.52,5.86] lag4

Reference: Lin et al. (2005, 087828 ) Period of Study: 1998-2001

Location: Toronto, North York, East York, Etobicoke, Scarborough, and York (Canada) Hospital Admissions Outcome (ICD-9): Respiratory infections including laryngitis, tracheitis, bronchitis, bronchiolitis, pneumonia, and influenza (464, 466, 480-487) Age Groups: 0-14 yr Study Design: Bidirectional casecrossover

N: 6782 respiratory infection hospitalizations Statistical Analyses: Conditional logistic regression (Cox proportional hazards model)

Covariates: Daily mean temp and dew point temp

Season: NR Dose-response Investigated? No Statistical Package: SAS 8.2 PHREG procedure Lags Considered: 1-7 day avg Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 20.41 (4.00-73.00)

SD = 10.14 Monitoring Stations: 4 Copollutant (correlation): PM 2.5 : r = 0.87

PM 10-2.5 : r = 0.76

CO: r = 0.10

SO 2 : r = 0.48

NO 2 : r = 0.54

O 3 : r = 0.54 PM Increment: 12.5 μg/m 3 OR Estimate [CI]: Adjusted for weather 4-day avg: 1.22 [1.10,1.34] 6-day avg: 1.25 [1.11,1.40] Adj for weather and other gaseous pollutants 4-day avg: 1.14 [0.99,1.32] 6-day avg: 1.20 [1.01,1.42]

Notes: OR’s were also categorized into “Boys” and “Girls,” yielding similar results



### December 2009 E-241

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lin et al, (2008, 126812 ) Period of Study: 1991-2001

Location: New York State, U.S. Outcome: Respiratory hospital admissions (ICD-9 466, 490-493, 496 Study Design: Time-series

Covariates: Demographic characteristics, PM 10 , meteorological conditions, day of the week, seasonality, long term trends and different lag periods Statistical Analysis: GAM and casecrossover design at the regional level and Bayesian hierarchical model at the state level Age Groups: Children 0-17 yr Pollutant: O 3 (PM 10 is secondary) Averaging Time: 24 h Mean (SD) Unit: 19.56 (10.92) μg/m 3 Range (Min, Max): 1.0, 90.00 Copollutant (correlation): Given in Fig 3 All PM 10 results are given in Fig 3

Reference: Lin et al. (2002, 026067 ) Period of Study: Jan 1981-Dec 1993

Location: Toronto Hospital Admissions Outcome (ICD-9): Asthma (493) Age Groups: 6-12 yr Study Design: Uni- and bi-directionalcase-crossover (UCC, BCC) and timeseries (TS)

N: 7,319 asthma admissions Statistical Analyses: Conditional logistic regression, GAM

Covariates: Maximum and minimum temp, avg relative humidity

Season: Apr-Sep, Oct-Mar Dose-response Investigated? No Statistical Package: NR Lags Considered: 1-7 day avg Pollutant: PM 10 Averaging Time: 6 days (predicted daily values) Mean (min-max): 30.16 (3.03-116.20)

SD = 13.61 Monitoring Stations: 1 Copollutant (correlation): PM 2.5 : r = 0.87

PM 10-2.5 : r = 0.83

CO: r = 0.38

SO 2 : r = 0.44

NO 2 : r = 0.52

O 3 : r = 0.44 PM Increment: 14.8 μg/m 3 RR Estimate [CI]: Adj for weather and gaseous pollutants BCC 5-day avg: 0.99 [0.90,1.09] BCC 6-day avg: 1.01 [0.90,1.12] TS 5-day avg: 1.03 [0.95,1.11] TS 6-day avg: 1.02 [0.94,1.11] Boys-adj for weather UCC 1-day avg: 1. 10 [1.04,1.17] UCC 2-day avg: 1. 10 [1.02,1.17] BCC 1-day avg: 1.04 [0.98,1.09] BCC 2-day avg: 1.01 [0.95,1.08] TS 1-day avg: 1.03 [0.99,1.07] TS 2-day avg: 1.01 [0.96,1.05] Girls-adj for weather UCC 1-day avg: 1. 07 [0.99,1.16] UCC 2-day avg: 1. 15 [1.04,1.26] BCC 1-day avg: 0.99 [0.92,1.06] BCC 2-day avg: 1.03 [0.95,1.12] TS 1-day avg: 0.99 [0.94,1.04] TS 2-day avg: 1.02 [0.96,1.08] Notes: The author also provides RR using UCC, BCC, and TS analysis for female and male groups for days 3-7, yielding similar results

Reference: Linares et al. (2006, 092846 ) Period of Study: Jan 1995-Dec 2000

Location: Madrid, Spain Outcome: Respiratory system diseases 460-519, bronchitis 460-496, pneumonia 480-487 Age Groups: <10 yr Study Design: Time series

N: ~15,000 admissions, 2192 days Statistical Analyses: Poisson regression, dummy variables to adjust for season and weather

Covariates: Temperature, difference in barometric pressure, relative humidity, pollen counts, influenza epidemics

Season: All Dose-response Investigated? Yes Statistical Package: S-Plus 2000 Lags Considered: 0-13 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 33.4 μg/m 3 , (13.7) Range (Min, Max): 6, 109 μg/m 3 Monitoring Stations: 24 Notes: Copollutant (correlation): PM 10 -SO 2 : 0.532

PM 10 -O 3 : -0.289

PM 10 -: 0.721

PM 10 -NO 2 : 0.711 PM Increment: 10 μg/m 3

RR Estimate

Bronchitis 1.09 [1.01, 1.16] lag 2

AR% Estimate

Bronchitis 7.9 [CI NR] lag2

Notes: Only statistically significant relative and attributable risks were presented by the authors.

The authors conducted multivariate modeling using a linear term to represent PM 10 . They also report an apparent estimated PM 10 effect threshold of 60 μg/m 3 , based on examination of a scatter plot of respiratory emergency hospital admissions and PM 10 levels.



### December 2009 E-242

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Luginaah, et al. (2005, 057327 ) Period of Study: Apr 1995-Dec 2000

Location: Windsor, Ontario, Canada Hospital Admission/ED:

admission

Outcome: All respiratory: 460-519 Age Groups: A ll, 0-14, 15-64, and >65 Study Design: Times-series, bidirectional case-crossover

N: 4214 admissions Statistical Analyses: Poisson regression, GAM w/ stringent convergence criteria or natural splines, conditional logistic regression

Covariates: Age, sex Maximum & minimum temperature, change in barometric pressure from previous day

Season: All Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 1-3 Pollutant: PM 10 Averaging Time: 24-h max Mean (SD): 50.6 ,(35.5) Range (Min, Max): 9, 349 Monitoring Stations: 4 Notes: Copollutant (correlation): PM 10 -NO 2 : 0.33

PM 10 -SO 2 : 0.22

PM 10 -CO: 0.21

PM 10 -O 3 : 0.33 PM Increment: Interquartile range (75th-25th) 31 μg/m 3 RR Estimates (Time Series) All Age Groups Females 0.996 [0.950, 1.044], lag 1 1.015 [0.963, 1.069], lag 2 1.022 [0.968, 1.078], lag 3 All Age Groups Males 1.008 [0.965, 1.054], lag 1 1.036 [0.986, 1.089], lag 2 1.027 [0.974, 1.083], lag 3 RR Estimates (Case Crossover) All Age Groups Females 1.034 [0.974, 1.098], lag 1 1.045 [0.972, 1.124], lag 2 1.054 [0.970, 1.145], lag 3 All Age Groups Males 0.997 [0.942, 1.056], lag 1 1.022 [0.953, 1.097], lag 2 1.008 [0.930, 1.092], lag 3 Notes: Results, stratified by age group available in manuscript.

Reference: Martins et al. (2002, 035059 ) Period of Study: May 1996-Sep 1998

Location: Sao Paulo, Brazil Hospital Admission/ED:

ER visits Outcome (ICD10): Chronic lower respiratory disease (CLRD) (40-47) Includes chronic bronchitis, emphysema, other COPDs, asthma, bronchiectasia Age Groups: >64 yr Study Design: Time series

N: 712 for CLRD 1 hospital Statistical Analyses: Poisson regression GAM, LOESS smoothers, no mention of stringent criteria

Covariates: Day of week, time minimum temperature, relative humidity

Season: All Statistical Package: S-Plus Lags Considered: 2-7 3 day ma Pollutant: PM 10 Averaging Time: Daily Mean (SD): 60.0 μg/m 3 , (26.3) Range (Min, Max): 22.8. 186.5 μg/m 3 PM Component: None Monitoring Stations: 12 Notes: Copollutant (correlation): PM 10 -CO: 0.73

PM 10 - NO 2 : 0.83

PM 10 -SO 2 : 0.72

PM 10 -O 3 : 0.35 PM Increment: 1 μg/m 3 Regression Coefficients (SE): 0.0024 (0.0023), 6 day ma

Notes: % Increase (SD) for ER visits per 2435 μg/m 3 (IQR) PM 10 (lag 6 day ma) presented graphically in text.



### December 2009 E-243

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Masjedi et al. (2003, 052100 ) Period of Study: Sep 1997-Feb 1998

Location: Tehran, Iran Hospital Admissions Outcome (ICD-9): Acute asthma and COPD exacerbations (ICD: NR) Age Groups: NR Study Design: Time series

N: 355 patients Statistical Analyses: Multiple stepwise regression, autoregression method (time series), Pearson correlation

Covariates: NR

Season: NR Dose-response Investigated? No Statistical Package: NR Lags Considered: 3-, 7-, and 10-day

mean Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 108.41 (14.5-506.60)

SD = 59.55 Monitoring Stations: 3 Copollutant: NR PM Increment: NR

Results: Time-series analysis

Asthma: β = 0.002 p = 0.32 COPD: β = 0.004 p = 0.02 Total Acute Resp Conditions: β = 0.006 p = 0.27 Correlation of 3-day mean

Asthma: r = -0.21 β = -0.16 p = 0.08 Correlation of weekly mean

Asthma: r = -0.27 β = -0.008 p = 0.12 Correlation of 10-day mean

Asthma: r = -0.38 β = -0.066 p = 0.089 Reference: McGowan et al. (2002, 030325 ) Period of Study: Jun 1988-Dec 1998

Location: Christchurch, New Zealand Hospital Admissions Outcome (ICD-9): Pneumonia (480- 487), acute respiratory infections (460- 466), chronic lung diseases (491-492, 494-496), asthma (493) Age Groups: <15 yr, 15-64, 65+ Study Design: Time series

N: 20,938 admissions Statistical Analyses: GAM with log link, Linear Regression Model

Covariates: Wind speed, relative humidity, temperature

Season: NR Dose-response Investigated? No Statistical Package: S-PLUS Lags Considered: 0-6 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 25.17 (0-283)

SD = 25.49 Monitoring Stations: 1 Copollutant: NR PM Increment: 14.8 μg/m 3 (IQR) % Increase [CI]: Respiratory Admissions (2-day lag) 0-14 yr: 3.62 [2.34,4.90] 15-64 yr: 3.39 [1.85,4.93] 65+ yr: 2.86 [1.23,4.49] All ages: 3.37 [2.34,4.40] Overall Acute respiratory infections: 4.53 [2.82,6.24] Pneumonia/influenza: 5.32 [3.46,7.18] Chronic lung diseases: 3.95 [2.15,5.75] Asthma: 1.86 [0.48,.3.24] Total Respiratory Admissions Same day lag: 2.52 [1.49,3.55] 1-day lag: 2.56 [1.53,3.59] 2-day lag: 3.37 [2.34,4.40] 3-day lag: 3.09 [2.06,4.12] 4-day lag: 3.13 [2.10,4.16] 5-day lag: 3.21 [2.18,4.24]; 6-day lag: 3.09 [2.06,4.12]



### December 2009 E-244

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Medina-Ramon et al. (2006, 087721 ) Period of Study: 1986-99

Location: 36 U.S. Cities Outcome: 490-496, except 493 (COPD), 480-487 (Pneumonia ) Age Groups: 65 + (U.S. Medicare beneficiaries) Study Design: Case crossover

N: 578,006 COPD admissions 1,384,813 Pneumonia admissions Statistical Analyses: Conditional logistic regression, Meta-analysis using REML random effects models

Covariates: Mean and variance of daily summer apparent temperature index, % 65+ living in poverty,% households with central air-conditioning mortality rate for emphysema among 65+(surrogate for smoking history), % PM 10 from traffic

Season: Warm(May -Sepnd Cold(Oct-Apr) Dose-response Investigated? No Statistical Package: SAS

STATA Lags Considered: 0-1 days Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 30.4 μg/m 3 (5.1) Monitoring Stations: at least one per city

Notes: PM 10 measurements made every 2, 3 or 6 days depending on the city. Copollutant: NR PM Increment: 10 μg/m 3 % change [Lower CI, Upper CI] lag:

COPD warm season 0.81(0.22,1.41) at lag 0 1.47(0.93,2.01) at lag 1

COPD cold season 0.06(-0.40,0.51) at lag 0 0.10(-0.30,0.49) at lag 1

Pneumonia warm season 0.84 (0.50,1.19) at lag 0 0.79 (0.45,1.13) at lag 1

Pneumonia cold season 0.30 (0.07,0.53) at lag 0 0.14 (-0.17,0.45) at lag 1

Reference: Meng et al., (2007, 093275 ) Period of Study: Nov 2000-Sep 2001

Location: Los Angeles and San Diego counties, California Outcome (ICD-NR): Poorly controlled asthma defined as (1) daily or weekly asthma symptoms or (2) at least 1 ED visit or hospitalization due to asthma over the past 12 mo Age Groups: > 18 yr Study Design: Time series

N: 1609 asthma patients Statistical Analyses: Logistic regression

Covariates: Age, sex, race/ethnicity, poverty level, insurance status, smoking behavior, employment, asthma medication use, and county

Season: NR Dose-response Investigated: No Statistical Package: NR Lags Considered: NR Pollutant: PM 10 Averaging Time: 24 h Mean (25-75th percentile): NR Monitoring Stations: NR Copollutant (correlation): PM 2.5 : r = 0.84

O 3 : r = -0.72

NO 2 : r = 0.83

CO: r = 0.42

Other variables:

Traffic: r = 0.14 PM Increment: 10 μg/m 3 OR Estimate [CI]: All Adults: 1.08 [0.82,1.43] 18-64 yr: 1.14 [0.84,1.55] 65+: 0.84 [0.41,1.73] Men: 0.72 [0.42,1.21] Women: 1.38 [0.99,1.94] Exposure above 44.01 μg/m 3 (annual concentration) All Adults: 1.56 [0.96,2.52] 18-64 yr: 1.40 [0.81,2.41] 65+: 2.23 [0.60,8.27] Men: 0.80 [0.27,2.41] Women: 2.06 [1.17,3.61]

Notes: This study focused more on the relation between poorly controlled asthma and traffic density.



### December 2009 E-245

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Middleton et al. (2008, 156760 ) Period of Study: 1995-1998, 2000-2004

Location: Nicosia, Cyprus Hospital Admissions/ED visits Outcome (ICD-NR): Hospital admissions for all respiratory disease (ICD-10: J00-J99). Age Groups Analyzed: All, also stratified by age (<15 vs.. >15 yr) Study Design: Time series N: Statistical Analyses: Generalized additive Poisson models

Covariates: Seasonality, day of the week, long- and short-term trend, temperature, relative humidity

Season: NR Dose-response Investigated: No Statistical package: STATA SE 9.0, and the MGCV package in the R software (R 2.2.0) Lags Considered: lag 0 -2 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD

median

5% - 95% range):

Cold: 57.6 (52.5

50.8

20.0-103.0 5.0-1370.6)

Warm: 53.4 (50.5

30.7

32.0-77.6 18.4-933.5) Monitoring Stations: 2 Copollutant (correlation): NR

Other variables: PM Increment: 10 μg/m 3 , and across quartiles of increasing levels of PM 10 Percentage increase estimate [CI]: All age/sex groups (Lag 0): All admissions: 0.85 (0.55, 1.15) Respiratory (all): 0.10 (-0.91, 1.11) Respiratory (cold months): -0.33 (-1.47, 0.82) Respiratory (warm months): 1.42 (-0.42, 3.31) CVD + RD: 0.56 (-0.21, 1.34) Nicosia residents (Lag 0): Respiratory (all): 0.25 (-0.84, 1.36) Respiratory (cold months): -0.22 (-1.45, 1.02) Respiratory (warm months): 1.80 (-0.22, 3.85) CVD + RD: 0.38 (-0.47, 1.23) Males (Lag 0): All admissions: 0.96 (0.54, 1.39) Respiratory (all): -0.06 (-1.37, 1.26) Respiratory (cold months): -0.16 (-1.76, 1.46) Respiratory (warm months): 1.10 (-1.47, 3.74) CVD + RD: 0.63 (-0.34, 1.62) Females (Lag 0): All admissions: 0.74 (0.31, 1.18) Respiratory (all): 0.39 (-1.21, 2.02) Respiratory (cold months): -0.26 (-2.18, 1.70) Respiratory (warm months): 3.27 (-0.00, 6.65) CVD + RD: 0.59 (-0.68, 1.87) Aged <15 yr (Lag 0): All admissions: 0.47 (-0.13, 1.08) Respiratory (all): -0.35 (-1.77, 1.08) Respiratory (cold months): -0.31 (-2.02, 1.42) Respiratory (warm months): -0.59 (-3.53, 2.45) Aged >15 yr (Lag 0): All admissions: 0.98 (0.63, 1.33) Respiratory (all): 0.59 (-0.87, 2.07) Respiratory (cold months): 0.02 (-1.76, 1.83) Respiratory (warm months): 3.89 (1.05, 6.80) Reference: Moore et al. (2008, 196685 ) Period of Study: 1983-2000

Location: California’s South Coast Air Basin Outcome: Hospital admissions for asthma (ICD-9 493) Study Design: Time-series

Covariates: Income, demographic and residential variables Statistical Analysis: HRMSM Age Groups: Children ages 0-19 yr Pollutant: O 3 (PM 10 secondary) Averaging Time: Quarterly Mean (SD) Unit: NR Range (Min, Max): NR Copollutant (correlation): 1hr O 3 : 0.52 8hr O 3 : 0.46 24 h NO : 0.53 2 24 h CO: 0.36 24 h SO 2 : 0.13 Results given are for O 3



### December 2009 E-246

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Nascimento et al. (2006, 093247 ) Period of Study: May 2000-Dec 2001

Location: São Jose dos Campos, Brazil Hospital Admissions Outcome (ICD-10): Pneumonia (J12- J18) Age Groups: 0-10 yr Study Design: Time series

N: 1265 admissions Statistical Analyses: GAM, Poisson regression

Covariates: Temperature, humidity

Season: NR Dose-response Investigated? Yes Statistical Package: S-Plus, SPSS Lags Considered: 0-7 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 40.2 (3.4-196.6)

SD = 26.9 Monitoring Stations: 2 Copollutant (correlation): SO 2 : r = 0.30

O 3 : r = 0.09

Other variables:

Admissions: r = 0.21 Temp: r = -0.14

Notes: All p < 0.05 PM Increment: 24.7 μg/m 3 Regression coefficients (SE): Same day: -0.00053 (0.00125) 1-day lag: 0.00029 (0.00057) 2-day lag: 0.00089 (0.00069) 3-day lag: 0.00122 (0.00053)* 4-day lag: 0.00126 (0.00055)* 5-day lag: 0.00098 (0.00071) 6-day lag: 0.00035 (0.00056) 7-day lag: -0.00067 (0.00123) *p < 0.05

Notes: Percent increase over all lag days is displayed in Fig 2

Reference: Neuberger et al. (2004, 093249 ) Period of Study: 1999-2000 (1 yr period)

Location: Vienna and Lower Austria Hospital Admissions Outcome (ICD-9): Bronchitis, emphysema, asthma, bronchiectasis, extrinsic allergic alveolitis, and chronic airway obstruction (490-496) Age Groups: 3.0-5.9 yr 7-10 yr

65+ Study Design: Time series

N: 366 days (admissions NR) Statistical Analyses: GAM

Covariates: SO 2 , NO, NO 2 , O 3 , temperature, humidity, and day of the week

Season: NR Dose-response Investigated? Yes Statistical Package: S-Plus 2000 Lags Considered: 0-14 days Pollutant: PM 10 Averaging Time: 24 h Maximum daily mean:

Vienna: 105

Rural area: NR Monitoring Stations: NR Copollutant: NR PM Increment: 10 μg/m 3 Log Relative Rate Estimate (p-value):

Vienna Male: 2 day lag = 4.217 (0.030) Association with tidal lung function: β = -1.067 (p-value = 0.241)

Notes: Effect parameters with significant coefficients for respiratory health included: male sex, allergy, asthma in family, and traffic for Vienna and age, allergy, asthma in family, and passive smoking for the rural area. Effect parameters with significant coefficients for log asthma score were allergy, asthma in family, and rain for Vienna and allergy, asthma in family, and passive smoking for the rural area.

Reference: Oftedal et al. (2003, 055623 ) Period of Study: 1995-2000

Location: Drammen, Norway Hospital Admissions

Outcome: All Respiratory (460-517) Age Groups: All Study Design: Time-series

N: ~4,458 admissions Statistical Analyses: Poisson regression, GAM w/ stringent convergence criteria

Covariates: Temperature, humidity, influenza epidemics, summer and Christmas vacation

Season: All Dose-response Investigated? Yes Statistical Package: S-Plus Lags Considered: 2-3 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 16.8 μg/m 3 , (10.2) 1994- 1997 16.5 μg/m 3 , (10.3) 1998-2000 16.6 , μg/m 3 (10.2) total period PM Component: Benzene, formaldehyde, toluene Monitoring Stations: NR Notes: Copollutant (correlation): Correlation between pollutants ranged from -0.47-0.78 with the exception of the VOCs studied

Notes: Benzene, formaldehyde and toluene also evaluated PM Increment: IQr = 11.04

RR Estimate 1.035 [0.990, 1.083] 1994-1997 0.992 [0.948, 1.037] 1998-2000 1.021 [0.990, 1.053] 1994-2000

2 Pollutant Model

PM 10 w/ benzene: 1.01 (0.978, 1.043)



### December 2009 E-247

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Peel et al. (2005, 056305 ) Period of Study: Jan 1993-Aug 2000

Location: Atlanta, Georgia ED visits

Outcome: Asthma (493, 786.09) COPD (491, 492, 496) URI (460-466, 477) Pneumonia (480-486) Age Groups: All ages. Secondary analyses conducted by age group: 0-1, 2-18, >18 Study Design: Time series

N: 31 hospitals Statistical Analyses: Poisson GEE for URI, asthma and all RD Poisson GLM for pneumonia and COPD)

Covariates: Avg temperature and dew point, pollen counts

Season: All (secondary analyses of warm season) Dose-response Investigated? Yes Statistical Package: SAS 8.3, S-Plus 2000 Lags Considered: 0-7 day , 3 day ma, 0-13 days unconstrained distributed lag Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 27.9 (12.3) μg/m 3

Percentiles: 10th: 13.2

90th: 44.7 Monitoring Stations:

“Several” Copollutant (correlation): 8 h O 3 : r = 0.59

1 h NO 2 : r = 0.49

1 h CO: r = 0.47

1 h SO 2 : r = 0.20

24-h PM 2.5 : 0.84

24 h PM 10-2.5 : r = 0.59

24 h UF: r = -0.13 Components: r ranged from 0.42-0.74 PM Increment: PM 10 : 10 μg/m 3 RR Estimate [Lower CI, Upper CI] All Respiratory Outcomes: 1.013 (1.004-1.021), 3 day ma

URI: 1.014 (1.004-1.025) , 3 day ma 1.073 (1.048-1.099) , 14-day dist. lag

Asthma: 1.009 (0.996-1.022), 3 day ma 1.099 (1.065-1.135), 14-day dist. lag: Pediatric Asthma 2-18yrs): 1.016 (0.998 -1.034)

Pneumonia: 1.011 (0.996-1.027) , 3 day ma 1.087 (1.044-1.132), 14-day dist. lag

COPD: 1.018 (0.994-1.043), 3 day ma 1.092 (1.023-1.165), 14-day dist. lag

Notes: RRs obtained using AQS 1993- 2000, AQS 1998-2000 and ARIES data compared. Infant (0-1 y) and pediatric (2-18 y) asthma was associated more strongly with PM 10 , PM 2.5 and OC than adult asthma.

Reference: Ren et al. (2006, 092824 ) Period of Study: Jan 1996-Dec 2001

Location: Brisbane, Australia Hospital Admissions Outcome (ICD-9): Respiratory diseases (460-519) excluding influenza (487.0-487.8) Age Groups: NR Study Design: Time series

N: NR Statistical Analyses: GAM

Covariates: Day of week, relative humidity, influenza outbreaks

Season: NR Dose-response Investigated? Yes Statistical Package: S-Plus Lags Considered: 0, 1, and 2 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 15.84 (2.5-60) Monitoring Stations: 1 Copollutant: NR PM Increment: NR

Coefficient Estimates: Respiratory Hospital Admissions Same day: -0.004296 1-day lag: -0.002474 2-day lag: -0.004229 *all statistically significant Respiratory Emergency Visits Same day: -0.000887 1-day lag: -0.004209 2-day lag: -0.003440

Notes: Relative risks were provided in graphical form (Fig 3)

Reference : Sauerzapf et al. (2009, 180082 ) Period of Study: Mar 2006-Mar 2007

Location: Norfolk, UK Outcome: COPD Study Design: Case-Crossover

Covariates: Environmental factors and Influenza Statistical Analysis: Logistic regression Statistical Package: SPSS 14 Age Groups: >18 yr

N: 1050 adult COPD admissions Pollutant: PM 10 Averaging Time: 24 h Mean (SD) Unit: Control: 19.87 (8.51) μg/m 3 Case: 20.47 (9.27) μg/m 3 Range (Min, Max):

Control: 9.77-34.27

Case: 10.04-35.03 Copollutant (correlation): NR Increment: 10 μg/m 3 Odds Ratio (95% CI) Lag 0-7, unadjusted: 1.079 (0.980- 1.188) Lag 0-8, adjusted: 1.101 (0.988-1.226) Lag 1-8, unadjusted: 1.056 (0.961- 1.161) Lag 1-8, adjusted: 1.054 (0.949-1.170)



### December 2009 E-248

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sinclair and Tolsma (2004, 088696 ) Period of Study: 25 Months

Location: Atlanta, Georgia Outpatient Visits

Outcome: Asthma (493) URI (460, 461, 462, 463, 464, 465, 466, 477) LRI (466.1, 480, 481, 482, 483, 484, 485, 486). Age Groups: < = 18 yr, 18+ yr (asthma) All ages (URI//LRI) Study Design: Times series

N: 25 mo 260,000-275,000 health plan members (Aug 1998-Aug 2000) Statistical Analyses: Poisson GLM

Covariates: Season, Day of week, Federal Holidays, Study Months

Season: NR Dose-response Investigated?: No Statistical Package: SAS Lags Considered: Three 3-day ma (0- 2, 2-5, 6-8) Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): PM 10 mass-29.03 μg/m 3 (11.61) Monitoring Stations: 1 Notes: Copollutant: NR PM Increment: 11.61 (1 SD) RR Estimate [Lower CI, Upper CI] lag: Child Asthma: 1.049 (S), lag 3-5 day LRI: 1.074 (S), 3-5 day lag

Notes: Numerical findings for significant results only presented in manuscript. Results for all lags presented graphically for each outcome (asthma, URI, and LRI).

Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 1995-Jun 2001

Location: Spokane, WA Hospital Admissions and ED visits

Outcome: All respiratory (460-519) Asthma (493) COPD (491,492, 494,496) Pneumonia (480-487) Acute URI not including colds and sinusitis (464, 466, 490) Age Groups: All, 15+ yr for COPD Study Design: Time series

N: 2373 visit records Statistical Analyses: Poisson regression, GLM with natural splines. For comparison also used GAM with smoothing splines and default convergence criteria.

Covariates: Season, temperature, relative humidity, day of week

Season: All Dose-response Investigated?: No Statistical Package: SAS, SPLUS Lags Considered: 1 -3 day Pollutant: PM 10 Averaging Time: 24-h avg Range (90% of concentrations): 7.9- 41.9 μg/m 3 Monitoring Stations:

1 Notes: Copollutant (correlation): PM 10 PM1 r = 0.50

PM 2.5 r = 0.62

PM 10-2.5 r = 0.94

CO r = 0.32 Temperature r = 0.11 PM Increment: 25 μg/m 3 RR Estimate [Lower CI, Upper CI] lag:

ER visits -- PM 10 All Respiratory Lag 1: 1.01 [0.99, 1.04] Lag 2: 1.01 [0.98, 1.03] Lag 3: 1.02 [0.99, 1.04] Acute Asthma Lag 1: 1.03 [0.98, 1.07] Lag 2: 1.01 [0.96, 1.05] Lag 3: 1.00 [0.95, 1.04] COPD (adult) Lag 1: 1.00 [0.93, 1.07] Lag 2: 0.99 [0.92, 1.06] Lag 3: 1.02 [0.95, 1.08] Hospital Admissions -- PM 10 All Respiratory Lag 1: 0.99 [0.95, 1.02] Lag 2: 0.99 [0.96, 1.02] Lag 3: 1.00 [0.97, 1.03] Asthma Lag 1: 1.03 [0.95, 1.12] Lag 2: 1.01 [0.94, 1.10] Lag 3: 1.00 [0.92, 1.09] COPD (adult) Lag 1: 0.98 [0.90, 1.07] Lag 2: 1.03 [0.96, 1.11] Lag 3: 1.02 [0.94, 1.09]



### December 2009 E-249

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sun et al. (2006, 090768 ) Period of Study: Jan 2004-Dec 2004

Location: Taichung, Taiwan (Central Taiwan) ED visits

Outcome: Asthma (493.xx) Age Groups: <55, <16, 16-55 yr Study Design: Cross-sectional

N: NR All diagnoses for all patients at 4 medical centers Statistical Analyses: Pearson’s correlations, multiple correlation coefficients from regression analyses.

Covariates: Only copollutants considered Dose-response Investigated? No Statistical Package: SPSS Lags Considered: None Pollutant: PM 10 Averaging Time: Monthly avg for 2004 Mean (SD): ~ 60.3 μg/m 3 (NR) (estimated from Fig)* Range (Min, Max): (~35, 80) Monitoring Stations: 11 Copollutant: NR Children ED Visits

r = 0.626

P = 0.015

Adult ED Visits

r = 0.384

P = 0.109

Reference: Szyszkowicz (2007, 092829 ) Period of Study: Jan 1992-Mar 2002

Location: Edmonton, Canada Outcome: ED visits for asthma (ICD- (493) Study Design: Time-series

Covariates: Temperature, relative humidity Statistical Analysis: Poisson regression Age Groups: All Pollutant: PM 10 Averaging Time: 24 h Mean (SD) Unit: 22.6 (13.1) μg/m 3

Median, IQR: 19.4, 15.0 Copollutant (correlation): NR Increment: IQR Percent Relative Risk (95% CI) *Only statistically significant results are presented in the paper* No lag, ≥ 10 yr Apr-Sep, All: 3.7 (1.5-6.0) Apr-Sep, Female: 4.5 (1.8-7.3) Apr-Sep, Male: 3.3 (0.1-6.7) 2 day lag, < 10 yr Year round, All: 2.7 (0.1-5.4) Apr-Sep, All: 6.3 (2.6-10.2) Apr-Sep, Male: 7.4 (3.1-11.9) 2 day lag, ≥ 10 yr Apr-Sep, All: 2.4 (0.1-4.7) Apr-Sep, Female: 3.9 (1.1-6.7) Reference: Tecer et al, (2008, 180030 ) Period of Study: Dec 2004-Oct 2005

Location: Zonguldak, Turkey Outcome: ED visits for respiratory problems (ICD-9 470-478, 493) Study Design: Bidirectional Casecrossover Covariates: Daily meteorological parameters Statistical Analysis: Conditional logistic regression Statistical Package: Stata Age Groups: 0-14 yr Pollutant: PM 10 Averaging Time: NR Mean, Unit: 53.3 μg/m 3 Range (Min, Max): 12-237.5 Copollutant (correlation):

PM 2.5 /PM 10 Mean: 0.56 Range: 0.17-0.88 Increment: 10 μg/m 3 Odds Ratio (95% CI) Asthma Lag 0: 1.14 (1.03-1.26) Lag 1: 0.92 (0.83-1.02) Lag 2: 0.92 (0.81-1.03) Lag 3: 1.01 (0.92-1.11) Lag 4: 1.16 (1.06-1.26) Allergic Rhinitis with Asthma Lag 0: 1.07 (1.01-1.13) Lag 1: 0.96 (0.91-1.02) Lag 2: 0.93 (0.88-0.99) Lag 3: 0.96 (0.90-1.02) Lag 4: 1.08 (1.02-1.14) Allergic Rhinitis Lag 0: 1.06 (0.99-1.13) Lag 1: 1.08 (1.01-1.16) Lag 2: 0.92 (0.87-0.99) Lag 3: 0.97 (0.92-1.03) Lag 4: 1.09 (1.03-1.16) Upper Respiratory Disease Lag 0: 0.88 (0.68-1.14) Lag 1: 1.17 (0.91-1.51) Lag 2: 1.00 (0.76-1.31) Lag 3: 0.95 (0.76-1.19) Lag 4: 1.15 (0.97-1.35) Lower Respiratory Disease Lag 0: 1.01 (0.86-1.19) Lag 1: 1.04 (0.88-1.23) Lag 2: 1.04 (0.92-1.18) Lag 3: 1.23 (1.07-1.41) Lag 4: 0.99 (0.90-1.08)



### December 2009 E-250

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Tolbert et al. (2007, 090316 ) Period of Study: 1993-2004

Location: Atlanta Metropolitan area, Georgia Hospital Admissions/ED visits Outcome (ICD-9): Combined RD group, including: Asthma (493, 786.07, 786.09), COPD (491, 492, 496), URI (460-465, 460.0, 477), pneumonia (480-486), and bronchiolitis (466.1, 466.11, and 466.19)) Age Groups Analyzed: All Study Design: Time series

N: 10,234,490 ER visits (283,360 and 1,072,429 visits included in the CVD and RD groups, respectively) Statistical Analyses: Poisson generalized linear models

Covariates: Long-term temporal trends, season (for RD outcome), temperature, dew point, days of week, federal holidays, hospital entry and exit

Season: All Dose-response Investigated: No Statistical package: SAS version 9.1 Lags Considered: 3-day ma(lag 0 -2) Pollutant: PM 10 Averaging Time: 24 h Mean (median IQR, range, 10th-90th percentiles): 26.6 (24.8

17.5-33.8

0.5-98.4 12.3-42.8) Monitoring Stations: NR Copollutant (correlation): O 3 : r = 0.59 NO 2 : r = 0.53 CO: r = 0.51 SO 2 : r = 0.21 Coarse PM: r = 0.67 PM 2.5 : r = 0.84 PM 2.5 SO 4 : r = 0.69 PM 2.5 EC: r = 0.61 PM 2.5 OC: r = 0.65 PM 2.5 TC: r = 0.67 PM 2.5 water-sol metals: r = 0.73 OHC: r = 0.53 PM Increment: 16.30 μg/m 3 (IQR) Risk ratio [95% CI]: Single pollutant models: RD: 1.015 (1.006-1.024)

Notes: Results of selected multipollutant models for respiratory disease are presented in Fig 2. Fig 2: PM 10 adjusted for CO, O 3 , NO 2 , or NO 2 /O 3 (nonwinter months only) Summary of results: PM 10 remained predictive of RD in non-winter months after adjustment for pollutants.

Reference: Tsai et al. (2006, 089768 ) Period of Study: 1996-2003

Location: Kaohsiung City, Taiwan Outcome: Asthma (493) Age Groups: All (universal health care covers >96% of the population) Study Design: Case crossover

N: 17,682 admissions 63 hospitals Statistical Analyses: Conditional Logistic Regression

Covariates: Temperature, humidity

Season: Warm and cool seasons Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-2 day cumulative Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 76.62 μg/m 3 (NR)

Percentiles: 25th: 41.73 50th(Median): 74.40

75th: 104.01 Range (Min, Max): (16.70, 232.00) Monitoring Stations: 6 Copollutant: NR PM Increment: 62.28 μg/m 3 OR Estimate [Lower CI, Upper CI] lag: Single-pollutant model, 0-2 day cumulative lag ≥ 25oC: 1.302 [1.155, 1.467] <25oC: 1.556 [1.398, 1.371] Two-pollutant models, 0-2 day cumulative lag PM 10 w/ SO 2 ≥ 25oC: 1.305 [1.156, 1.473] <25oC: 1.540 [1.374, 1.727] PM 10 w/ O 3 ≥ 25oC: 0.985 [0.842, 1.152] <25oC: 1.581 [1.402, 1.783] PM 10 w/ NO 2 ≥ 25oC: 1.237 [1.052, 1.455] <25oC: 1.009 [0.875, 1.163] PM 10 w/ CO ≥ 25oC: 1.156 [1.012, 1.320] <25oC: 1.300 [1.134, 1.490]



### December 2009 E-251

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ulirsch et al. (2007, 091332 ) Period of Study: Nov 1994-Mar 2000

Location: Pocatello, Idaho Chubbuck, Idaho Outcome: Respiratory Disease (460- 499, 509-519) Reactive Airway Disease (786.09) Age Groups: All age groups Study Design: Time series

N: 39,347 visits (TS1) 29,513 visits (TS2) Statistical Analyses: Poisson regression, GLM. Sensitivity Analyses

Covariates: Time, Temperature, Relative Humidity Influenza

Season: Warm/Cool Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 0-4 day lags

Notes: Time series (TS) 1 includes HA, ED and urgent care visits. TS 2 includes family practice data available after 1997 Pollutant: PM 10 Averaging Time: NR Mean (SD): TS1: 24.2 μg/m 3 (NR)

10th: 10.5

90th: 40.7

TS2: 23.2

10th: 10.0

90th: 37.4 Range (Min, Max): TS1: (3.0, 183.0) TS2: (3.0, 183.0) Monitoring Stations: 4 Notes: Copollutant (correlation): PM 10 w/ NO 2 : r = 0.47. PM 10 with other copollutants weakly correlated. PM Increment: Single Pollutant Models, TS1: 24.4 μg/m 3 Single Pollutant Models: TS2: 23.2 μg/m 3 Multipollutant Models: TS1/TS2: 50 μg/m 3 Mean Percentage Change, lag 0 TS 1: Single Pollutant All-age (all yr): 4.0 [1.4,6.7] 18-64: 3.4 [0.2, 6.7] 0-17: 4.3 [-0.1, 8.9] 65+: 5.6 [-1.4, 13.1] 0-17/65+: 5.5 [1.4, 9.6] All age (Cool season): 4.3 [1.3, 7.5] All age (Warm season): 6.7 [-0.8, 14.8] TS2: Single Pollutant All-age: 3.3 [0.3, 6.3] 18-64: 3.3 [-0.4, 7.0] 0-17: 5.0 [0.1, 10.1] 65+: 6.9 [-0.4, 14.7] Multipollutant (PM 10 + SO 2 ) All-age (all yr): TS1 10.8 TS2 17.5 18-64: TS1 8.0 TS2 9.1 0-17: TS1 10.8 TS2 32.7 65+: TS1 8.7 TS2 31.3 0-17/65+: TS1 14.2 TS2 25.3 All age (Cool season) TS1 11.9 Multipollutant (PM 10 + NO 2 ) All-age (all yr) TS1: TS2 16.3 18-64: TS1 9.3 TS2 17.3 0-17: TS1 4.6 TS2 18.7 65+: TS1 12.4 TS2 32.7 0-17/65+: TS1 9.5 32.7 All age (Cool season): TS1 11.1 TS2 16.8 Notes: Results from multipollutant model with PM 10 , SO 2 and NO 2 also available.

Reference: Vegni and Ros (2004, 087448 ) Period of Study: Sep 2001-Sep 2002

Location: Milan area, Italy Hospital Admissions Outcome (ICD-9): Respiratory, noninfectious admissions (ICD: NR) Age Groups: NR Study Design: Time series

N: 9881 admissions Statistical Analyses: Poisson regression

Covariates: Temperature, wind velocity, relative humidity, week day, holidays

Season: Spring, summer, fall, winter Dose-response Investigated? No Statistical Package: STATA v. 5 Lags Considered: 0, 1, and 2 days Pollutant: PM 10 Averaging Time: 24 h Mean (5th-95th percentile): Overall: 41.5 (13-98) SD = 28.2 Spring: 29.0 (10-51) SD = 12.6 Summer: 24.8 (10-40) SD = 9.9 Fall: 51.8 (21-114) SD = 27.1 Winter: 64.1 (20-135) SD = 35.7 Monitoring Stations: 1 Copollutant: NR PM Increment: Increase from 5th-95th percentile Spring: 85 μg/m 3 summer: 30 μg/m 3 Fall: 93 μg/m 3 Winter: 115 μg/m 3 RR Estimate [CI]: Overall: 1.10 [0.83,1.46] Adjusted: 0.97 [0.67,1.41]

Notes: 1-day and 2-day lags show similar results, with no association between PM 10 and daily hospital admissions



### December 2009 E-252

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Vigotti et al. (2007, 090711 ) Period of Study: Jan 2000-Dec 2000

Location: Pisa, Italy ED Visits

Outcome: Asthmatic attack (493), dry cough (468), acute bronchitis (466) Age Groups: <10 yr; 65+ yr Study Design: Time series

N: 966 Emergency room visits Statistical Analyses: Poisson regression, GAM, LOESS smoothers, stringent criteria

Covariates: Temperature, humidity, relative humidity, day of study, rainfall, influenza, day of-the-wk, holidays, time trend

Season: All yr Dose-response Investigated? No Statistical Package: NR Lags Considered: 0-5 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 35.4 (15.8) μg/m 3

Percentiles: 25th: NR 50th(Median): 31.6

75th: NR Range (Min, Max): (9.5, 100.1) Monitoring Stations:

2 Copollutant (correlation): PM 10 : NO 2 r = 0.58

CO r = 0.70 PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: <10 y: 10%[2.3, 18.2] lag 1 65+: 8.5% [1.5, 16.1] lag 2

Reference: Xirasagar et al. (2006, 093267 ) Period of Study: 1998-2001

Location: Taiwan Hospital Admission/ED:

Outcome: Asthma or Asthmatic Bronchitis (493) Age Groups: <2 yr old, 2~5 yr old, 6~14 yr old Study Design:

N: 27, 275 pediatric hospitalizations Statistical Analyses: ARIMA Modeling Spearman’s Correlations

Covariates: Season, ambient temp., rel. humidity, atmospheric pressure, rainfall, h of sunshine

Season: Spring: Feb-Apr Summer: May-Jul Fall: Aug-Oct Winter: Nov-Jan Dose-response Investigated? No Statistical Package: EViews 4 Lags Considered: NR Pollutant: PM 10 Averaging Time: Monthly means Mean (SD): 24.4 μg/m 3 (NR)

Percentiles: NR Range (Min, Max): NR PM Component: NR Monitoring Stations: 44 air quality monitoring banks. 23 weather observatories Notes: Copollutant (correlation): < 2 yr old: r = 0.315 2~5 yr old: r = 0.589 6~14 yr old: r = 0.493 PM Increment: NR RR Estimate [Lower CI, Upper CI] lag: NR AR Estimate [Lower CI, Upper CI] lag: NR

Notes: Plot of monthly asthma admission rates per 100,000 population by age group Plot of mean monthly concentration trends of criteria air pollutants Mean monthly trends of climatic factors

Other Outcomes Assessed? NR Other Exposures Assessed? Seasonality



### December 2009 E-253

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Wong et al., (2002, 023232 ) Period of Study: 1995-1997 (Hong Kong) and 1992-1994 (London)

Location: Hong Kong and London Hospital Admissions Outcome (ICD- NR): Asthma (493) for ages 15-64 and respiratory disease (460-519) for ages 65+ Age Groups: 15-64, 65+ Study Design: Time series

N: NR Statistical Analyses: Poisson regression, GAM

Covariates: Temperature, humidity, and influenza

Season: Warm (Apr-Sep) and cool (Oct-Mar) Dose-response Investigated? Yes Statistical Package: S-Plus Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): Hong Kong: 51.8 (14.1-163.8) SD = 25.0 London: 28.5 (6.8-99.8)

SD = 13.7 Monitoring Stations: NR Copollutant (correlation): Hong Kong NO 2 : r = 0.82 SO 2 : r = 0.30 O 3 : r = 0.54 London NO 2 : r = 0.68 SO 2 : r = 0.64 O 3 : r = 0.17

Other variables: Hong Kong Temp: r = -0.42 Humidity: r = -0.53 London Temp: r = 0.02 Humidity: r = -0.05 PM Increment: 10 μg/m 3 ER Estimate [CI]: Single-pollutant excess risk (mean lag 0-1 day) Asthma-Hong Kong: -1.1 [-2.4,0.1] Asthma-London: 1.4 [-0.1,3.0] Respiratory Disease-Hong Kong: 1.0 [0.5,1.5] Respiratory Disease-London: 0.4 [-0.3,1.2] Warm season Asthma-Hong Kong: -1.0 [-2.8, 0.8] Asthma-London: 0.6 [-1.9,3.1] Respiratory Disease-Hong Kong: 0.8 [0.1,1.4] Respiratory Disease-London: 1.8 [0.5,3.1] Cool season Asthma-Hong Kong: -1.2 [-2.8,0.4] Asthma-London: 1.6 [-0.3,3.6] Respiratory Disease-Hong Kong: 1.2 [0.6,1.9] Respiratory Disease-London: -0.5 [-1.5,0.5] Notes: RRs are shown graphically in Fig 1 and 2. Exposure response curves are provided in Fig 5 of the article

Reference: Wong et al. (2006, 093266 ) Period of Study: 2000-2002

Location: Hong Kong (8 districts) General Practitioner Visits Outcome (ICPC-2): Respiratory diseases/symptoms: upper respiratory tract infections (URTI), lower respiratory infections, influenza, asthma, COPD, allergic rhinitis, cough, and other respiratory diseases Age Groups: All ages Study Design: Time series

N: 269,579 visits Statistical Analyses: GAM, Poisson regression

Covariates: Season, day of the week, climate

Season: NR Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 0-3 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): Ranged from 43.4- 56.9 (dependent on location) Monitoring Stations: 1 per district Copollutant (correlation): PM 2.5 : r = 0.94

O 3 : r = 0.40

SO 2 : r = 0.28 PM Increment: 10 μg/m 3 RR Estimate [CI]:

Overall URTI 1.020 [1.016,1.025]

Overall Non-UTRI 1.025 [1.018,1.032]

Notes: RRs are also reported for each individual general practitioner yielding similar results



### December 2009 E-254

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Yang et al. (2007, 092847 ) Period of Study: 1996-2003

Location: Taipei, Taiwan Hospital Admission/ED:

Outcome: Asthma (493) Age Groups: All ages Study Design: Case-crossover

N: 25,602 asthma hospital admissions Statistical Analyses: NR

Covariates: Temperature, humidity, day of-the-wk, seasonality, long term trends

Season: All yr Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-2 Pollutant: PM 10 Averaging Time: NR Mean (SD): 48.99 μg/m 3

Percentiles: 25th: 32.64 50th(Median): 44.13

75th: 59.05 Range (Min, Max): (14.44, 234.91) PM Component: NR Monitoring Stations:

6 Stations Notes: Copollutant: NR PM Increment: 26.41 μg/m 3 OR Estimate [Lower CI, Upper CI] lag:

Asthma Single-Pollutant Model: Temperature >25 ° C: 1.046[0.971, 1.128] Temperature <25 ° C: 1.048[1.011, 1.251] Two-Pollutant Model: Adjusted for SO 2 : >25 ° C-1.006[0.920, 1.099]

<25 ° C-1.088[1.040, 1.138] Adjusted for NO 2 : >25 ° C-0.800[0.717, 0.892]

<25 ° C-0.982[0.937, 1.029] Adjusted for CO: >25 ° C-0.920[0.844, 1.002]

<25 ° C-1.029[0.984, 1.076] Adjusted for O 3 : >25 ° C-1.038[0.950, 1.134]

<25 ° C-1.042[1.004, 1.081] AR Estimate [Lower CI, Upper CI] lag: NR

Notes: Other Outcomes Assessed? NR Other Exposures Assessed? SO 2 , NO 2 , CO, O 3 Reference: Yang et al. (2007, 092847 ) Period of Study: 1996-2003

Location: Taipei, Taiwan Hospital Admission

Outcome: COPD (490-192), (494), (496) Age Groups: All ages Study Design: Case-crossover

N: 46,491COPD admissions, 47 hospitals Statistical Analyses: Conditional logistic regression

Covariates: Weather, day of-the-wk, seasonality, long term trends

Season: Warm/Cool Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-2 cumulative Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 48.99 μg/m 3

25th: 32.64 50th(Median): 44.13

75th: 59.05 Range (Min, Max): (14.44, 48.99) Monitoring Stations:

6 Stations Notes: Copollutant: NR PM Increment: 26.41 μg/m 3 OR Estimate [Lower CI, Upper CI] Single-Pollutant Model (0-2 day cum lag): Temperature >20 ° C: 1.133[1.098, 1.168] Temperature <20 ° C: 1.035[0.994, 1.077] Two-Pollutant Model: PM 10 w/ SO 2 : >20 ° C-1.180[1.139, 1.223] <20 ° C-1.004[0.954, 1.057] PM w/ NO :

10 2 >20 ° C-1.013[0.973, 1.055] <20 ° C-1.074[1.022, 1.129] PM w/ CO:

10 >20 ° C-1.061[1.023, 1.100] <20 ° C-1.067[1.016, 1.120] PM 10 w/ O 3 : >20 ° C-1.097[1.062, 1.133] <20 ° C-1.036[0.996, 1.079]



### December 2009 E-255

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Yang et al. (2004, 087488 ) Period of Study: Jun 1995-Mar 1999

Location: Vancouver area, British Columbia Hospital Admissions Outcome (ICD-9): Respiratory diseases (460-519), pneumonia only (480-486), asthma only (493) Age Groups: 0-3 yr Study Design: Case control, bidirectional case-crossover (BCC), and time series (TS)

N: 1610 cases Statistical Analyses: Chi-square test, Logistic regression, GAM (time-series), GLM with parametric natural cubic splines

Covariates: Gender, socioeconomic status, weekday, season, study yr, influenza epidemic month

Season: Spring, summer, fall, winter Dose-response Investigated? No Statistical Package: SAS (Case control and BCC), S-Plus (TS) Lags Considered: 0-7 days Pollutant: PM 10 Averaging Time: 24 h Mean (min-max): 13.3 (3.8-52.2)

SD = 6.1 Monitoring Stations: NR (data obtained from Greater Vancouver Regional District Air Quality Dept) Copollutant (correlation): PM 2.5 : r = 0.83

PM 10-2.5 : r = 0.83

CO: r = 0.46

O 3 : r = -0.08

NO 2 : r = 0.54

SO 2 : r = 0.61 PM Increment: 7.9 μg/m 3 (IQR) OR Estimate [CI]:

Values NR

Notes: Author states that ORs for PM 10 increased with lag time up to 3 days for both single and multiple-pollutant models.

1 All units expressed in μg/m 3 unless otherwise specified.



# Table E-13. Short-term expos ure-respiratory-ED/HA-PM 10-2.5 

# .

Reference Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Chen et al. (2005, 087555 ) Period of Study: Jun 1995-Mar 1999

Location: Vancouver area, BC Hospital Admissions Outcome (ICD-9): Acute respiratory infections (460-466), upper respiratory tract infections (470-478), pneumonia and influenza (480-487), COPD and allied conditions (490- 496), other respiratory diseases (500- 519) Age Groups: >65 yr Study Design: Time series

N: 12,869 Statistical Analyses: GLM

Covariates: Temp and relative humidity

Season: NR Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 1, 2, 3, 4, 5, 6, and 7-day avg Pollutant: PM 10-2.5 (μg/m 3 ) Averaging Time: 24 h Mean (min-max): 5.6 (0.1-24.6)

SD = 3.6 Monitoring Stations: 13 Copollutant (correlation): PM 2.5 : r = 0.38 PM 10 : r = 0.83 COH: r = 0.63 CO: r = 0.53 O 3 : r = -0.13 NO 2 : r = 0.54 SO 2 : r = 0.57 Other variables: Mean temp: r = 0.13 Rel humidity: r = -0.27 PM Increment: 4.2 μg/m 3 RR Estimate [CI]: Adj for weather conditions

Overall admission 1-day avg: 1.03 [1.00,1.06] 2-day avg: 1.05 [1.02,1.08] 3-day avg: 1.06 [1.02,1.09] Adj for weather conditions and copollutants

Overall admission 1-day avg: 1.02 [0.98,1.06] 2-day avg: 1.05 [1.01,1.10] 3-day avg: 1.06 [1.02,1.11]

Notes: RR’s were also provided for lags 4-7 in Table 3, yielding similar results



### December 2009 E-256

### Reference Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Fung et al. (2006, 089789 ) Period of Study: Jun 1995-Mar 1999

Location: Vancouver, Canada Hospital Admission/ED: Hospital Admission

Outcome: Respiratory diseases (460-519) Age Groups: Age > 65 Study Design: Time series

N: 26,275 individuals admitted Statistical Analyses: Poissonregression (spline 12 knots), casecrossover (controls +/7 days from case date), Dewanji and Moolgavkar (DM) method

Covariates: Long-term trends, dayof-the-week effect, weather

Season: All yr Dose-response Investigated? No Statistical Package: SPlus, R Lags Considered: 0-7 days Pollutant: PM 10-2.5 (μg/m 3 ) Averaging Time: 24-h avg Mean (SD) 5.6(3.88) μg/m 3 Range (Min, Max): (-2.9, 27.07) Monitoring Stations:

NR Notes: Copollutant (correlation): PM 10-2.5 PM 10 r = 0.83

PM 2.5 r = 0.34

CO r = 0.51

CoH r = 0.61

O 3 r = -0.11

NO 2 r = 0.52

SO 2 r = 0.57 PM Increment: : 4.3 μg/m 3

RR Estimate (65+ yr)

DM method: 1.011[0.998,1.024] lag 0 1.016[1.0,1.032] 3-day avg 1.020[1.001,1.039] 5-day avg 1.020[0.998,1.042] 7-day avg

Time series: 1.0168[1.003, 1.031] lag 0 1.020[1.003, 1.037] 3-day avg 1.019[0.999, 1.039] 5-day avg 1.018[0.994, 1.042] 7-day avg

Case-crossover: 1.019[1.003, 1.034] lag 0 1.019[1.009, 1.038] 3-day avg 1.020[0.999, 1.042] 5-day avg 1.018[0.994, 1.043] 7-day avg

Reference: Halonen et al. (2009, 180379 ) Period of Study: 1998-2004

Location: Helsinki, Finland Outcome: Hospital Admissions Age Groups: 65+ yr Study Design: Time series

N: NR Statistical Analyses: Poisson, GAM

Covariates: Temperature, humidity, influenza epidemics, high pollen episodes, holidays Dose-response Investigated? No Statistical Package: R Lags Considered: Lags 0-3 & 5-day (0-4) mean Pollutant: PM 10-2.5 Averaging Time: Daily Mean (SD): NR

Min: 0.0 25th percentile: 4.9 50th percentile: 7.5 75th percentile: 12.1

Max: 101.4 Monitoring Stations: NR Copollutant: PM<0.03, PM0.03-0.1, PM<0.1, PM<0.10.29, PM 2.5 , CO, NO 2 Co-pollutant Correlation PM<0.03: 0.14 PM0.03-0.1: 0.28 PM<0.1: 0.24 PM<0.10.29: 0.20 PM 2.5 : 0.25 PM Increment: Interquartile Range Percent Change (Lower CI, Upper CI): All Respiratory Mortality Lag 0: -0.66 (-4.16, 2.97) Lag 1: 2.90 (-0.48, 6.39) ‡ Lag 2: 0.35 (-3.03, 3.84) Lag 3: -0.38 (-3.67, 3.02) 5-day mean: 0.36 (-4.54, 5.51) Pneumonia HA Lag 0: 0.72 (-1.28, 2.77) Lag 1: 0.55 (-1.34, 2.49) Lag 2: 0.65 (-1.24, 2.58) Lag 3: 0.03 (-1.86, 1.96) 5-day mean: Asthma + COPD HA Lag 0: 2.49 (0.47, 4.56)* Lag 1: 1.37 (-0.66, 3.44) Lag 2: 0.7 (-1.36, 2.80) Lag 3: 1.97 (-0.02, 4.00)‡ 5-day mean: 2.67 (-0.17, 5.58)‡ Other HA Lag 0: 1.38 (-1.24, 4.06) Lag 1: -1.62 (-4.22, 1.05) Lag 2: -1.25 (-3.88, 1.45) Lag 3: 0.04 (-2.52, 2.67) 5-day mean: 0.24 (-3.62, 4.26) *p < 0.05, ‡p < 0.10



### December 2009 E-257

### Reference Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Host et al. (2007, 155851 ) Period of Study: 2000-2003

Location: Six French cities: Le Havre, Lille, Marseille, Paris, Rouen, and Toulouse Outcome (ICD-10): Daily hospitalizations for all respiratory diseases (J00-J99), respiratory infections (J10-J22). Age Groups: For all respiratory diseases: 0-14 yr, 15-64 yr, and ≥ 65 yr For respiratory infections: All ages Study Design: Time series

N: NR (Total population of cities: approximately 10 million) Statistical Analyses: Poisson regression

Covariates: Seasons, days of the week, holidays, influenza epidemics, pollen counts, temperature, and temporal trends Dose-response Investigated: No Statistical Package: MGCV package in R software (R 2.1.1) Lags Considered: Avg of 0-1 days Pollutant: PM 10-2.5 Averaging Time: 24 h Mean μg/m3 (5th -95th percentile): Le Havre: 7.3 (2.5-14.0) Lille: 7.9 (2.2-13.7) Marseille: 11.0 (4.5-21.0) Paris: 8.3 (3.2-15.9) Rouen: 7.0 (3.0-12.5) Toulouse: 7.7 (3.0-15.0) Monitoring Stations: 13 total: 1 in Toulouse

4 in Paris

2 each in other cities Copollutant (correlation): PM 2.5 : Overall: r>0.6 Ranged between r = 0.28 and r = 0.73 across the six cities. PM Increment: 10 μg/m 3 , and an 18.8 μg/m 3 increase (corresponding to an increase in pollutant levels between the lowest of the 5th percentiles and the highest of the 95th percentiles of the cities’ distributions) ERR (excess relative risk) Estimate [CI]: For all respiratory diseases (10 μg/m 3 increase): 0-14 yr: 6.2% [0.4, 12.3] 15-64 yr: 2.6% [-0.5, 5.8]

≥ 65 yr: 1.9% [-1.9, 5.9] For all respiratory diseases (18.8 μg/m 3 increase): 0-14 yr: 12.0 [0.8, 24.3] 15-64 yr: 5.0 [-0.9, 11.1]

≥ 65 yr: 3.7 [-3.6, 11.4] For respiratory infections (10 μg/m 3 ): All ages: 4.4% [0.9, 8.0] For respiratory infections (18 μg/m 3 ): All ages: 8.4% [1.7, 15.5]

Reference: Lin et al. (2005, 087828 ) Period of Study: 1998-2001

Location: Toronto, North York, East York, Etobicoke, Scarborough, and York (Canada) Hospital Admissions Outcome (ICD-9): Respiratory infections including laryngitis, tracheitis, bronchitis, bronchiolitis, pneumonia, and influenza (464, 466, 480-487) Age Groups: 0-14 yr Study Design: Bidirectional casecrossover

N: 6782 respiratory infection hospitalizations Statistical Analyses: Conditional logistic regression (Cox proportional hazards model)

Covariates: Daily mean temp and dew point temp

Season: NR Dose-response Investigated? No Statistical Package: SAS 8.2 PHREG procedure Lags Considered: 1- to 7-day avg Pollutant: PM 10-2.5 (μg/m 3 ) Averaging Time: 24 h Mean (min-max): 10.86 (0-45.00)

SD = 5.37 Monitoring Stations: 4 Copollutant (correlation): PM 2.5 : r = 0.33

PM 10 : r = 0.76

CO: r = 0.06

SO 2 : r = 0.29

NO 2 : r = 0.40

O 3 : r = 0.30 PM Increment: 6.5 μg/m 3 OR Estimate [CI]: Adjusted for weather 4-day avg: 1.16 [1.07,1.26] 6-day avg: 1.21 [1.10,1.32] Adj for weather and other gaseous pollutants 4-day avg: 1.13 [1.03,1.23] 6-day avg: 1.17 [1.06,1.29]

Notes: OR’s were also categorized into “Boys” and “Girls,” yielding similar results



### December 2009 E-258

### Reference Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Lin et al. (2002, 026067 ) Period of Study: Jan 1981-Dec 1993

Location: Toronto Hospital Admissions Outcome (ICD-9) : Asthma (493) Age Groups: 6-12 yr Study Design: Uni- and bi-directional case-crossover (UCC, BCC) and time-series (TS)

N: 7,319 asthma admissions Statistical Analyses: Conditional logistic regression, GAM

Covariates: Maximum and minimum temp, avg relative humidity

Season: Apr-Sep, Oct-Mar Dose-response Investigated? No Statistical Package: NR Lags Considered: 1- to 7-day avg Pollutant: PM 10-2.5 (μg/m 3 ) Averaging Time: 6 days (predicted daily values) Mean (min-max): 12.17 (0-68.00)

SD = 7.55 Monitoring Stations: 1 Copollutant (correlation): PM 2.5 : r = 0.44

PM 10 : r = 0.83

CO: r = 0.17

SO 2 : r = 0.28

NO 2 : r = 0.38

O 3 : r = 0.56 PM Increment: 8.4 μg/m 3 RR Estimate [CI]: Adj for weather and gaseous pollutants BCC 5-day avg: 1.14 [1.01,1.28] BCC 6-day avg: 1.17 [1.03,1.33] TS 5-day avg: 1.14 [1.05,1.23] TS 6-day avg: 1.15 [1.06,1.25] Boys-adj for weather UCC 1-day avg: 1. 08 [1.01,1.16] UCC 2-day avg: 1. 08 [0.99,1.17] BCC 1-day avg: 1.06 [1.00,1.14] BCC 2-day avg: 1.06 [0.98,1.14] TS 1-day avg: 1.08 [1.03,1.12] TS 2-day avg: 1.07 [1.01,1.13] Girls-adj for weather UCC 1-day avg: 1. 07 [0.97,1.18] UCC 2-day avg: 1. 16 [1.03,1.31] BCC 1-day avg: 0.98 [0.90,1.07] BCC 2-day avg: 1.05 [0.94,1.16] TS 1-day avg: 1.00 [0.94,1.06] TS 2-day avg: 1.05 [0.98,1.13] Notes: The author also provides RR using UCC, BCC, and TS analysis for female and male groups for day 3-7, yielding similar results

Reference: Peel et al. (2005, 056305 ) Period of Study: Jan 1993-Aug 2000

Location: Atlanta, Georgia ED visits

Outcome: Asthma (493, 786.09) COPD (491, 492, 496) URI (460-466, 477) Pneumonia (480-486) Age Groups: All ages. Secondary analyses conducted by age group: 0- 1, 2-18, >18 Study Design: Time series

N: 31 hospitals Statistical Analyses: Poisson GEE for URI, asthma and all RD Poisson GLM for pneumonia and COPD)

Covariates: Avg temperature and dew point, pollen counts

Season: All (secondary analyses of warm season) Dose-response Investigated? Yes Statistical Package: SAS 8.3 S-Plus 2000 Lags Considered: 0-7 days, 3-day ma, 0-13 days unconstrained distributed lag Pollutant: PM 10-2.5 (μg/m 3 ) Averaging Time: 24 h avg Mean (SD): 9.7 (4.7)

Percentiles: 10th: 4.4

90th: 16.2 Monitoring Stations:

“Several” Copollutant (correlation): 24 h PM 10 : r = 0.59

8 h O 3 : r = 0.35

1 h NO 2 : r = 0.46

1 h CO: r = 0.32

1 h SO 2 : r = 0.21

24 h PM 2.5 : r = 0.43 Components: r ranged from 0.23-0.51 PM Increment: 5 RR Estimate [Lower CI, Upper CI] All Respiratory Outcomes: 1.003 [0.982, 1.025] URI: 1.013 [0.987, 1.039] Asthma: 0.998 [0.987, 1.039] Pneumonia: 0.975 [0.940, 1.011] COPD: 0.948 [0.897, 1.003]



### December 2009 E-259

### Reference Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Peng et al. (2008, 156850 ) Period of Study: Jan 1999-Dec 2005

Location: 108 U.S. counties in the following states: Alabama, Arizona, California, Colorado, Connecticut, District of Columbia, Florida, Georgia, Idaho, Illinois, Indiana, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Utah, Virginia, Washington, West Virginia, Wisconsin Outcome (ICD-9): Emergency hospitalizations for respiratory disease, including COPD (490-492) and respiratory tract infections (464-466, 480 - 487) Age Groups: 65 + yr, 65-74, ,75 + Study Design: Time series

N: Approximately 12 million Medicare enrollees (1.4 million RD admissions) Statistical Analyses: Two-stage Bayesian hierarchical models: Overdispersed Poisson models for countyspecific data. Bayesian hierarchical models to obtain national avg estimate

Covariates: Day of the week, agespecific intercept, temperature, dew point temperature, calendar time, indicator for age of 75 yr or older. Some models were adjusted for PM 2.5

. Dose-response Investigated: No Statistical Package: R version 2.6.2 Lags Considered: 0-2 days Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (IQR): All counties assessed: 9.8 (6.9-15.0)

Counties in Eastern U.S.: 9.1 (6.6-13.1)

Counties in Western U.S.: 15.4 (10.3-21.8) Monitoring Stations: At least 1 pair of co-located monitors (physically located in the same place) for PM 10 and PM 2.5 per county Copollutant (correlation): PM 2.5 : r = 0.12

PM 10 : r = 0.75

Other variables: Median withincounty correlations between monitors: r = 0.60 PM Increment: 10 μg/m 3 Percentage change [95% CI]: Respiratory disease (RD): Lag 0 (unadjusted for PM 2.5 ): 0.33 [-0.21, 0.86] Lag 0 (adjusted for PM 2.5 ): 0.26 [-0.32, 0.84] Most values NR (see note) Notes: Fig 3: Percentage change in emergency hospital admissions for RD per 10 μg/m 3 increase in PM (single pollutant model and model adjusted for PM 2.5 concentration) Fig 4: Percentage change in emergency hospital admissions rate for CVD and RD per a 10 μg/m 3 increase in PM 10-2.5 (0-2 day lags, Eastern vs.. Western USA)

Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 1995-Jun 2001

Location: Spokane, WA Hospital Admissions and ED visits

Outcome: All respiratory (460-519) Asthma (493) COPD (491,492, 494,496) Pneumonia (480-487) Acute URI not including colds and sinusitis (464, 466, 490) Age Groups: All, 15+ yr for COPD Study Design: Time series

N: 2373 visit records Statistical Analyses: Poisson regression, GLM with natural splines. For comparison also used GAM with smoothing splines and default convergence criteria.

Covariates: Season, temperature, relative humidity, day of week

Season: All Dose-response Investigated? : No Statistical Package: SAS, SPLUS Lags Considered: 1 -3 days Pollutant: PM 10-2.5 (μg/m 3 ) Averaging Time: 24 h avg Range (90% of Concentrations): Reported for PM 2.5 and PM 10 only Monitoring Stations: 1 Copollutant (correlation): PM 10-2.5 PM1 r = 0.19

PM 2.5 r = 0.31

PM 10 r = 0.94

CO r = 0.32 Temperature r = 0.11 PM Increment: 25 μg/m 3 RR Estimate [Lower CI, Upper CI] lag:

ER visits:

PM 10-2.5 All Respiratory Lag 1: 1.01 [0.98, 1.04] Lag 2: 1.01 [0.98, 1.04] Lag 3: 1.02 [0.99, 1.05]

Acute Asthma Lag 1: 1.03 [0.98, 1.08] Lag 2: 1.01 [0.96, 1.07] Lag 3: 0.99 [0.94, 1.05] COPD (adult) Lag 1: 1.01 [0.93, 1.09] Lag 2: 0.98 [0.90, 1.06] Lag 3: 1.02 [0.95, 1.10]



### December 2009 E-260

### Reference Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Tecer et al. (2008, 180030 ) Period of Study: Dec 2004-Oct 2005

Location: Zonguldak, Turkey Outcome: ED visits for respiratory problems (ICD-9 470-478, 493) Study Design: Bidirectional Casecrossover Covariates: Daily meteorological parameters Statistical Analysis: Conditional logistic regression Statistical Package: Stata Age Groups: 0-14 yr Pollutant: PM 10-2.5 Averaging Time: NR Mean, Unit: 24.3 μg/m 3 Range (Min, Max): 4, 195.8 Copollutant (correlation):

PM 2.5 /PM 10-2.5 Mean: 1.49 Range: 0.21, 7.53 Increment: 10 μg/m 3 Odds Ratio (95% CI) Asthma Lag 0: 1.18 (1.01-1.39) Lag 1: 0.92 (0.78-1.08) Lag 2: 0.98 (0.84-1.15) Lag 3: 1.11 (0.97-1.27) Lag 4: 1.17 (1.05-1.31) Allergic Rhinitis with Asthma Lag 0: 0.96 (0.88-1.04) Lag 1: 1.08 (0.99-1.18) Lag 2: 0.93 (0.86-1.02) Lag 3: 0.94 (0.86-1.03) Lag 4: 1.10 (1.03-1.18) Allergic Rhinitis Lag 0: 1.06 (0.95-1.19) Lag 1: 1.17 (1.04-1.31) Lag 2: 0.92 (0.84-1.02) Lag 3: 0.99 (0.91-1.08) Lag 4: 1.15 (1.06-1.25) Upper Respiratory Disease Lag 0: 0.80 (0.54-1.19) Lag 1: 1.22 (0.92-1.61) Lag 2: 0.97 (0.70-1.33) Lag 3: 0.94 (0.66-1.33) Lag 4: 1.08 (0.88-1.32) Lower Respiratory Disease Lag 0: 0.90 (0.71-1.16) Lag 1: 1.20 (0.97-1.50) Lag 2: 1.00 (0.84-1.19) Lag 3: 1.26 (1.08-1.47) Lag 4: 1.02 (0.93-1.13)

Reference: Yang et al., (2004, 087488 ) Period of Study: Jun 1995-Mar 1999

Location: Vancouver area, British Columbia Hospital Admissions Outcome (ICD-9): Respiratory diseases (460-519), pneumonia only (480-486), asthma only (493) Age Groups: 0-3 yr Study Design: Case control, bidirectional case-crossover (BCC), and time series (TS)

N: 1610 cases Statistical Analyses: Chi-squaretest, Logistic regression, GAM (timeseries), GLM with parametric natural cubic splines

Covariates: Gender, socioeconomic status, weekday, season, study yr, influenza epidemic month

Season: Spring, summer, fall, winter Dose-response Investigated? No Statistical Package: SAS (Case control and BCC), S-Plus (TS) Lags Considered: 0-7 days Pollutant: PM 10-2.5 (μg/m 3 ) Averaging Time: 24 h Mean (min-max): 5.6 (0-24.6)

SD = 3.6 Monitoring Stations: NR (data obtained from Greater Vancouver Regional District Air Quality Dept) Copollutant (correlation): PM 2.5 : r = 0.39

PM 10 : r = 0.83

CO: r = 0.33

O 3 : r = -0.16

NO 2 : r = 0.37

SO 2 : r = 0.54 PM Increment: 4.2 μg/m 3 (IQR) OR Estimate [CI]: 3-day lag 1.12 [0.98,1.28] Adj for gaseous pollutants: 1.22 [1.02,1.48]

Notes: Author states that ORs for PM 10-2.5 increased with lag time up to 3 days for both single and multiple-pollutant models. More adjusted ORs and RRs are provided in Fig 1.

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-261

# Table E-14. Short-term expos ure-respiratory-ED/HA-PM 2.5 

# (including PM components/sources).

Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Andersen et al. (2008, 189651 ) Period of Study: May 2001-Dec 2004

Location: Copenhagen, Denmark Outcome (ICD-10): RD, including chronic bronchitis (J41-42), emphysema (J43), other chronic obstructive pulmonary disease (J44), asthma (J45), and status asthmaticus (J46). Pediatric hospital admissions for asthma (J45) and status asthmaticus (J46). Age Groups: > 5-18 yr (asthma) Study Design: Time series

N: NR Statistical Analyses: Poisson GAM

Covariates: Temperature, dew-point temperature, long-term trend, seasonality, influenza, day of the week, public holidays, school holidays (only for 5-18 yr olds), pollen (only for pediatric asthma outcome)

Season: NR Dose-response Investigated: No Statistical Package: R statistical software (gam procedure, mgcv package) Lags Considered: Lag 0-5 days, 4-day pollutant avg (lag 0-3) for CVD, 5-day avg (lag 0-4) for RD, and a 6-day avg (lag 0-5) for asthma. Pollutant: PM 2.5 Averaging Time: 24 h

Mean μ g/m3 (SD): 10(5)

Median: 9

IQR: 7-12 99th percentile: 28 Monitoring Stations: 1 Copollutant (correlation): NCtot: r = 0.40 NC100: r = 0.29 NCa12: r = 0.07 Nca23: r = -0.25 NCa57: r = 0.51 NCa212: r = 0.82 PM : r = 0.80

10 CO: r = 0.46 NO : r = 0.42

2 : r = 0.40 NO curbside: r = 0.28

X O 3 : r = -0.20 Other variables: Temperature: r = -0.01 Relative humidity: r = 0.21 PM Increment: 5 μ g/m 3 (IQR) Relative risk (RR) Estimate [CI]: RD hospital admissions (5-day avg, lag 0-4), age 65+: One-pollutant model: 1.00 [0.95-1.00] Adj for NCtot: 1.00 [0.95-1.06] Asthma hospital admissions (6-day avg lag 0-5), age 5-18: One-pollutant model: 1.15 [1.00-1.32] Adj for NCtot: 1.13 [0.98-1.32] Estimates for individual day lags reported only in Fig form (see notes): Notes: RD: No statistically or marginally significant associations. Positive associatons at Lag 4-5.Asthma: Wide confidence intervals make interpretation dificult. Positive associations at Lag 1, 2, 3.

Reference: Babin et al. (2007, 093250 ) Period of Study: Oct 2001-Sep 2004

Location: Washington, DC ED Visit/Admissions

Outcome: Asthma-493 Age Groups: 1-17 yr,1-4, 5-12, 13-17 Study Design: Time-series

N: NR Statistical Analyses: Poisson regression, spline w/ 12 knots to adjust for long term trend

Covariates: Temperature, mold, pollen, seasonal trends,

Season: All Dose-response Investigated? No Statistical Package: STATA Lags Considered: 0-4 Pollutant: PM 2.5 Averaging Time: 24 h

Mean: “low, never reached code red”

Percentiles: NR Range (Min, Max): NR Monitoring Stations: 3 Copollutant (correlation): NR PM Increment: 1 μg/m 3 %Change ED Visits Ages 5-12: -0.2 (-0.6,0.2), lag 0 % Change ED Admissions: Ages 5-12: -0.4 (-1.6,0.8), lag 0 Ages 1-17: 0.2 (-0.6,1.1), lag 0 AR Estimate [Lower CI, Upper CI] lag: NR

Notes: No significant interactions between PM and O 3 or other covariates were observed.



### December 2009 E-262

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Barnett et al. (2005, 087394 ) Period of Study: 1998-2001

Location: 5 Australian cities (Brisbane, Canberra, Melbourne, Perth, and Sydney) and 2 New Zealand cities (Auckland, Christchurch) Outcome (ICD: NR): All respiratory admissions (including asthma, pneumonia, and acute bronchitis) Age Groups: Children aged <1 yr, 1- 4 yr, and 5-14 yr Study Design: Matched casecrossover

N: ~2.4 million children <15 yr old Statistical Analyses: Random effects meta-analysis

Covariates: Temperature, current minus previous day ’s temperature, relative humidity, pressure, extremes of hot and cold, day of the week, public holiday, and day after public holiday

Season: Warm (Nov-Apr) and Cool (May-Oct) Dose-response Investigated? No Statistical Package: SAS Lags Considered: NR Pollutant: PM 2.5 Averaging Time: 24 h Mean (min-max): Auckland (A): 11.0 (2.1-37.6) Brisbane (B): 9.7 (3.2-122.8) Canberra (Ca): NR Christchurch (Ch): NR Melbourne (M): 8.9 (2.8-43.3) Perth (P): 8.1 (1.7-29.3) Sydney (S): 9.4 (2.4-82.1) Monitoring Stations: 1-3 per city Copollutant: NR PM Increment: 3.8 μg/m 3 (IQR) Percent Increase Estimate [CI]: Pneumonia & Acute Bronchitis: Single Pollutant Model <1 yr (B,M,P,S): 1.7 [ 0.0,3.4] 1-4 yr (B,M,P,S): 2.4 [0.1,4.7] Matched Multipollutant Model 1-4 yr with 1-h SO 2 (B,S): 1.9 [-1.7,5.6] 1-4 yr with temp (B,M,P,S): 2.3 [-0.4,5.1] Respiratory Admissions: Single Pollutant Model <1 yr (B,M,P,S): 2.4 [1.0,3.8] 1-4 yr (B,M,P,S): 1.7 [0.7,2.7] Matched Pollutant Model <1 yr with 1-h SO 2 (B,S): 3.1 [0.5,5.7] <1 yr with temp (B,M,P,S): 1.8 [0.2,3.4] 1-4 yr with PM 10 (B,M,P,S): 2.9 [0.2,5.6] 1-4 yr with 1-h SO 2 (B,S): 1.3 [-1.8,4.4] 1-4 yr with 1-h NO 2 (B,M,P,S): -1.5 [-3.2,0.2] 1-4 yr with temp (B,M,P,S,): 1.5 [-0.2,3.1]

Reference: Bell et al. (2008, 091268 ) Period of Study: 1995-2002

Location: Taipei, Taiwan Outcome (ICD-9): Hospital admissions for asthma (493), and pneumonia (486). Age Groups: All Study Design: Time series

N: 19,966 hospital admissions for pneumonia, and 10,231 for asthma Statistical Analyses: Poisson regression

Covariates: Day of the week, time, apparent temperature, long-term trends, seasonality

Season: All Dose-response Investigated: No Statistical Package: NR Lags Considered: lags 0-3 days, mean of lags 0-3 Pollutant: PM 2.5 Averaging Time: 24 h Mean (range IQR): 31.6 (0.50-355.0 20.2) Monitoring Stations: 2 Copollutant (correlation): NR PM Increment: 20 μg/m 3 (near IQR) Percentage increase estimate [95% CI]: Asthma: L0: 0.46 (-2.41, 3.42) L1: -1.36 (-4.33, 1.71) L2: -0.83 (-3.67, 2.10) L3: -0.78 (-3.63, 2.16) L03: -1.75 (-6.21, 2.92) Pneumonia: L0: 0.06 (-2.74, 2.94) L1: 0.34 (-2.446, 3.20) L2: -0.59 (-3.38, 2.29) L3: -0.44 (-3.22, 2.41) L03: -0.61 (-4.87, 3.85)

Reference: Bell et al. (2008, 091268 ) Period of Study: 1999-2005

Location: 202 U.S. counties Outcome (ICD-9): COPD (490-492), respiratory tract infections (464-466, 480-487) Age Groups: 65+ Study Design: Time series

N: NR Statistical Analyses: Two-stage Bayesian hierarchical model to find national avgFirst stage: Poisson regression (countyspecific)

Covariates: Day of the week, temperature, dew point temperature, temporal trends, indicator for persons 75+ yr, population size

Season: All, Jun-Aug (Summer), Sep-Nov (Fall), Dec-Feb (Winter), Mar-May (Spring) Dose-response Investigated: No Pollutant: PM 2.5 Averaging Time: 24 h Mean (μg/m3): Descriptive information presented in Fig S2 (boxplots): IQR: 8.7 μg/m 3 Monitoring Stations: NR Copollutant (correlation): NR PM Increment: 10 μg/m 3 Percent increase [95% PI]: Respiratory admissions: Lag 0 (all seasons): 0.22 [-0.12-0.56] Lag 0 (winter, national): 1.05 [0.29-1.82] Lag 0 (winter, northeast): 1.76 [0.60-2.93] Lag 0 (winter, southeast): 0.59 [-1.35-2.58] Lag 0 (winter, northwest): -0.07 [-6.74-7.08] Lag 0 (winter, southwest): 0.03 [-1.25-1.34] Lag 0 (spring, national): 0.31 [-0.47-1.11] Lag 0 (spring, northeast): 0.34 [-0.66-1.34] Lag 0 (spring, southeast): -0.06 [-1.77-1.68] Lag 0 (spring, northwest): -8.52 [-25.62-12.51] Lag 0 (spring, southwest): 1.87 [-2.00-5.90] Lag 0 (summer, national): -0.62 [-1.33-0.09]



### December 2009 E-263

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Statistical Package: NR Lags Considered: 0-2 day lags Lag 0 (summer, northeast): -0.8 [-1.65-0.07] Lag 0 (summer, southeast): -0.15 [-1.88-1.61] Lag 0 (summer, northwest): 0.25 [-21.46-27.96] Lag 0 (summer, southwest): 0.64 [-5.38-7.04] Lag 0 (fall, national): 0.02 [-0.63-0.67] Lag 0 (fall, northeast): -0.01 [-0.87-0.85] Lag 0 (fall, southeast): -0.58 [-2.06-0.91] Lag 0 (fall, northwest): -1.38 [-11.84-10.32] Lag 0 (fall, southwest): 1.77 [-0.73-4.33] Lag 1 (all seasons): 0.05 [-0.29-0.39] Lag 1 (winter): 0.50 [-0.27-1.27] Lag 1 (spring): -0.24 [-1.01-0.53] Lag 1 (summer): 0.28 [-0.39-0.95] Lag 1 (fall): 0.15 [-0.49-0.79] Lag 2 (all seasons): 0.41 [0.09-0.74] Lag 2 (winter, national): 0.72 [0.01-1.43] Lag 2 (winter, northeast): 0.79 [-0.21-1.80] Lag 2 (winter, southeast): 0.4 [-1.45, 2.27] Lag 2 (winter, northwest): -0.06 [-6.52-6.85] Lag 2 (winter, southwest): 1.2 [-0.10-2.52] Lag 2 (spring, national): 0.35 [-0.29-0.99] Lag 2 (spring, northeast): 0.04 [-0.88-0.97] Lag 2 (spring, southeast): 0.75 [-0.82-2.34] Lag 2 (spring, northwest): 2.29 [-14.26-22.03] Lag 2 (spring, southwest): 1.05 [-2.18-4.39] Lag 2 (summer, national): 0.57 [- 0.07-1.23] Lag 2 (summer, northeast): 0.77 [-0.01-1.56] |Lag 2 (summer, southeast): -0.52 [-2.07-1.06] Lag 2 (summer, northwest): 0.74 [-18.73-24.86] Lag 2 (summer, southwest): 2.41 [-2.61-7.69] Lag 2 (fall, national): 0.39 [-0.22-1.01] Lag 2 (fall, northeast): 0.12 [-0.82-1.07] Lag 2 (fall, southeast): 0.14 [-1.29-1.59] Lag 2 (fall, northwest): -0.74 [-10.08-9.58] Lag 2 (fall, southwest): 0.97[-1.36-3.36] Reference: Bell et al. (2009, 191007 ) Period of Study: 1999-2005

Location: 168 U.S. Counties Outcome: Respiratory hospital admissions Study Design: Retrospective Cohort

Covariates: Socio-economic conditions, long term temperature Statistical Analysis: Bayesian hierarchical model Age Groups: ≥ 65 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD) Unit: NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 20% of the population acquiring air conditioning Percent Change (95% CI) in community-specific PM health effect estimates for respiratory hospital admissions Any AC, including window units Yearly health effect: 44.5 (-87.5-176) Summer health effect: -74.8 (-417-267) Winter health effect: -32.5 (-245-180) Central AC Yearly health effect: 27.6 (-46.7-102) Summer health effect: -38.6 (-160-82.6) Winter health effect: 43.8 (-125-213)



### December 2009 E-264

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bell et al. (2009, 191007 ) Period of Study: 1999-2005

Location: 168 U.S. Counties Outcome: Respiratory HA Age Groups: 65+ Study Design: Time series

N: NR Statistical Analyses: Bayesian Hierarchical Regression

Covariates: Time trend, day of week, seasonality, dew point, temperature Statistical Package: NR Lags Considered: 0-2 Pollutant: PM 2.5 Averaging Time: Daily Mean: EC: 0.715 Ni: 0.002 V: 0.003 Min: EC: 0.309 Ni: 0.003 V: 0.001 Max: EC: 1.73 Ni: 0.021 V: 0.010 Interquartile Range: EC: 0.245 Ni: 0.001 V: 0.001 Interquartile Range of Percents: EC: 1.7 Ni: 0.01 V: 0.01 Monitoring Stations: NR Copollutant: Al, NH4+, As, Ca, Cl, Cu, EC, OMC, Fe, Pb, Mg. Ni, NO 3 -, K, Si, Na+, SO 4 =, Ti, V, Zn Co-pollutant Correlation: Ni, V: 0.48 V, EC: 0.33 Ni, EC: 0.30

Note: Pollutant concentrations available for all fractions of PM 2.5 PM Increment: Interquartile Range in the fraction of PM 2.5 Percent Increase (Lower CI, Upper CI): EC: 511 (80.7, 941), lag 0 EC + Ni: 399 (-45.1, 843), lag 0 EC + V: 386 (-74.8, 846), lag 0 EC + Ni, V: 362 (-98.0, 823), lag 0 Ni: 223 (36.9, 410), lag 0 Ni + EC: 176 (-18.7, 370), lag 0 Ni + V: 151 (-78.4, 381), lag 0 Ni + EC, V: 136 (-94.9, 368), lag 0 V: 392 (46.3, 738), lag 0 V + EC: 279 (-93.2, 651), lag 0 V+ Ni: 230 (-193.7, 653), lag 0 V + EC, Ni: 140 (-300, 579), lag 0 EC: -1.5 (80.7, 941), lag 1 EC: 17.5 (-22.3, 57.3), lag 2 Ni: -7.2 (-66.6. 52.1), lag 1 Ni: -4.9 (-22.3, 12.5), lag 2 V: -19.6 (-127, 88.3), lag 1 V: 10.5 (-21.5, 42.4), lag 2 HS education: -77.8 (-390, 234), lag 0 median income: 45.9 (-411, 503), lag0 Percent black: -53.1 (-557, 451), lag 0 Percent living in urban area: -41.9 (- 774.7, 691), lag 0 Population: -22.9 (-121, 75.3), lag 0 Notes: Interquartile ranges in percent HS education, median income, percent black, percent living in urban area, and population are 5.2 %, $9,223, 17.3%, 11.0%, and 549,283 respectively.

Reference: Chardon et al. (2007, 091308 ) Period of Study: 2000-2003

Location: Greater Paris Area, France Doctors house calls Outcome (ICPC2): Asthma (R96), Upper respiratory disease (URD R07, R21, R29, R75, R76, R02) , Lower respiratory disease (LRD, R05, R78) Age Groups: All Study Design: Time series

N: 8027 for asthma 52928 for LRD 74845 for URD Statistical Analyses: Quasi-Poisson, GAM, parametric penalized spline smoothers.

Covariates: Lagged and current temperature, humidity, long term trends, seasonality, pollen counts, influenza epidemic, days of the week, holidays, bank holidays

Season: All Dose-response Investigated? No Statistical Package: R Lags Considered: 0-3 days Pollutant: PM 2.5 Averaging Time: Mean of the daily

means Mean (SD): 14.7(7.34) μg/m 3

Percentiles : 25th: 9.5 50th(Median): 12.9

75th: 18.2 Range (Min, Max): (3, 69.6) Monitoring Stations : 1- 4 Copollutant:

PM 10 : r = 0.95

NO 2 : r = 0.68 PM Increment: 10 μg/m 3 % Change, lag 0-3-day avg

URD 6.0 (3.1, 9.1)

LRD 5.8 (2.8, 8.9)

Asthma 4.4 (-1.3, 10.4)



### December 2009 E-265

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chen et al. (2005, 087555 ) Period of Study: Jun 1995-Mar 1999

Location: Vancouver area, BC Hospital Admissions Outcome (ICD-9): Acute respiratory infections (460-466), upper respiratory tract infections (470-478), pneumonia and influenza (480-487), COPD and allied conditions (490-496), other respiratory diseases (500-519) Age Groups: >65 yr Study Design: Time series

N: 12,869 Statistical Analyses: GLM

Covariates: Temp and relative humidity

Season: NR Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 1-, 2-, 3-, 4-, 5-, 6-, and 7-day avg Pollutant: PM 2.5 Averaging Time: 24 h Mean (min-max): 7.7 (2.0-32.0)

SD = 3.7 Monitoring Stations: 13 Copollutant (correlation): PM 10 : r = 0.83 PM 10-2.5 : r = 0.38 COH: r = 0.39 CO: r = 0.23 O 3 : r = -0.01 NO 2 : r = 0.36 SO 2 : r = 0.42 Other variables: Mean temp: r = 0.41 Rel humidity: r = -0.23 PM Increment: 4.0 μg/m 3 (IQR) RR Estimate [CI]: Adj for weather conditions

Overall admission 1-day avg: 1.02 [0.99,1.05] 2-day avg: 1.02 [0.99,1.06] 3-day avg: 1.02 [0.98,1.05] Adj for weather conditions and copollutants

Overall admission 1-day avg: 1.01 [0.98,1.06] 2-day avg: 1.01 [0.98,1.05] 3-day avg: 1.00 [0.96,1.04]

Notes: RR’s were also provided for lags 4-7 in Table 3, yielding similar results

Reference: Chimonas and Gessner (2007, 093261 ) Period of Study: Jan 1999-Jun 2003

Location: Anchorage, Alaska Outcome (ICD-9): Asthma (493.0- 493.9) Lower respiratory illness-LRI (466.1, 466.0, 480-487, 490, 510-511) Inhaled quick-relief medication Steroid medication Age Groups: <20 yr old Study Design: Time series

N: 42,667 admissions Statistical Analyses: GEE for multivariable modeling

Covariates: Season, serial correlation, yr, weekend, temperature, precipitation, and wind speed

Season: NR Dose-response Investigated? No Statistical Package: SPSS (dataset), SAS (analysis) Lags Considered: 1 day and 1 wk Pollutant: PM 2.5 Averaging Time: 24 h and 1 wk Mean (min-max): Daily: 6.1 (0.5-69.8) Weekly: 5.8 (1.8-45.0) Monitoring Stations: NR Copollutant: N/A PM Increment: 5 μg/m 3 RR Estimate [CI]: Same Day Outpatient Asthma: 0.992 [0.964,1.024] Outpatient LRI: 0.952 [0.907,1.001] Inpatient Asthma: 0.936 [0.798,1.098] Inpatient LRI: 0.919 [0.823,1.027] Inhaled Steroid Prescriptions: 0.988 [0.902,1.083] Quick-relief Medication: 0.962 [0.901,1.028] Weekly (median increase) Outpatient Asthma: 0.983 [0.935,1.038] Outpatient LRI: 0.969 [0.874,1.075] Inpatient Asthma: 0.754 [0.513.1.109] Inpatient LRI: 0.943 [0.715,1.245] Inhaled Steroid Prescriptions: 1.018 [0.883,1.175] Quick-relief Medication: 0.978 [0.882,1.087]

Reference: Delfino et al. (2009, 191994 ) Period of Study: Oct 2003-Nov 2003

Location: Southern California Outcome: Respiratory hospital admissions Study Design: Time series Statistical Analysis: Poisson regression with GEE Age Groups: All Pollutant: PM 2.5 Averaging Time: Hourly Mean (SD) Unit by county: Los Angeles Before Fires: 27.2 (12.4) μg/m 3 During Fires: 54.1 (21.0) μg/m 3 After Fires: 15.9 (5.5) μg/m 3 Orange Before Fires: 23.2 (9.6) μg/m 3 During Fires: 64.3 (26.5) μg/m 3 After Fires: 15.5 (10.2) μg/m 3 Riverside Before Fires: 32.7 (14.7) μg/m 3 During Fires: 42.1 (25.5) μg/m 3 After Fires: 16.9 (10.2) μg/m 3 San Bernadino Before Fires: 35.7 (16.6) μg/m 3 During Fires: 45.3 (28.7) μg/m 3 After Fires: 18.5 (8.3) μg/m 3 San Diego Before Fires: 18.5 (6.7) μg/m 3 During Fires: 76.1 (66.6) μg/m 3 After Fires: 14.2 (7.2) μg/m 3 Increment: 10 μg/m 3 Relative Rate (Min CI, Max CI) All Respiratory, All Ages: All Periods: 1.009 (0.999-1.018) Pre-Wildfire: 1.022 (1.004-1.040) Wildfire: 1.028 (1.014-1.041), p = 0.639 Post-Wildfire: 0.999 (0.968-1.031), p = 0.198

All Respiratory, Ages 0-4: All Periods: 0.994 (0.967-1.021) Pre-Wildfire: 0.982 (0.921-1.046) Wildfire: 1.045 (1.010-1.082), p = 0.103 Post-Wildfire: 0.894 (0.807-0.991), p = 0.126

All Respiratory, Ages 5-19: All Periods: 1.014 (0.983-1.046) Pre-Wildfire: 1.026 (0.946-1.113) Wildfire: 1.027 (0.984-1.076), p = 0.990

Ventura Post-Wildfire: 0.958 (0.852-1.077), p = 0.354 All Respiratory, Ages 20-64: All Periods:



### December 2009 E-266

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Before Fires: 18.4 (8.3) μg/m 3 During Fires: 50.1 (50.5) μg/m 3 After Fires: 12.9 (4.3) μg/m 3 Copollutant (correlation): NR 1.015 (1.002-1.029) Pre-Wildfire: 1.036 (1.007-1.066) Wildfire: 1.024 (1.005-1.044), p = 0.534 Post-Wildfire: 1.007 (0.960-1.056), p = 0.315 All Respiratory, Ages 65-99: All Periods: 1.009 (0.996-1.022) Pre-Wildfire: 1.022 (0.994-1.050) Wildfire: 1.030 (1.011-1.049), p = 0.649 Post-Wildfire: 1.024 (0.967-1.074), p = 0.932

Asthma, All Ages, Male and Female: All Periods: 1.022 (1.001-1.042) Pre-Wildfire: 0.998 (0.949-1.050) Wildfire: 1.048 (1.021-1.076), p = 0.097 Post-Wildfire: 0.986 (0.910-1.068), p = 0.792

Asthma, All Ages, Male: All Periods: 1.010 (0.980-1.040) Pre-Wildfire: 1.021 (0.944-1.106) Wildfire: 1.031 (0.990-1.073), p = 0.848 Post-Wildfire: 1.063 (0.948-1.192), p = 0.553

Asthma, All Ages, Female: All Periods: 1.029 (1.001-1.058) Pre-Wildfire: 0.979 (0.913-1.050) Wildfire: 1.059 (1.022-1.097), p = 0.056 Post-Wildfire: 0.928 (0.829-1.037), p = 0.412

Asthma, Ages 0-4, Males and Females: All Periods: 0.996 (0.947-1.048) Pre-Wildfire: 0.924 (0.824-1.035) Wildfire: 1.083 (1.021-1.149), p = 0.017 Post-Wildfire: 0.924 (0.767-1.113), p = 0.999

Asthma, Ages 0-4, Males: All Periods: 1.018 (0.963-1.076) Pre-Wildfire: 0.942 (0.815-1.089) Wildfire: 1.086 (1.016-1.162), p = 0.101 Post-Wildfire: 1.057 (0.839-1.332), p = 0.380 Asthma, Ages 0-4, Females: All Periods: 0.937 (0.845-1.040) Pre-Wildfire: 0.880 (0.706-1.099) Wildfire: 1.073 (0.965-1.194), p = 0.116 Post-Wildfire: 0.699 (0.515-0.949), p = 0.214

Asthma, Ages 5-19, Males and Females: All Periods: 1.006 (0.966-1.048) Pre-Wildfire: 1.045 (0.936-1.167) Wildfire: 0.999 (0.935-1.068), p = 0.492 Post-Wildfire: 0.918 (0.788-1.069), p = 0.198 Asthma, Ages 5-19, Males: All Periods: 0.991 (0.935-1.051) Pre-Wildfire: 1.034 (0.892-1.198) Wildfire: 0.969 (0.883-1.064), p = 0.462 Post-Wildfire: 0.979 (0.806-1.189), p = 0.671 Asthma, Ages 5-19, Females: All Periods: 1.026 (0.964-1.092) Pre-Wildfire: 1.065 (0.901-1.260) Wildfire: 1.033 (0.943-1.132), p = 0.768 Post-Wildfire: 0.831 (0.640-1.079), p = 0.136

Asthma, Ages 20-64, Males and Females: All Periods: 1.043 (1.012-



### December 2009 E-267

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### Effect Estimates (95% CI) 1.076) Pre-Wildfire: 1.037 (0.957-1.123) Wildfire: 1.041 (0.995-1.090), p = 0.931 Post-Wildfire: 1.000 (0.882-1.132), p = 0.624 Asthma, Ages 20-64, Males: All Periods: 1.013 (0.954-1.077) Pre-Wildfire: 1.159 (0.996-1.349) Wildfire: 0.939 (0.837-1.053), p = 0.026 Post-Wildfire: 1.275 (1.020-1.595), p = 0.486

Asthma, Ages 20-64, Females: All Periods: 1.052 (1.015-1.090) Pre-Wildfire: 0.995 (0.904-1.096) Wildfire: 1.064 (1.014-1.116), p = 0.247 Post-Wildfire: 0.908 (0.780-1.056), p = 0.310

Asthma, Ages 65-99, Males and Females: All Periods: 1.027 (0.974- 1.082) Pre-Wildfire: 0.951 (0.849-1.064) Wildfire: 1.101 (1.030-1.178), p = 0.032 Post-Wildfire: 1.168 (0.967-1.412), p = 0.072

Asthma, Ages 65-99, Males: All Periods: 1.046 (0.957-1.142) Pre-Wildfire: 0.948 (0.804-1.116) Wildfire: 1.185 (1.077-1.305), p = 0.029 Post-Wildfire: 0.902 (0.629-1.294), p = 0.804

Asthma, Ages 65-99, Females: All Periods: 1.018 (0.958-1.081) Pre-Wildfire: 0.947 (0.813-1.102) Wildfire: 1.065 (0.977-1.162), p = 0.195 Post-Wildfire: 1.263 (1.024-1.557), p = 0.032

Acute Bronchitis and Bronchiolitis, All Ages: All Periods: 1.044 (0.990-1.102) Pre-Wildfire: 1.001 (0.890-1.126) Wildfire: 1.096 (1.018-1.179), p = 0.223 Post-Wildfire: 1.031 (0.870-1.222), p = 0.779

Acute Bronchitis and Bronchiolitis, Ages 0-4: All Periods: 1.017 (0.949-1.089) Pre-Wildfire: 0.987 (0.847-1.149) Wildfire: 1.092 (0.997-1.195), p = 0.276 Post-Wildfire: 0.910 (0.700-1.183), p = 0.588 Acute Bronchitis and Bronchiolitis, Ages 5-19: No Convergence

Acute Bronchitis and Bronchiolitis, Ages 20-64: All Periods: 1.039 (0.912-1.183) Pre-Wildfire: 1.001 (0.792-1.266) Wildfire: 1.044 (0.872-1.252), p = 0.778 Post-Wildfire: 1.259 (0.921-1.722), p = 0.275

Acute Bronchitis and Bronchiolitis, Ages 65-99: All Periods: 1.134 (1039-1.238) Pre-Wildfire: 1.073 (0.764-1.505) Wildfire: 1.143 (1.032-1.265), p = 0.730 Post-Wildfire: 1.190 (0.865-1.638), p = 0.652 COPD, Ages 20-99: All Periods: 1.018 (0.994-1.042) Pre-Wildfire: 1.007 (0.958-1.058) Wildfire: 1.038 (1.004-1.075), p = 0.320 Post-Wildfire: 1.024 (0.943-1.112),



### December 2009 E-268

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### Effect Estimates (95% CI) p = 0.728 COPD, Ages 20-64: All Periods: 1.022 (0.980-1.066) Pre-Wildfire: 0.995 (0.916-1.081) Wildfire: 1.068 (1.009-1.131), p = 0.161 Post-Wildfire: 1.015 (0.893-1.153), p = 0.728 COPD, Ages 65-99: All Periods: 1.019 (0.992-1.048) Pre-Wildfire: 1.014 (0.955-1.077) Wildfire: 1.031 (0.990-1.074), p = 0.660 Post-Wildfire: 1.023 (0.928-1.128), p = 0.878

Pneumonia, All Ages: All Periods: 1.009 (0.994-1.024) Pre-Wildfire: 1.045 (0.931-1.180) Wildfire: 1.028 (1.007-1.050), p = 0.420 Post-Wildfire: 0.980 (0.927-1.035), p = 0.045

Pneumonia, Ages 0-4: All Periods: 0.995 (0.944-1.049) Pre-Wildfire: 1.048 (0.931-1.180) Wildfire: 1.018 (0.948-1.092), p = 0.691 Post-Wildfire: 0.823 (0.649-1.044), p = 0.089 Pneumonia, Ages 5-19: All Periods: 1.031 (0.966-1.098) Pre-Wildfire: 1.017 (0.882-1.172) Wildfire: 1.064 (0.990-1.142), p = 0.586 Post-Wildfire: 1.017 (0.767-1.349), p = 0.998

Pneumonia, Ages 20-64: All Periods: 1.008 (0.982-1.035) Pre-Wildfire: 1.041 (0.982-1.104) Wildfire: 1.032 (0.994-1.072), p = 0.823 Post-Wildfire: 1.013 (0.913-1.124), p = 0.633

Pneumonia, Ages 65-99: All Periods: 1.011 (0.993-1.030) Pre-Wildfire: 1.050 (1.006-1.097) Wildfire: 1.029 (1.002-1.057), p = 0.445 Post-Wildfire: 0.985 (0.920-1.055), p = 0.127 Relative Rate (Min CI, Max CI) in relation to pre-wildfire period (1) All Respiratory, All Ages: Wildfire, unadjusted for PM 2.5 : 0.961 (0.916- 1.008) Wildfire, adjusted for PM 2.5 : 0.903 (0.850-0.960) Post-wildfire, unadjusted for PM 2.5 : 1.143 (1.072-1.219) Post-wildfire, adjusted for PM 2.5 : 1.173 (1.097-1.253) All Respiratory, Ages 0-4: Wildfire, unadjusted for PM 2.5 : 0.865 (0.757-0.989) Wildfire, adjusted for PM 2.5 : 0.842 (0.717-0.988) Post-wildfire, unadjusted for PM 2.5 : 1.152 (0.957-1.388) Post-wildfire, adjusted for PM 2.5 : 1.162 (0.954-1.415) All Respiratory, Ages 5-19: Wildfire, unadjusted for PM 2.5 : 1.098 (0.901-1.324) Wildfire, adjusted for PM 2.5 : 1.087 (0.863-1.370)



### December 2009 E-269

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### Effect Estimates (95% CI) Post-wildfire, unadjusted for PM 2.5 : 1.373 (1.089-1.732) Post-wildfire, adjusted for PM 2.5 : 1.467 (1.142-1.883) All Respiratory, Ages 20-64: Wildfire, unadjusted for PM 2.5 : 0.991 (0.922-1.066) Wildfire, adjusted for PM 2.5 : 0.923 (0.843-1.012) Post-wildfire, unadjusted for PM 2.5 : 1.074 (0.971-1.188) Post-wildfire, adjusted for PM 2.5 : 1.104 (0.992-1.228) All Respiratory, Ages 65-99: Wildfire, unadjusted for PM 2.5 : 0.932 (0.867-1.003) Wildfire, adjusted for PM 2.5 : 0.874 (0.795-0.959) Post-wildfire, unadjusted for PM 2.5 : 1.147 (1.045-1.259) Post-wildfire, adjusted for PM 2.5 : 1.193 (1.084-1.313) Asthma, All Ages: Wildfire, unadjusted for PM 2.5 : 1.088 (0.965-1.227) Wildfire, adjusted for PM 2.5 : 0.992 (0.856-1.149) Post-wildfire, unadjusted for PM 2.5 : 1.264 (1.085-1.473) Post-wildfire, adjusted for PM 2.5 : 1.336 (1.134-1.573) Asthma, Ages 0-4: Wildfire, unadjusted for PM 2.5 : 0.806 (0.632-1.029) Wildfire, adjusted for PM 2.5 : 1.282 (0.958-1.716) Post-wildfire, unadjusted for PM 2.5 : 1.092 (1.759-1.572) Post-wildfire, adjusted for PM 2.5 : 1.133 (0.777-1.654) Asthma, Ages 5-19: Wildfire, unadjusted for PM 2.5 : 1.254 (0.999-1.575) Wildfire, adjusted for PM 2.5 : 1.282 (0.958-1.716) Post-wildfire, unadjusted for PM 2.5 : 1.564 (1.160-2.109) Post-wildfire, adjusted for PM 2.5 : 1.629 (1.184-2.243) Asthma, Ages 20-64: Wildfire, unadjusted for PM 2.5 : 1.273 (1.067-1.518) Wildfire, adjusted for PM 2.5 : 1.221 (0.979-1.524) Post-wildfire, unadjusted for PM 2.5 : 1.362 (1.043-1.779) Post-wildfire, adjusted for PM 2.5 : 1.486 (1.111-1.987) Asthma, Ages 65-99: Wildfire, unadjusted for PM 2.5 : 0.869 (0.657-1.151) Wildfire, adjusted for PM 2.5 : 0.645 (0.450-0.925) Post-wildfire, unadjusted for PM 2.5 : 0.924 (0.606-1.408) Post-wildfire, adjusted for PM 2.5 : 1.005 (0.650-1.552)

Acute Bronchitis and Bronchiolitis, All Ages: Wildfire, unadjusted for PM 2.5 : 1.143 (0.878-1.490) Wildfire, adjusted for PM 2.5 : 0.959 (0.696-1.321)



### December 2009 E-270

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Post-wildfire, unadjusted for PM 2.5 : 1.482 (1.042-2.109) Post-wildfire, adjusted for PM 2.5 : 1.580 (1.089-2.291)

Acute Bronchitis and Bronchiolitis, Ages 0-4: Wildfire, unadjusted for PM 2.5 : 1.128 (0.819-1.555) Wildfire, adjusted for PM 2.5 : 0.899 (0.607-1.333) Post-wildfire, unadjusted for PM 2.5 : 1.520 (0.947-2.440) Post-wildfire, adjusted for PM 2.5 : 1.547 (0.954-2.507)

Acute Bronchitis and Bronchiolitis, Ages 5-19 No Correlation

Acute Bronchitis and Bronchiolitis, Ages 20-64: Wildfire, unadjusted for PM 2.5 : 1.350 (0.688-2.648) Wildfire, adjusted for PM 2.5 : 1.320 (0.608-2.863) Post-wildfire, unadjusted for PM 2.5 : 2.454 (1.068-5.640) Post-wildfire, adjusted for PM 2.5 : 2.515 (1.055-5.998)

Acute Bronchitis and Bronchiolitis, Ages 65-99: Wildfire, unadjusted for PM 2.5 : 1.166 (0.643-2.115) Wildfire, adjusted for PM 2.5 : 0.934 (0.422-20.66) Post-wildfire, unadjusted for PM 2.5 : 0.911 (0.428-1.942) Post-wildfire, adjusted for PM 2.5 : 0.997 (0.439-2.262) COPD, Ages 20-99: Wildfire, unadjusted for PM 2.5 : 0.988 (0.875-1.115) Wildfire, adjusted for PM 2.5 : 0.913 (0.779-1.069) Post-wildfire, unadjusted for PM 2.5 : 1.043 (0.885-1.228) Post-wildfire, adjusted for PM 2.5 : 1.064 (0.897-1.262) COPD, Ages 20-64: Wildfire, unadjusted for PM 2.5 : 0.967 (0.779-1.201) Wildfire, adjusted for PM 2.5 : 0.873 (0.660-1.156) Post-wildfire, unadjusted for PM 2.5 : 1.175 (0.862-1.601) Post-wildfire, adjusted for PM 2.5 : 1.311 (0.954-1.802) COPD, Ages 65-99: Wildfire, unadjusted for PM 2.5 : 1.002 (0.869-1.156) Wildfire, adjusted for PM 2.5 : 0.926 (0.767-1.117) Post-wildfire, unadjusted for PM 2.5 : 0.985 (0.811-1.196) Post-wildfire, adjusted for PM 2.5 : 0.981 (0.798-1.206) Pneumonia, All Ages: Wildfire, unadjusted for PM 2.5 : 0.943 (0.868-1.025) Wildfire, adjusted for PM 2.5 : 0.888 (0.799-0.986) Post-wildfire, unadjusted for PM 2.5 : 1.294 (1.158-1.446) Post-wildfire, adjusted for PM 2.5 : 1.318 (1.174-1.479)



### December 2009 E-271

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### Effect Estimates (95% CI)

Pneumonia, Ages 0-4: Wildfire, unadjusted for PM 2.5 : 0.938 (0.705-1.247) Wildfire, adjusted for PM 2.5 : 0.951 (0.678-1.333) Post-wildfire, unadjusted for PM 2.5 : 1.458 (0.974-20182) Post-wildfire, adjusted for PM 2.5 : 1.374 (0.885-2.133) Pneumonia, Ages 5-19: Wildfire, unadjusted for PM 2.5 : 0.891 (0.604-1.312) Wildfire, adjusted for PM 2.5 : 0.830 (0.541-1.272) Post-wildfire, unadjusted for PM 2.5 : 0.960 (0.588-1.569) Post-wildfire, adjusted for PM 2.5 : 0.969 (0.578-1.624) Pneumonia, Ages 20-64: Wildfire, unadjusted for PM 2.5 : 0.927 (0.795-1.081) Wildfire, adjusted for PM 2.5 : 0.837 (0.690-1.016) Post-wildfire, unadjusted for PM 2.5 : 1.314 (1.064-1.622) Post-wildfire, adjusted for PM 2.5 : 1.300 (1.047-1.615) Pneumonia, Ages 65-99: Wildfire, unadjusted for PM 2.5 : 0.959 (0.861-1.068) Wildfire, adjusted for PM 2.5 : 0.899 (1.782-1.033) Post-wildfire, unadjusted for PM 2.5 : 1.277 (1.102-1.481) Post-wildfire, adjusted for PM 2.5 : 1.331 (1.142-1.552) Reference: Dominici et al. (2006, 088398 ) Period of Study: 1999-2002

Location: 204 U.S. counties, located in: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Georgia, Hawaii, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Utah, Virginia, Washington, West Virginia, Wisconsin Outcome (ICD-9: Daily counts of hospital admissions for primary diagnosis of chronic obstructive pulmonary disease (490-492), and respiratory tract infections (464-466, 480-487). Age Groups: >65 yr Study Design: Time series

N: 11.5 million Medicare enrollees Statistical Analyses: Bayesian 2-stage hierarchical models.First stage: Poisson regression (countyspecific) Second stage: Bayesian hierarchical models, to produce a national avg estimate

Covariates: Day of the week, seasonality, temperature, dew point temperature, long-term trends

Season: NR Dose-response Investigated: No Statistical Package: R statistical software version 2.2.0 Lags Considered: 0-2 days, avg of days 0-2 Pollutant: PM 2.5 Averaging Time: 24 h Mean (μg/m 3 ) (IQR): 13.4 (11.3-15.2) Monitoring Stations: NR Copollutant (correlation): NR

Other variables: Median of pairwise correlations among PM 2.5 monitors within the same county for 2000: r = 0.91 (IQR: 0.81-0.95) PM Increment: 10 μg/m 3 (Results in figures see notes) Percent increase in risk [95% PI]: COPD (Lag 0): Age 65 +: 0.91 [0.18, 1.64] Age 65-74: 0.42 [-0.64, 1.48] Age 75+: 1.47 [0.54, 2.40] Respiratory tract infection: Age 65+: 0.92 [0.41, 1.43] Age 65-74: 0.93 [0.04, 1.82] Age 75+: 0.92 [0.32, 1.53]

Annual reduction in admissions attributable to a 10 μg/m 3 reduction in daily PM 2.5 level (95% PI): Cerebrovascular disease: Annual number of admissions: 226,641

Annual reduction in admissions: 1836 [680, 2992]

COPD: Annual number of admissions: 108,812

Annual reduction in admissions: 990 [196, 1785] Respiratory tract infections: Annual number of admissions: 226,620

Annual reduction in admissions: 2085 [929, 3241]



### December 2009 E-272

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### Effect Estimates (95% CI)

Reference: Dominici et al. (2006, 088398 ) Period of Study: 1999-2002

Location: U.S. (mainland) Outcome (ICD-9): Respiratory tract infections (464-466, 480-487) and Chronic Obstructive Pulmonary Disease (490-492) Age Groups: All >65 yr 65-74 yr >75 yr Study Design: Time series

N: 11.5 million at-risk Statistical Analyses: Bayesian 2-stage hierarchical models (day-to-dayvariation), Poisson regression (countyspecific RRs)

Covariates: Calendar time (seasonality and yr), temperature, dew point

Season: NR Dose-response Investigated? No Statistical Package: NR Lags Considered: 0, 1, 2 days Pollutant: PM 2.5 Averaging Time: Daily or every 3 days (depending on county)

Mean: 13.4 (IQR: 11.3-15.2) Monitoring Stations: NR (used data from Air Quality System database) Copollutant: NR PM Increment: 10 μg/m 3 Percentage Change in Hospital Admission Rates [PI]: COPD-Same day All >65: 0.91 [0.18,1.64] 65-74 yr: 0.42 [-0.64,1.48] >75: 1.47 [0.54,2.40] Respiratory Tract Infections-2-day lag All >65: 0.92 [0.41,1.43] 65-74 yr: 0.93 [0.04,1.82] >75: 0.92 [0.32,1.53]

Notes: Other lag data shown in Fig 2-4

Reference: Erbas et al. (2005, 073849 ) Period of Study: Jul 1989-Dec 1992

Location: Melbourne, Australia Outcome (ICD): COPD (490-492, 494, 496) Asthma (493) Age Groups: NR Study Design: Time series

N: NR Statistical Analyses: GLM, GAM, Parameter Driven Poisson Regression,Transitional Regression, SeasonalTrend decomposition based on Loess smoothing for seasonal adjustment

Covariates: Secular trends, seasonality, relative humidity, dry bulb temp, dew point temp

Season: NR Dose-response Investigated? Yes Statistical Package: S-Plus, SAS Lags Considered: 0-5 days Pollutant: PM0.1-1 (API) Averaging Time: 24 h Mean (min-max): NR Monitoring Stations: 9 Copollutant (correlation): NR PM Increment: Increase from the 10 th -90th percentile (value NR) RR Estimate [CI]:

COPD

GAM: 0.95 [0.91,1.00] GLM, PDM, TRM: NR

Asthma

NR

Notes: This study was used to demonstrate that conclusions are highly dependent on the type of model used



### December 2009 E-273

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### Effect Estimates (95% CI)

Reference: Fung et al. (2006, 089789 ) Period of Study: Jun 1995-Mar 1999

Location: Vancouver, Canada Hospital Admission/ED: Hospital Admission

Outcome: Respiratory diseases (460-519) Age Groups: Age >65 Study Design: Time series, case

crossover

N: 26,275 individuals admitted Statistical Analyses: Poissonregression (spline 12 knots), casecrossover (controls +/7 days from case date), Dewanji and Moolgavkar (DM) method

Covariates: Long-term trends, day-ofthe-week effect, weather

Season: All yr Dose-response Investigated? No Statistical Package: SPlus, R Lags Considered: 0-7 days Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): 7.72(3.61) Range (Min, Max): (2, 32) Monitoring Stations: NR Copollutant (correlation): PM 2.5 :

PM 10 r = 0.80

PM 10-2.5 r = 0.34

CO r = 0.23

CoH r = 0.38

O 3 r = -0.03

NO 2 r = 0.36

SO 2 r = 0.42 PM Increment: : 4 μg/m 3 RR Estimate (65+ yr)

DM method: 1.007[0.994, 1.020]

Current 1.007[0.990,1.023] 3 day 0.995[0.979,1.012] 5 day 0.995[0.971,1.020] 7 day

Time series: 1.003[0.989, 1.018]

Current 1.000[0.982, 1.018] 3 day 0.993[0.972, 1.014] 5 day 0.995[0.971, 1.020] 7 day

Case-crossover: 1.002[0.986, 1.019]

Current 1.001[0.981, 1.021] 3 day 0.988[0.966, 1.011] 5 day 0.984[0.959, 1.010] 7 day

Reference: Hinwood et al. (2006, 088976 ) Period of Study: Jan 1992-Dec 1998

Location: Perth, Australia Hospital Admission Outcome (ICD-9): COPD (490-496.99, except asthma), pneumonia /influenza (480-489.99), asthma Age Groups: All ages Study Design: Time stratified casecrossover

N: NR Statistical Analyses: Conditional logistic regression

Covariates: Time trend, season, temperature, humidity, day of wk, holidays

Season: All yr Dose-response Investigated? No Statistical Package: NR Lags Considered: 0-3 days Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): 9.2 (4.3)

Percentiles:

10th: 5.0

90th: 14.5 Monitoring Stations: 13 Notes: Copollutant: NR Increment: 1 μg/m 3

Notes: Odds ratio for PM 2.5 and all respiratory, COPD, pneumonia and asthma. Authors found an elevation in the odds ratio for lags 2 and 3 reaaching significance in all age groups for lag 3. For each increase of 1 μg/m 3

, the number of hospitalizations increases 0.2% for respiratory disease, 0.5% for pneumonia and 0.3% for asthna. PM 2.5 concentrations were also significantly associated with asthma for those aged under 15 yr with an estimated 0.5% increase in hospitalizations.



### December 2009 E-274

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### Effect Estimates (95% CI)

Reference: Hirshon et al. (2008, 180375 ) Period of Study: Jun 2002-Nov 2002

Location: Baltimore, Maryland Outcome: Hospital admissions for asthma Study Design: Time-series

Covariates: Spatial distance from pollution monitor, demographic variation, long term, seasonal and daily trends, weather and other pollutants Statistical Analysis: Overdispersed Poisson regression Age Groups: 0-17 yr Pollutant: PM 2.5 zinc Averaging Time: 24 h Mean (SD) Unit: 22.42 (25.14) μg/m 3 Range (Min, Max): NR Copollutant (correlation):

Ni: 0.41

Cr: 0.17

Fe: 0.54

Sulfate: 0.01

CO: 0.40

PM 2.5 : 0.39

O 3 : 0.01

NO 2 : 0.66

EC: 0.48 Increment: NR Relative Risk (95% CI), Best fit Model Medium = 8.63-20.76 ng/m 3 High = >20.76 ng/m 3 No Lag Medium: 1.12 (0.98-1.28) High: 1.09 (0.91-1.30) 1-day Lag Medium: 1.23 (1.07-1.41) High: 1.16 (0.97-1.39) 2-day Lag Medium: 1.11 (0.94-1.30) High: 1.15 (0.96-1.38) Controlling for Time Trends No Lag Medium: 1.08 (0.95-1.23) High: 0.98 (0.86-1.11) 1-day Lag Medium: 1.13 (1.003-1.28) High: 1.03 (0.91-1.16) 2-day Lag Medium: 1.13 () High: 0.98-1.31 Controlling for Time Trends and Additional Copollutants No Lag Medium: 1.12 (0.98-1.29) High: 1.09 (1.01-1.30) 1-day Lag Medium: 1.20 (1.04-1.38) High: 1.12 (0.93-1.35) 2-day Lag Medium: 1.12 (0.95-1.32) High: 1.19 (0.98-1.44) Reference: Host et al. (2007, 155851 ) Period of Study: 2000-2003

Location: Six French cities: Le Havre, Lille, Marseille, Paris, Rouen, and Toulouse Outcome (ICD-10): Daily hospitalizations for all respiratory diseases (J00-J99), respiratory infections (J10-J22). Age Groups: For all respiratory diseases: 0-14 yr, 15-64 yr, and ≥ 65 yr. For respiratory infections: All ages Study Design: Time series

N: NR (Total population of cities: approximately 10 million) Statistical Analyses: Poisson regression

Covariates: Seasons, days of the week, holidays, influenza epidemics, pollen counts, temperature, and temporal trends

Season: NR Dose-response Investigated: No Statistical Package: MGCV package in R software (R 2.1.1) Lags Considered: Avg of 0-1 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (5th -95th percentile): Le Havre: 13.8 (6.0-30.5) Lille: 15.9 (6.9-26.3) Marseille: 18.8 (8.0-33.0) Paris: 14.7 (6.5-28.8) Rouen: 14.4 (7.5-28.0) Toulouse: 13.8 (6.0-25.0) Monitoring Stations: 13 total: 1 in Toulouse

4 in Paris

2 each in other cities Copollutant (correlation): PM 10-2.5 : Overall: r > 0.6 Ranged between r = 0.28 and

r = 0.73 across the six cities. PM Increment: 10 μg/m 3 increase, and a 27 μg/m 3 increase (corresponding to the difference between the lowest of the 5th percentiles and the highest of the 95th percentiles of the cities’ distributions) ERR (excess relative risk) Estimate [CI]: For all respiratory diseases (27 μg/m 3 increase): 0-14 yr: 1.1% [-3.1, 5.5] 15-64 yr: 2.2% [-1.8, 6.4];

≥ 65 yr: 1.3% [-5.3, 8.2] For respiratory infections (10 μg/m 3 increase): All ages: 2.5% [0.1, 4.8] For respiratory infections (27 μg/m 3 increase): All ages: 7.0% [0.7, 13.6]



### December 2009 E-275

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ko et al. (2007, 091639 ) Period of Study: Jan 2000-Dec 2004

Location: Hong Kong, China ED Visits Outcome (ICD-9): COPD: Chronic bronchitis (491), Emphysema (492), Chronic airway obstruction (496) Age Groups: All ages Study Design: Time series

N: 15 hospitals, 119,225 admissions Statistical Analyses: Poisson regression, GAM with stringent convergence criteria, APHEA2 protocol.

Covariates: Time trend, season, temperature, humidity, other cyclical factors, day, day of wk, holidays

Season: All yr, interactions with season tested Dose-response Investigated? No Statistical Package: SPLUS 4.0 Lags Considered: 0-5 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 35.7 (20.6)

Percentiles:

25th: 19.4 50th(Median): 31.7

75th: 46.7 Range (Min, Max): (6.0, 163.2) Monitoring Stations: 14 Copollutant (correlation): PM 2.5 :

PM 10 r = 0.952

NO 2 r = 0.441

O 3 r = 0.394

SO 2 r = 0.282 PM Increment: PM 10 RR Estimate COPD: 1.002[0.998, 1.001] lag 0 1.003[0.999, 1.007] lag 1 1.011[1.007, 1.014] lag 2 1.013[1.010, 1.017] lag 3 1.011[1.008, 1.015] lag 4 1.009[1.006, 1.013] lag 5 1.004[0.999, 1.008]lag 0-1 1.010[1.006, 1.015]lag 0-2 1.018[1.013, 1.022]lag 0-3 1.024[1.019, 1.029]lag 0-4 1.031[1.026, 1.036]lag 0-5 4-Pollutant model: 1.014[1.007, 1.022] lag 0-5

3-Pollutant model: 1.011[1.004, 1.017] lag 0-5

Reference: Ko et al. (2007, 092844 ) Period of Study: Jan 2000-Dec 2005

Location: Hong Kong, China Hospital Admission Outcome (ICD-9): Asthma (493) Age Groups: All, 0-14, 15-56, 65+ Study Design: Time series

N: 69,716 admissions, 15 hospitals Statistical Analyses: Poisson regression, with GAM with stringent convergence criteria.

Covariates: Time trend, season, temperature, humidity, other cyclical factors

Season: All yr, evaluated effect of season in analysis Dose-response Investigated? No Statistical Package: SPLUS 4.0 Lags Considered: 0-5 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 36.4 (21.1)

Percentiles : 25th: 20.0 50th(Median): 32.5

75th: 47.7 Range (Min, Max): (6, 163) Monitoring Stations: 14 Copollutant (correlation): PM 2.5 : PM 10 r = 0.956 NO 2 r = 0.774 O r = 0.585

3 SO 2 r = 0.482 PM Increment: 10.0 μg/m 3

RR Estimate Asthma (Single-pollutant model): 1.008[1.004, 1.013] lag 0 1.004[1.000, 1.009] lag 1 1.004[1.000, 1.009] lag 2 1.009[1.005, 1.014] lag 3 1.006[1.001, 1.011] lag 4 1.002[0.998, 1.007] lag 5 1.009[1.004, 1.014] lag 0-1 1.012[1.007, 1.018] lag 0-2 1.017[1.011, 1.022] lag 0-3 1.020[1.014, 1.026] lag 0-4 1.021[1.015, 1.028] lag 0-5

Asthma in Age: 0-14: 1.024[1.013, 1.034] lag 0-5 14-65: 1.018[1.008, 1.029] lag 0-5 >65: 1.021[1.012, 1.030] lag 0-4

Asthma-Cold Season: 1.139[1.043, 1.244] lag 0-5

Reference: Lee et al. (2006, 090176 ) Period of Study: Jan 1997-Dec 2002

Location: Hong Kong, China Hospital Admission

Outcome: Asthma (493) Age Groups: <18 yr Study Design: Time series

N: 26,663 asthma admissions for asthma and 5821 admissions for influenza Statistical Analyses: Poisson regression, GAM

Covariates: Temperature, atmospheric pressure, relative humidity

Season: All Dose-response Investigated? No Statistical Package: SAS 8.02 Lags Considered: 0-5

Notes: Controls were admissions for influenza ICD9 487 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 45.3 μg/m 3 , (16.2)

Percentiles: 25th: 33.4 50th(Median): 43.0

75th: 54.0 Range (Min, Max): NR Monitoring Stations: 10 Copollutant (correlation):

PM 2.5 -PM 10 : 0.89

PM 2.5 -SO 2 : 0.48

PM 2.5 -NO 2 : 0.74

PM 2.5 -O 3 : 0.47 PM Increment: IQr = 20.6 μg/m 3

Percent increase: Single pollutant model: 5.10 [2.95, 7.30], lag 0 5.00 [2.88, 7.16], lag 1 5.48 [2.75, 6.95], lag 2 4.83 [2.78, 6.93], lag 3 6.59 [4.51, 8.72], lag 4 5.24 [3.18, 7.34 ], lag 5 Multipollutant model (SO 2 , NO 2 , CO, O 3 ) 3.24 [0.93, 5.60], lag 4



### December 2009 E-276

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Letz and Quinn (2005, 088752 ) Period of Study: Oct 2001-Aug 2002

Location: San Antonio,Texas Emergency Dept Visits Outcome (ICD-9): Asthma or reactive airway disease (493.0-493.9), wheezing (786.07), dyspnea (786.01-786.9), shortness of breath (786.05), bronchitis (490-496), or cough (786.2) Age Groups: NR (basic air force trainees) Study Design: Historic (retrospective) cohort

N: 149 ED visits Statistical Analyses: Pearson correlation

Covariates: NR

Season: NR Dose-response Investigated? No Statistical Package: SPSS Lags Considered: NR Pollutant: PM 2.5 Averaging Time: 24-h AQI AQI Range (min-max): (4-109) Monitoring Stations: Data obtained from the Texas Commission on Environmental Quality Copollutant (correlation): NR PM Increment: NR

Correlation with Outcomes: Same-day

All visits: r = 0.082

Proven asthmatic events: r = -0.042 3-day

All visits: r = 0.097

Proven asthmatic events: r = 0.011

Reference: Lin et al. (2005, 087828 ) Period of Study: 1998-2001

Location: Toronto, North York, East York, Etobicoke, Scarborough, and York (Canada) Hospital Admissions Outcome (ICD-9): Respiratory infections including laryngitis, tracheitis, bronchitis, bronchiolitis, pneumonia, and influenza (464, 466, 480-487) Age Groups: 0-14 yr Study Design : Bidirectional casecrossover

N: 6782 respiratory infection hospitalizations Statistical Analyses: Conditional logistic regression (Cox proportional hazards model)

Covariates: Daily mean temp and dew point temp

Season: NR Dose-response Investigated? No Statistical Package: SAS 8.2 PHREG procedure Lags Considered: 1- to 7-day avg Pollutant: PM 2.5 Averaging Time: 24 h Mean (min-max): 9.59 (0.25-50.50)

SD = 7.06 Monitoring Stations: 4 Copollutant (correlation): PM 10-2.5 : r = 0.33

PM 10 : r = 0.87

CO: r = 0.10

SO 2 : r = 0.47

NO 2 : r = 0.48

O 3 : r = 0.56 PM Increment: 7.8 μg/m 3 OR Estimate [CI]: Adjusted for weather 4-day avg: 1.11 [1.02,1.22] 6-day avg: 1.11 [1.00,1.24] Adj for weather and other gaseous pollutants 4-day avg: 0.94 [0.81,1.08] 6-day avg: 0.90 [0.76,1.07]

Notes: OR’s were also categorized into “Boys” and “Girls,” yielding similar results



### December 2009 E-277

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lin et al. (2002, 026067 ) Period of Study: Jan 1981-Dec 1993

Location: Toronto Hospital Admissions Outcome (ICD-9): Asthma (493) Age Groups: 6-12 yr Study Design: Uni- and bi-directionalcase-crossover (UCC, BCC) and timeseries (TS)

N: 7,319 asthma admissions Statistical Analyses: Conditional logistic regression, GAM

Covariates: Maximum and minimum temp, avg relative humidity

Season: Apr-Sep, Oct-Mar Dose-response Investigated? No Statistical Package: NR Lags Considered: 1- to 7-day avg Pollutant: PM 2.5 Averaging Time: 6 days (predicted daily values) Mean (min-max): 17.99 (1.22-89.59)

SD = 8.49 Monitoring Stations: 1 Copollutant (correlation):

PM 10 : r = 0.87

PM 10-2.5 : r = 0.44

CO: r = 0.45

SO 2 : r = 0.46

NO 2 : r = 0.50

O 3 : r = 0.21 PM Increment: 9.3 μg/m 3 RR Estimate [CI]: Adj for weather and gaseous pollutants BCC 5-day avg: 0.94 [0.85,1.03] BCC 6-day avg: 0.92 [0.83,1.02] TS 5-day avg: 0.96 [0.90,1.02] TS 6-day avg: 0.94 [0.88,1.01] Boys-adj for weather UCC 1-day avg: 1. 09 [1.04,1.15] UCC 2-day avg: 1. 09 [1.02,1.16] BCC 1-day avg: 1.01 [0.97,1.06] BCC 2-day avg: 0.99 [0.93,1.05] TS 1-day avg: 1.00 [0.97,1.04] TS 2-day avg: 0.98 [0.94,1.02] Girls-adj for weather UCC 1-day avg: 1. 06 [0.99,1.14] UCC 2-day avg: 1.11 [1.02,1.21] BCC 1-day avg: 0.99 [0.93,1.06] BCC 2-day avg: 1.02 [0.94,1.09] TS 1-day avg: 0.99 [0.95,1.04] TS 2-day avg: 1.00 [0.95,1.06] Notes: The author also provides RR using UCC, BCC, and TS analysis for female and male groups for days 3-7, yielding similar results

Reference: Magas et al. (2007, 090714 ) Period of Study: 2001-2003

Location: Oklahoma City Metro area, Oklahoma and Cleveland counties Hospital Admission/ED: Admissions

Outcome: Asthma 493.01-493.99 Age Groups: <15 yr Study Design: Time series

N: 1,270 admissions Statistical Analyses: Negative binomial regression

Covariates: Temperature, humidity, pollen count, mold

Season: All Dose-response Investigated? No Statistical Package: NR Lags Considered: 1 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Monitoring Stations: 10 Copollutant (correlation): NR Notes: Coefficient for PM 2.5 was not significant and thus not reported.

Reference: Mohr et al. (2008, 180215 ) Period of Study: Jun 2001-May 2003

Location: St. Louis, MO Outcome: Asthma ER Visits Age Groups: 2-17 yr Study Design: Time series Statistical Analyses: GEE Poisson models

Covariates: Season, weekend exposure, allergens Dose-response Investigated: No Statistical Package: SAS Lags Considered: 1 day Pollutant: PM 2.5 EC Averaging Time: 24 h

Std Dev: 0.1 Monitoring Stations: 1 Copollutant: NO X , SO 2 , O 3 Co-pollutant Correlation

NO X : 0.68* SO 2 : 0.09 O 3 : -0 06 *p ≤ 0.05 PM Increment: 0.1 μg/m 3

Relative Risk Effect (Lower CI, Upper CI): Weekend Exposure Summer: 1.05 (1.00, 1.11) Fall: 0.99 (0.97, 1.01) Winter: 0.96 (0.92, 1.00) Spring: 0.96 (0.92, 1.00)

Weekday Exposure Summer: 1.01 (0.98, 1.03) Fall: 1.00 (0.99, 1.01) Winter: 0.99 (0.96, 1.01) Spring: 0.98 (0.96, 1.01)



### December 2009 E-278

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Neuberger et al. (2004, 093249 ) Period of Study: 1999-2000 (1-yr period)

Location: Vienna and Lower Austria Hospital Admissions Outcome (ICD-9): Bronchitis, emphysema, asthma, bronchiectasis, extrinsic allergic alveolitis, and chronic airway obstruction (490-496) Age Groups: 3.0-5.9 yr 7-10 yr 65+ yr Study Design: Time series

N: 366 days (admissions NR) Statistical Analyses: GAM

Covariates: SO 2 , NO, NO 2 , O 3 , temperature, humidity, and day of the week

Season: NR Dose-response Investigated? Yes Statistical Package: S-Plus 2000 Lags Considered: 0-14 days Pollutant: PM 2.5 Averaging Time: 24 h Maximum daily mean:

Vienna: 96.4

Rural area: 48.0 Monitoring Stations: NR Copollutant (correlation): NR PM Increment: 10 μg/m 3 Log Relative Rate Estimate (p-value):

Vienna Male: 2-day lag = 5.467 (0.019) Female: 3-day lag = 5.596 (0.009)

Rural Male: 10-day lag = 9.893 (0.012) Female: 11-day lag = 10.529 (0.011) Association with tidal lung functioN: β = -0.987 (p-value = 0.091)

Notes: Effect parameters with significant coefficients for respiratory health included: male sex, allergy, asthma in family, and traffic for Vienna and age, allergy, asthma in family, passive smoking, and PM fraction for the rural area. Effect parameters with significant coefficients for log asthma score were allergy, asthma in family, and rain for Vienna and allergy, asthma in family, and passive smoking for the rural area. Cross-correlation coefficients are provided in Fig 1.

Reference: Ostro et al. (2008, 097971 ) Period of Study: 2000-2003

Location: Six California Counties Outcome: Respiratory disease (ICD-9 460-519) Study Design: Time-Series Statistical Analysis: Poisson Regression Statistical Package: R Age Groups: Children <19 yr Pollutant: PM 2.5 and components Averaging Time: 24 h Mean (SD) Unit: 19.4 μg/m 3

IQR: 14.6 μg/m 3 Copollutants: EC, OC, NO 2 , SO 4 , Cu, Fe, K, Si, Zn Increment: NR Relative Risk (Min CI, Max CI) Lag Full results are presented graphically in figures 1 and 2. Excess risks for all-yr respiratory hospital admissions in children <19yrs, 3-day lag PM : 4.1% (1.8-6.4)

2.5 EC: 5.4% (0.8-10.3) Fe: 4.7% (2.2-7.2) OC: 3.4% (1.1-5.7) Nitrates: 3.3% (1.1-5.5) Sulfates: 3.0% (0.4-5.7) Excess risks for cool season (Oct-Mar) respiratory hospital admissions in children <19yrs, 3 day lag PM : 5.1% (1.6-8.9)

2.5 EC: 6.8% (-0.2-14.2) Fe: 4.8% (1.7-8.0) K: 4.0% (0.3-7.7)



### December 2009 E-279

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 1995-Jun 2001

Location: Spokane, WA Hospital Admissions and ED visits

Outcome: All respiratory (460-519) Asthma (493) COPD (491,492, 494,496) Pneumonia (480-487) Acute URI not including colds and sinusitis (464, 466, 490) Age Groups: All, 15+ yr for COPD Study Design: Time series

N: 2373 visit records Statistical Analyses: Poisson regression, GLM with natural splines. For comparison also used GAM with smoothing splines and default convergence criteria.

Covariates: Season, temperature, relative humidity, day of week

Season: All Dose-response Investigated?: No Statistical Package: SAS, SPLUS Lags Considered: 1 -3 days Pollutant: PM 2.5 Averaging Time: 24-h avg Range (90% of Concentrations): 4.2-20.2 μg/m 3 Monitoring Stations:

One Notes: Copollutant (correlation): PM 2.5 PM1 r = 0.95

PM 10 r = 0.62

PM 10-2.5 r = 0.31

CO r = 0.62 Temperature r = 0.21 PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: ER visits: PM 2.5 All Respiratory Lag 1: 1.01 [0.98, 1.04] Lag 2: 1.02 [0.99, 1.04] Lag 3: 1.02 [0.99, 1.05] Acute Asthma Lag 1: 1.03 [0.98, 1.09] Lag 2: 1.00 [0.95, 1.05] Lag 3: 1.01 [0.96, 1.06] COPD (adult) Lag 1: 0.96 [0.89, 1.04] Lag 2: 1.01 [0.93, 1.09] Lag 3: 1.00 [0.93, 1.08] Hospital Admissions: PM 2.5 All Respiratory Lag 1: 0.98 [0.94, 1.01] Lag 2: 0.99 [0.96, 1.03] Lag 3: 1.01 [ 0.98, 1.05] Asthma Lag 1: 1.01 [0.91, 1.11] Lag 2: 1.03 [0.94, 1.13] Lag 3: 1.02 [0.93, 1.13] COPD (adult) Lag 1: 0.99 [0.91, 1.08] Lag 2: 1.06 [0.98, 1.16] Lag 3: 1.03 [0.94, 1.12] Reference: Tecer et al. (2008, 180030 ) Period of Study: Dec 2004-Oct 2005

Location: Zonguldak, Turkey Outcome: ED visits for respiratory problems (ICD-9 470-478, 493) Study Design: Bidirectional Casecrossover Covariates: Daily meteorological parameters Statistical Analysis: Conditional logistic regression Statistical Package: Stata Age Groups: 0-14 yr Pollutant: PM 2.5 Averaging Time: NR Mean, Unit: 29.1 μg/m 3 Range (Min, Max): 4.55, 95.65 Copollutant (correlation):

PM 2.5 /PM 10 Mean: 0.56 Range: 0.17-0.88

PM 2.5 /PM 10-2.5 Mean: 1.49 Range: 0.21-7.53 Increment: 10 μg/m 3 Odds Ratio (95% CI) Asthma Lag 0: 1.15 (0.99-1.34) Lag 1: 0.85 (0.70-1.03) Lag 2: 0.87 (0.73-1.04) Lag 3: 0.93 (0.79-1.10) Lag 4: 1.25 (1.05-1.50) Allergic Rhinitis with Asthma Lag 0: 1.21 (1.10-1.33) Lag 1: 0.84 (0.75-0.93) Lag 2: 0.89 (0.81-0.98) Lag 3: 0.99 (0.90-1.09) Lag 4: 1.06 (0.95-1.19) Allergic Rhinitis Lag 0: 1.08 (0.98-1.20) Lag 1: 1.03 (0.93-1.13) Lag 2: 0.89 (0.80-0.99) Lag 3: 0.98 (0.89-1.09) Lag 4: 1.18 (1.00-1.24) Upper Respiratory Disease Lag 0: 0.99 (0.49-2.00) Lag 1: 0.52 (0.22-1.20) Lag 2: 1.29 (0.75-2.22) Lag 3: 1.29 (0.69-2.43) Lag 4: 1.47 (0.87-2.50) Lower Respiratory Disease Lag 0: 1.06 (0.78-1.44) Lag 1: 0.85 (0.59-1.22) Lag 2: 1.08 (0.72-1.61) Lag 3: 1.18 (0.92-1.52) Lag 4: 0.72 (0.54-0.96)h Reference: Tolbert et al. (2007, 090316 ) Period of Study: Aug 1998-Dec 2004

Location: Atlanta Metropolitan area, Georgia Outcome (ICD-9): Combined RD group, including: Asthma (493, 786.07, 786.09), COPD (491, 492, 496), URI (460-465, 460.0, 477), pneumonia (480-486), and bronchiolitis (466.1, 466.11, and 466.19)) Age Groups: All Pollutant: PM 2.5 Averaging Time: 24 h Mean (median IQR, range, 10th-90th percentiles): PM 2.5 : 17.1 (15.6 11.0-21.9 0.8-65.8 7.9-28.8) PM 2.5 sulfate: 4.9 (3.9 2.4-6.2 PM Increment:

PM 2.5 : 10.96 μg/m 3 (IQR)

PM 2.5 sulfate: 3.82 μg/m 3 (IQR)

PM 2.5 total carbon: 3.63 μg/m 3 (IQR)

PM 2.5 OC: 2.61 μg/m 3 (IQR)

PM 2.5 EC: 1.15 μg/m 3 (IQR)

PM 2.5 water-soluble metals: 0.03 μg/m 3



### December 2009 E-280

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Study Design: Time series

N: NR for 1998-2004. For 1993-2004: 10,234,490 ER visits (283,360 and 1,072,429 visits included in the CVD and RD groups, respectively) Statistical Analyses: Poisson generalized linear models

Covariates: Long-term temporal trends, season (for RD outcome), temperature, dew point, days of week, federal holidays, hospital entry and exit

Season: All Dose-response Investigated: No Statistical Package: SAS version 9.1 Lags Considered: 3-day ma(lag 0 -2) 0.5-21.9 1.7-9.5) PM 2.5 OC: 4.4 (3.8 2.7-5.3 0.4-25.9 2.1-7.2) PM 2.5 EC: 1.6 (1.3 0.9-2.0 0.1-11.9 0.6-3.0) PM 2.5 water-soluble metals: 0.030 (0.023 0.014-0.039 0.003-0.202 0.009-0.059) Monitoring Stations: 1 Copollutant (correlation): Between PM 2.5 and: PM 10 : r = 0.84 O 3 : r = 0.62 NO 2 : r = 0.47 CO: r = 0.47 SO 2 : r = 0.17 PM 10-2.5 : r = 0.47; PM 2.5 SO 4 : r = 0.76; PM 2.5 EC: r = 0.65; PM 2.5 OC: r = 0.70; PM 2.5 TC: r = 0.71; PM 2.5 water-sol metals: r = 0.69 OHC: r = 0.50 Between PM 2.5 SO 4 and: PM 10 : r = 0.69 O 3 : r = 0.56 NO 2 : r = 0.14 CO: r = 0.14 SO 2 : r = 0.09 PM 10-2.5 : r = 0.32; PM 2.5 : r = 0.76; PM 2.5 EC: r = 0.32; PM 2.5 OC: r = 0.33; PM 2.5 TC: r = 0.34; PM 2.5 water-sol metals: r = 0.65 OHC: r = 0.47 Between PM 2.5 EC and: PM 10 : r = 0.61 O 3 : r = 0.40 NO 2 : r = 0.64 CO: r = 0.66 SO 2 : r = 0.22 PM 10-2.5 : r = 0.49 PM 2.5 : r = 0.65 PM 2.5 SO 4 : r = 0.32 PM 2.5 OC: r = 0.82 PM 2.5 TC: r = 0.91 PM 2.5 water soluble metals: r = 0.52 OHC: r = 0.35 Between PM 2.5 OC and: PM 10 : r = 0.65 O 3 : r = 0.54 NO 2 : r = 0.62 CO: r = 0.59 SO 2 : r = 0.17 PM 10-2.5 : r = 0.49 PM 2.5 : r = 0.70 PM 2.5 SO 4 : r = 0.33 PM 2.5 EC: r = 0.82 PM 2.5 TC: r = 0.98 PM 2.5 water-sol metals: r = 0.49 OHC: r = 0.37 Between PM 2.5 total carbon and: PM 10 : r = 0.67 O 3 : r = 0.52 NO 2 : r = 0.65 CO: r = 0.63 SO 2 : r = 0.19 PM 10-2.5 : r = 0.51 PM 2.5 : r = 0.71 (IQR) Risk ratio [95% CI] (single pollutant models):

PM 2.5 : RD: 1.005 [0.995-1.015]

PM 2.5 sulfate: RD: 1.007 [0.996-1.018]

PM 2.5 total carbon: RD: 1.001 [0.993-1.008]

PM 2.5 OC: RD: 1.003 [0.995-1.011]

PM 2.5 EC: RD: 0.996 [0.989-1.004]

PM 2.5 water-soluble metals: RD: 1.005 [0.995-1.015]



### December 2009 E-281

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

PM 2.5 SO 4 : r = 0.34 PM 2.5 EC: r = 0.91 PM 2.5 OC: r = 0.98 PM 2.5 water-sol metals: r = 0.52 OHC: r = 0.38 Between PM 2.5 water-soluble metals and: PM 10 : r = 0.73 O 3 : r = 0.43 NO 2 : r = 0.32 CO: r = 0.35 SO 2 : r = 0.06 PM 10-2.5 : r = 0.50 PM 2.5 : r = 0.69 PM 2.5 SO 4 : r = 0.65 PM 2.5 EC: r = 0.52 PM 2.5 OC: r = 0.49 PM 2.5 TC: r = 0.52 Reference: Wong et al. (2006, 093266 ) Period of Study: 2000-2002

Location: Hong Kong (8 districts) General Practitioner Visits Outcome (ICPC-2): Respiratory diseases/symptoms: upper respiratory tract infections (URTI), lower respiratory infections, influenza, asthma, COPD, allergic rhinitis, cough, and other respiratory diseases Age Groups: All ages Study Design: Time series

N: 269,579 visits Statistical Analyses: GAM, Poisson regression

Covariates: Season, day of the week, climate

Season: NR Dose-response Investigated? No Statistical Package: S-Plus Lags Considered: 0-3 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (min-max): 35.7 (9-120)

SD = 16.7 Monitoring Stations: 1 per district Copollutant (correlation):

PM 10 : r = 0.94 PM Increment: 10 μg/m 3 RR Estimate [CI]:

Overall URTI 1.021 [1.010,1.032]

Notes: RRs are also reported for each individual general practitioner yielding similar results

Reference: Yang Q et al. (2004, 087488 ) Period of Study: Jun 1995-Mar 1999

Location: Vancouver area, British Columbia Hospital Admissions Outcome (ICD-9): Respiratory diseases (460-519), pneumonia only (480-486), asthma only (493) Age Groups: 0-3 yr Study Design: Case control, bidirectional case-crossover (BCC), and time series (TS)

N: 1610 cases Statistical Analyses: Chi-square test, Logistic regression, GAM (time-series), GLM with parametric natural cubic splines

Covariates: Gender, socioeconomic status, weekday, season, study yr, influenza epidemic month

Season: Spring, summer, fall, winter Dose-response Investigated? No Statistical Package: SAS (Case control and BCC), S-Plus (TS) Lags Considered: 0-7 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (min-max): 7.7 (2.0-32.0)

SD = 3.7 Monitoring Stations: NR (data obtained from Greater Vancouver Regional District Air Quality Dept) Copollutant (correlation):

PM 10 : r = 0.83

PM 10-2.5 : r = 0.39

CO: r = 0.24

O 3 : r = -0.03

NO 2 : r = 0.37

SO 2 : r = 0.43 PM Increment: 4.0 μg/m 3 (IQR) OR Estimate [CI]:

Values NR

Notes: Author states that no significant association was found between PM 2.5 and respiratory disease hospitalizations.



### December 2009 E-282

### Reference Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zanobetti and Schwartz (2006, 090195 ) Period of Study: 1995-1999

Location: Boston, MA Hospital Admission/ED:

Outcome: Pneumonia (480-487) Age Groups: >65 y Study Design: Case-crossover, time stratified

N: 24,857 for Pneumonia Statistical Analyses: Condition logistic regression

Covariates: Season, long term trend, day of-the-wk, mean temperature, relative humidity, barometric pressure, extinction coefficient

Season: All yr Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-1

Notes: Also looked at MI cohort Pollutant: PM non-traffic Averaging Time: 24 h Percentiles (pneumonia cohort): 5th: -7.3 25th: -3.28 μg/m 3 50th(Median): -0.88

75th: 1.92

95th: 12.11 PM Component: BC Monitoring Stations: 4-5 monitors Copollutant (correlation): PM non-traffic: PM 2.5 r = 0.74 CO r = -0.01 NO 2 r = 0.14 O 3 r = -0.47 BC r = -0.01 PM Increment: PM non-traffic lag 0: 13.44 μg/m 3 PM non-traffic lag 0-1 avg: 10.28 μg/m 3 % change in Pneumonia: PM non-traffic -0.57 [-7.51, 6.36] lag 0 PM non-traffic -0.94 [-7.20, 5.32] mean lag 1

Reference: Zhong et al. (2006, 093264 ) Period of Study: Apr-Oct 2002

Location: Cincinnati, Ohio Hospital Admissions Outcome (ICD-9): Asthma (493- 493.91) Age Groups: 1-18 yr Study Design: Time series

N: 1254 admissions Statistical Analyses: Poisson multiple regression, GAM

Covariates: Season, temperature, humidity, O 3 , day of the week

Season: NR Dose-response Investigated? Yes Statistical Package: NR Lags Considered: 1-5 days Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): Apr: 12.4 (3.8) May: 13.6 (5.8) Jun: 21.6 (9.9) Jul: 25.8 (11.9) Aug: 20.3 (8.7) Sep: 19.5 (11.1) Oct: 12.8 (6.4) Monitoring Stations: NR (data obtained from the National Virtual Data System) Copollutant (correlation): NR

Notes: Author states all pairwise correlations were insignificant PM Increment: NR RR Estimate [CI]:

NR

Notes: This study focused primarily on aeroallergens and asthma visits

Reference: Zanobetti and Schwartz (2006, 090195 ) Period of Study: 1995-1999

Location: Boston, MA Outcome: Pneumonia (480-487) Age Groups: >65 y Study Design: Case-crossover, time stratified

N: 24,857 for Pneumonia Statistical Analyses: Condition logistic regression

Covariates: Season, long term trend, day of-the-wk, mean temperature, relative humidity, barometric pressure, extinction coefficient

Season: All yr Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-1

Notes: Also looked at MI cohort Pollutant: PM 2.5 Averaging Time: 24 h

Percentiles (pneumonia cohort) : 25th: 7.23 μg/m 3 50th(Median): 11.10

75th: 16.14 PM Component: Black Carbon (BC), PM non-traffic Monitoring Stations: 4-5 monitors Copollutant (correlation): PM 2.5 : CO r = 0.52 NO 2 r = 0.55 O 3 r = 0.20 BC r = 0.66 PM non-traffic r = 0.74 PM Increment: PM 2.5 lag 0: 17.17 μg/m 3

PM 2.5 lag 0-1 avg: 16.32 μg/m 3 % change in Pneumonia: 6.48[1.13, 11.43] lag 0 5.56[-0.45, 11.27] mean lag 1

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-283

# Table E-15. Short-term exp osure-respiratory-ED/HA- Other Size Fractions.

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Andersen et al. (2007, 093201 ) Period of Study: 2001-2004

Location: Copenhagen, Denmark Outcome (ICD10): Respiratory disease (J41-46) Asthma (J45, 46) Age Groups: 5-18 and >65 Study Design: Time-series

N: 1327 days ~1.5 million people at-risk Statistical Analyses: Poisson regression, GAM.

Covariates: Influenza epidemics,pollen, temperature, dew point, day-ofweek, holiday, season.

Season: All Dose-response Investigated? No Statistical Package: R with gam and mgcv packages. Lags Considered: 0-5 Pollutant: Number concentration (NC) of ultrafine & accumulation mode particles Averaging Time: 24 h Mean particles/cm3 (SD): NCtot (total): 8116 (3502) 25th: 4959 50th: 6243 75th: 8218 99th: 16189 IQR: 3259 NC100 (<100 nm): 6847 (2864) 25th: 5738 50th (Median): 7358 75th: 9645 99th: 19895 IQR: 3907 Mean particles/cm 3 for 4 size modes (median diameter (nm) noted): NCa12: 493(315) NCa23: 2253 (1364) NCa57: 5104 (2687) NCa212: 6847 (2864) Monitoring Stations: 3 (Background, rural Background, urban Curbside, urban)

Notes: NC exposure data available for n = 578 days. Information on distribution of 4 size modes provided in the paper. Copollutant (correlation): NCtot and PM 10 : r = 0.39 NCtot and PM 2.5 : r = 0.40 NCtot and NO 2 : r = 0.68 PM and PM : r = 0.8

10 2.5 “Low or no” correlations between 4 size modes NCa212 and PM 2. : r = 0.8 5 NCa212 and PM 10 : r = 0.63 NCa57 and NO 2 : r = 0.57 Notes: selected correlations reported in text, all correlations in annex to the manuscript PM Increment: Based on the IQR, specific to metric (see below).

RR Estimate: Single pollutant results, Asthma, (5-18 yr), lag 0-5: PM 2.5 : 1.15 [1, 1.32], IQr = 5 NCtot: 1.07 [0.98, 1.17], IQr = 3907 NC100: 1.06 [0.97, 1.16], IQr = 3259 NCa12: 1.08 [0.99, 1.18], IQr = 342 NCa212: 1.08 [1, 1.17], IQr = 495 NCa23: 1.09 [0.98, 1.21], IQr = 1786 NCa57: 1.02 [0.94, 1.12], IQr = 3026 2-pollutant results: NCa212 w/ PM 10 : 1.1 [0.96, 1.13], IQr = 495 NCtot w/ PM 10 : 1.03 [0.92, 1.15] NCtot w/ PM : 1.04 [0.85, 1.28] 2.5 All RD, (>65 yr), lag 0-4, single pollutant results: PM : 1 [0.95, 1.05]

2.5 NCtot: 1.04 [1, 1.07] IQr = 3907 NC100: 1.03 [0.99, 1.07], IQr = 3259 NC12: 1.01 [0.98, 1.05], IQr = 342 NC212: 1.04 [1.01, 1.08], IQr = 495 NCa23: 0.99 [0.94, 1.03], IQr = 1786 NCa57: 1.04 [1, 1.08], IQr = 3026 2-pollutant results: NCa212 w/ PM 10 : 1.01 [0.96, 1.07], IQr = 495 NCtot w/ PM 2.5 : 0.97 [0.89, 1.05] NCtot w/ PM 10 : 1 [0.96, 1.05] Notes: Multipollutant model results also included for models with 4 size modes.

Reference: Agarwal et al. (2006, 099086 ) Period of Study: 2000-2003

Location: Safdarjung area of Delhi Outcome (ICD-NR): COPD, asthma, emphysema Age Groups: NR Study Design: Time series

N: NR Statistical Analyses: Kruskal-Wallis one-way analysis, Chi-square, Multivariate linear regression

Covariates: Temp (min & max), relative humidity at 0830 and 1730 h, wind speed

Season: I (Jan-Mar), II (Apr-Jun), III (Jul-Sep), IV (Oct-Dec) Dose-response Investigated? Yes Statistical Package: SPSS Lags Considered: NR Pollutant: SPM (Suspended PM) Averaging Time: 8 h

Mean μg/m 3 (SD): Qtr I: 297.5 (34.6) Qtr II: 398.0 (85.6) Qtr III: 220.0 (78.0) Qtr IV: 399.0 (54.6) Monitoring Stations: 2 Copollutant (correlation): RSPM: r = 0.771

Other variables:

RH0830: r = -0.482

RH1730: r = -0.531

COPD: r = 0.474 PM Increment: NR RR Estimate [CI]: NR

Notes: This study analyzed seasonal variation of pollutants and health outcomes and correlations among the variables



### December 2009 E-284

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Agarwal et al. (2006, 099086 ) Period of Study: 2000-2003

Location: Safdarjung area of Delhi Outcome (ICD-NR): COPD, asthma, emphysema Age Groups: NR Study Design: Time series

N: NR Statistical Analyses: Kruskal-Wallis one-way analysis, Chi-square, Multivariate linear regression

Covariates: Temp (min & max), relative humidity at 0830 and 1730 h, wind speed

Season: I (Jan-Mar), II (Apr-Jun), III (Jul-Sep), IV (Oct-Dec) Dose-response Investigated? Yes Statistical Package: SPSS Lags Considered: NR Pollutant: RSPM (Respirable Suspended PM <10 μm) Averaging Time: 8 h

Mean μg/m 3 (SD): Qtr I: 119.0 (19.8) Qtr II: 132.0 (28.4) Qtr III: 75.0 (23.4) Qtr IV: 168.0 (40.6) Monitoring Stations: 2 Copollutant (correlation): SPM: r = 0.771

Other variables: Temp (min): r = -0.420

COPD: r = 0.353 PM Increment: NR RR Estimate [CI]: NR

Notes: This study analyzed seasonal variation of pollutants and health outcomes and correlations among the variables

Reference: Arbex et al. (2007, 091637 ) Period of Study: Mar 2003-Jul 2004

Location: Araraquara, Sao Paulo State, Brazil Hospital Admission Outcome (ICD10): Asthma (J15, J45) Age Groups: All Study Design: Time-series

N: 493 days, 1 hospital, 640 admissions Statistical Analyses: Generalized linear Poisson regression model with natural cubic spline, Mann-Whitney U Test

Covariates: Temperature and humidity

Season: All Dose-response Investigated? Yes, quintile analysis Statistical Package: SPSS V.11 & Splus 4.5 Lags Considered: 0-9 Pollutant: TSP Averaging Time: 24 h Mean (SD): 46.8 μg/m 3 (24.4) Range (Min, Max): 6.7-137.8 μg/m 3 Monitoring Stations: 1

Notes: TSP used as a proxy for fine & ultrafine particles since it is composed of 85-95% PM 2.5

. Copollutant (correlation): NR PM Increment: 10 μg/m 3

% Increase 6.96 [1.4-12.86] 2-day ma 9.090 [3.12-15.40] 3 day ma 10.28 [4.05-16.90] 4-day ma 11.63 [5.46-19.318] 5 day ma 12.61 [5.68-20.00] 6-day ma 12.56 [5.47-20.13] 7-day ma % Increase by TSP quintile: 9.25-28.45 μg/m 3 : : 1.00 28.46-48.85 μg/m 3 : : 1.55 [045-5.77] 48.86-69.06 μg/m 3 : : 2.46 [1.08-5.60] 69.07-88.44 μg/m 3 : : 2.77 [1.32-5.84] 88.45-108.9 μg/m 3 : : 2.94 [1.48-5.85] Notes: No TSP threshold for asthma admissions noted. Analysis of lag structure indicated that the acute effect of TSP on admissions started 1 day after TSP concentration increase and remained unchanged for next 4 days.

Notes: To evaluate the association between TSP generated from burning sugar cane and asthma hospital admissions.

Reference: Bartzokas et al. (2004, 093252 ) Period of Study: Jun 1992-May 2000

Location: Athens, Greece Outcome: Respiratory and cardiovascular diseases (combined) Age Groups: NR Study Design: Time series

N: 1554 patients Statistical Analyses: Simple linear regression and linear stepwise regression, Pearson correlation

Covariates: Temperature, atmospheric pressure, relative humidity, wind speed

Season: Warm (May-Sep) and cold (Nov-Mar) Dose-response Investigated? No Statistical Package: NR Lags Considered: NR Pollutant: PM4.5 (black smoke) Averaging Time: 10-day ma

Mean μg/m 3 (SD): NR Monitoring Stations: 1 Copollutant (correlation): N PM Increment: NR

Correlation with Number of Admissions: Entire yr Original: r = 0.18

Smoothed: r = 0.31 Warm period Original: r = 0.19

Smoothed: r = 0.30 Cold period Original: r = 0.18

Smoothed: r = 0.34 *All above values are statistically significant



### December 2009 E-285

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Erbas et al. (2005, 073849 ) Period of Study: Jul 1989-Dec 1992

Location: Melbourne, Australia Outcome (ICD): COPD (490-492, 494, 496) Asthma (493) Age Groups: NR Study Design: Time series

N: NR Statistical Analyses: GLM, GAM, Parameter Driven Poisson Regression,Transitional Regression, SeasonalTrend decomposition based on Loess smoothing for seasonal adjustment

Covariates: Secular trends, seasonality, relative humidity, dry bulb temp, dew point temp

Season: NR Dose-response Investigated? Yes Statistical Package: S-Plus, SAS Lags Considered: 0-5 days Pollutant: PM 0.1-1 (API) Averaging Time: 24 h Mean (min-max): NR Monitoring Stations: 9 Copollutant (correlation): NR PM Increment: Increase from the 10th90th percentile (value NR) RR Estimate [CI]:

COPD

GAM: 0.95 [0.91,1.00] GLM, PDM, TRM: NR

Asthma

NR

Notes: This study was used to demonstrate that conclusions are highly dependent on the type of model used

Reference: Halonen et al. (2008, 189507 ) Period of Study: 1998-2004

Location: Helsinki, Finland Outcome: Respiratory Hospitalizations & Mortality (ICD 10: J00-99) Age Groups: 65+ yr Study Design: Time series

N: NR Statistical Analyses: Poisson, GAM

Covariates: Temperature, humidity, influenza epidemics, high pollen episodes, holidays Dose-response Investigated? No Statistical Package: R Lags Considered: Lags 0-3 & 5-day (0-4) mean Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): NR

Min: 1.1 25th percentile: 5.5 50th percentile: 9.5 75th percentile: 11.7

Max: 69.5 Monitoring Stations: NR Copollutant: PM<0.03, PM0.03-0.1, PM<0.1, PM<0.10.29, PM 10-2.5 , CO, NO 2 Co-pollutant Correlation

PM<0.03: 0.14

PM0.03-0.1: 0.48

PM<0.1: 0.35

PM<0.10.29: 0.88

PM 10-2.5 : 0.25 PM Increment: Interquartile Percent Change (Lower CI, Upper CI): All Respiratory Mortality Lag 0: 2.67 (-0.39, 5.82) ‡ Lag 1: 1.59 (-1.43, 4.70) Lag 2: 0.03 (-2.99, 3.16) Lag 3: -0.11 (-3.13, 3.01) 5-day mean: 1.39 (-2.83, 5.81)

Pneumonia HA Lag 0: 0.93 (-0.85, 2.75) Lag 1: 2.41 (0.64, 4.21) Lag 2: 1.48 (-0.27, 3.26) Lag 3: 1.91 (0.14, 3.70) 5-day mean: 3.10 (0.60, 5.65)

Asthma + COPD HA Lag 0: 2.48 (0.60, 4.39) Lag 1: 2.62 (0.78, 4.49) Lag 2: 1.22(-0.62, 3.10) Lag 3: 0.59 (-1.28, 2.49) 5-day mean: 2.49 (-0.08, 5.12)

Other HA Lag 0: 0.05 (-2.38, 2.54) Lag 1: 0.2 (-2.17, 2.62) Lag 2: 2.03 (-0.29, 4.41) Lag 3: 1.72 (-0.63, 4.12) 5-day mean: 1.88 (-1.50, 5.36) *p < 0.05, ‡p < 0.10



### December 2009 E-286

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Llorca et al. (2005, 087825 ) Period of Study: Jan 1992-Dec 1995

Location: Torrelavega, Spain Outcome (ICD-9): Respiratory (460- 519) and cardiac (390-459) admissions (analyzed combined and individually) Age Groups: NR Study Design: Time series

N: 18,137 admissions Statistical Analyses: Stepwise multiple linear regression, Poisson regression, Spearman correlation

Covariates: Influenza, day of week, wind speed, northeast and southwest winds, minimum and maximum temperature

Season: NR Dose-response Investigated? No Statistical Package: STATA Intercooled, Release 6 Lags Considered: NR Pollutant: TSP (total suspended particles) Averaging Time: 24 h

Mean μg/m 3 (SD): 48.8 (23.7) Monitoring Stations: 3 Copollutant (correlation): SO 2 : r = -0.400 SH2: r = -0.392 NO: r = -0.109 NO 2 : r = -0.120

Other variables: Rain: r = -0.339 Max temp: r = 0.071 Min temp: r = -0.003 Avg temp: r = 0.035 Wind speed: r = -0.357 PM Increment: NR Rate Ratio Estimate [CI]: Cardiorespiratory Admissions Single-pollutant model: 0.92 [0.86,0.98] Five-pollutant model: 1.05 [0.97,1.14] Respiratory Admissions Single-pollutant model: 0.98 [0.89,1.08] Five-pollutant model: 0.91 [0.80,1.02]

Reference: Michaud et al. (2004, 188530 ) Period of Study: Jan 1997-May 2001

Location: Hilo, Hawaii ED visits

Outcome: Asthma/COPD (490-496) Respiratory Irritation (506-508) Age Groups: All Study Design: Time-series

N: 1,561 ER visits Statistical Analyses: Multiple linear regression

Covariates: Hourly temperature, minimum daily temperature, minimum daily temperature, humidity, yr, month, day of the week

Season: all Dose-response Investigated? No Statistical Package:

STATA 6.0

SAS Lags Considered: Previous night, 1,2,3 Pollutant: PM1 Averaging Time: 24-h avg Mean (SD): 1.91 (2.95) μg/m 3 Range (Min, Max): 0.0, 56.6 μg/m 3 Monitoring Stations: 2 Notes: Copollutant (correlation): NR PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Asthma, COPD (499-496): Adjusted for day, month & yr: 1.11 (0.92, 1.34), 00: 00-6: 00AM 1.14 (1.03, 1.26), lag 1 1.06 (0.83, 0.94), lag 2 0.91 (0.06, 1.05), lag 3 Asthma (493, 495): Adjusted for day, month & yr: 1.03 (0.90, 1.42), 00: 00-6: 00AM 1.02 (0.94, 1.21), lag 1 1.02 (0.99, 1.23), lag 2 0.97 (0.69, 1.15), lag 3 Bronchitis (490, 491): Adjusted for day, month & yr: 1.02 (0.82, 1.41), 00: 00-6: 00AM 1.07 (1.18, 1.49), lag 1 0.97 (0.60, 1.34), lag 2 0.93 (0.43, 1.18), lag 3 Notes: Crude and estimates adjusted for month and yr only also presented.

Notes: Volcanic fog = vog



### December 2009 E-287

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Migliaretti et al. (2005, 088689 ) Period of Study: 1997-1999

Location: Turin, Italy Cases: Asthma (493)

Controls: Admissions for nonrespiratory or cardiac conditions (460- 487, 490-493, 494-496, 500-519, 390- 405, 410-429) Age Groups: 0-14, 15-64, >64 Study Design: Case-control

N: Cases: 1,401

Controls: 201,071 Statistical Analyses: Logistic regression

Covariates: Gender, age, daily mean temperature, season, day of week, holidays, education level

Season: All Dose-response Investigated? No Lag: 0- to 2-day avg Pollutant: TSP Averaging Time: Means of daily total levels at stations Mean (SD): 105.3 μg/m 3 , (44.2)

Percentiles: 25th: NR 50th(Median): 96.0 μg/m 3

75th NR Monitoring Stations:

10 Notes: Copollutant (correlation): All seasons: NO 3 – TSP = 0.80

Winter: NO 3 – TSP = 0.77

Summer: NO 3 – TSP = 0.69 PM Increment: 10 μg/m 3 increase % Increase, lag 0-2-day avg 1 pollutant model: <15: 1.90[0.40, 3.40] 15-64: 2.30 [-0.01, 5.20] >64: 2.30 [1.10, 3.60] Total: 2.30[1.10, 3.60] % Increase, lag 0-2-day avg 2 pollutant model: <15: -0.12 [-0.03, 2.50] 15-64: 0.90 [-0.04, 5.61] >64: 1.2 [-0.01, 4.32] Total: 0.91 [-0.02, 3.11]

Reference: Migliaretti et al. (2004, 087425 ) Period of Study: 1997-1999

Location: Turin, Italy Outcome:

Cases: Asthma (493)

Controls: Non-respiratory or cardiac admissions (460-487, 490-493, 494- 496, 500-519, 390-405, 410-429) Age Groups: 0-15 Study Design: Case-control

N: Cases: 1,060

Controls: 25,523 Statistical Analyses: Logistic regression μg/m 3 increase

Covariates: Gender, age, daily mean temperature, season, day of week, holidays, solar radiation

Season: All Lags Considered: 1- to 3-day avg Pollutant: Total suspended particulate Averaging Time: Mean of admission day and 3 preceding days Mean (SD): 114.5 μg/m 3 , (42.8)

Percentiles:

25th: NR 50th(Median): 109.9 μg/m 3

75th: NR Monitoring Stations: 10 Notes: Copollutant (correlation): TSP-NO: 0.76 PM Increment: 10 μg/m 3 % Increase, lag 1-3-day avg <4 yr: 1.8% [0.00, 3.05] 4-15 yr: 3.0% [0.01, 5.08] all: 1.8% [0.03, 3.02] adjusted for all covariates

Notes: Multipollutant models also used

Reference: Neuberger et al. (2004, 093249 ) Period of Study: 1999-2000 (1-yr period)

Location: Vienna and Lower Austria Outcome (ICD-9): Bronchitis, emphysema, asthma, bronchiectasis, extrinsic allergic alveolitis, and chronic airway obstruction (490-496) Age Groups: 3.0-5.9 yr 7-10 yr 65+ yr Study Design: Time series

N: 366 days (admissions NR) Statistical Analyses: GAM

Covariates: SO 2 , NO, NO 2 , O 3 , temperature, humidity, and day of the week

Season: NR Dose-response Investigated? Yes Statistical Package: S-Plus 2000 Lags Considered: 0-14 days Pollutant: PM 1 Averaging Time: 24 h

Mean μg/m 3 (SD): NR Monitoring Stations: NR Copollutant (correlation): NR PM Increment: NR Effect parameters (Vienna children): Respiratory Health Male sex = 0.098 Allergy = 0.238 Asthma in family = 0.190 Traffic = 0.112 Log Asthma Score Allergy = 0.210 Asthma in family = 0.112 Rain = 0.257 *only significant coefficients are presented Association with tidal lung function: β = -1.059 (p-value = 0.060)

Notes: No significant associations between PM and respiratory mortality were found for either sex. Data is also provided for children in the rural area where age, allergy, asthma in family, passive smoking, and PM fraction had significant coefficients.



### December 2009 E-288

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Peel et al. (2005, 056305 ) Period of Study: Jan 1993-Aug 2000

Location: Atlanta, Georgia Hospital Admission/ED:

ED visits

Outcome: Asthma 493, 786.09 COPD 491, 492, 496 URI 460-466, 477 Pneumonia 480-486 Age Groups: All ages. Secondary analyses conducted by age group: Infants 0-1 yr Pediatric asthma 2-18 yr Adults >18 yr Study Design: Case-control All respiratory disease vs. finger wounds

N: 31 hospitals ED visits NR Statistical Analyses: Poisson generalized linear models

General linear models

Covariates: Avg temperature and dew point, pollen counts

Season: All Dose-response Investigated? Y es Statistical Package: SAS 8.3 S-Plus 2000 Lags Considered: 0-7 days and 14-day distributed lag Pollutant: UF (10-100nm) Averaging Time: 24-h avg Mean (SD): 3800 (40700)

Percentiles:

10th: 11500

90th: 74600 PM Component: Oxygenated hydrocarbons (OH), sulfate, acidity, EC (EC), OC (OC), water-soluble transition metals Monitoring Stations: “Several” Copollutant (correlation):

PM 10 : r = -0.13

O 3 : r = -0.13

NO 2 : r = 0.26

CO: r = 0.10

SO 2 : r = 0.24

PM 2.5 : r = -0.16

PM 10-2.5 : r = 0.13 Increment: 30,000 #/cm 3 All Respiratory Disease 0.984 [0.968-1.000]

URI 0.986 [0.966, 1.006]

Asthma 0.999 [0.977, 1.021]

Pneumonia 0.997 [0.953, 1.002]

COPD 0.982 [0.942, 1.022]

Reference: Simpson et al. (2005, 087438 ) Period of Study: 1996-1999

Location: Brisbane, Sydney, Melbourne, and Perth, Australia Outcome: All Respiratory (460-519) Asthma (493) COPD (490-492) Pneumonia, acute bronchitis (466, 480-486) Age Groups: All ages, split into f15-64 and >64 yr Study Design: Time-series

N: NR ~64,000 admissions Statistical Analyses: GAM w/ LOESS smoothers GLM w/ natural and penalized spline smoothers

Covariates: Temperature, relative humidity, rain, day of the week, public and school holidays, influenza epidemics, and controlled burn events

Season: All Dose-response Investigated? Yes Statistical Package: S-Plus

R Lags Considered: 1-3 days, 0- to 1-day avg Pollutant: BSP (indicator of particles <2 μm in diameter) (10 -4 m -1) Averaging Time: 24-h avg Mean (SD): Means only

Brisbane 0.3 10 -4 m -1 Sydney 0.3 10 -4 m -1

Melbourne 0.3 10 -4 m -1

Perth 0.3 10 -4 m -1 Range (Min, Max): Brisbane 0.0, 2.5 10 -4 m -1 Sydney 0.0, 1.6 10 -4 m -1 Melbourne 0.0, 2.2 10 -4 m -1 Perth 0.1, 1.8 10 -4 m -1 PM Component: Monitoring Stations: “network of sites across each city” Copollutant (correlation): NR PM Increment: “per unit increase” RR Estimate [Lower CI, Upper CI] lag: Single pollutant model Respiratory >64 yr 1.0401 [1.0045, 1.0770] lag1 1.0520 [1.0164, 1.0889] lag2; 1.0451 [1.0093, 1.0821] lag3 1.0552 [1.0082, 1.1045] lag 0-1 avg Asthma 15-64 yr 1.0641 [1.0006, 1.1315] lag2 1.0893 [1.0240, 1.1587] lag3 Asthma + COPD >64 yr 1.0713 [1.0179, 1.1276] lag3 1.0552 [1.0082, 1.1045] lag 0-1 avg Pneumonia & Acute Bronchitis >64 yr 1.0587 [1.0013, 1.1193] lag1 1.0636 [1.0056, 1.1249] lag 2 1.0769 [1.0046, 1.1544] lag 0-1 avg Multipollutant model Respiratory admissions >64 yr No other pollutants: 1.0552 [1.0082, 1.1045] lag 0-1 avg Max 1 h NO 2 1.0028 [0.9513, 1.0572] lag 0-1 avg Max 1 h O 3 1.0534 [1.0058-1.1033] lag 0-1 avg



### December 2009 E-289

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sinclair and Tolsma (2004, 088696 ) Period of Study: 25 mo

Location: Atlanta, Georgia Outpatient Visits

Outcome: Asthma (493) URI (460, 461, 462, 463, 464, 465, 466, 477) LRI (466.1, 480, 481, 482, 483, 484, 485, 486). Age Groups: < = 18 yr; 18+ yr (asthma); All ages (URI//LRI) Study Design: Times series

N: 25 mo 260,000-275,000 health plan members (Aug 1998-Aug 2000) Statistical Analyses: Poisson GLM

Covariates: Season, day of week, federal holidays, study months

Season: NR Dose-response Investigated?: No Statistical Package: SAS Lags Considered: Three 3-day ma (0-2, 2-5, 6-8) Pollutant: PM 2.5-10 (μg/m 3 ) Averaging Time: 24-h avg Mean (SD): PM coarse mass (2.5-10 μm)-9.67 μg/m 3 (4.74) Monitoring Stations: 1 Copollutant (correlation): NR PM Increment: 4.74 (1 SD) RR Estimate [Lower CI, Upper CI] lag:

Child Asthma: Coarse PM = 1.053 (S) 3-5 day lag

URI: Course PM = 1.021 (S) 3-5 day lag

LRI: Coarse PM = 1.07 (S) 3-5 day lag

Notes: Numerical findings for significant results only presented in manuscript. Results for all lags presented graphically for each outcome (asthma, URI, and LRI).

Reference: Sinclair and Tolsma (2004, 088696 ) Period of Study: 25 mo

Location: Atlanta, Georgia Outpatient Visits

Outcome: Asthma (493) URI (460, 461, 462, 463, 464, 465, 466, 477) LRI (466.1, 480, 481, 482, 483, 484, 485, 486). Age Groups: < = 18 yr, 18+ yr (asthma) All ages (URI//LRI) Study Design: Times series

N: 25 mo 260,000-275,000 health plan members (Aug 1998-Aug 2000) Statistical Analyses: Poisson GLM

Covariates: Season, day of week, federal holidays, study months

Season: NR Dose-response Investigated?: No Statistical Package: SAS Lags Considered: Three 3-day ma (0-2, 2-5, 6-8) Pollutant: UF (PM 10 -100 nm) Averaging Time: 24 h avg Mean (SD): PM 10 -100 nm area (μm2/cm 3 )- 249.33 (244.09) Monitoring Stations: 1 Copollutant (correlation): NR PM Increment: NR RR Estimate [Lower CI, Upper CI] lag:

Adult Asthma: Ultrafine PM area = 1.223 (S) 3-5 days lag

URI: Ultrafine PM: = 1.041 (S) 0-2 days lag

LRI: Ultrafine PM area = 1.099 (S) 6-8 days lag

Notes: Numerical findings for significant results only presented in manuscript. Results for all lags presented graphically for each outcome (asthma, URI, and LRI).



### December 2009 E-290

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 1995-Jun 2001

Location: Spokane, WA Hospital Admissions and ED visits Outcome: All respiratory (460-519) Asthma (493) COPD (491,492, 494,496) Pneumonia (480-487) Acute URI not including colds and sinusitis (464, 466, 490) Age Groups: All, 15+ yr for COPD Study Design: Time series

N: 2373 visit records Statistical Analyses: Poisson regression, GLM with natural splines. For comparison also used GAM with smoothing splines and default convergence criteria.

Covariates: Season, temperature, relative humidity, day of week

Season: All Dose-response Investigated?: No Statistical Package: SAS, SPLUS Lags Considered: 1 -3 days Pollutant: PM 1 Averaging Time: 24-h avg Range (90% of concentrations): 3.3-17.6 μg/m 3 Monitoring Stations: 1 Copollutant (correlation): PM 1 PM 2.5 r = 0.95

PM 10 r = 0.50

PM 10-2.5 r = 0.19

CO r = 0.63 PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag:

ED visits:

PM 1 All Respiratory Lag 1: 1.01 [0.98, 1.04] Lag 2: 1.02 [0.99, 1.06] Lag 3: 1.02 [0.99,1.06]

Acute Asthma Lag 1: 1.03 [0.97, 1.09] Lag 2: 0.99 [0.93, 1.05] Lag 3: 1.02 [0.96, 1.08] COPD (adult) Lag 1: 0.96 [0.87, 1.05] Lag 2: 1.02 [0.93, 1.12] Lag 3: 0.99 [0.90, 1.09]

Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 1995-Jun 2001

Location: Spokane, WA Hospital Admissions and ED visits Outcome: All respiratory (460-519) Asthma (493) COPD (491,492, 494,496) Pneumonia (480-487) Acute URI not including colds and sinusitis (464, 466, 490) Age Groups: All, 15+ yr for COPD Study Design: Time series

N: 2373 visit records Statistical Analyses: Poisson regression, GLM with natural splines. For comparison also used GAM with smoothing splines and default convergence criteria.

Covariates: Season, temperature, relative humidity, day of week

Season: All Dose-response Investigated?: No Statistical Package: SAS, SPLUS Lags Considered: 1 -3 days Pollutant: PM 2.5 Averaging Time: 24-h avg Range (90% of Concentrations): 4.2-20.2 μg/m 3 Monitoring Stations: 1 Notes: Copollutant (correlation): PM 2.5 PM1 r = 0.95

PM 10 r = 0.62

PM 10-2.5 r = 0.31

CO r = 0.62 Temperature r = 0.21 PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: ER visits: PM 2.5 All Respiratory Lag 1: 1.01 [0.98, 1.04] Lag 2: 1.02 [0.99, 1.04] Lag 3: 1.02 [0.99, 1.05] Acute Asthma Lag 1: 1.03 [0.98, 1.09] Lag 2: 1.00 [0.95, 1.05] Lag 3: 1.01 [0.96, 1.06] COPD (adult) Lag 1: 0.96 [0.89, 1.04] Lag 2: 1.01 [0.93, 1.09] Lag 3: 1.00 [0.93, 1.08] Hospital Admissions: PM 2.5 All Respiratory Lag 1: 0.98 [0.94, 1.01] Lag 2: 0.99 [0.96, 1.03] Lag 3: 1.01 [ 0.98, 1.05] Asthma Lag 1: 1.01 [0.91, 1.11] Lag 2: 1.03 [0.94, 1.13] Lag 3: 1.02 [0.93, 1.13] COPD (adult) Lag 1: 0.99 [0.91, 1.08] Lag 2: 1.06 [0.98, 1.16] Lag 3: 1.03 [0.94, 1.12]



### December 2009 E-291

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zanobetti and Schwartz (2006, 090195 ) Period of Study: 1995-1999

Location: Boston, MA Outcome: Pneumonia (480-487) Age Groups: >65 y Study Design: Case-crossover, time stratified

N: 24,857 for Pneumonia Statistical Analyses: Condition logistic regression

Covariates: Season, long term trend, day of-the-wk, mean temperature, relative humidity, barometric pressure, extinction coefficient

Season: All yr Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-1

Notes: Also looked at MI cohort Pollutant: PM 2.5 Averaging Time: 24 h

Percentiles (pneumonia cohort) : 25th: 7.23 μg/m 3 50th(Median): 11.10

75th: 16.14 PM Component: Black Carbon (BC), PM non-traffic Monitoring Stations: 4-5 monitors Copollutant (correlation): PM 2.5 : CO r = 0.52 NO 2 r = 0.55 O 3 r = 0.20 BC r = 0.66 PM non-traffic r = 0.74 PM Increment: PM 2.5 lag 0: 17.17 μg/m 3

PM 2.5 lag 0-1 avg: 16.32 μg/m 3 % change in Pneumonia: 6.48[1.13, 11.43] lag 0 5.56[-0.45, 11.27] mean lag 1

Reference: Zanobetti and Schwartz (2006, 090195 ) Period of Study: 1995-1999

Location: Boston, MA Outcome: Pneumonia (480-487) Age Groups: >65 y Study Design: Case-crossover, time stratified

N: 24,857 for Pneumonia Statistical Analyses: Condition logistic regression

Covariates: Season, long term trend, day of-the-wk, mean temperature, relative humidity, barometric pressure, extinction coefficient

Season: All yr Dose-response Investigated? No Statistical Package: SAS Lags Considered: 0-1

Notes: Also looked at MI cohort Pollutant: BC Averaging Time: 24 h Percentiles (pneumonia cohort) : 5th: 0.42 25th: 0.74 μg/m 3 50th(Median): 1.15 75th: 1.72 95th: 2.83 PM Component: PM non-traffic Monitoring Stations: 4-5 monitors Copollutant (correlation): BC: PM r = 0.66

2.5 CO r = 0.82 NO 2 r = 0.70 O r = -0.25

3 PM non-traffic r = -0.01 PM Increment: BC lag 0: 2.05 μg/m 3 BC lag 0-1 avg: 1.69 μg/m 3 % change in Pneumonia: BC-10.76[4.54, 15.89] lag 0 BC-11.71[4.79, 17.36] mean lag 1

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-292

# E.3. Short-Term Exposure and Mortality

Table E-16. Short-term exposure-mortality - PM 10 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Aga et al. (2003, 054808 ) Period of Study: ~5 yr for most cities, during the 1990s

Location: 28 European cities (APHEA2) Outcome: Nonaccidental Mortality (<800) Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups: All ages

>65 Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): (15, 66) Copollutant: BS

Note: PM 10 only measured in 21 cities. Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: All ages Fixed effects: 0.71% (0.60,0.83) 0-1 Random effects: 0.67% (0.47,0.87) 0-1 >65 Fixed effects: 0.79% (0.66,0.92) 0-1 Random effects: 0.74% (0.52,0.95) 0-1 Models with effect modifiers (>65) 24-h NO : 2 25th Percentile: 0.30% (0.07,0.53) 75th Percentile: 0.97% (0.82,1.11) 24-h temperature: 25th Percentile: 0.44% (0.25,0.64) 75th Percentile: 0.91% (0.77,1.05) 24-h relative humidity: 25th Percentile: 0.98% (0.82,1.14) 75th Percentile: 0.52% (0.33,0.71) Age standardized annual mortality rate: 25th Percentile: 0.93% (0.77,1.09) 75th Percentile: 0.61% (0.43,0.79) Proportion individuals >65 25th Percentile: 0.67% (0.50,0.83) 75th Percentile: 0.85% (0.71,0.99) Northwest/Central East: 25th Percentile: 0.81% (0.63,0.98) 75th Percentile: 0.26% (-0.05,0.57) Northwest/South: 25th Percentile: 0.81% (0.63,0.98) 75th Percentile: 1.04% (0.81,1.27) Reference: Analitis et al. (2006, 088177 ) Period of Study: NR

Location: 29 European cities (APHEA2) Outcome: Mortality: Cardiovascular diseases (390-459) Respiratory diseases (460-519) Study Design: Time-series Statistical Analyses: 2-stage hierarchical modeling Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: Range: 9-64 μg/m 3 Range (Min, Max): NR Copollutant: BS

Note: PM 10 only measured in 21 cities. Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Cardiovascular: Fixed effects: 0.64% (0.47, 0.80) 0-1 Random effects: 0.76% (0.47, 1.05) 0-1 0.90% (0.57, 1.23) 0-5 Respiratory: Fixed effects: 0.58% (0.21, 0.95) 0-1 Random effects: 0.71% (0.22, 1.20) 0-1 1.24% (0.49, 1.99) 0-5 Reference: Ballester et al. (2002, 030371 ) Period of Study: 1990-1996

Location: 13 Spanish cities Outcome: Mortality: Nonaccidental (<800) Cardiovascular diseases (390-459) Respiratory diseases (460-519) Study Design: Ecological time series Statistical Analyses: Poisson GAM, LOESS Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Huelva: 42.5 (15) Madrid: 37.8 (17.7) Sevilla: 45.1 (14) Range (Min, Max): NR Copollutant: BS

TSP

SO 2 Note: PM 10 only measured in 3 cities. Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Nonaccidental: Random effects: 1.006 (0.998, 1.015) 0-1 Fixed Effects: 1.005 (1.001, 1.010) 0-1 PM +SO : 1.013 (1.006, 1.020) 0-1

10 2 Cardiovascular: 1.012 (1.005, 1.018) 0-1 PM +SO :

10 2 Random effects: 1.024 (1.001, 1.048) 0-1 Fixed effects: 1.021 (1.007, 1.035) 0-1 Respiratory: 1.013 (1.001, 1.026) 0-1 PM 10 +SO 2 : 1.003 (0.983, 1.023) 0-1



### December 2009 E-293

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bateson and Schwartz (2004, 086244 ) Period of Study: 1988-1991

Location: Cook County, Illinois Outcome: Mortality: Heart Disease (390-429) Respiratory (460-519) Study Design: Bi-directional casecrossover Statistical Analyses: Conditional logistic regression Age Groups: ≥ 65 Study population: 65,180 elderly residents with history of hospitalization for heart or lung disease Pollutant: PM 10 Averaging Time: 24-h avg Mean (SE) unit: 37.6 (15.5) μg/m 3 Range (Min, Max): (3.7, 128) Copollutant: NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: All-cause: 1.14% (0.44, 1.85) 0-1 Modification of Effect by Prior Diagnosis Myocardial Infarction: 1.98% (-0.25, 4.26) 0-1 Diabetes: 1.49% (-0.06, 3.07) 0-1 Congestive heart failure: 1.28% (-0.06, 2.64) 0-1 COPD: 0.58% (-0.82, 2.00) 0-1 Conduction Disorders: 0.64% (-0.61, 1.90) 0-1 All other heart or lung diseases: 0.74% (-0.29, 1.79) 0-1

All-cause Men 65: 2.0% (0.3, 3.8) 0-1 75: 1.5% (-0.2, 3.1) 0-1 85: 0.9% (-0.7, 2.5) 0-1 95: 0.3% (-1.3, 1.9) 0-1 All: 1.3% (0.4, 2.3) 0-1 Women 65: 0.1% (-1.6, 1.9) 0-1 75: 0.7% (-1.1, 2.4) 0-1 85: 1.2% (-0.5, 3.0) 0-1 95: 1.8% (0.03, 3.6) 0-1 All: 1.0% (0.1, 1.9) 0-1 Total 65: 1.1% (-0.12, 2.3) 0-1 75: 1.1% (-0.1, 2.3) 0-1 85: 1.2% (-0.0, 2.4) 0-1 95: 1.2% (0.0, 2.4) 0-1 All: 1.1% (0.4, 1.9) 0-1 Reference: Bell et al. (2009, 191007 ) Period of Study: 1987-2000

Location: 84 U.S. Counties Outcome: Mortality Study Design: Time-series

Covariates: Socio-economic conditions, long term temperature Statistical Analysis: Bayesian hierarchical model Age Groups: All Pollutant: PM 10 Averaging Time: 24 h Mean (SD) Unit: NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 20% of the population acquiring air conditioning Percent Change (95% CI) in community-specific PM health effect estimates for mortality Any AC, including window units Yearly health effect: -30.4 (-80.4-19.6) Summer health effect: 29.9 (-84-144) Winter health effect: -573 (-9100-7955) Central AC Yearly health effect: -39 (-81.4-3.3) Summer health effect: 20. (-60.3-64.3) Winter health effect: -1777 (-5755-2201) Reference: Bell et al. (2007, 093256 ) Period of Study: 1999-2005

Location: U.S. Outcome: Mortality Age Groups: 65+ Study Design: Time series

N: NR Statistical Analyses: Bayesian Hierarchical Regression

Covariates: Time trend, day of week, seasonality, dew point, temperature Statistical Package: NR Lags Considered: 0-2 Pollutant: PM 10 Averaging Time: Daily

Mean: Ni: 0.002

Min: Ni: 0.003

Max: Ni: 0.021 Interquartile Range: Ni: 0.001 Interquartile Range of Percents: Ni: 0.01 Monitoring Stations: NR Copollutant: Al, NH4+, As, Ca, Cl, Cu, EC, OMC, Fe, Pb, Mg. Ni, NO 3 -, K, Si, Na+, SO 4 =, Ti, V, Zn Co-pollutant Correlation Ni, V: 0.48 Ni, EC: 0.30

Note: Pollutant concentrations available for all fractions of PM 2.5 PM Increment: Interquartile Range in the fraction of PM 2.5 Percent Increase in PM 10 Health Effect (Lower CI, Upper CI) Ni: 14.8 (-8.1, 37.7), lag 0 Ni: 14.7 (4.0, 25.3), lag 1 Ni: 14.7 (1.8, 27.5), lag 2 HS education: -31.9 (-82.4, 18.6) median income: -12.3 (-62.3, 37.7) Percent black: 48.7 (-15.8, 113) Percent living in urban area: -20.1 (- 102, 61.7) Population: 5.1 (-14.4, 24.5)

Notes: Interquartile ranges in percent HS education, median income, percent black, percent living in urban area, and population are 5.2 %, $9,223, 17.3%, 11.0%, and 549,283 respectively.



### December 2009 E-294

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bellini et al. (2007, 097787 ) Period of Study: 1996-2002

Location: 15 Italian cities Outcome: Mortality All-cause (nonaccidental) (<800) Cardiovascular (390-459) Respiratory (460-519) Study Design: Meta-analysis Statistical Analyses: Poisson GLM Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant: SO 2 NO 2 CO

O 3 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: All-cause: 0.31% (-0.19, 0.74) 0-1 Winter: 0.08% 0-1 Summer: 1.95% 0-1 PM 10 +O 3 : 0.30% 0-1 PM 10 +NO 2 : 0.08% 0-1 Respiratory: 0.54% (-0.91, 1.74) 0-1 Winter: 0.27% 0-1 Summer: 3.61% 0-1 PM 10 +O 3 : 0.55% 0-1 PM 10 +NO 2 : 0.19% 0-1 Cardiovascular: 0.54% (0.02, 1.02) 0-1 Winter: 0.20% 0-1 Summer: 2.79% 0-1 PM 10 +O 3 : 0.57% 0-1 PM 10 +NO 2 : 0.39% 0-1 Reference: Burnett et al. (2004, 086247 ) Period of Study: 1981-1999

Location: 12 Canadian cities Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: 1. Poisson, natural splines 2. Random effects regression model Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): PM 2.5 : 12.8 PM 10-2.5 : 11.4 Range (Min, Max): NR Copollutant (correlation): NO 2 O 3 SO 2 CO

Note: PM 10 measurement calculated as the sum of PM 2.5 and PM 10-2.5 measurements. Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag:

1981-1999

PM 10 : 0.57% (0.05, 0.89) 1

PM 10 +NO 2 : 0.07% (-0.44, 0.58) 1

Reference: Cakmak et al. (2007, 091170 ) Period of Study: Jan 1997-Dec 2003

Location: Chile-7 cities Outcome: Mortality: Nonaccidental (<800) Cardiovascular diseases (390-459) Respiratory diseases (460-519) Study Design: Time-series Statistical Analyses: Poisson Random effects regression model Age Groups: All age

≤ 64 yr 65-74 yr 75-84 yr

≥ 85 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 84.9 Range (Min, Max): NR Copollutant (correlation): O 3 : r = -0.16-0.13

SO 2 : r = 0.37-0.77

CO: r = 0.49-0.82

Note: Correlations are between pollutants for seven monitoring stations. Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental: 0.97% (-1.09, 2.76) 0 1.31% (-1.56, 3.68) 0-5 PM 10 +O 3 +SO 2 +CO: 0.80% (-0.87, 2.28) 0 ≤ 64: 0.52% (-0.55, 1.51) 0 0.49% (-0.51, 1.43) 0-5 65-75: 1.07% (-1.23, 3.03) 0 1.31% (-1.57, 3.69) 0-5 75-84: 1.41% (-1.71, 3.94) 0 1.93% (-2.57, 5.30) 0-5 ≥ 85: 1.56% (-1.94, 4.34) 0 2.14% (-2.97, 5.85) 0-5 Apr-Sep: 1.03% (-1.17, 2.93) 0 1.37% (-1.64, 3.82) 0-5 Oct-Mar: 0.07% (-0.07, 0.21) 0 0.15% (-0.15, 0.44) 0-5 Cardiovascular: 1.14% (-1.31, 3.21) 0 1.49% (-1.82, 4.14) 0-5 Respiratory: 2.03% (-2.75, 5.56) 0 3.11% (-5.25, 8.25) 0-5



### December 2009 E-295

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chen et al. (2008, 190106 ) Period of Study: 2001-2004

Location: Shanghai, China Outcome (ICD9: 2001; ICD10: 2002-2004): Mortality: Nonaccidental causes (ICD9 <800; ICD10 A00-R99) Cardiovascular (ICD9 390-459; I CD10 I00-I99) Respiratory (ICD9 460-519; ICD10 J00-J98) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 102.0 Range (Min, Max): (14.0-566.8) Copollutant (correlation):

SO 2 r = 0.64

NO 2 r = 0.71 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental Single Pollutant: 0.26% (0.14, 0.37) PM 10 +SO 2 : 0.08% (-0.07, 0.22) PM 10 +NO 2 : 0.01% (-0.14, 0.17) PM 10 +SO 2 +NO 2 : 0.00% (-0.16, 0.16) Cardiovascular mortality Single Pollutant: 0.27% (0.10, 0.44) PM 10 +SO 2 : 0.12% (-0.10, 0.34) PM 10 +NO 2 : 0.01% (-0.22, 0.25) PM 10 +SO 2 +NO 2 : 0.01% (-0.23, 0.25) Respiratory mortality Single Pollutant: 0.27% (-0.01, 0.56) PM 10 +SO 2 : -0.04% (-0.41, 0.33) PM 10 +NO 2 : -0.05% (-0.45, 0.34) PM 10 +SO 2 +NO 2 : -0.10% (-0.50, 0.30) Reference: Daniels et al. (2004, 087343 ) Period of Study: 1987-1994

Location: 20 Largest U.S. cities Outcome: Mortality: Total (Nonaccidental) mortality Cardiovascular-Respiratory (390-448) (480-486, 487, 490-496, 507) Other-cause mortality Study Design: Time-series Statistical Analyses: City-Specific Estimates: Poisson GLM, natural cubic splines Combined Estimates: 2-stage Bayesian hierarchical model Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Los Angeles: 46.0 New York: 28.8 Chicago: 35.6 Dallas-Ft. Worth: 23.8 Houston: 30.0 San Diego: 33.6 Santa Ana-Anaheim: 37.4 Phoenix: 39.7 Detroit: 40.9 Miami: 25.7 Philadelphia: 35.4 Minneapolis: 26.9 Seattle: 25.3 San Jose: 30.4 Cleveland: 45.1 San Bernardino: 37.0 Pittsburgh: 31.6 Oakland: 26.3 Atlanta: 34.4 San Antonio: 23.8 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Total (nonaccidental): 0.17% (0.03, 0.30) 0 0.20% (0.07, 0.33) 1 0.28% (0.16, 0.41) 0-1 avg Cardiovascular-Respiratory: 0.17% (-0.01, 0.35) 0 0.27% (0.09, 0.44) 1 0.30% (0.18, 0.51) 0-1 avg

Other-cause: 0.17% (-0.03, 0.37) 0 0.12% (-0.07, 0.31) 1 0.20% (0.01, 0.38) 0-1 avg

Threshold Models: Total Mortality Threshold = 15 μg/m 3 0.30% (0.17, 0.42) 0-1 avg Threshold = 0 μg/m 3 0.28% (0.16, 0.41) 0-1 avg Threshold = 20 μg/m 3 0.30% (0.16, 0.43) 0-1 avg



### December 2009 E-296

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: De Leon et al. (2003, 055688 ) Period of Study: Jan 1985-Dec 1994

Location: New York, New York Outcome: Mortality: Circulatory (390-459) Cancer (140-239) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups: All ages <75 yr >75 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 33.27 μg/m 3 IQR (25th, 75th): (22.67, 40.83) Copollutant (correlation):

O 3 CO

SO 2 NO 2 Increment: 18.16 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: All Ages Cancer: 1.014 (1.000, 1.029) 0-1 -w/out respiratory: 1.011 (0.996, 1.026) 0-1 -w/ respiratory: 1.051 (0.998, 1.107) 0-1 Circulatory: 1.025 (1.014, 1.035) 0-1 -w/out respiratory: 1.022 (1.012, 1.033) 0-1 -w/ respiratory: 1.054 (1.022, 1.086) 0-1 <75 yr Cancer: 1.003 (0.985, 1.021) 0-1 -w/out respiratory: 1.002 (0.983, 1.022) 0-1 -w/ respiratory: 1.009 (0.943, 1.078) 0-1 Circulatory: 1.027 (1.012, 1.043) 0-1 -w/out respiratory: 1.027 (1.011, 1.043) 0-1 -w/ respiratory: 1.033 (0.980, 1.089) 0-1 >75 yr Cancer: 1.033 (1.009, 1.058) 0-1 -w/out respiratory: 1.025 (1.000, 1.050) 0-1 -w/ respiratory: 1.129 (1.041, 1.225) 0-1 -w/out pneumonia: 1.026 (1.002, 1.050) 0-1 -w/ pneumonia: 1.183 (1.058, 1.323) 0-1 -w/out COPD: 1.032 (1.008, 1.057) 0-1 -w/ COPD: 1.008 (0.849, 1.197) 0-1 Circulatory: 1.025 (1.012, 1.038) 0-1 -w/out respiratory: 1.022 (1.008, 1.035) 0-1 -w/ respiratory: 1.066 (1.027, 1.106) 0-1 -w/out pneumonia: 1.023 (1.010, 1.036) 0-1 -w/ pneumonia: 1.078 (1.018, 1.141) 0-1 -w/out COPD: 1.025 (1.012, 1.038) 0-1 -w/ COPD: 1.058 (0.991, 1.130) 0-1 Reference: Dominici et al. (2003, 042804 ) Period of Study: 1987-1994

Location: 88 U.S. cities Outcome: Mortality: All-cause (nonaccidental) (<800) Cardiac (390-448) Respiratory (490-496) Influenza (487) Pneumonia (480-486, 507) Other causes Study Design: Time-series Statistical Analyses: 2-stage Bayesian hierarchical model Age Groups: <65 yr; 65-74 yr; ≥ 75 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Cardio-respiratory 0.31% (0.15, 0.50) 1

All-cause 0.22% (0.10, 0.38) 1

Other causes 0.13% (-0.05, 0.29) 1

Reference: Dominici et al. (2004, 059158 ) Period of Study: 1987-1994

Location: 90 U.S. cities (NMMAPS) Outcome: Mortality: Total (nonaccidental) Study Design: Time-series Statistical Analyses: Poisson. GAM, GLM Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag:

α = 3 0.2% (0.05, 0.35)



### December 2009 E-297

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Dominici et al. (2004, 096951 ) Period of Study: 1986-1993

Location: 10 U.S. cities Outcome: Mortality: Total (nonaccidental) Study Design: Time-series Statistical Analyses: 2-stage Bayesian hierarchical model Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Birmingham 34.8 Canton 28.4 Colorado Springs 27.5 Minneapolis/St. Paul 28.1 Seattle 32.2 Spokane 42.9 Chicago 36.3 Detroit 36.7 New Haven 28.6 Pittsburgh 36.0 New York: 28.8 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Combined analysis: 0.26% (-0.37, 0.65) 0-1 Separate analysis: 0.28% (-0.12, 0.63) 0-1

Notes: A separate analysis assumes the mortality data does not provide any information on the log relative rates of mortality.

Reference: Dominici et al. (2007, 097361 ) Period of Study: PM 10 : 1987-2000

PM 2.5 : 1999-2000

Location: 100 U.S. counties (NMMAPS) Outcome: Mortality: All-cause (nonaccidental) Cardiorespiratory

Other-cause Study Design: Time-series Statistical Analyses: 2-stage Bayesian hierarchical model Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: PM 10 All-cause: East: 1987-1994: 0.29% (0.12, 0.46) 1 1995-2000: 0.13% (-0.19, 0.44) 1 1987-2000: 0.25% (0.11, 0.39) 1 West: 1987-1994: 0.12% (-0.07, 0.30) 1 1995-2000: 0.18% (-0.07, 0.44) 1 1987-2000: 0.12% (-0.02, 0.26) 1 National: 1987-1994: 0.21% (0.10, 0.32) 1 1995-2000: 0.18% (0.00, 0.35) 1 1987-2000: 0.19% (0.10, 0.28) 1 Cardiorespiratory: East: 1987-1994: 0.39% (0.16, 0.63) 1 1995-2000: 0.30% (-0.13, 0.73) 1 1987-2000: 0.34% (0.15, 0.54) 1 West: 1987-1994: 0.17% (-0.07, 0.40) 1 1995-2000: 0.13% (-0.23, 0.50) 1 1987-2000: 0.14% (-0.05, 0.33) 1 National: 1987-1994: 0.28% (0.14, 0.43) 1 1995-2000: 0.21% (-0.03, 0.44) 1 1987-2000: 0.24% (0.13, 0.36) 1 Other-cause: East: 1987-1994: 0.21% (-0.03, 0.44) 1 1995-2000: 0.00% (-0.49, 0.50) 1 1987-2000: 0.15% (-0.09, 0.39) 1 West: 1987-1994: 0.09% (-0.21, 0.38) 1 1995-2000: 0.23% (-0.15, 0.62) 1 1987-2000: 0.17% (-0.07, 0.41) 1 National: 1987-1994: 0.15% (-0.02, 0.32) 1 1995-2000: 0.17% (-0.07, 0.41) 1 1987-2000: 0.15% (0.00, 0.29)1 Reference: Dominici et al. (2007, 099135 ) Period of Study: 2000-2005

Location: 72 U.S. counties representing 69 communities Outcome: Total mortality Study Design: Time-series Statistical Analyses: 2-stage Bayesian hierarchical model Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR The study does not provide results quantitatively.

Note: The study investigated whether county-specific short-term effects of PM 10 on mortality are modified by longterm county-specific nickel or vanadium PM 2.5 concentrations.



### December 2009 E-298

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Fischer et al. (2003, 043739 ) Period of Study: 1986-1994

Location: The Netherlands Outcome: Mortality: Nonaccidental (<800) Pneumonia (480-486) COPD (490-496) Cardiovascular (390-448) Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups: <45 yr 45-64 yr 65-74 yr ≥ 75 yr Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: 34 Range (Min, Max): (10, 278) Copollutant: BS

O 3 NO 2 SO 2 CO Increment: 80 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Cardiovascular <45: 0.906 (0.728, 1.128) 0-6 45-64: 1.023 (0.945, 1.106) 0-6 65-74: 1.002 (0.945, 1.062) 0-6 ≥ 75: 1.016 (0.981, 1.052) 0-6 COPD <45: 1.153 (0.587, 2.268) 0-6 45-64: 1.139 (0.841, 1.541) 0-6 65-74: 1.166 (0.991, 1.372) 0-6 ≥ 75: 1.066 (0.965, 1.178) 0-6 Pneumonia <45: 1.427 (0.806, 2.525) 0-6 45-64: 1.712 (1.042, 2.815) 0-6 65-74: 1.240 (0.879, 1.748) 0-6 ≥ 75: 1.123 (1.011, 1.247) 0-6 Reference: Fischer et al. (2004, 055605 ) Period of Study: Jun 2003-Aug 2003

Location: The Netherlands Outcome: Total mortality Study Design: NR Statistical Analyses: NR Age Groups: All ages Pollutant: PM 10 Averaging Time: Weekly avg Mean (SD): 2000: 31 2002: 33 2003: 35 IQR (25th, 75th): NR Copollutant: O 3 The study does not present quantitative results.

Notes: The study estimates the number of deaths attributable to PM 10 during the summers of 2000, 2002, and 2003.

Reference: Forastiere et al. (2005, 086323 ) Period of Study: 1998-2000

Location: Rome, Italy Outcome: Mortality: Ischemic heart disease (410-414) Study Design: Time-stratified casecrossover Statistical Analyses: Conditional logistic regression Age Groups: >35 Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 52.1 (22.2) IQR (25th, 75th): (36.0, 65.7) Copollutant (correlation): PNC: r = 0.38 CO: r = 0.34 NO 2 : r = 0.45 SO 2 : r = 0.23 O 3 : r = 0.13 Increment: 29.7 μg/m 3 % Increase (Lower CI, Upper CI) lag: 4.8% (0.1, 9.8) 0 4.9% (0.0, 10.1) 1 3.8% (-1.0, 8.9) 2 2.8% (-2.0, 7.7) 3 6.1% (0.6, 11.9) 0-1

Reference: Forastiere et al. (2007, 090720 ) Period of Study: 1998-2001

Location: Rome, Italy Outcome: Mortality: Natural (<800) Malignant neoplasms (140-208) Diabetes mellitus (250) Hypertensive disease (401-405) Previous acute myocardial infarction (410, 412) Other ischemic heart diseases (411, 413-414) Conduction disorders (426) Dysrhythmia (427) Heart failure (428) Cerebrovascular disease (430-438) Peripherical artery disease (440-448) COPD (490-496) Study Design: Time-stratified casecrossover Statistical Analyses: Conditional logistic regression Age Groups: >35 Pollutant: PM 10 Averaging Time: 24-h avg Mean Range (SD) unit: 51.0 (21.0) μg/m 3 IQR (25th, 75th): (36.1, 63.0) Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental: 1.1% (0.7, 1.6) 0-1

Low income: 1.9% 0-1

Low SES: 1.4% 0-1 High income: 0.0% 0-1 High SES: 0.1% 0-1 Low PM Area: 0.9% (-0.4, 2.1) 0-1 High PM Area: 1.47% (0.4, 2.5) 0-1



### December 2009 E-299

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Forastiere et al. (2008, 186937 ) Period of Study: 1997-2004

Location: 9 Italian cities Outcome: Mortality: Nonaccidental (<800) Study Design: Time-stratified case-

crossover Statistical Analyses: Conditional logistic regression Age Groups: >35 Pollutant: PM 10 Averaging Time: 24-h avg Mean Range (SD) unit:

35.1-71.5 Range (5th, 95th):

Lowest 5th: 14.3 Highest 95th: 147.0 Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Total: 0.60% (0.31, 0.89) 0-1 Age 35-64: -0.20% (-0.77, 0.37) 0-1 65-74: 0.51% (0.05, 0.98) 0-1 75-84: 0.59%(0.20, 0.97) 0-1 ≥ 85: 0.97% (0.53, 1.42) 0-1 ≥ 65: 0.75% (0.42, 1.09)

Sex Men: 0.72% (0.37, 1.07) 0-1 Women: 0.83% (0.33, 1.33) 0-1 Median income (by census block) Low (<20th percentile): 0.80% (-0.02, 1.62) 0-1 Mid-low (20th-50th percentile): 0.68% (0.25, 1.12) 0-1 Mid-high (51st-80th percentile): 0.85% (0.40, 1.30) 0-1 High (>80th percentile): 0.30% (-0.25, 0.86) 0-1

Location of death Out-of-hospital: 0.71% (0.32, 1.11) 0-1 Discharged 2-28 days before death: 1.34% (0.49, 2.20) 0-1 In-hospital: 0.65% (0.33, 0.97) 0-1 Nursing home: -0.04% (-1.02, 0.95) 0-1 Reference: Goldberg et al. (2003, 035202 ) Period of Study: 1984-1993

Location: Montreal, Quebec, Canada Outcome: Mortality: Congestive Heart Failure (428) Study Design: Time-series Statistical Analyses: Poisson, natural splines Age Groups: ≥ 65 Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): PM 10 : 32.2 (17.6) IQR (25th, 75th): PM 10 : (19.7, 41.1) Copollutant (correlation): PM 2.5 , TSP, Sulfate, CoH, SO 2 , NO 2 , CO, O 3 This study does not present results quantitatively for PM 10

Reference: Goldberg et al. (2003, 035202 ) Period of Study: 1984-1993

Location: Montreal, Quebec, Canada Outcome: Mortality: Diabetes (250) Study Design: Time-series Statistical Analyses: Poisson, natural spline Age Groups: ≥ 65 Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): PM 10 : 32.2 (17.6) μg/m 3 IQR (25th, 75th): PM 10 : (19.7, 41.1) Copollutant (correlation): PM 2.5 , Sulfate, CoH, SO 2 , NO 2 , CO, O 3 This study does not present results quantitatively for PM 10

Reference: Kan and Chen (2003, 087372 ) Period of Study: Jan 2000-Dec 2001

Location: Shanghai, China Outcome: Mortality: Nonaccidental (<800) Cardiovascular (390-459) COPD (490-496) Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups: All ages <65 yr 65-75 yr >75 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 91.14 (51.85) Range (Min, Max): (17.0, 385.0) Copollutant (correlation):

SO 2 : r = 0.71

NO 2 : r = 0.73 Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Nonaccidental: All ages: 1.003 (1.001, 1.005) 0 <65: 1.001 (0.997, 1.005) 0 65-75: 1.005 (1.001, 1.008) 0 >75: 1.003 (1.001, 1.006) 0

Cardiovascular: All ages: 1.003 (1.000, 1.006) 0 <65: 1.002 (0.994, 1.010) 0 65-75: 1.003 (0.998, 1.008) 0 >75: 1.003 (1.000, 1.006) 0

COPD: All ages: 1.005 (0.999, 1.011) 0 <65: 1.004 (0.981, 1.027) 0 65-75: 0.996 (0.986, 1.007) 0 >75: 1.006 (1.000, 1.012) 0

Multipollutant models: SO 2 : 1.001 (0.998, 1.003) 0 NO 2 : 1.001 (0.998, 1.003) 0 SO 2 +NO 2 : 1.000 (0.997, 1.003) 0



### December 2009 E-300

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Kan and Chen (2003, 087372 ) Period of Study: Jan 2000-Dec 2001

Location: Shanghai, China Outcome: Mortality: Nonaccidental (<800) Cardiovascular (390-459) COPD (490-496) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 91.14 (51.85) IQR (25th, 75th): (54, 114) Copollutant (correlation):

SO 2 : r = 0.71

NO 2 : r = 0.73 Increment: 10 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag: Nonaccidental: Bidirectional referent days: 7 days: 1.000 (0.9988, 1.002) 0-1 ma 7 and 14 days: 1.002 (1.000, 1.004) 0-1 ma 7, 14, and 21 days: 1.003 (1.001, 1.005) 0-1 ma Unidirectional referent days: 7 days: 1.015 (1.012, 1.018) 0-1 ma 7 and 14 days: 1.017 (1.015, 1.019) 0-1 ma 7, 14, and 21 days: 1.019 (1.012, 1.021) 0-1 ma Bidirectional referent days (7, 14, and 21 days): Cardiovascular: 1.004 (1.001, 1.007) 0-1 ma COPD: 1.006 (0.999, 1.013) 0-1 ma Nonaccidental: PM 10 +SO 2 : 0.997 (0.994, 1.025) 0-1 ma PM 10 +NO 2 : 0.997 (0.994, 1.025) 0-1 ma PM 10 +SO 2 +NO 2 : 0.995 (0.992, 1.025) 0-1 ma Reference: Kan et al. (2005, 087561 ) Period of Study: Apr 2003-May 2003

Location: Beijing, China Outcome: Mortality: Severe acute respiratory syndrome (SARS) Study Design: Time-series Statistical Analyses: Poisson, GAM, smoothing spline Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 149.1 (8.1) Range (Min, Max): (34, 246) Copollutant:

SO 2 NO 2 Increment: 10 μg/m 3

R elative Risk (Lower CI, Upper CI) lag: 0.99 (0.96-1.03) 0 1.00 (0.97-1.04) 1 1.02 (0.98-1.06) 2 1.04 (0.99-1.09) 3 1.06 (1.00-1.11) 4 1.06 (1.00-1.12) 5 1.05 (0.98-1.12) 6

Reference: Kan et al. (2007, 091267 ) Period of Study: Mar 2004-Dec 2005

Location: Shanghai, China Outcome (ICD10): Mortality: Total (nonaccidental) (A00-R99) Cardiovascular (I00-I99) Respiratory (J00-J98) Study Design: Time-series Statistical Analyses: Poisson GAM, penalized splines Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 107.9 (2.39) μg/m 3 Range (Min, Max): (22.0, 403.0) Copollutant (correlation): PM 10 PM 2.5 : r = 0.84 PM 10-2.5 : r = 0.88 O 3 : r = 0.21 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag:

PM 10 Total: 0.16% (0.02, 0.30) 0-1 Cardiovascular: 0.31% (0.10, 0.53) 0-1 Respiratory: 0.33% (-0.08, 0.75) 0-1



### December 2009 E-301

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Kan et al. (2008, 156621 ) Period of Study: Jan 2001-Dec 2004

Location: Shanghai, China Outcome: Mortality: Total (nonaccidental) (A00-R99) Cardiovascular (I00-I99) Respiratory (J00-J98) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages; 0-4 yr 5-44 yr 45-64 yr

≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Warm season: 87.4 (1.8) Cool season: 116.7 (2.8) Entire period: 102.0 (1.7) Range (Min, Max): NR Copollutant (correlation): SO 2 NO 2 O 3 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental Warm season: 0.21 (0.09, 0.3) 0-1 Cool season: 0.26 (0.22, 0.30) 0-1 Entire period: 0.25 (0.14, 0.37) 0-1 Female: 0.33 (0.18, 0.48) 0-1 Male: 0.17 (0.03, 0.32) 0-1 5-44: 0.04 (-0.52, 0.59) 0-1 45-64: 0.17 (-0.11, 0.45) 0-1 ≥ 65: 0.26 (0.15, 0.38) 0-1 Cardiovascular Warm season: 0.22 (-0.14, 0.58) 0-1 Cool season: 0.25 (0.05, 0.45) 0-1 Entire period: 0.27 (0.10, 0.44) 0-1 Respiratory Warm season: -0.28 (-0.93, 0.38) 0-1 Cool season: 0.58 (0.25, 0.92) 0-1 Entire period: 0.27 (-0.01, 0.56) 0-1 Stratified by Educational Attainment Nonaccidental: Low: 0.33 (0.19, 0.47) 0-1 High: 0.18 (0.01, 0.36) 0-1 Cardiovascular: Low: 0.30 (0.10, 0.51) 0-1 High: 0.23 (-0.03, 0.50) 0-1 Respiratory: Low: 0.36 (0.00, 0.72) 0-1 High: 0.02 (-0.43, 0.47) 0-1 Reference: Keatinge and Donaldson (2006, 087536 ) Period of Study: 1991-2002

Location: London, England Outcome: Mortality: Total (nonaccidental) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups: ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant: O 3 SO 2 Increment: 10 μg/m 3 Mortality per 106 (Lower CI, Upper CI) lag: PM 10 +Temp: 2.1 (0.9, 3.3) 0-2 avg PM 10 +Temp+Acclim: 1.6 (0.4, 2.8) 0-2 avg PM 10 +Temp+Acclim+Acclim x T: 1.5 (0.3, 2.6) 0-2 avg PM 10 +Temp+Acclim+Acclim x T+Sun: 1.4 (0.2, 2.5) 0-2 avg PM 10 +Temp+Acclim+Acclim x T+Sun+Wind: 0.8 (-0.4, 1.9) 0-2 avg PM 10 +Temp+Acclim+Acclim x T+Sun+Wind+Abs. Humid.: 0.8 (-0.3, 1.9) 0-2 avg PM 10 +Temp+Acclim+Acclim x T+Sun+Wind+Abs. Humid.+ Rain: 0.9 (-0.3, 2.0) 0-2 avg PM 10 +Temp+Abs. Humid.: 1.9 (0.7, 3.1) 0-2 avg Reference: Kettunen et al. (2007, 091242 ) Period of Study: 1998-2004

Location: Helsinki, Finland Outcome (ICD10): Mortality: Stroke (I60-I61, I63-I64) Study Design: Time-series Statistical Analyses: Poisson GAM, penalized thin-plate splines Age Groups: ≥ 65 Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: Cold Season: 16.3 Warm Season: 16.5 Range (Min, Max): Cold Season: (3.1, 136.7) Warm Season: (3.3, 67.4) Copollutant: PM 2.5 PM 10-2.5 UFP O 3 CO NO 2 Increment: Cold Season: 13.8 μg/m 3 Warm Season: 9.8 μg/m 3 % Increase (Lower CI, Upper CI) lag: Cold Season -0.56% (-3.32, 2.29) 0 -0.93% (-3.55, 1.75) 1 -1.68% (-4.30, 1.00) 2 -1.53% (-4.14, 1.14) 3

Warm Season 10.89% (0.95, 21.81) 0 8.56% (-0.88, 18.90) 1 2.06% (-6.76, 11.71) 2 -2.89% (-11.32, 6.34) 3



### December 2009 E-302

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Kim et al. (2003, 155899 ) Period of Study: Jan 1995-Dec 1999

Location: Seoul, Korea Outcome (ICD10): Mortality: Nonaccidental (all except S01-S99, T01-T98) Cardiovascular (I00-I52) Respiratory (J00-J98) Cerebrovascular (I60-I69) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 69.19 (10.36) IQR (25th, 75th): (44.82, 87.95) Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: All cause: 2.8% (1.8, 3.7) 0 2.8% (1.9, 3.7) 1 1.4% (0.5, 2.3) 2 3.7% (2.1, 5.4) distributed lag (6-day)

Respiratory: 8.3% (4.3, 12.5) 0 6.4% (2.7, 10.2) 1 6.5% (2.7, 10.4) 2 13.9% (6.8, 21.5) distributed lag (6-day)

Pneumonia: 11.6% (4.2, 19.6) 0 9.0% (2.1, 16.3) 1 7.7% (0.8, 15.2) 2 17.1% (4.1, 31.7) distributed lag (6-day ) COPD: 4.2% (-1.2, 10.0) 0 3.5% (-1.5, 8.9) 1 1.4% (-3.7, 6.8) 2 12.2% (2.5, 22.9) distributed lag (6-day ) Cardiovascular: 2.0% (-0.9, 5.0) 0 3.3% (0.6, 6.2) 1 2.9% (0.1, 5.8) 2 4.4% (-0.6, 9.6) distributed lag (6-day) Myocardial infarction: 2.6% (-2.3, 7.8) 0 5.8% (1.0, 10.7) 1 5.5% (0.7, 10.6) 2 4.9% (-3.4, 13.9) distributed lag (6-day)

Cerebrovascular: 3.2% (0.8, 5.5) 0 3.1% (0.9, 5.3) 1 2.4% (0.1, 4.6) 2 6.3% (2.3, 10.5) distributed lag (6-day)

Ischemic stroke: -0.6% (-5.6, 4.7) 0 0.6% (-4.2, 5.7) 1 -0.1% (-4.9, 5.1) 2 10.3% (1.0, 20.4) distributed lag (6-day) Reference: Kim et al. (2004, 087417 ) Period of Study: Jan 1997-Dec 2001

Location: Seoul, Korea Outcome: Mortality: Nonaccidental Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 68.23 (36.36) μg/m 3 IQR (25th, 75th): (42.56, 84.67) Copollutant (correlation): NR Increment: 42.11 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: 1.021 (1.009, 1.035)



### December 2009 E-303

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Le Tertre et al. (2005, 087560 ) Period of Study: NR

Location: 21 European cities (APHEA-2) Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: Empirical Bayes Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant: NO 2 Increment: 1.0 μg/m 3 β coefficient (SE) lag: Athens: 0.001311 (0.0003) Barcelona: 0.000575 (0.0002) Basel: 0.000462 (0.0005) Birmingham: 0.000305 (0.0003) Budapest: -0.000248 (0.0005) Cracow: 0.000155 (0.0004) Erfurt: -0.000465 (0.0004) Geneva: -0.000059 (0.0005) Helsinki: 0.000389 (0.0004) London: 0.000591 (0.0002) Lyon: 0.001554 (0.0005) Madrid: 0.000372 (0.0003) Milan: 0.000901 (0.0002) Paris: 0.000411 (0.0003) Prague: 0.000097 (0.0002) Rome: (0.001333 (0.0003) Stockholm: 0.000479 (0.0009) Tel Aviv: 0.000522 (0.0003) Teplice: 0.000876 (0.0004) Torino: 0.000938 (0.0002) Zurich: 0.000365 (0.0004) Toulouse: NR (NR) Overall: 0.00055 (0.000098) Reference: Lee et al. (2007, 093042 ) Period of Study: Jan 2000-Dec 2004

Location: Seoul, Korea Outcome (ICD10): Mortality: Nonaccidental (A00-R99) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): w/ Asian dust days: 70.00 (47.80) w/o Asian dust days: 65.77 (33.60) Asian dust days only: 188.49 (142.85) Copollutant: CO NO 2 SO 2 O 3 Increment: 41.49 μg/m 3 % Increase (Lower CI, Upper CI) lag: Model with Asian Dust Days 0.7% (0.2, 1.3) 1-3 Model without Asian dust days 1.0% (0.2, 1.8) 1-3

Reference: Lee and Shaddick (2007, 156685 ) Period of Study: Jan 1993-Dec 1997

Location: Cleveland, Ohio Detroit, Michigan Minneapolis, Minnesota Pittsburgh, Pennsylvania Outcome (ICD10): Mortality:

Nonaccidental Study Design: Time-series Statistical Analyses: 1. Bayesian, penalized spline 2. Likelihood, penalized spline Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Constant model Cleveland: 1.0049 1 Detroit: 1.0046 1 Minneapolis: 1.0052 1 Pittsburgh: 1.0045 1 Reference: Martins et al. (2004, 087457 ) Period of Study: Jan 1997-Dec 1999

Location: São Paulo, Brazil Outcome (ICD10): Mortality: Respiratory (J00-J99) Study Design: Time-series Statistical Analyses: Poisson GLM, natural cubic splines Age Groups: ≥ 60 Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Cerqueira Cesar: 42.5(22.9) Santa Amaro: 49.6(32.1) Central: 52.1(23.5) Penha: 40.4(23.8) Santana: 72.6(24.5) Sao Miguel Paulista: 68.6(31.0) Range (Min, Max): NR The study does not present quantitative results.



### December 2009 E-304

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Nawrot et al. (2007, 098619 ) Period of Study: Jan 1997-Dec 2003

Location: Flanders, Belgium Outcome: Mortality: Nonaccidental (<800) Cardiovascular (390-459) Respiratory (460-519) Study Design: Time-series Statistical Analyses: Main analysis: Segmented regression models Sensitivity analysis: Poisson GAM, LOESS Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: Winter: 43.3(0.88) Spring: 39.5(0.88) summer: 37.7(0.91) Fall: 37.2(0.88) Range (Min, Max): NR Copollutant (correlation): NR Increment: Main analysis: NR Sensitivity analysis: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Highest season-specific PM 10 quartile vs. the lowest season-specific PM 10 quartile Summer: 7.8% (6.1, 9.6) Spring: 6.3% (4.7, 7.8) Fall: 2.2% (0.58, 3.8) Winter: 1.4% (0.06, 2.9) Warm months (Jun, Jul, Aug): 7.9% (6.2, 9.6) Cold months (Dec, Jan, Feb): 1.5% (0.22, 3.3) Intermediate months (Mar, Apr, May, Sep, Oct, Nov): 4.2% (2.9, 5.6) Warmer Periods (Apr-Sep) Nonaccidental: 1.5% (1.1, 2.0) 0 Respiratory: 2.0% (0.6, 3.7) 0 Cardiovascular: 1.8% (1.1, 2.4) 0



### December 2009 E-305

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: O’Neill et al. (2004, 087429 ) Period of Study: 1996-1998

1994-1995

Location: Mexico City, Mexico Outcome: Mortality:

Nonaccidental Study Design: Time-series Statistical Analyses: Poisson, natural cubic spline Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Range : Hi-Vol: 46.3-164.0 TEOM: 48.2-107.5 Predicted: 30.2-162.4 Impactor: 58.4 Range (Min, Max): Xalostoc Hi-Vol: (40.0, 335.0) TEOM: (16.5, 291.2) Predicted: (60.6, 320.0)

Tlalnepantla Hi-Vol: (25.0, 264.0) TEOM: (10.4, 275.9) Predicted: (17.7, 175.0)

Merced Hi-Vol: (17.0, 266.0) TEOM: (9.4, 318.7) Predicted: (12.3, 160.8)

Cerro de la Estrella Hi-Vol: (15.0, 292.0) TEOM: (13.7, 268.3) Predicted: (11.2, 154.4) Pedregal (1996-1998) Hi-Vol: (5.0, 226.0) TEOM: (7.8, 264.4) Predicted: (-0.5, 86.3) Pedregal (1994-1995) Hi-Vol: (24.0, 114.0) TEOM: (8.7, 152.5) Impactor: (15.0, 154.0) Predicted: (3.9, 75.9) Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: TEOM 0.04% (-0.12, 0.20) 0 -0.02% (-0.18, 0.13) 1 -0.01% (-0.27, 0.25) 2 -0.03% (-0.19, 0.13) 3 -0.03% (-0.19, 0.13) 4 -0.05% (-0.21, 0.11) 5 0.05% (-0.25, 0.35) 0-5 Predicted -0.05% (-0.29, 0.19) 0 0.09% (-0.16, 0.34) 1 -0.12% (-0.43, 0.20) 2 -0.02% (-0.26, 0.21) 3 -0.14% (-0.37, 0.09) 4 -0.05% (-0.28, 0.18) 5 0.00% (-0.39, 0.38) 0-5 Sierra-Anderson High Volume Air Sampler 0.02% (-0.29, 0.32) 0 0.13% (-0.27, 0.54) 1 0.21% (-0.10, 0.52) 2 0.53% (0.07, 0.99) 3 0.11% (-0.20, 0.41) 4 0.38% (0.07, 0.70) 5 GAM: 2 LOESS terms, default convergence 1.68% (0.45, 2.93) 0 -0.36% (-1.56, 0.86) 1 -0.21% (-1.40, 1.00) 2 -0.18% (-1.40, 1.05) 3 1.31% (0.08, 2.55) 4 1.49% (0.25, 2.73) 5 1.77% (-0.26, 3.83) 0-5 Parametric: cubic splines 5 df 1.45% (0.09, 2.83) 0 -0.71% (-2.06, 0.67) 1 -0.59% (-1.95, 0.79) 2 -0.70% (-2.09, 0.71) 3 0.92% (-0.46, 2.32) 4 1.17% (-0.19, 2.55) 5 1.17% (-1.54, 3.95) 0-5 10 df 1.60% (0.20, 3.02) 0 -0.80% (-2.18, 0.60) 1 -0.73% (-2.11, 0.68) 2 -1.05% (-2.49, 0.40) 3 0.64% (-0.79, 2.10) 4 1.05% (-0.36, 2.48) 5 0.51% (-2.60, 3.71) 0-5 2 df 1.79% (0.48, 3.11) 0 -0.09% (-1.38, 1.22) 1 0.10% (-1.18, 1.40) 2 0.20% (-1.10, 1.52) 3 1.60% (0.30, 2.91) 4 1.72% (0.43, 3.04) 5 1.90% (-0.36, 4.21) 0-5 Reference: O’Neill et al. (2005, 098094 ) Period of Study: 1996-1998

1996-1999

Location: Mexico City and Monterrey, Mexico Outcome: Mortality: Nonaccidental Cardiovascular (390-460) Respiratory (460-520)

Other-causes Study Design: Time-series Statistical Analyses: Poisson, natural cubic splines Age Groups: All ages, 0-15, ≥ 65 Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Mexico City: 75.8 (31.4) Monterrey: 50.0 (23.5) Range (Min, Max): Mexico City: (18.0, 233.9) Monterrey: (6.2, 230.8) Copollutant: O 3 The study focuses on the temperature-mortality relationship and only includes PM 10 as a covariate in models.



### December 2009 E-306

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: O'Neill et al. (2008, 192314 ) Period of Study: Jan 1998-Dec 2002

Location: Mexico City, Mexico Santiago, Chile São Paulo, Brazil Outcome: Study Design: Time-series

Covariates: Temperature, day of week, temporal trends, sex Statistical Analysis: Poisson regression Statistical Package: S-Plus Age Groups: Adults over 21 yr Pollutant: PM 10 Averaging Time: 24 h Mean (SD) μg/ m 3 : Mexico City: 53.8 (24.9) São Paulo: 48.9 (21.9) Santiago: 78.7 (33.0) Range (Min, Max): Mexico City: 1.08-192.2

São Paulo: 12.0-171.3 Santiago: 8.0-218.6 Copollutant: NR Increment: 10 μg/m 3Percent increase (95% CI) in allcause adult mortality (>22yrs) by educational level and sex Mexico City All Adults, Concurrent Day None: 0.76 (0.17-1.36) Primary: 0.27 (-0.19-0.72) Secondary: 0.19 (-0.19-0.57) ≥ 12 yr: 0.83 (0.03-1.63) All Adults, Lag 1 None: 0.62 (0.02-1.22) Primary: 0.62 (0.17-1.08) Secondary: 0.29 (-0.09-0.90) ≥ 12 yr: 0.58 (-0.21-1.38) All Adults, Distributed Lags 0-5 None: 0.91 (-0.07-1.89) Primary: 0.48 (-0.27-1.24) Secondary: 0.27 (-0.36-0.90) ≥ 12 yr: 0.75 (-0.49-2.02) All Adults, df (yr) None: 5.4 Primary: 6.0 Secondary: 6.0 ≥ 12 yr: 3.0 Women, Concurrent Day None: 0.65 (-0.08-1.38) Primary: 0.48 (-0.13-1.09) Secondary: 0.35 (-0.16-0.86) ≥ 12 yr: 1.64 (0.69-2.59) Women, Lag 1 None: 0.62 (-0.12-1.36) Primary: 1.03 (0.42-1.64) Secondary: 0.59 (0.08-1.11) ≥ 12 yr: 1.79 (0.84-2.75) Women, Distributed Lags 0-5 None: 0.46 (-0.74-1.68) Primary: 1.39 (0.42-2.36) Secondary: 0.51 (-0.30-1.33) ≥ 12 yr: 1.71 (0.61-2.83) Women, df (yr) None: 5.4 Primary: 4.4 Secondary: 4.8 ≥ 12 yr: 1.0 Men, Concurrent Day None: 0.75 (-0.21-1.72) Primary: 0.52 (-0.11-1.15) Secondary: 0.56 (0.08-1.05) ≥ 12 yr: 1.20 (0.25-2.17) Men, Lag 1 None: 0.45 (-0.51-1.42) Primary: 0.70 (0.06-1.34) Secondary: 0.47 (-0.02-0.95) ≥ 12 yr: 0.74 (-0.22-1.70) Men, Distributed Lags 0-5 None: 1.24 (-0.25-2.75) Primary: 0.65 (-0.39-1.69) Secondary: 0.88 (0.11-1.66) ≥ 12 yr: 1.07 (-0.41-2.57) Men, df (yr) None: 3.8 Primary: 5.6 Secondary: 4.6 ≥ 12 yr: 3.8

São Paulo All Adults, Concurrent Day None: 0.77 (-0.28-1.82) Primary: 1.27 (0.78-1.76) Secondary: 0.93 (-0.07-1.94) ≥ 12 yr: 2.93 (2.00-2.88) All Adults, Lag 1 None: 0.70 (-0.34-1.76) Primary: 1.32 (0.83-1.82) Secondary: 1.91 (0.58-2.60) ≥ 12 yr: 2.20 (1.27-3.15)



### December 2009 E-307

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) All Adults, Distributed Lags 0-5 None: 0.76 (-0.91-2.46) Primary: 1.34 (0.55-2.14) Secondary: 1.91 (0.35-2.60) ≥ 12 yr: 2.20 (1.27-3.15) All Adults, df (yr) None: 4.0 Primary: 4.0 Secondary: 2.8 ≥ 12 yr: 1.6 Women, Concurrent Day None: 1.93 (0.87-3.00) Primary: 1.72 (1.04-2.41) Secondary: 0.85 (-0.21-1.92) ≥ 12 yr: 1.84 (0.56-3.13) Women, Lag 1 None: 1.41 (0.34-2.48) Primary: 1.64 (0.96-2.33) Secondary: 1.43 (0.36-2.50) ≥ 12 yr: 2.27 (0.99-3.56) Women, Distributed Lags 0-5 None: 2.00 (0.40-3.63) Primary: 2.05 (0.96-3.14) Secondary: 1.61 (0.07-3.17) ≥ 12 yr: 3.35 (1.49-5.25) Women, df (yr) None: 2.4 Primary: 3.6 Secondary: 1.4 ≥ 12 yr: 0.8 Men, Concurrent Day None: -0.43 (-2.15-1.32) Primary: 1.36 (0.71-2.02) Secondary: 1.74 (0.77-2.72) ≥ 12 yr: 2.81 (1.71-3.92) Men, Lag 1 None: -0.44 (-2.17-1.33) Primary: 1.44 (0.79-2.10) Secondary: 1.52 (0.55-2.49) ≥ 12 yr: 1.48 (0.38-2.59) Men, Distributed Lags 0-5 None: -0.30 (-3.09-2.56) Primary: 1.67 (0.65-2.70) Secondary: 1.06 (-0.34-2.49) ≥ 12 yr: 3.18 (1.60-4.79) Men, df (yr) None: 4.4 Primary: 3.2 Secondary: 0.8 ≥ 12 yr: 1.2 Santiago All Adults, Concurrent Day None: 1.44 (0.53-2.36) Primary: 0.06 (-0.21-0.34) Secondary: 0.42 (0.06-0.78) ≥ 12 yr: 1.32 (0.60-2.05) All Adults, Lag 1 None: 2.08 (1.16-30.1) Primary: 0.53 (0.25-0.81) Secondary: 0.55 (0.19-0.91) ≥ 12 yr: 1.31 (0.59-2.04) All Adults, Distributed Lags 0-5 None: 3.18 (1.60-4.78) Primary: 0.58 (0.10-1.06) Secondary: 1.10 (0.48-1.73) ≥ 12 yr: 2.00 (0.93-3.07) All Adults, df (yr) None: 3.6 Primary: 5.6 Secondary: 4.0 ≥ 12 yr: 1.6 Women, Concurrent Day None: 0.91 (-0.06-1.89) Primary: 0.31 (-0.06-0.68) Secondary: 0.84 (0.33-1.36) ≥ 12 yr: 0.60 (-0.32-1.52) Women, Lag 1



### December 2009 E-308

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) None: 1.58 (0.58-2.58) Primary: 0.79 (0.42-1.17) Secondary: 0.76 (0.25-1.28) ≥ 12 yr: 0.53 (-0.39-1.45) Women, Distributed Lags 0-5 None: 1.15 (-0.48-2.80) Primary: 1.05 (0.41-1.69) Secondary: 1.29 (0.40-2.19) ≥ 12 yr: 1.06 (-0.27-2.41) Women, df (yr) None: 2.6 Primary: 4.8 Secondary: 4.4 ≥ 12 yr: 1.0 Men, Concurrent Day None: 0.05 (-1.02-1.12) Primary: -0.11 (-0.5-0.28) Secondary: 0.18 (-0.31-0.68) ≥ 12 yr: 1.52 (0.70-2.35) Men, Lag 1 None: 0.61 (-0.44-1.68) Primary: 0.23 (-0.16-0.62) Secondary: 0.49 (0.00-0.98) ≥ 12 yr: 1.03 (0.21-1.86) Men, Distributed Lags 0-5 None: 2.08 (0.28-3.91) Primary: 0.16 (-0.50-0.82) Secondary: 1.27 (0.43-2.12) ≥ 12 yr: 1.98 (0.76-3.20) Men, df (yr) None: 2.8 Primary: 4.8 Secondary: 4.4 ≥ 12 yr: 1.6Percent increase (95% CI) in allcause adult mortality ( ≥ 65yrs) by educational level and sex Mexico City All Adults, Concurrent Day None: 0.41 (-0.25-1.08) Primary: 0.40 (-0.15-0.95) Secondary: 0.50 (-0.01-1.01) ≥ 12 yr: 1.51 (0.39-2.63) All Adults, Lag 1 None: 0.20 (-0.47-0.87) Primary: 0.80 (0.24-1.36) Secondary: 0.60 (0.09-1.12) ≥ 12 yr: 1.09 (-0.02-2.22) All Adults, Distributed Lags 0-5 None: 0.27 (-0.83-1.38) Primary: 0.99 (0.07-1.91) Secondary: 0.30 (-0.56-1.16) ≥ 12 yr: 1.83 (0.09-3.59) All Adults, df (yr) None: 5.6 Primary: 5.4 Secondary: 6.0 ≥ 12 yr: 3.2 Women, Concurrent Day None: 0.49 (-0.30-1.29) Primary: 0.39 (-0.33-1.11) Secondary: 0.52 (-0.16-1.20) ≥ 12 yr: 1.29 (0.12-2.48) Women, Lag 1 None: 0.73 (-0.07-1.54) Primary: 1.24 (0.52-1.97) Secondary: 0.55 (-0.13-1.23) ≥ 12 yr: 1.50 (0.32-2.70) Women, Distributed Lags 0-5 None: 0.75 (-0.56-2.08) Primary: 1.43 (0.29-2.59) Secondary: 0.06 (-1.01-1.15) ≥ 12 yr: 1.48 (0.10-2.87) Women, df (yr) None: 5.4 Primary: 4.2 Secondary: 4.8



### December 2009 E-309

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

≥ 12 yr: 0.6 Men, Concurrent Day None: 0.90 (-0.23-2.04) Primary: 0.37 (-0.40-1.16) Secondary: 0.78 (0.07-1.49) ≥ 12 yr: 1.66 (0.30-3.04) Men, Lag 1 None: -0.15 (-1.27-0.98) Primary: 0.26 (-0.53-1.05) Secondary: 0.93 (0.22-1.65) ≥ 12 yr: 0.95 (-0.41-2.32) Men, Distributed Lags 0-5 None: 0.80 (-0.95-2.58) Primary: 0.29 (-0.99-1.58) Secondary: 1.06 (-0.08-2.21) ≥ 12 yr: 1.76 (-0.35-3.91) Men, df (yr) None: 3.8 Primary: 5.6 Secondary: 4.6 ≥ 12 yr: 3.8

São Paulo All Adults, Concurrent Day None: 0.60 (-0.48-1.70) Primary: 0.59 (1.00-2.19) Secondary: 1.21 (-0.01-2.44) ≥ 12 yr: 2.80 (1.67-3.94) All Adults, Lag 1 None: 0.62 (-0.47-1.72) Primary: 1.48 (0.89-2.07) Secondary: 2.31 (1.08-3.55) ≥ 12 yr: 2.52 (1.40-3.66) All Adults, Distributed Lags 0-5 None: 0.91 (-0.84-2.69) Primary: 1.73 (0.79-2.67) Secondary: 3.25 (1.39-5.16) ≥ 12 yr: 3.63 (2.01-5.29) All Adults, df (yr) None: 4.0 Primary: 3.8 Secondary: 2.6 ≥ 12 yr: 1.6 Women, Concurrent Day None: 1.82 (0.71-2.94) Primary: 1.84 (1.05-2.64) Secondary: 0.62 (-0.55-1.81) ≥ 12 yr: 1.00 (-0.27-2.29) Women, Lag 1 None: 1.36 (0.25-2.49) Primary: 1.76 (0.97-2.56) Secondary: 1.57 (0.39-2.76) ≥ 12 yr: 1.39 (0.12-2.68) Women, Distributed Lags 0-5 None: 1.80 (0.12-3.51) Primary: 1.97 (0.73-3.22) Secondary: 1.89 (0.19-3.61) ≥ 12 yr: 2.53 (0.70-4.40) Women, df (yr) None: 2.4 Primary: 3.4 Secondary: 1.2 ≥ 12 yr: 0.8 Men, Concurrent Day None: -0.67 (-2.50-1.19) Primary: 1.82 (1.00-2.65) Secondary: 2.46 (1.31-3.63) ≥ 12 yr: 1.73 (0.47-3.00) Men, Lag 1 None: -0.59 (-2.42-1.26) Primary: 1.59 (0.78-2.41) Secondary: 2.64 (1.49-3.80) ≥ 12 yr: 0.89 (-0.35-2.15) Men, Distributed Lags 0-5 None: 1.50 (-1.52-4.60) Primary: 2.46 (1.20-3.74) Secondary: 2.24 (0.56-3.95) ≥ 12 yr: 1.45 (-0.34-3.29)



### December 2009 E-310

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Men, df (yr) None: 4.6 Primary: 3.0 Secondary: 0.8 ≥ 12 yr: 1.0 Santiago All Adults, Concurrent Day None: 1.49 (0.54-2.45) Primary: 0.28 (-0.03-0.59) Secondary: 0.58 (0.13-1.04) ≥ 12 yr: 2.32 (1.50-3.15) All Adults, Lag 1 None: 2.20 (1.24-3.17) Primary: 0.74 (0.43-1.05) Secondary: 0.64 (0.20-1.11) ≥ 12 yr: 2.20 (1.36-3.04) All Adults, Distributed Lags 0-5 None: 3.21 (1.54-4.90) Primary: 0.92 (0.38-1.46) Secondary: 1.46 (0.67-2.25) ≥ 12 yr: 4.02 (2.78-5.27) All Adults, df (yr) None: 3.8 Primary: 5.2 Secondary: 4.0 ≥ 12 yr: 1.8 Women, Concurrent Day None: 1.39 (0.41-2.39) Primary: 0.4 (0.01-0.8) Secondary: 0.91 (0.29-1.53) ≥ 12 yr: 0.87 (-0.02-1.78) Women, Lag 1 None: 1.83 (0.83-2.85) Primary: 0.98 (0.58-1.38) Secondary: 0.73 (0.11-1.35) ≥ 12 yr: 0.76 (-0.15-1.68) Women, Distributed Lags 0-5 None: 2.47 (0.85-4.11) Primary: 1.2 (0.52-1.88) Secondary: 1.71 (0.65-2.78) ≥ 12 yr: 0.87 (-0.02-1.78) Women, df (yr) None: 2.4 Primary: 4.8 Secondary: 4.4 ≥ 12 yr: 0.6 Men, Concurrent Day None: 0.54 (-0.51-1.61) Primary: 0.34 (-0.12-0.80) Secondary: 0.25 (-0.40-0.91) ≥ 12 yr: 1.97 (1.09-2.86) Men, Lag 1 None: 0.84 (-0.21-1.91) Primary: 0.43 (-0.03-0.89) Secondary: 0.61 (-0.04-1.26) ≥ 12 yr: 1.57 (0.67-2.46) Men, Distributed Lags 0-5 None: 2.41 (0.64-4.22) Primary: 0.80 (0.02-1.59) Secondary: 1.58 (0.45-2.71) ≥ 12 yr: 2.99 (1.66-4.33) Men, df (yr) None: 2.0 Primary: 4.4 Secondary: 4.4 ≥ 12 yr: 1.8



### December 2009 E-311

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Peng et al. (2005, 087463 ) Period of Study: 1987-2000

Location: 100 U.S. cities (NMMAPS) Outcome: Mortality:

Nonaccidental Study Design: Time-series Statistical Analyses: Bayesian semiparametric hierarchical models Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: 27.1 Range (Min, Max): (13.2, 48.7) Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Winter: -0.4% (-0.30, 0.21) 0 0.15% (-0.08, 0.39) 1 0.10% (-0.13, 0.33) 2 Spring: 0.32% (0.08, 0.56) 0 0.14% (-0.14, 0.42) 1 0.05% (-0.21, 0.32) 2 Summer: 0.13% (-0.11, 0.37) 0 0.36% (0.11, 0.61) 1 -0.03% (-0.27, 0.21) 2 Fall: 0.05% (-0.16, 0.25) 0 0.14% (-0.06, 0.34) 1 0.13% (-0.08, 0.35) 2 All Seasons: 0.09% (-0.01, 0.19) 0 0.19% (0.10, 0.28) 1 0.08% (-0.03, 0.19) 2 PM10 only (45 cities): Winter: 0.15% (-0.16, 0.45) 1 Spring: 0.13% (-0.21, 0.48) 1 Summer: 0.30% (-0.10, 0.69) 1 Fall: 0.07% (-0.23, 0.37) 1 PM10 + O3 (45 cities): Winter: 0.18% (-0.16, 0.52) 1 Spring: 0.10% (-0.30, 0.49) 1 Summer: 0.33% (-0.14, 0.81) 1 Fall: 0.08% (-0.25, 0.41) 1 PM10 + O3 (45 cities): Winter: 0.13% (-0.24, 0.49) 1 Spring: 0.1% 9(-0.18, 0.56) 1 Summer: 0.28% (-0.13, 0.70) 1 Fall: -0.01% (-0.34, 0.31) 1 PM10 + NO2 (45 cities): Winter: 0.21% (-0.18, 0.60) 1 Spring: 0.19% (-0.17, 0.54) 1 Summer: 0.34% (0.01, 0.68) 1 Fall: 0.13% (-0.12, 0.39) 1 Reference: Penttinen et al. (2004, 087432 ) Period of Study: 1988-1996

Location: Helsinki, Finland Outcome: Mortality: Total (nonaccidental) (<800) Cardiovascular (390-459) Respiratory (460-519) Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups: 15-64 yr 65-74 yr ≥ 75 yr Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: 21 μg/m 3 Range (Min, Max): (0.2, 213) Copollutant (correlation): O 3 : r = -0.09 NO 2 : r = 0.50 CO: r = 0.45 SO 2 : r = 0.61 TSP: r = 0.72 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Total (nonaccidental) -0.23% (-1.47, 1.01) 0 0.88% (-0.32, 2.08) 1 0.11 (-0.51, 0.73) 0-3 avg Cardiovascular -1.22% (-3.00, 0.56) 0 0.63% (-1.09, 2.35) 1 0.08% (-0.96, 0.81) 0-3 avg Respiratory 3.94% (0.01, 7.87) 0 3.96% (0.11, 7.81) 1 2.13% (0.03, 4.22) 0-3 avg Reference: Qian et al. (2007, 093054 ) Period of Study: 2001-2004

Location: Wuhan, China Outcome: Mortality: Total (nonaccidental) (<800) Cardiovascular (390-459) Stroke (430-438) Cardiac Diseases (390-398) Respiratory (460-519) Cardiopulmonary Study Design: Time-series Statistical Analyses: Poisson GAM, natural splines Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 141.8 3 Range (Min, Max): (24.8, 477.8) Copollutant (correlation):

NO 2 SO 2 O 3 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental 0.36% (0.19, 0.53) 0 0.28% (0.12, 0.45) 1 0.43% (0.24, 0.62) 0-1 0.08% (-0.15, 0.31) 0-4 <45 yr 0.28% (-0.26, 0.82) 0 0.45% (-0.06, 0.96) 1 0.53% (-0.08, 1.13) 0-1 0.41% (-0.31, 1.13) 0-4 ≥ 45 yr 0.36% (0.19, 0.54) 0 0.27% (0.10, 0.44) 1 0.42% (0.22, 0.62) 0-1 0.05% (-0.18, 0.29) 0-4 <65 yr



### December 2009 E-312

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

<45 yr

≥ 45 yr <65 yr

≥ 65 yr 0.20% (-0.08, 0.49) 0 0.25% (-0.03, 0.52) 1 0.33% (0.01, 0.66) 0-1 0.01% (-0.38, 0.39) 0-4 ≥ 65 yr 0.41% (0.21, 0.61) 0 0.30% (0.10, 0.49) 1 0.46% (0.24, 0.69) 0-1 0.10% (-0.16, 0.37) 0-4

Cardiovascular 0.51% (0.28, 0.75) 0 0.35% (0.12, 0.58) 1 0.58% (0.31, 0.84) 0-1 0.35% (0.05, 0.66) 0-4 <45 yr 0.59% (-0.62, 1.82) 0 0.93% (-0.22, 2.08) 1 1.07% (-0.27, 2.42) 0-1 1.15% (-0.40, 2.72) 0-4 ≥ 45 yr 0.51% (0.27, 0.75) 0 0.33% (0.10, 0.56) 1 0.56% (0.30, 0.83) 0-1 0.33% (0.02, 0.63) 0-4 <65 yr 0.27% (-0.23, 0.76) 0 0.30% (-0.16, 0.77) 1 0.42% (-0.12, 0.97) 0-1 0.43% (-0.19, 1.06) 0-4 ≥ 65 yr 0.57% (0.31, 0.83) 0 0.36% (0.11, 0.61) 1 0.61% (0.32, 0.90) 0-1 0.33% (0.00, 0.67) 0-4

Stroke 0.44% (0.16, 0.72) 0 0.41% (0.14, 0.68) 1 0.58% (0.27, 0.89) 0-1 0.45% (0.09, 0.81) 0-4 <45 yr 1.18% (-0.45, 2.83) 0 1.66% (0.11, 3.24) 1 1.91% (0.10, 3.75) 0-1 2.72% (0.58, 4.89) 0-4 ≥ 45 yr 0.42% (0.14, 0.70) 0 0.37% (0.10, 0.65) 1 0.55% (0.23, 0.86) 0-1 0.39% (0.03, 0.76) 0-4 <65 yr 0.26% (-0.35, 0.87) 0 0.38% (-0.20, 0.96) 1 0.48% (-0.19, 1.16) 0-1 0.57% (-0.21, 1.35) 0-4 ≥ 65 yr 0.49% (0.17, 0.80) 0 0.41% (0.11, 0.72) 1 0.61% (0.26, 0.96) 0-1 0.42% (0.02, 0.83) 0-4

Cardiac 0.49% (0.08, 0.89) 0 0.28% (-0.11, 0.67) 1 0.49% (0.04, 0.94) 0-1 0.22% (-0.29, 0.74) 0-4 <45 yr 0.25% (-1.64, 2.17) 0 0.56% (-1.22, 2.38) 1 0.61% (-1.47, 2.74) 0-1 -0.42% (-2.80, 2.02) 0-4 ≥ 45 yr 0.49% (0.09, 0.91) 0 0.27% (-0.12, 0.66) 1 0.48% (0.03, 0.94) 0-1 0.25% (-0.27, 0.77) 0-4



### December 2009 E-313

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) <65 yr 0.00% (-0.89, 0.90) 0 0.12% (-0.73, 0.98) 1 0.13% (-0.86, 1.13) 0-1 0.05% (-1.08, 1.20) 0-4 ≥ 65 yr 0.60% (0.17, 1.03) 0 0.32% (-0.10, 0.74) 1 0.57% (0.09, 1.06) 0-1 0.26% (-0.29, 0.82) 0-4

Respiratory 0.71% (0.20, 1.23) 0 0.63% (0.13, 1.13) 1 0.86% (0.28, 1.44) 0-1 0.19% (-0.48, 0.87) 0-4 <45 yr 1.74% (-1.28, 4.86) 0 2.52% (-0.30, 5.42) 1 2.95% (-0.41, 6.42) 0-1 3.47% (-0.61, 7.73) 0-4 ≥ 45 yr 0.69% (0.18, 1.21) 0 0.58% (0.09, 1.08) 1 0.81% (0.23, 1.39) 0-1 0.13% (-0.54, 0.80) 0-4 <65 yr 0.06% (-1.30, 1.43) 0 -0.53% (-1.83, 0.79) 1 -0.32% (-1.84, 1.22) 0-1 -0.72% (-2.47, 1.05) 0-4 ≥ 65 yr 0.79% (0.27, 1.31) 0 0.76% (0.26, 1.26) 1 0.99% (0.41, 1.57) 0-1 0.30% (-0.38, 0.98) 0-4 Cardiopulmonary 0.46% (0.23, 0.69) 0 0.35% (0.13, 0.57) 1 0.53% (0.28, 0.79) 0-1 0.11% (-0.19, 0.42) 0-4 <45 yr 0.71% (-0.48, 1.92) 0 1.26% (0.14, 2.4) 1 1.39% (0.06, 2.74) 0-1 1.41% (-0.18, 3.03) 0-4 ≥ 45 yr 0.45% (0.23, 0.68) 0 0.32% (0.10, 0.54) 1 0.51% (0.25, 0.77) 0-1 0.08% (-0.23, 0.38) 0-4 <65 yr 0.14% (-0.34, 0.61) 0 0.15% (-0.30, 0.61) 1 0.23% (-0.30, 0.76) 0-1 0.11% (-0.52, 0.74) 0-4 ≥ 65 yr 0.53% (0.28, 0.78) 0 0.39% (0.15, 0.63) 1 0.60% (0.32, 0.88) 0-1 0.11% (-0.22, 0.45) 0-4

Two-pollutant Models Nonaccidental PM 10 +NO 2 : 0.14% (-0.07, 0.36) 0 PM 10 +SO 2 : 0.37% (0.20, 0.55) 0 PM 10 +O 3 : 0.34% (0.17, 0.51) 0

Cardiovascular PM 10 +NO 2 : 0.34% (0.04, 0.63) 0 PM 10 +SO 2 : 0.53% (0.28, 0.77) 0 PM 10 +O 3 : 0.50% (0.26, 0.74) 0

Stroke PM 10 +NO 2 : 0.28% (-0.07, 0.63) 0 PM 10 +SO 2 : 0.49% (0.21, 0.78) 0 PM 10 +O 3 : 0.44 (0.16, 0.72) 0



### December 2009 E-314

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Cardiac PM 10 +NO 2 : 0.24% (-0.27, 0.75) 0 PM 10 +SO 2 : 0.43 (0.01, 0.84) 0 PM 10 +O 3 : 0.44% (0.03, 0.85) 0

Respiratory PM 10 +NO 2 : 0.46% (-0.19, 1.12) 0 PM 10 +SO 2 : 0.64% (0.11, 1.18) 0 PM 10 +O 3 : 0.67% (0.15, 1.20) 0 Cardiopulmonary PM 10 +NO 2 : 0.26% (-0.02, 0.55) 0 PM 10 +SO 2 : 0.46% (0.23, 0.70) 0 PM 10 +O 3 : 0.44% (0.21, 0.67) 0 Reference: Qian et al. (2008, 156894 ) Period of Study: Jul 2001-Jun 2004

Location: Wuhan, China Outcome: Mortality: Total (nonaccidental) (<800) Cardiovascular (390-459) Stroke (430-438) Cardiac diseases (390-398, 410-429) Respiratory (460-519) Cardiopulmonary (390-459, 460-519) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines and penalized splines Age Groups: All ages <65 yr

≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Normal temperature: 145.7 (64.6) Low temperature: 117.3 (49.5) High temperature: 96.3 (27.9) Range (Min, Max): NR Copollutant (correlation): Normal temperature: NO 2 : r = 0/72 SO : r = 0.59

2 O 3 : r = 0.06 Low temperature: NO 2 : r = 0.83 SO 2 : r = 0.74 O 3 : r = 0.19 High temperature: NO 2 : r = 0.68 SO 2 : r = 0.15 O 3 : r = 0.65 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental: Normal: All ages: 0.36 (0.17, 0.56) 0-1 <65: 0.23 (-0.10, 0.56) 0-1 ≥ 65: 0.51 (0.18, 0.64) 0-1 PM 10 +NO 2 : 0.07 (-0.17, 0.30) 0-1 PM 10 +SO 2 : 0.27 (0.06, 0.47) 0-1 PM 10 +O 3 : 0.38 (0.18, 0.58) 0-1 Low: All ages: 0.62 (-0.09, 1.34) 0-1 <65: 1.78 (0.52, 3.05) 0-1 ≥ 65: 0.22 (-0.61, 1.05) 0-1 PM 10 +NO 2 : 0.24 (-0.49, 0.97) 0-1 PM 10 +SO 2 : 0.45 (-0.27, 1.17) 0-1 PM +O 3 : 0.72 (0.00, 1.44) 0-1

10 High: All ages: 2.20 (0.74, 3.68) 0-1 <65: 2.34 (-0.09, 4.83) 0-1 ≥ 65: 2.14 (0.42, 3.89) 0-1 PM 10 +NO 2 : 1.87 (0.42, 3.35) 0-1 PM 10 +SO : 2.12 (0.67, 3.60) 0-1 2 PM 10 +O 3 : 2.15 (0.55, 3.77) 0-1

Cardiovascular: Normal: All ages: 0.39 (0.11, 0.66) 0-1 <65: 0.17 (-0.40, 0.73) 0-1 ≥ 65: 0.44 (0.14, 0.74) 0-1 PM 10 +NO 2 : 0.11 (-0.23, 0.45) 0-1 PM 10 +SO : 0.27 (-0.02, 0.55) 0-1 2 PM 10 +O 3 : 0.42 (0.15, 0.70) Low: All ages: 0.72 (-0.25, 1.70) 0-1 <65: 2.63 (0.67, 4.63) 0-1 ≥ 65: 0.24 (-0.84, 1.32) 0-1 PM 10 +NO 2 : 0.37 (-0.62, 1.38) 0-1 PM 10 +SO 2 : 0.50 (-0.47, 1.49) 0-1 PM 10 +O 3 : 0.82 (-0.16, 1.80) 0-1 High: All ages: 3.28 (1.24, 5.37) 0-1 <65: 4.32 (0.10, 8.71) 0-1 ≥ 65: 3.03 (0.77, 5.34) 0-1 PM 10 +NO 2 : 3.00 (0.95, 5.09) 0-1 PM 10 +SO 2 : 3.20 (1.16, 5.29) 0-1 PM 10 +O 3 : 3.71 (1.50, 5.96) 0-1

Stroke: Normal: All ages: 0.38 (0.06, 0.70) <65: 0.17 (-0.53, 0.88) 0-1 ≥ 65: 0.43 (0.07, 0.79) 0-1 PM 10 +NO 2 : 0.09 (-0.31, 0.49) 0-1 PM 10 +SO 2 : 0.31 (-0.03, 0.64) 0-1 PM +O 3 : 0.38 (0.05, 0.71) 0-1

10 Low: All ages: 0.67 (-0.50, 1.85) 0-1 <65: 2.85 (0.34, 5.42) 0-1 ≥ 65: 0.11 (-1.22, 1.45) 0-1 PM 10 +NO 2 : 0.29 (-0.90, 1.51) 0-1 PM 10 +SO 2 : 0.53 (-0.65, 1.73) 0-1



### December 2009 E-315

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

PM 10 +O 3 : 0.69 (-0.48, 1.87) 0-1 High: All ages: 2.35 (-0.03, 4.78) 0-1 <65: 4.54 (-0.79, 10.16) 0-1 ≥ 65: 1.83 (-0.83, 4.57) PM 10 +NO 2 : 2.05 (-0.34, 4.49) 0-1 PM 10 +SO 2 : 2.31 (-0.07, 4.74) 0-1 PM 10 +O 3 : 2.77 (0.25, 5.35) 0-1

Cardiac: Normal: All ages: 0.32 (-0.14, 0.79) 0-1 <65: -0.04 (-1.07, 1.01) 0-1 ≥ 65: 0.40 (-0.10, 0.91) 0-1 PM 10 +NO 2 : 0.02 (-0.57, 0.60) 0-1 PM 10 +SO 2 : 0.11 (-0.38, 0.61) 0-1 PM 10 +O 3 : 0.41 (-0.06, 0.89) 0-1 Low: All ages: 0.50 (-1.10, 2.13) 0-1 <65: 1.79 (-1.65, 5.35) 0-1 ≥ 65: 0.19 (-1.55, 1.95) 0-1 PM 10 +NO 2 : 0.12 (-1.53, 1.80) 0-1 PM 10 +SO 2 : 0.14 (-1.48, 1.78) 0-1 PM 10 +O 3 : 0.72 (-0.90, 2.37) 0-1 High: All ages: 3.31 (-0.22, 6.97) 0-1 <65: 2.71 (-4.58, 10.56) 0-1 ≥ 65: 3.45 (-0.41, 7.46) 0-1 PM 10 +NO 2 : 3.01 (-0.54, 6.69) 0-1 PM 10 +SO 2 : 3.17 (-0.37, 6.84) 0-1 PM 10 +O 3 : 4.92 (0.96, 9.03) 0-1

Respiratory: Normal: All ages: 0.80 (0.25, 1.35) 0-1 <65: -0.35 (-1.85, 1.18) 0-1 ≥ 65: 0.93 (0.38, 1.50) 0-1 PM 10 +NO 2 : 0.30 (-0.39, 0.99) 0-1 PM 10 +SO 2 : 0.64 (0.07, 1.22) 0-1 PM 10 +O 3 : 0.84 (0.28, 1.41) 0-1 Low: All ages: 1.07 (-0.76, 2.95) 0-1 <65: -1.13 (-6.33, 4.35) 0-1 ≥ 65: 1.30 (-0.57, 3.20) 0-1 PM 10 +NO 2 : 0.44 (-1.46, 2.36) 0-1 PM 10 +SO 2 : 0.80 (-1.05, 2.69) 0-1 PM 10 +O 3 : 1.11 (-0.73, 2.99) 0-1 High: All ages: 1.15 (-3.54, 6.07) 0-1 <65: -3.42 (-15.82, 10.80) 0-1 ≥ 65: 1.76 (-3.03, 6.78) 0-1 PM 10 +NO 2 : 0.63 (-4.07, 5.55) 0-1 PM 10 +SO 2 : 1.03 (-3.66, 5.94) 0-1 PM 10 +O 3 : 2.66 (-2.44, 8.02) 0-1 Cardiopulmonary: Normal: All ages: 0.45 (0.19, 0.70) 0-1 <65: 0.07 (-0.47, 0.61) 0-1 ≥ 65: 0.53 (0.25, 0.81) 0-1 PM 10 +NO 2 : 0.15 (-0.17, 0.47) 0-1 PM 10 +SO 2 : 0.34 (0.07, 0.61) 0-1 PM 10 +O 3 : 0.43 (0.17, 0.70) 0-1 Low: All ages: 0.69 (-0.22, 1.61) 0-1 <65: 1.95 (0.04, 3.90) 0-1 ≥ 65: 0.43 (-0.57, 1.44) 0-1 PM 10 +NO 2 : 0.33 (-0.61, 1.27) 0-1 PM 10 +SO 2 : 0.50 (-0.42, 1.43) 0-1 PM 10 +O 3 : 0.76 (-0.16, 1.68) 0-1 High: All ages: 3.02 (1.03, 5.04) 0-1 <65: 3.49 (-0.66, 7.81) 0-1 ≥ 65: 2.91 (0.74, 5.12) 0-1 PM 10 +NO 2 : 2.70 (0.72, 4.73) 0-1 PM 10 +SO 2 : 2.95 (0.96, 4.97) 0-1 PM 10 +O 3 : 3.32 (1.16, 5.53) 0-1



### December 2009 E-316

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ren et al. (2006, 092824 ) Period of Study: Jan 1996-Dec 2001

Location: Brisbane, Australia Outcome: Mortality:

Nonaccidental Cardiovascular (390-448) Study Design: Time-series Statistical Analyses: Poisson GAM, cubic spline Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 15.84 Range (Min, Max): (2.5, 60) Copollutant: O 3 The study presents quantitative results associated with an incremental increase in temperature, not PM 10

.

Reference: Roberts (2004, 087924 ) Period of Study: 1987-1994

Location: Cook County, Illinois Allegheny County, Pennsylvania Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: Poisson GAM, smooth splines Poisson GLM, natural cubic splines Age Groups: ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: Cook County Lower Temp.: 29.24 Middle Temp.: 30.03 Upper Temp.: 52.76 Allegheny County Lower Temp.: 16.50 Middle Temp.: 24.97 Upper Temp.: 55.42 Range (10th, 90th): Cook County Lower Tem.: (16.42, 46.42) Middle Temp.: (14.79, 56.33) Upper Temp.: (30.81, 82.81) Allegheny County Lower Temp.: (5.14, 34.54) Middle Temp.: (8.91, 57.91) Upper Temp.: (30.91, 88.99) Increment: 10 μg/m 3 % Increase (SE) lag:

GLM Cook

α = 0.5 No Interaction: 0.288% (0.157) 0 Low Temp.: -0.272% (0.380) 0 Middle Temp.: 0.344% (0.165) 0 Upper Temp.: 0.281% (0.239) 0 No Interaction: 0.359% (0.149) 1 Low Temp.: -0.168% (0.372) 1 Middle Temp.: 0.361% (0.156) 1 Upper Temp.: 0.616% (0.250) 1 No Interaction: 0.465% (0.176) 0-1 ma Low Temp.: 0.043% (0.397) 0-1 ma Middle Temp.: 0.506% (0.184) 0-1 ma Upper Temp.: 0.464% (0.256) 0-1 ma No Interaction: 0.633% (0.214) 0-3 ma Low Temp.: 0.365% (0.419) 0-3 ma Middle Temp.: 0.638% (0.222) 0-3 ma Upper Temp.: 0.718% (0.295) 0-3 ma

α = 1 No Interaction: 0.117% (0.157) 0 Low Temp.: -0.351% (0.406) 0 Middle Temp.: 0.161% (0.165) 0 Upper Temp.: 0.096% (0.264) 0 No Interaction: 0.141% (0.150) 1 Low Temp.: -0.366% (0.397) 1 Middle Temp.: 0.161% (0.156) 1 Upper Temp.: 0.301% (0.278) 1 No Interaction: 0.260% (0.181) 0-1 ma Low Temp.: -0.163% (0.431) 0-1 ma Middle Temp.: 0.305% (0.188) 0-1 ma Upper Temp.: 0.207% (0.291) 0-1 ma No Interaction: 0.289% (0.225) 0-3 ma Low Temp.: 0.014% (0.459) 0-3 ma Middle Temp.: 0.311% (0.231) 0-3 ma Upper Temp.: 0.301% (0.334) 0-3 ma

α = 2 No Interaction: 0.060% (0.158) 0 0 Low Temp.: -0.464% (0.486) 0 0 Middle Temp.: 0.115% (0.168) 0 0 Upper Temp.: -0.022% (0.319) 0 0 No Interaction: 0.101% (0.152) 1 Low Temp.: -0.432% (0.484) 1 Middle Temp.: 0.089% (0.160) 1 Upper Temp.: 0.455% (0.327) 1 No Interaction: 0.129% (0.184) 0-1 ma Low Temp.: -0.320% (0.546) 0-1 ma Middle Temp.: 0.157% (0.193) 0-1 ma Upper Temp.: 0.130% (0.346) 0-1 ma No Interaction: 0.090% (0.236) 0-3 ma Low Temp.: -0.319% (0.572) 0-3 ma Middle Temp.: 0.105% (0.244) 0-3 ma Upper Temp.: 0.193% (0.412) 0-3 ma



### December 2009 E-317

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Allegheny α = 0.5 No Interaction: 0.078% (0.209) 0 Low Temp.: -0.759% (0.643) 0 Middle Temp.: 0.207% (0.216) 0 High Temp.: -0.367% (0.364) 0 No Interaction: 0.189% (0.206) 1 Low Temp.: -0.335% (0.691) 1 Middle Temp.: 0.293% (0.215) 1 High Temp.: -0.171% (0.349) 1 No Interaction: 0.224% (0.246) 0-1 ma Low Temp.: -0.753% (0.763) 0-1 ma Middle Temp.: 0.353% (0.253) 0-1 ma High Temp.: -0.142% (0.382) 0-1 ma No Interaction: 0.526% (0.300) 0-3 ma Low Temp.: 0.050% (0.733) 0-3 ma Middle Temp.: 0.688% (0.310) 0-3 ma High Temp.: -0.043% (0.436) 0-3 ma

α = 1 No Interaction: 0.078% (0.211) 0 Low Temp.: -0.694% (0.656) 0 Middle Temp.: 0.214% (0.219) 0 High Temp.: -0.533% (0.430) 0 No Interaction: 0.179% (0.207) 1 Low Temp.: -0.283% (0.718) 1 Middle Temp.: 0.273% (0.217) 1 High Temp.: -0.221% (0.396) 1 No Interaction: 0.221% (0.249) 0-1 ma Low Temp.: -0.731% (0.794) 0-1 ma Middle Temp.: 0.348% (0.258) 0-1 ma High Temp.: -0.253% (0.447) 0-1 ma No Interaction: 0.464% (0.309) 0-3 ma Low Temp.: 0.056% (0.780) 0-3 ma Middle Temp.: 0.626% (0.319) 0-3 ma High Temp.: -0.356% (0.516) 0-3 ma

α = 2 No Interaction: 0.034% (0.217) 0 Low Temp.: -1.059% (0.715) 0 Middle Temp.: 0.162% (0.230) 0 High Temp.: -0.233% (0.489) 0 No Interaction: 0.130% (0.214) 1 Low Temp.: -0.189% (0.800) 1 Middle Temp.: 0.157% (0.226) 1 High Temp.: 0.070% (0.471) 1 No Interaction: 0.183% (0.260) 0-1 ma Low Temp.: -0.918% (0.907) 0-1 ma Middle Temp.: 0.279% (0.273) 0-1 ma High Temp.: -0.001% (0.526) 0-1 ma No Interaction: 0.270% (0.331) 0-3 ma Low Temp.: -0.105% (0.898) 0-3 ma Middle Temp.: 0.394% (0.346) 0-3 ma High Temp.: -0.287% (0.615) 0-3 ma GAM Cook

α = 0.5 No Interaction: 0.438% (0.151) 0 Low Temp.: -0.178% (0.364) 0 Middle Temp.: 0.439% (0.163) 0 Upper Temp.: 0.627% (0.197) 0 No Interaction: 0.495% (0.144) 1 Low Temp.: -0.114% (0.361) 1 Middle Temp.: 0.460% (0.151) 1 Upper Temp.: 0.938% (0.208) 1 No Interaction: 0.710% (0.169) 0-1 ma Low Temp.: 0.151% (0.379) 0-1 ma Middle Temp.: 0.686% (0.180) 0-1 ma Upper Temp.: 0.952% (0.214) 0-1 ma No Interaction: 0.923% (0.203) 0-3 ma Low Temp.: 0.532% (0.402) 0-3 ma Middle Temp.: 0.855% (0.210) 0-3 ma Upper Temp.: 1.289% (0.251) 0-3 ma

α = 1 No Interaction: 0.190% (0.154) 0



### December 2009 E-318

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Low Temp.: -0.338% (0.414) 0 Middle Temp.: 0.242% (0.162) 0 Upper Temp.: 0.161% (0.230) 0 No Interaction: 0.239% (0.146) 1 Low Temp.: -0.283% (0.406) 1 Middle Temp.: 0.248% (0.152) 1 Upper Temp.: 0.453% (0.244) 1 No Interaction: 0.353% (0.174) 0-1 ma Low Temp.: -0.074% (0.437) 0-1 ma Middle Temp.: 0.388% (0.182) 0-1 ma Upper Temp.: 0.345% (0.251) 0-1 ma No Interaction: 0.453% (0.213) 0-3 ma Low Temp.: 0.190% (0.460) 0-3 ma Middle Temp.: 0.455% (0.219) 0-3 ma Upper Temp.: 0.557% (0.294) 0-3 ma

α = 2 No Interaction: 0.071% (0.157) 0 0 Low Temp.: -0.534% (0.478) 0 0 Middle Temp.: 0.132% (0.165) 0 0 Upper Temp.: 0.011% (0.264) 0 0 No Interaction: 0.099% (0.150) 1 Low Temp.: -0.467% (0.472) 1 Middle Temp.: 0.109% (0.156) 1 Upper Temp.: 0.329% (0.278) 1 No Interaction: 0.168% (0.180) 0-1 ma Low Temp.: -0.371% (0.525) 0-1 ma Middle Temp.: 0.216% (0.188) 0-1 ma Upper Temp.: 0.116% (0.290) 0-1 ma No Interaction: 0.149% (0.227) 0-3 ma Low Temp.: -0.291% (0.557) 0-3 ma Middle Temp.: 0.174% (0.233) 0-3 ma Upper Temp.: 0.210% (0.340) 0-3 ma

Allegheny α = 0.5 No Interaction: 0.245% (0.203) 0 Low Temp.: -0.727% (0.648) 0 Middle Temp.: 0.314% (0.216) 0 High Temp.: 0.308% (0.287) 0 No Interaction: 0.446% (0.199) 1 Low Temp.: -0.307% (0.701) 1 Middle Temp.: 0.469% (0.211) 1 High Temp.: 0.556% (0.285) 1 No Interaction: 0.522% (0.237) 0-1 ma Low Temp.: -0.646% (0.761) 0-1 ma Middle Temp.: 0.567% (0.251) 0-1 ma High Temp.: 0.640% (0.307) 0-1 ma No Interaction: 0.977% (0.282) 0-3 ma Low Temp.: 0.307% (0.733) 0-3 ma Middle Temp.: 1.027% (0.296) 0-3 ma High Temp.: 1.001% (0.352) 0-3 ma

α = 1 No Interaction: 0.107% (0.209) 0 Low Temp.: -0.819% (0.699) 0 Middle Temp.: 0.229% (0.219) 0 High Temp.: -0.214% (0.350) 0 No Interaction: 0.223% (0.205) 1 Low Temp.: -0.316% (0.751) 1 Middle Temp.: 0.295% (0.216) 1 High Temp.: 0.002% (0.341) 1 No Interaction: 0.267% (0.246) 0-1 ma Low Temp.: -0.797% (0.840) 0-1 ma Middle Temp.: 0.372% (0.257) 0-1 ma High Temp.: 0.035% (0.372) 0-1 ma No Interaction: 0.534% (0.302) 0-3 ma Low Temp.: 0.029% (0.810) 0-3 ma Middle Temp.: 0.660% (0.314) 0-3 ma High Temp.: 0.071% (0.431) 0-3 ma



### December 2009 E-319

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

α = 2 No Interaction: 0.061% (0.214) 0 Low Temp.: -1.048% (0.749) 0 Middle Temp.: 0.206% (0.226) 0 High Temp.: -0.332% (0.419) 0 No Interaction: 0.145% (0.211) 1 Low Temp.: -0.278% (0.816) 1 Middle Temp.: 0.210% (0.223) 1 High Temp.: -0.105% (0.394) 1 No Interaction: 0.180% (0.256) 0-1 ma Low Temp.: -1.028% (0.931) 0-1 ma Middle Temp.: 0.298% (0.269) 0-1 ma High Temp.: -0.114% (0.441) 0-1 ma No Interaction: 0.275% (0.324) 0-3 ma Low Temp.: -0.384% (0.915) 0-3 ma Middle Temp.: 0.436% (0.338) 0-3 ma High Temp.: -0.366% (0.513) 0-3 ma Reference: Roberts (2004, 087924 ) Period of Study: 1987-1994

Location: Cook County, Illinois Allegheny County, Pennsylvania Outcome: Mortality:

Nonaccidental Study Design: Time-series Statistical Analyses: Poisson GLM Age Groups: ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max):

Max = 89 The study does not present quantitative results.

Reference: Roberts (Roberts, 2005, 087992 ) Period of Study: Cook County: 1987-2000. Allegheny County: 1987-1998

Location: Cook County, Illinois Allegheny County, Pennsylvania Outcome: Mortality:

Nonaccidental Study Design: Time-series Statistical Analyses: Poisson Age Groups: ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: NR β (SE) lag: Standard Model Cook County 0.000127 (0.000264) 0 -0.000042 (0.000249) 1 -0.000441 (0.000246) 2 Allegheny County 0.000693 (0.000437) 0 0.000356 (0.000423) 1 0.000524 (0.000415) 2

Moving Total Model Cook County 0.000150 (0.000187) k = 2 -0.000047 (0.000153) k = 3 0.000009 (0.000133) k = 4 Allegheny County 0.000633 (0.000310) k = 2 0.000542 (0.000255) k = 3 0.000598 (0.000351) k = 4 Reference: Roberts (2006, 089762 ) Period of Study: 1987-2000

Location: Cook County, Illinois Suffolk County, Massachusetts (NMMAPS) Outcome: Mortality:

Nonaccidental Study Design: Time-series Statistical Analyses: Poisson GLM Age Groups: ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Cook County: 33.7 (19.4) Suffolk County: 25.9 (11.8) Range (10th, 90th): Cook County: (13.4, 58.1) Suffolk County: (14.0, 41.7) Copollutant (correlation): Cook County CO: r = 0.30 NO 2 : r = 0.53 SO 2 : r = 0.45 O 3 : r = 0.44 Suffolk County CO: r = 0.33 NO 2 : r = 0.43 SO 2 : r = 0.23 O 3 : r = 0.36 Increment: Cook County: 19.4 μg/m 3 Suffolk County: 14.0 μg/m 3 % Increase (SD) lag: Cook County Standard Model: 0.49% (0.25) 0 Proposed Model: 0.29% (0.16) 0 Standard Model: 0.67% (0.25) 0-2 avg Proposed Model: 0.49% (0.25) 0-2 avg Suffolk County Standard Model: 0.88% (1.27) 0 Proposed Model: 0.85% (0.84) 0 Standard Model: 1.60% (0.71) 0-2 avg Proposed Model: 1.35% (0.73) 0-2 avg



### December 2009 E-320

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Roberts and Martin (2006, 097799 ) Period of Study: 1987-2000

Location: Cook County, Illinois (NMMAPS) Outcome: Mortality: Nonaccidental Study Design: Time-series Statistical Analyses: Dose-response1. Piecewise linear relationship (nothreshold) with change point at 25 μg/m 3 and 50 μg/m 3

2. Piecewise linear relationship (threshold), exposure below 25 μg/m 3 no effect, and exposures above 50 μg/m 3 having a different effect then exposures between 25 μg/m 3 and 50 μg/m 3 Age Groups: ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR IQR (25th, 75th): (23.9, 45.4) Suffolk County: (14.0, 41.7) Copollutant (correlation): NR The study does not present quantitative results.

Reference: Roberts and Martin (2006, 088670 ) Period of Study: 1987-2000

Location: 109 U.S. cities (NMMAPS) Outcome: Mortality: Nonaccidental Cardiorespiratory Study Design: Time-series Statistical Analyses: Poisson 2-stage Bayesian hierarchical model Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR IQR (25th, 75th): NR Copollutant (correlation): NR Increment : NR β x 1000 (SE x 1000) lag: Nonaccidental Model 1 Base df: 0.079 (0.050) 0 Double df: 0.044 (0.046) 0 Half df: 0.107 (0.052) 0 Base df: 0.180 (0.044) 1 Double df: 0.149 (0.047) 1 Half df: 0.254 (0.048) 1 Base df: 0.059 (0.056) 2 Double df: 0.024 (0.056) 2 Half df: 0.143 (0.054) 2

Model 2 Base df: 0.115 (0.037) 0-2 ma Double df: 0.107 (0.034) 0-2 ma Half df: 0.145 (0.039) 0-2 ma Cardio-respiratory Model 1 Base df: 0.103 (0.068) 0 Double df: 0.056 (0.067) 0 Half df: 0.134 (0.066) 0 Base df: 0.232 (0.060) 1 Double df: 0.179 (0.067) 1 Half df: 0.309 (0.059) 1 Base df: 0.210 (0.078) 2 Double df: 0.144 (0.075) 2 Half df: 0.305 (0.079) 2

Model 2 Base df: 0.168 (0.047) 0-2 ma Double df: 0.140 (0.044) 0-2 ma Half df: 0.196 (0.051) 0-2 ma Notes: Model 1 uses current day’s mortality count, while Model 2 uses a 3- day moving total mortality count.



### December 2009 E-321

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Roberts and Martin (2007, 156917 ) Period of Study: 1987-2000

Location: 8 U.S. cities and >100 U.S. cities (NMMAPS) Outcome: Mortality: Total (nonaccidental) Cardiorespiratory Study Design: Time-series Statistical Analyses: Poisson Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Increment: 10 μg/m 3 β x 1000 (SE x 1000) lag: 8 U.S. cities Distributed Lag Model: 0.229 0-2 Weighted Model: 0.315 0-2 Standard Model: 0.276 0 -0.062 1 0.476 2

90 U.S. cities Total (nonaccidental) Standard Model: 0.078 (0.039) 0 0.182 (0.037) 1 0.108 (0.036) 2 Moving Total Model: 0.131 (0.023) 0-2 Weighted Model: 0.274 (0.075) 0-2 Cardio-respiratory Standard Model: 0.096 (0.055) 0 0.232 (0.053) 1 0.226 (0.051) 2 Moving Total Model: 0.174 (0.032) 0-2 Weighted Model: 0.389 (0.105) 0-2 Notes: The 8 U.S. cities consist of Chicago, Cleveland, Denver, El Paso, Houston, Nashville, Pittsburgh, and Salt Lake City.



### December 2009 E-322

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Roberts and Martin (2007, 156916 ) Period of Study: 1987-2000

Location: 10 U.S. cities (NMMAPS) Outcome: Mortality: Nonaccidental Study Design: Time-series Statistical Analyses: Poisson Age Groups: ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Anchorage: 27.32 Chicago: 36.95 Cleveland: 39.83 Detroit: 40.78 El Paso: 40.14 Minneapolis/St. Paul: 28.01 Pittsburgh: 35.09 Salt Lake City: 37.40 Seattle: 28.72 Spokane: 34.52 Range (Min, Max): NR Increment: NR β Coefficient (SE) lag:

Pooled Estimates Combined Model (Unconstrained Distributed Lag Model + Piecewise Linear Dose-Response Function) Change-point: 60 μg/m 3 Slope below: 0.00130 (0.00016) 0-5 Slope above: -0.00163 (0.00026) 0-5 Change-point: 30 μg/m 3 Slope below: 0.00014 (0.00039) 0-5 Slope above: -0.00003 (0.00015) 0-5 Piecewise Linear Dose-Response Model Change-point: 60 μg/m 3 Slope below: 0.00044 (0.00011) 3-day ma Slope above: -0.00077 (0.00020) 3- day ma Change-point: 30 μg/m 3 Slope below: 0.00022 (0.00026) 3-day ma Slope above: -0.00004 (0.00011) 3-day ma Polynomial Distributed Lag Model (degree 2) 0.00046 (0.00011) 0-5 Reference: Samoli et al. (2005, 087436 ) Period of Study: 1990-1997

Location: 22 European cities (APHEA2) Outcome: Mortality: All-cause (nonaccidental) (<800) Cardiovascular (390-459) Respiratory (460-519) Study Design: Time-series Statistical Analyses: Hierarchical modeling: 1. Poisson GAM, penalized splines 2. Multivariate modeling Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: Range: (Stockholm: 14 μg/m 3 to Torino: 65 μg/m 3 ) Percentile (90th): Range: (Stockholm: 27 μg/m 3 to Torino: 129 μg/m 3 ) Copollutant (correlation): BS The study does not present quantitative results.

Reference: Schwartz (2004, 078998 ) Period of Study: 1986-1993

Location: 14 U.S. cities Outcome: Mortality: Nonaccidental (<800) Study Design: Case-crossover

Time-series Statistical Analyses: Conditional logistic regression

Poisson Age Groups: All ages

Notes: Case days matched to referent days that had the same temperature. Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag:

Overall: Two stage: 0.36% (0.22, 0.50) 1 Single stage: 0.33% (0.19, 0.46) 1 More winter temperature lags: Two Stage: 0.39% (0.23, 0.56) 1 One stage: 0.32% (0.19, 0.46) 1 Time stratified with temperature matching: Two Stage: 0.39% (0.19, 0.58) 1 One Stage: 0.53% (0.34, 0.72) 1 Poisson regression: 0.40% (0.18, 0.62) 1



### December 2009 E-323

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Schwartz (2004, 053506 ) Period of Study: 1986-1993

Location: 14 U.S. cities Outcome: Mortality: Nonaccidental (<800) Study Design: Case-crossover Statistical Analyses: Time-stratified conditional logistic regression Age Groups: All ages

Notes: Case days matched to referent days based on concentration of gaseous air pollutants. Matched on the following conditions: 1. 24-h avg SO 2 within 1 ppb 2. Daily-maximum O 3 within 2 ppb 3. 24-h avg NO 2 within 1 ppb 4. 24-h avg CO within 0.03 ppm Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: Range: 23-36 μg/m 3 IQR (25th, 75th): Range 25th: 17-24 μg/m 3 Range 75th: 31-57 μg/m 3 Copollutant (correlation): CO

SO 2 NO 2 O 3 Increment: 10 μg/m 3 β x 1000 (SE x 1000) lag: Matched on CO: 0.527 (0.251) 0-1 avg

Matched on O 3 : 0.451 (0.170) 0-1 avg

Matched on NO 2 : 0.784 (0.185) 0-1 avg

Matched on SO 2 : 0.811 (0.175) 0-1 avg

Reference: Sharovsky et al. (2004, 156976 ) Period of Study: Jul 1996-Jun 1998

Location: São Paulo, Brazil Outcome: Mortality: Myocardial infarction Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups: ≥ 35 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 58.2 (25.8) Range (Min, Max): (23, 186) Copollutant (correlation): CO: r = 0.73 SO 2 : r = 0.72 Increment: 10 μg/m 3 β (SE) lag:

PM 10 : 0.001 (0.001)

PM 10 +CO+SO 2 : 0.0004 (0.0008)

Reference: Simpson et al. (2005, 087438 ) Period of Study: 1/1996-12/1999

Location: 4 Australian cities Outcome: Mortality: Nonaccidental (<800) Cardiovascular (390-459) Respiratory (460-519) Study Design: Time-series meta-analysis Statistical Analyses: Poisson GAM, natural splines Poisson GLM, natural splines Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Brisbane: 16.60 Sydney: 16.30 Melbourne: 18.20 Range (Min, Max): Brisbane: (2.6, 57.6) Sydney: (3.7, 75.5) Melbourne: (3.3, 51.9)

Copollutant: PM 2.5 CO NO 2 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: 0.2% (-0.8, 1.2)

Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 1995-Dec 1999

Location: Spokane, Washington Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (9th, 95th): (7.9, 41.9) μg/m 3 Copollutant (correlation): PM 10 PM 10-2.5 : r = 0.94 CO: r = 0.32 Increment : : 25 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: 1.00 (0.97, 1.03) 1 0.98 (0.95, 1.01) 2 1.00 (0.97, 1.03) 3

Reference: Staniswalis et al. (2005, 087473 ) Period of Study: 1992-1995

Location: El Paso, Texas Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: Poisson Principal component analysis (PCA) Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): (0.2, 133.4)

Notes: The chemical composition and size distribution of PM was not available, therefore, the study used wind speed as a surrogate variable for the PM 10 composition. Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Poisson regression: 1.7% 3

PCA: 24-hly measurements: 2.06% 3 Daily avg: 1.7% 3

Reference: Stafoggia et al. (2008, 157005 ) Period of Study: 1997-2004 Outcome: Mortality: Total (nonaccidental) (<800) Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD) unit: Bologna: 50.4 (31.7) Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Cardiovascular All yr: 0.63% (0.31, 1.38) 0-1



### December 2009 E-324

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Location: 9 Italian cities Cardiovascular (390-459) Respiratory (460-519)

Other natural causes Study Design: Time-stratified casecrossover Statistical Analyses: Conditional logistic regression Age Groups: ≥ 35 yr Florence: 37.5 (16.6) Mestre: 48.1 (26.8) Milan: 57.9 (38.0) Palermo: 36.2 (21.7) Pisa: 35.1 (14.9) Rome: 47.3 (19.9) Taranto: 59.8 (18.9) Turin: 71.5 (38.1) Range (Min, Max): NR Copollutant (correlation): NR Winter: 0.15% (-0.29, 0.59) 0-1 Spring: 0.72% (-0.07, 1.52) 0-1 Summer: 2.90% (1.14, 4.69) 0-1 Fall: 1.37% (0.43, 2.32) 0-1 Apparent Temperature <50th Percentile: 0.31% (-0.06, 0.67) 0-1 50th-75th Percentile: 2.05% (0.47, 3.66) 0-1 >75th Percentile: 2.68% (1.20, 4.17) 0-1

Respiratory All yr: 0.98% (0.27, 1.70) 0-1 Winter: 0.41% (-0.67, 1.51) 0-1 Spring: 2.99% (1.18, 4.83) 0-1 Summer: 3.89% (0.19, 7.73) 0-1 Fall: 0.45% (-1.11, 2.03) 0-1 Apparent Temperature <50th Percentile: 0.54% (-0.47, 1.57) 0-1 50th-75th Percentile: 3.15% (0.64, 5.73) 0-1 >75th Percentile: 4.12% (0.44, 7.93) 0-1

Other natural causes All yr: 0.37% (0.09, 0.66) 0-1 Winter: 0.14% (-0.36, 0.63) 0-1 Spring: 0.29% (-0.47, 1.05) 0-1 Summer: 2.15% (0.90, 3.42) 0-1 Fall: 0.70% (-0.41, 1.83) 0-1 Apparent Temperature <50th Percentile: 0.07% (-0.27, 0.41) 0-1 50th-75th Percentile: 1.08% (-0.02, 2.19) 0-1 >75th Percentile: 2.30% (1.06, 3.56) 0-1 Total (nonaccidental) All yr: 0.53% (0.25, 0.80) 0-1 Winter: 0.20% (-0.08, 0.49) 0-1 Spring: 0.62% (0.14, 1.10) 0-1 Summer: 2.54% (1.31, 3.78) 0-1 Fall: 1.21% (0.37, 2.06) 0-1 Apparent Temperature <50th Percentile: 0.21% (-0.06, 0.47) 0-1 50th-75th Percentile: 1.60% (0.64, 2.57) 0-1 >75th Percentile: 2.55% (1.58, 3.52) 0-1 β coefficient (SE) lag: Linear interaction PM 10 and Apparent Temperature Cardiovascular <50th Percentile: -0.000117 (0.000415) 0-1 50th-75th Percentile: 0.003445 (0.001407) 0-1 >75th Percentile: 0.002764 (0.001795) 0-1

Respiratory <50th Percentile: 0.001119 (0.000943) 0-1 50th-75th Percentile: -0.001120 (0.003480) 0-1 >75th Percentile: 0.005306 (0.004350) 0-1

Other natural causes <50th Percentile: 0.000411 (0.000383) 0-1 50th-75th Percentile: -0.001526 (0.001207) 0-1 >75th Percentile:



### December 2009 E-325

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 0.002564 (0.001958) 0-1 Total (nonaccidental) <50th Percentile: 0.000246 (0.000269) 0-1 50th-75th Percentile: 0.000584 (0.000880) 0-1 >75th Percentile: 0.002396 (0.001629) 0-1 Reference: Stölzel et al. (2007, 091374 ) Period of Study: Sep 1995-Aug 2001

Location: Erfurt, Germany Outcome: Mortality: Total (nonaccidental) (<800) Cardio-respiratory (390-459, 460-519, 785, 786) Study Design: Time-series Statistical Analyses:

Poisson GAM Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD) unit: : 31.9 (23.2) IQR (25th, 75th): (16.5, 39.5) Copollutant (correlation):

MC0.1-0.5: r = 0.85

MC0.01-2.5: r = 0.84

NO: r = 0.54

NO 2 : r = 0.62

CO: r = 0.50 Increment: 23 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Total (nonaccidental) 1.004 (0.980 1.029) 0 1.004 (0.981 1.027) 1 0.998 (0.976 1.021) 2 0.984 (0.962 1.006) 3 0.993 (0.972 1.015) 4 0.990 (0.969 1.012) 5 Cardio-respiratory 1.007 (0.981 1.034) 0 1.006 (0.981 1.032) 1 0.996 (0.971 1.021) 2 0.977 (0.953 1.002) 3 0.994 (0.970 1.018) 4 0.993 (0.969 1.017) 5 Reference: Sullivan et al. (2003, 043156 ) Period of Study:

1985-1994

Location: Western Washington Outcome: Out-of-hospital cardiac arrest Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups: 19-79 Study Population: Out-of-hospital cardiac arrests: 1,206 Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: Lag 0: 28.05 Lag 1: 27.97 Lag 2: 28.40 Range (Min, Max): (7.38, 89.83) Copollutant (correlation): SO 2 CO Notes: Study used nephelometry to measure particles and equated the measurements to PM 2.5 concentrations. Increment: : 16.51 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag:

Overall 1.05 (0.87, 1.27)

0 0.91 (0.75, 1.11)

1 1.03 (0.82, 1.28)

2



### December 2009 E-326

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sunyer et al. (2002, 034835 ) Period of Study: 1985-1995

Location: Barcelona, Spain Outcome: Mortality: Respiratory mortality Study Design: Case-crossover Statistical Analyses: Condition logistic regression Age Groups: >14 Study population: Asthmatic individuals: 5,610 Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: 61.2 Range (Min, Max): (17.3, 240.7) Copollutant: BS NO 2 O 3 SO 2 CO Increment: 32.7 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag:

Asthmatic individuals with 1 ED visit 0.884 (0.672, 1.162) 0-2 avg

Asthmatic individuals with >1 ED visit 1.084 (0.661, 1.778) 0-2 avg

Asthma/COPD individuals with >1 ED visit 1.011 (0.746, 1.368) 0-2 avg

Reference: Touloumi et al. (2005, 087477 ) Period of Study: 1990-1997

Location: 7 European cities (London, Budapest, Stockholm, Zurich, Paris, Lyon, Madrid) (APHEA2) Outcome: Mortality: Total (nonaccidental) (<800) Cardiovascular (390-459) Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Median (SD) unit: London: 25.1 Budapest: 40.2 Stockholm: 13.7 Zurich: 27.5 Paris: 22.2 Lyon: 38.5 μ Madrid: 33.4 IQR (25th, 75th): London: (20.3, 33.9) Budapest: (34.3, 45.8) Stockholm: (10.3, 19.1) Zurich: (19.2, 38.5) Paris: (16.0, 33.0) Lyon: (29.7, 50.4) Madrid: (27.6, 41.0) Copollutant (correlation): NR Increment: 10 μg/m 3 β (x 1000) (SE (x 1000)): Total (nonaccidental) No control: 0.4834 (0.1095) Reported Influenza Data Count ID: 0.4967 (0.1089) I1 ID: 0.4740 (0.1090) MI ID: 0.5019 (0.1096) RI-ID: 0.4735 (0.1091) SF ID: 0.6714 (0.1080) Estimated Influenza Data APHEA-2: 0.5550 (0.1076) I1 EID: 0.5640 (0.1073) MI EID: 0.5872 (0.1100) RI EID: 0.5872 (0.1074) SF EID: 0.6641 (0.1073)

Cardiovascular No control: 0.8432 (0.1665) Reported Influenza Data Count ID: 0.8896 (0.1662) I1 ID: 0.8545 (0.1661) MI ID: 0.8693 (0.1674) RI-ID: 0.8649 (0.1665) SF ID: 1.0107 (0.1659) Estimated Influenza Data APHEA-2: 0.9389 (0.1654) I1 EID: 0.9485 (0.1648) MI EID: 1.0440 (0.1686) RI EID: 0.9718 (0.1653) SF EID: 1.0585 (0.1652) Notes: I1 = one indicator for all epidemics M1 = multiple indicators, one per epidemic R1 = indicators for intervals indicating the range of influenza counts SF = separate smooth function during epidemic periods.

Reference: Tsai et al. (2003, 050480 ) Period of Study: 1994-2000

Location: Kaohsiung, Taiwan Outcome: Mortality: Total (nonaccidental) (<800) Respiratory (460-519) Circulatory (390-459) Study Design: Bidirectional casecrossover Statistical Analyses: Conditional logistic regression Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 81.45 Range (Min, Max): (20.50, 232.00) Copollutant: SO 2 NO 2 CO O 3 Increment: 67.00 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag: Total (nonaccidental) 1.000 (0.947, 1.056) 0-2 avg Respiratory 1.023 (0.829, 1.264) 0-2 avg Circulatory 0.971 (0.864, 1.092) 0-2 avg



### December 2009 E-327

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Vajanapoom et al. (2002, 042542 ) Period of Study: 1992-1997

Location: Bangkok, Thailand Outcome: Mortality: Total (nonaccidental) (<800) Respiratory (460-519) Cardiovascular (390-459)

Other-causes Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups: All ages 55-64 yr 65-74 yr

≥ 75 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 68.0 (23.9) IQR (25th, 75th): (50.1, 80.7) Copollutant (correlation): NR Increment: 30 μg/m 3 % Increase (Lower CI, Upper CI) lag: Total (nonaccidental) All ages: 2.3% (1.3, 3.3) 0-4 ma 55-64: 1.5% (-0.8, 3.9) 0-4 ma 65-74: 4.2% (2.0, 6.3) 0-4 ma ≥ 75: 3.9% (2.1, 5.6) 0-4 ma

Cardiovascular All ages: 0.8% (-0.9, 2.4) 0 55-64: -2.5% (-6.3, 1.3) 0 65-74: 2.9% (-0.7, 6.5) 0 ≥ 75: 1.6% (-1.8, 5.0) 0

Respiratory All ages: 5.1% (0.6, 9.6) 0-2 ma 55-64: 1.4% (-11.3, 14.2) 0-2 ma 65-74: 2.8% (-9.5, 15.2) 0-2 ma ≥ 75: 10.2% (-0.1, 20.5) 0-2 ma

Other-causes All ages: 2.4% (1.3, 3.5) 0-4 ma 55-64: 1.7% (-1.1, 4.5) 0-4 ma 65-74: 5.6% (3.1, 8.1) 0-4 ma ≥ 75: 3.7% (1.8, 5.6) 0-4 ma Reference: Vedal et al. (2003, 039044 ) Period of Study: Jan 1994-Dec 1996

Location: Vancouver, British Columbia, Canada Outcome: Mortality: Total (nonaccidental) (<800) Respiratory (460-519) Cardiovascular (390-459) Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 14.4 (5.9) Range (Min, Max): (4.1, 37.2) Copollutant (correlation): O 3 : r = 0.48 SO 2 : r = 0.76 NO : r = 0.84

2 CO: r = 0.71 The study does not present quantitative results

Reference: Venners et al. (2003, 089931 ) Period of Study: Jan 1995-Dec 1995

Location: Chongqing, China Outcome: Mortality: Total (nonaccidental) (<800) Study Design: Time-series Statistical Analyses: Poisson GAM, cubic spline Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 146.8 Range (Min, Max): (44.7, 666.2) Copollutant: SO 2 Notes: PM 10 was measured for only 7 mo of the study period. Increment: 100 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: 1.00 (0.93, 1.07) 0 0.98 (0.91, 1.04) 1 1.00 (0.93, 1.07) 2 0.96 (0.90, 1.03) 3 0.97 (0.90, 1.03) 4 0.99 (0.93, 1.06) 5

Reference: Vichit-Vadakan et al. (2008, 157095 ) Period of Study: Jan 1999-Dec 2003

Location: Bangkok, Thailand Outcome (ICD10): Mortality: Nonaccidental (A00-R99) Cardiovascular (I00-I99) Ischemic heart diseases (I20-I25) Stroke (I60-I69) Conduction disorder (I44-I49) Respiratory (J00-J98) Lower Respiratory Infection (J10-J22) COPD (J40-J47) Asthma (J45-J46) Senility (R54) Study Design: Time-series Statistical Analyses: Poisson, natural cubic spline Age Groups: All ages 0-4 yr 5-44 yr 18-50 yr 45-64 yr ≥ 50 yr ≥ 65 yr ≥ 75 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 52.1 (20.1) Range (Min, Max): (21.3, 169.2) Copollutant (correlation): NR Increment: 10 μg/m 3 % Excess Risk (Lower CI, Upper CI) lag: Cause-specific mortality: Nonaccidental: 1.3% (0.8, 1.7) 0-1 Cardiovascular: 1.9% (0.8, 3.0) 0-1 Ischemic heart disease: 1.5% (-0.4, 3.5) 0-1 Stroke: 2.3% (0.6, 4.0) 0-1 Conduction disorders: -0.%3 (-5.9, 5.6) 0-1 Cardiovascular: ≥ 65 1.8 (0.2, 3.3) 0-1 Respiratory: All ages: 1.0 (-0.4, 2.4) 0-1 ≤ 1: 14.6 (2.9, 27.6) 0-1 ≥ 65: 1.3 (-0.8, 3.3) 0-1 LRI: <5: 7.7 (-3.6, 20.3) 0-1 COPD: 1.3 (-1.8, 4.4) 0-1 Asthma: 7.4 (1.1, 14.1) 0-1 Senility: 1.8 (0.7, 2.8) 0-1 Age-specific for nonaccidental 0-4: 0.2 (-2.0, 2.4) 0-1 5-44: 0.9 (0.2, 1.7) 0-1 18-50: 1.2 (0.5, 1.9) 0-1 45-64: 1.1 (0.4, 1.9) 0-1 ≥ 50: 1.4 (0.9, 1.9) 0-1



### December 2009 E-328

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

≥ 65: 1.5 (0.9, 2.1) 0-1 ≥ 75: 2.2 (1.3, 3.0) 0-1 Sex-specific for nonaccidental Male: 1.2 (0.7, 1.7) 0-1 Female: 1.3 (0.7, 1.9) 0-1

Nonaccidental 1.2 (0.8, 1.6) 0 0.9 (0.6, 1.3) 1 0.9 (0.5, 1.3) 2 0.8 (0.4, 1.2) 3 0.3 (-0.1, 0.7) 4 1.3 (0.8, 1.7) 0-1 1.4 (0.9, 1.9) 0-4

Cardiovascular 1.5 (0.5, 2.6) 0 1.7 (0.7, 2.7) 1 1.6 (0.6, 2.6) 2 0.8 (-0.1, 1.8) 3 -0.1 (-1.1, 0.9) 4 1.9 (0.8, 3.0) 0-1 1.9 (0.6, 3.2) 0-4

Respiratory 1.0 (-0.3, 2.3) 0 0.8 (-0.5, 2.0) 1 1.1 (-0.1, 2.3) 2 1.3 (0.1, 2.6) 3 0.7 (-0.6, 1.9) 4 1.0 (-0.4, 2.4) 0-1 1.9 (1.2, 2.6) 0-4 ≥ 65 1.5 (0.9, 2.0) 0 1.1 (0.6, 1.7) 1 1.1 (0.6, 1.6) 2 1.2 (0.6, 1.7) 3 0.7 (0.2, 1.2) 4 1.5 (0.9, 2.1) 0-1 1.9 (1.2, 2.6) 0-4 Sensitivity analysis: Nonaccidental (df): 3: 1.3 (0.9, 1.8) 4: 1.2 (0.8, 1.7) 6: 1.3 (0.8, 1.7) 6, with SO 2 : 1.2 (0.8, 1.7) 6, with NO 2 : 1.0 (0.2, 1.8) 6, with O 3 : 1.1 (0.6, 1.7) 9: 1.1 (0.7, 1.6) 12: 1.1 (0.6, 1.5) 15: 1.2 (0.7, 1.6) Cardiovascular (df): 3: 1.8 (0.8, 2.7) 4: 1.6 (0.7, 2.6) 6: 1.7 (0.7, 2.7) 6, with SO 2 : 2.0 (0.9, 3.3) 6, with NO 2 : 2.3 (0.2, 4.3) 6, with O 3 : 1.8 (0.5, 3.2) 9: 1.7 (0.6, 2.8) 12: 1.8 (0.7 to 3.0) 15: 2.2 (0.9, 3.4)



### December 2009 E-329

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Villeneuve et al. (2003, 055051 ) Period of Study: 1986-1999

Location: Vancouver, Canada Outcome: Mortality: Nonaccidental (<800) Cardiovascular (401-440) Respiratory (460-519) Cancer (140-239) Study Design: Time-series Statistical Analyses: Poisson, natural splines Age Groups: ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Daily 14.0 Every 6th Day 19.6 Range (Min, Max): Daily (3.8, 52.2) Every 6th Day (3.5, 63.0) Copollutant: SO 2 CO NO 2 O 3 PM 2.5 PM 10-2.5 Increment: 15.4 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental 3.7% (-0.5, 8.0) 0-2 avg 2.6% (-0.9, 6.1) 0 2.7% (-0.7, 6.2) 1 1.9% (-1.4, 5.3) 2

Cardiovascular 3.4% (-2.7, 9.8) 0-2 avg 5.1% (0.0, 10.4) 0 1.3% (-3.8, 6.7) 1 0.6% (-4.3, 5.7) 2

Respiratory PM 10 0.1% (-9.5, 10.8) 0-2 avg 1.0% (-7.5, 10.4) 0 0.4% (-7.7, 9.3) 1 -1.3% (-8.9, 7.1) 2

Cancer 1.2% (-6.9, 10.1) 0-2 avg -2.5% (-8.8, 4.3) 0 2.3% (-4.6, 9.6) 1 3.3% (-3.7, 10.8) 2 Reference: Welty et al. (2008, 157134 ) Period of Study: 1987-2000

Location: Chicago, Illinois Outcome: Mortality: Total (nonaccidental) Study Design: Time-series Statistical Analyses: Poisson-Gibbs Sampler Bayesian Distributed Lag Model Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Excess Risk (Lower CI, Upper CI) lag: Poisson-Gibbs Sampler 0.17% (0.01, 0.34) 3 -0.24% (-0.73, 0.23) 0-14

Unconstrained: -0.19% (-0.86, 0.48) 0-14

Bayesian Distributed Lag Model -0.21% (-0.86, 0.41) 0-14 Reference: Welty and Zeger (2005, 087484 ) Period of Study: 1987-2000

Location: 100 U.S. cities (NMMAPS) Outcome: Mortality: Total (nonaccidental) (<800) Study Design: Time-series Statistical Analyses: Bayesian hierarchical model Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (SE) lag: Distributed Lag Model: Seasonally-Temporally Varying Temperature variables: 0, 1-2, 1-7, 1-14 S(t, 1 × yr): 0.229 (0.053) 1 S(t, 2 × yr): 0.220 (0.053) 1 S(t, 4 × yr): 0.187 (0.050) 1 S(t, 8 × yr): 0.178 (0.049) 1

Temperature variables: 0, 1-2, 1-7, 1-14, 0×1-2, 0×1-7, 1-2 × 1-7 S(t, 1 × yr): 0.195 (0.048) 1 S(t, 2 × yr): 0.200 (0.051) 1 S(t, 4 × yr): 0.176 (0.050) 1 S(t, 8 × yr): 0.149 (0.050) 1

Distributed Lag Model: Nonlinear Temperature variables: 0, 1-2, 1-7, 1-14 S(t, 4 × yr): 0.239 (0.053) 1

Temperature variables: 0, 1-2, 1-7, 1-14, 0×1-2, 0×1-7, 1-2 × 1-7 S(t, 4 × yr): 0.172 (0.045) 1 Temperature variables: S(0,2), S(1-2,2), S(1-7,2), S(1-14,2) S(t, 4 × yr): 0.186 (0.046) 1 Temperature variables: S(0,2), S(1-2,2), S(1-7,2), S(1-14,2), S(0×1-2,2), S(0×1-7,2), S(1-2 × 1-7,2) S(t, 4 × yr): 0.189 (0.047) 1



### December 2009 E-330

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Temperature variables: S(0,4), S(1-2,4), S(1-7,4), S(1-14,4) S(t, 4 × yr): 0.175 (0.046) 1 Temperature variables: S(0,4), S(1-2,4), S(1-7,4), S(1-14,4), S(0×1-2,4), S(0×1-7,4), S(1-2 × 1-7,4) S(t, 4 × yr): 0.190 (0.048) 1

Temperature variables: 0, 1-2, 1-7 S(t, 4 × yr): 0.252 (0.053) 1

Temperature variables: 0, 1-2, 1-7, 0×1-2, 0×1-7, 1-2 × 1-7 S(t, 4 × yr): 0.186 (0.044) 1 Temperature variables: S(0,2), S(1-2,2), S(1-7,2) S(t, 4 × yr): 0.198 (0.046) 1 Temperature variables: S(0,2), S(1-2,2), S(1-7,2), S(0×1-2,2), S(0×1-7,2), S(1-2 × 1-7,2) S(t, 4 × yr): 0.201 (0.047) 1 Temperature variables: S(0,4), S(1-2,4), S(1-7,4) S(t, 4 × yr): 0.189 (0.045) 1 Temperature variables: S(0,4), S(1-2,4), S(1-7,4), S(0×1-2,2), S(0×1-7,4), S(1-2 × 1-7,2) S(t, 4 × yr): 0.205 (0.047) 1 Temperature variables: S(0,4), S(1-2,4) S(t, 4 × yr): 0.250 (0.045) 1 Temperature variables: S(0,4), S(1-2,4), S(0×1-2,4) S(t, 4 × yr): 0.253 (0.044) 1 Temperature variables: S(0,4) S(t, 4 × yr): 0.220 (0.045) 1 Notes: 0 indicates current-day temperature 1-r indicates avg of lag 1 through lag r temperature S (, ρ ) indicates a natural spline smooth with ρ degrees of freedom. S (t, α x yr) indicates the natural spline smooth of time with degrees of freedom equal to α x (number of yr of data).



### December 2009 E-331

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Wong et al. (2007, 098391 ) Period of Study: Jan 1998-Dec 1998

Location: Hong Kong, China Outcome: Mortality: Total (nonaccidental) (<800) Cardiorespiratory (390-519) Study Design: Main analysis: Timeseries Sensitivity analysis: Case-crossover, case-only Statistical Analyses: Main analysis: Poisson GAM Sensitivity analysis: Conditional logistic regression Age Groups: ≥ 30 yr; ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 48.1 (24.3) Range (Min, Max): (15.5, 140.5) Copollutant:

NO 2 SO 2 O 3 Increment: 10 μg/m 3 % Excess Risk (Lower CI, Upper CI) lag: Main Analysis Nonaccidental Smokers: ≥ 301: .80% (0.35, 3.26) 0 1.77% (0.46, 3.11) 2 ≥ 65: 3.20% (1.36, 5.07) 0 2.42% (0.73, 4.13) 2

Never-smokers ≥ 30: -0.37% (-2.23, 1.52) 0 -0.03% (-1.72, 1.66) 2 ≥ 65P -0.70% (-2.81, 1.46) 0 -0.13% (-2.04, 1.80) 2 Cardiorespiratory Smokers ≥ 30: 1.43% (-0.86, 3.78) 0 2.32% (0.24, 4.44) 2 ≥ 65: 2.98% (0.47, 5.55) 0 2.61% (0.31, 4.95) 2

Never-smokers ≥ 30: 0.02% (-2.75, 2.87) 0 -0.79% (-3.33, 1.82) 2 ≥ 65: 0.25% (-2.62, 3.19) 0 -0.66% (-3.29, 2.04) 2 Sensitivity Analysis Poisson Regression Nonaccidental ≥ 30: 1.81% (0.21, 3.44) 0 1.93% (0.32, 3.56) 2 1.99% (0.14, 3.87) 0-3 ≥ 65: 2.31% (0.37, 4.29) 0 2.16% (0.20, 4.15) 2 2.57% (0.30, 4.89) 0-3 Cardiorespiratory ≥ 30: 1.04% (-1.45, 3.59) 0 2.18% (-0.35, 4.77) 2 1.66% (-1.24, 4.64) 0-3 ≥ 65: 1.69% (-0.93, 4.37) 0 2.44% (-0.23, 5.18) 2 2.30% (-0.80, 5.50) 0-3 Case-only: Logistic Regression Nonaccidental ≥ 30: 1.79% (0.21, 3.37) 0 1.94% (0.33, 3.56) 2 ≥ 65: 2.30% (0.42, 4.17) 0 2.16% (0.26, 4.07) 2 Cardiorespiratory ≥ 30: 1.01% (-1.37, 3.40) 0 2.16% (-0.28, 4.61) 2 ≥ 65: 1.65% (-0.96, 4.27) 0 2.42% (-0.27, 5.12) 2

Case-crossover Nonaccidental ≥ 30: 2.54% (0.35, 4.78) 0 1.35% (-0.81, 3.56) 2 ≥ 65: 3.96% (1.37, 6.63) 0 2.20% (-0.35, 4.81) 2 Cardiorespiratory ≥ 30: 0.48% (-2.74, 3.80) 0 3.24% (-0.03, 6.61) 2 ≥ 65: 2.17% (-1.40, 5.86) 0 3.43% (-0.13, 7.13) 2 Reference: Wong et al. (2007, 093278 ) Period of Study: Jan 1998-Dec 1998 Outcome: Mortality: Total (nonaccidental) (<800) Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 48.1 (24.3) Increment: 10 μg/m 3 % Excess Risk (Lower CI, Upper CI) lag: Nonaccidental



### December 2009 E-332

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Location: Hong Kong, China Cardiorespiratory (390-519) Study Design: Main analysis: Timeseries Sensitivity analysis: Case-only Statistical Analyses: Main analysis: Poisson GAM, natural cubic spline Sensitivity analysis: Logistic regression Age Groups: ≥ 30 yr; ≥ 65 yr Range (Min, Max): (15.5, 140.5) Copollutant: NO 2 SO 2 O 3 Exercise ≥ 30: 0.13% (-1.16, 1.44) 1 ≥ 65: 0.24% (-1.16, 1.67) 1

Never-exercise ≥ 30: 1.04% (0.07, 2.02) 1 ≥ 65: 1.26% (0.27, 2.27) 1 Cardio-respiratory Exercise ≥ 30: 0.46% (-1.43, 2.39) 1 ≥ 65: 0.30% (-1.65, 2.29) 1

Never-exercise ≥ 30: 0.97% (-0.36, 2.32) 1 ≥ 65: 0.98% (-0.45, 2.43) 1 Difference in % Excess Risk (Exercise vs. Never-Exercise) Nonaccidental Poisson Regression ≥ 30: -2.86% (-4.03 to -1.67) 1 ≥ 65: -3.06% (-4.37 to -1.74) 1 Case-only ≥ 30: -2.91% (-4.04 to -1.77) 1 ≥ 65: -3.12% (-4.38 to -1.84) 1 Cardiorespiratory Poisson regression ≥ 30: -2.55% (-4.32 to -0.75) 1 ≥ 65: -2.64% (-4.48 to -0.76) 1 Case-only ≥ 30: -2.63% (-4.32 to -0.92) 1 ≥ 65: -2.73% (-4.50 to -0.92) 1 Adjusted Case-only Nonaccidental Sex ≥ 30: -2.88% (-1.73 to -4.01) 1 ≥ 65: -3.09% (-1.82 to -4.35) 1

Education ≥ 30: -2.94% (-1.80 to -4.07) 1 ≥ 65: -3.18% (-1.90 to -4.44) 1 Job ≥ 30: -2.88% (-1.74 to -4.02) 1 ≥ 65: -3.11% (-1.83 to -4.37) 1 Smoking ≥ 30: -2.82% (-1.66 to -3.96) 1 ≥ 65: -2.97% (-1.68 to -4.25) 1

Illness time ≥ 30: -2.94% (-1.80 to -4.07) 1 ≥ 65: -3.16% (-1.88 to -4.42) 1 Cardiorespiratory Sex ≥ 30: -2.61% (-0.89 to -4.29) 1 ≥ 65: -2.71% (-0.90 to -4.48) 1

Education ≥ 30: -2.58% (-0.85 to -4.27) 1 ≥ 65: -2.77% (-0.95 to -4.54) 1

Job ≥ 30: -2.68% (-0.96 to -4.37) 1 ≥ 65: -2.68% (-0.88 to -4.46) 1 Smoking ≥ 30: -2.46% (-0.73 to -4.17) 1 ≥ 65: -2.50% (-0.68 to -4.29) 1

Illness Time ≥ 30: -2.63% (-0.91 to -4.32) 1 ≥ 65: -2.73% (-0.92 to -4.51) 1



### December 2009 E-333

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Case-only by Exercise Group (Never as Reference) Nonaccidental ≥ 30 Low: -3.34% (-5.77 to -0.85) 1 Moderate: -6.32% (-8.55 to -4.03) 1 High: -1.74% (-3.06 to -0.40) 1 ≥ 65 Low: -3.79% (-6.67 to -0.82) 1 Moderate: -7.78% (-10.39 to -5.10) 1 High: -1.77% (-3.21 to -0.31) 1 Cardiorespiratory ≥ 30 Low: -3.95% (-7.77, 0.04) 1 Moderate: -8.50% (-11.84 to -5.02) 1 High: -0.62% (-2.58, 1.38) 1 ≥ 65 Low: -3.97% (-8.17, 0.43) 1 Moderate: -9.42% (-13.00 to -5.69) 1 High: -0.68% (-2.71, 1.38) 1 Reference: Wong et al. (2002, 025436 ) Period of Study: 1995-1998

Location: Hong Kong, China Outcome: Mortality: Respiratory (461-519) COPD (490-496) Pneumonia & Influenza (480-487) Cardiovascular (390-459) IHD (410-414) Cerebrovascular (430-438) Study Design: Time-series Statistical Analyses: Poisson Age Groups: ≥ 30 yr; ≥ 65 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 51.53 (24.79) Range (Min, Max): (14.05, 163.79) Copollutant (correlation):

NO 2 : r = 0.780

SO 2 : r = 0.344

O 3 : r = 0.538 Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Respiratory 1.008 (1.001 to 1.014) 1 COPD 1.017 (1.002, 1.033) 0-3 Pneumonia & Influenza 1.007 (0.999, 1.015) 2 Cardiovascular 1.003 (0.998, 1.016) 2 IHD 1.013 (1.001, 1.025) 0-3 Cerebrovascular 1.007 (0.998, 1.016) 2 Respiratory PM 10 +SO 2 +O 3 +NO 2 : 1.005 (0.992, 1.010) 1 COPD PM 10 +SO 2 +O 3 +NO 2 : 0.991 (0.968, 1.015) 0-3 PM 10 +O 3 +NO 2 : 0.993 (0.970, 1.016) 0-3 Pneumonia & Influenza PM 10 +SO 2 +O 3 +NO 2 : 1.002 (0.991, 1.013) 2 IHD 0.994 (0.978, 1.009) 0-3



### December 2009 E-334

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Wong et al. (2008, 157152 ) Period of Study: Bangkok: 1999-2003 Hong Kong: 1996-2002 Shanghai & Wuhan: 2001-2004

Location: Bangkok, Thailand Hong Kong, Shanghai, and Wuhan, China Outcome (ICD10): Mortality: Natural causes (A00-R99) Cardiovascular (I00-I99) Respiratory (J00-J98) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages

≥ 65 yr

≥ 75 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Bangkok: 52.0 Hong Kong: 51.6 Shanghai: 102.0 Wuhan: 141.8 Range (Min, Max): Bangkok: (21.3, 169.2) Hong Kong: (13.7, 189.0) Shanghai: (14.0, 566.8) Wuhan: (24.8, 477.8)

Copollutant: NO 2 SO 2 O 3 Increment: 10 μg/m 3 % Excess Risk (Lower CI, Upper CI) lag: Random Effects (4 cities) Natural causes: 0.55% (0.26, 0.85) 0-1 Cardiovascular: 0.58% (0.22, 0.93) 0-1 Respiratory: 0.62% (0.22, 1.02) 0-1 Random Effects (3 Chinese cities) Natural causes: 0.37% (0.21, 0.54) 0-1 Cardiovascular: 0.44% (0.19, 0.68) 0-1 Respiratory: 0.60% (0.16, 1.04) 0-1 Sensitivity Analysis Random Effects (4 cities) Omit PM 10 >95th: 0.53% (0.27, 0.78) 0-1 Omit PM 10 >75th: 0.53% (0.29, 0.78) 0-1 Omit PM 10 >180 μg/m 3 : 0.65% (0.24, 1.06) 0-1 Omit stations with high traffic source: 0.55% (0.26, 0.85) 0-1 Warm season-dichotomous variables: 0.86% (0.11, 1.60) 0-1 Add temperature at lag 1-2 days: 0.51% (0.23, 0.79) 0-1 Add temperature at lag 3-7 days: 0.35% (0.14, 0.57) 0-1 Daily PM 10 defined by centering: 0.54% (0.26, 0.82) 0-1 Natural spline with (8, 4, 4f: 0.54% (0.26, 0.81) 0-1 Penalized spline: 0.52% (0.26, 0.77) 0-1 Random Effects (3 Chinese cities) Omit PM 10 >95th: 0.47% (0.21, 0.73) 0-1 Omit PM 10 >75th: 0.55% (0.24, 0.85) 0-1 Omit PM 10 >180 μg/m 3 : 0.46% (0.15, 0.76) 0-1 Omit stations with high traffic source: 0.38% (0.20, 0.57) 0-1 Warm season-dichotomous variables: 0.43% (0.10, 0.76) 0-1 Add temperature at lag 1-2 days: 0.36% (0.18, 0.53) 0-1 Add temperature at lag 3-7 days: 0.25% (0.10, 0.40) 0-1 Daily PM 10 defined by centering: 0.37% (0.21, 0.53) 0-1 Natural spline with (8, 4, 4f: 0.36% (0.23, 0.49) 0-1 Penalized spline: 0.34% (0.23, 0.45) 0-1 Reference: Wong et al. (2008, 157151 ) Period of Study: Jan 1996-Dec 2002

Location: Hong Kong Outcome (ICD10): Mortality: Nonaccidental (A00-T99 Z00-Z99) Cardiovascular (I00-I99) Respiratory (J00-J98) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 51.6 (25.3) Range (Min, Max): (13.5, 188.5) Copollutant:

NO 2 SO 2 O 3 Increment: 10 μg/m 3 % Excess Risk (Lower CI, Upper CI) lag: Nonaccidental: Low SDI 0.37 (-0.10, 0.84) 0 0.40 (-0.04, 0.84) 1 0.14 (-0.28, 0.57) 2 -0.12 (-0.55, 0.30) 3 -0.14 (-0.56, 0.28) 4

Middle SDI 0.70 (0.34, 1.07) 0 0.48 (0.14, 0.82) 1 0.35 (0.02, 0.68) 2 0.18 (-0.14, 0.51) 3 0.17 (-0.16, 0.50) 4 High SDI 0.22 (-0.29, 0.73) 0 0.46 (-0.01, 0.94) 1 0.29 (-0.17, 0.75) 2 -0.05 (-0.51, 0.40) 3 -0.06 (-0.51, 0.40) 4

All areas



### December 2009 E-335

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 0.45 (0.19, 0.72) 0 0.40 (0.15, 0.64) 1 0.22 (-0.02, 0.45) 2 0.00 (-0.24, 0.23) 3 0.03 (-0.20, 0.26) 4

Cardiovascular: Low SDI 0.14 (-0.77, 1.06) 0 0.64 (-0.21, 1.49) 1 0.24 (-0.58, 1.07) 2 -0.27 (-1.09, 0.55) 3 0.01 (-0.80, 0.83) 4

Middle SDI 0.66 (0.00, 1.34) 0 0.49 (-0.13, 1.12) 1 0.80 (0.20, 1.40) 2 0.65 (0.06, 1.25) 3 0.52 (-0.07, 1.12) 4 High SDI 0.83 (-0.08, 1.75) 0 0.89 (0.04, 1.75) 1 0.12 (-0.70, 0.95) 2 -0.09 (-0.91, 0.73) 3 0.04 (-0.77, 0.86) 4

All areas 0.52 (0.05, 1.00) 0 0.58 (0.14, 1.03) 1 0.43 (0.00, 0.86) 2 0.14 (-0.28, 0.57) 3 0.23 (-0.20, 0.65) 4

Respiratory: Low SDI 0 0.69 (-0.44, 1.82) 0 1 0.55 (-0.50, 1.61) 1 2 0.36 (-0.66, 1.39) 2 3 -0.24 (-1.25, 0.78) 3 4 -0.17 (-1.17, 0.85) 4

Middle SDI 0.31 (-0.50, 1.13) 0 0.77 (0.01, 1.53) 1 0.85 (0.12, 1.59) 2 0.66 (-0.07, 1.39) 3 0.69 (-0.03, 1.42) 4 High SDI 0.27 (-0.85, 1.40) 0 0.72 (-0.32, 1.78) 1 1.46 (0.45, 2.47) 2 0.70 (-0.30, 1.71) 3 0.48 (-0.52, 1.48) 4

All areas 0.39 (-0.20, 0.99) 0 0.70 (0.15, 1.26) 1 0.89 (0.36, 1.42) 2 0.45 (-0.08, 0.98) 3 0.43 (-0.10, 0.96) 4 High SDI vs. Middle SDI Nonaccidental: 0.23 (-0.25, 0.72) 0-1 Cardiovascular: 0.49 (-0.40, 1.40) 0-1 Respiratory: 0.49 (-0.58, 1.58) 0-1 High SDI vs. Low SDI Nonaccidental: 0.12 (-0.42, 0.67) 0-1 Cardiovascular: 0.82 (-0.20, 1.86) 0-1 Respiratory: -0.15 (-1.39, 1.10) 0-1

Trend Test Nonaccidental: 0.04 (-0.15, 0.22) 0-1 Cardiovascular: 0.27 (-0.07, 0.61) 0-1 Respiratory: -0.04 (-0.46, 0.37)



### December 2009 E-336

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

0-1 SDI = Social Deprivation Index. The higher the SDI the lo wer the SES of the individual.

Reference: Yang et al. (2004, 055603 ) Period of Study: 1994-1998

Location: Taipei, Taiwan Outcome: Mortality: Nonaccidental (<800) Circulatory (390-459) Respiratory (460-519) Study Design: Bi-directional casecrossover Statistical Analyses: Conditional logistic regression Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): 51.99 Range (Min, Max): (13.71, 211.30) Copollutant: SO 2 NO 2 CO O 3 Increment: 31.43 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag:

Nonaccidental 0.995 (0.971, 1.020) 0 Respiratory 0.986 (0.906, 1.074) 0 Circulatory 0.988 (0.942, 1.035)



### December 2009 E-337

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zanobetti et al. (2003, 042812 ) Period of Study: 1990-1997

Location: 10 European cities (APHEA2) Outcome: Mortality: Nonaccidental (<800) Circulatory (390-459) Respiratory (460-519) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups: 15-64 yr 65-74 yr

≥ 75 yr Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Athens: 42.7 (12.9) Budapest: 41 (9.1) Lodz: 53.5 (15.5) London: 28.8 (13.7) Madrid: 37.8 (17.7) Paris: 22.5 (11.5) Prague: 76.2 (45.7) Rome: 58.7 (17.4) Stockholm: 15.5 (7.9) Tel Aviv: 50.3 (57.5) Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Cardiovascular 0.69% (0.31, 1.08) 0-1 avg 40-day distributed lag 1.99% (1.44, 2.54) 4th degree 1.97% (1.38, 2.55)

Unrestricted Respiratory 0.74% (-0.17, 1.66) 0-1 avg 40-day distributed lag 4.21% (1.70, 6.79) 4th degree 4.20% (1.08, 7.42)

Unrestricted Unrestricted distributed lags Cardiovascular 1.34% (0.89, 1.79) 20 1.72% (1.20, 2.25) 30 1.97% (1.38, 2.55) 40

Respiratory 1.71% (-0.65, 4.12) 20 2.62% (0.19, 5.11) 30 4.20% (1.08, 7.42) 40 40-day lags Nonaccidental 15-64 -0.25% (-0.87, 0.36) 4th degree -0.01 (-0.76, 0.75) Unrestricted 65-74 0.78% (0.23, 1.33) 4th degree 0.74% (0.02, 1.45) Unrestricted ≥ 75 1.84% (0.92, 2.78) 4th degree 1.94% (1.07, 2.81) Unrestricted

Cardiovascular 65-74 2.06% (1.05, 3.09) 4th degree 1.62 (0.54, 2.70) Unrestricted ≥ 75 2.35% (1.42, 3.29) 4th degree 2.52% (1.57, 3.48) Unrestricted

Respiratory ≥ 75 4.57% (1.25, 7.99) 4th degree 4.52% (0.89, 8.28) Unrestricted



### December 2009 E-338

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zeka et al. (2005, 088068 ) Period of Study: Jan 1989-Dec 2000

Location: 20 U.S. cities Outcome (ICD10): Mortality: All-cause (nonaccidental) (V01-Y98) Heart Disease (I01-I51) IHD (I20-I25) Myocardial infarction (I21, I22) Dysrhythmias (I46-I49) Heart failure (I50) Stroke (I60-I69) Respiratory (J00-J99) Pneumonia (J12-J18) COPD (J40-J44, J47) Study Design: Time-stratified casecrossover Statistical Analyses: Conditional logistic regression Age Groups: All ages Pollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Birmingham: 31.9 (18.0) μg/m 3 Boulder: 22.1 (11.3) Caton: 26.6 (11.5) Chicago: 33.7 (16.4) Cincinnati: 31.4 (13.9) Cleveland: 37.5 (18.7) Colorado Springs: 24.0 (13.2) Columbus: 28.5 (12.5) Denver: 28.5 (12.8) Detroit: 32.1 (17.7) Honolulu: 15.9 (6.8) Minneapolis: 24.7 (12.3) Nashville: 30.1 (12.1) New Haven: 25.4 (14.4) Pittsburgh: 30.2 (18.5) Provo: 33.7 (22.2) Seattle: 26.4 (14.7) Salt lake City: 35.0 (20.8) μ Terra Haute: 29.2 (14.6) μ Youngstown: 30.8 (13.9) Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Single-lag model All-Cause (nonaccidental) 0.20% (0.08, 0.32) 0 0.35% (0.21, 0.49) 1 0.24% (0.14, 0.34) 2 Respiratory 0.34% (-0.07, 0.75) 0 0.52% (0.15, 0.89) 1 0.51% (0.16, 0.86) 2 COPD -0.06% (-0.63, 0.51) 0 0.43% (-0.14, 1.00) 1 0.39% (-0.16, 0.94) 2 Pneumonia 0.50% (0.09, 1.09) 0 0.59% (-0.12, 1.30) 1 0.82% (0.25, 1.39) 2 Heart disease 0.12% (-0.06, 0.30) 0 0.30% (0.12, 0.48) 1 0.37% (0.17, 0.57) 2 IHD 0.19% (-0.03, 0.41) 0 0.41% (0.19, 0.63) 1 0.43% (0.10, 0.76) 2 Myocardial Infarction 0.36% (-0.05, 0.77) 0 0.17% (-0.18, 0.52) 1 0.13% (-0.22, 0.48) 2 Heart Failure 0.17% (-0.63, 0.97) 0 -0.01% (-0.81, 0.79) 1 0.78% (-0.004, 1.56) 2 Dysrhythmias -0.23% (-1.41, 0.95) 0 0.37% (-0.47, 1.21) 1 0.33% (-0.55, 1.21) 2 Stroke 0.09% (-0.49, 0.60) 0 0.41% (-0.02, 0.84) 1 0.14% (-0.27, 0.55) 2

Unconstrained distributed lag model All-cause (nonaccidental) 0.45% (0.25, 0.65) 0-3 Respiratory 0.87% (0.38, 1.36) 0-3 COPD 0.43% (-0.35, 1.21) 0-3 Pneumonia 1.24% (0.46, 2.02) 0-3 Heart Disease 0.50% (0.25, 0.75) 0-3 IHD 0.65% (0.32, 0.98) Myocardial Infarction 0.36% (-0.25, 0.97) 0-3 Heart Failure 0.60% (-0.50, 1.70) 0-3 Dysrhythmias 0.20% (-1.03, 1.43) 0-3 Stroke 0.46% (-0.13, 1.05) 0-3 Reference: Zeka et al. (2006, 088749 ) Period of Study: Jan 1989-Dec 2000

Location: 20 U.S. cities Outcome (ICD10): Mortality: All-cause (nonaccidental) (V01-Y98) Heart Disease (I01-I51) Myocardial infarction (I21, I22) Stroke (I60-I69) Respiratory (J00-J99) Study Design: Time-stratified casePollutant: PM 10 Averaging Time: 24-h avg Mean (SD): Birmingham: 31.9 (18.0) μg/m 3 Boulder: 22.1 (11.3) Caton: 26.6 (11.5) Chicago: 33.7 (16.4) Cincinnati: 31.4 (13.9) Cleveland: 37.5 (18.7) Colorado Springs: 24.0 (13.2) Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: All-cause (nonaccidental) Male: 0.46% (0.28, 0.64) 1-2 avg Female: 0.37% (0.17, 0.57) 1-2 avg White: 0.40% (0.22, 0.58) 1-2 avg Black: 0.37% (-0.02, 0.76) 1-2 avg

Age: <65: 0.25% (0.01, 0.49) 1-2 avg 75: 0.23% (-0.06, 0.52) 1-2 avg



### December 2009 E-339

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

crossover Statistical Analyses: Conditional logistic regression Age Groups: All ages <65 yr 65-75 yr >75 yr Columbus: 28.5 (12.5) Denver: 28.5 (12.8) Detroit: 32.1 (17.7) Honolulu: 15.9 (6.8) Minneapolis: 24.7 (12.3) Nashville: 30.1 (12.1) New Haven: 25.4 (14.4) Pittsburgh: 30.2 (18.5) Provo: 33.7 (22.2) Seattle: 26.4 (14.7) Salt lake City: 35.0 (20.8) Terra Haute: 29.2 (14.6) Youngstown: 30.8 (13.9) Range (Min, Max): NR Copollutant (correlation): NR >75: 0.64% (0.44, 0.84) 1-2 avg

Educational Attainment: Low (<8 yr): 0.62% (0.29, 0.95) 1-2 avg Medium (8-12 yr): 0.36% (0.12, 0.60) 1-2 avg High (>12 yr): 0.27% (-0.004, 0.54) 1-2 avg

Location of Death: In hospital: 0.22% (0.04, 0.40) 1-2 avg Out of hospital: 0.71% (0.51, 0.91) 1-2 avg

Season: Winter: 0.28% (0.04, 0.52) 1-2 avg Summer: 0.19% (-0.22, 0.60) 1-2 avg Transition (spring/fall): 0.49% (0.25, 0.73) 1-2 avg

Respiratory Male: 0.71% (0.004, 1.42) 0-3 Female: 1.04% (0.33, 1.75) 0-3 White: 0.88% (0.33, 1.43) 0-3 Black: 0.71% (-0.56, 1.98) 0-3

Age: <65: 0.94% (-0.31, 2.19) 0-3 65-75: 0.87% (-0.25, 1.99) 0-3 >75: 0.88% (0.17, 1.59) 0-3

Educational Attainment: Low (<8 yr): 0.82% (-0.32, 1.96) 0-3 Medium (8-12 yr): 0.88% (0.12, 1.64) 0-3 High (>12 yr): 0.88% (-0.04, 1.80) 0-3

Location of Death: In hospital: 0.78% (0.17, 1.39) 0-3 Out of hospital: 1.09% (0.25, 1.93) 0-3

Season: Winter: -0.007% (-0.87, 0.86) 0-3 Summer: 0.69% (-0.68, 2.06) 0-3 Transition (spring/fall): 1.57% (0.86, 2.28) 0-3

Heart Disease Male: 0.54% (0.23, 0.85) 2 Female: 0.46% (0.15, 0.77) 2 White: 0.50% (0.25, 0.75) 2 Black: 0.64% (0.13, 1.15) 2

Age: <65: 0.04% (-0.45, 0.53) 2 65-75: 0.60% (0.13, 1.07) 2 >75: 0.65% (0.30, 1.00) 2

Educational Attainment: Low (<8 yr): 0.72% (0.23, 1.21) 2 Medium (8-12 yr): 0.38% (0.07, 0.69) 2 High (>12 yr): 0.54% (0.13, 0.95) 2

Location of Death: In hospital: 0.15% (-0.14, 0.44) 2 Out of hospital: 0.93% (0.60, 1.26) 2

Season: Winter: 0.41% (-0.002, 0.82) 2 Summer: 0.52 (0.03, 1.01) 2 Transition (spring/fall): 0.56% (0.13, 0.99) 2



### December 2009 E-340

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Myocardial Infarction Male: 0.21% (-0.40, 0.82) 0 Female: 0.59% (0.08, 1.10) 0 White: 0.24% (-0.27, 0.75) 0 Black: 0.99% (0.05, 1.93) 0 <65: 0.12% (-0.76, 1.00) 0 65-75: 0.92% (0.21, 1.63) 0 >75: 0.16% (-0.58, 0.90) 0

Educational Attainment: Low (<8 yr): 0.33% (-0.83, 1.49) 0 Medium (8-12 yr): 0.79% (0.28, 1.30) 0 High (>12 yr): -0.13% (-0.82, 0.56) 0

Location of Death: In hospital: 0.34% (-0.11, 0.79) 0 Out of hospital: 0.48% (-0.23, 1.19) 0

Season: Winter: 0.32% (-0.37, 1.01) 0 Summer: 0.30% (-0.82, 1.42) 0 Transition (spring/fall): 0.38% -0.31, 1.07) 0

Stroke Male: 0.11% (-0.58, 0.80) 1 Female: 0.59% (-0.04, 1.22) 1 White: 0.48% (0.01, 0.95) 1 Black: 0.13% (-0.87, 1.13) 1

Age: <65: 0.09% (-1.09, 1.27) 1 65-75: -0.46% (-1.42, 0.50) 1 >75: 0.80% (0.27, 1.33) 1

Educational Attainment: Low (<8 yr): 0.07% (-1.44, 1.58) 1 Medium (8-12 yr): 0.29% (-0.32, 0.90) 1 High (>12 yr): 0.52% (-0.28, 1.32) 1

Location of Death: In hospital: 0.06% (-0.49, 0.61) 1 Out of hospital: 0.87% (0.05, 1.69) 1

Season: Winter: -0.09% (-0.93, 0.75) 1 Summer: 0.67% (-0.31, 1.65) 1 Transition (spring/fall): 0.51% (-0.20, 1.22) 1Contributing causes of disease: Allcause Secondary pneumonia present: 0.67% (0.16, 1.18) 1-2 avg Secondary pneumonia absent: 0.34% (0.16, 0.52) 1-2 avg Secondary heart failure present: 0.42% (0.01, 0.83) 1-2 avg Secondary heart failure absent: 0.37% (0.19, 0.55) 1-2 avg Secondary stroke present: 0.85% (0.30, 1.40) 1-2 avg Secondary stroke absent: 0.32% (0.14, 0.50) 1-2 avg Diabetes present: 0.57% (0.02, 1.12) 1-2 avg Diabetes absent: 0.34% (0.14, 0.54) 1-2 avg

Respiratory Secondary pneumonia present: 1.28% (-0.33, 2.89) 0-3 Secondary pneumonia absent: 0.78% (0.15, 1.41) 0-3 Secondary heart failure present: 1.48% (0.07, 2.89) 0-3 Secondary heart failure absent:



### December 2009 E-341

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 0.79% (0.26, 1.32) 0-3 Secondary stroke present: 1.95% (-0.11, 4.01) 0-3 Secondary stroke absent: 0.80% (0.29, 1.31) 0-3 Diabetes present: 1.96% (-0.22, 4.14) 0-3 Diabetes absent: 0.82% (0.31, 1.33) 0-3

Heart Disease Secondary pneumonia present: 0.66% (-0.63, 1.95) 2 Secondary pneumonia absent: 0.49% (0.27, 0.71) 2 Secondary stroke present: 0.73% (-0.05, 1.51) 2 Secondary stroke absent: 0.48% (0.24, 0.72) 2 Diabetes present: 0.34% (-0.42, 1.10) 2 Diabetes absent: 0 .52% (0.28, 0.76) 2 Myocardial Infarction Secondary pneumonia present: 1.54% (-1.05, 4.13) 0 Secondary pneumonia absent: 0.42% (0.05, 0.79) 0 Secondary stroke present: 0.50% (-1.38, 2.38) 0 Secondary stroke absent: 0.36% (-0.05, 0.77) 0 Diabetes present: 0.70% (-0.38, 1.78) 0 Diabetes absent: 0.41% (0.04, 0.78) 0

Stroke Secondary pneumonia present: 1.74% (0.35, 3.13) 1 Secondary pneumonia absent: 0.29% (-0.16, 0.74) 1 Secondary heart failure present: 1.01% (-0.77, 1.79) 1 Secondary heart failure absent: 0.38% (-0.05, 0.81) 1 Diabetes present: 1.02% (-0.53, 2.57) 1 Diabetes absent: 0.37% (-0.08, 0.82) 1

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-342

# Table E-17. Short-term exposure-mortality - PM 10-2.5 

# .

Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Burnett et al. (2004, 086247 ) Period of Study: 1981-1999

Location: 12 Canadian cities Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: 1. Poisson, natural splines 2. Random effects regression model Age Groups: All ages Pollutant: P10-2.5 Averaging Time: 24-h avg Mean (SD): 11.4 Range (Min, Max): NR Copollutant: NO 2 O

3 SO 2 CO PM 10 PM 2.5 Note: PM 10 measurement calculated as the sum of PM 2.5 and PM 10-2.5 measurements. Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag:

1981-1999

PM 10-2.5 : 0.31% (-0.66, 1.33) 1

PM 10-2.5 +NO 2 : 0.65% (-0.23, 1.59) 1

Reference: Kan et al. (2007, 091267 ) Period of Study: Mar 2004-Dec 2005

Location: Shanghai, China Outcome (ICD10): Mortality: Total (nonaccidental) (A00-R99) Cardiovascular (I00-I99) Respiratory (J00-J98) Study Design: Time-series Statistical Analyses: Poisson GAM, penalized splines Age Groups: All ages Pollutant: PM 10-2.5 Averaging Time: 24-h avg Mean (SD): 56.4 (1.34) Range (Min, Max): (8.3, 235.0) Copollutant (correlation): PM 10 : r = 0.88

PM 2.5 : r = 0.48

O 3 : r = 0.07 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Total: 0.12% (-0.13, 0.36)

0-1 Cardiovascular: 0.34% (-0.05, 0.73)

0-1 Respiratory: 0.40% (-0.34, 1.13)

0-1

Reference: Kettunen et al. (2007, 091242 ) Period of Study: 1998-2004

Location: Helsinki, Finland Outcome (ICD10): Mortality: Stroke (I60-I61, I63-I64) Study Design: Time-series Statistical Analyses: Poisson GAM, penalized thin-plate splines Age Groups: ≥ 65 yr Pollutant: PM 10-2.5 Averaging Time: 24-h avg Median (SD) unit: Cold Season: 6.7

Warm Season: 8.4 Range (Min, Max): Cold Season: (0.0, 101.4) Warm Season: (0.0, 42.0) Copollutant: O 3 , CO, NO 2 PM 10 PM 2.5 UFP Increment: Cold Season: 8.3 μg/m 3 Warm Season: 5.7 μg/m 3 % Increase (Lower CI, Upper CI) lag: Cold Season: -1.04% (-6.63, 4.89) 0 -2.49% (-7.57, 2.88) 1. -4.93% (-9.99, 0.41) 2 -4.33% (-9.32, 0.93) 3 Warm Season: 7.05% (-1.88, 16.80) 0 4.38% (-4.26, 13.81) 1: -1.19% (-9.45, 7.84) 2 1.42% (-6.79, 10.34) 3

Reference: Klemm et al. (2004, 056585 ) Period of Study: Aug 1998-Jul 2000

Location: Fulton and DeKalb counties, Georgia (ARIES) Outcome: Mortality: Nonaccidental (<800) Cardiovascular (390-459) Respiratory (460-519) Cancer (140-239) Study Design: Time-series Statistical Analyses: Poisson GLM, natural cubic splines Age Groups: <65 yr, ≥ 65 yr Pollutant: PM 10-2.5 Averaging Time: 24-h avg Mean (SD): 9.69 (3.94) Range (Min, Max): (1.71, 25.17) Copollutant: PM 2.5 O 3 NO 2 CO SO 2 Acid EC OC SO 4 Oxygenated Hydrocarbons Nonmethane hydrocarbons NO 3 Increment: NR β (SE) lag: Quarterly Knots: 0.00433 (0.00333) 0-1 Monthly Knots: 0.00617 (0.00360) 0-1 Biweekly Knots: 0.00516 (0.00381) 0-1



### December 2009 E-343

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Respiratory mortality Study Design: Cohort

Covariates: Temperature, humidity Statistical Analysis: autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (SD) Unit: 14.0 (9.5) μg/m 3 Range (Min, Max): 0.1, 93.1 Copollutant: PM 2.5 -1, PM1 Increment: 10 μg/m 3 Odds Ratio (95%CI) Lag Single Pollutant Model Avg L0-1: 1.000 (0.944-1.060), p = 0.991 L1: 1.002 (0.955-1.052), p = 0.931 L2: 1.070 (1.023-1.118), p = 0.003

Multi-pollutant Model Avg L0-1: 1.002 (0.937-1.071), p = 0.958 L1: 0.998 (0.943-1.056), p = 0.0.936 L2: 1.033 (0.980-1.089), p = 0.226

Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Cardiovascular mortality Study Design: Cohort

Covariates: Temperature, humidity Statistical Analysis: Autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (SD) Unit: 14.0 (9.5) μg/m 3 Range (Min, Max): 0.1, 93.1 Copollutant: PM 2.5 -1, PM1 Increment: 10 μg/m 3 Odds Ratio (95%CI) Lag Avg L0-1: 1.054 (1.019-1.089), p = 0.002 L1: 1.059 (1.031-1.072), p = 0.000 L2: 1.044 (1.017-1.072), p = 0.001

Multi-pollutant Model Avg L0-1: 1.053 (1.013-1.094), p = 0.009 L1: 1.059 (1.026-1.094), p = 0.001 L2: 1.044 (1.012-1.078), p = 0.007

Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Cerebrovascular mortality Study Design: Cohort

Covariates: Temperature, humidity Statistical Analysis: Autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 10-2.5 Averaging Time: 24 h Mean (SD) Unit: 14.0 (9.5) μg/m 3 Range (Min, Max): 0.1, 93.1 Copollutant: PM 2.5 -1, PM1 Increment: 10 μg/m 3 Odds Ratio (95%CI) Lag Avg L0-1: 1.087 (1.018-1.161), p = 0.013 L1: 1.086 (1.030-1.145), p = 0.002 L2: 1.051 (0.997-1.108), p = 0.064

Multi-pollutant Model Avg L0-1: 1.103 (1.022-1.191), p = 0.011 L1: 1.098 (1.030-1.171), p = 0.004 L2: 1.076 (1.010-1.146), p = 0.023

Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 1995-Dec 1999

Location: Spokane, Washington Outcome: Mortality: Nonaccidental (< 800) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages Pollutant: PM 10-2.5 Averaging Time: 24-h avg Mean (SD) unit: NR Range (9th, 95th): NR Copollutant (correlation): PM1: r = 0.19 PM 2. : r = 0.31 5 PM 10 : r = 0.94 CO: r = 0.32 This study does not present quantitative results for PM 10-2.5

.

Reference: Stieb et al. (2002, 025205 ) Period of Study: Publication dates of studies: 1985-Dec 2000 Mortality series: 1958-1999

Location: 40 cities (11 Canadian cities, 19 U.S. cities, Santiago, Amsterdam, Erfurt, 7 Korean cities) Outcome: Mortality: All-cause (nonaccidental) Study Design: Meta-analysis Statistical Analyses: Random effects model Age Groups: All ages Pollutant: PM 10-2.5 Averaging Time: NR Mean (SD): NR Range (Min, Max): NR Copollutant: Varied between studies: PM 2.5 , O 3 , SO 2 , NO 2 , CO Increment: 13.0 μg/m 3 % Increase (Lower CI, Upper CI) lag: Single-pollutant models: 10 studies

PM 10-2.5 : 1.2% (0.5, 1.9) Multipollutant models: 6 studies

PM 10-2.5 : 0.9% (-0.3, 2.0)



### December 2009 E-344

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Villeneuve et al. (2003, 055051 ) Period of Study: 1986-1999

Location: Vancouver, Canada Outcome: Mortality: Nonaccidental (<800) Cardiovascular (401-440) Respiratory (460-519) Cancer (140-239) Study Design: Time-series Statistical Analyses: Poisson, natural splines Age Groups: ≥ 65 Pollutant: PM 10-2.5 Averaging Time: 24-h avg Mean (SD): Daily: 6.1 Every 6th Day 8.3 Range (Min, Max): Daily: (0.0, 72.0) Every 6th Day: (0.7, 35.0)

Copollutant: PM 2.5 PM 10 SO 2 CO NO 2 O 3 Increment: 11.0 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental 1.4% (-2.5, 5.4) 0-2 avg 1.0% (-1.9, 4.0) 0 -1.1% (-4.0, 1.8) 1 2.0% (-1.0, 5.1) 2

Cardiovascular 5.9% (-0.2, 12.4) 0-2 avg 5.9% (1.1, 10.8) 0 1.4% (-3.3, 6.4) 1 2.2% (-2.0, 6.7) 2

Respiratory -1.0% (-9.8, 8.8) 0-2 avg -1.5% (-9.4, 7.1) 0 -1.5% (-8.4, 6.0) 1 0.1% (-6.4, 6.9) 2

Cancer 4.4% (-3.6, 13.1) 0-2 avg 3.1% (-2.9, 9.4) 0 -1.0% (-6.9, 5.3) 1 4.0% (-2.1, 10.4) 2 Reference: Wilson et al. (2007, 157149 ) Period of Study: 1995-1997

Location: Phoenix, Arizona Outcome: Mortality:

Cardiovascular Study Design: Time-series Statistical Analyses: Poisson GAM, nonparametric smoothing spline Age Groups: >25 Pollutant: PM 10-2.5 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Excess Risk (Lower CI, Upper CI) lag: Central Phoenix: 2.4% (-1.2, 6.1) 0-5 ma

Middle Phoenix: 3.8% (0.3, 7.5) 0-5 ma 3.4% (1.0, 5.8) 1 3.0% (0.7, 5.4) 2

Outer Phoenix: 1.6% (-1.9, 5.2) 0-5 ma

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-345

# Table E-18. Short-term exposure-mortality - PM 2.5 

# (including PM components/sources).

Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Basu et al. (2008, 098716 ) Period of Study: May 1999-Sept 2003

Location: 9 California counties Outcome (ICD10): Mortality: Nonaccidental (V01-Y98) Study Design: (1) Main analysis: Case-crossover (2) Sensitivity analysis: Time-series Statistical Analyses: (1) Main analysis: conditional logistic regression (2) Sensitivity analysis: Poisson GAM Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SE) unit: Contra Costa: 8.6 Fresno: 7.6 Kern: 11.3 Los Angeles: 19.8 Orange: 17.0 Riverside: 28.4 Sacramento: 8.8 San Diego: 13.4 Santa Clara: 10.8 IQR (25th, 75th): Contra Costa: (5.8, 10.1) Fresno: (3.8, 9.8) Kern: (8.0, 13.5) Los Angeles: (14.7, 23.3) Orange: (11.8, 21.0) Riverside: (17.9, 36.1) Sacramento: (5.8, 10.1) San Diego: (10.3, 15.8) Santa Clara: (7.2, 13.8) Copollutant (correlation): PM r = 0.45

10 O 3 (1hr) r = 0.28 O 3 (8hr) r = 0.22 CO r = 0.45 NO 2 r = 0.43 The study does not provide results quantitatively.

Reference: Dominici et al. (2007, 097361 ) Period of Study: PM 10 : 1987-2000 PM 2.5 : 1999-2000

Location: 100 U.S. counties (NMMAPS) Outcome: Mortality: All-cause (nonaccidental) Cardiorespiratory Other-cause Study Design: Time-series Statistical Analyses: 2-stage Bayesian hierarchical model Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag:

1999-2000: All-cause: 0.29% (0.01, 0.57) 1 Cardiorespiratory: 0.38% (-0.07, 0.82) 1

Reference: Dominici et al. (2007, 099135 ) Period of Study: 2000-2005

Location: 72 U.S. counties representing 69 communities Outcome: Total mortality Study Design: Time-series Statistical Analyses: 2-stage Bayesian hierarchical model Age Groups: All ages Pollutant: PM 2.5 , Nickel, speciated fine PM, and Vanadium Averaging Time: Annual avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR The study does not provide results quantitatively.

Note: The study investigated whether county-specific short-term effects of PM 10 on mortality are modified by longterm county-specific nickel or vanadium PM 2.5 concentrations.

Reference: Franklin et al. (2007, 091257 ) Period of Study: 1997-2002

Location: 27 U.S. communities Outcome: Mortality: All-cause (nonaccidental (<800) Cardiovascular (390-429) Respiratory (460-519) Stroke (430-438) Study Design: Time-stratified casecrossover Statistical Analyses: Conditional logistic regression Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): 15.7 μg/m 3 Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: All-cause (nonaccidental): 0.67% (-0.12, 1.46) 0 1.21% (0.29, 2.14) 10.82% (0.02, 1.63) 0-1

Respiratory: 1.31% (-0.10, 2.73) 0 1.78% (0.20, 3.36) 1 1.67% (0.19, 3.16) 0-1

Cardiovascular: 0.34% (-0.61, 1.28) 0 0.94% (-0.14, 2.02) 1. 0.54% (-0.47, 1.54) 0-1

Stroke: 0.62% (-0.69, 1.94) 0 1.03% (0.02, 2.04) 1. 0.67% (-0.23, 1.57) 0-1



### December 2009 E-346

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Age ≥ 75: All cause: 1.66% (0.62, 2.70) 1 Respiratory: 1.85% (0.27, 3.44) 1 Cardiovascular: 1.29% (0.15, 2.42) 1 Stroke: 1.52% (0.37, 2.67) 1

Age<75: All cause: 0.62% (-0.30, 1.55) 1 Respiratory: 1.53% (-0.67, 3.74) 1 Cardiovascular: 0.26% (-1.04, 1.56) 1 Stroke: -0.78% (-2.32, 0.76) 1

Male: All cause: 1.06% (0.07, 2.06) 1 Respiratory: 1.90% (0.14, 3.65) 1 Cardiovascular: 0.52% (-0.63, 1.66) 1 Stroke: 0.79% (-0.42, 2.02) 1

Female: All cause: 1.34% (0.40, 2.27) 1 Respiratory: 1.57% (-0.22, 3.35) 1 Cardiovascular: 1.30% (0.14, 2.46) 1 Stroke: 0.79% (-0.51, 2.09) 1

East: ll cause: 1.95% (0.50, 3.40)1 Respiratory: 2.66% (0.33, 5.00) 1 Cardiovascular: 1.52% (0.06, 2.98) 1 Stroke: 1.16% (-0.40, 2.73) 1

West: All cause: 0.05% (-1.80, 1.89) 1 Respiratory: 0.67% (-2.00, 3.34) 1| Cardiovascular: 0.11% (-2.03, 2.24) 1| Stroke: 0.94% (-0.38, 2.26) 1

PM 2.5 >15 μg/m 3 : All cause: 1.10% (-0.43, 2.64) 1 Respiratory: 1.42% (-0.84, 3.68) 1 Cardiovascular: 0.88% (-0.87, 2.62) 1 Stroke: 0.91% (-0.28, 2.10) 1

PM 2.5 ≤ 15 μg/m 3 : All cause: 1.41% (-0.49, 3.30) 1 Respiratory: 2.46% (-0.49, 5.42) 1 Cardiovascular: 1.09% (-1.15, 3.32) 1 Stroke: 1.36% (-0.56, 3.27) 1

Effect of A/C at percentile of air conditioning prevalence: 25th percentile (45% prevalence of A/C): All cause: 1.50% (0.13, 2.88) 1 Respiratory: 2.27% (0.27, 4.27) 1 Cardiovascular: 1.04% (-0.54, 2.63) 1 Stroke: 1.04% (-0.44, 2.53) 1 75th percentile (80% prevalence of A/C): All cause: 0.85% (-0.64, 2.35) 1 Respiratory: 1.04% (-1.29, 3.37) 1 Cardiovascular: 0.81% (-0.93, 2.61) 1 Stroke: 1.03% (-0.76, 2.83) 1

Effect of A/C at percentile of air conditioning prevalence in cities with summer peaking PM 2.5 concentrations: 25th percentile (45% prevalence of A/C): All cause: 1.01% (-0.30, 2.32) 1 Respiratory: 0.76% (-1.38, 2.90) 1 Cardiovascular: 0.43% (-0.86, 1.72) 1 Stroke: -0.18% (-2.08, 1.73) 1 75th percentile (77% prevalence of A/C): All cause: -0.55% (-1.95, 0.85) 1



### December 2009 E-347

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) Respiratory: -2.08% (-4.47, 0.31) 1 Cardiovascular: -1.02% (-2.44, 0.41) 1 Stroke: 0.69% (-1.19, 2.57) 1 Reference: Franklin et al. (2008, 097426 ) Period of Study: 2000-2005

Location: 25 U.S. communities Outcome (ICD10): Mortality: Nonaccidental (V01-Y98) Respiratory (J00-J99) Cardiovascular (I01-I52) Stroke (I60-J69) Study Design: Time-series Statistical Analyses: 1st stage: Poisson, cubic spline2nd stage: Random effects metaanalysis Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Range Mean (SD):

Winter: 9.6-34.4 Spring: 6.7-27.6

Summer: 7.6-26.0

Fall: 9.5-32.1 Range (Min, Max): NR Copollutant: Al, As, Br, Cr, EC, Fe, K, Mn, Na + , Ni, NO 3 – , NH 4, OC, Pb, Si, SO 4 2– , V, Zn Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental: 0.74% (0.41, 1.07) 0-1 Cardiovascular: 0.47% (0.02, 0.92) 0-1 Respiratory: 1.01% (-0.03, 2.05) 1-2 Stroke: 0.68% (-0.21, 1.57) 0-1 Winter: 0.15% (-0.42, 0.72) 0-1 Spring: 1.88% (1.29, 2.48) 0-1 Summer: 0.99% (0.35, 1.68) 0-1 Fall: 0.19% (-0.25, 0.64) 0-1 West: 0.51% (0.10, 0.92) 0-1

East & Central: 0.92% (0.44, 1.39) 0-1 % Increase per 10 μg/m 3 increase in PM 2.5 for an IQR increase in species to PM 2.5 mass proportion Univariate analysis Al: 0.58% As: 0.55% Br: 0.38 Cr: 0.33% EC: 0.06% Fe: 0.12% K: 0.41% Mn: 0.14% Na+: 0.20% Ni: 0.37% NO 3 -: -0.49% NH4: 0.04% OC: -0.02% Pb: 0.17% Si: 0.41% SO 4 2– : 0.51% V: 0.30% Zn: 0.23% Multivariate (1) Al: 0.79% Ni: 0.34% SO 4 2– : 0.75% Multivariate (2) Al: 0.61% Ni: 0.35% As: 0.58% Reference: Holloman et al. (2004, 087375 ) Period of Study: 1999-2001

Location: 7 North Carolina counties Outcome (ICD10): Mortality: Cardiovascular (I00-I99) Study Design: Time-series Statistical Analyses: 3-stage Bayesian hierarchical model Age Groups: >16 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: 2.5% (-3.9 to 9.6)

0 4.0% (-3.3 to 12.2)

1 11.4% (2.8-19.8)

2 -1.1% (-7.5 to 5.2)

3



### December 2009 E-348

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Hopke et al. (2006, 088390 ) Period of Study: Washington, DC: Aug 1988-Dec 1997. Phoenix, Arizona: Mar 1995-Jun 1998

Location: Washington, DC and surrounding counties Phoenix, Arizona Outcome: Mortality: Total (nonaccidental)

Cardiovascular Cardiovascular-Respiratory Study Design: Source-apportionment Statistical Analyses: Receptor modeling Age Groups: All ages Pollutant: Source-apportioned PM 2.5 : Washington, DC: Soil Traffic Secondary Sulfate Nitrate Residual Oil Wood Smoke Sea Salt Incinerator Primary Coal Phoenix, Arizona: Crustal Traffic Vegetation and Wood Burning Secondary Sulfate Metals Sea Salt Primary Coal Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR The study does not present quantitative results.

Reference: Ito et al. (2006, 088391 ) Period of Study: Aug 1988-Dec 1997

Location: Washington, DC and surrounding counties Outcome: Mortality: Total (nonaccidental)

Cardiovascular Cardiovascular-Respiratory Study Design: Time-series Source-apportionment Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages Pollutant: Source-apportioned PM 2.5 : Soil Traffic Secondary Sulfate Nitrate Residual Oil Wood Smoke Sea Salt Incinerator Primary Coal Averaging Time: 24-h avg Mean (SD): 17.8 (8.7) Range (Min, Max): NR Copollutant (correlation): NR Increment: PM 2.5 = 28.7 μg/m 3 PM 2.5 Sources 5-95th = Not reported % Increase (Lower CI, Upper CI) lag: Secondary sulfate (variance-weighted mean percent excess mortality) 6.7% (1.7, 11.7) 3

Primary coal-related PM 2.5 (mean percent excess mortality) 5.0% (1.0, 9.1) 3 Residual oil (mean percent excess mortality) 2.7% (-1.1, 6.5) 2

Traffic-related PM 2.5 (mean percent excess mortality) 2.6% (-1.6, 6.9) NR

Soil-related PM 2.5 (mean percent excess mortality) 2.1% (-0.8, 4.9) NR

PM 2.5 Sensitivity analysis: 2 df/yr: 7.9% (3.3, 12.6) 3 4 df/yr: 8.3% (3.7, 13.1) 3 8 df/yr: 8.3% (3.7, 13.2) 3 16 df/yr: 8.1% (3.1, 13.2) 3 Reference: Kan et al. (2007, 091267 ) Period of Study: Mar 2004-Dec 2005

Location: Shanghai, China Outcome (ICD10): Mortality: Total (nonaccidental) (A00-R99) Cardiovascular (I00-I99) Respiratory (J00-J98) Study Design: Time-series Statistical Analyses: Poisson GAM, penalized splines Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): 52.3 (1.57) Range (Min, Max): (2.0, 330.3) Copollutant (correlation): PM 10 : r = 0.84 PM 10-2.5 : r = 0.48 O 3 : r = 0.31 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Total: 0.36% (0.11, 0.61) 0-1 Cardiovascular: 0.41% (0.01, 0.82) 0-1 Respiratory: 0.95% (0.16, 1.73) 0-1



### December 2009 E-349

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Kettunen et al. (2007, 091242 ) Period of Study: 1998-2004

Location: Helsinki, Finland Outcome (ICD10): Mortality: Stroke (I60-I61, I63-I64) Study Design: Time-series Statistical Analyses: Poisson GAM, penalized thin-plate splines Age Groups: ≥ 65 Pollutant: PM 2.5 Averaging Time: 24-h avg Median (SD) unit: Cold Season: 8.2 Warm Season: 7.8 Range (Min, Max): Cold Season: (1.1, 69.5) Warm Season: (1.1, 41.5)

Copollutant: O 3 CO NO 2 PM 10 PM 10-2.5 UFP Increment: Cold Season: 6.7 μg/m 3 Warm Season: 5.7 μg/m 3 % Increase (Lower CI, Upper CI) lag: Cold Season -0.19% (-3.77, 3.51) 0 -0.17% (-3.73, 3.52) 1 0.59% (-2.95, 4.26) 2 0.46% (-3.10, 4.15) 3

Warm Season 6.86% (0.37, 13.78) 0 7.40% (1.33, 13.84) 1 4.01% (-1.79, 10.14) 2 -1.72% (-7.38, 4.29) 3

Reference: Klemm et al. (2004, 056585 ) Period of Study: Aug 1998-Jul 2000

Location: Fulton and DeKalb counties, Georgia (ARIES) Outcome: Mortality: Nonaccidental (<800) Cardiovascular (390-459) Respiratory (460-519) Cancer (140-239) Study Design: Time-series Statistical Analyses: Poisson GLM, natural cubic splines Age Groups: <65

≥ 65 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): 19.62 (8.32) Range (Min, Max): (5.29, 48.01) Copollutant: PM 10-2.5 O

3 NO 2 CO SO 2 Acid EC OC SO 4 Oxygenated Hydrocarbons Nonmethane hydrocarbons NO 3 Increment: NR β (SE) lag: Quarterly Knots:

PM 2.5 : 0.00398 (0.00161)

0-1 Monthly Knots:

PM 2.5 : 0.00544 (0.00184)

0-1 Biweekly Knots:

PM 2.5 : 0.00369 (0.00201)

0-1

Reference: Lippmann et al. (2006, 091165 ) Period of Study: 2000-2003

Location: 60 U.S. cities (NMMAPS) Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: Poisson GLM Age Groups: All ages Pollutant: Speciated Fine PM: Al, Ar, Cr, Cu, EC, Fe, Mn, Ni, Nitrate, OC, Pb, Se, Si, Sulfate, V, Zn Averaging Time: Annual avg Mean (SD): R Range (Min, Max): NR The study does not present quantitative results.

Reference: Mar et al. (2005, 087566 ) Period of Study: 1995-1997

Location: Phoenix, Arizona Outcome: Mortality: Nonaccidental (<800) Cardiovascular (390-448) Study Design: Time-series Statistical Analyses: Poisson GLM Age Groups: ≥ 65 Pollutant: Source-apportioned PM 2.5 : Soil Traffic Secondary Sulfate Nitrate Residual Oil Wood Smoke Sea Salt Incinerator Primary Coal Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Increment: PM 2.5 Sources 5-95th = NR % Increase (median percent excess risk) lag: Secondary sulfate: 16.0% 0

Traffic: 13.2% 1 Copper (Cu) smelter: 12.0% 0

Sea salt: 10.2% 5

Biomass/wood combustion: 8.6% 3



### December 2009 E-350

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Ostro et al. (2006, 087991 ) Period of Study: Jan 1999-Dec 2002

Location: 9 California counties (CALFINE) Outcome (ICD10): Mortality: Total mortality (respiratory, cardiovascular, ischemic heart disease, diabetes) Respiratory (J00-J98) Cardiovascular (I00-I99) Ischemic heart disease (I20-I25) Diabetes (E10-E14) Study Design: Time-series Statistical Analyses: Poisson, natural splines and penalized splines Age Groups: All ages >65 yr Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): Contra Costa: 14 Fresno: 23 Kern: 22 Los Angeles: 21 Orange: 21 Riverside: 29 Sacramento: 14 Santa Clara: 15 San Diego: 16 Range (Min, Max): Contra Costa: (1, 77) Fresno: (1, 160) Kern: (1, 155) Los Angeles: (4, 85) Orange: (4, 114) Riverside: (2, 120) Sacramento: (1, 108) Santa Clara: (2, 74) San Diego: (0, 66) Copollutant (correlation): NO 2 r = 0.56 CO r = 0.60 O 3 (1h) r = -0.14 O 3 (8h) r = -0.22 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag: Penalized splines All ages: All-cause: 0.2% (-0.2, 0.7) 2 0.6% (0.2, 1.0) 0-1

Cardiovascular: 0.3% (-0.1, 0.7) 2 0.6% (0.0, 1.1) 0-1

Respiratory: 1.3% (0.1, 2.6) 2 2.2% (0.6, 3.9) 0-1

>65: All-cause: 0.2% (-0.2, 0.7) 2 0.7% (0.2, 1.1) 0-1

Ischemic heart disease: 0.3% (-0.5, 1.0) 0-1 Males: 0.5% (-0.2, 1.2) 0-1 Females: 0.8% (0.3, 1.3) 0-1 Whites: 0.8% (0.2, 1.3) 0-1 Blacks: 0.1% (-0.9, 1.2) 0-1 Hispanics: 0.8% (-0.1, 1.6) 0-1 In hospital: 0.6% (-0.1, 1.3) 0-1 Out of hospital: 0.6% (0.1, 1.1) 0-1 High school graduates: 0.4% (0.0, 0.8) 0-1 Non-high school graduates: 0.9% (-0.1, 1.9) 0-1

Natural splines All cause 4 df: 0.5% (-0.1, 1.1) 0-1 8 df: 0.4% (-0.1, 0.9) 0-1 12 df: 0.3% (-0.1, 0.7) 0-1

Cardiovascular 4 df: 0.4% (-0.2, 0.9) 0-1 8 df: 0.1% (-0.5, 0.6) 0-1 12 df: 0.0% (-0.6, 0.6) 0-1

Respiratory 4 df: 2.1% (0.2, 4.1) 0-1 8 df: 1.6% (-0.5, 3.6) 0-1 12 df: 1.3% (-0.3, 2.9) 0-1

>65 All cause 4 df: 0.7% (0.0, 1.3) 0-1 8 df: 0.4% (-0.1, 0.9) 0-1 12 df: 0.3% (-0.1, 0.8) 0-1



### December 2009 E-351

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Ostro et al. (2007, 091354 ) Period of Study: PM 2.5 speciation analysis: Jan 2000-Dec 2003. PM 2.5 analysis: Jan 1999-Dec 2003

Location: 6 California counties (2000-2003). 9 California counties (1999-2003) (CALFINE) Outcome (ICD10): Mortality: Total (nonaccidental) mortality Respiratory (J00-J98) Cardiovascular (I00-I99) Study Design: Time-series Statistical Analyses: Poisson, natural splines Age Groups: >65 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): 2000-2003: 19.28 1999-2003: 18.6 Range (Min, Max): NR Copollutant (correlation): EC: r = 0.53 OC: r = 0.62 NO 3 : r = 0.65 SO 4 : r = 0.32 Al: r = 0.02 Br: r = 0.54 Ca: r = 0.23 Cl: r = 0.15 Cu: r = 0.23 Fe: r = 0.38 K: r = 0.52 Mn: r = 0.21 Ni: r = 0.11 Pb: r = 0.27 S: r = 0.35 Si: r = 0.16 Ti: r = 0.24 V: r = 0.20 Zn: r = 0.51 Increment: 14.6 μg/m 3 % Increase (Lower CI, Upper CI) lag:

Cardiovascular 1.6% (0.0, 3.1)

3

Notes: The study does not present all estimates quantitatively.

Reference: Ostro et al. (2008, 097971 ) Period of Study: Jan 2000-Dec 2003

Location: 6 California counties Outcome (ICD10): Mortality: Cardiovascular (I00-I99) Study Design: Time-series Statistical Analyses: Poisson, natural cubic splines and natural splines Age Groups: Pollutant: PM 2.5 , EC, OC, NO 3 , SO 4 , Ca, Cl, Cu, Fe, K, S, Si, Ti, Zn Averaging Time: 24-h avg Mean (SD): PM 2.5 : 19.28 EC: 0.966 OC: 7.129 NO 3 : 5.415 SO : 1.908

4 Ca: 0.080 Cl: 0.094 Cu: 0.007 Fe: 0.124 K: 0.117 S: 0.648 Si: 0.168 Ti: 0.009 Zn: 0.012 Range (95th): PM 2.5 : 46.91 EC: 2.57 OC: 15.91 NO 3 : 17.46 SO : 5.18

4 Ca: 0.20 Cl: 0.41 Cu: 0.02 Fe: 0.34 K: 0.26 S: 1.70 Si: 0.43 Ti: 0.02 Zn: 0.04 The study does not present quantitative results.

Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Respiratory mortality Study Design: Cohort

Covariates: Temperature, humidity Statistical Analysis: Autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 2.5-1 Averaging Time: 24 h Mean (SD) Unit: 5.5 (3.8) μg/m 3 Range (Min, Max): 0.6, 45.5 Copollutant: PM 10-2.5 , PM 1 Increment: 10 μg/m 3 Odds Ratio (95%CI) lag Avg L0-1: 0.998 (0.849-1.174), p = 0.981 L1: 1.014 (0.886-1.161), p = 0.838 L2: 1.295 (1.141-1.470), p = 0.000

Multi-pollutant Model Avg L0-1: 0.987 (0.806-1.208), p = 0.898 L1: 1.022 (0.859-1.214), p = 0. L2: 1.206 (1.028-1.416), p = 0.022



### December 2009 E-352

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Cardiovascular mortality Study Design: Cohort

Covariates: Temperature, humidity Statistical Analysis: Autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 2.5-1 Averaging Time: 24 h Mean (SD) Unit: 5.5 (3.8) μg/m 3 Range (Min, Max): 0.6, 45.5 Copollutant: PM 10-2.5 , PM 1 Increment: 10 μg/m 3 Odds Ratio (95%CI) lag Avg L0-1: 1.100 (1.002-1.207), p = 0.046 L1: 1.112 (1.031-1.200), p = 0.006 L2: 1.078 (0.999-1.163), p = 0.052

Multi-pollutant Model Avg L0-1: 0.994 (0.885-1.116), p = 0.920 L1: 0.984 (0.892-1.086), p = 0.754 L2: 0.981 (0.891-1.079), p = 0.688 Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Cerebrovascular mortality Study Design: Cohort

Covariates: Temperature, humidity Statistical Analysis: Autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 2.5-1 Averaging Time: 24 h Mean (SD) Unit: 5.5 (3.8) μg/m 3 Range (Min, Max): 0.6, 45.5 Copollutant: PM 10-2.5 , PM 1 Increment: 10 μg/m 3 Odds Ratio (95%CI) lag Avg L0-1: 1.083 (0.897-1.307), p = 0.406 L1: 1.121 (0.964-1.303), p = 0.140 L2: 0.984 (0.841-1.152), p = 0.839

Multi-pollutant Model Avg L0-1: 0.899 (0.712-1.135), p = 0.371 L1: 0.905 (0.743-1.102), p = 0.321 L2: 0.868 (0.711-1.060), p = 0.165 Reference: Rainham et al. (2005, 088676 ) Period of Study: 1981-1999

Location: Toronto, Canada Outcome: Mortality: Total (nonaccidental) (<800) Cardiorespiratory (390-459 480-519)

Other-causes Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): All yr: 17.0 (8.7) Winters (Dec-Feb): 17.2 (6.8) Summers (Jun-Aug): 18.8 (10.2) Range (Min, Max): NR Copollutant:

CO

NO 2 SO 2 O 3 Increment: NR % Increase (Lower CI, Upper CI) lag: Winter and Winter Synoptic Events Winter Total: 0.998% (0.997, 1.000) 2 Cardiorespiratory: 0.998 (0.996, 1.000) 2 Other: 0.998% (0.996, 1.000) 2

Dry Moderate Total: 1.001% (0.996, 1.007) 1 Cardiorespiratory: 1.005 (0.998, 1.011) 1 Other: 0.997% (0.989, 1.006) 0

Dry Polar Total: 0.998% (0.995, 1.001) 2 Cardiorespiratory: 0.995 (0.991, 0.999) 2 Other: 1.002% (0.998, 1.005) 1

Moist Moderate Total: 0.998% (0.993, 1.002) 2 Cardiorespiratory: 1.003 (0.995, 1.010) 1 Other: 0.997% (0.991, 1.004) 1

Moist Polar Total: 1.001% (0.998, 1.005) 1 Cardiorespiratory: 1.002 (0.997, 1.007) 2 Other: 1.003% (0.999, 1.007) 0

Moist Tropical Total: 1.007% (0.965, 1.203) 0 Cardiorespiratory: 1.123 (1.031, 1.224) 2 Other: 1.248% (1.123, 1.387) 0

Transition Total: 1.003% (0.996, 1.009) 1 Cardiorespiratory: 0.996 (0.987, 1.004) 0 Other: 0.997% (0.990, 1.004) 0 Summer and summer Synoptic Events Summer Total: 1.000% (1.000, 1.001) 0 Cardiorespiratory: 1.001 (1.000, 1.002) 0



### December 2009 E-353

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) Other: 1.001% (1.000, 1.002) 0

Dry Moderate Total: 1.001% (0.999, 1.002) 2 Cardiorespiratory: 1.002 (0.999, 1.004) 2 Other: 0.999% (0.997, 1.002) 0

Dry Polar Total: 1.002% (0.999, 1.005) 2 Cardiorespiratory: 0.996 (0.991, 1.000) 0 Other: 1.003% (0.999, 1.007) 2

Dry Tropical Total: 1.016% (1.006, 1.027) 0 Cardiorespiratory: 1.017 (1.005, 1.030) 2 Other: 1.017% (1.003, 1.031) 0

Moist Moderate Total: 1.002% (1.000, 1.004) 2 Cardiorespiratory: 1.003 (0.999, 1.006) 2 Other: 1.004% (1.001, 1.006) 0

Moist Polar Total: 1.005% (0.998, 1.011) 1 Cardiorespiratory: 1.008 (0.997, 1.018) 0 Other: 1.003% (0.995, 1.011) 1

Moist Tropical Total: 0.999% (0.997, 1.001) 2 Cardiorespiratory: 0.996 (0.993, 1.000) 2 Other: 0.998% (0.995, 1.001) 1

Transition Total: 1.005% (0.996, 1.014) 1 Cardiorespiratory: 1.007 (0.994, 1.020) 1 Other: 1.002% (0.996, 1.008) 2



### December 2009 E-354

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Rosenthal et al. (2008, 156925 ) Period of Study: Jul 2002-Jul 2006

Location: Indianapolis, Indiana Outcome: Non-Dead on Arrival (DOA) Out-of-Hospital Cardiac Arrests (OHCA)

Witnessed non-DOA OHCA Study Design: Case-crossover Statistical Analyses: Time-stratified conditional logistic regression Age Groups: All ages Study Population: Non-DOA OHCA: 1,374

Witnessed non-DOA OHCA: 511 Pollutant: PM 2.5 Averaging Time: 24-h avg Hourly Mean (SD): NR IQR (25th, 75th): All non-DOA All heart rhythms: (9.4, 19.5) OHCA: (9.6, 19.5) Referents: (9.3, 19.5) Asystole: (9.2, 19.4) OHCA: (9.2, 19.7) Asystole: (9.2, 19.2) Witnessed non-DOA hourly All heart rhythms: (8.8, 20.7) OHCA: (8.8, 21.9) Referents: (8.8, 20.4) Asystole: (8.5, 19.8) OHCA: (9.4, 21.3) Referents: (8.3, 19.1) Copollutant (correlation): NR Increment: 10 μg/m 3 Hazard Ratio (Lower CI, Upper CI) lag: Out-of-Hospital non-DOA Cardiac Arrests All 1.02 (0.94, 1.11) 0 1.00 (0.92, 1.08) 1 0.98 (0.90, 1.06) 2 1.00 (0.92, 1.08) 3 1.02 (0.92, 1.12) 0-1 avg 1.01 (0.91, 1.12) 0-2 avg 1.02 (0.91, 1.14) 0-3 avg Asystole 1.03 (0.91, 1.17) 0 1.00 (0.89, 1.13) 1 1.01 (0.90, 1.13) 2 0.98 (0.87, 1.10) 3 1.03 (0.90, 1.18) 0-1 avg 1.05 (0.90, 1.22) 0-2 avg 1.04 (0.88, 1.22) 0-3 avg Vfib 1.08 (0.92, 1.28) 0 1.02 (0.87, 1.21) 1 0.96 (0.80, 1.14) 2 1.10 (0.93, 1.31) 3 1.06 (0.88, 1.28) 0-1 avg 1.01 (0.82, 1.25) 0-2 avg 1.05 (0.83, 1.32) 0-3 avg PEA 0.92 (0.77, 1.08) 0 0.98 (0.83, 1.15) 1 0.96 (0.82, 1.14) 2 0.95 (0.82, 1.10) 3 0.96 (0.80, 1.17) 0-1 avg 0.98 (0.80, 1.21) 0-2 avg 0.98 (0.78, 1.21) 0-3 avg

Witnessed Out-of-Hospital non-DOA Cardiac Arrests (lag represents h in which or h before OHCA occurred) All: 1.12 (1.01, 1.25) 0 White: 1.18 (1.03, 1.35) 0 60-75: 1.25 (1.05, 1.49) 0 Asystole: 1.22 (1.01, 1.59) 0 Reference: Schwartz et al. (2002, 025312 ) Period of Study: 1979-Late 1980’s

Location: 6 U.S. cities Outcome: Mortality: Total (nonaccidental) (<800) Study Design: Time-series Statistical Analyses: Hierarchical modeling: 1. Poisson GAM, LOESS 2. Multivariate modeling Age Groups: All ages Pollutant: PM 2.5 , PM 2.5 sources (Traffic, Coal, Residual Oil) Averaging Time: 24-h avg Mean (SD):

PM 2.5 Range: (Madison: 11.3 to Steubenville: 30.5) Traffic Range: (Steubenville: 1.5 to Boston: 4.8) Coal Range: (Madison: 4.9 to Steubenville: 19.2) Residual Oil Range: (Boston: 0.5 to Steubenville: 0.9) Range (Min, Max): NR The study does not present quantitative results.



### December 2009 E-355

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Simpson et al. (2005, 087438 ) Period of Study: Jan 1996-Dec 1999

Location: 4 Australian cities Outcome: Mortality: Nonaccidental (<800) Cardiovascular (390-459) Respiratory (460-519) Study Design: Time-series meta-analysis Statistical Analyses: Poisson GAM, natural splines Poisson GLM, natural splines Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): Brisbane: PM 2.5 : 7.50 Sydney: PM 2.5 : 9.00 Melbourne: PM 2.5 : 9.30 Perth: PM 2.5 : 9.0 μg/m 3

Range (Min, Max): Brisbane: PM 2.5 : (1.9, 19.7) Sydney: PM 2.5 : (2.4, 35.3) Melbourne: PM 2.5 : (2.7, 35.1) Perth: PM 2.5 : (2.8, 37.3) Copollutant: CO, NO 2 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) lag:

PM 2.5 0.9% (-0.7, 2.5)

Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 1995-Dec 1999

Location: Spokane, Washington Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): NR Range (9th, 95th): PM 2.5 : (4.2, 20.2) Copollutant (correlation): PM 2.5 : r = 0.95 PM 10 : r = 0.62 PM 10-2.5 : r = 0.31 CO: r = 0.62 Increment: PM 2.5 : 10 μg/m 3 PM 10 : 25 μg/m 3 Relative Risk (Lower CI, Upper CI) lag:

PM 2.5 (0.97, 1.04) 1 0.99 (0.96, 1.03) 2 1.00 (0.97, 1.03) 3

Reference: Stieb et al. (2002, 025205 ) Period of Study: Publication dates of studies: 1985-Dec 2000 Mortality series: 1958-1999

Location: 40 cities (11 Canadian cities, 19 U.S. cities, Santiago, Amsterdam, Erfurt, 7 Korean cities) Outcome: Mortality: All-cause (nonaccidental) Study Design: Meta-analysis Statistical Analyses: Random effects model Age Groups: All ages Pollutant: PM 2.5 Averaging Time: NR Mean (SD): NR Range (Min, Max): NR Copollutant: Varied between studies: O 3 SO 2 NO 2 CO Increment: PM 2.5 : 18.3 μg/m 3 % Increase (Lower CI, Upper CI) lag: Single-pollutant models

18 studies

PM 2.5 : 2.0% (1.2, 2.7) Multipollutant models

8 studies

PM 2.5 : 1.3% (0.6, 1.9)

Reference: Sullivan et al. (2003, 043156 ) Period of Study: 1985-1994

Location: Western Washington Outcome: Out-of-hospital cardiac arrest Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups: 19-79 Study Population: Out-of-hospital cardiac arrests: 1,206 Pollutant: PM 2.5 Averaging Time: 24-h avg Median (SD) unit:

PM 10 Lag 0: 28.05 Lag 1: 27.97 Lag 2: 28.40 Range (Min, Max): PM 10 : (7.38, 89.83) Copollutant (correlation): SO 2 , CO

Notes: Study used nephelometry to measure particles and equated the measurements to PM 2.5 concentrations. Increment: PM 10 : 16.51 μg/m 3 PM 2.5 : 13.8 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag: Overall PM 10 1.05 (0.87, 1.27) 0 0.91 (0.75, 1.11) 1 1.03 (0.82, 1.28) 2 PM 2.5 0.94 (0.88, 1.01) 0 0.94 (0.88, 1.02) 1 1.00 (0.93, 1.08) 2 PM 2.5 : Stratified by subject characteristics ≤ 55 0.95 (0.76, 1.18) 0 0.89 (0.71, 1.12) 1 0.95 (0.75, 1.20) 2 >55 0.94 (0.88, 1.02) 0 0.95, (0.88, 1.03) 1 1.01 (0.93, 1.10) 2 Male 0.95 (0.87, 1.03) 0 0.96 (0.88, 1.04) 1 1.01 (0.93, 1.10) 2 Female 0.93 (0.82, 1.06) 0 0.92 (0.80, 1.07) 1 0.98 (0.83, 1.15) 2 White



### December 2009 E-356

### Study Design & Methods Concentrations1 Effect Estimates (95% CI) 0.93 (0.86, 1.01) 0 0.95 (0.88, 1.03) 1 1.03 (0.95, 1.12) 2 Non-White 1.09 (0.88, 1.36) 0 0.96 (0.75, 1.22) 1 0.88 (0.68, 1.14) 2 Current Smoker 1.05 (0.92, 1.19) 0 0.98 (0.86, 1.12) 1 1.06 (0.92, 1.22) 2 Nonsmoker 0.93 (0.85, 1.01) 0 0.93 (0.85, 1.02) 1 0.97 (0.89, 1.07) 2 Drinker 1.13 (0.92, 1.39) 0 1.15 (0.94, 1.41) 1 1.16 (0.92, 1.45) 2 Nondrinker 0.94 (0.86, 1.03) 0 0.93 (0.85, 1.02) 1 1.00 (0.92, 1.10) 2 Activity Level-Unrestricted 0.96 (0.89, 1.03) 0 0.96 (0.89, 1.04) 1 1.01 (0.93, 1.10) 2 Activity Level-Limited 0.82 (0.56, 1.20) 0 0.70 (0.45, 1.09) 1 0.97 (0.65, 1.43) 2 PM 2.5 : Stratified by disease state Heart disease 0.95 (0.87, 1.04) 0 0.97 (0.89, 1.07) 1 1.06 (0.96, 1.16) 2 Ischemic Heart Disease 0.91 (0.80, 1.04) 0 0.97 (0.84, 1.11) 1 1.09 (0.95, 1.26) 2 Active Angina 0.98 (0.81, 1.20) 0 1.07 (0.88, 1.31) 1 1.08 (0.89, 1.32) 2 Congestive Heart Failure 0.91 (0.80, 1.03) 0 0.99 (0.87, 1.13) 1 1.11 (0.97, 1.26) 2 Supraventricular tachycardia 1.41 (0.97, 2.04) 0 1.55 (1.07, 2.25) 1 1.23 (0.84, 1.82) 2 Bradycardia 0.97 (0.64, 1.46) 0 1.29 (0.85, 1.96) 1 1.30 (0.84, 2.01) 2 Asthma (0.80, 1.27) 0 0.92 (0.71, 1.19) 1 0.93 (0.71, 1.22) 2 COPD 1.00 (0.86, 1.17) 0 1.04 (0.88, 1.23) 1 1.08 (0.92, 1.28) 2

PM 2.5 : Persons with prior recognized heart disease stratified by smoking status All heart disease Current smoker 1.08 (0.92, 1.26) 0 1.06 (0.89, 1.26) 1 1.29 (1.06, 1.55) 2 Nonsmoker 0.91 (0.82, 1.02) 0 0.94 (0.84, 1.05) 1 0.99 (0.88, 1.11) 2 Ischemic Heart Disease



### December 2009 E-357

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Current smoker 1.06 (0.84, 1.34) 0 0.99 (0.75, 1.30) 1 1.39 (1.04, 1.86) 2 Nonsmoker 0.86 (0.73, 1.02) 0 0.93 (0.78, 1.11) 1 0.99 (0.83, 1.18) 2 Active Angina Current smoker 1.28 (0.88, 1.86) 0 1.26 (0.79, 2.01) 1 1.57 (0.99, 2.48) 2 Nonsmoker 0.87 (0.68, 1.12) 0 0.93 (0.72, 1.21) 1 0.91 (0.70, 1.17) 2 Congestive Heart Failure Current smoker 1.00 (0.79, 1.28) 0 1.03 (0.78, 1.35) 1 1.46 (1.10, 1.96) 2 Nonsmoker 0.88 (0.76, 1.03) 0 0.96 (0.82, 1.12) 1 0.99 (0.84, 1.17) 2 Supraventricular tachycardia Current smoker 12.80 (1.05, 156.57) 0 2.56 (0.82, 7.99) 1 1.15 (0.46, 2.86) 2 Nonsmoker 1.19 (0.74, 1.90) 0 1.35 (0.87, 2.10) 1 1.15 (0.73, 1.82) 2 Bradycardia Nonsmoker 0.84 (0.14, 4.95) 0 0.42 (0.03, 5.34) 1 0.51 (0.05, 5.79) 2 Nonsmoker 0.99 (0.63, 1.55) 0 1.42 (0.90, 2.24) 1 1.39 (0.88, 2.20) 2 Reference: Thurston et al. (2005, 097949 ) Period of Study: Washington, DC: Aug 1988-Dec 1997. Phoenix, Arizona: 1995-1997

Location: Washington, DC and surrounding counties Phoenix, Arizona Outcome: Mortality: Total (nonaccidental) (<800) Cardiovascular (390-448) Study Design: Time-series Source-apportionment Statistical Analyses: Poisson GLM, natural splines Age Groups: Washington, DC: All ages Phoenix, Arizona: ≥ 65 Pollutant: PM 2.5 , and source apportioned PM 2.5 : Crustal Traffic Secondary SO 4 Secondary NO 3 Wood Oil Salt Incinerator Averaging Time: 24-h avg Median (SD) unit: NR Range (Min, Max): NR Copollutant: PM 2.5 species (Na, Mg, Al, Si, P, S, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Br, Rb, Sr, Y, Zr, Mo, Rh, Pd, Ag, Cd, Sn, Sb, Te, I, Cs, Ba, La, W, Au, Hg, Pb, OC, EC) Increment: 10 μg/m 3

% Increase: Total (nonaccidental): Secondary sulfate:

Phoenix: 5.2% Washington, DC: 3.8%

Motor vehicles:

Phoenix: 0.9% Washington, DC: 4.2%



### December 2009 E-358

### Study Design & Methods Concentrations1 Effect Estimates (95% CI)

Reference: Villeneuve et al. (2003, 055051 ) Period of Study: 1986-1999

Location: Vancouver, Canada Outcome: Mortality: Nonaccidental (<800) Cardiovascular (401-440) Respiratory (460-519) Cancer (140-239) Study Design: Time-series Statistical Analyses: Poisson, natural splines Age Groups: ≥ 65 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): Daily PM 2.5 : 7.9 Every 6th Day PM 2.5 : 11.6 Range (Min, Max): Daily PM 2.5 : (2.0, 32.0) Every 6th Day PM 2.5 : (1.8, 43.0)

Copollutant: SO 2 CO NO 2 O 3 Increment: PM 2.5 (Daily): 9.0 μg/m 3 PM 2.5 (6th Day): 15.7 μg/m 3 % Increase (Lower CI, Upper CI) lag: Nonaccidental PM 2.5 (Daily) -0.1% (-5.1, 5.2) 0-2 avg -0.1% (-4.1, 4.1) 0 -0.3% (-4.2, 3.7) 1 0.5% (-3.3, 4.4) 2 PM 2.5 (6th Day) -2.8% (-7.5, 2.1) 0 2.0% (-2.6, 7.0) 1 4.5% (-0.3, 9.5) 2

Cardiovascular PM 2.5 (Daily) 1.5% (-6.1, 9.7) 0-2 avg 4.3% (-1.7, 10.7) 0 -1.0% (-7.0, 5.4) 1 -0.5% (-6.5, 5.9) 2 PM 2.5 (6th Day) -1.5% (-8.9, 6.5) 0 -2.0% (-9.3, 5.8) 1 3.0% (-4.2, 10.8) 2 Respiratory PM 2.5 (Daily) -0.7% (-13.1, 13.4) 0-2 avg 6.7% (-3.7, 18.3) 0 -3.0% (-12.8, 7.9) 1 -5.8% (-15.2, 4.7) 2 PM 2.5 (6th Day) 10.0% (-4.7, 26.8) 0 8.3% (-5.4, 24.0) 1 0.3% (-12.4, 14.9) 2

Cancer PM 2.5 (Daily) -0.3% (-9.4, 9.8) 0-2 avg -4.5% (-11.2, 2.8) 0 2.7% (-5.0, 11.0) 1 2.5% (-5.1, 10.7) 2 PM 2.5 (6th Day) -5.1% (-13.8, 4.5) 0 -0.3% (-9.7, 11.0) 1 0.2% (-9.1, 10.4) 2 Reference: Wilson et al. (2007, 157149 ) Period of Study: 1995-1997

Location: Phoenix, Arizona Outcome: Cardiovascular Study Design: Time-series Statistical Analyses: Poisson GAM, nonparametric smoothing spline Age Groups: >25 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 % Excess Risk (Lower CI, Upper CI) lag: Central Phoenix: 11.5% (2.8, 20.9) 0-5 ma 6.6% (1.1, 12.5) 1 2.0% (-3.2, 7.5) 2 Middle Phoenix: 2.9% (-4.9, 11.4) 0-5 ma 6.4% (1.1, 11.9) 2 Outer Phoenix: 1.6% (-6.2, 10.0) 0-5 ma

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-359

# Table E-19. Short-term exposure-mortal ity - other PM size fractions.

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Respiratory mortality Study Design: Cohort

Covariates: Temperature, humidity Statistical Analysis: Autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 1 Averaging Time: 24 h Mean (SD) Unit: 20.0 (10.3) μg/m 3 Range (Min, Max): 1.9, 80.1 Copollutant: PM 10-2.5 , PM 2.5-1 Increment: 10 μg/m 3 Odds Ratio (95%CI) lag Avg L0-1: 1.005 (0.960-1.053), p = 0.824 L1: 1.012 (0.969-1.056), p = 0.599 L2: 1.042 (0.998-1.087), p = 0.063

Multi-pollutant Model Avg L0-1: 1.007 (0.957-1.059), p = 0.799 L1: 1.008 (0.961-1.058), p = 0.739 L2: 1.010 (0.963-1.059), p = 0.678 Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Cardiovascular mortality Study Design: Cohort

Covariates: temperature, Humidity Statistical Analysis: Autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 1 Averaging Time: 24 h Mean (SD) Unit: 20.0 (10.3) μg/m 3 Range (Min, Max): 1.9, 80.1 Copollutant: PM 10-2.5 , PM 2.5-1 Increment: 10 μg/m 3 Odds Ratio (95%CI) lag Avg L0-1: 1.028 (1.000-1.057), p = 0.054 L1: 1.029 (1.003-1.056), p = 0.030 L2: 1.023 (0.996-1.050), p = 0.091 Multi-pollutant Model Avg L0-1: 1.025 (0.995-1.057), p = 0.688 L1: 1.028 (1.000-1.058), p = 0.053 L2: 1.024 (0.995-1.053), p = 0.110 Reference: Perez et al. (2008, 156020 ) Period of Study: Mar 2003-Dec 2005

Location: Barcelona, Spain Outcome: Cerebrovascular mortality Study Design: Cohort

Covariates: Temperature, humidity Statistical Analysis: Autoregressive Poisson regression models Statistical Package: NR Age Groups: All deaths Pollutant: PM 1 Averaging Time: 24 h Mean (SD) Unit: 20.0 (10.3) μg/m 3 Range (Min, Max): 1.9, 80.1 Copollutant: PM 10-2.5 , PM 2.5-1 Increment: 10 μg/m 3 Odds Ratio (95%CI) lag Avg L0-1: 1.037 (0.981-1.097), p = 0.202 L1: 1.056 (1.003-1.113), p = 0.039 L2: 1.020 (0.968-1.075), p = 0.460

Multi-pollutant Model Avg L0-1: 1.042 (0.981-1.107), p = 0.179 L1: 1.063 (1.004-1.124), p = 0.035 L2: 1.034 (0.976-1.095), p = 0.255 Reference: Slaughter et al. (2005, 073854 ) Period of Study: Jan 995-Dec 1999

Location: Spokane, Washington Outcome: Mortality: Nonaccidental (<800) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups: All ages Pollutant: PM 1 Averaging Time: 24-h avg Mean (SD): NR Range (9th, 95th) PM 1 : (3.3, 17.6) Copollutant (correlation): PM 1 PM 2.5 : r = 0.95 PM 10 : r = 0.50 PM 10-2.5 : r = 0.19 CO: r = 0.63 This study does not present quantitative results for PM 1

.

Reference: Stölzel et al. (2007, 091374 ) Period of Study: Sept 1995-Aug 2001

Location: Erfurt, Germany Outcome: Mortality: Total (nonaccidental) (<800) Cardio-respiratory (390-459, 460-519, 785, 786) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups: All ages Pollutant: MC 0.1-0.5 , MC 0.01-2.5 Averaging Time: 24-h avg Mean (SD): MC 0.1-0.5 : 17.6 (14.8) MC : 22.3 (19.2)

0.01-2.5 IQR (25th, 75th): MC 0.1-0.5 : (8.4, 21.5) MC 0.01-2.5 : (10.5, 27.3) Copollutant (correlation): MC 0.1-0.5 NO: r = 0.52 NO 2 : r = 0.60 CO: r = 0.58 MC 0.01-2.5 NO: r = 0.51 NO : r = 0.58

2 CO: r = 0.57 Increment: MC 0.1-0.5 : 13.1 μg/m 3 MC 0.01-2.5 : 16.8 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Total (nonaccidental) MC 0.1-0.5 1.010 (0.986 1.034) 0 1.006 (0.983 1.029) 1 1.007 (0.985 1.029) 2 0.994 (0.973 1.016) 3



### December 2009 E-360

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 1.002 (0.981 1.023) 4 0.997 (0.976 1.018) 5 MC 0.01-2.5 1.007 (0.985 1.030) 0 1.005 (0.984 1.026) 1 1.003 (0.983 1.023) 2 0.989 (0.970 1.009) 3 1.002 (0.982 1.022) 4 0.998 (0.979 1.018) 5 Cardio-respiratory MC0.1-0.5 1.004 (0.977 1.031) 0 1.004 (0.979 1.029) 1 1.001 (0.978 1.026) 2 0.991 (0.967 1.014) 3 1.000 (0.977 1.023) 4 1.000 (0.976 1.023) 5 MC0.01-2.5 1.001 (0.977 1.026) 0 0.999 (0.976 1.022) 1 0.998 (0.976 1.021) 2 0.985 (0.964 1.007) 3 1.001 (0.980 1.022) 4 1.003 (0.981 1.024) 5



### December 2009 E-361

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Yamazaki et al. (2007, 090748 ) Period of Study: 1995-1998

Location: Hong Kong, China Outcome: Mortality: Intracerebral hemorrhage (431) Ischaemic stroke (434) Study Design: Time-stratified casecrossover Statistical Analyses: Conditional logistic regression Age Groups: ≥ 65 Pollutant: PM7 Averaging Time: 1-h avg Mean (SD): Warmer Months (Apr-Sep): 40.3 Colder Months (Oct-Mar): 39.4 Range (Min, Max): NR Copollutant (correlation): Warmer Months NO 2 : r = 0.46-0.63 Ox: r = -0.14 to 0.20 Colder Months NO 2 : 0.42-0.79 Ox: r = -0.36 to -0.14 Increment: 30 μg/m 3 Odds Ratio (Lower CI, Upper CI) lag: 24-h avg concentrations Intracerebral hemorrhage Warmer months: 1.041 (0.984, 1.102) 0 Colder months: 1.005 (0.951, 1.061) 0

Ischaemic stroke Warmer months: 1.027 (0.993, 1.062) 0 Colder months: 1.005 (0.973, 1.039) 0

Exposure measured jointly as 24-h and 1-h mean concentrations Warmer months Intracerebral hemorrhage 1-h with 200 μg/m 3 threshold: 2.397 (1.476, 3.892) 2 h 24-h: 1.019 (0.960, 1.082) 0

Ischaemic stroke 1-h with 200 μg/m 3 threshold: 1.051 (0.750, 1.472) 2 h 24-h: 1.018 (0.983, 1.055) 0

Warmer months Intracerebral hemorrhage 1-h with 200 μg/m 3 threshold: 0.970 (0.712, 1.322) 2 h 24-h: 1.015 (0.958, 1.075) 0

Ischaemic stroke 1-h with 200 μg/m 3 threshold: 1.040 (0.855, 1.265) 2 h 24-h: 1.003 (0.968, 1.039) 0

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-362

# E.4. Long-Term Exposure and Cardiovascular Outcomes

Table E-20. Long-term exposure - ca rdiovascular morbidit y outcomes - PM 10 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Baccarelli et al. (2008, 157984 ) Period of Study: 1995-2005

Location: Italy (Lombardy region) Outcome (ICD9 and ICD10): Deep Vein Thrombosis (DVT) Prothrombin time (PT) Activated partial thromboplastin time (aPTT) Age Groups: 18-84yrs Study Design: Case-control (DVT outcome) Cross-sectional (PT and aPTT outcomes)

N: 871 cases 1210 controls (randomly selected from friends and nonblood relatives of cases Frequency matched by age to cases) Statistical Analyses: Unconditional logistic regression (DVT outcome) Linear regression (PT and aPTT outcomes)

Covariates: Sex, area of residence, education, factor V Leiden or G20210A prothrombin mutation, current use of oral contraceptives or hormone therapy (Variables controlled using penalized regression splines with 4 df) age, BMI, day of yr (for seasonality), index date, ambient temperature

Season: covariate Dose-response Investigated? Yes Statistical Package: STATA v9.0 and R v2.2.0 Pollutant: PM 10 Averaging Time: 1 yr (immediately preceding the diagnosis date for cases or the date of examination for controls) assessed other averaging periods presented in supplements (90 days, 180 days, 270 days, 2 yr) Mean (SD): NR

Percentiles: NR Range (Min, Max): Range for tertiles of exposure:

1: 12.0-44.2

2: 44.3-48.1

3: 48.2-51.5 Monitoring Stations: Monitors from 53 sites exposure assigned by dividing area into 9 regions Copollutant (correlation): NR PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Estimated changes of PT associated with PM 10 : Among DVT cases : -0.12 (-0.23, 0.00), p = 0.04 Among Controls: -0.06 (-0.11, 0.00) , p = 0.04 Estimated changes of aPTT associated with PM 10 : Among Controls: -0.09 (-0.19, 0.01) , p = 0.07 Among DVT cases: 0.01 (-0.03, 0.04) , p = 0.78

Risk of DVT associated with PM 10 (avg of 1 yr preceding diagnosis/exam date): | All subjects: 1.70 (1.30, 2.23), p < 0.001 Sex: Male: 2.07 (1.50, 2.84) , p < 0.001 Female: 1.40 (1.02, 1.92) , p = 0.04 P for interaction: p = 0.02 Age: 18-35yrs: 1.57 (1.11, 2.24), p = 0.01 36-50yrs: 1.97 (1.41, 2.77) , p < 0.001 51-84yrs: 1.54 (0.90, 2.63) , p = 0.12 P for interaction: p = 0.99 Premenopausal women with current use of oral contraceptives: No: 1.53 (0.86, 2.72) , p = 0.14 Yes: 0.87 (0.46, 1.67), p = 0.68 P for interaction: p = 0.11 Postmenopausal women with current use of hormone therapy: No: 1.60 (0.72, 3.54), p = 0.24 Yes: 0.85 (0.29, 2.45), p = 0.76 P for interaction: p = 0.27 Current use of oral contraceptive or hormone replacement therapy: No: 1.64 (1.05, 2.57), p = 0.03 Yes: 0.97 (0.58, 1.61), p = 0.89 P for interaction: p = 0.048 Body Mass Index: 13.3-22.0: 1.47 (0.97, 2.23), p = 0.07; 22.1-24.9: 1.72 (1.17, 2.54), p = 0.006 25.0-53.3: 1.83 (1.03, 3.24), p = 0.04 P for interaction: p = 0.37 Education: Elementary/middle school: 1.93 (1.35, 2.76), p < 0.001 High school: 1.72 (1.24, 2.39), p = 0.001 College: 1.35 (0.74, 2.45), p = 0.33 P for interaction: p = 0.21 Deficiencies of natural anticoagulant proteins: None: 1.66 (1.26, 2.18), p < 0.001 Any: 2.56 (0.91, 7.18), p = 0.07 P for interaction: p = 0.41 Factor V Leiden or G20210A prothrombin mutation: None: 1.69 (1.27, 2.23), p < 0.001 Any: 1.79 (1.05, 3.05), p = 0.03 P for interaction: p = 0.83 Hyperhomocysteinemia:



### December 2009 E-363

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) No: 1.66 (1.26, 2.19), p < 0.001 Yes: 2.19 (1.33, 3.61), p = 0.002 P for interaction: p = 0.25 Any cause of thrombophilia: No: 1.59 (1.19, 2.13), p = 0.002 Yes: 1.96 (1.34, 2.87), p < 0.001 P for interaction: p = 0.27 Year of diagnosis: 1995-97: 1.61 (1.06, 2.46), p = 0.03 1998-00: 1.34 (0.90, 1.99), p = 0.15 2001-05: 2.14 (1.04, 4.39), p = 0.04 P for interaction: p = 0.12 Risk of DVT associated with PM 10 over varying averaging times: 90 days: 0.91 (0.80, 1.03), p = 0.12 180 days: 0.96 (0.82, 1.13), p = 0.63 270 days: 1.26 (1.01, 1.57), p = 0.04 365 days: 1.70 (1.30, 2.23), p = 0.0001 2 yr: 1.47 (1.01, 2.14), p = 0.04 Risk of DVT associated with PM 10 (yr preceding diagnosis/exam date) sensitivity analysis to evaluate the effect of different methods for adjusting for long-term trends: Handling of long-term time trends: Ignored: 1.13 (0.89, 1.42), p = 0.31 Dummy variable for each yr: 1.78 (1.31, 2.44), p = 0.0003 Linear term: 1.32 (1.02, 1.69), p = 0.03 Penalized spline, 2 df: 1.54 (1.19, 2.00), p = 0.001 Penalized spline, 3 df: 1.64 (1.26, 2.14), p = 0.0002 Penalized spline, 4 df: 1.70 (1.30, 2.23), p = 0.0001 Penalized spline, 5 df: 1.70 (1.29, 2.22), p = 0.0002 Penalized spline, 6 df: 1.66 (1.26, 2.19), p = 0.0003 Penalized spline, 7 df: 1.60 (1.21, 2.13), p = 0.001 Penalized spline, 8 df: 1.55 (1.15, 2.10), p = 0.004 Reference: Baccarelli et al. (2009, 188183 ) Period of Study: Jan 1995-Sept 2005

Location: Lombardia Region, Italy Outcome: Deep Vein Thrombosis Study Design: Case-control

Covariates: Age, Sex, area of residence, BMI, education, medication

use Statistical Analysis: Logistic regression Statistical Package: Stata Pollutant: PM 10 Risk of DVT measured with regards to distance of residence from major road. Specific levels of PM 10 not given. Increment: NA Relative Risk (95%CI) of DVT All subjects, age-adjusted: 1.33 (1.03-1.71), p = 0.03 All subjects, adjusted for covariates: 1.47 (1.10-1.96), p = 0.008 All subjects, adjusted for covariates and background PM 10 exposure: 1.47 (1.11- 1.96), p = 0.008



### December 2009 E-364

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Calderon-Garciduenas et al. (2008, 156317 ) Period of Study: Children recruited between Jul 2003 and Dec 2004

Location: Mexico (northeast or southwest Mexico city or Polotitlan) Outcome (ICD9 and ICD10): Plasma Endothelin-1 (ET-1) and pulmonary arterial pressure (PAP) Age Groups: 6-13 yr 7.9 ± 1.3 yr Study Design: Cross-sectional

N: 81 children Statistical Analyses: Analysis of variance by parametric one-wayanalysis of variance and the NewmanKeuls multiple comparison post test, Pearson’s correlation

Covariates: Doesn’t appear to have performed multivariable analyses However, collected information on age, place and length of residency, daily outdoor time, household cooking methods, parents’ occupational history, family history of atopic illnesses and respiratory disease, and personal history of otolaryngologic and respiratory symptoms

Season: No Dose-response Investigated? No Statistical Package: STATA v8.3, or GraphPad Software, Inc. Pollutant: PM 10 ( μ g/m 3 ) Exposures assessed quantitatively in Mexico City only

No monitors in Polotitlan Averaging Time: 1, 2, and 7 days before the exam

Pollutant concentrations between 0700 and 1900 h were used for the estimates Mean (SD): Presented only in figures

Percentiles: NR Range (Min, Max): Presented only in figures Monitoring Stations: 4 (2 in northeast and 2 in southwest Mexico City)

Residence and school within 5 mi of one of these monitors) Copollutant (correlation): O 3 PM Increment: NA Effect Estimate [Lower CI, Upper CI]:

No health effects models with measured PM concentrations were presented Used city of residence to assign exposure No multivariable analyses presented Authors presented (statistically significantly) elevated ET-1 levels among children residing in both areas of Mexico City as compared to Polotitlan (control city): Mean ± SE (pg/mL)

Control: 1.23 ± 0.06 Southwest Mexico City: 2.40 ± 0.14 Northeast Mexico City: 2.09 ± 0.10 Mexico City (overall): 2.24 ± 0.12 Authors presented (statistically significantly) elevated PAP levels among children residing in both areas of Mexico City as compared to Polotitlan (control city): Mean ± SE (mmHg)

Control: 14.6 ± 0.4 Southwest Mexico City: 16.7 ± 0.6 Northeast Mexico City: 18.6 ± 0.9 Mexico City (overall): 17.3 ± 0.5

Correlation between ET-1 and time spent outdoors: r = 0.31, p = 0.0012

Correlation between PAP and time spent outdoors: r = 0.42, p = 0.0008



### December 2009 E-365

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Diez Roux et al. (2008, 156401 ) Period of Study: Baseline data collected Jun 2000-Aug 2002 Exposure assessed retrospectively between Aug 1982 and baseline date

Location: USA (6 field centers: Baltimore, MD Chicago, IL Forsyth Co, NC Los Angeles, CA New York, NY St. Paul, MN Outcome (ICD9 and ICD10): Three measures of subclinical atherosclerosis (common carotid intimal-medial thickness (CIMT), coronary artery calcification, and ankle-brachial index (ABI)) Age Groups: 44-84 yr (MESA cohort) Study Design: Cross-sectional retrospective cohort

N: 5172 for coronary calcium analysis 5037 for CIMT analysis 5110 for ABI analysis Statistical Analyses: Generalized Additive Models (Binomial regression: presence of calcification Linear regression: CIMT, ABI, amount of calcium among persons with non-zero calcification)

Covariates: Age, sex, race/ethnicity, socioeconomic factors, cardiovascular risk factors (BMI, hypertension, high density lipoprotein and low density lipoprotein cholesterol, smoking, diabetes, diet, physical activity models presented with and without adjustment for cardiovascular RFs)

Season: NA Dose-response Investigated? No Statistical Package: NR Pollutant: PM 10 ( μ g/m 3 ) Averaging Time: 20-yr imputed mean Mean (SD): 34.1 (7.5)

Percentiles: NR Range (Min, Max): NR Monitoring Stations: A spatio-temporal model was used to predict monthly PM 2.5 exposures based on the geographic location of each participant’s residence. Copollutant (correlation with 20-yr imputed mean): PM 10 20-yr observed mean

r = 0.93

PM 2.5 20-yr imputed mean

r = 0.73

PM 10 2001 imputed mean

r = 0.75

PM 10 2001 observed mean

r = 0.80

PM 2.5 2001 mean

r = 0.86 PM Increment: 21.0 μ g/m 3 (approx. 10th-90th percentile) Effect Estimate [Lower CI, Upper CI]: CIMT: Relative difference (95% CI): 1.01 (1.00, 1.02) Adj. for additional CVD RFs: 1.02 (1.00, 1.03) ABI: Mean difference (95% CI): 0.002 (-0.005, 0.009) Adj. for additional CVD RFs: 0.001 (-0.006, 0.009) Coronary calcium: Relative prevalence (95% CI): 1.02 (0.96, 1.07) Adj. for additional CVD RFs: 1.02 (0.96, 1.08) Coronary calcium (in those with calcium): Relative difference (95% CI): 0.98 (0.84, 1.13) Adj. for additional CVD RFs: 1.01 (0.86, 1.18) Found no clear heterogeneity by age, sex, lipid status, smoking status, diabetes status, BMI, education or study site.



### December 2009 E-366

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Maheswaran et al. (2005, 088683 ) Period of Study: 1994-1998

Location: Sheffield, United Kingdom Outcome (ICD9 and ICD10): Stroke mortality (ICD9: 430-438) and Emergency hospital admissions (ICD10: I60-I69) Age Groups: ≥ 45 yr Study Design: Small area ecological cross-sectional

N: 1030 census enumeration districts (CEDs) 108 CEDs excluded from PM analyses due to artifacts in the modeled emissions data. The analysis was based on 2979 deaths, 5122 admissions and a population of 199,682 Statistical Analyses: Poisson regression

Covariates: Age, sex, socioeconomic deprivation, and smoking prevalence(some models also included age-bydeprivation interaction)

Season: NA Dose-response Investigated? Yes, examined quintiles of exposure Statistical Package: SAS Pollutant: PM 10 ( μ g/m 3 ) Averaging Time: 5-yr avg Mean (SD): Presented mean values and ranges for each quintile of exposure: 1: 16.0 (<16.8) 2: 17.5 ( ≥ 16.8, <18.2) 3: 18.8 ( ≥ 18.2, <19.3) 4: 19.8 ( ≥ 19.3, <20.6) 5: 23.3 ( ≥ 20.6) Monitoring Stations: Used air pollution model incorporating point, line and grid sources of pollution and meteorological data. Copollutant (correlation): CO (r = 0.82)

NO X (r = 0.87) PM Increment: NA Effect Estimate [Lower CI, Upper CI]: Rate Ratios (95%CI) for stroke mortality adjusted for overdispersion by quintile of PM 10 level Adjusted for sex and age: 1: 1 (ref) 2: 0.95 (0.84, 1.08) 3: 1.12 (0.99, 1.27) 4: 1.16 (1.03, 1.32) 5: 1.39 (1.23, 1.58) Adjusted for sex, age, deprivation, and smoking: 1: 1 (ref) 2: 0.94 (0.83, 1.07) 3: 1.08 (0.94, 1.24) 4: 1.12 (0.97, 1.29) 5: 1.33 (1.14, 1.56) Rate Ratios (95%CI) for emergency hospital admissions because of stroke by quintile of PM 10 level Adjusted for sex and age: 1: 1 (ref) 2: 1.06 (0.95, 1.17) 3: 1.10 (0.99, 1.23) 4: 1.25 (1.12, 1.38) 5: 1.40 (1.26, 1.55) Adjusted for sex, age, deprivation, and smoking: 1: 1 (ref) 2: 1.01 (0.91, 1.13) 3: 0.98 (0.87, 1.10) 4: 1.08 (0.96, 1.22) 5: 1.13 (0.99, 1.29) Rate Ratios (95%CI) for stroke mortality in relation to spatially smoothed (using a 1-km radius) modeled outdoor air pollution quintiles Adjusted for sex, age, socioeconomic deprivation, age by deprivation interaction, and smoking prevalence: 1: 1 (ref) 2: 0.86 (0.75, 0.98) 3: 1.05 (0.92, 1.21) 4: 1.03 (0.89, 1.19) 5: 1.24 (1.05, 1.47) Rate Ratios (95%CI) for emergency hospital admissions because of stroke in relation to spatially smoothed modeled outdoor air pollution quintiles Adjusted for sex, age, socioeconomic deprivation, age by deprivation interaction, and smoking prevalence: 1: 1 (ref) 2: 1.05 (0.94, 1.17) 3: 1.07 (0.95, 1.20) 4: 1.06 (0.94, 1.20) 5: 1.15 (1.01, 1.31)



### December 2009 E-367

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Maheswaran et al. (2005, 090769 ) Period of Study: 1994-1998

Location: Sheffield, United Kingdom Outcome (ICD9 and ICD10): Coronary Heart Disease (CHD) mortality (ICD9: 410-414) and Emergency hospital admissions (ICD10: I20-I25) Age Groups: ≥ 45 yr Study Design: Small area ecological cross-sectional

N: 1030 census enumeration districts (CEDs) 108 CEDs excluded from PM analyses due to artifacts in the modeled emissions data. Results based on 6857 deaths, 11407 hospital admissions and 199,682 people aged ≥ 45 yr Statistical Analyses: Poisson regression

Covariates: Age, sex, socioeconomic deprivation, and smoking prevalence(some models also included age-bydeprivation interaction)

Season: NA Dose-response Investigated? Yes, examined quintiles of exposure Statistical Package: SAS Pollutant: PM 10 ( μ g/m 3 ) Averaging Time: 5-yr avg Mean (SD): Presented mean values and ranges for each quintile of exposure: 1: 16.0 (<16.8) 2: 17.5 ( ≥ 16.8, <18.2) 3: 18.8 ( ≥ 18.2, <19.3) 4: 19.8 ( ≥ 19.3, <20.6) 5: 23.3 ( ≥ 20.6) Monitoring Stations: Study used an air pollution model incorporating points, lines, and grids as sources of pollution, and meteorological data. Copollutant (correlation): CO (r = 0.82)

NO X (r = 0.87) PM Increment: NA Effect Estimate [Lower CI, Upper CI]: Rate Ratios (95%CI) for CHD mortality in relation to modeled outdoor air polluti on quintiles, adjusted for overdispersion Adjusted for sex and age: 1: 1 (ref) 2: 1.06 (0.98, 1.16) 3: 1.10 (1.01, 1.21) 4: 1.23 (1.13, 1.35) 5: 1.30 (1.19, 1.43) Adjusted for sex, age, deprivation, and smoking: 1: 1 (ref) 2: 1.03 (0.94, 1.12) 3: 1.00 (0.90, 1.11) 4: 1.08 (0.98, 1.20) 5: 1.08 (0.96, 1.20) Adjusted for sex, age, deprivation, and smoking (spatially smoothed using a 1km radius): 1: 1 (ref) 2: 0.97 (0.89, 1.07) 3: 1.00 (0.90, 1.10) 4: 1.03 (0.93, 1.15) 5: 1.07 (0.96, 1.21) Rate Ratios (95%CI) for emergency hospital admissions from CHD in relation to modeled outdoor air pollution quintiles Adjusted for sex and age: 1: 1 (ref) 2: 1.08 (0.98, 1.19) 3: 1.11 (1.01, 1.22) 4: 1.17 (1.07, 1.29) 5: 1.36 (1.23, 1.50) Adjusted for sex, age, deprivation, and smoking: 1: 1 (ref) 2: 1.03 (0.93, 1.13) 3: 0.96 (0.86, 1.07) 4: 0.97 (0.87, 1.08) 5: 1.01 (0.90, 1.14) Adjusted for sex, age, deprivation, and smoking (spatially smoothed using a 1km radius): 1: 1 (ref) 2: 1.01 (0.92, 1.11) 3: 1.04 (0.93, 1.15) 4: 0.97 (0.87, 1.08) 5: 1.07 (0.95, 1.20)



### December 2009 E-368

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: O’Neill et al. (2007, 156006 ) Period of Study: 2000-2004

Location: USA (6 field centers: Baltimore, MD Chicago, IL Forsyth Co, NC Los Angeles, CA New York, NY St. Paul, MN Outcome (ICD9 and ICD10): Creatinine adjusted urinary albumin excretion Assessed 2 ways: continuous log urinary albumin/creatine ration (UACR)and clinically defined micro- or macroalbuminuria (UACR ≥ 25 mg/g) vs. normal levels Age Groups: 44-84 yr Study Design: Cross-sectional analyses and prospective cohort analyses

N: 3901 participants free of clinical CVD at baseline Statistical Analyses: At baseline: multiple linear regression (continuous outcome) Binomial regression (dichotomous outcome) 3-yr change: repeated measures model with random subject effects (estimate 3- yr change in log UACR by levels of exposure)

Covariates: Age, gender, race, BMI, cigarette status, ETS, percent dietary protein For repeated measures models: time

Time x PM 10 Season: NA Dose-response Investigated? Yes, examined quartiles of exposure Statistical Package: SAS Pollutant: PM 10 Averaging Time: Avg of previous month, avg of previous 2 mo (recent exposures) 20-yr directly monitored PM 10 avg, 20-yr imputed PM 10 avg (longer-term exposures) Mean (SD): Previous 20 yr: 34.7 (7.0) Previous month: 27.5 (7.9)

Percentiles: NR Range (Min, Max): NR Monitoring Stations: NR (used closest monitor to residence to assign exposure 20-yr imputed PM 10 was derived using a space-time model) Copollutant (correlation): PM 2.5 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Adjusted mean differences in log UACR (mg/g) per increase in PM 10 among participants seen at baseline Previous 30 days Full sample: -0.42 (-0.085, 0.002) Within 10 km: -0.023 (-0.079, 0.034) Previous 60 days Full sample: -0.056 (-0.106 to -0.005) Within 10 km: -0.040 (-0.106, 0.025) 20 yr PM 10 (nearest monitors) Full sample: -0.019 (-0.072, 0.033) Within 10 km: 0.009 (-0.067, 0.085) Imputed 20 yr exposure Full sample: -0.002 (-0.038, 0.035) Within 10 km: 0.016 (-0.033, 0.066) Adjusted relative prevalence of microalbuminuria vs. high-normal and normal levels (below 25 mg/g) per increase in PM 10 among participants without macroalbuminuria during the baseline visit Previous 30 days: 0.88 (0.76, 1.02) Previous 60 days: 0.83 (0.70, 0.99) 20 yr PM 10 (nearest monitors): 0.92 (0.77, 1.08) Imputed 20 yr exposure: 0.98 (0.87, 1.10) Adjusted mean 3-yr change (SE) in log UACR (mg/g) by quartiles of 1982-2002 exposure to PM 10 from ambient monitors among participants seen in 2000-20004 Full sample Quartile: 18.5 to <29.3: 0.147 (0.024) 29.3 to <33.1: 0.159 (0.024) 33.1 to <36.3: 0.163 (0.024) 36.3 to 55.7: 0.174 (0.023) p-trend: 0.42 Within 10 km Quartile: 18.5 to <29.3: 0.159 (0.030) 29.3 to <33.1: 0.155 (0.031) 33.1 to <36.3: 0.167 (0.028) 36.3 to 55.7: 0.152 (0.036) p-trend: 0.99Interactions with either 20 yr or shorterterm PM exposure were not significant (p < 0.01) by gender, age, city, race/ethnicity or study site.

Reference: Puett et al, (2008, 156891 ) Period of Study: 1992-2002

Location: Northeastern metropolitan U.S. Outcome: Nonfatal myocardial infarction Study Design: Cohort

Covariates: Age in months, state of residence, yr and season Statistical Analysis: Cox proportional hazard Statistical Package: SAS Age Groups: 30-55 Pollutant: PM 10 Averaging Time: 3-, 12-, 24-, 36- and 48-mo ma Mean (SD) Unit: NR Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μ g/m 3

Hazard Ratio, 95% CI, 12 month ma 0.94 (0.77-1.15)



### December 2009 E-369

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Rosenlund et al. (2006, 114678 ) Period of Study: 1992-1994

Location: Stockholm County, Sweden Outcome (ICD9 and ICD10): Myocardial infarction (MI) Age Groups: 45-70 yr Study Design: Case-control

N: 1397 cases

1870 controls Statistical Analyses: Logistic regression (main analysis) Also performed multinomial logistic regression to assess cases as nonfatal, fatal in the hospital within 28 days, and out-of-hospital death within 28 days with all controls as reference

Covariates: Age, sex, and hospital catchment area (frequency matched variables) Smoking, physical inactivity, diabetes, SES

Also assessed but did not include hypertension, BMI, job strain, diet, passive smoking, alcohol consumption, coffee intake, and occupational exposure to motor exhaust and other combustion products

Season: NA Dose-response Investigated? No Statistical Package: STATA v8.2 Pollutant: PM 10 (modeled traffic-related pollution; also modeled PM 2.5 , but since the PM correlation was high (r = 0.998) only PM 10 results were presented) ( μ g/m 3 ) Averaging Time: 30 yr (PM only assessed during 2000, thus assumed constant levels during 1960-2000) Median (5th-95th percentile):

Cases: 2.6 (0.5-6.0)

Controls: 2.4 (0.6-5.9) Range (Min, Max): NR Monitoring Stations: NR Copollutant (correlation): NO 2 (r = 0.93) CO (r = 0.66)

SO 2 PM Increment: 5 μg/m 3 (5th to 95th percentile distribution among controls) Effect Estimate [Lower CI, Upper CI]: Association of 30-yr avg exposure to air pollution from traffic with MI Logistic regression All cases: 1.00 (0.79, 1.27) Multinomial logistic regression Nonfatal cases: 0.92 (0.71, 1.19) Fatal cases: 1.39 (0.94, 2.07) In-hospital death: 1.21 (0.75, 1.94) Out-of-hospital death: 1.84 (1.00, 3.40) After adjustment for heating-related SO 2 , the estimate for fatal MI was 1.40 (0.86-2.26) for PM 10

.



### December 2009 E-370

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zanobetti & Schwartz (2007, 091247 ) Period of Study: 1985-1999

Location: 21 U.S. cities (Birmingham, Alabama Boulder, Colorado Canton, Ohio Chicago, Illinois Cincinnati, Ohio Cleveland, Ohio Colorado Springs, Colorado Columbus, Ohio Denver, Colorado Detroit, Michigan Honolulu, Hawaii Houston, Texas Minneapolis-St. Paul, Minnesota Nashville, Tennessee New Haven, Connecticut Pittsburgh, Pennsylvania Provo-Orem, Utah Salt Lake City, Utah Seattle, Washington Steubenville, Ohio and Youngstown, Ohio) Outcome (ICD9 and ICD10): Death, subsequent myocardial infarction (MI ICD9 codes 410.0-410.9), and a first admission for congestive heart failure (CHF ICD9 code 428) Age Groups: ≥ 65 yr Study Design: Cohort

N: 196,000 persons discharged alive following an acute MI Statistical Analyses: Cox’s Proportional Hazards Regression Meta-regression for city-specific results

Covariates: Age, sex, race, type of MI, number of days of coronary care and intensive care, previous diagnoses for atrial fibrillation, and secondary or previous diagnoses for COPD, diabetes, and hypertension, and for season of initial event (time period, and, sex, race, and type of MI were treated as stratification variables)

Season: Assessed as a confounder Dose-response Investigated? No Statistical Package: NR Pollutant: PM 10 Averaging Time: Yearly avg of pollution for that yr and lags up to the 3 previous yr (distributed lag) Mean (SD): 28.8 (all cities SD not reported)

Percentiles: 10, 50, and 90 percentiles listed individually for each city (Table 2) Range (Min, Max): NR Monitoring Stations: NR (obtained data from the U.S. EPA Aerometric Information Retrieval System) Copollutant (correlation): None PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Hazard ratio (95%CI) for an increase in PM for the yr of failure and for the distributed lag from the yr of failure up to 3 previous yr Death PM 10 annual: 1.11 (1.05, 1.19), p = 0.001 Distributed lag model Lag 0: 1.04 (0.96, 1.14), p = 0.336 Lag 1: 1.07 (0.99, 1.14), p = 0.070 Lag 2: 1.14 (1.10, 1.18), p = 0.000 Lag 3: 1.06 (0.99, 1.12), p = 0.077 Sum lags 0-3: 1.34 (1.14, 1.52), p = 0.000 CHF PM 10 annual: 1.11 (1.03, 1.21), p = 0.009 Distributed lag model Lag 0: 1.09 (1.01, 1.18), p = 0.030 Lag 1: 1.09 (1.01, 1.19), p = 0.038 Lag 2: 1.13 (1.02, 1.25), p = 0.014 Lag 3: 1.04 (0.97, 1.12), p = 0.260 Sum lags 0-3: 1.41 (1.19, 1.66), p = 0.000 2nd MI PM 10 annual: 1.17 (1.05, 1.31), p = 0.003 Distributed lag model Lag 0: 1.09 (0.92, 1.30), p = 0.325 Lag 1: 1.12 (0.97, 1.30), p = 0.108 Lag 2: 1.15 (1.08, 1.23), p = 0.000 Lag 3: 1.01 (0.94, 1.09), p = 0.783 Sum lags 0-3: 1.43 (1.12, 1.82), p = 0.005 Hazard Ratio (95%CI) for an increase in PM (sum of the previous 3 yr distributed lag) for the sensitivity analyses Death Subjects with follow-up starting after 2nd MI: 1.33 (1.15, 1.55), p = 0.000 Subjects admitted between 1985-1996: 1.45 (1.26, 1.68), p = 0.000 2nd cohort definition (yr defined at time of MI): 1.29 (1.15, 1.44), p = 0.000 CHF Subjects with follow-up starting after 2nd MI: 1.42 (1.22, 1.65), p = 0.000 Subjects admitted between 1985-1996: 1.51 (1.26, 1.81), p = 0.000 2nd MI Subjects admitted between 1985-1996: 1.62 (1.23, 2.13), p = 0.001 Note: Age and sex effect modification results presented in Fig 1 Used meta-regression to examine predictors of heterogeneity across city and found that most predictors were not significant modifiers of PM (Table 7)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-371

# Table E-21. Long-term ef fects-cardiovascular- PM 2.5 

# (including PM components/sources).

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Allen et al. (2009, 156209 ) Period of Study: Oct 2000-Sep 2002 (exposure averaging period)

outcome assessed in 2002

Location: 5 U.S. communities (Chicago, Illinois Forsyth County, North Carolina Los Angeles, California Northern Manhattan and the Bronx, New York and St. Paul, Minnesota) part of MESA (Multi-ethnic Study of Atherosclerosis) Outcome (ICD9 and ICD10): Abdominal aortic calcium (AAC), a marker of systemic atherosclerosis (quantitative measure of interest was the Agatston score) Age Groups: 46-88 yr Study Design: Cross-sectional

N: 1,147 participants (sensitivity analysis among 1,269 participants) Statistical Analyses: 2-part modeling approach: 1) Modeled relative risk of having any AAC using a log link and a Gaussian error model Sensitivity analysis used modified Poisson regression with robust error variance2) Multiple linear regression of the logtransformed AAC Agatston score (among those with AAC>0) Sensitivity analysis modeled allparticipants by adding 1 prior to logtransforming

Covariates: Age, gender, race/ethnicity, BMI, smoking status, pack-yr of smoking, diabetes, education, annual income, blood lipid concentration, blood pressure, and medications Assessed impact of gender, age, diabetes, obesity, use of lipid-lowering medications, education, income, race/ethnicity, and employment status on heterogeneity of effects (or in sensitivity analyses)

Season: NA Dose-response Investigated? NR Statistical Package: SAS v9.1 Pollutant: PM 2.5 Averaging Time: 2-yr averaging period (Oct 2000-Sep 2002) Mean (SD): 15.8 (3.6) μ g/m 3

Percentiles: NR Range (Min, Max): 10.6-24.7 μg/m 3 Monitoring Stations: All monitors with 1) the objective of “population exposure,” “regional transport,” or “general/background; ) and 2) at least 50% data reporting in each of 8 3- month periods over the averaging time

Used monitors located within 50 km of a study participant’s residence Copollutant (correlation): Assessed traffic by roadway proximity PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Results for fully adjusted models under different participant inclusion, employment status, and roadway proximity criteria. Presence/Absence of Calcium RR (95% CI) Inclusion criteria: <10yrs at address: 1.04 (0.89, 1.22) ≥ 10yrs at address: 1.06 (0.96, 1.16) ≥ 10yrs at address & <10km from monitor: 1.08 (0.98, 1.18) ≥ 20yrs at address: 1.10 (0.99, 1.22) ≥ 20yrs at address & <10km from monitor: 1.11 (1.00, 1.24) <10yrs at address & employed: 1.02 (0.87, 1.20) ≥ 20yrs at address & employed: 1.07 (0.89, 1.27) <10yrs at address & not employed: 1.10 (1.00, 1.22) ≥ 20yrs at address & not employed: 1.16 (1.02, 1.31) <10yrs at address & near major road: 0.85 (0.69, 1.05) ≥ 20yrs at address & not near major road: 1.10 (0.99, 1.23) Log-transformed Agatston Score (Agatston >0) % Change (95% CI) Inclusion criteria: <10yrs at address: -6.6 (-64.0, 50.9) ≥ 10yrs at address: 8.0 (-29.7, 45.7) ≥ 10yrs at address & <10km from monitor: 19.7 (-19.6, 58.9) ≥ 20yrs at address: 14.4 (-32.8, 61.7) ≥ 20yrs at address & <10km from monitor: 24.6 (-24.6, 73.8) <10yrs at address & employed: 29.1 (-25.7, 83.8) ≥ 20yrs at address & employed: 43.8 (-32.4, 119.9) <10yrs at address & not employed: -15.1 (-66.3, 36.1) ≥ 20yrs at address & not employed: -14.1 (-72.6, 44.4) <10yrs at address & near major road: 34.0 (-44.2, 112.1) ≥ 20yrs at address & not near major road: 3.9 (-39.9, 47.8) Log-transformed Agatston Score (all) % Change (95% CI) Inclusion criteria: <10yrs at address: - 8.5 (-81.3, 64.2) ≥ 10yrs at address: 40.7 (-11.5, 92.8) ≥ 10yrs at address & <10km from monitor: 60.7 (5.9, 115.4) ≥ 20yrs at address: 64.1 (-1.73, 129.9) ≥ 20yrs at address & <10km from monitor: 79.2 (10.1, 148.3) <10yrs at address & employed: 33.5 (-35.9, 102.9) ≥ 20yrs at address & employed: 55.8 (-37.2, 148.7) <10yrs at address & not employed: 54.8 (-23.8, 133.4) ≥ 20yrs at address & not employed: 89.3 (-3.7, 182.3) <10yrs at address & near major road: -30.6 (-141.3, 80.1) ≥ 20yrs at address & not near major



### December 2009 E-372

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) road: 51.3 (-8.3, 110.8) Exploratory/sensitivity analyses (also presented in figures): Detectable AAC RR (95%CI): Among women: 1.14 (1.00, 1.30) Among persons >65yrs: 1.10 (1.01, 1.19) Among users of lipid-lowering medications: 1.14 (1.00, 1.30) Among Hispanics: 1.22 (1.03, 1.45) Imputing missing covariates among residentially stable participants: 1.08 (0.98, 1.19) Agatston score % change (95%CI): Among Hispanics: 64 (-4, 133) Among persons earning >$50,000: 72 (5, 139) Agatston score including those with Agatston = 0 % change (95%CI): Fully adjusted model: 41 (-12, 93) Among persons >65yrs: 75 (8, 143) Among diabetics: 149 (29, 270) Among users of lipid-lowering medications: 121 (25, 217) Among Hispanics: 141 (45, 236) Imputing missing Covariates: 49 (1.3, 100.1)



### December 2009 E-373

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Auchincloss et al. (2008, 156234 ) Period of Study: Jul 2000-Aug 2002

Location: 6 U.S. communities (Baltimore City and Baltimore County, Maryland Chicago, Illinois Forsyth County, North Carolina Los Angeles, California Northern Manhattan and the Bronx, New York and St. Paul, Minnesota) part of MESA (Multi-ethnic Study of Atherosclerosis) Outcome (ICD9 and ICD10): Blood pressure: systolic (SBP), diastolic (DBP), mean arterial (MAP), pulse pressure (PP) Avg of 2nd and 3rd BP measurement used for analyses Age Groups: 45-84 yr Study Design: Cross-sectional (MultiEthnic Study of Atherosclerosis baseline examination)

N: 5,112 persons (free of clinically apparent cardiovascular disease) Statistical Analyses: Linear regression Secondary analyses used log binomial models to fit a binary hypertension outcome

Covariates: Age, sex, race/ethnicity, per capita family income, education, BMI, diabetes status, cigarette smoking status, exposure to ETS, high alcohol use, physical activity, BP medication use, meteorology variables, and copollutants Examined site as a potential confounder and effect modifier Heterogeneity of effects also examined by traffic-related exposures, age, sex, type 2 diabetes, hypertensive status, cigarette use

Season: Adjusted for temperature and barometric pressure to adjust for seasonality (because seasons vary by the study sites) Also performed sensitivity analyses adjusting for season to examine the potential for residual confounding not accounted for by weather variables Dose-response Investigated? Assessed nonlinear relationships-no evidence of strong threshold/nonlinear effects for PM 2.5 Statistical Package: NR Pollutant: PM 2.5 Averaging Time: 5 exposure metrics constructed: prior day, avg of prior 2 days, prior 7 days, prior 30 days, and prior 60 days Mean (SD): Prior day: 17.0 (10.5) Prior 2 days: 16.8 (9.3) Prior 7 days: 17.0 (6.9) Prior 30 days: 16.8 (5.0) Prior 60 days: 16.7 (4.4)

Percentiles: NR Range (Min, Max): NR Monitoring Stations: Used monitor nearest the participant’s residence to calculate exposure metrics Copollutant (correlation):

SO 2 NO 2 CO Traffic-related exposures (straight-line distance to a highway; total road length around a residence) PM Increment: 10 μg/m 3 (approx. equivalent to difference between 90th and 10th percentile for prior 30 day mean) Effect Estimate [Lower CI, Upper CI]: Adjusted mean difference (95% CI) in PP and SBP (mmHg) per 10 μg/m 3 increase in PM 2.5 (avg for the prior 30 days) Pulse Pressure Adjustment variables: Person-level Covariates: 1.04 (0.25, 1.84) Person-level cov., weather: 1.12 (0.28, 1.97) Person-level cov., weather, gaseous copollutants: 2.66 (1.61, 3.71) Person-level cov., study site: 0.93 (-0.04, 1.90) Person-level cov., study site, weather: 1.11 (0.01, 2.22) Person-level cov., study site, weather, gaseous copollutants: 1.34 (0.10, 2.59) Systolic Blood Pressure Adjustment variables: Person-level Covariates: 0.66 (-0.41, 1.74) Person-level cov., weather: 0.99 (-0.15, 2.13) Person-level cov., weather, gaseous copollutants: 2.8 (1.38, 4.22) Person-level cov., study site: 0.86 (-0.45, 2.17) Person-level cov., study site, weather: 1.32 (-0.18, 2.82) Person-level cov., study site, weather, gaseous copollutants: 1.52 (-0.16, 3.21) Additional results: Associations became stronger with longer averaging periods up to 30 days. For example: Adjusted (personal covariates and weather) mean differences in PP: Prior day: -0.38 (-0.76, 0.00) Prior 2 days: -0.22 (-0.65, 0.21) Prior 7 days: 0.52 (-0.08, 1.11) Prior 30 days: 1.12 (0.28, 1.97) Prior 60 days: 1.08 (0.11, 2.05) (Pattern held for additional adjustments and for SBP results. Therefore, only results for 30-day mean differences were presented) Additional results (not presented): None of DBP results were statistically significant. Rresults for MAP were similar to SBP, though weaker and generally not significant Effect modification: associations between PM 2.5 and BP were stronger for persons taking medications, with hypertension, during warmer weather, in the presence of high NO 2 , residing ≤ 300m from a highway, and surrounded by a high density of roads (Fig 1) Associations were not modified for age, sex, diabetes, cigarette smoking, study site, high levels of CO or SO 2 , season , nor residence ≤ 400m fro a highway

Note: supplementary material available on-line



### December 2009 E-374

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Calderón-Garcidueñas et al. (2009, 192107 ) Period of Study: Sept 2004-Jan 2005

Location: Mexico City and Polotitlan, Mexico Outcome: Flow cytometry Study Design: Panel

Covariates: NR Statistical Analysis: Pearson’s Correlation Statistical Package: Stata Age Groups: 9.7 ± 1.2 yr Pollutant: PM 2.5 Averaging Time: 1-, 2- and 7-day avg Mean (SD) Unit: 35.89 ± 0.93 μ g/m 3 Range (Min, Max): NR Copollutant: PM 10 , O 3 Increment: NR Flow cytometry results and their statistical significance in control vs. exposed children CD3 Exposed: 62.9±1.8 Control: 67.1±1.7 P = 0.1 CD4 Exposed: 39.3±1.3 Control: 38.2±1.4 P = 0.57 CD8 Exposed: 24.0±0.95 Control: 27.3±1.0 P = 0.02 CD4/CD8 Exposed: 1.7±0.14 Control: 1.4±0.07 P = 0.09 CD3-/CD19+ Exposed: 11.8±1.0 Control: 14.8±1.0 P = 0.04 CD56+ Exposed: 11.5±1.2 Control: 12.4±1.5 P = 0.63 CD56+/CD3-NK Exposed: 14.0±9.5 Control: 7.0±2.7 P = 0.003 HLA-DR+ Exposed: 27.5±4.2 Control: 17.0±2.4 P = 0.04 mCD14+ Exposed: 66.5±2.3 Control: 80.6±1.8 P = <0.001 CD14/CD69 Exposed: 0.20±0.07 Control: 1.0±0.26 P = <0.001 CD4/CD69 Exposed: 0.08±0.03 Control: 3.1±0.65 P = <0.001



### December 2009 E-375

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Diez Roux et al. (2008, 156401 ) Period of Study: Baseline data collected Jun 2000-Aug 2002 Exposure assessed retrospectively between Aug 1982 and baseline date

Location: USA (6 field centers: Baltimore, MD Chicago, IL Forsyth Co, NC Los Angeles, CA New York, NY St. Paul, MN Outcome (ICD9 and ICD10): Three measures of subclinical atherosclerosis (common carotid intimal-medial thickness (CIMT), coronary artery calcification, and ankle-brachial index (ABI)) Age Groups: 44-84 yr Study Design: Cross-sectional

N: 5172 for coronary calcium analysis 5037 for CIMT analysis 5110 for ABI analysis Statistical Analyses: Generalized Additive Models (Binomial regression: presence of calcification Linear regression: CIMT, ABI, amount of calcium)

Covariates: Age, sex, race/ethnicity, socioeconomic factors, cardiovascular risk factors (BMI, hypertension, high density lipoprotein and low density lipoprotein cholesterol, smoking, diabetes, diet, physical activity Models presented with and without adjustment for cardiovascular RFs)

Season: NA Dose-response Investigated? No Statistical Package: NR Pollutant: PM 2.5 Averaging Time: 20-yr imputed mean Mean (SD): 21.7 (5.0)

Percentiles: NR Range (Min, Max): NR Monitoring Stations: NR Long-term exposure to PM estimated based on residential history reported retrospectively all addresses geocoded

ambient AP obtained from U.S. EPA Copollutant (correlation): PM 10 20-yr observed mean r = 0.64 PM 10 20-yr imputed mean r = 0.73 PM 10 2001 mean r = 0.43 PM 2.5 2001 mean r = 0.64 Due to high correlation among PM exposures, only results of mean 20-yr exposures are reported. PM Increment: 12.5 μ g/m 3 (approx. 10th-90th percentile) Effect Estimate [Lower CI, Upper CI]: CIMT: Relative difference (95% CI): 1.01 (1.00, 1.01) Adj. for additional CVD RFs: 1.01 (1.00, 1.02) 1.02 ABI: Mean difference (95% CI): 0.000 (-0.006, 0.006) Adj. for additional CVD RFs: -0.001 (-0.006, 0.006) Coronary calcium: Relative prevalence (95% CI): 1.01 (0.96, 1.05) Adj. for additional CVD RFs: 1.01 (0.96, 1.06) 1.02 Coronary calcium (in those with calcium): Relative difference (95% CI): 0.99 (0.88, 1.12) Adj. for additional CVD RFs: 1.01 (0.89, 1.14)



### December 2009 E-376

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hoffman et al. (2007, 091163 ) Period of Study: 2000-2003

Location: Ruhr area of Germany (3 large cities: Essen, Mulheim, and Bochum) Outcome (ICD9 and ICD10): Coronary artery calcification (CAC) Age Groups: 45-74 yr Study Design: Cross-sectional

N: 4494 participants Statistical Analyses: Linear regression (outcome = natural logarithm of CAC score + 1) Logistic regression (outcome = CAC score above/below the age- and gender-specific 75th percentile)

Covariates: City and area of residence, age, sex, education, smoking, ETS, physical inactivity, waist-to-hip ratio, diabetes, blood pressure, and lipids (and household income in a subset)

Season: NA Dose-response Investigated? Yes, PM was also categorized into quartiles for analyses Statistical Package: NR Pollutant: PM 2.5 Averaging Time: 1 yr (2002, midpoint of the study) Mean (SD): Total: 22.8 (1.5) High traffic exposure ( ≤ 100m): 22.9 (1.4) Low traffic exposure (>100m): 22.8 (1.5) Percentiles: Q1: 21.54 Q2: 22.59 Q3: 23.75 10th-90th percentile: 3.91 Range (Min, Max): NR Monitoring Stations: Daily mean PM 2.5 values for 2002 were estimated with the EURAD model using data from official emission inventories, meteorological information, and regional topographical data. Copollutant (correlation): None (Traffic was assessed using distance to roadways) Correlation between modeled daily avg of PM 2.5 and measured PM 2.5 : 0.86- 0.88, depending on season. PM Increment: 3.91 μg/m 3 (10th-90th percentile) Effect Estimate [Lower CI, Upper CI]: Percent change (95%CI) in CAC associated with an increase in PM 2.5 Unadjusted: 12.7 (-7.0, 36.4) Model 1 (adjusted for distance to major road): 12.3 (-7.3, 35.9) Model 2 (model 1 + city and area of residence): 29.7 (0, 68.3) Model 3 (model 2 + age, sex, education): 24.2 (0, 55.1) Model 4 (model 3 + smoking, ETS, physical inactivity, waist-to-hip ratio): 17.9 (-5.3, 46.7) Model 5 (model 4 + diabetes, blood pressure, LDL, HDL, triglycerides): 17.2 (-5.6, 45.5) Adjusted ORs (95%CI) for the association between the top quarter of PM exposure vs. the low quarter of PM exposure and a CAC score above the age- and sex-specific 75th percentiles All: 1.22 (0.96, 1.54) No CHD: 1.22 (0.95, 1.57) Men: 1.09 (0.78, 1.53) Women: 1.34 (0.97, 1.87) Age <60 yr: 1.18 (0.83, 1.68) Age >60 yr: 1.27 (0.93, 1.75) Nonsmokers: 1.17 (0.89, 1.53) Current smokers: 1.30 (0.83, 2.05) Educational level Low: 1.16 (0.86, 1.57) Medium: 1.30 (0.83, 2.05) High: 1.62 (0.81, 3.25) Additional notes: No clear dose-response relationship demonstrated when exposure assessed in quartiles (Fig 2) Participants who had not been working full-time during the last 5 yr showedstronger effects, with possible doseresponse between PM 2.5 and CAC (results presented in Fig 3)

Reference: Hoffman et al. (2006, 091162 ) Period of Study: Dec 2000-Jul 2003

Location: Ruhr area of Germany (2 large cities: Essen, Mulheim) Outcome (ICD9 and ICD10): Clinically manifest CHD (defi ned as self-reported history of a ‘hard’ coronary event, i.e. myocardial infarction or application of a coronary stent or angioplasty or bypass surgery) Age Groups: 45-75 yr Study Design: Cross-sectional (German Heinz Nixdorf RBCALL study)

N: 3399 participants Statistical Analyses: Multivariable logistic regression

Covariates: Sex, diabetes, hypertension, smoking status, ETS, educational level, physical activity, BMI, triglycerides, age, cigarettes smoked per day, WHR, LDL, HDL, HbAIc, indicator variable for cities, indicator variable for living in northern part of cities. Statistical Package: SAS v8.2 Pollutant: PM 2.5 (μg/m 3 ) Averaging Time: Yearly mean estimated with model for yr 2002 (on a spatial scale of 5 km) Mean (SD): Total: 23.3 (1.4) High traffic: 23.4 (1.4) Low traffic: 23.3 (1.4)

Percentiles: NR Range (Min, Max): NR Monitoring Stations: NR Copollutant (correlation): None (Traffic was assessed using distance to roadways) Effect Estimate [Lower CI, Upper CI]:

Model 1: PM 2.5 + high traffic exposure 0.92 (0.36, 2.39) Model 2: model 1 + age, sex 0.83 (0.31, 2.27) Model 3: model 2 + education, diabetes, HbAIc, BMI, WHR, smoking status, ETS, physical activity, city, area of residence 0.56 (0.16, 2.01) Model 4: model 3 + hypertension, lipids 0.55 (0.14, 2.11) Modeled vs. Measured: r = 0.86-0.88, depending on season



### December 2009 E-377

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hoffmann et al, (2009, 190376 ) Period of Study: 2000-2003

Location: Ruhr area, Germany Outcome: Peripheral Arterial Disease Study Design:

Covariates: Height, weight, medication use, diabetes, physical activity level, smoking, socioeconomic status, education, population density Statistical Analysis: NR Statistical Package: NR Age Groups: 45-75 yr Pollutant: PM 2.5 Averaging Time: Daily Mean (SD) Unit: 22.96 (0.85) Range (Min, Max): NR Copollutant (correlation): NR Increment: 3.91 μ g/m 3 Odds Ratio (95%CI) for prevalence of peripheral arterial disease 0.87 (0.57-1.34)

Reference: Kunzli et al. (2005, 087387 ) Period of Study: 1998-2003

Location: Los Angeles Basin Outcome (ICD9 and ICD10): Carotid intima-media thickness (CIMT) Age Groups: Less than 40 yr excluded Mean age = 59.2 ± 9.8 Study Design: Cross-sectional

N: 798 participants Statistical Analyses: Linear regression

Covariates: Age, sex, education, income, smoking, ETS, blood pressure, LDL cholesterol, treatment with antihypertensives or lipid-lowering medications

Season: NA Dose-response Investigated? Yes, assessed PM 2.5 in quartiles Statistical Package: NR Pollutant: PM 2.5 (μg/m 3 ) Averaging Time: GIS/geostatics model to estimate ‘long-term mean ambient concentrations of PM 2.5 ’ derived from data collected in 2000, including data from 23 state and local monitoring stations. Mean (SD): 20.3 ± 2.6

Percentiles: NR Range (Min, Max): 5.2, 26.9 Monitoring Stations: 23 monitors Copollutant (correlation): None PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Percent change (95%CI) in CIMT associated with an increase in PM 2.5 concentrationBased on a linear model with log intimamedia thickness as dependent variable Total population: Unadjusted: 5.9 (1.0, 10.9) , p = 0.018 Adjusted for age, sex, education, income: 4.4 (0.0, 9.0) , p = 0.056 Adjusted for above + smoking, ETS, multivitamins, alcohol: 4.2 (-0.2, 8.9) , p = 0.064 Among Females ≥ 60 yr: Unadjusted: 19.2 (8.8, 30.5) , p = 0.001 Adjusted for age, sex, education, income: 15.7 (5.7, 26.6) , p = 0.002 Adjusted for above + smoking, ETS, multivitamins, alcohol: 13.8 (4.0, 24.5) , p = 0.002 Among those taking lipid-lowering therapy: Unadjusted: 15.8 (2.1, 31.2) , p = 0.024 Adjusted for age, sex, education, income: 13.3 (0, 28.5) , p = 0.031 Adjusted for above + smoking, ETS, multivitamins, alcohol: 13.3 (-0.3, 28.8) , p = 0.060 For the observed contrast between lowest and highest exposure: Approximately 20 μg/ m 3 Æ 12.1% (2.0- 231%) increase in CIMT. Among nonsmokers: 6.6% (1.0-12.3%).

The estimate was small and not significant in current and former smokers. Women: In the range of 6-9% per 10 μg/m 3

Unadjusted means of CIMT across quartiles of exposure were 734, 753, 758, and 774 μ m

Adjusted means trend across exposure groups, p = 0.041 Stratified results presented in figures

Reference: Miller et al. (2007, 090130 ) Period of Study: 1994-2003

Location: 36 U.S. metropolitan areas (Women’s Health Initiative) Outcome (ICD9 and ICD10): First cardiovascular event (myocardial infarction, coronary revascularization, stroke, and death from either coronary heart disease [categorized as “definite” or “possible”] or cerebrovascular disease) Age Groups: 50-79 yr (median age at Pollutant: PM 2.5 (μg/m 3 ) Averaging Time: Annual avg concentration in 2000 (used to represent long-term exposure) Mean (SD): Individual exposure: 13.5 (3.7) Citywide avg exposure: 13.5 (3.3) PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Estimated Hazards Ratio (95%CI) for the time to the first cardiovascular event or death associated with an increase in PM 2.5 Any cardiovascular event (first event) Overall: 1.24 (1.09, 1.41)



### December 2009 E-378

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) enrollment: 63) Study Design: Cohort (median followup of 6 yr)

N: 65,893 postmenopausal women without previous cardiovascular disease Statistical Analyses: Cox-proportional hazards regression

Covariates: Age, race/ethnicity, smoking status, the number of cigarettes smoked per day, the numberof yr of smoking, systolic blood pressure, education level, household income, BMI, and presence or absenceof diabetes, hypertension, or hypercholesterolemia (also evaluated ETS, occupation, physical activity, diet,alcohol consumption, waist circumference, waist-to-hip ratio, medical history, medications, and presence orabsence of a family history of cardiovascular disease as possible confounders in extended models)

Season: NA Dose-response Investigated? Statistical Package: SAS v8.0, STATA v8.0 Median: 13.4 Percentiles: Quintile ranges: 1: 3.4, 10.9 2: 11.0, 12.4 3: 12.5, 14.2 4: 14.3, 16.4 5: 16.5, 28.3 IQR: 11.6-18.3 10th-90th Personal: 9.1-18.3 City-wide: 9.3-17.8 Range (Min, Max): Personal exposure: 3.4, 28.3 Citywide exposure: 4.0, 19.3 Monitoring Stations: 573 monitors

The nearest monitor to the location of each residence was used to assign exposure (monitor within 30 mi of residence Median of 20 monitors per city (range: 4-78)) Copollutant (correlation): PM 10 SO 2 NO 2 CO

O 3 Between cities: 1.15 (0.99, 1.32) Within cities: 1.64 (1.24, 2.18) Coronary heart disease (first event): Overall: 1.21 (1.04, 1.42) Between cities: 1.13 (0.95, 1.35) Within cities: 1.56 (1.11, 2.19) Cerebrovascular disease (first event): Overall: 1.35 (1.08, 1.68) Between cities: 1.20 (0.94, 1.54) Within cities: 2.08 (1.28, 3.40) MI (first event): Overall: 1.06 (0.85, 1.34) Between cities: 0.97 (0.75, 1.25) Within cities: 1.52 (0.91, 2.51) Coronary revascularization (first event): Overall: 1.20 (1.00, 1.43) Between cities: 1.14 (0.93, 1.39) Within cities: 1.45 (0.98, 2.16) Stroke (first event): Overall: 1.28 (1.02, 1.61) Between cities: 1.12 (0.87, 1.45) Within cities: 2.08 (1.25, 3.48) Any death from cardiovascular cause: Overall: 1.76 (1.25, 2.47) Between cities: 1.63 (1.10, 2.40) Within cities: 2.28 (1.10, 4.75) Coronary heart disease death (definite diagnosis): Overall: 2.21 (1.17, 4.16) Between cities: 2.22 (1.06, 4.62) Within cities: 2.17 (0.60, 7.89) Coronary heart disease death (possible diagnosis): Overall: 1.26 (0.62, 2.56) Between cities: 1.20 (0.54, 2.63) Within cities: 1.57 (0.29, 8.51)

Cerebrovascular disease death: Overall: 1.83 (1.11, 3.00) Between cities: 1.58 (0.90, 2.78) Within cities: 2.93 (1.03, 8.38) Estimated Hazard Ratios for cardiovascular events associated with an increase in PM 2.5 according to selected characteristics (presented adjusted H and adjusted H including adjustment for city) Any cardiovascular event: H: 1.24 (1.09, 1.41) H (city): 1.69 (1.26, 2.27) Household income <$20,000: H: 1.30 (1.10, 1.53) H (city): 1.75 (1.28, 2.40) Household income $20,000-49,999: H: 1.23 (1.08, 1.41) H (city): 1.69 (1.25, 2.27) Household income ≥ $50,000: H: 1.20 (1.02, 1.40) 6 H (city): 1.66 (1.22, 2.26) P for trend: HR: p = 0.34 HR (city): p = 0.54 Education: Not high-school graduate: H: 1.40 (1.11, 1.75) H (city): 1.88 (1.32, 2.67) Education: High school grad/trade school/GED: H: 1.33 (1.14, 1.55) H (city): 1.79 (1.32, 2.44) Education: Some college or associate degree: H: 1.26 (1.09, 1.44)



### December 2009 E-379

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) H (city): 1.74 (1.29, 2.34) Education: Bachelor’s degree or higher: H: 1.11 (0.94, 1.31) H (city): 1.54 (1.13, 2.10) P for trend: H: p = 0.07 H (city): p = 0.15 Age <60 yr: H: 1.21 (0.84, 1.73) H (city): 1.66 (1.05, 2.61) Age 60-69 yr: H: 1.14 (0.93, 1.39) H (city): 1.53 (1.09, 2.14) Age ≥ 70 yr: H: 1.34 (1.11, 1.63) H (city): 1.85 (1.34, 2.56) P for trend: H: p = 0.20 H (city): p = 0.20 Current smoker: H: 1.68 (1.06, 2.66) H (city): 2.28 (1.33, 3.92) Former smoker: H: 1.24 (1.01, 1.52) H (city): 1.71 (1.23, 2.39) Never smoked: H: 1.18 (0.99, 1.40) H (city): 1.60 (1.16, 2.21) Living with smoker currently: H: 1.28 (0.84, 1.97) H (city): 1.65 (0.99, 2.76) Living with smoker formerly: H: 1.18 (1.00, 1.38) H (city): 1.59 (1.16, 2.16) Living with smoker never: H: 1.39 (1.07, 1.80) H (city): 1.90 (1.31, 2.78) BMI <22.5: H: 0.99 (0.80, 1.21) H (city): 1.35 (0.96, 1.88) BMI 22.5-24.7: H: 1.16 (0.96, 1.40) H (city): 1.58 (1.14, 2.19) BMI 24.8-27.2: H: 1.24 (1.05, 1.45) H (city): 1.69 (1.24, 2.30) BMI 27.3-30.9: H: 1.38 (1.18, 1.61) H (city): 1.88 (1.38, 2.56) BMI >30.9: H: 1.35 (1.12, 1.64) H (city): 1.84 (1.33, 2.55) P for trend: H: p = 0.003 H (city): p = 0.007 Waist-to-hip ratio <0.74: H: 1.07 (0.90, 1.29) H (city): 1.45 (1.05, 2.00) Waist-to-hip ratio 0.74-0.77: H: 1.12 (0.95, 1.31) H (city): 1.51 (1.11, 2.06) Waist-to-hip ratio 0.78-0.80: H: 1.24 (1.07, 1.44) H (city): 1.68 (1.23, 2.27) Waist-to-hip ratio 0.81-0.86: H: 1.30 (1.13, 1.50) H (city): 1.76 (1.30, 2.38) Waist-to-hip ratio >0.86: H: 1.29 (1.11, 1.50) H (city): 1.75 (1.29, 2.37) Waist circumference <73 cm: H: 1.05 (0.86, 1.27) H (city): 1.43 (1.02, 1.99) Waist circumference 73-78 cm: H: 1.20 (1.02, 1.41) H (city): 1.63 (1.19, 2.23) Waist circumference 79-85 cm: H: 1.22 (1.05, 1.41) H (city): 1.66 (1.22, 2.24) Waist circumference 86-95 cm: H: 1.33 (1.15, 1.53) H (city): 1.80 (1.33, 2.43) Waist circumference >95 cm: H: 1.27 (1.07, 1.51) H (city): 1.73 (1.26, 2.36) P for trend: H: p = 0.06 H (city): p = 0.07 Hormone-replacement therapy-Current Use: H: 1.33 (1.09, 1.61) H (city): 1.85 (1.32, 2.58) Hormone-replacement therapy-No Current Use: H: 1.16 (0.98, 1.39)



### December 2009 E-380

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) H (city): 1.57 (1.14, 2.17) Diabetes-yes: H: 0.96 (0.67, 1.37) H (city): 1.24 (0.78, 1.96) Diabetes-no: H: 1.28 (1.12, 1.47) H (city): 1.75 (1.30, 2.36) Hypertension-yes: H: 1.22 (1.02, 1.45) H (city): 1.65 (1.09, 2.27) Hypertension-no: H: 1.26 (1.05, 1.51) H (city): 1.74 (1.25, 2.40) Hypercholesterolemia-yes: H: 1.25 (0.94, 1.67) H (city): 1.71 (1.15, 2.54) Hypercholesterolemia-no: H: 1.23 (1.07, 1.42) H (city): 1.69 (1.25, 2.28) Family history of CVD- yes: H (city): 1.80 (1.32, 2.44) Family history of CVD- no: H: 1.07 (0.83, 1.37) H (city): 1.46 (1.00, 2.12) Time lived in current state: ≥ 20 yr: H: 1.21 (1.06, 1.39) H (city): 1.66 (1.23, 2.23) Time lived in current state: 10-19 yr: H: 1.39 (1.12, 1.72)’ H (city): 1.97 (1.40, 2.79) Time lived in current state: ≤ 9 yr: H: 1.54 (1.06, 2.26) H (city): 2.24 (1.39, 3.59) Health insurance coverage-yes: H: 1.22 (1.07, 1.39) H (city): 1.71 (1.27, 2.30) Health insurance coverage-no: H: 1.82 (0.81, 4.10) H (city): 2.65 (1.12, 6.28) Time spent outdoors: <30 min: H: 1.09 (0.86, 1.39) H (city): 1.56 (1.05, 2.31) Time spent outdoors: ≥ 30 min H: 1.26 (1.05, 1.50) H (city): 1.82 (1.29, 2.57) Reference : O'Neill et al. (2007, 156006 ) Period of Study: 2000-2004

Location: USA (6 field centers: Baltimore, MD Chicago, IL Forsyth Co, NC Los Angeles, CA New York, NY St. Paul, MN Outcome (ICD9 and ICD10): Creatinine adjusted urinary albumin excretion Assessed 2 ways: continuous log urinary albumin/creatine ration (UACR)and clinically defined micro- or macroalbuminuria (UACR ≥ 25 mg/g) vs. normal levels Age Groups: 44-84 yr Study Design: Prospective cohort analyses (MESA cohort)

N: 3901 participants, free of clinical CVD at baseline Statistical Analyses: Multiple linear regression (continuous outcome) Binomial regression (dichotomous outcome)

Covariates: Age, gender, race, BMI, cigarette status, ETS, percent dietary protein

Season: NA Dose-response Investigated? Yes, examined quartiles of exposure Statistical Package: SAS Pollutant: PM 2.5 (μg/m 3 ) Averaging Time: Avg of previous month, avg of previous 2 mo (recent exposures) 20-yr imputed PM 2.5 avg (longer-term exposures) Mean (SD): Previous month: 16.5 (4.8)

Percentiles: NR Range (Min, Max): NR Monitoring Stations: NR (used closest monitor to residence to assign value for recent exposures 20-yr PM 2.5 exposures were imputed using a space-time model.) Copollutant (correlation): PM 10 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Adjusted mean differences in log UACR (mg/g) per increase in PM 2.5 among participants seen at baseline Previous 30 days Full sample: -0.017 (-0.087, 0.052) Within 10 km: 0.026 (-0.067, 0.119) Previous 60 days Full sample: -0.040 (-0.121, 0.042) Within 10 km: -0.013 (-0.122, 0.097) Imputed 20 yr exposure Full sample: 0.002 (-0.048, 0.052) Within 10 km: -0.012 (-0.076, 0.053) Adjusted relative prevalence of microalbuminuria vs. high-normal and normal levels (below 25 mg/g) per increase in PM 2.5 among participants without macroalbuminuria during the baseline visit Previous 30 days: 0.94 (0.77, 1.16) Previous 60 days: 0.90 (0.71, 1.14) Imputed 20 yr exposure: 0.98 (0.84, 1.14)



### December 2009 E-381

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Solomon et al. (2003, 156994 ) Period of Study: Exposures measures 1966-1969 Health endpoints assessed via questionnaire, yr not reported but apparently 30 yr after exposure assessment (given the 30 yr residency requirement)

Location: United Kingdom Outcome (ICD9 and ICD10): Ischemic heart disease (a self-reported history of medically diagnosed angina or heart attack) Age Groups: 45 yr and older Study Design: Cross-sectional

N: 1,166 women Statistical Analyses: Log linear modeling

Covariates: Smoking, passive smoking in childhood, tenancy, social class, worked in industry with respiratory hazard, childhood hospital admission for chest problem, diabetes, BMI

Season: NA Dose-response Investigated? No Statistical Package: STATA Pollutant: Black smoke (μg/m 3 ) Averaging Time: Exposure measures performed 1966-1969

women had to live within 5 miles of their current address for the past 30 yr to be included Mean (SD): 11 wards with pollution measures were categorized into high (mean >120 μg/m 3 ) and low (mean <50 μg/m 3 ) exposure categories when classified according to their black smoke levels during 1966-69 SD not reported

Percentiles: NR Range (Min, Max): NR Monitoring Stations: NR Copollutant (correlation): SO 2 (health results not presented) PM Increment: Categorical Effect Estimate [Lower CI, Upper CI]: Association of particulate pollution in place of residence and ischemic heart disease Low (ref): 1.0 High: 1.0 (0.7, 1.4)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-382

# E.5. Long-Term Exposure and Respiratory Outcomes

Table E-22. Long-term exposure - r espiratory morbidity outcomes - PM 10 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ackermann-Liebrich et al. (1997, 077537 ) Period of Study: 1991-1993

Location: Switzerland (Aarau, Basel, Davos, Geneva, Lugano, Montana, Payerne, Wald) Outcome: Pulmonary function Age Groups: 18-60 yr Study Design: Cross-sectional

N: 9651 people Statistical Analyses: Regression analysis

Covariates: Age, sex, height, weight, education level, nationality, workplace exposure Season: NR Dose-response Investigated? No Statistical Package: NR Pollutant: PM 10 Averaging Time: Continuously measured, 12-mo. avg. used Mean (SD): 21.2 (7.4) Range: (10.1-33.4) Copollutant (correlation): SO 2 : r = 0.93

NO 2 : r = 0.91

O 3 : r = -0.55 Summer Daytime O 3 : r = 0.31

Excess O 3 : r = 0.67

Altitude: r = -0.77 PM Increment: 10 μg/m 3 Regression Coefficient β (Lower CI, Upper CI) for air pollutants as predictors of pulmonary function FVC: -0.0345 (-0.0407 to -0.0283) p < 0.001 FEV 1 : -0.0160 (-0.0225 to -0.0095) p < 0.001 Percent Change (Lower CI, Upper CI) associated with increase in avg annual air pollution concentration Healthy Never-smokers FVC: -3.39 p < 0.001 FEV : -1.59 1 p < 0.001 All Never-smokers FVC: -3.14 p < 0.001 FEV : -1.06 1 p < 0.001 Former Smokers FVC: -3.03 p < 0.001 FEV : -0.42 1 Current Smokers FVC: -3.21 p < 0.001 FEV : -1.35 1 p < 0.001 All FVC: -3.14 p < 0.001 FEV : -1.03 1 p < 0.001 Long-term Residents FVC: -3.16 p < 0.001 FEV : -0.96 1 p < 0.001 Reference: Avol et al. (2001, 020552 ) Period of Study: 1993-1998

Location: Southern California Outcome: FVC, FEV 1 , MMEF, PEFR Age Groups: 10 yr Study Design: cohort

N: 110 Statistical Analyses: Linear regression

Covariates: Sex, race, cohort entry yr, annual avg change in height, weight, BMI Dose-response Investigated? No Pollutant: PM 10 Averaging Time: 24-h PM 10 avgd over 1994 Mean (SD): 15.0-66.2 PM Increment: 10 μg/m 3 Mean Change (Lower CI, Upper CI) FVC: -1.8 (-9.1, 5.5)

FEV 1 : -6.6 (-13.5, 0.3) MMEF: -16.6 (-32.1 to -1.1) PEFR: -34.9 (-59.8 to -10.0)



### December 2009 E-383

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bayer-Oglesby et al. (2005, 086245 ) Period of Study: 1992-2001

Location: Switzerland (Lugano, Zurich, Bern, Geneva, Anieres, Biel, Langnau, Payerne, & Montana) Outcome: Respiratory symptoms (chronic cough, bronchitis, cold, dry cough, conjunctivitis, wheeze, sneezing, asthma, & hay fever) Age Groups: 6-15 yr Study Design: Cross-sectional

N: 9,591 children Statistical Analyses: Logistic regression models

Covariates: Age, sex, nationality, parental education, number of siblings, farming status, low birth weight, breast feeding, smoking, family history of asthma, bronchitis and/or atopy, mother who smokes, indoor humidity, mode of cooking & heating, carpeting, pets, removal of carpets/pets for health reasons, completed questionnaire & month, days max temperature <0°C, mother’s belief of association between environmental exposures & respiratory health Dose-response Investigated? Yes Statistical Package: STATA Pollutant: PM 10 Averaging Time: 12-mo avg Mean (SD): NR Range (Min, Max): NR Monitoring Stations : 9 Copollutant (correlation): NR PM Increment: 10 μg/m 3 “Fig 2 shows that declining levels of PM 10 were associated with declining prevalence of chronic cough, bronchitis, common cold, nocturnal dry cough, and conjunctivitis symptoms. For wheezing, sneezing, asthma, and hay fever, no significant association could be seen with declining PM 10 levels.” “Fig 3 illustrates that, on an aggregate level, across regions the mean change in PM 10 levels (r pearson = 0.81, p = 0.008). The strongest decline of adjusted prevalence of nocturnal dry cough was observed in Geneva, Lugano, and Anieres, where the strongest reduction of PM 10 had also been achieved.”

Reference: Burr et al. (2004, 087809 ) Period of Study: 3 wk in Jul and Jan 1997 and 2 wk in Nov 1996 and Apr 1997

Location: North Wales, England Outcome: Self-report of symptoms only for wheeze, cough, phlegm, rhinitis, and itchy eyes. Age Groups: all Study Design: Repeated measures

N: 386 persons in congested streets and 425 in the uncongested streets in 1996/1997. Of these, 165 and 283 completed the second phase of the study. Pollutant: PM 10 Averaging Time: Mean hourly concentrations Mean (SD): SD NR Congested streets - 1996-97 35.2 1998-99 27.2 Uncongested Streets 1996-97 11.6 1998-99 8.2 Monitoring Stations : 1 in congested street and 1 in uncongested Percent change PM10 in congested streets: 22.7 Percent change PM10 in uncongested streets: 28.9 Uncongested street sampling site was 20 m from the congested street sampler. The opening of the by-pass produced a reduction in pollution in the congested streets. The health effects of these changed is likely to be greater for nasal and ocular symptoms than for lower respiratory symptoms. Uncertainty about the causality arises from low response rates and conflicting trends in respiratory and nasal symptoms.



### December 2009 E-384

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Calderón-Garcidueñas et al. (2006, 091253 ) Period of Study: 1999, 2000

Location: Southwest Mexico City & Tlaxcala, Mexico Outcome: Hyperinflation, interstitial markings-measured by chest radiograph, and lung function-FVC, FEV 1 , PEF, FEF25-75, measured using spirometry tests Age Groups: 5-13 yr Study Design: Cohort

N: 249 (total), 230 (Southwest Mexico City), 19 (Tlaxcala) Statistical Analyses: Bayes test, Spearman rank correlation, multiple regression

Covariates: Age, sex Dose-response Investigated? No Statistical Package: SAS 8.2 Pollutant: PM 10 Averaging Time: 1 yr Mean (SD): Mexico City 1999-48 2000-45

Tlaxacala: 1994-2000: <NAAQS std Monitoring Stations : Southwest Mexico City-2 Tlxacala-periodic air monitoring data Copollutant: O 3 PM Increment: NR % Change: % of children with FEV 1 <80% expected value: Mexico City (n = 77): 7.8% Tlaxacala (n = 19): 0% % children with hyperinflation: Mexico City: 65.6% No hyperinflation: 79 Mild: 72 Moderate: 56 Severe: 23 Tlaxacala: 5.3% No hyperinflation: 18 Mild: 1 Moderate: 0 Severe: 0 % children with interstitial markings: Mexico City: 52.6% Number with: No interstitial markings: 19 Mild: 0 Moderate: 0 Severe: 0 Tlaxacala: 0% No interstitial markings: 109 Mild: 112 Moderate: 9 Severe: 0 Reference: Calderon-Garciduen  as, et al. (2003, 156316 ) Period of Study: Jan 1999-Jun 2000

Location: Mexico City, Tuxpam, and Tlaxcala, Mexico Outcome: Respiratory system changes Age Groups: 5-17 yr Study Design: Case-control of subjects examined for this study

N: 174 cases, 27 controls, children Statistical Analyses: Chi-square test with Yates correction, Spearman’s rank correlation test. Dose-response Investigated? No Statistical Package: SAS 8.2 Pollutant: PM 10 Averaging Time: 12 h (daytime 08: 00- 20: 00) and nighttime (20: 00-08: 00) Mean (SD): Mexico City Day/Night

Jan-Jun 1999 76.0/50.0

Jul-Dec 1999 42.8/22.5

Jan-Jun 2000 75.2/47.5 Daily ambient exposure of children to a complex mixture of air pollutants produces significant chest X-ray abnormalities, a decrease in predicted values of FEF 25-75 , FEF 75 , and the FEV 1 /FVC ratio in association with interstitial marking on chest X-rays, a mild restrictive pattern by spirometry, peripheral blood abnormalities, and an imbalance of serum cytokines.

Reference: Cavanagh et al. (2007, 189802 ) Period of Study: Mar-Aug 2004

Location: Christchurch, New Zealand Outcome: A clinical study of excretion of 1-hydroypyrene (1-OHP) as a marker of PAH exposure Age Groups: Non-smoking males aged 12-18 yr Study Design: Comparison of 2 high pollution events and 2 low pollution events

N: 89 male students in a boarding school Statistical Analyses: Wilcoxon signedrank test for paired observations, MannWhitney U test

Season: Winter Dose-response Investigated? No Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Fall Low Outdoor 19 Indoor NA Winter I Outdoor 43 Indoor 38 Winter II Outdoor 72 Indoor 84 Winter Low Outdoor 12 Indoor 16 Monitoring Stations : One inside the boarding house, and one outside Urinary 1-OHP were raised after highpollutions events. Peaks were slightly higher than for U.S. non-smokers of similar ages and slightly lower than for German non-smokers of similar ages. Urinary 1-OHP was slightly higher inasthmatics compared to nonasthmatics.

There were no indoor sources of PAHs (wood-burning stoves, tobacco smoke). Diet is another source of PAHs, but all students ate in the boarding house. These results suggest 1-OHP could be used as a biomarker of ambient air pollution.



### December 2009 E-385

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Downs et al. (2007, 092853 ) Period of Study: 1991, 2002

Location: Switzerland Outcome: FEV 1 , FEV 1 as % of FVC, FEF25-75 Age Groups: 18-60 yr Study Design: Prospective Cohort

N: 4742 people Statistical Analyses: Linear random effects models

Covariates: Age, sex, height, parental smoking, season, education, nationality, occupational exposure, smoking (status, pack-yr), atopy, BMI Dose-response Investigated? Yes-linear fit best Statistical Package: SAS 9.1, STATA 8.2, R 2.4 Pollutant: PM 10 Averaging Time: Annual

Mean: Mean interval exposure: 238 μg/m 3 /yr

Percentiles:

25th: 197

75th: 287 PM Increment: 10 μg/m 3 reduction in annual mean

Percent / absolute reduction in annual decline in lung function over 11-yr period (95% CI):

Annual decline in FEV 1 reduced by 9% / 3.1 mL (0.03-6.2)

Annual decline in FEF 25-75 reduced by 16% / 11.3 mL/second (4.3-18.2)

Annual decline in FEV 1 as a percentage of FVC of 0.06 (0.01-0.12) A reduction in interval exposure of 109 μ g per m 3 cubic meter-yr (equivalent to a reduction of 10 μ g/m 3 in the annual avg during the mean follow-up time of 10.9 yr) was associated with: A reduction of 6.9 mL (95% CI, 2.1 to 11.7) in the annual decline in FEV 1 A 22% reduction in the annual decline in FEF25-75 (i.e., by 14.0 mL per second 95% CI, 3.1 to 24.8)

Reference: Gauderman et al. (2000, 012531 ) Period of Study: 1993-1997

Location: Southern California Outcome: FVC, FEV 1 , MMEF, FEF75 Age Groups: Fourth, seventh, or tenth graders Study Design: Cohort

N: 3035 subjects Statistical Analyses: Linear regression

Covariates: Height, weight, BMI, asthma, smoking, exercise, room temperature, barometric pressure Dose-response Investigated? Yes Statistical Package: SAS Pollutant: PM 10 Averaging Time: 24-h avg PM 10 Mean (SD): PM 10 51.5 Copollutant (correlation): PM 2.5 r = 0.96

O 3 r = -0.32

PM 10-2.5 r = 0.92

NO 2 r = 0.65 Inorg. Acid r = 0.68 PM 10 Increment: 51.5 μg/m 3 % Change (Lower CI, Upper CI) PM 10 -4th grade FVC -0.58 (-1.14 to -0.02) FEV -0.85 (-1.59 to -0.10) 1 MMEF -1.32 (-2.43 to -0.20) FEF 75 -1.63 (-3.14 to -0.11)

PM 10 -7th grade FVC -0.45 (-1.03, 0.13) FEV -0.44 (-1.10, 0.23) 1 MMEF -0.48 (-2.51, 1.59) FEF 75 -0.50 (-2.26, 1.29)

PM 10 -10th grade FVC 0.07 (-0.99, 1.13) FEV -0.46 (-1.84, 0.94) 1 MMEF -0.71 (-4.87, 3.63) FEF 75 -1.54 (-5.61, 2.71) Reference: Gauderman et al. (2002, 026013 ) Period of Study: 1996-2000

Location: Southern California Outcome: Lung function development: FEV 1 , maximal midexpiratory flow (MMEF) Age Groups: Fourth grade children (avg age = 9.9 yr) Study Design: Cohort study

N: 1678 children, 12 communities Statistical Analyses: Mixed model linear regression

Covariates: Height, BMI, doctordiagnosed asthma and cigarette smoking in previous yr, respiratory illness and exercise on day of test, interaction of each of these variables with sex, barometric pressure, temperature at test time, indicator variables for field technician and spirometer Dose-response Investigated? Yes Statistical Package: SAS (10) Pollutant: PM 10 Averaging Time: Annual 24-h avg Mean (SD): The avg levels were presented in an online data supplement (Fig E1) Monitoring Stations : 12 Copollutant (correlation): O 3 (10 AM to 6 PM) r = 0.13

O 3 r = -0.37

NO 2 r = 0.64 Acid vapor r = 0.79

PM 2.5 r = 0.95

PM 10-2.5 r = 0.95

EC r = 0.86

OC r = 0.97 PM Increment: 51.5 μg/m 3

Association Estimate: None of the pulmonary function tests had a statistically significant correlation with PM 10 FEV 1 r = -0.12 p = 0.63 MMEF r = -0.22 p = 0.30



### December 2009 E-386

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Gauderman et al. (2004, 056569 ) Period of Study: Air pollution data ascertainment: 1994-2000. Spirometry testing: Spring 2001-Spring 2003

Location: 12 Communities in Southern California Outcome: Lung function FVC, FEV 1 , MMEF (Maximal midexpiratory flow rate) Age Groups: Children, Avg age 10 yr Study Design: Prospective Cohort Study

N: 12 Communities 2,034 Children 24,972 child-months Statistical Analyses: Linear regression of changes in sex-and-community specific lung growth function and PM

Covariates: Random effect for communities

Season: ALL (except for PM 2.5 ) Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 10 Averaging Time: 24-h measurements over each yr used to create annual avg Mean: Means are presented in figures only. Range (Min, Max): ~15, ~65 Monitoring Stations : 12 Copollutant (correlation):

O 3 : r = 0.18

NO 2 : r = 0.67

PM 2.5 : r = 0.95

EC: r = 0.85

OC: r = 0.97 PM Increment: Most to least polluted community Range: PM 10 : 51.4 μg/m 3 EC: 1.2 μg/m 3 OC: 10.5 μg/m 3 Difference in Lung Growth [Lower CI, Upper CI]; FVC -60.2 (-190.6 to 70.3) FEV 1 -82.1 (-176.9 to 12.8) MMEF -154.2 (-378.3 to 69.8)

EC: FVC -77.7 (-166.7 to 11.3) FEV 1 -87.9 (-146.4 to -29.4) MMEF -165.5 (-323.4 to -7.6)

OC: FVC -58.6 (-196.1 to 78.8) FEV 1 -86.2 (-185.6 to 13.3) MMEF -151.2 (-389.4 to 87.1)

Correlation with % below 80% predicted Lung function (p-value) PM 10 : 0.66 (0.02) EC: 0.74 (0.006) Reference: Gauderman et al. (2007, 090121 ) Period of Study: 1993-2004

Location: 12 Southern California Communities Outcome: pulmonary function tests FVC, FEV 1 , MMEF/FEF25.75 Age Groups: Children (mean age 10 at recruitment, followed for 8 yr) Study Design: Cohort Study (Children’s Health Study)

N: 3677 children (1718 in cohort 1 recruited 1993 and 1959 in cohort 2 recruited 1996) 22686 pulmonary function tests. Statistical Analyses: Hierarchical mixed effects model with linear splines

Covariates: Adjustments for height, height squared, BMI, BMI squared, present asthma status, exercise or respiratory illness on day of test, smoking in previous yr, field technician, traffic indicator (distance from freeway, distance from major roads), random effects for participant and community. Dose-response Investigated? no Statistical Package: SAS Pollutant: PM 10 Monitoring Stations : 1 in each community PM Increment: 51.4 μg/m 3 Pollutant effect reported as difference in 8 yr lung function growth from least to most polluted community. Negative difference indicates growth deficits associated with exposure. For PM 10 FEV growth deficit is -111



### December 2009 E-387

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Goss et al. (2004, 055624 ) Period of Study: 1999-2000

Location: USA Outcome: Cystic Fibrosis pulmonary exacerbations, FEV 1 Age Groups: > 6 Study Design: Cohort

N: 11484 patients Statistical Analyses: Logistic regression, t-tests, Mann-Whitney tests, Chi-squared tests, polytomous regression, multiple linear regression

Covariates: Age, sex, lung function, weight, insurance status, pancreatic insufficiency, airway colonization, genotype, median household income by census tract, zipcode. Dose-response Investigated? No Statistical Package: STATA, SAS Pollutant: PM 10 Averaging Time: Annual mean of 24-h avg Mean (SD): 24.8(7.8) mg/m 3

Percentiles: 25th: 20.3 50th(Median): 24.0

75th: 28.9 Monitoring Stations : 626 PM Increment: 10 μg/m 3 Odds Ratio Estimate [Lower CI, Upper CI]: Odds of having 2 or more pulmonary exacerbations as compared to 1 or less in 2000 1.08 (1.02 -1.15) Odds of having 2 or more pulmonary exacerbations as compared to no exacerbations in 2000 1.09 (1.02 -1.17)

Decrease in FEV 1 38ml(18-58)

Reference: Hanigan et al, (2008, 156518 ) Period of Study: Fire Season (AprNov) from 1996-2005

Location: Darwin, Australia Outcome: Respiratory admissions Study Design: Time-series

Covariates: Race, age Statistical Analysis: Over-dispersed Poisson generalized linear models Statistical Package: R Age Groups: All Pollutant: PM 10 Averaging Time: Daily levels estimated from visibility data

Mean Unit: *Only reported for 2005* 15.31 μg/m 3 Range (Min, Max): 6.93, 31.12 Copollutant (correlation): NR Increment: 10 μg/m 3 Percent Increase (95% CI) *Full results reported visually in Fig 3* Total Respiratory Admissions 4.81 % (-1.04-11.01) Indigenous Respiratory Admissions, No Lag 9.40% (1.04-18.46) Non-Indigenous Respiratory Admissions, No Lag 3.14% (-2.99-9.66) Indigenous Respiratory Admissions, Lag 3 15.02% (3.73-27.54) Non-Indigenous Respiratory Admissions, Lag 3 0.67% (-7.55-9.61) Indigenous Asthma Admissions, Lag 1 16.27% (3.55-40.17) Non-Indigenous Asthma Admissions, Lag 1 8.54% (-5.60-24.80) Reference: Ho et al. (2007, 093265 ) Period of Study: Oct 1995-Mar 1996

Location: Taiwan, Republic of China Outcome: Asthma Age Groups: 10-17 yr Study Design: Screened junior high students for asthma, collected meteorological data to determine the relationship.

N: 69,367 Statistical Analyses: Logistic regression model, the maximum likelihood estimation with Fisher’s scoring algorithm, stepwise regression model, Wald statistic, Akaike criteria. GEE, GENMOD

Covariates: Wind, barometric pressure, temperature, rain, humidity

Season: Fall-spring Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 10 Averaging Time: Monthly Monitoring Stations : 72 Odds Ratio from stepwise regression model: Females (n = 32, 648) 0.993 [0.990-0.997]

Males: NS Higher PM 10 concentration resulted in less asthma prevalence. However, a higher number of rain days seemed to reduce asthma prevalence Rain days might interact with PM 10

.



### December 2009 E-388

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hong et al. (2004, 156565 ) Period of Study: 2001

Location: Kerinci, SP7, and Pelalawan, Indonesia Outcome: Respiratory symptoms Age Groups: <12 yr Study Design: Disproportionate random sampling was used to select 100 households from each village. An interviewer interviewed all children through the caregiver/parent to obtain symptoms in the past 2 wk (cough, cold, phlegm) and the last 12 mo.

N: 382 children Statistical Analyses: Chi-square test, analysis of variance, prevalence rates, adjusted odds ratios, multivariate adjusted odds ratios from multiple logistic regression models, allowing for clustering.

Covariates: Age, gender, no. of children in household, household income, floor area of house, fuel for cooking, no. of smokers in household, personal and family medical history. Dose-response Investigated? No Statistical Package: SPSS STATA v.7 Pollutant: PM 10 Averaging Time: 24-h measurements were taken daily from 2 wk before he field survey to 1 mo after the survey Mean (SD): Kerinci 102.9 (49.6) μg/m 3 SP7 73.7 (41.7) Pelalawan 26.1 (14.5)

P<0.01 Range (Min, Max): Kerinci 25, 184 SP7 13, 138 Pelalawan 10, 66 Monitoring Stations : 3 PM Increment: Low (Pelalawan), Medium (SP7), & High (Kerinci) PM Exposure Odds Ratios (95% CI) for Symptoms by village: Cough/cold past 2 wks Pelalawan 1.00 SP7 2.03 (1.04, 3.96) Kerinci 3.17 (1.43, 7.07) Respiratory symptoms last 12 mo Pelalawan 1.00 SP7 1.15 (0.58, 2.26) Kerinci 1.42 (0.62, 3.25) Ever had rhinitis w/o flu Pelalawan 1.00 SP7 2.17 (0.57, 8.29) Kerinci 0.56 (0.11, 2.83) Ever had wheezing Pelalawan 1.00 SP7 0.85 (0.35, 2.08) Kerinci 1.18 (0.46, 3.01)



### December 2009 E-389

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Horak et al. (2002, 034792 ) Period of Study: 1994-1997

Location: Lower Austria Outcome: Lung function growth measured by changes in: 1. FVC (forced vital capacity)

2. FEV 1 3. MEF 25 -75 (midexpiratory flow between 25-75% of the forced vital capacity) Age Groups: 2-3 grade schoolchildren (mean age = 8) Study Design: Prospective cohort with repeated measures

N: 975 children Statistical Analyses: Linear regression GEE, nonstationary M-dependent correlation structure

Covariates: Gender, atopy, ETS exposure, baseline lung function, first height, height difference, school site

Season: Winter, summer Dose-response Investigated? No Pollutant: PM 10 Mean (SD): Winter: 21.0 (4.8) Summer: 17.4 (2.8) Range (Min, Max):

Winter: 9.4-30.5

Summer: 11.7-28.9 Monitoring Stations : NR, stations were located in the immediate vicinity of each of the 8 elementary schools Copollutant (correlation): Winter

O 3 : (r = -0.581)

SO 2 (r = 0.520)

NO 2 (r = 0.595)

Summer

O 3 (r = -0.429)

SO 2 (r = 0.335)

NO 2 (r = 0.412) PM Increment: 1 μg/m 3

 Mean per unit increase in PM (p-value)

Outcome: difference per day of FVC (mL/day) Summer: 0.001 (0.938) Winter: 0.008 (0.042) Controlling for temperature: Summer: -0.007 (0.417) Winter: -0.003 (0.599) Controlling for O 3 : Summer: 0.001 (0.911) Winter: 0.010 (0.019) Controlling for NO 2 : Summer: -0.018 (0.056) Winter: 0.015 (0.000) Controlling for SO 2 : Summer: 0.005 (0.575) Winter: 0.004 (0.492) In non-asthmatic children: Summer: -0.003 (0.710) Winter: 0.009 (0.030) In group not exposed to ETS: Summer: 0.014 (0.154) Winter: 0.012 (0.0018) In group exposed to ETS: Summer: 0.022 (0.088) Winter: 0.003 (0.656) Outcome: difference per day of FEV 1 (mL/day) Summer: -0.023 (0.003) Winter: 0.001 (0.885) Controlling for temperature: Summer: -0.034 (0.000) Winter: -0.011 (0.016) Controlling for O 3 : Summer: -0.022 (0.008) Winter: 0.004 (0.338) Controlling for NO 2 : Summer: -0.038 (0.000) Winter: 0.011 (0.005) Controlling for SO 2 : Summer: -0.022 (0.010) Winter: -0.005 (0.358) Outcome: difference per day MEF 25-75 (mL/day) Summer: -0.090 (0.000) Winter: -0.008 (0.395) Controlling for temperature: Summer: -0.112 (0.000) Winter: -0.013 (0.295) Controlling for O 3 : Summer: -0.087 (0.000) Winter: -0.008 (0.434) Controlling for NO 2 : Summer: -0.102 (0.000) Winter: 0.005 (0.610) Controlling for SO 2 : Summer: -0.095 (0.000) Winter: -0.011 (0.474)



### December 2009 E-390

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hwang et al. (2006, 088971 ) Period of Study: 2001

Location: Taiwan Outcome: Peak expiratory flow rate (PEFR), Forced Expiratory Volume in 1 second (FEV 1 ), Forced Vital Capacity (FVC), Self reported “frequent coughing,” Self reported “shortness of breath,” Self reported “ irritation of respiratory tract” Age Groups: 24-55 yr (mean = 40) Study Design: Cohort

N: 120 men (60 traffic policemen and 60 controls) Statistical Analyses: ANOVA, odds ratios calculated from 2X2 table Dose-response Investigated? No Pollutant: PM 10 Mean (SD): 55.58 (16.57)

Percentiles: 25th: 42.96 50th(Median): 53.81

75th: 70.37 Range (Min, Max): 29.36, 99.58 Monitoring Stations : 22 Copollutant (correlation): NO X (r = 0.34) SO 2 (r = 0.58) CO (r = 0.27) O 3 (r = 0.28) PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] Single pollutant model: 1.00 [0.99, 1.02] Controlling for NO X : 0.99 [0.97, 1.00] Controlling for CO: 1.00 [0.99, 1.01] Controlling for O 3 : 1.00 [0.99, 1.02]

Reference: Hwang et al, (2008, 134420 ) Period of Study: 2001-2003

Location: Taiwan Outcome: Oral Cleft Study Design: Case-control

Covariates: Maternal age, plurality, gestational age, population density and season of conception Statistical Analysis: Logistic regression Age Groups: Infants Pollutant: PM 10 Averaging Time: hourly Mean (SD) Unit: Avg: 54.83 ± 13.07 μg/m 3 Spring: 64.44 ± 16.21 μg/m 3 Summer: 39.11 ± 8.31 μg/m 3 Fall: 47.76 ± 11.77 μg/m 3 Winter: 68.00 ± 21.88 μg/m 3

Range (Min, Max): Avg: 20.75-78.05 μg/m 3 Spring: 23.33-94.33 μg/m 3 Summer: 17.33-60.00 μg/m 3 Fall: 21.00-72.00 μg/m 3 Winter: 21.33-116.00 μg/m 3

Copollutant (correlation): CO: -0.19 NO X : 0.56 O 3 : 0.39 SO 2 : 0.50 Increment: 10 μg/m 3 Odds Ratio (Min CI, Max CI); Single Pollutant Model Month 1: 1.01 (0.96-1.06) Month 2: 1.00 (0.95-1.05) Month 3: 0.99 (0.95-1.05) Two Pollutant Model (O 3 + PM 10 ) Month 1: 0.99 (0.94-1.04) Month 2: 0.99 (0.94-1.04) Month 3: 0.98 (0.93-1.04) Two Pollutant Model (CO + PM 10 ) Month 1: 1.01 (0.96-1.06) Month 2: 1.00 (0.95-1.05) Month 3: 0.99 (0.95-1.05) Two Pollutant Model (NO + PM 10 ) X Month 1: 1.02 (0.97-1.08) Month 2: 1.01 (0.95-1.07) Month 3: 1.01 (0.95-1.07) Three Pollutant Model (O 3 + CO + PM 10 ) Month 1: 0.99 (0.94-1.04) Month 2: 0.99 (0.94-1.04) Month 3: 0.99 (0.93-1.04) Three Pollutant Model (O 3 + NO X + PM 10 ) Month 1: 1.00 (0.94-1.06) Month 2: 0.98 (0.92-1.05) Month 3: 1.00 (0.93-1.06)



### December 2009 E-391

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ingle et al. (2005, 089014 ) Period of Study: May 2003-Apr 2004

Location: Jalgaon City, India Outcome: Peak expiratory flow rate (PEFR), Forced Expiratory Volume in 1 second (FEV 1 ), Forced Vital Capacity (FVC), Self reported “frequent coughing,” Self reported “shortness of breath,” Self reported “ irritation of respiratory tract” Age Groups: 24-55 yr (mean = 40) Study Design: Cohort

N: 120 men (60 traffic policemen and 60 controls) Statistical Analyses: ANOVA, odds ratios calculated from 2X2 table Dose-response Investigated? No Pollutant: PM 10 Mean (SD): Location-specific means: Prabhat: 224 (27) Ajanta: 269 (41) Icchdevi: 229 (24) Monitoring Stations : 3 OR Estimate [p-value] Self reported frequent coughing 2.96 [p < 0.05] Self reported shortness of breath 1.22 [p < 0.05] Self reported irritation in respiratory tract 7.5 [p < 0.05] Observed/expected lung function p-value for difference between groups: FVC (L) Traffic policemen: 0.82 Controls: 0.99 Traffic policemen: Obs = 3.03 ± 1.7 Exp = 3.70 ± 2.8 Controls: Obs = 3.18 ± 0.91 Exp = 3.19 ± 1.71 FEV 1 (L) Traffic policemen: 0.73 Controls: 1.18 Traffic policemen: Obs = 2.27 ± 1.05 Exp = 3.08 ± 2.7 Controls: Obs = 3.61 ± 0.90 Exp = 3.06 ± 0.91 PEFR (L/s) Traffic policemen: 0.66 Controls: 0.92 Traffic policemen: Obs = 6.05 ± 2.15 Exp = 9.21 ± 0.47 Controls: Obs = 5.54 ± 1.85 Exp = 6.11 ± 2.31 Reference: Islam et al. (2007, 090697 ) Period of Study: 2006

Location: 12 California communities Outcome: Respiratory symptoms, Asthma Study Design: Longitudinal study cohort Statistical Analyses: Cox proportional hazards regression Age Groups: 7-9 10-11 >11 Pollutants: PM 10 Averaging Time: 24-h avg Copollutants (correlation): O 3 NO 2 EC

OC The study doesn’t present quantitative results on PM 10

.



### December 2009 E-392

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Janssen et al. (2003, 133555 ) Period of Study: Apr 1997-Jul 1998

Location: Netherlands-24 schools Outcome: Symptoms of asthma and allergic disease (asthma, conjunctivitis, hay fever, itchy rash, eczema, phlegm, bronchitis), skin prick test (SPT) reaction to allergens, lung function (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV 1 ], and positive test for fall in FEV 1 ≥ 15% after inhalation of maximal 23 mL hypertonic saline [BHR = bronchial hyper-responsiveness]) Age Groups : 7-12 yr old Study Design: Cohort

N: 24 schools (see notes) Statistical Analyses: Multilevel model

Covariates: Age, sex, non-Dutch nationality, cooking on gas, current parental smoking, current pet possession, parental education level, number of persons in the household, presence of an unvented water heater in kitchen, questionnai re not filled out by the mother, presence of mold stains in kitchen or living room or bedroom, parental respiratory symptoms, distance of home to motorway, cough or cold at time of lung function measurement, bronchitis or severe cold or flu in 3 wk preceding measurement, season Dose-response Investigated? No Statistical Package : MLwiN Pollutant: PM 2.5 Averaging Time: Annual Mean (SD): 20.5 μg/m 3 (2.2)

Percentiles:

25th: 18.6 50th (Median): 20.4

75th: 22.1 Range (Min, Max): 17.3, 24.4 PM Increment: ‘Difference between the maximum and the minimum of the exposure indicator’ (3.5 μg/m 3 ) RR Estimate [Lower CI, Upper CI] lag: Current wheeze 1.51 (0.90, 2.53) Asthma ever 1.03 (0.59, 1.82) Current conjunctivitis 2.08 (1.17, 3.71) Hay fever ever 2.28 (1.13, 4.57) Current itchy rash 1.63 (0.91, 2.89) Eczema ever 1.31 (0.94, 1.83) Current phlegm 1.53 (0.74, 3.19) Current bronchitis 1.71 (0.84, 3.50) Elevated total IgE 1.45 (0.74, 2.84) Any allergen (spt reactivity) 1.33 (0.83, 2.11) Indoor allergens (spt reactivity) 1.17 (0.70, 1.94) Outdoor allergens (spt reactivity) 1.90 (1.06, 3.40) FVC < 85% predicted 0.54 (0.29, 1.00) FEV 1 < 85% predicted 0.88 (0.37, 2.09) BHR 0.93 (0.51, 1.68) Notes: Fig 1 of the article illustrates the association between exposures, including PM 2.5 , and various respiratory symptoms among children with and without a positive SPT and positive BHR. In general, the association between PM 2.5 and respiratory symptoms were higher for children with a positive SPT or BHR, except for the outcome of current phlegm. This effect appeared to be the strongest for children with a positive BHR, particularly for current wheeze and current bronchitis. The authors also reported separate analyses for children with SPT reactivity for indoor and outdoor allergens, but did not report any clear differences between the two groups. The authors did report, in the text, that the OR of PM 2.5 exposure for children sensitized for outdoor allergens was 7.64 for current itchy rash (p < 0.05).



### December 2009 E-393

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference : Kan, et al. (2007, 091383 ) Period of Study: 1987-1992

Location: Four Communities in the U.S.: Forsyth County, North Carolina Jackson, Mississippi northwest suburbs of Minneapolis, Minnesota and Washington County, Maryland. Outcome: FEV 1 and FVC Age Groups: Middle-aged (mean age was 54.2 yr) Study Design: Hierarchical regression

N: 15,792 Statistical Analyses: SAS PROC MIXED

Covariates: Distance to major roads, traffic exposure, age, ethnicity, sex, smoking, environmental tobacco smoke exposure, occupation, education, medical history, BMI. Dose-response Investigated? No Statistical Package: SPSS Version 11 for traffic density,

SAS Version 9.1.2 for statistical analysis Pollutant: PM 10 Averaging Time: 24-h PM 10 averaged over study period PM Component: Vehicle emissions Monitoring Stations : 0 Copollutant:

NO 2 O 3 RR Estimate (Lower CI, Upper CI): (Note: for ARIC participants living <150 meters from major roads) Women FEV 1 (mL) Age-adjusted model -29.5 (-52.2 to -6.9) Multivariate model -15.7 (-34.4 to -2.9) FVC (mL) Age-adjusted model -33.2 (-60.4 to -5.9) Multivariate model -24.2 (-46.2,-2.3) FEV 1 /FVC (%) Age-adjusted model -0.1(-0.5,0.2) Multivariate model 0.1 (-0.3,0.4) Men FEV 1 (mL) Age-adjusted model -38.4 (-76.7,0.6) Multivariate model -6.4 (-38.1,25.3) FVC (mL) Age-adjusted model -17.0(-62.0,28.0) Multivariate model 10.9(-24.7,46.5) FEV 1 /FVC (%) Age-adjusted model -0.05 (-0.9,0.0) Multivariate model -0.3 (-0.7,0.2) Reference: Kim et al. (2005, 087418 ) Period of Study: Mar and Dec 2000

Location: Incheon & Ganghwa, Korea Outcome: Lung function (FEV 1 , FVC) Age Groups: Middle school students Study Design: Panel

N: 368 children Statistical Analyses: Generalized liner model

Covariates: Gender, grade

Season: Spring and fall Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 10 Averaging Time: Monthly Mean (SD): Incheon Mar 64 Dec 54 Ganghwa Mar 64 Dec 53 Range (Min, Max): NR PM Increment: NR OR Estimate [Lower CI, Upper CI]: ‘‘The present study showed that the values of FEV 1 and FVC were greater in Dec than in Mar for both male and female students at all academic yr...Because only the level of PM 10 was significantly higher for Mar than for Dec in both areas, the authors suggest that decrements of pulmonary function in Mar for both areas are associated with the increased level of PM 10 ‘‘

Reference: Kim et al. (2004, 087383 ) Period of Study: Mar-Jun (spring) 2001 Sep-Nov (fall) 2001

Location: Alameda County, CA Outcome: Asthma, bronchitis Age Groups: Children (in grades 3-5) Study Design: Cross-sectional

N: 1109 children, 871 (long term resident children), 462 (long term related females), 403 (long term related males) Statistical Analyses: 2-stage multiple logistic regression model

Covariates: Respiratory illness before age of 2, household mold/moisture, pests, maternal history of asthma (for asthma) Season: Spring and fall Dose-response Investigated? Yes Statistical Package: SAS 8.2 Pollutant: PM 10 Averaging Time: 9 wk Mean (SD): Study Avg 30 Monitoring Stations : 10 Copollutant (correlation): r2 is approximately 0.9 for all copollutants – BC, PM 2.5 , NO X , NO 2 , NO (NO X -NO 2 ) PM Increment: 1.4 (IQR) OR Estimate [Lower CI, Upper CI]: Bronchitis All subjects: 1.03 [0.99, 1.07] LTR subjects: 1.02 [0.98, 1.07] LTR females: 1.04 [1.01, 1.09] LTR males: 1.01 [0.95, 1.06] Asthma All subjects: 1.02 [0.96, 1.09] LTR subjects: 1.04 [0.97, 1.12] LTR females: 1.09 [0.92, 1.29] LTR males: 1.02 [0.94, 1.10] Asthma excluding outlier school having a larger proportion of Hispanics All subjects: 1.06 [0.97, 1.16] LTR subjects: 1.08 [0.98, 1.19] LTR females: 1.09 [0.96, 1.24] LTR males: 1.08 [0.97, 1.19]



### December 2009 E-394

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Kumar et al. (2004, 089873 ) Period of Study: 1999-2001

Location: Mandi Gobindgarh and Morinda, Punjab State, northern India Outcome: Chronic respiratory symptoms & Spirometric ventilatory defect Age Groups: >15 yr Study Design: Cross-sectional

N: 3603 individuals Statistical Analyses: Logistic regression

Covariates: Age, gender, migration, SES, smoking, type of cooking fuel use Dose-response Investigated? No Pollutant: PM 10 Mean (SD): Study town 112.8 (17.9) Reference town 75.8 (2.9) PM 10 Increment: Low vs. High OR (Lower CI, Upper CI) p-value Chronic respiratory symptoms Low 1.00 (ref) High 1.5 (1.2, 1.8) <0.001 Spirometric ventilatory defect Low 1.00 (ref) High 2.4 (2.0-2.9) <0.001

Reference: Leonardi et al. (2000, 010272 ) Period of Study: 1996

Location: 17 cities of Central Europe (Bulgaria, Czech Republic, Hungary , Poland, Romania, Slovakia) Outcome: Immune biomarkers Age Groups: 9-11 Study Design: Cross-sectional

N: 366 school children Statistical Analyses: Linear regression

Covariates: Age, gender, parental smoking, laboratory of analysis, recent respiratory illness Dose-response Investigated? No Statistical Package: STATA Pollutant: PM 10 Averaging Time: Annual PM 10 Mean (SD): PM 10 : 65 (14) Range (Min, Max):

PM 10 : (41, 96) 5th, median, & 95th percentile

PM 10 : 41, 63, 90 % Change (Lower CI, Upper CI) p-value PM 10 Neutrophils -5 (-33, 36) >.20 Total lymphocytes 20 (-6, 54); .150 B lymphocytes 42 (-3, 107); .067 Total T lymphocytes 30 (-2, 73); .072 CD4+ 28 (-10, 82); .177 CD8+ 29 (-5, 75); .097 CD4/CD8 7 (-20, 43) >.20 NK 33 (-10, 97); .157 Total IgG 11 (-10, 38) >.20 Total IgM 5 (-21, 39) >.20 Total IgA11 (-16, 46) >.20 Total IgE -8 (-62, 123) >.20 Reference: Lichtenfels et al, (2007, 097041 ) Period of Study: 2001-2003

Location: São Paulo, Brazil Outcome: Secondary sex ratio Study Design: Retrospective Cohort

Covariates: NR Statistical Analysis: Correlation Coefficient Age Groups: Infants Pollutant: PM 10 Averaging Time: Annual Mean (SD) Unit: 2001: 49.8 (10.5) μg/m 3 2002: 48.5 (11.4) μg/m 3 2003: 49.4 (14.4) μg/m 3 Range (Min, Max): 31.71-60.96 μg/m 3 Copollutant (correlation): NR Increment: NR

Correlation Coefficient: R2 = 0.7642, P = 0.13

Reference: Lubinski, et al. (2005, 087563 ) Period of Study: 1993-1997

Location: Poland Outcome: Pulmonary function TLC: total lung capacity ITGV: interthoracic gas volume ITGV%TLC: ITGV percent total lung capacity Raw: airway resistance FVC: forced vital capacity FEV 1 : forced expiratory volume, 1 second FEV 1 %FVC: FEV 1 percent forced vital capacity PEF: peak expiratory flow FEF50: forced expiratory flow Age Groups: 18-23 males, healthy Study Design: Ecological crosssectional study

N: 1278 subjects Statistical Analyses: Multiple linear regression, ANOVA

Covariates: Report unclear on whether or not there was covariate control, but may include NO 2 and SO 2 Dose-response Investigated? No Pollutant: PM 10 Averaging Time: 12 mo Mean (SD): A: Highest Pollution Region Katowice 67-125 Krakow 41-49 B: Moderate Pollution Region Bielsko-Biala 29-48 Opole 18-45 Lodz 23-38 Warsaw 35-45 Wroclaw 28-76 Zagan 5-35 C: Lowest Pollution Region Gizycko 5-18 Hel 12-18 Ostroda 23-33 Swinoujscie 7-16 Ustka 12-26 Copollutant: NO 2 , SO 2 PM Increment: 1 μg/m 3 Slope, multiple regression

TLC PM : -0.05

10 +SO 2 : 0.03 +NO : -0.06 2 ITGV PM : 0.01

10 +SO 2 : -0.07 +NO : -0.07 2 ITGV%TLC PM : -0.06

10 +SO 2 : 0.08 +NO : 0.00 2 Raw PM : 0.075

10 +SO 2 : -0.08 +NO : 0.127 2 FVC PM : 0.045

10 +SO 2 : 0.045 +NO 2 : -0.14 FEV 1 PM : 0.031

10 +SO 2 : -0.08 +NO 2 : -0.12 FEV 1 %FVC PM : 0.00

10 +SO 2 : -0.14 +NO : -0.048 2 PEF PM : -0.18

10 +SO 2 : 0.056 +NO : -0.09 2 FEF50 PM : 0.031

10 +SO 2 : -0.11 +NO 2 : -0.04



### December 2009 E-395

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: McConnell et al. (1999, 007028 ) Period of Study: 1993

Location: Southern California Outcome: Bronchitis, chronic cough, phlegm Age Groups: Children: 4th, 7th, & 10th graders Study Design: Cross-sectional

N: 3676 people Statistical Analyses: Logistic regression

Covariates: Age, sex, race, grade, health insurance Dose-response Investigated? Yes Pollutant: PM 10 Averaging Time: Yearly avg 24 h PM 10 Mean (SD): 34.8 Range (Min, Max): 13.0, 70.7 Copollutant (correlation): NO 2 r = 0.74 O 3 r = 0.32 Acid r = 0.54 PM 2.5 r = 0.90 NO 2 r = 0.83 O 3 r = 0.50 Acid r = 0.71 PM 10 Increment: 19 μg/m 3 Children w/ asthma Bronchitis: 1.4 (1.1,1.8) Phlegm: 2.1 (1.4, 3.3) Cough: 1.1 (0.8, 1.7) Children w/ wheeze, no asthma Bronchitis: 0.9 (0.7, 1.3) Phlegm: 0.9 (0.6, 1.4) Cough: 1.2 (0.9, 1.8) Children w/ no wheeze, no asthma Bronchitis: 0.7 (0.4, 1.0) Phlegm: 0.8 (0.6, 1.3) Cough: 0.9 (0.7, 1.2)

Reference: McConnell et al. (2003, 049490 ) Period of Study: 1993-1999

Location: 12 Southern CA communities Outcome: Bronchitis symptoms Age Groups: 9-19 Study Design: Communities selected on basis of historic levels of criteria pollutants and low residential mobility.

N: 475 children Statistical Analyses: 3 stage regression combined to give a logistic mixed effects model

Covariates: Sex, ethnicity, allergies history, asthma hist ory, SES, insurance status, current wheeze, current exposure to ETS, personal smoking status, participation in team sports, in utero tobacco exposure through maternal smoking, family history of asthma, amount of time routinely spent outside by child during 2-6 pm. Dose-response Investigated? No Statistical Package: SAS Glimmix

macro Pollutant: PM 10 Averaging Time: 4-yr avg Mean (SD): .30.8(13.4) μg/m 3 Range (Min, Max): 15.7-63.5 PM Component: particulate OC and EC Copollutant (correlation): PM 2.5 : r = 0.79

PM 10-2.5 : r = 0.79 Inorganic acid: r = 0.72 Organic Acid: r = 0.59

EC: r = 0.71

OC: r = 0.70

NO 2 : r = 0.20

O 3 : r = 0.64 PM Increment: Between community range 47.8 μg/m 3 Between community unit 1 μg/m 3 Within community 1 μg/m 3 OR Estimate [Lower CI, Upper CI] Between community per range 1.72(0.93-3.20)| Between Community per unit 1.01(1.00- 1.02)| Within community per unit 1.04(0.99- 1.10)

Reference: McConnell et al. (2002, 023150 ) Period of Study: 1993-1998

Location: 12 communities in Southern California (grouped into either high and low pollution communities) Outcome: Asthma (new diagnosis) Age Groups: 9-12 yr, 12-13 yr, 15-16 yr Study Design: Cohort

N: 3535 Statistical Analyses: Multivariate proportion hazard model

Covariates: Sex, age, ethnic origin, BMI, child history of allergies and asthma history, SES, maternal smoking, time spent outside, history of wheezing, ownership of insurance (yes/no), number and type of sports played Dose-response Investigated? Yes Statistical Package: SAS 8.1 Pollutant: PM 10 Averaging Time: 4 yr Mean (SD): Low pollution communities: 21.6 (3.8) High pollution communities: 43.3 (12.0)

Percentiles: Low pollution communities: 50th(Median): 20.8 High pollution communities: 50th(Median): 43.3 Range (Min, Max): Low pollution communities: 16.62, 27.3 High pollution communities: 33.5, 66.9 Monitoring Stations: 12 Copollutant (correlation): PM 2.5 : r = 0.96 NO 2 : r = 0.65 O 3 RR Estimate [Lower CI, Upper CI] lag: Low PM communities: 1.0 [ref] 0 sport 1.5 [1.0, 2.2] 1 sport 1.2 [0.7, 1.9] 2 sports 1.7 [0.9, 3.2] ≥ 3 sports High PM communities: 1.0 [ref] 0 sport 1.1 [0.7, 1.7] 1 sport 0.9 [0.5, 1.7] 2 sports 2.0 [1.1, 3.6] ≥ 3 sports

High vs. Low PM 10 communities: 0.8 (0.6, 1.0) Incidence-N (incidence) number of sports: Low PM communities: 49 (0.023) 0 54 (0.032) 1 22 (0.024) 2 13 (0.033) ≥ 3 High PM communities: 55 (0.021) 0 36 (0.021) 1 14 (0.018) 2 16 (0.033) ≥ 3



### December 2009 E-396

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: McConnell, et al. (2006, 180226 ) Period of Study: 1996-1999

Location: 12 Southern California communities Outcome: Prevalence of bronchitic symptoms (yrly). Age Groups: 10-15-yr-old Study Design: Longitudinal cohort

N: 475 asthmatic children Statistical Analyses: Multilevel logistic mixed effects models.

Covariates: Age, second-hand smoke Personal smoking history Sex, race. Dose-response Investigated? No Statistical Package: SAS with GLIMMIX macro Pollutant: PM 10 Averaging Time: 365 days

Percentiles: Community by yr (n = 48 = 12 communities · 4 yr)

25th: NR 50th(Median): 3.4

75th: NR Range (Min, Max): Community by yr (n = 48 = 12 communities · 4 yr): (0.89, 8.7) Monitoring Stations : 12 Copollutant: O 3 , NO 2 , EC , OC, Acid vapor (acetic and formic acid) PM Increment: 6.1 μ g/m 3 OR Estimate [Lower CI, Upper CI] PM 10 Dog (n = 292): 1.60 [1.12: 2.30] No dog (n = 183): 0.89 [0.57: 1.39] PM 10 *Dog interaction p-value: 0.02 Cat (n = 202): 1.47 [0.96: 2.24] No Cat (n = 273): 1.20 [0.83: 1.73] PM 10 *Cat interaction p-value: 0.41 Neither pet (n = 112): 0.91 [0.53: 1.56] Cat only (n = 71): 0.84 [0.42: 1.66] Dog only (n = 161): 1.41 [0.91: 2.19] Both pets (n = 131): 1.89 [1.15: 3.10] Results suggest that dog ownership, a source of residential exposure to endotoxin, may worsen the severity of respiratory symptoms from exposure to air pollutants in asthmatic children.

Reference: Meng et al. (2007, 093275 ) Period of Study: Nov 2000 and Sep 2001 (collection of health data)

Location: Los Angeles and San Diego counties Outcome: Poorly controlled asthma vs. controlled asthma Age Groups: 18-64, 65+ Study Design: Long-term exposure study Comparison of cases and controls

N: 1,609 adults (represented individuals age 18+ who reported ever having been diagnosed as having asthma by a physician and had their address successfully geocoded) Statistical Analyses: Logistic regression to evaluate associations between TD (traffic density) and annual avg air pollution concentrations and poorly controlled asthma. Used sample weights that adjusted for unequal probabilities of selection into the CHIS sample.

Covariates: Age, sex, race/ethnicity, family federal poverty level, county, insurance status, delay in care for asthma, taking medications, smoking behavior, self-reported health status, employment, physical activity Dose-response Investigated? yes Pollutant: PM 10 Averaging Time: 24 h over 1 yr Copollutant (correlation):

O 3 : r = -0.72

NO 2 : r = 0.83

PM 2.5 : r = 0.84

CO: r = 0.42

TD: r = 0.14 PM Increment: Continuous data: per 10 μg/m 3 OR Estimate [Lower CI, Upper CI] lag: All Adults: 1.08 [0.82, 1.43] Non-Elederly Adults: 1.14 [0.84, 1.55] Elderly: 0.84 [0.41, 1.73] Women: 1.38 [0.99, 1.94]



### December 2009 E-397

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Millstein et al. (2004, 088629 ) Period of Study: Mar-Aug, 1995, and Sep 1995-Feb 1996

Data were taken from the Children’s Health Study

Location: Alpine, Atascadero, Lake Arrowhead, Lake Elsinore, Lancaster, Lompoc, Long Beach, Mira Loma, Riverside, San Dimas, Santa Maria, and Upland, CA Outcome: Wheezing & asthma medication use (ICD9 NR) Age Groups: 4th grade students, mostly 9 yr at the time of the study Study Design: Cohort Study, stratified into 2 seasonal groups/

N: 2081 enrolled, 2034 provided parentcompleted questionnaire. Statistical Analyses: Multilevel, mixedeffects logistic model.

Covariates: Contagious respiratory disease, ambient airborne pollen and other allergens, temperature, sex, age race, allergies, pet cats, carpet in home, environmental tobacco smoke, heating fuel, heating system, water damage in home, education level of questionnaire signer, physician diagnosed asthma.

Season: Mar-Aug, 1995, and Sep, 1995 to Feb, 1996 Statistical Package: GLIMMIX SAS 8.00 macro for generalized linear mixed models. Lags Considered: 14 Pollutant: PM 10 Averaging Time: Monthly means for PM 10

. PM Component: Nitric acid, formic acid, acetic acid Monitoring Stations : 1 central location in each community Copollutant (correlation):

O 3 : r = 0.76

NO 2 : r = 0.39

PM 2.5 : r = 0.91 PM Increment: IQR 13.39 μg/m 3 Odds Ratio [lower CI, Upper CI]

Annual

PM 10 : 0.93 [0.67, 1.27] Mar-Aug

PM 10 : 0.91 [0.46, 1.80] Sep-Feb

PM 10 : 0.65 [0.40, 1.06]

Reference: Neuberger et al. (2004, 093249 ) Period of Study: Jun 1999-Jun 2000

Location: Austria (Vienna and a rural area near Linz) Outcome: Questionnaire derived asthma score, and a 1-5 point respiratory health rating by parent Age Groups: 7-10 yr Study Design: Cross-sectional survey

N: about 2000 children Statistical Analyses: Mixed models linear regression-used factor analysis to develop the “asthma score”

Covariates: Pre-existing respiratory conditions, temperature, rainy days, # smokers in household, heavy traffic on residential street, gas stove or heating, molds, sex, age of child, allergies of child, asthma in other family members Dose-response Investigated? No Statistical Package: NR Lags Considered: 4 week avg (preceding interview) Pollutant: PM 10 Averaging Time: 24 h Copollutant (correlation): PM 2.5 (r = 0.94) in Vienna PM Increment: 10 μg/m 3 Change in mean associated unit increase in PM (p-value) lag Respiratory Health score Vienna: 0.005 (p>0.05) lag 4 week avg Rural area: 0.008 (p>0.05) lag 4 week avg

Asthma score Vienna: 0.006 (p>0.05) lag 4 week avg Rural area: -0.001 (p>0.05) lag 4 week avg

Reference: Oftedal et al. (2008, 093202 ) Period of Study: 2001-2002

Location: Oslo, Norway Outcome: Lung function (PEF, FEF25%, FEF50%, FEV 1 , FVC) Age Groups: 9-10 yr Study Design: Cross-sectional

N: 1847 children Statistical Analyses: Linear regression

Covariates: Height, age, BMI, birth weight, temperature, maternal smoking,

sex Dose-response Investigated? Yes Statistical Package: SPSS, STATA, S-Plus Lags Considered: 1-3 Pollutant: PM 10 IQR:

PM 10 in 1st yr of life: 10.3

PM 10 lifetime: 5.8 PM Increment: Per IQR β (Lower CI, Upper CI) PM 10 in 1st yr of life PEF -72.5 (-122.3 to -22.7) FEF25% -77.4 (-133.4 to -21.4) FEF50% -53.9 (-102.6. to -5.2) FEV 1 -6.7 (-24.1, 10.7) FVC 0.5 (-18.5, 19.6)

PM 10 lifetime exposure PEF -66.4 (-109.5 to -23.3) FEF25% -61.5 (-110.0 to -13.1) FEF50% -45.6 (-87.7 to -3.5) FEV 1 -7.3 (-22.4, 7.7) FVC -2.1 (-18.6, 14.4)



### December 2009 E-398

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Parker et al. (2009, 192359 ) Period of Study: 1999-2005

Location: U.S. Outcome: Respiratory allergy/hayfever Study Design: Cohort

Covariates: Survey yr, age, family structure, usual source of care, health insurance, family income relative to federal poverty level, race/ethnicity Statistical Analysis: Logistic regression Statistical Package: SUDAAN Age Groups: 73,198 children aged 3-17 yr Pollutant: PM 10 Averaging Time: NR

Median: 24.1 μg/m 3

IQR: 20.8-28.7 Copollutant (correlation): Summer O 3 : 0.26 SO 2 : -0.19 NO 2 : 0.48 PM 2.5 : 0.51 PM 10-2.5 : 0.86 Increment: 10 μg/m 3 Odds Ratio (95% CI) Single Pollutant Model, variable N Adjusted: 1.04 (0.99-1.09)

Reference: Penard-Morand et al. (2005, 087951 ) Period of Study: Mar 1999-Oct 2000

Mean concentrations of NO 2 , SO 2 , PM 10 , and O 3 were taken from Jan 1998-Dec 2000

Location: 6 French cities: Bordeaux, Clermont-Ferrand, Cr eteil, Marseille, Strasbourg, Reims. Outcome: Flexural dermatitis Asthma (493) Rhinoconjunctivitis Atopic dermatitis Wheeze Allergic rhinitis Atopy EIB (exercise-induced bronchial reactivity) Age Groups: 9-11 yr Study Design: Cross-sectional

N: 9615 Children (6672 complete examination and questionnaire info) Statistical Analyses: Logistic regression Marginal Model (GENMOD)

Covariates: Age, Sex, Family history of allergy, Passive smoking

Parental education

Season: All Excluding end of spring and during summer for clinical examinations Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 10 Averaging Time: 3 yr Mean (SD): Low concentrations: 26.9 High Concentrations: 23.8 Range (Min, Max):

Low concentrations: 10-20 High concentrations: 21.5-29.5 Copollutant (correlation):

\ NO 2 : r =.46

SO 2 : r =.76

O 3 : r = -.02 Monitoring Stations : 16 PM Increment: 10 μg/m 3 (IQR) OR Estimate [Lower CI, Upper CI]: EIB (during exam): 1.43 (1.02-2.01) Flexural dermatitis (during exam): 0.79 (0.59-1.07) Wheeze (past yr): 1.05 (0.72-1.54) Asthma (past yr): 1.23 (0.77-1.95) Rhinoconjunctivitis (past yr): 1.17 (0.86-1.59) Atopic dermatitis (past yr): 1.28 (0.96-1.71) Asthma (lifetime): 1.32 (0.96-1.81) Allergic rhinitis (lifetime): 1.32 (1.04-1.68) Atopic dermatitis (lifetime): 1.09 (0.88-1.36) Atopy (lifetime): 0.98(0.80-1.22) Pollen: 1.14 (0.85-1.53) Indoor: 0.91 (0.72-1.15) Moulds: 1.00 (0.53-1.88) Highest correlated pollutant adjustments: EIB (during exam): 1.16 (0.72-1.85) Flexural dermatitis (during exam): 0.93 0(.60-1.43) Wheeze (past yr): 1.31 (0.71-2.36) Asthma (past yr): 1.25 (0.66-2.37) Rhinoconjunctivitis (past yr): 1.22 (0.98-1.68) Atopic dermatitis (past yr): 1.63 (1.07-2.49) Asthma (lifetime): 1.11 (0.70-1.74) Allergic rhinitis (lifetime): 1.19 (0.94-1.59) Atopic dermatitis (lifetime): 1.47 (1.07-2.00) Atopy (lifetime): 0.93(0.69-1.26) Pollen: 1.30 (0.98-1.57) Indoor: .83 (0.63-1.12) Molds: 1.62 (0.64-4.09) Reference: Peters et al., (1999, 087237 ) Period of Study: 1986-1990, 1994

Location: Southern California Outcome: Asthma, cough, bronchitis, wheeze Age Groups: 4th, 7th, & 10th graders Study Design: Cohort

N: 3676 children Statistical Analyses: Stepwise logistic regression

Covariates: Community, grade, race, sex, height, BMI, asthma in parents, hay fever, health insurance, plants in home, mildew in home, passive smoke exposure, pest infestation, carpet, vitamin supplements, active smoking, pets, gas stove, air conditioner Dose-response Investigated? Yes Pollutant: PM 10 Averaging Time: 24-h PM 10 averaged over 1994 Mean based on data collected during 1986-1990, 1994: Alpine 37.4, 21.3 Atascadero 28.0, 20.7 Lake Elsinore 59.5, 34.7 Lake Gregory 38.3, 24.2 Lancaster 47.0, 33.6 Lompoc 30.0, 13.0 Long Beach 49.5, 38.8 Mira Loma 84.9, 70.7 Riverside 84.9, 45.2 San Dimas 67.0, 36.7 Santa Maria 28.0, 29.2 Upland 75.6, 49.0 PM Increment: 25 μg/m 3 OR (Lower CI, Upper CI) for respiratory illness Based on 1986-1990 pollutant levels Ever asthma 0.93 (0.76, 1.13) Current asthma 1.09 (0.86, 1.37) Bronchitis 0.94 (0.74, 1.19) Cough 1.06 (0.93, 1.21) Wheeze 1.05 (0.89, 1.25) Based on 1994 pollutant levels Ever asthma 0.87 (0.67, 1.14) Current asthma 1.11 (0.81, 1.54) Bronchitis 0.90 (0.65, 1.26) Cough 1.14 (0.96, 1.35) Wheeze 1.01 (0.79, 1.29)



### December 2009 E-399

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Pierse, et al. (2006, 088757 ) Period of Study: 2 yr (once in 1998 and once in 2001—surveys)

Location: Leicestershire, UK Outcome: Cough without a cold Night time cough

Current wheeze Age Groups: 1-5 yr Study Design: Cross-sectional (cohorts)

N: 4400 children Statistical Analyses: Binomial generalized linear models (compared with likelihood ratio tests) Spatial variograms (due to the spatial concerns)

Covariates: Age, Gender

Mother/father has asthma Coal heating the home, Smoking by household member in the home, Either parent continued education past 16 yr of age, Pre-term birth, Breast feeding, Gas cooking, Presence of pets, Number of cigarettes smoked by mother, Overcrowding, Single parenthood, Diet Dose-response Investigated? Yes(Fig. 2 shows evidence of doseresponse effect based on surveys, states in discussion). Statistical Package: SAS 8.2

S-Plus 6.1 Pollutant: PM 10 Averaging Time: Annual PM 10 Mean (SD): 1998: 1.47

2001: 1.33

Percentiles: 25th: 1998 (.73) and 2001 (.8) 75th: 1998 (1.93) and 2001 (1.84) PM Increment: 10 μg/m 3 (IQR) Unadjusted OR estimates [Lower CI, Upper CI]: Cough without cold (1998): 1.22 (1.10 to 1.36) Cough without cold (2001): 1.46 (1.27 to 1.68) Night-time cough (1998): 1.11 (1.01 to 1.23) Night-time cough (2001): 1.25 (1.09 to 1.43) Current wheeze (1998): 0.99 (0.89 to 1.10) Current wheeze (2001): 1.09 (0.93 to 1.30) Adjusted OR Estimate [Lower CI, Upper CI]: Cough without cold (1998): 1.21 (1.07 to 1.38) Cough without cold (2001): 1.56 (1.32 to 1.84) Night-time cough (1998): 1.06 (0.94 to 1.19) Night-time cough (2001): 1.25 (1.06 to 1.47) Current wheeze (1998): 0.99 (0.88 to 1.12) Current wheeze (2001): 1.28 (1.04 to 1.58) When the child was originally asymptomatic in 1998: Unadjusted OR estimates [Lower CI, Upper CI]: Cough without cold (2001): 1.68 (1.39 to 2.03) Night-time cough (2001): 1.21 (1.00 to 1.46) Current wheeze (2001): 1.22 (0.92 to 1.62) Adjusted OR Estimate [Lower CI, Upper CI]: Cough without cold (2001): 1.62 (1.31 to 2.00) Night-time cough (2001): 1.19 (0.96 to 1.47) Current wheeze (2001): 1.42 (1.02 to 1.97)



### December 2009 E-400

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Qian et al. (2005, 093283 ) Period of Study: 1990-1992

Location: Forsythe, NC Minneapolis, MN Jackson, MS. Outcome: FVC, FEV 1 , FEV 1 /FVC Age Groups: Middle aged (avg 56.8 yr) Study Design: Cross-sectional

N: 10,240 people Statistical Analyses: Regression equations, multiple linear regression analyses

Covariates: Smoking status, recent use of respiratory medication, current respiratory symptoms, chronic lung diseases, field center Dose-response Investigated? No Statistical Package: SAS software, version 9.1 Pollutant: PM 10 Averaging Time: Annual Mean (SD): 27.9 (2.8)

Percentiles: 25th: 25.8 50th(Median): 27.5

75th: 30.2 Range (Maximum-Minimum): 12.2 Monitoring Stations : 3 (Minneapolis, MN) 5 (Jackson, MS) and 9 (Forsythe, NC) Copollutant: O 3 PM Increment: 2.8 μg/m 3 (1 SD) Effect Estimate: In Never Smokers FVC ß = -0.0108, SE = 0.0026, p =.0001 FEV 1 ß = -0.0082, SE = 0.0029, p =.0047 FEV 1 /FVC ß = -0.0024, SE = 0.0023, p =.2787 Smoking status Current n = 2377, FVC = -1.96, FEV 1 = -2.23, FEV 1 /FVC = -0.94 Former n = 3858, FVC = -1.25, FEV 1 = -1.10, FEV 1 /FVC = -0.30 Never n = 4005, FVC = -1.12, FEV 1 = -0.63, FEV 1 /FVC = 0.06 Recent Use of Respiratory Medication Yes n = 424, FVC = -2.65, FEV 1 = -3.89, FEV 1 /FVC = -3.00 No n = 9816, FVC = -1.41, FEV 1 = -1.20, FEV 1 /FVC = -0.24 Current Respiratory Symptoms Yes n = 4340, FVC = -1.68, FEV 1 = -1.70, FEV 1 /FVC = -0.63 No n = 5900, FVC = -1.05, FEV 1 = -0.63, FEV 1 /FVC = 0.05 Chronic Lung Diseases Yes n = 1374, FVC = -1.95, FEV 1 = -2.31, FEV 1 /FVC = -1.18 No n = 8866, FVC = -1.35, FEV 1 = -1.10, FEV 1 /FVC = -0.19 Field Center Forsythe, NC n = 3504, FVC = -0.03, FEV 1 = 0.05, FEV 1 /FVC = -0.33 Minneapolis, MN n = 3793, FVC = 0.50, FEV 1 = 0.54, FEV 1 /FVC = -0.30 Jackson, MS n = 2943, FVC = -0.01, FEV 1 = 0.17, FEV 1 /FVC = -0.32 Reference: Rios et al. (2004, 087800 ) Period of Study: 1998-2000

Location: the metropolitan area of Rio de Janiero, Brazil, Duque de Caxias (DC) and Seropedica (SR) Outcome: Wheezing, asthma, cough at night Age Groups: 13-14 yr Study Design: Cohort

N: 4064 students Statistical Analyses: Cchi-squared

Covariates: Sex, type of school, time of residence, domestic smoking, residents per home Dose-response Investigated? Yes Statistical Package: EpiInfo Pollutant: PM 10 Averaging Time: Weekly measurements used to create annual PM estimate Mean (SD): DC 1998: 147 1999: 115 2000: 110 Total: 124 SR 1998: 37 1999: 31 2000: 37 Total: 35 Monitoring Stations : NR PM Increment: High vs. Low Global Cut-Off Score %, p-val: DC Male: 15.0 Female: 22.3, p < .05† Private School: 16.6 Public School: 19.4, p < .05* <5yr residence: 20.9 >5yr residence: 16.8 No domestic smoking exposure: 17.6 Domestic smoking exposure: 20.4, p < .05† <5 residents per home: 18.4 5+ residents per home: 19.5 SR Male: 12.3 Female: 19.7, p < .05† Private School: 28.3, p < .05*† Public School: 14.7 <5yr residence: 10.8 >5yr residence: 16.5 No domestic smoking exposure: 14.8 Domestic smoking exposure: 18.3 <5 residents per home: 15.6 5+ residents per home: 17.4 Notes: The Global Cut-off Score encompasses replies to the asthma component of ISAAC’s written questionnaire that establishes a cut-off from which is defined the presence of asthma for the Brazilian population. *Comparing the cities in the same controlled variable †Comparing the controlled variable in the same city



### December 2009 E-401

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Rojas-Martinez et al. (2007, 091064 ) Period of Study: 1996-1999

Location: Mexico City, Mexico Outcome: Lung function: FEV 1 , FVC, FEF25-75% Age Groups: Children 8 yr old at time of cohort recruitment Study Design: School-based “dynamic” cohort study

N: 3170 children 14,545 observations Statistical Analyses: Three-level generalized linear mixed models with unstructured variance-covariance matrix

Covariates: Age, body mass index, height, height by age, weekday spent outdoors, environmental tobacco smoke, previous-day mean air pollutant concentration, time since first test Dose-response Investigated? No Statistical Package: SA Pollutant: PM 10 Averaging Time: 6 mo Mean (SD): 6-mo averaging

SD: NR

Mean: 75.6

Percentiles: 6-mo averaging

25th: 55.8 50th(Median): 67.5

75th: 92.2 Monitoring Stations : 5 sites for PM 10 , 10 for other pollutants Copollutant:

O 3 NO 2 PM Increment: IQR 6-LC: 36.4 Slope [Lower CI, Upper CI] Girls One-pollutant model FVC: -39 [-47: -31] FEV: -29 [-36: -21] FEF25-75%: -17 [-36: 1] FEV 1 /FVC: 0.12 [0.07: 0.17] Two-pollutant model: PM 10 , 6-LC & O 3 FVC: -30 [-39: -22] FEV: -24 [-31: -16] FEF25-75%: -9 [-26: 9] FEV 1 /FVC: 0.10 [0.06: 0.15] PM 10 , 6-LC & NO 2 FVC: -21 [-30: -13] FEV: -17 [-25: -8] FEF25-75%: -23 [-43: -4] FEV 1 /FVC: 0.07 [0.02: 0.13] Multipollutant model: PM 10 , 6-LC, O 3 , & NO 2 FVC: -14 [-23: -5] FEV: -11 [-20: -3] FEF25-75%: -7 [-27: 12] FEV 1 /FVC: 0.08 [0.03: 0.13] Boys One-pollutant model FVC: -33 [-41: -25] FEV: -27 [-34: -19] FEF25-75%: -18 [-34: -2] FEV 1 /FVC: 0.04 [-0.01: 0.09] Two-pollutant model: PM 10 , 6-LC & O 3 FVC: -28 [-36: -19] FEV: -22 [-30: -15] FEF25-75%: -10 [-27: 7] FEV 1 /FVC: 0.04 [-0.01: 0.09] FEV 1 /FVC: 0.24 [0.13: 0.34] PM 10 , 6-LC & NO 2 FVC: -16 [-26: -7] FEV: -19 [-27: -10] FEF25-75%: -26 [-44: -9] FEV 1 /FVC: 0.005 [-0.06: 0.05] Multipollutant model PM 10 , 6-LC, O 3 , & NO 2 FVC: -12 [-22: -3] FEV: -15 [-23: -6] FEF25-75%: -12 [-30: 6] FEV 1 /FVC: -0.002 [-0.06: 0.05] Reference: Schikowski et al. (2005, 088637 ) Period of Study: 1985-1994

Location: Rhine-Ruhr Basin of Germany [Dortmund (1985, 1990), Duisburg (1990), Gelsenkirchen (1986, 1990), and Herne (1986)] Outcome: Respiratory symptoms & pulmonary function Age Groups: Age 54-55 Study Design: Cross-sectional

N: 4757 women Statistical Analyses: Linear & Logistic regressions, including random effects model

Covariates: Age, smoking, SES, occupational exposure, form of heating, BMI, height

Season: NR Dose-response Investigated? No Statistical Package: SAS Lags Considered: NR Pollutant: PM 10 Averaging Time: NR Min, P25, Median, Mean, P75, Max

Annual Mean 35, 40, 43, 44, 47, 53 5-yr Mean 39, 43, 47, 48, 53, 56 Monitoring Stations : 7 Copollutant (correlation): NR PM Increment: 7 μg/m 3 OR (Lower CI, Upper CI) for asthma symptoms Annual means Chronic bronchitis 1.00 (0.85, 1.18) Chronic cough 1.03 (0.87, 1.23) Frequent cough 1.01 (0.93, 1.10) COPD 1.37 (0.98, 1.92) p < 0.1 FEV 1 0.953 (0.916, 0.989) p < 0.1 FVC 0.966 (0.940, 0.992) p < 0.1 FEV 1 /FVC 0.989 (0.978, 1.000) p < 0.1 Five yr means Chronic bronchitis 1.13 (0.95, 1.34) Chronic cough 1.11 (0.93, 1.31) Frequent cough 1.05 (0.94, 1.17) COPD 1.33 (1.03, 1.72) p < 0.1 FEV 1 0.949 (0.923, 0.975) p < 0.05 FVC 0.963 (0.945, 0.982) p < 0.05 FEV 1 /FVC 0.989 (0.980, 0.997) p < 0.1 Reference: Schindler et al, (2009, Outcome: Respiratory Symptoms Pollutant: PM 10 Increment: 10 μg/m 3



### December 2009 E-402

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

191950 ) Period of Study: 1991-2002

Location: Switzerland Study Design: Prospective Cohort Statistical Analysis: Logistic Regression Model Age Groups: Adults, 18-60 yr of age at start of study

Covariates: Sex, age, level of education, Swiss citizenship, BMI, parental smoking, parental history of asthma/atopy, early respiratory infection, smoking status, pack yr, daily number of cigarettes, yr since smoking cessation, passive smoking in general/at work, occupational exposure to airbourne irritants Averaging Time: Annual Mean (SD) Unit: Range (Min, Max): Copollutant (correlation): NR Odds Ratio (95%CI) of reporting symptoms at second interview Entire Sample, New Reports Regular Cough: 0.77 (0.62-0.97) Regular Phlegm: 0.74 (0.56-0.99) Chronic Cough or Phlegm: 0.78 (0.62-0.98) Wheezing: 1.01 (0.74-1.39) Wheezing with Dyspnea: 0.70 (0.49-1.01) Wheezing without Cold: 1.06 (0.76-1.50) Entire Sample, Persistent Reports Regular Cough: 0.55 (0.39-0.78) Regular Phlegm: 0.82 (0.52-1.33) Chronic Cough or Phlegm: 0.67 (0.40-1.15) Wheezing: 0.50 (0.32-0.80) Wheezing with Dyspnea: 0.59 (0.30-1.23) Wheezing without Cold: 0.61- (0.35- 1.12) Persistent Non-Smokers, New Reports Regular Cough: 0.86 (0.63-1.19) Regular Phlegm: 0.70 (0.49-0.99) Chronic Cough or Phlegm: 0.71 (0.52-0.99) Wheezing: 0.93 (0.60-1.46) Wheezing with Dyspnea: 0.77 (0.50-1.20) Wheezing without Cold: 1.11 (0.66-1.92) Persistent Non-Smokers, Persistent Reports Regular Cough: 0.28 (0.14-0.60) Regular Phlegm: 0.87 (0.43-1.84) Chronic Cough or Phlegm: 0.35 (0.16-0.81) Wheezing: 0.53 (0.28-1.08) Wheezing with Dyspnea: 0.76 (0.30-2012) Wheezing without Cold: 0.61 (0.26-1.52) Gender-specific odds ratio (95%CI) of reporting symptoms at second interview New Reports Regular Cough, p = 0.73 Men: 0.75 (0.53-1.06) Women: 0.81 (0.58-1.15) Regular Phlegm, p = 0.41 Men: 0.85 (0.60-1.20) Women: 0.68 (0.46-1.00) Chronic Cough or Phlegm: 0.36 Men: 0.87 (0.63-1.21) Women: 0.71 (0.51-0.97) Wheezing, p = 0.20 Men: 0.83 (0.57-1.20) Women: 1.20 (0.78-1.87) Wheezing with Dyspnea, p = 0.11 Men: 0.56 (0.36-0.87) Women: 1.00.57-1.842 Wheezing without Cold, p = 0.43 Men: 0.95 (0.63-1.42) Women: 1.25 (0.72-2.17) Persistent Reports Regular Cough, p = 0.02 Men: 0.75 (0.48-1.18) Women: 0.31 (0.17-0.56) Regular Phlegm, p = 0.33 Men: 0.65 (0.37-1.12) Women: 1.04 (0.47-2.34) Chronic Cough or Phlegm: 0.47 Men: 0.68 (0.39-1.20) Women: 0.47 (0.20-1.11) Wheezing, p = 0.29 Men: 0.34 (0.17-0.72)



### December 2009 E-403

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Women: 0.57 (0.32-1.01) Wheezing with Dyspnea, p = 0.63 Men: 0.56 (0.16-1.95) Women: 0.37 (0.13-1.05) Wheezing without Cold, p = 0.57 Men: 0.34 (0.12-0.91) Women: 0.49 (0.21-1.15) Odds Ratio (95%CI) of reporting symptoms at second interview with additional adjustment for annual outdoor PM exposure at baseline Entire Sample Regular Cough, p = 0.0003 New Reports: 0.77 (0.61-0.97) Persistent Reports: 0.55 (0.39-0.78) Regular Phlegm, p = 0.13 New Reports: 0.77 (0.59-1.02) Persistent Reports: 0.79 (0.46-1.33) Chronic Cough or Phlegm, p = 0.02 New Reports: 0.78 (0.62-0.98) Persistent Reports: 0.64 (0.40-1.02) Wheezing, p = 0.002 New Reports: 0.91 (0.63-1.33) Persistent Reports: 0.47 (0.31-0.72) Wheezing with Dyspnea, p = 0.03 New Reports: 0.65 (0.43-0.98) Persistent Reports: 0.55 (0.28-1.10) Severe Wheezing, p = 0.28 New Reports: 0.96 (0.66-1.40) Persistent Reports: 0.62 (0.34-1.12) Non-Smokers Regular Cough, p < 0.001 New Reports: 0.87 (0.63-1.19) Persistent Reports: 0.29 (0.16-0.52) Regular Phlegm, p = 0.07 New Reports: 0.70 (0.50-0.99) Persistent Reports: 0.67 (0.34-1.33) Chronic Cough or Phlegm, p = 0.008 New Reports: 0.72 (0.52-0.99) Persistent Reports: 0.38 (0.17-0.84) Wheezing, p = 0.07 New Reports: 0.87 (0.52-1.48) Persistent Reports: 0.48 (0.25-0.91) Wheezing with Dyspnea, p = 0.36 New Reports: 0.76 (0.48-1.19) Persistent Reports: 0.70 (0.27-1.82) Severe Wheezing, p = 0.57 New Reports: 1.11 (0.64-1.93) Persistent Reports: 0.64 (0.26-1.54) Reference: Sharma et al. (2004, 156974 ) Period of Study: Nov 2002-Apr 2003

Location: 3 sections in Kanpur City, India: 1) Indian Institute of Technology Kanpur (IITK) 2) Vikas Nagar (VN) 3) Juhilal Colony (JC) Outcome: Lung function Age Groups: 20-55 yr Study Design: Cohort

N: 91 people Statistical Analyses: Linear regression

Covariates: NR

Season: Fall, Winter, spring Dose-response Investigated? No Statistical Package: Microsoft Excel Lags Considered: 1-day lag & 5-day

ma Pollutant: PM 10 Averaging Time: 24 h Mean (SD): IITK 184 (40) VN 295 (58) JC 293 (90)

PM Component: Lead, Nickel, Cadmium, Chromium, Iron, Zinc Benzene soluble fraction (includes polycyclic aromatic hydrocarbons [PAHs]) Copollutant (correlation): Δ PEF = mean daily deviations in PEF PM 10 - Δ PEF: (-0.52) PM 10 -PM 2.5 : (0.67) PM 10 -PM 10 (1-day lag): (0.45) PM 10 -PM 2.5 (1-day lag): (0.46) PM Increment: 1 μg/m 3

Δ PEF (difference or change in peak expiratory flow)

-0.0318 L/min



### December 2009 E-404

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Tager et al. (2005, 087538 ) Period of Study: Apr 2000-Jun 2000, Feb 2001-Jun 2001,

Feb 2002-Jun 2002

Location: Los Angeles, California San Francisco, California Outcome: Lung Function (FEV 1 , FVC, PEFR, FEF75, FEF25-75, FEF25-75/FVC ratio) Age Groups: 16-21+ y/o College Freshman Study Design: Retrospective cohort

N: 255 students 108 Men (M) 147 Women (W) Statistical Analyses: Multivariate Linear Regression

Covariates: Sex, height, weight, area of residence, age, race, ETS exposure, respiratory disease history Dose-response Investigated? No Pollutant: PM 10 Averaging Time: Cumulative lifetime exposure Median : Prior to 1987: M: 73 W: 71 1987 and later: M: 36 W: 34 Lifetime: M: 48 W: 45 Range (Min, Max): Prior to 1987: M: 34, 117 W: 31, 124 1987 and later: M: 18, 68 W: 20, 61 Lifetime: M: 21, 80 W: 18, 71 Monitoring Stations : Between 1 and 3 Copollutant (correlation): O 3 prior to 1987: r = 0.68 O 3 1987 and later: r = 0.81 O 3 -Lifetime: r = 0.57 PM Increment: 1 μg/m 3 Parameter Estimates (SD) (Lifetime PM 10 , Interaction PM 10 FEF25-75/FVC)

LnFEF75: M: -0.009 (0.0009), 0.009 (0.007) W: -0.010 (0.0007), 0.008 (0.0005)

Reference: Tamura et a. (2003, 087445 ) Period of Study: 1998-1999

Location: Bangkok, Thailand Outcome: Non-specific respiratory disease (Chronic bronchitis, acute bronchitis, bronchial asthma, dyspnea and wheezing) Age Groups: Adults Study Design: Cross-sectional

N: 1603 policemen Statistical Analyses: Multiple logistic regression

Covariates: Age, smoking status Dose-response Investigated? Yes Statistical Package: SPSS Pollutant: PM 10 Averaging Time: 24 h Mean (SD): Heavily Polluted 80-190 Moderately Polluted 60-69

Control 59 Monitoring Stations : 13 PM Increment: Heavily Polluted vs. Moderately Polluted vs. Control Number and Prevalence (%) of respiratory disease among heavily polluted, moderately polluted, and control areas. Heavily Polluted Chronic bronchitis 16 (3.0) Acute bronchitis 19 (3.5) Bronchial asthma 5 (0.9) Dyspnea & wheezing 49 (9.2) Any 1 of above 69 (13.0) Persistent cough 11 (2.1) Persistent phlegm 27 (1.3) Cough & phlegm 6 (1.1) Moderately Polluted Chronic bronchitis 8 (2.4) Acute bronchitis 12 (9.0) Bronchial asthma 2 (0.6) Dyspnea & wheezing 23 (6.8) Any 1 of above 37 (10.9) Persistent cough 1 (0.3) Persistent phlegm 11 (3.3)| Cough & phlegm 1 (0.3) Control Chronic bronchitis 6 (1.9) Acute bronchitis 11 (3.3) Bronchial asthma 0 (0.0) Dyspnea & wheezing 23 (7.2) Any 1 of above 31 (9.4) Persistent cough 1 (0.3) Persistent phlegm 8 (2.4) Cough & phlegm 1 (0.3)



### December 2009 E-405

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Wheeler and Ben-Schlomo (2005, 188766 ) Period of Study: 1995-1997

Location: England Outcome: FEV 1 Age Groups: 16-79 yr Study Design: Data from Health Survey for England were coupled geographically with air pollution measurements on a 1 km grid.

N: 26,426 households with 39,251 adults Statistical Analyses: Logistic regression, least squares regression

Covariates: Age, sex, height, body mass index, smoking status, household passive smoke exposure, inhaler use in the previous 24-h, doctor diagnosis of asthma. Dose-response Investigated? No Pollutant: PM 10 Averaging Time: 1996 annual mean Mean (SD): 23.95 (3.58) Range (Min, Max): 17.87-43.37 β (95%CI) for Height-age standardized FEV1 by ambient air quality index p-value

Male Good (ref) Poor -0.023 (-0.030 to -0.016)

<0.001

Female Good (ref) Poor -0.019 (-0.026 to -0.013)

<0.001

Reference: Zhang et al., (2002, 034814 ) Period of Study: 1993-1996

Location: 4 Chinese cities (urban and suburban location in each city): Guangzhou, Wuhan, Lanzhou, Chongqing Outcome: Interview-self reports of symptoms: Wheeze (ever wheezy when having a cold) Asthma (diagnosis by doctor) Bronchitis (diagnosis by doctor), Hospitalization due to respiratory disease (ever) Persistent cough (coughed for at least 1 month per yr with or apart from colds) Persistent phlegm (brought up phlegm or mucus from the chest for at least 1 month per yr with or apart from colds) Age Groups: Elementary school students age range: 5.4-16.2 Study Design: Cross-sectional

N: 7,557 returned questionnaires 7,392 included in first stage of analysis Statistical Analyses: 2-stage regression approach: Calculated odds ratios and 95% CIs of respiratory outcomes and covariates Second stage consisted of variance-weighted linear regressions that examined associations between district-specific adjusted prevalence rates and district-specific ambient levels of each pollutant.

Covariates: Age, gender, breast-fed, house type, number of rooms, sleeping in own or shared room, sleeping in own or shared bed, home coal use, ventilation device used, homes smokiness during cooking, eye irritation during cooking, parental smoking, mother’s education level, mother’s occupation, father’s occupation, questionnaire respondent, yr of questionnaire administration, season of questionnaire administration, parental asthma prevalence Pollutant: PM 10 Averaging Time: 2 yr Mean (SD): 151 (56)

IQR: 87 Range (Min, Max): Gives range (max.-min.):

80 Monitoring Stations : 2 types: municipal monitoring stations over a period of 4 yr (1993-1996) Schoolyards of participating children over a period of 2 yr (1995-1996) PM Increment: Interquartile range corresponded to 1 unit of change. RR Estimate [Lower CI, Upper CI] lag: Association between persistent phlegm and PM 10 : 3.21 (1.55, 6.67) p < 0.05 Between and within city modeled ORs, scaled to interquartile range of concentrations for each pollutant. No associations between any type of respiratory outcome and PM 10 When scaled to an increment of 50 μg/m 3 of PM 10 , ORs were:

Wheeze: 1.07

Asthma: 1.18

Bronchitis: 1.53 Hospitalization: 1.17 Persistent cough: 1.20 Persistent phlegm: 1.95

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-406

# Table E-23. Long-term exposure - r espiratory morbidity outcomes - PM 10-2.5 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chattopadhyay et al. (2007, 147471 ) Period of Study: NR

Location: Three different points in Kolkata, India: North, South, and Central Outcome: pulmonary function tests (respiratory impairments) Age Groups : All ages Study Design: Cross-sectional

N: 505 people studied for PFT total population of Kolkata not given Statistical Analyses: Frequencies

Covariates: Meteorologic data (i.e. temperature, wind direction, wind speed, and humidity) Dose-response Investigated? No Pollutant: PM<3.3-0.4 Averaging Time: 8 h Mean (SD):

North Kolkata: 266.1

Central Kolkata: 435.3

South Kolkata: 449.1 Unit (i.e. μg/m 3 ): μg/m 3 Monitoring Stations : 1 Copollutant (correlation):

PM 10 PM<10-3.3 PM Increment: NR Respiratory impairments (SD): North Kolkata Male (n=137) Restrictive: 4 (2.92) Obstructive: 5 (3.64) Combined Res. And Obs.: 6 (4.37) Total: 15 (10.95) Female (n=152) Restrictive: 3 (1.97) Obstructive: 5 (3.28) Combined Res. And Obs.: 0 Total: 8 (5.26) Total (n=289) Restrictive: 7 (2.42) Obstructive: 10 (3.46) Combined Res. And Obs.: 6 (2.07) Total: 23 (7.96)

Central Kolkata Male (n=44) Restrictive: 6 (13.63) Obstructive: 1 (2.27) Combined Res. And Obs.: 1 (2.27) Total: 8 (18.18) Female (n=50) Restrictive: 3 (6.00) Obstructive: 2 (4.00) Combined Res. And Obs.: 0 Total: 5 (10.00) Total (n=94) Restrictive: 9 (9.57) Obstructive: 3 (3.19) Combined Res. And Obs.: 1 (1.06) Total: 13 (13.82)

South Kolkata Male (n=52) Restrictive: 1 (1.92) Obstructive: 2 (3.84) Combined Res. And Obs.: 3 (5.76) Total: 6 (11.53) Female (n=70) Restrictive: 2 (2.85) Obstructive: 1 (1.42) Combined Res. And Obs.: 0 Total: 3 (4.28) Total (n=122) Restrictive: 3 (2.45) Obstructive: 3 (2.45) Combined Res. And Obs.: 3 (2.45) Total: 9 (7.37)



### December 2009 E-407

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chattopadhyay et al. (2007, 147471 ) Period of Study: NR

Location: Three different points in Kolkata, India: North, South, and Central Outcome: Pulmonary function tests (respiratory impairments) Age Groups : All ages Study Design: Cross-sectional

N: 505 people studied for PFT Total population of Kolkata not given Statistical Analyses: Frequencies

Covariates: Meteorologic data (i.e. temperature, wind direction, wind speed, and humidity) Dose-response Investigated? No Pollutant: PM<10-3.3 Averaging Time: 8 h Mean (SD):

North Kolkata: 269.8

Central Kolkata: 679.2

South Kolkata: 460.1 Monitoring Stations : 1 Copollutant (correlation):

PM 10 PM<3.3-0. PM Increment: NR Respiratory impairments (SD): North Kolkata Male (n=137) Restrictive: 4 (2.92) Obstructive: 5 (3.64) Combined Res. And Obs.: 6 (4.37) Total: 15 (10.95) Female (n=152) Restrictive: 3 (1.97) Obstructive: 5 (3.28) Combined Res. And Obs.: 0 Total: 8 (5.26) Total (n=289) Restrictive: 7 (2.42) Obstructive: 10 (3.46) Combined Res. And Obs.: 6 (2.07) Total: 23 (7.96)

Central Kolkata Male (n=44) Restrictive: 6 (13.63) Obstructive: 1 (2.27) Combined Res. And Obs.: 1 (2.27) Total: 8 (18.18) Female (n=50) Restrictive: 3 (6.00) Obstructive: 2 (4.00) Combined Res. And Obs.: 0 Total: 5 (10.00) Total (n=94) Restrictive: 9 (9.57) Obstructive: 3 (3.19) Combined Res. And Obs.: 1 (1.06) Total: 13 (13.82)

South Kolkata Male (n=52) Restrictive: 1 (1.92) Obstructive: 2 (3.84) Combined Res. And Obs.: 3 (5.76) Total: 6 (11.53) Female (n=70) Restrictive: 2 (2.85) Obstructive: 1 (1.42) Combined Res. And Obs.: 0 Total: 3 (4.28) Total (n=122) Restrictive: 3 (2.45) Obstructive: 3 (2.45) Combined Res. And Obs.: 3 (2.45) Total: 9 (7.37) Reference: Dales et al., (2008, 156378 ) Period of Study: Location: Windsor, ON Outcome: Pulmonary function and inflammation Age Groups: Grades 4-6 Study Design: Cross-sectional prevalence design Statistical Analyses: Multivariate linear regression

Covariates: Ethnic background, smokers at home, pets at home, acute respiratory illness, medication use Pollutant: PM 10-2.5 Averaging Time: Annual

Mean: 7.25

5th: 6.02

95th: 8.23 Copollutant:

SO 2 NO 2 Increment: Tertiles of exposure FEV 1 : <7.04: 2.18 ± 0.01 7.04-7.53: 2.19 ± 0.02 >7.53: 2.14 ± 0.01 FVC: <7.04: 2.52 ± 0.02 7.04-7.53: 2.53 ± 0.02 >7.53: 2.48 ± 0.02 eNO: <7.04: 15.48 ± 0.63 7.04-7.53: 16.73 ± 0.76 >7.53: 16.59 ± 0.79



### December 2009 E-408

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Gauderman et al. (2000, 012531 ) Period of Study: 1993-1997

Location: Southern California Outcome: FVC, FEV 1 , MMEF, FEF75 Age Groups: Fourth, seventh, or tenth graders Study Design: Cohort

N: 3035 subjects Statistical Analyses: Linear regression

Covariates: Height, weight, BMI, asthma, smoking, exercise, room temperature, barometric pressure Dose-response Investigated? Yes Statistical Package: SAS Pollutant: PM 10-2.5 Averaging Time: 24-h avg PM 10 & annual avg of 2-wk avg PM 2.5 Mean (SD): PM 10-2.5 25.6 Copollutant (correlation):

O 3 r = -0.29

NO 2 r = 0.44 Inorg. Acid r = 0.43 Increment: 25.6 μg/m 3 % Change (Lower CI, Upper CI) PM 10-2.5 -4th grade FVC -0.57 (-1.20 to -0.06) FEV 1 -0.90 (-1.71 to -0.09) MMEF -1.37 (-2.57 to -0.15) FEF75 -1.62 (-3.24, 0.04) PM 10-2.5 -7th grade FVC -0.35 (-1.02, 0.31) FEV 1 -0.49 (-1.21, 0.24) MMEF -0.64 (-2.83, 1.60) FEF75 -0.74 (-2.65, 1.20) PM 10-2.5 -10th grade FVC -0.17 (-1.32, 0.99) FEV 1 -0.68 (-2.15, 0.81) MMEF -1.41 (-5.85, 3.25) FEF75 -2.32 (-6.60, 2.17) Reference: Gauderman et al. (2002, 026013 ) Period of Study: 1996-2000

Location: Southern California Outcome: Lung function development: FEV 1 , maximal mid-expiratory flow (MMEF) Age Groups: Fourth grade children (avg age = 9.9 yr) Study Design: Cohort study

N: 1678 children, 12 communities Statistical Analyses: Mixed model linear regression

Covariates: Height, BMI, doctordiagnosed asthma and cigarette smoking in previous yr, respiratory illness and exercise on day of test, interaction of each of these variables with sex, barometric pressure, temperature at test time, indicator variables for field technician and spirometer Dose-response Investigated? Yes Statistical Package: SAS (10) Pollutant: PM 10-2.5 Averaging Time: Annual 24-h avg Mean (SD): The avg levels were presented in an online data supplement (Fig E1) Monitoring Stations : 12 Copollutant (correlation):

O 3 (10 AM to 6 PM) r = 0.10

O 3 r = -0.31

NO 2 r = 0.46 Acid vapor r = 0.63

PM 10 r = 0.95

PM 10-2.5 r = 0.81

EC r = 0.71

OC r = 0.96 PM Increment: 29.1 μg/m 3

Association Estimate:

PM 10-2.5 was not correlated with any of the pulmonary function tests that were analyzed

Reference: Leonardi et al. (2000, 010272 ) Period of Study: 1996

Location: 17 cities of Central Europe (Bulgaria, Czech Republic, Hungary , Poland, Romania, Slovakia) Outcome: Immune biomarkers Age Groups: 9-11 Study Design: Cross-sectional

N: 366 school children Statistical Analyses: Linear regression

Covariates: Age, gender, parental smoking, laboratory of analysis, recent respiratory illness Dose-response Investigated? No Statistical Package: STATA Pollutant: PM 10-2.5 Averaging Time: Subtracting PM 2.5 from PM 10 provides avg PM 10-2.5 Mean (SD): PM 10-2.5 : 20 (5) Range (Min, Max):

PM 10-2.5 : (12, 38) 5th, median, & 95th percentile

PM 10-2.5 : 12, 19, 29 % Change (Lower CI, Upper CI) p-value PM 10-2.5 Neutrophils 1 (-27, 38) >.20 Total lymphocytes 8 (-15, 38) >.20 B lymphocytes 22 (-16, 76) >.20 Total T lymphocytes 2 (-25, 37) >.20 CD4+ -1 (-30, 41) >.20 CD8+ 3 (-25, 41) >.20 CD4/CD8 0 (-23, 30) >.20 NK 1 (-33, 51) >.20 Total IgG -3 (-21, 18) >.20 Total IgM 19 (-9, 55) >.20 Total IgA 16 (-12, 52) >.20 Total IgE -29 (-70, 70) >.20



### December 2009 E-409

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: McConnell et al. (2003, 049490 ) Period of Study: 1993-1999

Location: 12 Southern CA communities Outcome: Bronchitic symptoms Age Groups: 9-19 Study Design: Communities selected on basis of historic levels of criteria pollutants and low residential mobility.

N: 475 children Statistical Analyses: 3 stage regression combined to give a logistic mixed effects model

Covariates: Sex, ethnicity, allergies history, asthma hist ory, SES, insurance status, current wheeze, current exposure to ETS, personal smoking status, participation in team sports, in utero tobacco exposure through maternal smoking, family history of asthma, amount of time routinely spent outside by child during 2-6 pm. Dose-response Investigated? No Statistical Package: SAS Glimmix

macro Pollutant: PM 10-2.5 Averaging Time: 4-yr avg Mean (SD): 17.0(6.4) Range (Min, Max): 10.2-35.0 Copollutant (correlation):

PM 2.5 : r = 0.24

PM 10 : r = 0.79 Inorganic acid: r = 0.38 Organic Acid: r = 0.35

EC: r = 0.30

OC: r = 0.27

NO 2 : r = -0.22

O 3 : r = 0.29 PM Increment: Between community range 24.8 μg/m 3 Between community unit 1 μg/m 3 Within community 1 μg/m 3 OR Estimate [Lower CI, Upper CI] Between community per range 1.38(0.65-2.92) Between Community per unit 1.01(0.98-1.04) Within community per unit 1.02(0.95-1.10)

Reference: Millstein et al. (2004, 088629 ) Outc ome: Wheezing & asthma medication use Period of Study: Mar-Aug, 1995, and Sep 1995-Feb 1996 Age Groups: 4th grade students, mostly 9 yr at the time of the study Study Design: Cohort Study, stratified into 2 seasonal groups/

N: 2081 enrolled, 2034 provided parentcompleted questionnaire. Statistical Analyses: Multilevel, mixedeffects logistic model.

Covariates: Contagious respiratory disease, ambient airborne pollen and other allergens, temperature, sex, age race, allergies, pet cats, carpet in home, environmental tobacco smoke, heating fuel, heating system, water damage in home, education level of questionnaire signer, physician diagnosed asthma. Data were taken from the Children’s Health Study

Location: Alpine, Atascadero, Lake Arrowhead, Lake Elsinore, Lancaster, Lompoc, Long Beach, Mira Loma, Riverside, San Dimas, Santa Maria, and Upland, CA

Season: Mar-Aug, 1995, and Sep, 1995 to Feb, 1996 Statistical Package: SAS 8.00 Lags Considered: 14 Pollutant: PM 10-2.5 Averaging Time: monthly PM Component: Nitric acid, formic acid, acetic acid Monitoring Stations : 1 central location in each community Copollutant (correlation):

NO 2 : r = 0.29

O 3 : r = 0.77

PM 2.5 : r = -0.08 PM Increment: IQR 11.44 μg/m 3 Odds Ratio [lower CI, Upper CI]

Annual

PM 10-2.5 : 0.96 [0.74, 1.25] Mar-Aug

PM 10-2.5 : 0.93 [0.54, 1.59] Sep-Feb

PM 10-2.5 : 0.68 [0.46, 1.01]

Reference: (Parker et al., 2009, 192359 ) Period of Study: 1999-2005

Location: U.S. Outcome: Respiratory allergy/hayfever Study Design: Cohort

Covariates: Survey yr, age, family structure, usual source of care, health insurance, family income relative to federal poverty level, race/ethnicity Statistical Analysis: Logistic regression Statistical Package: SUDAAN Age Groups: 73,198 children aged 3-17 yr Pollutant: PM 10-2.5 Averaging Time: NR

Median: 11.2 μg/m 3

IQR: 8.2-15.2 Copollutant (correlation): Summer O 3 : 0.16 SO 2 : -0.33 NO 2 : 0.29 PM 2.5 : 0.02 PM 10 : 0.86 Increment: 10 μg/m 3 Odds Ratio (95% CI) Single Pollutant Model, variable N Adjusted: 1.01 (0.95-1.07) Single Pollutant Model, constant N Adjusted: 1.13 (1.04-1.46) Multi-pollutant Model: 1.16 (1.06-1.24)



### December 2009 E-410

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zhang et al. (2002, 034814 ) Period of Study: 1993-1996

Location: 4 Chinese cities (urban and suburban location in each city): Guangzhou, Wuhan, Lanzhou, Chongqing Outcome: Interview-self reports of symptoms: Wheeze (ever wheezy when having a cold) Asthma (diagnosis by doctor) Bronchitis (diagnosis by doctor), Hospitalization due to respiratory disease (ever) Persistent cough (coughed for at least 1 month per yr with or apart from colds) Persistent phlegm (brought up phlegm or mucus from the chest for at least 1 month per yr with or apart from colds) Age Groups: Elementary school students age range: 5.4-16.2 Study Design: Cross-sectional

N: 7,557 returned questionnaires 7,392 included in first stage of analysis Statistical Analyses: 2-stage regression approach: Calculated odds ratios and 95% CIs of respiratory outcomes and covariates Second stage consisted of variance-weighted linear regressions that examined associations between district-specific adjusted prevalence rates and district-specific ambient levels of each pollutant.

Covariates: Age, gender, breast-fed, house type, number of rooms, sleeping in own or shared room, sleeping in own or shared bed, home coal use, ventilation device used, homes smokiness during cooking, eye irritation during cooking, parental smoking, mother’s education level, mother’s occupation, father’s occupation, questionnaire respondent, yr of questionnaire administration, season of questionnaire administration, parental asthma prevalence Pollutant: PM 10-2.5 Averaging Time: 2 yr Mean (SD): 59 (28)

Percentiles: 25th: NR 50th(Median): NR

75th: NR

IQR: 42 Range (Min, Max): Gives range (max.-min.): 80 Monitoring Stations : 2 types: municipal monitoring stations over a period of 4 yr (1993-1996) Schoolyards of participating children over a period of 2 yr (1995-1996) PM Increment: Interquartile range corresponded to 1 unit of change. RR Estimate [Lower CI, Upper CI] lag:

Association between bronchitis and PM 10-2.5 : 2.20 (1.14, 4.26) p < 0.05 Association between persistent cough and PM 10-2.5 : 1.46 (1.12, 1.90) p < 0.05 Between and within city associations: Bronchitis: 3.18 (between city) Persistent phlegm (between city): 2.78

When scaled to an increment of 50 μg/m 3 of PM 10-2.5 associations (ORs) between respiratory outcome and PM 10-

2.5 were: Wheeze: 1.14

Asthma: 1.34

Bronchitis: 2.56 Hospitalization: 1.58 Persistent cough: 1.57 Persistent phlegm: 3.45

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-411

# Table E-24. Long-term exposure - r espiratory morbidity outcomes - PM 2.5 

# (including PM components/sources).

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: AnnesiMaesano et al.(2007, 091348 ) Period of Study: Mar 1999-Oct 2000

Location: France(Bordeaux, ClermontFerrand, Creteil, Marseille, Strasbourg,, & Reims) Outcome: EIB, Flexural atopic dermatitis, asthma, rhiniconjuctivitis, allergic rhinitis Age Groups: Children mean 10.4 ± 0.7 yr Study Design: Semi-individual design

N: 5338 Statistical Analyses: Logistic regression

Covariates: Age, sex, family history of allergy, passive smoking

Season: NR Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 2.5 Averaging Time: 5-day mean (Mon.-Fri.) over a 13-wk to 24-wk span Residential Proximity Level Mean (SD): Low conc: 8.7 High conc: 20.7 Range (Min, Max): Low conc: (1.6, 12.2) High conc: (12.5, 54.0) City Level Mean (SD): Low conc: 9.6 High conc: 23.0 Range (Min, Max): Low conc: (4.7, 12.7) High conc: (13.0, 54.5) PM Increment: High vs. Low Allergic and respiratory morbidity OR Estimate (Lower CI, Upper CI) Proximity Level EIB (C) 1.35 (1.10, 1.67) Fl. Atopic dermatitis (C) 2.51 (2.06, 3.06) Asthma (P) 1.11 (0.88, 1.39) Atopic asthma (P) 1.43 (1.07, 1.91) Non-atopic asthma (P) 0.73 (0.49, 1.07) Rhiniconjunctivitis (P) 0.94 (0.77, 1.15) Atopic dermatitis (P) 1.05 (0.88, 1.27) Asthma (L) 1.00 (0.82, 1.22) Allergic Rhinitis (L) 1.09 (0.93, 1.27) Atopic dermatitis (L) 0.94 (0.82, 1.09) City Level EIB (C) 1.43 (1.15, 1.78) Fl. Atopic dermatitis (C) 2.06 (1.69, 2.51) Asthma (P) 1.31 (1.04, 1.66) Atopic asthma (P) 1.58 (1.17, 2.14) Non-atopic asthma (P) 1.00 (0.68, 1.49) Rhiniconjunctivitis (P) 0.98 (0.80, 1.20) Atopic dermatitis (P) 1.08 (0.90, 1.30) Asthma (L) 1.09 (0.89, 1.33) Allergic Rhinitis (L) 1.13 (0.97, 1.33) Atopic dermatitis (L) 0.95 (0.82, 1.09) Notes: C = Current P = Past yr L = Lifetime Allergic sensitization OR Estimate (Lower CI, Upper CI) Proximity Level All allergens 1.19 (1.04, 1.36) Indoor allergens 1.29 (1.11, 1.50) Outdoor allergens 1.02 (0.85, 1.23) Moulds 1.13 (0.78, 1.65) City Level All allergens 1.32 (1.15, 1.51) Indoor allergens 1.51 (1.29, 1.76) Outdoor allergens 1.06 (0.88, 1.28) Molds 1.00 (0.69, 1.46) Reference: Bakke et al. (2004, 156246 ) Period of Study: Jan 1989-Jun 2002

Location: One of Norway’s major construction companies Outcome: Spirometric measurements Age Groups: All ages, mean = 39 yr Study Design: Cohort

N: 651 male construction workers Statistical Analyses: Multiple linear regression models

Covariates: Age, yr for nonsmokers and ever smokers Dose-response Investigated? No Statistical Package: SYSTAT 10.0 and SPSS 11.0 Pollutant: Respirable dust Averaging Time: 5-8 h Mean (SD): Drill and blast workers: 6.3 (2.8) Tunnel concrete workers: 6.1 (3.1) Shotcreting operators: 19 (11) TBM workers: 16 (6.6) Outdoor concrete workers: 1.4 (0.73) Foremen: 0.28 (0.48) Engineers: 0.09 (0.28) Unit (i.e. μg/m 3 ): mg · y/m 3 Monitoring Stations : 16 tunnel sites visited with sampling equipment Copollutant (correlation): Total dust: r = 0.99

α quartz: r = 0.48 NO 2 : r = 0.75 CO: r = 0.61 Oil mist: r = 0.83 Oil vapor: r = 0.68 VOC: r = 0.89 PM Increment: NR-exposure respirable dust Effect Estimate (Lower CI, Upper CI): Lung function changes predicted by multiple linear regression models using one exposure variable adjusted for age and observation time by non-smokers and ever smokers

Non-smokers: ß = -16.0 (-24- -6.8)

SE = 4.5

Ever smokers: ß = -9.3 (-17- -1.6)

SE = 4.0



### December 2009 E-412

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bakke et al. (2004, 156246 ) Period of Study: Jan 1989-Jun 2002

Location: One of Norway’s major construction companies Outcome: Spirometric measurements Age Groups: All ages, mean = 39 yr Study Design: Cohort

N: 651 male construction workers Statistical Analyses: Multiple linear regression models

Covariates: Age, yr for nonsmokers and ever smokers Dose-response Investigated?

No Statistical Package:

SYSTAT 10.0 and SPSS 11.0 Pollutant: Total dust Averaging Time: 5-8 h Mean (SD): Drill and blast workers: 18 (7.8) Tunnel concrete workers: 21 (11) Shotcreting operators: 73 (41) TBM workers: 48 (20) Outdoor concrete workers: 6.5 (3.4) Foremen: 0.78 (1.3) Engineers: 0.27 (0.78) Unit (i.e. μg/m 3 ): mg · y/m 3

Monitoring Stations : 16 tunnel sites visited with sampling equipment Copollutant (correlation): Respirable dust: r = 0.99

α quartz: r = 0.42 NO 2 : r = 0.67 CO: r = 0.49 Oil mist: r = 0.81 Oil vapor: r = 0.64 VOC: r = 0.91 PM Increment: NR-exposure expirable dust Lung function changes predicted by multiple linear regression models using one exposure variable adjusted for age and observation time by non-smokers and ever smokers Non-smokers: ß = -4.0 (-6.5-1.4)

SE = 1.3 Ever smokers: ß = -2.0 (-4.2-0.23)

SE = 1.1

Reference: Bennett et al. (2007, 156268 ) Period of Study: 1992-2005

Location: Melbourne, Australia Outcome: Respiratory symptoms (from questionnaire) Age Groups: All ages, mean = 37.2 yr Study Design: Cohort

N: 1446 Statistical Analyses: Logistic regression models

Covariates: Age, gender, use of ß2-agonists, use of inhaled corticosteroids, smoking, yr of data collection, and avg daily exposure to PM 2.5 in the 12 mo corresponding to the time frame of symptoms Dose-response Investigated? No Statistical Package: STATA, version 9 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 6.8 Range (Min, Max): (1.8-73.3) Monitoring Stations : up to 3 PM Increment: NR Effect Estimate [Lower CI, Upper CI]: Respiratory symptoms in last 12 mo and exposure to ambient PM over the same period

2.5 Within-person (longitudinal) effects Wheeze: OR = 1.08 (0.79-1.48), p = 0.62 SOB on waking: OR = 1.34 (0.84-2.16), p = 0.22 Cough (AM): OR = 0.74 (0.47-1.15), p = 0.18 Phlegm (AM): OR = 1.55 (0.95-2.53), p = 0.08 Cough w/ phlegm (AM): OR = 1.28 (0.70-2.33), p = 0.42 Asthma attack: OR = 0.91 (0.55-1.49), p = 0.69 Between-person (cross-sectional) effects Wheeze: OR = 1.32 (0.82-2.10), p = 0.25 SOB on waking: OR = 1.29 (0.46-3.60), p = 0.63 Cough (AM): OR = 0.21 (0.07-0.62), p = 0.01 Phlegm (AM): OR = 0.49 (0.16-1.44), p = 0.19 Cough w/ phlegm (AM): OR = 0.28 (0.08-0.97), p = 0.05 Asthma attack: OR = 0.52 (0.17-1.59), p = 0.26



### December 2009 E-413

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Brauer et al., 2007, 090691 ) Period of Study: 1999-2000

Location: The Netherlands Outcome: Allergen sensitivity (any, indoor, outdoor, food, total) IgE>100 IU/mL Asthma (probable, MD-diagnosed, ever MD-diagnosed) Bronchitis (MD-diagnosed, ever MD-diagnosed) Dry cough at night Itchy rash Itchy rash/eczema Ear/Nose/Throat (ENT) infection Eczema, MD-diagnosed Eczema, ever MD-diagnosed Flu/serious cold, MD-diagnosed Wheeze (ever, early, early frequent, persistent) Age Groups: Very young children (<4-yr-old) enrolled prenatally Study Design: Prospective birth cohort study

N: ~4000 subjects Statistical Analyses: Multiple logistic regression Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: 12 mo Mean (SD): SD: NR

16.9

Percentiles: 25th: 14.8 50th(Median): 17.3

75th: 18.1 Range (Min, Max): (13.5, 25.2) Monitoring Stations : 40 Copollutant (correlation): Soot: r = 0.97

NO 2 : r = 0.93 PM Increment: IQR 3.3 μ g/m 3 Notes: Traffic-related pollution (PM 2.5 , soot, NO 2 ) was associated with respiratory infections, asthma, and allergic sensitization in children during the first 4 yr of life. Symptom At 4-Yr-Old Wheeze 4-yr-old: 1.23 [1.00: 1.51] Early-life: 1.20 [0.99: 1.46] Asthma, MD-diagnosed 4-yr-old: 1.15 [0.82: 1.62] Early-life: 1.32 [0.96: 1.83] Dry cough at night 4-yr-old: 1.11 [0.94: 1.31] Early-life: 1.14 [0.98: 1.33] Bronchitis, MD-diagnosed 4-yr-old: 0.88 [0.66: 1.18] Early-life: 0.86 [0.66: 1.11] ENT infection 4-yr-old: 1.13 [0.98: 1.31] Early-life: 1.17 [1.02: 1.34] Flu/serious cold, MD-diagnosed 4-yr-old: 1.21 [1.02: 1.42] Early-life: 1.25 [1.07: 1.46] Itchy rash 4-yr-old: 0.96 [0.82: 1.11] Early-life: 0.98 [0.85: 1.14] Eczema, MD-diagnosed 4-yr-old: 1.00 [0.88: 1.21] Early-life: 0.98 [0.82: 1.17] Allergen Sensitivity At 4-Yr-Old Allergen, any: 1.55 [1.13: 2.11] Allergen, indoor: 1.03 [0.69: 1.55] Allergen, outdoor: 0.93 [0.54: 1.58] Allergen, food: 1.75 [1.23: 2.47] Allergen, total IgE>100 IU/mL: 0.84 [0.59: 1.18] Cumulative Allergy/Asthma Symptoms At 4-Yr-Old Wheeze, ever: 1.22 [1.06: 1.41] Asthma, ever MD-diagnosed: 1.32 [1.04: 1.69] Asthma, probable: 1.08 [0.90: 1.30] Wheeze, early: 1.16 [1.00: 1.34] Wheeze, persistent: 1.19 [0.96: 1.48] Wheeze, early frequent: 1.19 [0.96: 1.47] Bronchitis, ever MD-diagnosed: 0.96 [0.81: 1.13] Itchy rash/eczema: 0.99 [0.88: 1.13] Eczema, ever MD-diagnosed: 0.98 [0.85: 1.13]



### December 2009 E-414

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Brauer et al., 2007, 090691 ) Period of Study: 1999-2000

Location: The Netherlands Outcome: Allergen sensitivity (any, indoor, outdoor, food, total) IgE>100 IU/mL Asthma (probable, MD-diagnosed, ever MD-diagnosed) Bronchitis (MD-diagnosed, ever MD-diagnosed) Dry cough at night Itchy rash Itchy rash/eczema Ear/Nose/Throat (ENT) infection Eczema, MD-diagnosed Eczema, ever MD-diagnosed Flu/serious cold, MD-diagnosed Wheeze (ever, early, early frequent, persistent) Age Groups: Very young children (<4-yr-old) enrolled prenatally Study Design: Prospective birth cohort study

N: ~4000 subjects Statistical Analyses: Multiple logistic regression Dose-response Investigated? No Pollutant: Soot (as PM 2.5 absorbance) Averaging Time: 12 mo Mean (SD): 1.71

Percentiles: 25th: 1.33 50th(Median): 1.78

75th: 1.91 Range (Min, Max): (0.77, 3.68) Unit (i.e. μg/ m 3 ) : 1E-5/m Monitoring Stations : 40 Copollutant (correlation):

NO 2 : r = 0.96

PM 2.5 : r = 0.97 PM Increment: IQR 0.58 E-5/m Notes: Traffic-related pollution (PM 2.5 , soot, NO 2 ) was associated with respiratory infections, asthma, and allergic sensitization in children during the first 4 yr of life. Symptom At 4-Yr-Old Wheeze 4-yr-old: 1.18 [0.98: 1.41] Early-life: 1.18 [1.00: 1.40] Asthma, MD-diagnosed 4-yr-old: 1.15 [0.85: 1.55] Early-life: 1.30 [0.98: 1.71] Dry cough at night 4-yr-old: 1.13 [0.97: 1.30] Early-life: 1.14 [1.00: 1.31] Bronchitis, MD-diagnosed 4-yr-old: 0.90 [0.69: 1.16] Early-life: 0.88 [0.69: 1.11] ENT infection 4-yr-old: 1.15 [1.01: 1.31] Early-life: 1.16 [1.03: 1.31] Flu/serious cold, MD-diagnosed 4-yr-old: 1.18 [1.02: 1.36] Early-life: 1.19 [1.04: 1.37] Itchy rash 4-yr-old: 0.94 [0.82: 1.08] Early-life: 0.97 [0.85: 1.10] Eczema, MD-diagnosed 4-yr-old: 0.99 [0.84: 1.17] Early-life: 0.97 [0.83: 1.14] Allergen Sensitivity At 4-Yr-Old Allergen, any: 1.45 [1.11: 1.91] Allergen, indoor: 1.02 [0.71: 1.46] Allergen, outdoor: 0.95 [0.59: 1.52] Allergen, food: 1.64 [1.21: 2.23] Allergen, total IgE>100 IU/mL: 0.80 [0.59: 1.09] Cumulative Allergy/Asthma Symptoms At 4-Yr-Old Wheeze, ever: 1.18 [1.04: 1.34] Asthma, ever MD-diagnosed: 1.26 [1.02: 1.56] Asthma, probable: 1.06 [0.90: 1.24] Wheeze, early: 1.11 [0.97: 1.26] Wheeze, persistent: 1.18 [0.98: 1.42] Wheeze, early frequent: 1.14 [0.95: 1.37] Bronchitis, ever MD-diagnosed: 0.95 [0.82: 1.10] Itchy rash/eczema: 0.99 [0.89: 1.11] Eczema, ever MD-diagnosed: 0.99 [0.87: 1.12] Reference: Brauer et al. (2002, 035192 ) Period of Study: NR

Location: The Netherlands Outcome: Questionnaire derived wheezing, dry nighttime cough, ear, nose and throat infections, skin rash Physician diagnosed asthma, bronchitis, influenza, eczema Age Groups: age 2 Study Design: Prospective cohort

N: 4146 children Statistical Analyses: Logistic regression

Covariates: Maternal age, maternalsmoking, mattress cover (allergenfree), maternal education, paternal education, gender, gas stove, gas water heater, any other siblings, ethnicity, breastfeeding, mold at home, pets, allergies in mother, allergies in father Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: 4 2-wk periods dispersed throughout 1 yr, adjusted for temporal trend Mean (SD): 16.9

Percentiles: 10th: 14.0

25th: 15.0 50th(Median): 17.3

75th: 18.2

90th: 19.1 Range (Min, Max): 13.5, 25.2 Monitoring Stations: 40 Copollutant (correlation): Soot: r = 0.99 NO 2 : r = 0.97 PM Increment: 3.2 μg/m 3 OR Estimate [Lower CI, Upper CI]; Unadjusted Wheeze 1.14 (0.99-1.30) Asthma 1.08 (0.84-1.37) Dry cough at night 1.10 (0.95-1.27) Bronchitis 1.00 (0.85-1.18) E, N, T infections 1.14 (0.99-1.33) Flu 1.15 (1.03-1.28) Itchy rash 1.07 (0.95-1.20) Eczema 1.02 (0.90-1.16) Adjusted Wheeze 1.14 (0.98-1.34) Asthma 1.12 (0.84-1.50) Dry cough at night 1.04 (0.88-1.23) Bronchitis 1.04 (0.85-1.26) E, N, T infections 1.20 (1.01-1.42) Flu 1.12 (1.00-1.27) Itchy rash 1.01 (0.88-1.16) Eczema 0.95 (0.83-1.10)



### December 2009 E-415

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference : Brauer et al. (2002, 035192 ) Period of Study: NR

Location: The Netherlands Outcome: Questionnaire derived wheezing, dry nighttime cough, ear, nose and throat infections, skin rash Physician diagnosed asthma, bronchitis, influenza, eczema Age Groups: Age 2 Study Design: Prospective cohort

N: 4146 children Statistical Analyses: Logistic regression

Covariates: Maternal age, maternalsmoking, mattress cover (allergenfree), maternal education, paternal education, gender, gas stove, gas water heater, any other siblings, ethnicity, breastfeeding, mold at home, pets, allergies in mother, allergies in father Dose-response Investigated? No Pollutant: PM 2.5 “soot” Averaging Time: 4 2-wk periods dispersed throughout 1 yr, adjusted for temporal trend Mean (SD): 16.9 10-5/m Percentiles: 10th: 1.16 25th: 1.38 50th(Median): 1.78 75th: 1.92 90th: 2.19 Range (Min, Max): 0.77, 3.68 Unit (i.e. μg/ m 3 ): 10-5/m Monitoring Stations : 40 Copollutant (correlation): PM 2.5 (r = 0.99) NO 2 (r = 0.96) PM Increment: 0.54 x 10-5/m (equivalent to 0.8 μg/m 3 EC) OR Estimate [Lower CI, Upper CI] Unadjusted Wheeze 1.11 [0.99-1.24] Asthma 1.07 [0.87-1.31] Dry cough at night 1.08 [0.95-1.21] Bronchitis 0.98 [0.85-1.12] E, N, T infections 1.12 [0.99-1.27] Flu 1.13 [1.03-1.23] Itchy rash 1.07 [0.97-1.19] Eczema 1.01 [0.91-1.13] Adjusted Wheeze 1.11 [0.97-1.26] Asthma 1.12 [0.88-1.43] Dry cough at night 1.02 [0.88-1.17] Bronchitis 0.99 [0.84-1.17] E, N, T infections 1.15 [1.00-1.33] Flu 1.09 [0.98-1.21] Itchy rash 1.02 [0.91-1.15] Eczema 0.96 [0.85-1.08]

Reference: Brauer et al. (2006, 090757 ) Period of Study: 1997-2001

Location: Germany

The Netherlands Outcome: Otitis Media (parental report of doctor’s diagnosis prior to age 2 yr) Age Groups: 0-2 yr Study Design: Prospective Cohort Study

N: 4,379 children total The Netherlands: 3,714 Germany: 665 Statistical Analyses: Logistic regression

Covariates: Sex, parental atopy, maternal education, siblings, maternal smoking during pregnancy, ETS exposure at home, use of gas for cooking, indoor moulds and dampness, number of siblings, breast-feeding, and presence of pets in the home

Season: All Dose-response Investigated? No Pollutant: PM 2.5 PM Component: EC (EC) Averaging Time: 8 wk (4 2-week periods dispersed throughout 1 yr, adjusted for temporal trends) Mean: The Netherlands: PM 2.5 : 16.9 EC: 1.72 Germany: PM 2.5 : 13.4 EC: 1.76 Range (Min, Max): The Netherlands: PM 2.5 : 13.5, 25.2 EC: 0.77, 3.68 Germany: PM 2.5 : 12.0, 21.9 EC: 1.40, 4.39 Monitoring Stations : 80 (40 for each cohort) PM Increment: PM 2.5 : 3 μg/m 3 (~ IQR) EC: ~0.5 μg/m 3 (~ IQR)

OR Estimate [Lower CI, Upper CI]

The Netherlands: PM :

2.5 At age 1: 1.13 (0.98-1.32) At age 2: 1.13 (1.00-1.27) EC: At age 1: 1.11 (0.98-1.26) At age 2: 1.10 (1.00-1.22) Germany: PM 2.5 : At age 1: 1.19 (0.73-1.92) At age 2: 1.24 (0.84-1.83) EC: At age 1: 1.12 (0.83-1.51) At age 2: 1.10 (0.86-1.41)

Reference: Burr et al. (2004, 087809 ) Period of Study: 3 wk in Jul and Jan 1997 and 2 wk in Nov 1996 and Apr 1997

Location: North Wales, England Outcome: Self-report of symptoms only for wheeze, cough, phlegm, rhinitis, and itchy eyes. Age Groups: All Study Design: Repeated measures

N: 386 persons in congested streets and 425 in the uncongested streets in 1996/1997. Of these, 165 and 283 completed the second phase of the study. Pollutant: PM 2.5 Averaging Time: Mean hourly concentrations Mean (SD): Congested Streets 1996-97 21.2 1998-99 16.2 Uncongested Streets 1996-97 6.7 1998-99 4.9 Monitoring Stations : 1 in congested street and 1 in uncongested % change PM 10 in congested streets: 23.6 % change PM 10 in uncongested streets: 26.6 Uncongested street sampling site was 20 m from the congested street sampler. The opening of the by-pass produced a reduction in pollution in the congested streets. The health effects of these changed are likely to be greater for nasal and ocular symptoms than for lower respiratory symptoms. Uncertainty about the causality arises from low response rates and conflicting trends in respiratory and nasal symptoms.



### December 2009 E-416

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: CalderónGarcidueñas et al. (2006, 091253 ) Period of Study: 1999-2000

Location: Southwest Mexico City & Tlaxcala, Mexico Outcome: Hyperinflation, interstitial markings-measured by chest radiograph, and lung function-FVC, FEV 1 , PEF, FEF25-75, measured using spirometry tests Age Groups: 5-13 yr Study Design: Cohort1999-

N: 249 (total), 230 (Southwest Mexico City), 19 (Tlaxcala) Statistical Analyses: Bayes test, Spearman rank correlation, multiple regression

Covariates: Age, sex Dose-response Investigated? No Statistical Package: SAS 8.2 Pollutant: PM 2.5 Averaging Time: 1 yr Mean (SD): 21

2000-19

Tlaxacala:

1994-2000: <NAAQS std Mexico City Monitoring Stations: Southwest Mexico City-2 Tlxacala-periodic air monitoring data Cop ollutant: O 3 PM Increment: NR % Change:

% of children with FEV 1 <80% expected value: Mexico City (n = 77): 7.8% Tlaxacala (n = 19): 0% % children with hyperinflation: Mexico City: 65.6% Number with: No hyperinflation: 79 Mild: 72 Moderate: 56 Severe: 23

Tlaxacala: 5.3% Number with: No hyperinflation: 18 Mild: 1 Moderate: 0 Severe: 0 % children with interstitial markings: Mexico City: 52.6% Number with: No interstitial markings: 19 Mild: 0 Moderate: 0 Severe: 0

Tlaxacala: 0% Number with: No interstitial markings: 109 Mild: 112 Moderate: 9 Severe: 0 Reference: Cesaroni et al. (2008, 156326 ) Period of Study: Data on PM emissions collected in 2002 cross-sectional survey carried out in 1995

Location: Rome, Italy Outcome: Self-reported chronic bronchitis or emphysema, asthma, and rhinitis Age Groups: 25-59 yr Study Design: Cross-sectional

N: 9,488 subjects who had been residents in same place for at least 3 yr and who had participated in an extension of the I SAAC initiative in Italy in 1994 & 1995 Statistical Analyses: GEE with a logit link

Covariates: Sex, age, smoking habits, education level, and variable to account for correlation of data for members of the same family Effect Modifiers: stratified analysis by smoking status (only presented for the traffic score variable) Also stratified by education level (data not shown) Dose-response Investigated: Wald test to calculate p for trend Pollutant: PM emissions (estimated) Emissions estimated using a model/method based on factors such as vehicle park, driving conditions, emission factors, fuel consumption, fuel properties, road gradients, and climatic conditions

Mean: 0.12 kg/km 2

SD: 0.081 Odds Ratios for quartil es of PM emissions: Chronic bronchitis or emphysema (n = 397): 1st: 1.00 2nd: 0.96 (0.71, 1.30) 3rd: 0.90 (0.66, 1.23) 4th: 1.05 (0.77, 1.42) p-trend = 0.871 Asthma (n = 472): 1st: 1.00 2nd: 1.10 (0.84, 1.44) 3rd: 0.94 (0.71, 1.24) 4th: 1.06 (0.80, 1.39) p-trend = 0.980 Rhinitis (n = 1227): 1st: 1.00 2nd: 1.41 (1.17, 1.69) 3rd: 1.11 (0.92, 1.34) 4th: 1.37 (1.14, 1.64) p-trend = 0.018



### December 2009 E-417

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Dales et al., (2008, 156378 ) Period of Study: Location: Windsor, ON Outcome: Pulmonary function and inflammation Age Groups: Grades 4-6 Study Design: Cross-sectional prevalence design Statistical Analyses: Multivariate linear regression

Covariates: Ethnic background, smokers at home, pets at home, acute respiratory illness, medication

use Pollutant: PM 2.5 Averaging Time: Annual

Mean: 15.4

5th: 14.2

95th: 17.2 Copollutant:

SO 2 NO 2 Increment: Tertiles of exposure FEV 1 : <15.19: 2.16 ± 0.01 15.19-15.96: 2.17 ± 0.02 >15.96: 2.18 ± 0.01 FVC: <15.19: 2.51 ± 0.02 15.19-15.96: 2.50 ± 0.02 >15.96: 2.52 ± 0.02 eNO: <15.19: 16.08 ± 0.70 15.19-15.96: 15.80 ± 0.76 >15.96: 16.79 ± 0.72

Reference: Gauderman et al. (2000, 012531 ) Period of Study: 1993-1997

Location: Southern California Outcome: FVC, FEV 1 , MMEF, FEF75 Age Groups: Fourth, seventh, or tenth graders Study Design: Cohort

N: 3035 subjects Statistical Analyses: Linear regression

Covariates: Height, weight, BMI, asthma, smoking, exercise, room temperature, barometric pressure Dose-response Investigated? Yes Statistical Package: SAS Pollutant: PM 2.5 Averaging Time: Annual avg of 2-wk avg PM 2.5 Mean (SD): PM 2.5 25.9 Copollutant (correlation):

03: r = -0.32

PM 10-2.5 : r = 0.76

NO 2 : r = 0.74 Inorg. Acid: r = 0.79 Increment: 25.9 μg/m 3 % Change (Lower CI, Upper CI) PM -4th grade

2.5 FVC -0.47 (-0.94, 0.01) FEV 1 -0.64 (-1.28, 0.01) MMEF -1.03 (-1.95 to -0.09) FEF75 -1.31 (-2.57 to -0.03) PM 2.5 -7th grade FVC -0.42 (-0.89, 0.05) FEV 1 -0.32 (-0.88, 0.24) MMEF -0.29 (-1.99, 1.44) FEF75 -0.26 (-1.75, 1.25) PM 2.5 -10th grade FVC 0.19 (-0.68, 1.07) FEV -0.25 (-1.41, 0.93) 1 MMEF -0.17 (-3.66, 3.46) FEF75 -0.79 (-4.27, 2.82)

Reference: Gauderman et al. (2002, 026013 ) Period of Study: 1996-2000

Location: Southern California Outcome: Lung function development: FEV 1 , maximal midexpiratory flow (MMEF) Age Groups: Fourth grade children (avg age = 9.9 yr) Study Design: Cohort study

N: 1678 children, 12 communities Statistical Analyses: Mixed model linear regression

Covariates: Height, BMI, doctordiagnosed asthma and cigarette smoking in previous yr, respiratory illness and exercise on day of test, interaction of each of these variables with sex, barometric pressure, temperature at test time, indicator variables for field technician and spirometer Dose-response Investigated? Yes Statistical Package: SAS (10) Pollutant: PM 2.5 Averaging Time: Annual 24-h avg Mean (SD): The avg levels were presented in an online data supplement (Fig E1) PM Component: EC and OC. Monitoring Stations : 12 Copollutant (correlation):

O 3 : (10 AM to 6 PM) r = 0.14

O 3 : r = -0.39

NO 2 : r = 0.77 Acid vapor: r = 0.87

PM 10 : r = 0.95

PM 10-2.5 : r = 0.81

EC: r = 0.93

OC: r = 0.89 PM Increment: 22.2 μg/m 3

Association Estimate: Non-statistically significant negative correlation between PM 2.5 and FEV 1 and FVC growth rates were observed. MMEF growth rates had a negative correlation with PM 2.5 (r = -0.43 p = 0.05). PM 2.5 was not significantly correlated to FEV 1 (r = -0.31 p = 0.25)



### December 2009 E-418

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Gauderman et al., 2004, 056569 ) Period of Study: Air pollution data ascertainment: 1994-2000. Spirometry testing: spring 2001-spring 2003

Location: 12 Communities in Southern California Outcome: Lung function FVC, FEV 1 , MMEF (Maximal midexpiratory flow rate) Age Groups: Children, Avg age 10 yr Study Design: Prospective Cohort Study

N: 12 Communities 2,034 children 24,972 child-mo Statistical Analyses: Linearregression of changes in sex-andcommunity specific lung growth function and PM

Correlation between % with low attained FEV 1 and PM.

Covariates: Random effect for communities Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 2.5 Averaging Time: 2-wk measurements used to create annual avg Mean: Means are presented in figures only. Range (Min, Max): ~6, ~27 Monitoring Stations : 12 Copollutant (correlation): PM 10 : r = 0.95

O 3 : r = 0.18

NO 2 : r = 0.79

EC: r = 0.91

OC: r = 0.91 PM Increment: Most to least polluted community Range: 22.8 μg/m 3 Difference in Lung Growth [Lower CI, Upper CI]; FVC -60.1 (-166.1 to 45.9)

FEV 1 -79.7 (-153.0 to ¡6.4) MMEF -168.9 (-345.5 to 7.8)Correlation with % below 80% predicted Lung function (pvalue)

PM 2.5 : 0.79 (0.002)

Reference: Gauderman et al. (2007, 090121 ) Period of Study: 1993-2004

Location: 12 Southern California Communities Outcome: Pulmonary function tests FVC, FEV 1 , MMEF/FEF25.75 Age Groups: Children (mean age 10 at recruitment, followed for 8 yr) Study Design: Cohort Study (Children’s Health Study)

N: 3677 children (1718 in cohort 1 recruited 1993 and 1959 in cohort 2 recruited 1996) 22686 pulmonary function tests. Statistical Analyses: Hierarchical mixed effects model with linear splines

Covariates: Adjustments for height, height squared, BMI, BMI squared, present asthma status, exercise or respiratory illness on day of test, smoking in previous yr, field technician, traffic indicator (distance from freeway, distance from major roads), random effects for participant and community. Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 2.5 Monitoring Stations : 1 in each community PM Increment: 22.8 μg/m 3 Pollutant effect reported as difference in 8 yr lung function growth from least to most polluted community. Negative difference indicate growth deficits associated with exposure. For PM 2.5 FEV growth deficit is -100

Reference: Gehring et al. (2002, 036250 ) Period of Study: 1995-2002

Location: Munich, Germany Outcome: Wheezing, cough without infection, dry cough at night, obstructive, spastic or asthmoid bronchitis, respiratory infections, sneezing, runny/stuffed nose Age Groups: 0-2 yr Study Design: Prospective cohort

N: 1756 infants Statistical Analyses: Logistic regression

Covariates: Sex, parental atopy (yes/no), maternal education, siblings (y/n), environmental tobacco smoke at home (y/n), use of gas for cooking (y/n), home dampness (y/n), indoor moulds Pollutant: PM 2.5 Mean (SD): PM 2.5 mass: 13.4

PM 2.5 absorb. 1.77 * 10-5/m

Percentiles: PM 2.5 mass: 10th: 12.2

25th: 12.5 50th(Median): 13.1

75th: 14.0

90th: 14.9

PM 2.5 absorbance:

10th: 1.47 * 10-5

25th: 1.54 * 10-5 PM Increment: PM 2.5 mass: 1.5 μg/m 3 PM 2.5 absorb. 0.4 * 10-5/m (IQR) RR Estimate [Lower CI, Upper CI] Wheeze (PM 2.5 mass) Age of 1 yr: All: 0.91 (0.76-1.09) Males: 0.91 (0.72-1.16) Females: 0.94 (0.70-1.27) Age of 2 yr: All: 0.96 (0.83-1.12) Males: 0.93 (0.76-1.14) Females: 1.04 (0.83-1.30) Cough W/O Infection (PM 2.5 mass) Age of 1 yr: All: 1.34 (1.11-1.61) Males: 1.43 (1.14-1.80) Females: 1.19 (0.84-1.70) Dry Cough At Night (PM 2.5 mass) Age of 1 yr: All: 1.31 (1.07-1.60) Males: 1.39 (1.08-1.78) Females: 1.17 (0.81-1.68)



### December 2009 E-419

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) (y/n), keeping of dogs (y/n) and cats (y/n) study (GINI or LISA) Dose-response Investigated? No 50th(Median): 1.70 * 10-5

75th: 1.88 * 10-5

90th: 2.13 * 10-5 Range (Min, Max):

PM 2.5 mass: 11.9, 21.9

PM 2.5 absorbance:

1.38 to 4.39 * 10-5

PM 2.5 mass:

PM 2.5 absorbance: 1/m PM Component: PM 2.5 mass

PM 2.5 absorbance (as a marker of diesel soot) Monitoring Stations : 40 Copollutant (correlation):

NO 2 : r = 0.99

PM 2.5 absorbance and NO 2 : r = 0.95

PM 2.5 mass and PM 2.5 absorbance: r = 0.96 Age of 2 yr: All: 1.20 (1.02-1.42) Males: 1.25 (1.01-1.55) Females: 1.13 (0.86-1.48) Bronchitis (PM 2.5 mass) Age of 1 yr: All: 0.98 (0.80-1.20) Males: 0.97 (0.76-1.25) Females: 0.98 (0.68-1.41) Age of 2 yr: All: 0.92 (0.78-1.09) Males: 0.92 (0.74-1.14) Females: 0.91 (0.68-1.21) Resp Infections (PM 2.5 mass) Age of 1 yr: All: 1.04 (0.91-1.19) Males: 1.04 (0.87-1.25) Females: 1.06 (0.87-1.31) Age of 2 yr: All: 0.98 (0.80-1.20) Males: 0.99 (0.74-1.31): Females: 0.98 (0.73-1.31) Sneezing/Runny Nose ( PM 2.5 mass) Age of 1 yr: All: 1.01 (0.85-1.20) Males: 0.97 (0.77-1.24) Females: 1.08 (0.84-1.41) Age of 2 yr: All: 0.96 (0.82-1.12) Males: 0.91 (0.73-1.12) Females: 1.04 (0.83-1.31) Wheeze (PM 2.5 absorbance) Age of 1 yr: All: 0.93 (0.78-1.12) Males: 0.91 (0.71-1.15) Females: 1.01 (0.74-1.37) Age of 2 yr: All: 0.98 (0.84-1.14) Males: 0.92 (0.75-1.13) Females: 1.07 (0.85-1.36) Cough W/O Infection (PM 2.5 absorbance) Age of 1 yr: All: 1.32 (1.10-1.59) Males: 1.38 (1.11-1.71) Females: 1.25 (0.87-1.78) Dry Cough At Night (PM 2.5 absorbance) Age of 1 yr: All: 1.27 (1.04-1.55) Males: 1.31 (1.04-1.67) Females: 1.16 (0.79-1.71) Age of 2 yr: All: 1.16 (0.98-1.37) Males: 1.17 (0.95-1.44) Females: 1.12 (0.84-1.48) Bronchitis (PM 2.5 absorbance) Age of 1 yr: All: 0.99 (0.81-1.22) Males: 1.00 (0.78-1.27) Females: 0.94 (0.63-1.39) Age of 2 yr: All: 0.94 (0.79-1.12) Males: 0.91 (0.72-1.13) Females: 0.95 (0.71-1.28) Resp Infections ( PM 2.5 absorbance) Age of 1 yr: All: 1.03 (0.90-1.18) Males: 1.03 (0.86-1.23) Females: 1.05 (0.85-1.30) Age of 2 yr: All: 0.99 (0.80-1.22) Males: 0.96 (0.73-1.26) Females: 1.04 (0.75-1.43) Sneezing/Runny Nose ( PM 2.5 absorbance) Age of 1 yr: All: 0.95 (0.79-1.14) Males: 0.90 (0.70-1.16) Females: 1.06 (0.80-1.39) Age of 2 yr: All: 0.92 (0.78-1.09) Males: 0.83 (0.66-1.05) Females: 1.06 (0.83-1.34))



### December 2009 E-420

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Goss et al. (2004, 055624 ) Period of Study: 1999-2000

Location: USA Outcome: Cystic Fibrosis pulmonary exacerbations, FEV 1 Age Groups: Children and adults over the age of 6 Study Design: Ccohort

N: 11484 patients Statistical Analyses: Logistic regression, t-tests, Mann-Whitney tests, Chi-squared tests, polytomous regression, multiple linear regression

Covariates: Age, sex, lung function, weight, insurance status, pancreatic insufficiency, airway colonization, genotype, median household income by census tract, zipcode. Dose-response Investigated? No Statistical Package: STATA, SAS Pollutant: PM 2.5 Averaging Time: Annual mean of 24-h avg Mean (SD): 13.7(4.2)

Percentiles: 25th: 11.8 50th(Median): 13.9

75th: 15.9 Monitoring Stations : 713 PM Increment: 10 μg/m 3 Odds Ratio Estimate [Lower CI, Upper CI]: Odds of having 2 or more pulmonary exacerbations as compared to 1 or less in 2000 1.21 (1.07 -1.33) Odds of having 1 pulmonary exacerbation as compared to no exacerbations in 2000 0.70 (0.59-0.98)

Decrease in FEV 1 155ml(115-194)

Decrease in FEV 1 in 2000 after adjusting for FEV 1 in 1999 24ml(7-40)

Reference: HertzPicciotto et al. (2005, 088678 ) Period of Study: May 1994-Mar 1999

Location: Teplice and Prachatice, Czech Republic Outcome: Developmental immunotoxicity as assessed by neonatal immunophenotypes Age Groups: Not specified: every woman who delivered in the two aforementioned districts were asked to participate Study Design: Cohort study

N: 1397 mother-infant pairs Statistical Analyses: Multiple linear regression with lymphocyte percentage as responding variable and pollutant exposure to 14day averaging period before the date of cord blood collection

Covariates: Season, length of labor, parity, number of previous stillbirths, medication during delivery, working status of mother, maternal education, exposure to active and secondhand smoke, family history of allergy, self-reports of workplace exposure to dust during pregnancy, self-reported maternal chronic or severe respiratory diseases during pregnancy. Ambient temperature and season were controlled for. Dose-response Investigated? Yes Statistical Package: SUDAAN (version 8) Pollutant: PM 2.5 Averaging Time: 24 h 14 day avg Mean (SD): Overall 24 h: 24.8 14-day avg: Teplice: 30.1

Prachatice 19.8 PM Component: PAHs Monitoring Stations : 2 stations: Teplice and Prachatice PM Increment: 25 μg/m 3 Adjusted for 3-day temperature and season, PM 2.5 exposure during the 14 days before birth was associated with reducedT-lymphocyte fractions CD4+, CD3+ and an increase in Blymphocyte fraction (CD19+). The associations were not quantitatively reported anywhere else in the paper other than in Fig 2 and Table 3



### December 2009 E-421

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (HertzPicciotto et al., 2007, 135917 ) Period of Study: 1994-98 + follow-ups at up to 4.5 yr of age for child

Location: Czech Republic districts of Teplice and Prachatice Outcome: Lower respiratory illnesses, majority being acute laryngitis, tracheitis, bronchitis.

ICD10 codes J04 and J20 Age Groups: Birth-4.5 yr of age. Study Design: Longitudinal follow up of a stratified random sample of mother-infant pairs from previous Pregnancy Outcome Study. Low birth weight and preterm births sampled at higher fractions.

N: 1133 children Statistical Analyses: Generalized linear longitudinal models, GEE to adjust for within subject correlations, robust variance estimates were obtained. Model fit judged using Akaike Information criterion.

Covariates: Age of child, breast feeding, environmental tobacco smoke, season, day of week, yr of birth, gender, birth weight, pregnancy data including age at delivery, length of gestation, maternal hypertension and diabetes, infant APGAR score, maternal work history, demographics, lifestyle, reproductive and medical histories, temperature, fuel type, other children in household Dose-response Investigated? No Statistical Package: SUDAAN version 8 Pollutant: PM 2.5 Averaging Time: Used 3-, 7-, 14-, 30- and 45-day avg Mean (SD): Daily mean 22.3 (sd 16 for 3-day avg, 11 for 45-day avg) PM Increment: 25 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Bronchitis, birth-23 mo of age Categorical model High 30-day avg PM 2.5 (greater than 50 μg/m 3 ) 2.26(1.81-2.82) Medium 30-day avg PM 2.5 (between 25 and 50 μg/m 3 ) 1.48(1.32-1.65) Continuous model 1.30(1.08-1.58) Bronchitis, 2-4.5 yr of age Categorical model High 30-day avg PM 2.5 (greater than 50 μg/m 3 ) 3.66(2.07-6.48) Medium 30-day avg PM 2.5 (between 25 and 50 μg/m 3 ) 1.60(1.41-1.82) Continuous model 1.23(0.94-1.62) Notes: Results of other averaging periods shown in plots.

Reference: (Hogervorst et al., 2006, 156559 ) Period of Study: NR

Location: Maastricht, the Netherlands (six schools selected) Outcome: Decreased lung function Age Groups: 8-13 yr old Study Design: Multivariate linear regression (enter method) analysis

N: 342 children Statistical Analyses: ANOVA, Chi square Covariates: Independent variables: Age, height, gender, smoking at home by parents, pets, use of ventilation hoods during cooking, presence of unvented geysers, tapestry in the home, indoor/outdoor time, education level of parents. Dependent variables: lung function indices Dose-response Investigated? No Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): 19.0 (3.2) Monitoring Stations : 6 Copollutant:

PM 10 TSP PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag:

FEV 3.62 [0.50,7.63]

FVC 1.80 [-2.10, 5.80]

FEF 5.93 [-2.34, 14.89]



### December 2009 E-422

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Islam et al. (2007, 090697 ) Period of Study: 1993-2001

Location: 12 communities in Southern California, U.S. Outcome: New onset asthma Age Groups: 9-10 yr Study Design: Cohort

N: 2057 Statistical Analyses: Cox proportional hazard model

Covariates: Community, sex, race/ethnicity

Season: All Dose-response Investigated? No Statistical Package: SAS V 9.1 Lags Considered: 0-2 yr Pollutant: PM 2.5 Range (Min, Max):

“Low” PM 2.5 Communities (5.7-8.5) “High” PM 2.5 Communities (13.7-29.5) Monitoring Stations : 12 Copollutant: NO 2 , acid vapor, PM 10 and elemental and OC correlated as a “non-O 3 package” of pollutants with a similar pattern relative to each other across the 12 communities. PM Increment: NR IR Estimate [Lower CI, Upper CI] Low PM FVC ≤ 90: 19.4 (7.5, 50.5) FVC 90-110: 16.8 (7.0, 40.1) FVC >110: 7.9 (2.9, 21.9) FEV 1 ≤ 90: 23.7 (9.4, 59.4) FEV 1 90-110: 15.6 (6.5, 37.4) FEV 1 >110: 6.5 (2.3, 18.7) FEF25-75 ≤ 90: 21.1 (8.8, 50.5) FEF25-75 90-110: 11.9 (4.7, 30.0) FEF25-75 >110: 6.4 (2.3, 18.2) Overall: 14.2 (7.0, 28.7) High PM FVC ≤ 90: 14.2 (5.1, 39.6) FVC 90-110: 25.6 (11.1, 59.2) FVC >110: 16.7 (6.5, 42.9) FEV 1 ≤ 90: 20.8 (8.0, 54.0) FEV 1 90-110: 23.1 (10.0, 53.7) FEV 1 >110: 18.8 (7.5, 47.3) FEF25-75 ≤ 90: 23.8 (10.2, 55.6) FEF25-75 90-110: 23.9 (9.9, 57.7) FEF25-75 >110: 15.9 (6.3, 40.5) Overall: 18.4 (9.4, 35.9) Reference: Karr et al. (2007, 090719 ) Period of Study: 1995-2000

Location: South Coast Air Basin of southern California Outcome: Bronchioloitis Study Design: Case-control. Cases included subjects with a record of a single hospitalization with a discharge diagnosis of acute bronchiolitis.10 controls per case were matched on birth date and gestational age.

N: 18,595 cases 169,472 controls Statistical Analyses: Conditional logistic regression to estimate relative risk of hospitalization for bronchiolitis.

Covariates: Confounders included in the model were: gender, parity, chronic lung disease, cardiac and pulmonary anomalies, SES covariates Age, Gestational age, and season of birth were controlled for by matching Dose-response Investigated? Yes Statistical Package: STATA (Version 8) Pollutant: PM 2.5 Averaging Time: 24 h (lifetime monthly avg from birth & 30 days preceding cases hospitalization) Mean (SD): 25

Percentiles: 25th: 19 50th(Median): 23

75th: 29 Range (Min, Max): 6 to 111 Monitoring Stations: 17 PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] Sub-chronic and chronic exposure: OR = 1.09 (1.04-1.14) Adjusted for adjusted: Sub-chronic OR = 1.10 (1.04, 1.16) Chronic OR = 1.09 (1.03-1.15) Adjusted for CO and NO 2 : Sub-chronic OR = 1.14 (1.07, 1.21) Chronic OR = 1.12 (1.06, 1.20) Adjusted for O 3 , CO, and NO 2 : Chronic OR = 1.15 (1.08, 1.22) Sub-chronic OR = 1.13 (1.06, 1.21)

Reference: (Kim et al., 2004, 087383 ) Period of Study: Mar-Jun (spring) 2001 Sep-Nov (fall) 2001

Location: Alameda County, CA Outcome: Asthma, bronchitis Age Groups: Children (grades 3-5) Study Design: Cross-sectional

N: 1109 children, 871 (long term resident children), 462 (long term related females), 403 (long term related males) Statistical Analyses: 2-stage multiple logistic regression model

Covariates: Respiratory illness before age of 2, household mold/moisture, pests, maternal history of asthma (for asthma) Season: spring and fall Dose-response Investigated? Yes Statistical Package: SAS 8.2 Pollutant: PM 2.5 Averaging Time: 10 wk Mean (SD): Study Avg 12 Monitoring Stations : 10 Copollutant (correlation): r2 is approximately 0.9 for all copollutants-Black Carbon (BC), PM 10 , NO X , NO 2 , NO (NO X -NO 2 ) PM Increment: 0.7 (IQR) OR Estimate [Lower CI, Upper CI]: Bronchitis All subjects: 1.02 [1.00, 1.08] LTR subjects: 1.03 [1.01, 1.08] LTR females: 1.04 [1.02, 1.05] LTR males: 1.02 [0.99, 1.05] Asthma All subjects: 1.00 [0.96, 1.12] LTR subjects: 1.01 [0.97, 1.06] LTR females: 1.06 [0.99, 1.15] LTR males: 0.99 [0.95, 1.04] Asthma excluding outlier school having a larger proportion of Hispanics All subjects: 1.04 [0.96, 1.12] LTR subjects: 1.03 [0.94, 1.13] LTR females: 1.03 [0.91, 1.17] LTR males: 1.03 [0.94, 1.18]



### December 2009 E-423

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Leonardi et al. (2000, 010272 ) Period of Study: 1996

Location: 17 cities of Central Europe (Bulgaria, Czech Republic, Hungary , Poland, Romania, Slovakia) Outcome: Immune biomarkers Age Groups: 9-11 Study Design: Cross-sectional

N: 366 school children Statistical Analyses: Linear regression

Covariates: Age, gender, parental smoking, laboratory of analysis, recent respiratory illness Dose-response Investigated? No Statistical Package: STATA Pollutant: PM 2.5 Averaging Time: Annual PM 2.5 Mean (SD): PM 2.5 : 46 (10) Range (Min, Max):

PM 2.5 : (29, 67) 5th, median, & 95th percentile

PM 2.5 : 29, 44, 67 % Change (Lower CI, Upper CI) p-value PM 2.5 Neutrophils -10 (-45, 46) >.20 Total lymphocytes 49 (11, 101); .008 B lymphocytes 63 (4, 155); .034 Total T lymphocytes 72 (32 123) <.001 CD4+ 80 (34 143) <.001 CD8+ 61 (17, 119); .003 CD4/CD8 16 (-17, 62) >.20 NK 63 (3, 158); .035 Total IgG 24 (2, 52); .034 Total IgM -9 (-32, 22) >.20 Total IgA -1 (-25, 32) >.20 Total IgE -4 (-61, 137) >.20 Reference: McConnell (1999, 007028 ) Period of Study: 1993

Location: Southern California Outcome: Bronchitis, chronic cough, phlegm Age Groups: Children: 4th, 7th, & 10th graders Study Design: Cross-sectional

N: 3676 people Statistical Analyses: Logistic regression

Covariates: Age, sex, race, grade, health insurance Dose-response Investigated? Yes Pollutant: PM 2.5 Averaging Time: Yearly 2-wk avg Mean (SD): 15.3 Range (Min, Max): 6.7, 31.5 Copollutant (correlation):

NO 2 r = 0.83

O 3 r = 0.50

Acid r = 0.71 Child Respiratory symptoms OR Estimate (Lower CI, Upper CI)

PM 2.5 Increment: 15 μg/m 3 Children w/ asthma Bronchitis: 1.4 (0.9, 2.3) Phlegm: 2.6 (1.2, 5.4) Cough: 1.3 (0.7, 2.4) Children w/ wheeze, no asthma Bronchitis: 0.9 (0.6, 1.4) Phlegm: 1.0 (0.6, 1.8) Cough: 1.1 (0.6, 1.9) Children w/ no wheeze, no asthma Bronchitis: 0.5 (0.3, 1.0) Phlegm: 0.8 (0.4, 1.5) Cough: 0.9 (0.6, 1.3) Reference: McConnell et al. (2003, 049490 ) Period of Study: 1993-1999

Location: 12 Southern CA communities Outcome: Bronchitic symptoms Age Groups: 9-19 Study Design: Communities selected on basis of historic levels of criteria pollutants and low residential mobility.

N: 475 children Statistical Analyses: 3 stage regression combined to give a logistic mixed effects model

Covariates: Sex, ethnicity, allergies history, asthma history, SES, insurance status, current wheeze, current exposure to ETS, personal smoking status, participation in team sports, in utero tobacco exposure through maternal smoking, family history of asthma, amount of time routinely spent outside by child during 2-6 pm. Dose-response Investigated? No Statistical Package: SAS Glimmix

macro Pollutant: PM 2.5 Averaging Time: 4-yr avg Mean (SD): 13.8(7.7) Range (Min, Max): 5.5-28.5 Copollutant (correlation): PM 10 : r = 0.79

PM 10-2.5 : r = 0.24 Inorganic acid: r = 0.76 Organic Acid: r = 0.58

EC: r = 0.83

OC: r = 0.84

NO 2 : r = 0.54

O 3 : r = 0.72 PM Increment: Between community range 23 μg/m 3 Between community unit 1 μg/m 3 Within community 1 μg/m 3 OR Estimate [Lower CI, Upper CI] Between community per range 1.81(1.14-2.88) Between Community per unit 1.03(1.01-1.05) Within community per unit 1.09(1.01-1.17)



### December 2009 E-424

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: McConnell et al. (2003, 049490 ) Period of Study: 1993-1999

Location: 12 Southern CA communities Outcome: Bronchitic symptoms Age Groups: 9-19 Study Design: Communities selected on basis of historic levels of criteria pollutants and low residential mobility.

N: 475 children Statistical Analyses: 3 stage regression combined to give a logistic mixed effects model

Covariates: Sex, ethnicity, allergies history, asthma history, SES, insurance status, current wheeze, current exposure to ETS, personal smoking status, participation in team sports, in utero tobacco exposure through maternal smoking, family history of asthma, amount of time routinely spent outside by child during 2-6 pm. Dose-response Investigated? No Statistical Package: SAS Glimmix

macro Pollutant: EC Averaging Time: 4-yr avg Mean (SD): 0.71(0.41) Range (Min, Max): 0.1-1.2 Copollutant (correlation): PM 2.5 : r = 0.83

PM 10 : r = 0.71

PM 10-2.5 : r = 0.30 Inorganic acid: r = 0.82 Organic Acid: r = 0.66

OC: r = 0.88

NO 2 : r = 0.54

O 3 : r = 0.68 PM Increment: Between community range 1.1 μg/m 3 Between community unit 1 μg/m 3 Within community 1 μg/m 3 OR Estimate [Lower CI, Upper CI] Between community per range 1.64(1.06-2.54) Between Community per unit 1.55(1.05-2.30) Within community per unit 2.63(0.83-8.33)

Reference: McConnell et al. (2003, 049490 ) Period of Study: 1993-1999

Location: 12 Southern CA communities Outcome: Bronchitic symptoms Age Groups: 9-19 Study Design: Communities selected on basis of historic levels of criteria pollutants and low residential mobility.

N: 475 children Statistical Analyses: 3 stage regression combined to give a logistic mixed effects model

Covariates: Sex, ethnicity, allergies history, asthma history, SES, insurance status, current wheeze, current exposure to ETS, personal smoking status, participation in team sports, in utero tobacco exposure through maternal smoking, family history of asthma, amount of time routinely spent outside by child during 2-6 pm. Dose-response Investigated? No Statistical Package: SAS Glimmix

macro Pollutant: OC Averaging Time: 4-yr avg Mean (SD): 4.5(2.7) Range (Min, Max): 1.4-11.6 Copollutant (correlation): PM 2.5 : r = 0.84

PM 10 : r = .70

PM 10-2.5 : r = 0.27 Inorganic acid: r = 0.83 Organic Acid: r = 0.69

EC: r = 0.88

NO 2 : r = 0.67

O 3 : r = 0.81 PM Increment: Between community range 10.2 μg/m 3 Between community unit 1 μg/m 3 Within community 1 μg/m 3 OR Estimate [Lower CI, Upper CI] Between community per range 1.74(0.89-3.4) Between Community per unit 1.06(0.99-1.13) Within community per unit 1.41(1.12-1.78)



### December 2009 E-425

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: McConnell, et al. (2006, 180226 ) Period of Study: 1996-1999

Location: 12 Southern California communities Outcome: Prevalence of bronchitic symptoms (yrly). Age Groups: 10-15-yr-old Study Design: Longitudinal cohort

N: 475 asthmatic children Statistical Analyses: Multilevel logistic mixed effects models.

Covariates: Age, second-hand smoke Personal smoking history Sex, race. Dose-response Investigated? No Statistical Package: SAS Pollutant: PM 2.5 Averaging Time: 365 days Percentiles: Community by yr (n = 48 = 12 communities · 4 yr) 25th: NR 50th(Median): 3.4 75th: NR Range (Min, Max): Community by yr (n = 48 = 12 communities · 4 yr): (0.89, 8.7) Monitoring Stations : 12

Copollutant: O 3 NO 2 EC OC Acid vapor (acetic and formic acid) PM Increment: 3.4 μ g/m 3 OR Estimate [Lower CI, Upper CI] PM 2.5 Dog (n = 292): 1.56 [1.15: 2.12] No dog (n = 183): 1.03 [0.71: 1.49] PM 2.5 *Dog interaction p-value: 0.06 Cat (n = 202): 1.30 [0.90: 1.88] No Cat (n = 273): 1.36 [0.99: 1.83] PM 2.5 *Cat interaction p-value: 0.87 Neither pet (n = 112): 1.11 [0.71: 1.74] Cat only (n = 71): 0.85 [0.46: 1.57] Dog only (n = 161): 1.53 [1.04: 2.25] Both pets (n = 131): 1.58 [1.02: 2.46] Results suggest that dog ownership, a source of residential exposure to endotoxin, may worsen the severity of respiratory symptoms from exposure to air pollutants in asthmatic children. Although PM 2.5 was associated at a statistically significant level with ownership of both cats and dogs, it appears that dog ownership (with or without a cat) specifically worsens the association between PM 2.5 and respiratory symptoms in asthmatic children.

Reference: (Meng et al., 2007, 093275 ) Period of Study: Nov 2000 and Sep 2001

Location: Los Angeles and San Diego counties Outcome: Poorly controlled asthma vs. controlled asthma

ICD9NR Age Groups: 18-64, 65+ Study Design: Long-term exposure study comparison of cases and controls

N: 1,609 adults (represented individuals age 18+ who reported ever having been diagnosed as having asthma by a physician and had their address successfully geocoded) Statistical Analyses: Logistic regression to evaluate associations between TD (traffic density) and annual avg air pollution concentrations and poorly controlled asthma. Used sample weights that adjusted for unequal probabilities of selection into the CHIS sample.

Covariates: Age, sex, race/ethnicity, family federal poverty level, county, insurance status, delay in care for asthma, taking medications, smoking behavior, self-reported health status, employment, physical activity Dose-response Investigated? yes Pollutant: PM 2.5 Averaging Time: 24 h Copollutant (correlation):

O 3 : r = -0.76

NO 2 : r = 0.87

PM 10 : r = 0.84

CO: r = 0.52

TD: r = 0.13 Results for PM 2.5 were nonsignificant and not reported quantitatively.



### December 2009 E-426

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Millstein, J et al. (2004, 088629 ) Period of Study: Mar-Aug 1995, and Sep 1995-Feb 1996

Data were taken from the Children’s Health Study

Location: Alpine, Atascadero, Lake Arrowhead, Lake Elsinore, Lancaster, Lompoc, Long Beach, Mira Loma, Riverside, San Dimas, Santa Maria, and Upland, CA Outcome: Wheezing & asthma medication use (ICD 9 NR) Age Groups: 4th grade students, mostly 9 yr at the time of the study Study Design: Cohort Study, stratified into 2 seasonal groups/

N: 2081 enrolled, 2034 provided parent-completed questionnaire. Statistical Analyses: Multilevel, mixed-effects logistic model.

Covariates: Contagious respiratory disease, ambient airborne pollen and other allergens, temperature, sex, age race, allergies, pet cats, carpet in home, environmental tobacco smoke, heating fuel, heating system, water damage in home, education level of questionnaire signer, physician diagnosed asthma.

Season: Mar-Aug, 1995, and Sep, 1995 to Feb, 1996 Statistical Package: GLIMMIX SAS 8.00 macro for generalized linear mixed models. Lags Considered: 14 Pollutant: PM 2.5 Averaging Time: Integrated values for successive 2-wk periods PM Component: Nitric acid, formic acid, acetic acid Monitoring Stations : 1 central location in each community Copollutant (correlation):

O 3 : r = 0.09

NO 2 : r = 0.28

PM 10 : r = 0.33

PM 10-2.5 : r = -0.08 PM Increment: IQR: 5.24 μg/m 3 Odds Ratio [lower CI, Upper CI]

Annual

PM 2.5 : 1.04 [0.83, 1.29] Mar-Aug

PM 2.5 : 0.91 [0.64, 1.30] Sep-Feb

PM 2.5 : 1.18 [0.89, 1.58]

Reference: Morgenstern et al. (2007, 090747 ) Period of Study: Mar 1999-Jul 2000

Location: Munich, Germany Outcome: Asthma, wheezing, spastic/obstructive bronchitis. Dry cough at night, respiratory infections, sneezing, runny/stuffed nose without a cold. Age Groups: at 1 yr & at 2 yr Study Design: Cohort

N: 3577 children for the prediction models. Respiratory data available for 3129 children at 1 yr. Statistical Analyses: Pearson’s correlation coefficient, prediction error expressed as root mean squared error (RMSE), multiple logistic regression with confounding factors, odds ratios

Covariates: Sex, Parental atopy (genetic predisposition to allergies), environmental tobacco smoke at home, maternal education >or <12 yr, sibling, gas stove, home dampness, indoor mold, pets. Since it was not feasible to measure personal exposure to NO 2 , PM 2.5 , and PM 2.5 absorbance, exposure modeling was used. Statistical Package: SAS V.8.02 Pollutant: PM 2.5 Averaging Time: Annual Mean (SD): 12.8

Percentiles: 25th: 12.5 50th(Median): 12.9

75th: 13.3 Range (Min, Max): 6.8, 15.3 Monitoring Stations : 40: traffic, n = 17 and background, n = 23. Copollutant (correlation):

PM 2.5 absorbance r = 0.49

NO 2 r = 0.45 PM Increment: 1.04 μg/m 3 Odds Ratio [Lower CI, Upper CI] Adjusted OR for PM 2.5 and: sneezing, runny/stuffed nose during the first yr of life was 1.16 [1.01, 1.34] At age 1 yr For wheezing 1.01 [0.87, 1.18] For cough without infection 1.05 [0.88, 1.25] For dry cough at night1.08 [0.86, 1.27] For asthmatic, spastic, or obstructive bronchitis 1.04 [0.90, 1.29] For respiratory infection1.05 [0.88, 1.22] For sneezing, runny or stuffed nose 1.16 [1.01, 1.34] At age 2 yr For wheezing 1.10 [0.96, 1.25] For cough without infection NA, insufficient sample For dry cough at night 1.03 [0.86, 1.19] For asthmatic, spastic, or obstructive bronchitis 1.05 [0.92, 1.20] For respiratory infection 1.09 [0.94, 1.07] For sneezing, runny or stuffed nose 1.19 [1.04, 1.36]



### December 2009 E-427

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Morgenstern et al. (2007, 090747 ) Period of Study: May 1999-Jul 2000

Location: Munich, Germany Outcome: Asthma, wheezing, spastic/obstructive bronchitis. Dry cough at night, respiratory infections, sneezing, runny/stuffed nose without a cold. Age Groups: at 1 yr & at 2 yr Study Design: Cohort

N: 3577 children for the prediction models. Respiratory data were available for 3129 children at 1 yr. Statistical Analyses: Pearson’s correlation coefficient, prediction error expressed as root mean squared error (RMSE), multiple logistic regression with confounding factors, odds ratios

Covariates: Sex, Parental atopy (genetic predisposition to allergies), environmental tobacco smoke at home, maternal education >or <12 yr, sibling, gas stove, home dampness, indoor mold, pets. Since it was not feasible to measure personal exposure to NO 2 , PM 2.5 , and PM 2.5 absorbance, exposure modeling was used. Statistical Package: SAS V.8.02 Pollutant: PM 2.5 Absorbance (PM 2.5 ab) Averaging Time: Annual Mean (SD): 1.7 10 -5 m -1,

Percentiles: 25th: 1.6 10 -5 m -1 50th(Median): 1.7 10 -5 m -1

75th: 1.8 10 -5 m -1 Range (Min, Max): 1.3, 3.2 10 -5 m -1 Unit (i.e. μg/ m 3 ): 10 -5 m -1 Monitoring Stations : 40: traffic, n = 17 and background, n = 23. PM Increment: 0.22 x 10 -5 Odds Ratio [Lower CI, Upper CI] no lag At age 1 yr For wheezing 0.97 [0.77, 1.23] For cough without infection 1.16 [0.87, 1.54] For dry cough at night1.09 [0.78, 1.51] For asthmatic, spastic, or obstructive bronchitis 1.14 [0.88, 1.48] For respiratory infections1.03 [0.86, 1.24] For sneezing, runny or stuffed nose 1.30 [1.03, 1.65] At age 2 yr For wheezing 1.09 [0.90, 1.33] For cough without infection NR insufficient data For dry cough at night1.18 [0.93, 1.50] For asthmatic, spastic, or obstructive bronchitis 0.85 [0.30, 2.34] For respiratory infections1.05 [0.79, 1.39] For sneezing, runny or stuffed nose 1.27 [1.04, 1.56]

Reference: Oftedal et al. (2008, 093202 ) Period of Study: 2001-2002

Location: Oslo, Norway Outcome: Lung function (PEF, FEF25%, FEF50%, FEV 1 , FVC) Age Groups: 9-10 yr Study Design: Cross-sectional

N: 1847 children Statistical Analyses: Linear regression

Covariates: Height, age, BMI, birth weight, temperature, maternal smoking, se Dose-response Investigated? Yes Statistical Package: SPSS, STATA, S-Plus Lags Considered: 1-3 Pollutant: PM 2.5 IQR:

PM 2.5 in 1st yr of life: 6.2

PM 2.5 lifetime: 3.6 PM Increment: Per IQR β (Lower CI, Upper CI)

PM 2.5 in 1st yr of life PEF -76.1 (-122.2 to -30.0) FEF25% -75.6 (-127.4 to -23.8) FEF 50% -62.4 (-107.4 to -17.4)

FEV 1 -12.7 (-28.8, 3.4) FVC -2.9 (-20.5, 14.7)

PM 2.5 lifetime exposure PEF -57.7 (-94.4 to -21.1) FEF25% -51.8 (-93.1 to -10.6) FEF 50% -48.4 (-84.2 to -12.6)

FEV 1 -10.4 (-23.2, 2.4) FVC -3.9 (-17.9, 10.1)

Reference: (Parker et al., 2009, 192359 ) Period of Study: 1999- 2005

Location: U.S. Outcome: Respiratory allergy/hayfever Study Design: Cohort

Covariates: Survey yr, age, family structure, usual source of care, health insurance, family income relative to federal poverty level, race/ethnicity Statistical Analysis: Logistic regression Statistical Package: SUDAAN Age Groups: 73,198 children aged 3-17 yr Pollutant: PM 2.5 Averaging Time: NR

Median: 13.1

IQR: 10.9-15.2 Copollutant (correlation):

Summer O 3 : 0.10

SO 2 : 0.21

NO 2 : 0.53

PM 10-2.5 : 0.02

PM 10 : 0.51 Increment: 10 μg/m 3 Odds Ratio (95% CI) Single Pollutant Model, variable N Adjusted: 1.16 (1.04-1.30) Single Pollutant Model, constant N Adjusted: 1.23 (1.04-1.46) Multi-pollutant Model: 1.29 (1.07-1.56)



### December 2009 E-428

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sekine et al. (2004, 090762 ) Period of Study: 1987-1994

Location: Nine districts in the Tokyo, Japan metropolitan area: Chuo ward, Ohta ward, Shibuya ward, Itabashi ward, Hachioji City, Tachikawa City, Ome City, Machida City, Tanashi City Outcome: Pulmonary function tests Age Groups: 30-59 yr Study Design: Cross-sectional and longitudinal

N: 500 females Statistical Analyses: Multiple logistic regression analysis

Covariates: Group (classification by air pollution level), pulmonary function at initial test, age and height at the time of the initial test, number of yr investigated, yr of residence in the area, type of heater, housing structure, and job status. Dose-response Investigated? No Statistical Package: SAS Pollutant: Suspended PM (SPM) Averaging Time: Measured each month for three consecutive days (72 h) Mean (SD): 28.1-63.3 Range (Min, Max): 3.4-140.6 Copollutant (correlation): NO 2 Results of multiple logistic regression analysis for respiratory symptoms Persistent cough Group 3: OR = 1.00 Group 2: OR = 1.02 (0.70-1.48) Group 1: OR = 1.07 (0.67-1.70) Persistent phlegm Group 3: OR = 1.00 Group 2: OR = 1.51 (1.11-2.04) Group 1: OR = 1.78 (1.26-2.53) Asthma Group 3: OR = 1.00 Group 2: OR = 1.99 (0.82-4.83) Group 1: OR = 2.66 (0.98-7.19) Wheeze Group 3: OR = 1.00 Group 2: OR = 1.39 (0.95-2.01) Group 1: OR = 1.34 (0.85-2.11) Breathlessness Group 3: OR = 1.00 Group 2: OR = 0.84 (0.47-1.50) Group 1: OR = 2.70 (1.48-4.91)

Reference: Sharma et al. (2004, 156974 ) Period of Study: Nov 2002-Apr 2003

Location: 3 sections in Kanpur City, India 1) Indian Institute of Technology Kanpur (IITK) 2) Vikas Nagar (VN) 3) Juhilal Colony (JC) Outcome: Lung function Age Groups: 20-55 yr Study Design: Cohort

N: 91 people Statistical Analyses: Linear regression

Covariates: NR

Season: Fall, Winter, spring Dose-response Investigated? No Statistical Package:

Microsoft Excel Lags Considered: 1 day lag & 5-day ma Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): IITK 158 (22) VN 85 (30) JC 59 (9) PM Component: Lead, Nickel , Cadmium , Chromium , Iron , Zinc Benzene soluble fraction (includes polycyclic aromatic hydrocarbons [PAHs]) Copollutant (correlation): Δ PEF = mean daily deviations in PEF PM 2.5 - Δ PEF: -0.30 PM 2.5 -PM 10 : 0.67 PM 2.5 -PM 10 (1-day lag): 0.49 PM 2.5 -PM 2.5 (1-day lag): 0.88 PM Increment: 1 μg/m 3

Δ PEF (difference or change in peak expiratory flow)

-0.0297 L/min

Reference: (Singh et al., 2003, 052686 ) Period of Study: NR

Location: Jaipur, India Outcome: Lung function (peak expiratory flow variability) Age Groups: Medical school-aged students Study Design: Cross sectional

N: 313 nonsmoker students Statistical Analyses: Amplitude % mean was used as the measure of PEF variability. Mean value of amplitude % mean of peak flow variability were compared for in the two groups by application of Student’s t-test. The two groups were: living on campus and commuters. Dose-response Investigated? Yes Pollutant: Respirable suspended PM (RSPM) Averaging Time: 8 h Mean (SD): Roadside: 1,666 Campus: 177 Monitoring Stations : 2 It appears that no associations between particulates and the outcome of interest were calculated and reported in this study



### December 2009 E-429

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Solomon et al., 2003, 087441 ) Period of Study: 1966-1997

Location: United Kingdom: Northern England, North-West Midlands, and Wales. Outcome: Cardio-respiratory morbidity Age Groups: 45 yr and older Study Design: Cross-sectional

N: 1,166 women Statistical Analyses: Prevalence ratios were reported for ischemic heart disease, asthma, productive cough, wheeze, and use of an inhaler for asthma or other breathing problems.

Covariates: Smoked, passive smoking in childhood, tenancy, SES, worked in industry with respiratory hazards, childhood admission to hospital for chest problem, diabetes, BMI were all controlled for as potential confounders. Dose-response Investigated? yes Statistical Package: STATA Pollutant: Black Smoke Averaging Time: Annual RR Estimate [Lower CI, Upper CI] The findings provide no indication that prolonged residence in places that have had relatively high levels of particulate air pollution causes an important increase in cardio-respiratory morbidity. Prevalence ratios are based on high vs. low pollution with low as referent. Particulate pollution in place of residence: Rr = 1.0 (0.7-1.4) for ischemic heart disease; Rr = 0.7 (0.5-1.0) for asthma Rr = 1.0 (0.7 -1.5) for productive cough

Reference: Suglia et al. (2008, 157027 ) Period of Study: Mar 1986-Oct 1992

Location: Boston, MA Outcome: Lung function Age Groups: 18-42 Study Design: Prospective cohort

N: 272 women of childbearing age Statistical Analyses: Linear regression

Covariates: Height, age, weight, race/ethnicity, yr, education Dose-response Investigated? yes-tertiles of exposure Statistical Package: SAS v. 9.0 Pollutant: Black Carbon (BC) Averaging Time: Annual Mean (SD): 0.62 (0.15) PM Increment: 0.22 μg/m 3 (IQR) Effect Estimate [Lower CI, Upper CI] FEV : -1.08 (-2.5, 0.3) 1 FVC: -0.62 (-1.9, 0.6) FEF25-75%: -2.97 (-5.8 to -0.2) Current Smokers: FEV 1 : 0.62 (-2.1, 3.4) FVC: 0.64 (-2.0, 3.3) FEF25-75%: -2.63 (-3.7, 8.9) Former Smokers: FEV 1 : -4.40 (-7.8 to -1.0) FVC: -3.11 (-6.1 to -0.2) FEF25-75%: -8.78 (-14.7 to -2.9) Nonsmokers: FEV : -0.98 (-2.9, 0.9) 1 FVC: -0.32 (-2.0, 1.4) FEF25-75%: -4.39 (-8.1 to -0.6) Exposure-response relationship presented graphically in Fig 1: the highest BC exposure group had decreases in FEV 1 , FVC, and FEF25-75% compared with the lowest tertile group, although these differences were not statistically significant.

Reference: (Sunyer et al., 2006, 089771 ) Period of Study: initial selection: 1991-1993, follow-up Jun 2000-Dec 2001

Location: 21 centers in 10 European countries Outcome: Chronic bronchitis Age Groups: Mean age (range) Males- 42.62 (38.12-45.62) Females- 42.57 (39.92-45.69) Study Design: Hierarchical models

N: 6924 Statistical Analyses: General additive models (GAM)

Covariates: Smoking, age at end of education, occupational group, occupational exposures, respiratory infections during childhood, rhinitis, asthma, traffic intensity at household level. Statistical Package: STATA-8 Pollutant: PM 2.5 Averaging Time: 18 mo Mean (SD): 3.7-44.9 Copollutants: NO 2 , SO 2 PM Increment: NR Odds ratio [Lower CI, Upper CI] Chronic phlegm prevalence at follow up Males: 0.97 [0.70,1.35]



### December 2009 E-430

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Zhang et al. (2002, 034814 ) Period of Study: 1993-1996

Location: 4 Chinese cities (urban and suburban location in each city): Guangzhou, Wuhan, Lanzhou, Chongqing Outcome: Interview-self reports of symptoms: Wheeze (ever wheezy when having a cold) Asthma (diagnosis by doctor) Bronchitis (diagnosis by doctor) Hospitalization due to respiratory disease (ever) Persistent cough (coughed for at least 1 month per yr with or apart from colds) Persistent phlegm (brought up phlegm or mucus from the chest for at least 1 month per yr with or apart from colds). Age Groups: Elementary school students age range: 5.4-16.2 Study Design: Cross-sectional

N: 7,557 returned questionnaires 7,392 included in first stage of analysis Statistical Analyses: 2-stage regression approach:

Calculated odds ratios and 95% CIsof respiratory outcomes and covariates Second stage consisted of variance-weighted linear regressions that examined associations between district-specific adjusted prevalence rates and district-specific ambient levels of each pollutant.

Covariates: Age, gender, breast-fed, house type, number of rooms, sleeping in own or shared room, sleeping in own or shared bed, home coal use, ventilation device used, homes smokiness during cooking, eye irritation during cooking, parental smoking, mother’s education level, mother’s occupation, father’s occupation, questionnaire respondent, yr of questionnaireadministration, season of questionnaire administration, parental asthma prevalence. Pollutant: PM 2.5 Averaging Time: 2 yr Mean (SD): 92 (31)

Percentiles:

25th: NR 50th(Median): NR

75th: NR

IQR: 39 Range (Min, Max): Gives range (max.-min.):

PM 2.5 -98 Monitoring Stations : 2 types: municipal monitoring stations over a period of 4 yr (1993-1996) schoolyards of participating children over a period of 2 yr (1995-1996) PM Increment: Interquartile range corresponded to 1 unit of change. RR Estimate [Lower CI, Upper CI] lag:

No association between PM 2.5 and any type of respiratory morbidity. No between or within city association between PM 2.5 and any type of respiratory morbidity. When scaled to an increment of 50 μg/m 3 increase in PM 2.5 , association (ORs) between respiratory outcome and PM 2.5 was: Wheeze: 1.06

Asthma: 1.29

Bronchitis: 1.68 Hospitalization: 1.08 Persistent cough: 1.24 Persistent phlegm: 3.09

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-431

# Table E-25. Long-term exposure - respiratory mo rbidity outcomes - other PM size fractions.

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: El-Zein et al. (2007, 093043 ) Period of Study: 2000-2004

Location: Beirut, Lebanon ED Admissions

Outcome: Acute respiratory symptoms: asthma, URTI, pneumonia, bronchitis Age Groups: <17 Study Design: Ecological (natural experiment comparing admissions before and after ban on diesel fuel)

N: 5 hospitals, 7573 admissions OctFeb, 4303 admissions Oct-Dec Statistical Analyses: T-test, Poisson regression

Covariates: Month of Year, temperature, humidity, orthogonalized rainfall

Season: Oct-Dec (excluding flu season) and Oct-Feb Dose-response Investigated? No Statistical Package: NR Lags Considered: 1-2 yr before the ban compared to 1-2 yr after the ban Pollutant: PM from diesel Range (Min, Max): NR PM Component: NR Monitoring Stations: 1

Notes: Did not look at specific exposure data looked at outcome with respect to a timeline that plotted admissions before and after a ban on diesel fuel. Copollutant: NR PM Increment: NA β (p-value): 2-yr pre-ban vs. 2-yr post-ban Oct to Feb All Resp: 0.128 (0.32) Asthma: -0.176 (0.16) Bronchitis: 0.505 (0.02) Pneumonia: 0.287 (0.17) URTI: -0.265 (0.41) Oct to Dec All Resp: -0.022 (0.87) Asthma: -0.21 (0.07) Bronchitis: 0.2 (0.35) Pneumonia: -0.065 (0.78) URTI: -0.628 (0.05) 2-yr pre-ban vs. 1-yr post-ban Oct-Feb All Resp: -0.093 (0.45) Asthma: -0.208 (0.05) Bronchitis: 0.286 (0.32) Pneumonia: -0.07 (0.76) URTI: -0.715 (0.11) Oct to Dec All Resp: -0.147 (0.02) Asthma: -0.147 (0.00) Bronchitis: -0.011 (0.96) Pneumonia: -0.214 (0.15) URTI: -0.885 (0.06) 1-yr pre-ban vs. 1-yr post-ban Oct-Feb All Resp: -0.165 (0.04) Asthma: -0.212 (0.09) Bronchitis: 0.059 (0.85) Pneumonia: -0.034 (0.84) URTI: -1.023 (0.00) Oct to Dec All Resp: -0.17 (0.00) Asthma: -0.131 (0.00) Bronchitis: -0.145 (0.001) Pneumonia: -0.168 (0.12) URTI: -1.036 (0.00) Reference: Kasamatsu et al. (2006, 156627 ) Period of Study: 2001-2002

Location: Shenyang, China Outcome: FVC, FEV 1 , PEF, FEF75 Age Groups: School Children aged 8- 10 Study Design: Children in three schools in three types of areas (commercial city area, residential city area, residential suburban area) invited to participate

N: 322 children participated, 244 have complete data. Statistical Analyses: Genralized estimating equations

Covariates: Age, height, Dose-response Investigated? No Statistical Package: SAS Lags : Considered: previous quarter. Pollutant: PM 7 Averaging Time: Avg of 4 separate 2-7 consecutive day measurements within each designated measurement month of the quarter Mean (SD): School A 7/2001 86.4(14.2) 10/2001 114.1(35.1) 1/2002 118.2(28.2) 4/2002 182.7(102.1) School B 7/2001 90.1(8.3) 10/2001 161.5(45.7) 1/2002 118.8(28.2) 4/2002 152.0(31.3) School C 7/2001 78.1(16.9) 10/2001 131.2(29.6) 1/2002 142.2(37.6) 4/2002 173.6(121.5) PM Component: mainly pollutants associated with coal heating Monitoring Stations : 1 at each location PM Increment: 63.0 μg/m 3 Mean change of pulmonary function value [Lower CI, Upper CI] at lag 0 Boys FVC -0.095(-0.170,-0.019) FEV 1 -0.088(-0.158,-0.019) PEF -0.170(-0.365,0.032) FEF75 -0.063(-0.183,0.050) Girls FVC -0.082(-0.145,-0.019) FEV 1 -0.069(-0.126,-0.006) PEF 0.095(-0.095,0.290) FEF75 -0.032(-0.151,0.082) Mean change of pulmonary function value [Lower CI, Upper CI] at lag 1(previous quarter) Boys FVC -0.145(-0.189,-0.095) FEV 1 -0.095(-0.139,-0.057) PEF -0.082(-0.208,0.050) FEF75 0.013(-0.063,0.088) Girls FVC -0.126(-0.170,-0.088) FEV 1 -0.101(-0.139,-0.063) PEF -0.101(-0.227,0.025) FEF75 -0.057(-0.132,0.019)



### December 2009 E-432

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Kasamatsu et al.(2006, 156627 ) Period of Study: 2001-2002

Location: Shenyang, China Outcome: FVC, FEV 1 , PEF, FEF75 Age Groups: School Children aged 8- 10 Study Design: Children in three schools in three types of areas (commercial city area, residential city area, residential suburban area) invited to participate

N: 322 children participated, 244 have complete data. Statistical Analyses: Genralized estimating equations

Covariates: Age, height, Dose-response Investigated? no Statistical Package: SAS Lags: Considered: previous quarter. Pollutant: PM 2.1 Averaging Time: Avg of 4 separate 2-7 consecutive day measurements within each designated measurement month of the quarter Mean (SD): School A 7/2001 47.6(6.4) 10/2001 54.2(20.5) 1/2002 68.9(15.8) 4/2002 115.8(76.7) School B 7/2001 45.6(6.5) 10/2001 74.4(27.1) 1/2002 63.3(17.9) 4/2002 96.3(27.6) School C 7/2001 42.5(9.5) 10/2001 59.7(13.1) 1/2002 76.4(22.1) 4/2002 123.0(100.9) PM Component: mainly pollutants associated with coal heating Monitoring Stations : 1 at each location PM Increment: 42.1 μg/m 3 Mean change of pulmonary function value [Lower CI, Upper CI] at lag 0 Boys FVC -0.126(-0.181,-0.076) FEV 1 -0.122(-0.173,-0.076) PEF -0.164(-0.303,-0.025) FEF75 -0.046(-0.131,0.038) Girls FVC -0.110(-0.156,-0.067) FEV 1 -0.101(-0147,-0.059) PEF 0.008(-0.131,0.147) FEF75 -0.055(-0.139,0.030) Mean change of pulmonary function value [Lower CI, Upper CI] at lag 1(previous quarter) Boys FVC -0.099(-0.145,-0.053) FEV 1 -0.059(-0.106,-0.020) PEF -0.040(-0.158,0.086) FEF75 0.026(-0.046,0.092) Girls FVC -0.086(-0.125,-0.046) FEV 1 -0.066(-0.106,-0.026) PEF -0.079(-0.198,0.040) FEF75 -0.033(-0.106,0.040)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-433

# E.6. Long-Term Exposure and Cancer

Table E-26. Long-term exposure - cancer outcomes - PM 10 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Abbey et al., 1999, 047559 ) Period of Study: 1977-1992

Location: California Outcome (ICD9): Lung Cancer Mortality (162) Age Groups: 27-95 at baseline Study Design: Cohort (AHSMOG)

N: 6,338 nonsmoking CA Seventh-Day Adventists Statistical Analyses: Time-dependent, gender-specific, Cox proportional hazards regression models

Covariates: Age, smoking, education, occupation, BMI Pollutant: PM 10 Averaging Time: Monthly estimates from 1966-1992 Mean (SD): 51.24 (16.63)

Percentiles: IQR: 24.08 Range (Min, Max): 0, 83.9 Correlations: SO 4 : r = 0.68) SO : r = 0.31

2 O : r = 0.77

3 NO 2 : r = 0.56 Lag: 3 yr PM Increment: 24.08 (IQR) RR, males: 3.36 [1.57, 7.19] RR, females: 1.33 [0.60, 2.96]

PM 10 above 100μg/ m 3 (days per yr) IQR: 43 days/yr Males: 2.38 (1.42, 3.97) Females: 1.08 (0.55, 2.13)

Reference: Beeson et al. (1998, 048890 ) Period of Study: 1977-1992

Location: California Outcome (ICD9: Lung Cancer Mortality (ICDO-1: 162, ICDO-2: C34.0-C34.9) Age Groups: 27-95 at baseline Study Design: Cohort (AHSMOG)

N: 6,338 nonsmoking CA Seventh-Day Adventists (non-Hispanic white) Statistical Analyses: Time-dependent, gender-specific, Cox proportional hazards regression models

Covariates: Smoking, Education, Age, Alcohol Statistical Package: SAS Lags Considered: 3 yr Pollutant: PM 10 Averaging Time: Averaged monthly estimates from 1966-1992 Mean (SD): 51 (16.52)

Percentiles: IQR: 24 Range (Min, Max): 0, 84 PM Increment: 24 (IQR) RR, males: 5.21 [1.94, 13.99] RR, females: Positive, but not statistically significant

Reference: Binkova et al. (2007, 156273 ) Period of Study: Feb 2001

Location: Prague, Czech Republic Outcome: Total DNA adducts (bulky aromatic PAH-DNA adducts and ... Age Groups: 22-50 yr Study Design: Case Control

N: 53 occupationally exposed policemen and 52 control policemen Statistical Analyses: Multivariate logistic regression, Mann-Whitney u-test

Covariates: Smoking. Vitamin C, polymorphisms of XPD repair gene in exon 23 and 6 and GSTM 1 and XRCC1 genes

Season: Winter Pollutant: PM 10 Range (Min, Max): 32-55 Monitoring Stations: 2 (and personal monitors) No relationship between short term exposure to C-PAHs evaluated by personal monitors and DNA adduct level. Genetic damage was observed in city policemen working in winter outdoors in the Prague downtown area they had slightly elevated aromatic DNA adduct levels, which was statistically significant for a distinct DNA adduct spot that could originate from ambient exposure to B[ α ]P.

Total PAH-DNA adducts : p = 0.065 Exposed: 0.92 ± 0.28 adducts/108 nucleotids

Control: 0.82 ± 0.23 adducts/108 nucleotids B[ α ]P-like adducts: Exposed: 0.122 ± 0.36 adducts/108 nucleotids

Control: 0.099 ± 0.035 adducts/108 nucleotids Multiple regression “like” B[ α ]P-DNA adduct for air pollution exposure group: B = 0.016, p = 0.01



### December 2009 E-434

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Liu et al., 2009, 190292 ) Period of Study: 1995-2005

Location: Taiwan Outcome: Bladder Cancer Mortality (ICD-9 188) Age Groups: 50-69 Study Design: Case-crossover Statistical Analysis: Multiple Logistic Regression Statistical Package: NR

Covariates: none Dose-response Investigated? No Pollutant: PM 10 Averaging Time: Annual mean of 24-h avg Tertiles (median): T1: ≤ 52.80 T2: 53.04-71.72 T3: 72.24-90.29 Copollutant: O 3 , CO, NO 2 , SO 2 Copollutant (correlation): NR Monitoring Sattions: 64 Increment: Odds Ratio (Min CI, Max CI) Lag T1 vs. T1: 1.00 (ref) T2 vs. T1: 1.08 (0.83-1.41) T3 vs. T1: 1.39 (1.06-1.83)

P for trend = .020

Reference: (Pope et al., 2002, 024689 ) Period of Study: 1982-1998

Location: 50 U.S. states, District of Columbia, and Puerto Rico Outcome (ICD9): Lung cancer mortality (162) Age Groups: Ages >30 yr Study Design: Longitudinal cohort (Cancer Prevention Study II)

N: 1.2 million people Statistical Analyses: Cox proportional hazard, generalized additive

Covariates: Age, sex, race, education, smoking status, marital status, occupational exposure, diet, body-mass index, alcohol consumption Pollutant: PM 10 Mean (SD): 1982-1998: 28.8(5.9) Effect estimates: Effect estimates were recorded in Fig 5 and not presented quantitatively anywhere else

Reference: Sram et al, (2007, 188457 ) Period of Study: Jan and Mar of 2004

Location: Prague, Czech Republic Outcome: Chromosomal aberrations Study Design: Panel

Covariates: Urinary cotinine, plasma levels of vitamins A, E and C, folate, total cholesterol, HDL and LDL cholesterols, and triglycerides Statistical Analysis: Bivariate correlations, ANOVA, Mann-Whitney, Kruskal-Wallis and Spearman rank correlation Statistical Package: STATISTICA Age Groups: 61 city policemen, aged 34 ± 8 yr, spending 8+ h outdoors Pollutant: PM 10 Averaging Time: NR Mean (SD) Unit: Jan: 55.6 μg/m 3 Mar: 36.4 μg/m 3 Copollutant: PM 2.5 Results not given by PM increment.

Reference: Sram et al, (2007, 188457 ) Period of Study: Jan and Mar of 2004

Location: Prague, Czech Republic Outcome: Chromosomal aberrations Study Design: Panel

Covariates: Urinary cotinine, plasma levels of vitamins A, E and C, folate, total cholesterol, HDL and LDL cholesterols, and triglycerides Statistical Analysis: Bivariate correlations, ANOVA, Mann-Whitney, Kruskal-Wallis and Spearman rank correlation Statistical Package: STATISTICA Age Groups: 61 city policemen, aged 34 ± 8 yr, spending 8+ h outdoors Pollutant: PM 2.5 Averaging Time: NR Mean (SD) Unit: Jan: 44.4 μg/m 3 Mar: 24.8 μg/m 3 Copollutant: PM 10 Results not given by PM increment.



### December 2009 E-435

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Tarantini et al., 2009, 192010 )Period of Study: NR

Location: Brescia, Italy Outcome: DNA methylation content estimated by Alu, LINE-1 and iNOS analysis Study Design: Panel

Covariates: age, BMI, smoking, number of cigarettes/day Statistical Analysis: Mixed effects models Statistical Package: NR Age Groups: 63 male workers between 27 and 55 yr, mean age 44. Pollutant: PM 10 Averaging Time: NR Mean (SD) Unit: NR Individual Exposure Range: 73.4- 1220 μg/m 3 Copollutant (correlation): NR Difference in DNA Methylation before and after work exposure, mean (SE) Alu (%5mC): 0.00 (0.08), p = 0.99 LINE-1 (%5mC): 0.02 (0.11), p = 0.89 iNOS (%5mC): -0.61 (0.26), p = 0.02

Reference: (Vineis et al., 2006, 192089 ) Period of Study: 1990-1999

Location: 10 European countries Outcome: Lung cancer Study Design: Nested case-control

Covariates: Age, sex, country, smoking status, time since recruitment, education, BMI, physical activity, intake of fruit, vegetables, meat, alcohol and energy Statistical Analysis: Conditional logistic regression models Statistical Package: NR Age Groups: 35-74 at recruitment Pollutant: PM 10 Averaging Time: NR Mean by Country (μg/ m 3 ): France Ile-de-France 1990-1994: 22.3 1995-1999: 19.9 Northeast France 1990-1994: 30.2 1995-1999: 29.5 Italy Turin 1990-1994: 73.4 1995-1999: 61.1 Florence 1990-1994: 40.4 1995-1999: 33.3 United Kingdom Oxford 1990-1994: 29.0 1995-1999: 25.5 Cambridge 1990-1994: NR 1995-1999: 25.4 The Netherlands Utrecht 1990-1994: 42.8 1995-1999: 40.0 Bilthoven 1990-1994: 39.0 1995-1999: 37.2 Germany Heidelberg 1990-1994: NR 1995-1999: 27.0 Potsdam 1990-1994: 32.0 1995-1999: 28.9 Range (Min, Max): NR Copollutant: NO 2 , O 3 , SO 2 Increment: 10 μg/m 3 Odds Ratios (Min CI, Max CI) for increase in lung cancer per increment increase in PM 10 0.91 (0.70-1.18)

Reference : (Wei et al., 2009, 192361 ) Period of Study: Nov 2006-Jan 2007

Location: Peking, China Outcome: Urinary 8-OHdG increase Study Design: Panel

Covariates: NR Statistical Analysis: Analysis of variance model with autoregressive terms Statistical Package: SAS Age Groups: Two nonsmoking security guards, ages 18 and 20 Pollutant: PM 2.5 Averaging Time: 24 h

Median: 154.87 μg/m 3

IQR: 166.29 Copollutant (correlation): NA Increment: 166.29 μg/m 3 8-OHdG Concentrations, pre and post-work shift, subjects avgd

Pre-work: 1.83

Post-work: 6.92 Concentration Changes (95%CI) of 8- OHdG per IQR Increase Pre-work: 0.256 (0.040, 0.472), p = 0.021 Post-work: 2.370 (0.907, 3.833), p = 0.002

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-436

# Table E-27. Long-term exposure - cancer outcomes - PM 2.5 

# (including PM components/sources).

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Baccarelli et al, (2009, 188183 ) Period of Study: Jan 1999-Jun 2007

Location: Boston, Massachusetts Outcome: DNA methylation of LINE-1 and Alu Study Design: Panel

Covariates: age, BMI, smoking status, pack-yr, statin use, fasting blood glucose, diabetes mellitus, percent lymphocytes and neutrophils in differential blood count, day of the week, season, temperature Statistical Analysis: Mixed effects models Statistical Package: SAS Age Groups: 719 elderly individuals, mean age 73.3, range 55-100 yr Pollutant: PM 2.5 Averaging Time: NR Mean (SD) Unit: 4h: 12.2 (7.7) μg/m 3 1 day: 10.9 (6.3) μg/m 3 2 day: 10.6 (5.2) μg/m 3 3 day: 10.4 (4.8) μg/m 3 4 day: 10.3 (4.3) μg/m 3 5d: 10.2 (3.9) μg/m 3 6d: 10.3 (3.5) μg/m 3 7d: 10.3 (3.3) μg/m 3 Copollutants: Black carbon, Sulfate Increment: SD for each lag Correlation Coefficient (95% CI) Lag for LINE-1 Methylation 4h: -0.07 (-0.13, -0.01), p = 0.03 1 day: -0.09 (-0.16, -0.02), p = 0.008 2 day: -0.10 (-0.17, -0.03), p = 0.003 3 day: -0.10 (-0.17, --0.04), p = 0.003 4 day: -0.10 (-0.16, -0.03), p = 0.004 5d: -0.10 (-0.16, -0.03), p = 0.004 6d: -0.11 (-0.17, -0.04), p = 0.001 7d: -0.13 (-0.19, -0.06), p < 0.001 Correlation Coefficient (95% CI) Lag for Alu Methylation 4h: 0.03 (-0.03, 0.09), p = 0.28 1 day: -0.01 (-0.07, 0.05), p = 0.74 2 day: -0.01 (-0.07, 0.05), p = 0.82 3 day: -0.01 (-0.07, 0.05), p = 0.78 4 day: -0.01 (-0.07, 0.05), p = 0.75 5d: -0.01 (-0.07, 0.05), p = 0.84 6d: -0.01 (-0.07, 0.05), p = 0.74 7d: -0.01 (-0.07, 0.05), p = 0.71 Correlation Coefficient (95% CI) LINE-1 Methylation and ma of pollutant levels 4h: -0.04 (-0.11, 0.03), p = 0.24 7d: -0.11 (-0.18, -0.05), p = 0.001

Reference: Binkova et al. (2007, 156273 ) Period of Study: Feb 2001

Location: Prague, Czech Republic Outcome: Bulky aromatic PAH-DNA adducts Age Groups: 22-50 yr Study Design: Case Control

N: 53 exposed policemen and 52 control policemen Statistical Analyses: Multivariate logistic regression, Mann-Whitney, Rank-Sum U-test

Covariates: Smoking. Vitamin C, polymorphisms of XPD repair gene in exon 23 and 6 and GSTM 1 gene

Season: Winter Pollutant: PM 2.5 Range (Min, Max): 27-38 c-PAHs: range = 18-22 ng/m 3 B[a]P: range = 2.5-3.1 ng/m 3 Monitoring Stations: 2 Genetic damage was observed in city policemen working in winter outdoors in the Prague downtown area They had slightly elevated aromatic DNA adduct levels, which was more pronounced for a distinct DNA adduct spot that could originate from ambient exposure to B[ α ]P. Total DNA-adduct level Exposed: 0.92±0.28 adducts/108 nucleotides Control: 0.82±0.23 adducts/108 nucleotides p = 0.065 “Like” B[ α ]P-derived DNA adducts Exposed: 0.122±0.036 Control: 0.101±0.035 p < 0.01 Multiple Regression (exposed vs. control) B = 0.016, p = 0.011



### December 2009 E-437

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Brunekreef et al, (2009, 191947 ) Period of Study: 1987-1996

Location: The Netherlands Outcome: Air pollution related lung cancer deaths (ICD-9 162) Study Design: Case-cohort

Covariates Individual: Sex, age, Quetelet index, smoking status, passive smoking status, educational level, occupation, occupational exposure, marital status, alcohol use, intake of vegetables, fruits, energy, saturatured and monounsaturated fatty acids, trans fatty acids, total fiver, folic acid and fish Area-level: Percent of population with income below the 40th percentile and above the 80th percentile Statistical Analysis: Cox proportional hazards Statistical Package: Stata, SPSS, R Age Groups: 120,000 adults aged 55- 69 yr at enrollment Pollutant: PM 2.5 , estimated from PM 10 levelsf Averaging Time: 24 h

50th Percentile: 28 μg/m 3 Range (Min, Max): 23-37 Copollutant (correlation):

NO 2 : 0.75

Black Smoke: 0.84

NO: 0.69

SO 2 : 0.43 Increment: 10 μg/m 3 Relative Risk (95% CI) for associations between PM 2.5 and lung cancer incidence

Case Cohort Unadjusted: 0.93 (0.71-1.22) Adjusted: 0.67 (0.41-1.10) Unadjusted Complete: 0.87 (0.60-1.25)

Full Cohort Unadjusted: 0.96 (0.79-1.18) Adjusted: 0.81 (0.63-1.04) Unadjusted Complete: 0.92 (0.74-1.15)

Reference: Liu et al. (2008, 156708 ) Period of Study: 1995-2005

Location: Taiwan Outcome: Brain cancer deaths

ICD9: 191 Age Groups : 29 yr of age or younger Study Design: Matched case-control by sex, yr of birth and death

N: 340 matched pairs Statistical Analyses: Conditional logistic regression

Covariates: Age, gender, urbanization level of residence, nonpetrochemical air pollution exposure level No direct measures of pollutants used an index to assign petrochemical air pollution exposure (each municipality was assigned an exposure by dividing the number of workers per municipality employed in the petrochemical industry by the municipalities total population). Study participants divided into tertiles based on this index. People who lived in the group of municipalities with the highest levels of air pollutants arising from petrochemical sources were at a statistically significant increased risk for brain cancer development compared to the group living in municipalities with the lowest petrochemical air pollution exposure index. Effect Measure: OR (95%CI) Tertile 1: 1. ?0 Tertile 2: 1.54 (0.98-2.42) Tertile 3: 1.65 (1.00-2.73) P for trend <0.01

Reference: Nafstad et al. (2004, 087949 ) Period of Study: 1972-1998

Location: Oslo, Norway Outcome: Lung cancer

ICD7 162.1-162.9 Age Groups: 40-49 yr old men Study Design: Cohort

N: 16,209 males Statistical Analyses: Cox regression models (proportional hazards)

Covariates: Age at inclusion, smoking habits, education

Season: all yr PM values had small variations in exposure level, and strong correlations with another pollutant of interest (SO 2 ) and were not considered in analyses. Copollutants: SO 2 NO X No effect estimates for PM

Reference: (Pope and Burnett, 2007, 090928 ) Period of Study: 1982-1998

Location: 50 U.S. states, District of Columbia, and Puerto Rico Outcome: Lung cancer mortality (162) Age Groups: >30 yr Study Design: Longitudinal cohort (Cancer Prevention II Study)

N: 415,000 CPS II patients with information involving PM 10 Statistical Analyses: Cox proportionalhazard, incorporating a spatial randomeffects component

Covariates: Age, sex, race, education, ETS, smoking status, marital status, occupational exposure, diet, body-mass index, alcohol consumption Pollutant: PM 2.5 Mean (SD): 1979-1983: 21.1(4.6) 1999-2000: 14.0(3.0) Avg: 17.7(3.7) Averaging time: 1982-1998 PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Lung Cancer: 1979-1983: 1.08[1.01, 1.16] 1999-2000: 1.13[1.04, 1.22] Avg: 1.14[1.04, 1.23] RR results were also presented in Fig 2-5. Authors found that PM 2.5 had the strongest association with increased risk of all-cause, cardiopulmonary, and lung cancer mortality.



### December 2009 E-438

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Sram et al, (2007, 188457 ) Period of Study: Feb 2001

Location: Prague, Czech Republic Outcome: Chromosomal aberrations Study Design: Panel

Covariates: Urinary cotinine, plasma levels of vitamins A, E and C Statistical Analysis: Bivariate correlations, ANOVA, Mann-Whitney, Kruskal-Wallis and Spearman rank correlation Statistical Package: STATISTICA, SAS Age Groups: 53 city policemen, aged 22-50 yr, spending 8+ h outdoors Pollutant: PM 10 Averaging Time: NR Range: 32-55μg/m 3 Copollutant: PM 2.5 Results not given by PM increment.

Reference: Sram et al, (2007, 188457 ) Period of Study: Feb 2001

Location: Prague, Czech Republic Outcome: Chromosomal aberrations Study Design: Panel

Covariates: Urinary cotinine, plasma levels of vitamins A, E and C Statistical Analysis: Bivariate correlations, ANOVA, Mann-Whitney, Kruskal-Wallis and Spearman rank correlation Statistical Package: STATISTICA, SAS Age Groups: 53 city policemen, aged 22-50 yr, spending 8+ h outdoors Pollutant: PM 2.5 Averaging Time: NR Range: 27-38μg/m 3 Copollutant: PM 10 Results not given by PM increment.

Reference: Tovalin et al. (Tovalin et al., 2006, 091322 ) Period of Study: Apr-May 2002

Location: Mexico City and Puebla Outcome: DNA damage (comet tail length) Age Groups: 18-60 Study Design: Panel Study

N: 55 male workers Statistical Analyses: Mann-Whitney test, Chi-square, Spearman’s correlation, logistic regression Statistical Package: SPSS and STATA Pollutant: PM 2.5 Personal monitoring values observed in this study reported in Tovalin et al. 2003 Median Personal Exposure to PM 2.5 : Mexico City Outdoor Worker: 133 μg/m 3 Indoor Worker: 86.6 μg/m 3

Puebla Outdoor Worker: 122 μg/m 3 Indoor Worker: 78.3 μg/m 3 OR for being a highly damaged worker: 1.02 (1.01-1.04), p = 0.03 Correlation between comet tail length and PM 2.5: 0.57, p = 0.000 OR for being a highly damaged worker: 1.03, p ≤ 0.07 Comet Tail Length Outdoor Worker: 46.80 μm Indoor Worker: 30.11 μm p < 0.01 Percent Highly DNA Damaged Cells Outdoor Worker: 68% Indoor Worker: 20%

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-439

# Table E-28. Long-term exposure - cancer outcomes - other PM size fractions.

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Pope et al., 2002, 024689 ) Period of Study: 1982-1998

Location: 50 U.S. states, District of Columbia, and Puerto Rico Outcome: Lung cancer mortality (162) Age Groups: Ages >30 yr who were members of a household with at least 1 individual ≥ 45yrs. Study Design: Longitudinal cohort (Cancer Prevention Study II)

N: 359,000 CPS II participants with information regarding PM15 and PM15-PM 2.5 Statistical Analyses: Cox proportionalhazard, incorporating a spatial randomeffects component

Covariates: Age, sex, race, education, ETS, smoking status, marital status, occupational exposure, diet, body-mass index, alcohol consumption Smoking covariates adjusted for: Indicator: current smoker, former smoker, pipe or cigar smoker, started smoking before or after age 18 Continuous, current and former smokers: yr smoked, yr smoked squared, cigarettes per day, cigarettes per day squared, number of h per day exposed to passive cigarette smoke. Pollutant: PM 15 Mean (SD): 1979-1983: 40.3(7.7)

Pollutant: PM15-2.5 Mean (SD): 1979-1983: 19.2(6.1) Averaging Time: 1979-1983 Relative risks effect estimates were recorded in Fig 5 and not presented quantitatively anywhere else.

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-440

# E.7. Long-Term Exposure and Reproductive Effects

Table E-29. Long-term exposure - reproductive outcomes - PM 10 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Bell at al. (2007, 091059 ) Period of Study: 1999-2002

Location: Connecticut-Fairfield, Hartford, New Haven, New London, Windham, Massachusetts-Barnstable, Berkshire, Bristol, Essex, Hampden, Middlesex, Norfolk, Plymouth, Suffolk, Worcester Outcome: Low birth weight Age Groups: Neonates Study Design: Cross-sectional

N: 358,504 births Statistical Analyses: Multiple logistic and linear regressions

Covariates: Child’s sex, mother’s education, tobacco use, mother’s marital status, mother’s race, time prenatal care began, mother’s age, birth order, gestation length Dose-response Investigated? No Statistical Package: NR Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 22.3 (5.3) Monitoring Stations: NR Copollutant: NO 2 , CO, SO 2 Gestation exposure correlation:

PM 2.5 : r = 0.77

NO 2 : r = 0.55 PM Increment: 7.4 μg/m 3 ( IQR) Difference in birth weight [Lower CI, Upper CI] per IQR for the gestational period: - 8.2 [-11.1 to -5.3] Difference in birth weight by race of mother [Lower CI, Upper CI]: Black: -7.9 [-16.0, 0.2] White: -9.0 [-12.2 to -5.9] Range among trimester models for change in birth weight per IQR increase (min, max)

trimester: -6.6 to -4.7 3rd OR Estimate for birth weight <2500 g [Lower CI, Upper CI] per IQR for the gestational period: 1.027 [0.991, 1.064]

Notes : Analyses using first births alone yielded similar results. Two pollutant models for uncorrelated pollutants were analyzed but not presented quantitatively.

Reference: Brauer et al. (2008, 156292 ) Period of Study: 1999-2002

Location: Vancouver, BC Outcome: Preterm birth, SGA, LBW Age Groups: Study Design: Crosssectional

N: 70,249 births Statistical Analyses: Logistic regression

Covariates: Sex, parity, month and yr of birth, maternal age and smoking, neighborhood level income and education Statistical Package: SAS Pollutant: PM 10 Averaging Time: 24-h Mean (SD): 12.7 Range (Min, Max): 5.6, 35.4 Monitoring Stations: 19 Copollutant: NO NO 2 CO SO 2 O 3 PM Increment: 1 μg/m 3 Effect Estimate [Lower CI, Upper CI] pollutant assessed for entire pregnancy period: SGA: 1.02 (0.99, 1.05) LBW: 1.01 (0.95, 1.08) Preterm (<30 wk): 1.13 (0.95, 1.35)



### December 2009 E-441

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Chen et al. (2002, 024945 ) Period of Study: 1991-1999

Location: Washoe County, Nevada Outcome: Birth weight Age Groups: Sngle births with gestational age between 37-44 wk and maternal all ages Study Design: Cross-sectional

N: 33,859 single births Statistical Analyses: multiple linear and logistic regression

Covariates: infant sex, maternal residential city, education, medical risk factors, active tobacco use, drug use, alcohol use, prenatal care, mother’s age, race and ethnicity of mothers and weight gain of mothers Dose-response Investigated? No Statistical Package: SPSS 10.0 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 31.53 (22.32)

Percentiles: 25th: 16.80 50th(Median): 26.30

75th: 39.35 Range (Min, Max): (0.97-157.32) Monitoring Stations: 4 Copollutant: CO

O 3 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Using continuous pollutant variables Model 1-PM 10 1 trimester Crude model: ß = -0.186 (0.225) Adjusted model: ß = -0.082 (0.221) 2 trimester Crude model: ß = 0.045 (0.223) Adjusted model: ß = -0.020 (0.221) 3 trimester Crude model: ß = -0.509 (0.231) Adjusted model: ß = -0.395 (0.227) Whole Crude model: ß = -0.823 (0.459) Adjusted model: ß = -0.726 (0.483) Model 2 CO and PM 10 3 trimester Crude model: ß = -1.044 (0.457) Adjusted model: ß = -1.078 (0.445) O 3 and PM 10 3 trimester Crude model: ß = -1.035 (0.385) Adjusted model: ß = -0.966 (0.378) Model 3 PM 10 , O 3 , and CO 3 trimester Crude model: ß = -1.070 (0.458) Adjusted model: ß = -1.102 (0.446) Whole Crude model: ß = -1.413 (0.733) Adjusted model: ß = -1.332 (0.738) Using categorical pollutant variables-3 trimester Model 1-PM 10 Adjusted model: ß = -10.243 (5.235) Model 2 PM 10 and CO Adjusted model: ß = -11.883 (6.108) PM 10 and O 3 Adjusted model: ß = -9.144 (5.860) Model 3 PM 10 , CO, and O 3 Adjusted model: ß = -10.937 (6.222) Using logistic regression (ref value = <19.72 μg/m 3 Exposure to PM 10 at 3 trimester at >44.74 μg/m 3 : OR = 1.105 (0.714-1.709) Between 19.72-44.74 μg/m 3 : OR = 1.050 (0.811-1.360)

Notes: Crude model: model with airpollutant variables controlled with gestational age only. Adjusted model: model with air-pollutant variables controlled with confounding variables including gestational age, infant sex, maternal residential city, education, medical risk factors, active tobacco use, drug use, alcohol use, the trimester begins prenatal visits, total prenatal visits, mother’s age, race and ethnicity of mother, and weight gain of mother.



### December 2009 E-442

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Dales et al. (2004, 087342 ) Period of Study: Jan 1984-Dec 1999

Location: Canada (12 cities) Outcome: SIDS (a sudden, unexplained death of a child <1 yr of age for which a clinical investigation and autopsy fail to reveal a cause of death) Age Groups: Infants <1 yr Study Design: Time-series

N: Total population of 12 cities: 10,310,309 1556 cases of SIDS over study period Statistical Analyses: Random-effects regression model for count data (a linear association between air pollution and the incidence of SIDS was assumed on the logarithmic scale)

Covariates: Weather factors (daily mean temp, daily mean relative humidity, maximum change in barometric pressure, all measured on the day of death), length of time-period adjustment, seasonal indicator variables, and size-fractionated PM

Season: Used piece-wise constant functions in time that varied by 3, 6, or 12 mo Dose-response Investigated? No Statistical Package: NR Pollutant: PM 10 Averaging Time: 24-hs (PM measures every 6 days gaseous pollutants every day) Mean (IQR): PM 10 : 23.43 (15.56) Range (Min, Max): IQR presented above Monitoring Stations: When data were available from more than 1 monitoring site, they were avgd Copollutant:

PM 2.5 PM 10 CO

NO 2 O 3 SO 2 Notes: The abstract reports no association between increased daily rates of SIDS and fine particles measured every sixth day. However, no effect estimates presented for PM (only gaseous pollutants adjusted for PM).



### December 2009 E-443

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Dugandzic et al. (2006, 088681 ) Period of Study: Jan 1988-Dec 2000

Location: Nova Scotia, Canada Outcome: Low birth weight (LBW) (<2500 grams) Age Groups: Babies born ≥ 37 wk (full term) Study Design: Cross-sectional

N: 74,284 births Statistical Analyses: Logistic regression

Covariates: Maternal age, parity, prior fetal death, prior neonatal death, prior low birth weight infant, smoking during pregnancy, neighborhood family income, infant gender, gestational age, weight change, yr of birth

Season: All Dose-response Investigated? Yes Statistical Package: SAS Pollutant: PM 10 Averaging Time: 24-h Mean (SD):

Percentiles: 25th: 14 50th(Median): 16

75th: 19 Range (Min, Max): Max: 53 Monitoring Stations: 18 Copollutant: SO 2 , O 3 Notes: Only 3 stations monitored more than 1 pollutant. Daily data were available for gaseous pollutants while particulate levels were measured every sixth day. PM Increment: 1) IQR (5 μg/m 3 ) 2) Quartiles (first quartile is the reference) Exposure period: first trimester Unadjusted model 2nd quartile: 1.24 (0.95, 1.62) 3rd quartile: 1.25 (0.96, 1.62) 4th quartile: 1.28 (1.00, 1.65) Per IQR: 1.09 (1.00, 1.18) Adjusted model 2nd quartile: 1.24 (0.94, 1.64) 3rd quartile: 1.24 (0.95, 1.64) 4th quartile: 1.33 (1.02, 1.74) Per IQR: 1.09 (1.00, 1.19) Adjusted for Birth Year model 2nd quartile: 1.14 (0.86, 1.52) 3rd quartile: 1.08 (0.82, 1.44) 4th quartile: 1.11 (0.84, 1.48) Per IQR: 1.03 (0.94, 1.14) Exposure period: second trimester Unadjusted model 2nd quartile: 0.98 (0.76, 1.28) 3rd quartile: 1.09 (0.84, 1.40) 4th quartile: 1.00 (0.77, 1.28) Per IQR: 1.00 (0.91, 1.09) Adjusted model 2nd quartile: 1.02 (0.77, 1.34) 3rd quartile: 1.16 (0.89, 1.51) 4th quartile: 1.09 (0.83, 1.42) Per IQR: 1.02 (0.93, 1.12) Adjusted for Birth Year model 2nd quartile: 0.99 (0.75, 1.31) 3rd quartile: 1.10 (0.84, 1.45) 4th quartile: 1.01 (0.76, 1.34) Per IQR: 1.00 (0.90, 1.10) Exposure period: third trimester Unadjusted model 2nd quartile: 0.93 (0.72, 1.20) 3rd quartile: 1.07 (0.83, 1.37) 4th quartile: 0.92 (0.71, 1.18) Per IQR: 0.95 (0.87, 1.05) Adjusted model 2nd quartile: 0.96 (0.73, 1.26) 3rd quartile: 1.14 (0.88, 1.48) 4th quartile: 1.03 (0.79, 1.35) Per IQR: 0.99 (0.89, 1.09) Adjusted for Birth Year model 2nd quartile: 0.92 (0.70, 1.21) 3rd quartile: 1.04 (0.80, 1.36) 4th quartile: 0.92 (0.69, 1.22) Per IQR: 0.94 (0.85, 1.05) Reference: Gilboa, et al. (2005, 087892 ) Period of Study: Jan 1996-Dec 2000

Location: Seven Counties in Texas, USA: (Bexar, Dallas, El Paso, Harris, Hidalgo, Tarrant, Travis) Outcome: Birth defects Age Groups: Newborn babies Study Design: Case-control

N: 5,338 newborn babies

4574 controls Statistical Analyses: Logistic regression

Covariates: Alcohol consumption during pregnancy, attendant of delivery (i.e., the person who delivered the baby (physician/nursemaid-wife vs. other)), gravidity, marital status, maternal age, maternal education, maternal illness, maternal race/ethnicity, parity, place of delivery, plurality, prenatal care, season of conception, and tobacco use during pregnancy Control frequency matched to cases by vital status, yr and maternal county of residence Pollutant: PM 10 Averaging Time: NR

Percentiles: 25th: <19.5 50th(Median): 19.5-<23.8

75th: 23.8-<29.0

100th: ≥ 29.0 Monitoring Stations: The Environmental Protection Agency provided raw data or hourly (for gases) or daily (for PM) air pollution concentrations for the seven study counties Copollutant: CO, NO 2 , O 3 , SO 2 PM Increment: calculated as quartiles of avg concentration during wk 3-8 of pregnancy Isolated Cardiac Defects Aortic artery and valve defects: 25th: 0.40 (0.15, 1.03) 50th: 0.45 (0.18, 1.13) 75th: 0.68 (0.28, 1.65) Atrial Sepal defects: 25th: 1.41 (0.86, 2.31) 50th: 2.13 (1.34, 3.37) 75th: 2.27 (1.43, 3.60) Pulmonary artery and valve defects: 25th: 1.14 (0.62, 2.10) 50th: 0.79 (0.41, 1.55) 75th: 0.68 (0.33, 1.40) Ventricular Sepal defects: 25th: 0.83 (0.61, 1.11) 50th: 1.12 (0.85, 1.48) 75th: 0.98 (0.73, 1.32) Multiple Cardiac Defects Conotruncal defects: 25th: 1.13 (0.79, 1.62) 50th: 1.20 (0.84, 1.72) 75th: 1.26 (0.86, 1.84)



### December 2009 E-444

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Season: Covariate in model Dose-response Investigated? Yes Statistical Package: SAS v 8.2 Endocardial cushio n and mitral valve defects: 25th: 0.82 (0.54, 1.25) 50th: 0.66 (0.42, 1.05) 75th: 0.63 (0.38, 1.03) Isolated Oral Clefts Cleft lip with or without palate: 25th: 1.29 (0.90, 1.85) 50th: 1.45 (1.01, 2.07) 75th: 1.37 (0.94,2.00) Cleft palate: 25th: 0.99 (0.55, 1.78) 50th: 1.14 (0.64, 2.03) 75th: 1.11 (0.60, 2.06) Individual Birth Defects Aortic valve stenosis: 25th: 0.91 (0.53, 1.57) 50th: 0.86 (0.50, 1.50) 75th: 1.12 (0.63, 1.99) Atrial Sepal defects: 25th: 1.10 (0.89, 1.35) 50th: 1.28 (1.04, 1.57) 75th: 1.26 (1.03, 1.55) Coarctation of the aorta: 25th: 0.78 (0.53, 1.15) 50th: 0.68 (0.45, 1.02) 75th: 0.75 (0.48, 1.15) Endocardial cushion defects: 25th: 0.87 (0.49, 1.55) 50th: 1.12 (0.64, 1.96) 75th: 0.89 (0.47, 1.65) Ostium secundum: 25th: 1.15 (0.85, 1.55) 50th: 1.13 (0.83, 1.53) 75th: 1.06 (0.77, 1.48) Pulmonary artery atresia without ventricular Sepal defects: 25th: 1.93 (1.08, 3.45) 50th: 2.01 (1.11, 3.64) 75th: 0.86 (0.41, 1.83) Pulmonary valve stenosis: 25th: 1.16 (0.88, 1.55) 50th: 1.25 (0.94, 1.66) 75th: 1.27 (0.94, 1.71) Tetralogy of Fallot: 25th: 1.21 (0.72, 2.01) 50th: 1.40 (0.84, 2.33) 75th: 1.45 0.85, 2.48) Ventricular Sepal defects: 25th: 1.06 (0.90, 1.24) 50th: 1.10 (0.94, 1.29) 75th: 1.08 (0.92, 1.27)



### December 2009 E-445

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Gouveia et al. (2004, 055613 ) Period of Study: 1997

Location: São Paulo, Brazil Outcome: Birth weight Age Groups: Singleton full term live births within 1000 g to 5500 g Study Design: Cross sectional study

N: 179,460 live births Statistical Analyses: GAM and Logistic regression models

Covariates: Maternal age, length of gestation, season, infant gender, maternal education, number of antenatal care visits, parity, and the type of delivery

Season: All seasons Dose-response Investigated? Yes Statistical Package: S-Plus 2000 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 60.3 (25.2) Range (Min, Max): (25.5-153.0) Monitoring Stations: maximum of 12 sites Copollutant (correlation): CO: r = 0.9

SO 2 NO 2 O 3 PM Increment: 10 μg/m 3

Mean [Lower CI, Upper CI]: Changes in birth weight (in g) First trimester = -13.7 (-27.0, -0.4) Second trimester = -4.4 (-18.9, 10.1) Third trimester = 14.6 (0.0, 29.2) RR Estimate [Lower CI, Upper CI]: (RR estimates are adjusted odds ratios for low birth weight according to quartiles of air pollution in each trimester of pregnancy.) 1st quartile First trimester = 1 (REF) Second trimester = 1 (REF) Third trimester = 1 (REF) 2nd quartile First trimester = 1.105 (0.994, 1.229) Second trimester = 1.003 (0.904, 1.113) Third trimester = 1.004 (0.914, 1.104) 3rd quartile First trimester = 1.049 (0.903, 1.219) Second trimester = 1.074 (0.920, 1.254) Third trimester = 1.003 (0.861, 1.169) 4th quartile First trimester = 1.144 (0.878, 1.491) Second trimester = 1.252 (1.028, 1.525) Third trimester = 0.970 (0.780, 1.205) Multiple linear regression coefficients (SE) obtained from single, dual, and three pollutant models Single pollutant model = -1.37 (0.68) Two pollutant (PM 10 and CO) = -0.51 (0.87) Two pollutant (PM 10 and SO 2 ) = -0.94 (0.75) Three pollutant = -0.47 (0.88) Reference: Ha et al. (2003, 042552 ) Period of Study: Jan 1995-Dec 1999

Location: Seoul, South Korea Outcome: Post-neonate total and respiratory mortality Age Groups: 1 month-1 yr 2 yr-65 yr, >65 yr Study Design: Time-series

N: 1045 post-neonate deaths, 67,597 2- 65 yr old deaths, 100,316 >65 yr old deaths Statistical Analyses: Generalized additive model

Covariates: Seasonality, temperature, relative humidity, day of the week Dose-response Investigated? No Statistical Package: S Plus Lags Considered: 0, 1, 2, 3, 4, 5, 6, 7, ma from 1-5 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 69.2 (31.6)

Percentiles: 25th: 44.8 50th(Median): 64.2

75th: 87.7 Range (Min, Max): 10.5 μg/m 3

, 245.4 μg/m 3 Monitoring Stations: 27 Copollutant (correlation):

NO 2 : r = 0.73

SO 2 : r = 0.62

O 3 : r = -0.02

CO: r = 0.63 PM Increment: 42.9 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Total Mortality: 1 month-1 yr (post-neonates): 1.142 [1.096, 1.190] lag 0 2 yr-65 yr: 1.008 [1.006, 1.010] lag 0 >65 yr (elderly): 1.023 [1.023, 1.024] lag 0 Respiratory Mortality: 1 month-1 yr (post-neonates): 2.018 [1.784, 2.283] lag 0 2 yr-65 yr: 1.066 [1.044, 1.090] lag 0 >65 yr (elderly): 1.063 [1.055, 1.072] lag 0



### December 2009 E-446

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Hansen, et al. (2006, 089818 ) Period of Study: Jul 2000-Jun 2003

Location: Brisbane, Australia Outcome: Pre-term birth (<37 wk) Age Groups: Newborn babies Study Design: Cross-sectional

N: 1583 live pre-terms births 28,200 singleton live births Statistical Analyses: Multiple logistic regression models

Covariates: Neonate gender, mother’s age, parity, indigenous status, number of antenatal visits, marital status, number of previous abortions/miscarriages, type of delivery, and index of SES

Season: all Dose-response Investigated? Yes Statistical Package: SAS version 8.2 Pollutant: PM 10 Averaging Time: recorded hourly, avgd daily Mean (SD): 19.6 (9.4) Range (Min, Max): 4.9, 171.7 Monitoring Stations: 5 Copollutant (correlation): Fine PM or bsp, 0.1 to <2.5 μg in diameter (0.58 to 0.76)

O 3 (0.54 to 0.83)

NO 2 (0.54 to 0.75)

PM 10 (0.80 to 0.93)

Note: Correlations presented are for the individual pollutant across monitoring stations (not correlations between PM 10 and the pollutant.) PM Increment: Trimester One 4.5 μg/m 3 Last 90 days prior to birth 5.7 μg/m 3 Odds Ratio [Lower CI, Upper CI]:

Trimester 1 1.15 [1.06, 1.25] Last 90 days prior to birth 1.04 [0.92, 1.16]

Reference: Hansen et al. (2007, 090703 ) Period of Study: Jul 2000-Jun 2003

Location: Brisbane, Australia Outcome: Birth weight and Small for Gestational Age (SGA <10th percentile for age and gender)Head circumference (HC) and crownheel length (CHL) among subsample Study Design: Cross-sectional

N: 26,617 births (birth weight analysis) and 21,432 (HC and CHL analyses) Statistical Analyses: Logistic (SGA) and linear (birth weight, HC, CHL) regressions

Covariates: Gender, gestational age (with a quadratic term), maternal age, parity, number of previous abortions/miscarriages, marital status, indigenous status, number of antenatal visits, type of delivery, an index of SES, and season of birth

Season: Assessed as a covariate Dose-response Investigated? Yes, assessed exposures as quartiles Statistical Package: SAS v8.2 Pollutant: PM 10 Averaging Time: Trimester and monthly avg were used in analyses (calculated as the mean of daily values Hourly data was use to calculate daily

means City-wide avg used) Mean (SD): 19.6 (9.4) Percentiles: 25th: 14.6 50th: 18.1 75th: 22.7 Range (Min, Max): (4.9, 171.7) Monitoring Stations: 5 Copollutant (correlation): By trimesters: PM 10 T1: PM 10 T2: r = 0.12 PM T3: r = -0.55

10 O 3 T1: r = 0.77 O 3 T2: r = 0.28 O T3: r = -0.61

3 NO 2 T1: r = 0.32 NO 2 T2: r = -0.65 NO T3: r = -0.17

2 visibility reducing particles (bsp) T1: r = 0.82 visibility reducing particles (bsp) T2: r = -.15 visibility reducing particles (bsp) T3: r = -0.50 PM 10 T1: r = 0.12 PM 10 T2: PM T3: r = 0.04

10 O 3 T1: r = -0.11 O 3 T2: r = 0.80 O T3: r = 0.18

3 NO 2 T1: r = 0.77 NO 2 T2: r = 0.25 NO T3: r = -0.72

2 visibility reducing particles (bsp) T1: r = 0.23 visibility reducing particles (bsp) T2: r = 0.80 visibility reducing particles (bsp) T3: r = -0.24 PM 10 T1: r = -0.55 PM 10 T2: r = 0.04 PM 10 T3: PM Increment: IQR (8.1 μg/m 3 ) Effect Estimate [Lower CI, Upper CI]: Change ( β ) in mean birth weight (g) associated with trimester-specific exposures Trimester 1: Continuous exposure: -3.2 (-11.9, 5.5) Quartiles of exposure: 1: Ref 2: -4.7 (-19.7, 10.2) 3: 4.2 (-12.9, 21.3) 4: -0.2 (-19.2, 18.8) p-trend: 0.864 Trimester 2: Continuous exposure: 0.4 (-9.4, 10.2) Quartiles of exposure: 1: Ref 2: 12.7 (-2.3, 27.6) 3: 7.6 (-10.6, 25.7) 4: 1.0 (-18.7, 20.7) p-trend: 0.922 Trimester 3: Continuous exposure: 3.6 (-6.9, 14.0) Quartiles of exposure: 1: Ref 2: 2.9 (-12.8, 18.7) 3: 18.5 (0.0, 36.9) 4: 4.3 (-15.8, 24.4) p-trend: 0.524ORs for SGA associated with trimesterspecific exposures Trimester 1: Continuous exposure: 1.04 (0.96, 1.12) Quartiles of exposure: 1: Ref 2: 1.23 (1.07, 1.42) 3: 1.12 (0.95, 1.31) 4: 1.12 (0.94, 1.34) p-trend: 0.361 Trimester 2: Continuous exposure: 0.95 (0.88, 1.04) Quartiles of exposure: 1: Ref 2: 0.96 (0.83, 1.11) 3: 1.06 (0.89, 1.25) 4: 0.98 (0.81, 1.18) p-trend: 0.962 3: -0.02 (-0.08, 0.04) 4: -0.02 (-0.08, 0.05) p-trend: 0.605 Trimester 2: Continuous exposure: -0.01 (-0.04, 0.02)



### December 2009 E-447

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

O 3 T1: r = -0.56 O 3 T2: r = -0.18

O 3 T3: r = 0.81

NO 2 T1: r = -0.20

NO 2 T2: r = 0.75

NO 2 T3: r = 0.22 visibility reducing particles (bsp) T1: r = -0.62 visibility reducing particles (bsp) T2: r = 0.19 visibility reducing particles (bsp) T3: r = 0.79 Quartiles of exposure: 1: Ref Trimester 3: Continuous exposure: 0.93 (0.85, 1.03) Quartiles of exposure: 1: Ref 2: 0.90 (0.78, 1.04) 3: 0.81 (0.68, 0.96) 4: 0.86 (0.71, 1.04) p-trend: 0.098 Change ( β ) in mean head circumference (HC cm) associated with trimester-specific exposures Trimester 1: Continuous exposure: -0.01 (-0.04, 0.02) Quartiles of exposure: 1: Ref 2: -0.02 (-0.07, 0.04) 2: 0.03 (-0.02, 0.08) 3: 0.00 (-0.06, 0.06) 4: -0.01 (-0.08, 0.05) p-trend: 0.538 Trimester 3: Continuous exposure: 0.02 (-0.02, 0.05) Quartiles of exposure: 1: Ref 2: 0.02 (-0.04, 0.07) 3: 0.07 (0.01, 0.13) 4: 0.04 (-0.03, 0.11) p-trend: 0.171 Change ( β ) in mean crown-heel length (CHL cm) associated with trimester-specific exposures Trimester 1: Continuous exposure: 0.00 (-0.05, 0.05) Quartiles of exposure: 1: Ref 2: 0.02 (-0.07, 0.11) 3: 0.01 (-0.10, 0.11) 4: 0.04 (-0.07, 0.16) p-trend: 0.511 Trimester 2: Continuous exposure: 0.07 (0.01, 0.13) Quartiles of exposure: 1: Ref 2: 0.10 (0.01, 0.18) 3: 0.11 (0.00, 0.21) 4: 0.13 (0.01, 0.24) p-trend: 0.049 Trimester 3: Continuous exposure: -0.01 (-0.07, 0.05) Quartiles of exposure: 1: Ref 2: -0.02 (-0.11, 0.07) 3: 0.10 (-0.01, 0.21) 4: -0.01 (-0.13, 0.10) p-trend: 0.883



### December 2009 E-448

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference : (Hansen et al., 2009, 192362 ) Period of Study: Jan 1997-Dec 2004

Location: Brisbane, Australia Outcome: Birth defects- artery and valve, atrial and ventricular Sepal, conotruncal, endocardial cushion and mitral valve, cleft lip and palate Study Design: Case-control

Covariates: Mother’s age, marital status, indigenous status, previous pregnancies, last menstrual period, area-level socioeconomic status, distance to a pollution monitor Statistical Analysis: Conditional logistic regression Statistical Package: R Age Groups: Neonates Pollutant: PM 10 Averaging Time: daily Mean (SD) Unit: 18.0 μg/m 3 Range (Min, Max): (4.4, 151.7) Copollutant (correlation): NR Increment: 4μg/m 3 Odds Ratios (95% CI) for risk of defect Aortic Artery and Valve Defects All Births, Matched: 1.10 (0.76-1.56) Births ≤ 12km to Monitor: 1.83 (1.16-2.98) Births ≤ 6km to Monitor: 1.43 (0.73-2.90) All Births, Unmatched: 1.09 (0.84-1.39) Atrial Sepal Defects All Births, Matched: 1.06 (0.86-1.30) Births ≤ 12km to Monitor: 1.07 (0.84-1.37) Births ≤ 6km to Monitor: 0.88 (0.60-1.27) All Births, Unmatched: 1.14 (0.98-1.33) Pulmonary Artery and Valve Defects All Births, Matched: 0.90 (0.61-1.29) Births ≤ 12km to Monitor: 0.69 (0.43-1.08) Births ≤ 6km to Monitor: 1.46 (0.76-2.73) All Births, Unmatched: 0.99 (0.78-1.24) Ventricular Sepal Defects All Births, Matched: 0.87 (0.73-1.04) Births ≤ 12km to Monitor: 0.85 (0.69-1.03) Births ≤ 6km to Monitor: 0.90 (0.68-1.18) All Births, Unmatched: 1.15 (1.02-1.30) Conotruncal Defects All Births, Matched: 0.80 (0.54-1.19) Births ≤ 12km to Monitor: 0.94 (0.55-1.49) Births ≤ 6km to Monitor: 0.66 (0.27-1.45) All Births, Unmatched: 0.97 (0.74-1.24) Endocardial Cushion and Mitral Valve Defects All Births, Matched: 1.29 (0.82-2.04) Births ≤ 12km to Monitor: 1.28 (0.75-2.19) Births ≤ 6km to Monitor: 0.90 (0.44-1.86) All Births, Unmatched: 0.94 (0.68-1.26) Cleft Lip All Births, Matched: 1.05 (0.72-1.51) Births ≤ 12km to Monitor: 1.16 (0.72-1.82) Births ≤ 6km to Monitor: 1.03 (0.56-1.82) All Births, Unmatched: 1.01 (0.79-1.27) Cleft Palate All Births, Matched: 0.69 (0.50-0.93) Births ≤ 12km to Monitor: 0.53 (0.29-0.87) Births ≤ 6km to Monitor: 0.71 (0.49-1.00) All Births, Unmatched: 0.89 (0.72-1.10) Cleft Lip with or without Cleft Palate All Births, Matched: 1.05 (0.84-1.30) Births ≤ 12km to Monitor: 1.03 (0.79-1.34) Births ≤ 6km to Monitor: 0.83 (0.58-1.19) All Births, Unmatched: 1.04 (0.89-1.21)\



### December 2009 E-449

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Jalaludin et al. (2007, 156601 ) Period of Study: 1998-2000

Location: Sydney, Australia Outcome: Gestational age (categorized: preterm birth: <37 wk

term birth: ≥ 37 wk but <42 wk) Age Groups: Infants Study Design: Cross-sectional

N: 123,840 singleton births of >20 wk gestation Statistical Analyses: Logistic regression

Covariates: Sex of child, maternal age, maternal smoking during pregnancy, gestational age at first antenatal visit, whether mother identifies as being Aboriginal or Torres Strait Islander, whether first pregnancy, season of conception, SES, (temperature and relative humidity were not significant in single variable models and therefore, were not included)

Season: Examined as covariate and effect modifier Dose-response Investigated? No Statistical Package: SAS v8 Pollutant: PM 10 Averaging Time: 24 h avg used to calculate the mean concentration over the first trimester, the 3 mo preceding birth, the first month after the estimated date of conception, and the month prior to delivery Mean (SD): (24 h avg) All yr: 16.3 (6.38) Summer: 18.2 (7.20) Fall: 17.0 (6.23) Winter: 14.5 (5.57) Spring: 15.7 (5.82) Monitoring Stations: 14 stations within the Sydney metropolitan area (levels avgd to provide 1 estimate for the entire study area) Copollutant (correlation): PM 10 PM 2.5 (r = 0.83) CO (r = 0.28) NO 2 (r = 0.48) O 3 (r = 0.50) SO 2 (r = 0.42) Notes: Correlations between monitoring stations measuring PM 10 ranged from 0.67 to 0.91 PM Increment: 1 μg/m 3 Effect Estimate [Lower CI, Upper CI]: ORs (air pollutant concentration during the 1st trimester and preterm birth by season) Fall: 1.462 (1.267, 1.688) Winter: 1.343 (1.190, 1.516) Spring: 1.119 (0.973, 1.288) Summer: 0.913 (0.889, 0.937) ORs (air pollutant concentrations during different exposure periods and preterm birth for all of Sydney and among only those residing within 5 km of a monitoring station) 1 month preceding birth Sydney: 0.991 (0.979, 1.003) 5km: 1.008 (0.993, 1.022) 3 mo preceding birth Sydney: 0.989 (0.975, 1.004) 5km: 1.012 (0.995, 1.030) 1st month of gestation Sydney: 0.983 (0.973, 0.993) 5km: 0.957 (0.914, 1.002) 1st trimester Sydney: 0.987 (0.973, 1.001) 5km: 1.009 (0.978, 1.041) Notes: Authors note that effect of PM 10 on preterm birth for infants conceived during the fall did not remain in 2 pollutant models (ORs between 0.77 and 1.04)

Reference: Kaiser et al. (2004, 076674 ) Period of Study: 1995-1997

Location: 25 U.S. counties (23 metropolitan areas): Jackson, AL Fresno, CA Los Angeles, CA Sacramento, CA San Diego, CA San Francisco, CA Denver, CO Hartford, CT Cook, IL Baltimore, MD Wayne, MI St. Louis, MO Bronx, NY Kings, NY New York, NY Philadelphia, PA El Paso, TX Harris, TX Dallas, TX Oklahoma, OK Tulsa, OK Providence, RI Salt Lake City, UT King, WA Milwaukee, WI Outcome: Postneonatal death: All cause, SIDS (798.0) Respiratory disease (460-519) Age Groups: Infants between 1-12 mo Study Design: Attributable risk assessment

N: 700,000 infants (# deaths NR) Statistical Analyses: Risk assessment methods described in: Kunzli et al. Public-health impact of outdoor and traffic-related air pollution: a European assessment. Lancet 2000, 356: 795- 801.

Covariates: Maternal education, maternal ethnicity, parental marital status, maternal smoking during pregnancy, infant’s month and yr of birth, avg temperature in the first 2 mo of life

Season: All adjusted for month/yr of birth Dose-response Investigated? NR Statistical Package: NR Lags Considered: Annual, county-level

mean Pollutant: PM 10 Averaging Time: “annual mean levels” in each county Mean (SD): 28.4 Range (Min, Max): County range: 18.0, 44.8 Monitoring Stations: NR

Notes: 14 out of 25 counties had PM 10 levels >25 μg/m 3 PM Increment: Analysis 1: 16.4 μg/m 3 (difference between reference level of 12 μg/m 3 and observed mean level of 28.4 μg/m 3 ) Analysis 2: 13 μg/m 3 (difference between reference level of 12 μg/m 3 and 25 μg/m 3 ) AR Estimate [Lower CI, Upper CI]: Analysis 1: All cause 6% [3, 11] SIDS 16% [9, 23] Respiratory 24% [7, 44] Attributable # deaths per 100,000 infants: All cause 14.7 [7.3, 25.6] SIDS 11.7 [6.8, 16.6] Respiratory 2.3 [0.7, 4.1] Analysis 2: All cause 5% [2, 8] SIDS 12% [7, 18] Respiratory 19% [6, 34] Attributable # deaths per 100,000 infants: All cause 10.9 [5.5, 19.1] SIDS 9.0 [5.3, 12.8] Respiratory 1.8 [0.5, 3.2] Notes: - Authors did not extrapolate attributable cases below 12 μg/m 3 (i.e., reference level was set at 12 μg/m 3 )

-Attributable risks are based on the RRs reported by Woodruff et al, 1997 for a 10 μg/m 3 increase: All cause 1.04 [1.02-1.07] SIDS 1.12 [1.07, 1.17] Respiratory 1.20 [1.06, 1.36]

Reference: (Kim et al., 2007, 156642 ) Period of Study: May 2001-May 2004 Outcome (ICD9 and ICD10): LBW (low birth weight, less than 2500 g at later than gestational week 37), premature delivery (birth before the completion of Pollutant: PM 10 Averaging Time: Used hourly exposure levels to calculate avg PM increment: 10 μg/m 3

Preterm: 1st Trimester Odds Ratios:



### December 2009 E-450

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Location: Seoul, Korea the 37th week), stillbirth (intrauterine fetal death), IUGR (birth weight lower than the 10th percentile for the given gestational age), and congenital anomaly (a defect in the infant’s body structure) Age Groups: Infants Study Design: Cross-sectional (women visiting the clinic for prenatal care were recruited with follow-up until discharge after delivery)

N: 1514 observations (births) Statistical Analyses: Multiple logistic and linear regression (in addition, for birth weight, used generalized additive model to account for long-term trends and nonlinear relationships between the response variable and the predictors, and to produce smoothed plots of the relationship between PM and birth weight)

Covariates: Adjustment 1: infant sex, infant order, maternal age and education, paternal education, season of birth Adjustment 2: adjustment 1 factors plus alcohol, maternal BMI, maternal weight prior to delivery (collected information on smoking, ETS, parity, past history of illnesses, history of illnesses during pregnancy but did not use in analyses due to small numbers or non-significance)

Season: Adjusted for season of delivery Dose-response Investigated? Yes Statistical Package: SAS 8.01, S-Plus 2000 exposure levels at each trimester, each month of pregnancy, and 6 wk before delivery from the nearest monitoring station (based on home address of mother) Also created categories within each pregnancy period (<25th percentile [referent], 25th to 50th percentile, and >50th percentile) Mean (SD): Range of PM means across pregnancy periods: 88.7-89.7 Monitoring Stations: 27 stations Crude: 0.95 (0.90, 1.01) Adj 1: 0.93 (0.87, 1.00) Adj 2: 0.93 (0.85, 1.01) 2nd Trimester Odds Ratios: Crude: 0.99 (0.94, 1.06) Adj 1: 0.98 (0.92, 1.04) Adj 2: 1.00 (0.93, 1.07) 3rd Trimester Odds Ratios: Crude: 1.02 (0.98, 1.06) Adj 1: 1.05 (1.00, 1.10) Adj 2: 1.05 (0.99, 1.11) LBW : 1st Trimester Odds Ratios: Crude: 1.02 (0.93, 1.12) Adj 1: 1.03 (0.93, 1.14) Adj 2: 1.07 (0.96, 1.19) 2nd Trimester Odds Ratios: Crude: 1.03 (0.94, 1.14) Adj 1: 1.04 (0.93, 1.17) Adj 2: 1.07 (0.94, 1.22) 3rd Trimester Odds Ratios: Crude: 1.04 (0.97, 1.11) Adj 1: 1.05 (0.97, 1.14) Adj 2: 1.05 (0.96, 1.16) IUGR : 1st Trimester Odds Ratios: Crude: 1.07 (0.97, 1.19) Adj 1: 1.07 (0.95, 1.21) Adj 2: 1.14 (0.99, 1.31) 2nd Trimester Odds Ratios: Crude: 0.97 (0.85, 1.12) Adj 1: 0.97 (0.82, 1.13) Adj 2: 0.93 (0.77, 1.13) 3rd Trimester Odds Ratios: Crude: 0.82 (0.68, 0.99) Adj 1: 0.88 (0.72, 1.08) Adj 2: 0.85 (0.67, 1.08) Birth defect : 1st Trimester Odds Ratios: Crude: 1.08 (0.98, 1.20) Adj 1: 1.12 (1.00, 1.25) Adj 2: 1.08 (0.95, 1.22) 2nd Trimester Odds Ratios: Crude: 1.09 (0.99, 1.21) Adj 1: 1.11 (0.98, 1.26) Adj 2: 1.16 (1.00, 1.34) 3rd Trimester Odds Ratios: Crude: 1.00 (0.90, 1.11) Adj 1: 0.97 (0.86, 1.08) Adj 2: 0.97 (0.87, 1.10) Stillbirth : 1st Trimester Odds Ratios: Crude: 0.83 (0.76, 0.90) Adj 1: 0.93 (0.85, 1.02) Adj 2: 0.95 (0.85, 1.02) 2nd Trimester Odds Ratios: Crude: 0.99 (0.93, 1.05) Adj 1: 1.03 (0.95, 1.11) Adj 2: 1.07 (0.98, 1.17) 3rd Trimester Odds Ratios: Crude: 1.14 (1.10, 1.18) Adj 1: 1.09 (1.04, 1.15) Adj 2: 1.08 (1.02, 1.14) LBW (categorical PM exposure): 1st Trimester ORs: <25th: 1.0 25th-50th: 0.5 (0.1, 3.2) >50th: 1.0 (0.3, 3.8) 3rd Trimester ORs: <25th: 1.0 25th-50th: 1.3 (0.2, 10.4) >50th: 3.0 (0.5, 18.5) 6 wk before birth ORs: <25th: 1.0 25th-50th: 3.2 (0.3, 33.7) >50th: 5.2 (0.6, 47.6) Changes in Birth We ight (95%CI) per 10 μg/m 3 increase in PM concentration:



### December 2009 E-451

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 1st trimester: 7.8 (1.2, 14.5) 2nd trimester: -0.3 (-7.3, 6.8) 3rd trimester: -2.1 (-7.5, 3.4) 1st month: 4.4 (-1.0, 9.8) 2nd month: 6.4 (0.6, 12.2) 3rd month: 4.3 (-1.5, 10.2) 4th month: 3.0 (-3.7, 9.6) 5th month: -3.9 (-10.5, 2.7) 6th month: 0.1 (-5.7, 5.8) 7th month: 0.1 (-5.1, 5.3) 8th month: 0.0 (-4.5, 4.5) 9th month: 1.8 (-2.3, 5.9) Last 6 wk: -4.8 (-9.9, 0.4) Reference: Lee et al. (2003, 043202 ) Period of Study: Jan 1996-Dec 1998

Location: Seoul, South Korea Outcome: Low birth weight (LBW), <2500 g Age Groups: Child-bearing age women and their newborn children-delivered at 37-44 gestational wk Study Design: Cross-section

N: 388,905 full-term single births Statistical Analyses: Generalized additive model, LOESS, Akaike’s criterion,

Covariates: Infant sex, birth order, maternal age, parental education level, time trend and gestational age.

Season: All Dose-response Investigated? Yes Statistical Package: NR Pollutant: PM 10 Averaging Time: Arithmetic avg of hourly measurements at 20 stations Mean (SD): 71.1 (30.1) Percentiles: 25th: 47.4 50th(Median): 67.6 75th: 89.3 Range (Min, Max): 18.4, 236.9 Monitoring Stations: 20 Copollutant (correlation): 1st trimester: PM 10 -CO: 0.47 PM 10 -SO 2 : 0.78 PM -NO : 0.66

10 2 2nd trimester: PM 10 -CO: 0.68 PM 10 -SO 2 : 0.82 PM 10 -NO 2 : 0.81 3rd trimester: PM 10 -CO: 0.69 PM 10 -SO 2 : 0.85 PM 10 -NO 2 : 0.80 PM Increment: IQR, 41.9 RR Estimate [Lower CI, Upper CI]: 1st trimester: 1.03 [1.00, 1.07] 2nd trimester: 1.04 [1.00, 1.08] 3rd trimester: 1.00 [0.95, 1.04] All trimesters: 1.06 [1.01, 1.10] Low exposure in last 5 mo using IQR during last 5 mo: 0.94 [0.85, 1.05] Low exposure in first 5 mo using IQR during first 5 mo: 1.04 [1.01, 1.08]

Notes: Birth weight was decreased by 19.6 g for an IQR increase in the 2nd trimester.

The OR for LBW increased for female children, fourth or higher order child, mother <20 yr of age, and low parental education level.

Reference: Leem et al. (2006, 089828 ) Period of Study: 2001-2002

Location: Incheon, Korea Outcome (ICD9 and ICD10): Age Groups: Pre-term delivery Study Design: Cross-sectional

N: Cases : 2,082 Controls: 50,031 Statistical Analyses: Log-binomial regression (corrected for overdispersion Used the log link function)

Covariates: Maternal age, parity, sex, season of birth, and education level of each parent

Season: Controlled as a covariate Dose-response Investigated? Yes, assessed quartiles of exposure Statistical Package: NR Pollutant: PM 10 Averaging Time: Trimesters (daily hourly data used to calculate) Range (Min, Max): Reported ranges within quartiles by trimester: 1st Trimester: 4: 64.57-106.39 3: 53.84-64.56 2: 45.95-53.83 1: 26.99-45.94 3rd Trimester: 4: 65.63-95.91 3: 56.07-65.62 2: 47.07-56.06 1: 33.12-47.06 Monitoring Stations: 27 monitoring stations

Pollutant levels for each area were predicted from the levels recorded at the monitors using ordinary block kriging Copollutant (correlation):

SO 2 (r = 0.13)

NO 2 (r = 0.37) CO (r = 0.27) Effect Estimate [Lower CI, Upper CI]: Crude and Adjusted RR for preterm delivery and exposure during the 1st trimester Crude Quartiles of exposure: 4: 1.07 (0.95, 1.21) 3: 1.02 (0.90, 1.15) 2: 1.06 (0.94, 1.20) 1: 1.00 Adjusted Quartiles of exposure: 4: 1.27 (1.04, 1.56) 3: 1.13 (0.94, 1.37) 2: 1.14 (0.97, 1.34) 1: 1.00 p-trend: 0.39 Crude and Adjusted RR for preterm delivery and exposure during the 3rd trimester Crude Quartiles of exposure: 4: 1.06 (0.94, 1.20) 3: 1.06 (0.94, 1.19) 2: 1.05 (0.93, 1.18) 1: 1.00 Adjusted Quartiles of exposure: 4: 1.09 (0.91, 1.30) 3: 1.04 (0.90, 1.21) 2: 1.05 (0.91, 1.20) 1: 1.00 p-trend: 0.33



### December 2009 E-452

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Lin et al. (2004, 095787 ) Period of Study: Jan 1998-Dec 2000

Location: São Paulo, Brazil Outcome: Neonatal death Age Groups: Neonates (infants 0-28 days after birth) Study Design: Time series

N: 1096 days, 6697 deaths Statistical Analyses: Poisson regression (GAM)

Covariates: Non-parametric LOESS smoothers to control for: time (long term trend), temperature, humidity, and day of week Also controlled for holidays with linear term

Season: All Dose-response Investigated? No Statistical Package: NR Lags Considered: Lag 0, “ma from 2 to 7 days”

Notes: No explicit control for season apart from temperature Pollutant: PM 10 Averaging Time: Daily values Mean (SD): 48.62 (21.18) Range (Min, Max): 13.9, 157.3 Monitoring Stations: NR (indicated more than 1) Copollutant (correlation):

CO r = 0.71

NO 2 r = 0.76

SO 2 r = 0.80

O 3 r = 0.36 PM Increment: 1 μg/m 3 Log relative rate (standard error) lag Single pollutant model 0.0017 (0.0008) lag 0 This translates to a 4.0% [95% CI: 0.3, 7.9] increase in neonatal mortality for a 23.3 μg/m 3 increase in PM 10 Two-pollutant model 0.0000 (0.0011) lag 0

Notes: -In two-pollutant model with PM 10 and SO 2 (which are highly correlated), effect of PM disappeared and effect of SO 2 remained constant - Results from pollutant ma from 2-7 days not reported, authors indicate effects only found for lag 0 (same day levels) - Confidence intervals reported in abstract are incompatible with β s/standard errors and plotted results in text: abstract indicates a 4% increase in mortality with 95% CI: 2-6 for a 23.3 μg/m 3 increase in PM 10 Reference: (Lin et al., 2004, 089827 ) Period of Study: 1995-1997

Location: Taipei and Kaoshiung, Taiwan Outcome: Low birth weight (<2500 grams) Age Groups: Newborns Study Design: Cross-sectional

N: 92,288 infants Statistical Analyses: Logistic regression

Covariates: Gender, birth order, gestational weeks, season of birth, maternal age, maternal education, copollutants

Season: All Dose-response Investigated? Yes Statistical Package: NR Lags Considered: The 9-month pregnancy period for each infant, and each trimester Pollutant: PM 10 Averaging Time: NR, “daily measurements” Mean (SD): Reported by monitoring station: Taipei: 1. 48.78 2. 46.29 3. 48.79 4. 50.80 5. 52.54 Kaohsiung 1. 69.99 2. 63.39 3. 64.89 4. 75.79 5. 77.27 Monitoring Stations: 10 (5 in each city)

Notes: All pregnant women/infants included in study lived within 3 km of an air quality monitoring station Pollution assigned based on nearest air quality station to the maternal residence Co-pollutant: CO, SO 2 , O 3 , NO 2 PM Increment: Tertiles Entire pregnancy T1: <46.4 ppb T2: 46.4-63.1 ppb T3: >63.1 ppb First trimester T1: <45.8 ppb T2: 45.8-67.6 ppb T3: >67.6 ppb Second trimester T1: <44.6 ppb T2: 44.6-64.2 ppb T3: >64.2 ppb Third trimester T1: <43.7 ppb T2: 43.7-63.7 ppb T3: >63.7 ppb RR Estimate [Lower CI, Upper CI] Entire pregnancy T1: 1.00 T2: 0.96 [0.83, 1.11] T3: 0.87 [0.71, 1.05] First trimester T1: 1.00 T2: 0.96 [0.84, 1.09] T3: 0.97 [0.80, 1.17] Second trimester T1: 1.00 T2: 1.03 [0.90, 1.17] T3: 1.00 [0.83, 1.21] Third trimester T1: 1.00 T2: 1.02 [0.90, 1.16] T3: 0.97 [0.81, 1.17] Notes: RR for births in Kaoshiung vs. Taipei: 1.13 [1.03, 1.24]

Reference: Lipfert et al. (2000, 004103 ) Period of Study: 1990

Location: U.S. Outcome: Infant mortality Including respiratory mortality (traditional definition, ICD9 460-519), expanded definition (adds ICD9 769 and 770) Age Groups: Infants Study Design: Cross-sectional

N: 2,413,762 infants in 180 counties Pollutant: PM 10 Averaging Time: Yearly avg used Mean (SD): 33.1 (9.17) (based on 180 counties) Range (Min, Max): (16.9, 59) Monitoring Stations: NR Copollutant (correlation): PM Increment: NR (present regression coefficients) Effect Estimate [Lower CI, Upper CI]: Presented regression coefficients (standard errors) (3 PM exposures regressed jointly) bold = p <0.05 Cause of death: All Birth weight: All PM 10 : 0.0114 (0.0015)



### December 2009 E-453

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) (Ns differ for various models) Statistical Analyses: Logistic regression

Covariates: Mother’s smoking, education, marital status, and race

Month of birth And county avg heating degree days Dose-response Investigated? NR Statistical Package: NR PM 10 SO 4 2– (r = 0.10)

NSPM 10 -non-sulfate portion of PM 10 (r = 0.91) CO (r = 0.27)

SO 2 (r = 0.04)

Notes: TSP-based sulfate was adjusted for compatibility with the PM 10 -based data SO 4 2– : -0.0002 (0.0061) NSPM 10 : 0.0115 (0.0014) Cause of death: All Birth weight: LBW PM 10 : 0.0088 (0.0019) SO 4 2– : 0.0265 (0.0080) NSPM 10 : 0.0086 (0.0020) Cause of death: All Birth weight: normal PM 10 : 0.0092 (0.0024) SO 4 2– : -0.0488 (0.0098) NSPM 10 : 0.0096 (0.0024) Cause of death: All neonatal Birth weight: All PM 10 : 0.0126 (0.0018) SO 4 2– : 0.0267 (0.0076) NSPM 10 : 0.0126 (0.0018) Cause of death: All neonatal Birth weight: LBW PM 10 : 0.0086 (0.0022) SO 4 2– : 0.0388 (0.0088) NSPM 10 : 0.0093 (0.0022) Cause of death: All neonatal Birth wt: normal PM 10 : 0.0123 (0.0041) SO 4 2– : -0.0334 (0.0169) NSPM 10 : 0.0125 (0.0040) Cause of death: All post neonatal Birth wt: All PM 10 : 0.0091 (0.0024) SO 4 2– : -0.0474 (0.0100) NSPM 10 : 0.0096 (0.0024) Cause of death: All post neonatal Birth wt: LBW PM 10 : 0.0096 (0.0043) SO 4 2– : -0.0247 (0.0173) NSPM 10 : 0.0101 (0.0042) Cause of death: All post neonatal Birth wt: normal PM 10 : 0.0074 (0.0030) SO 4 2– : -0.0569 (0.0121) NSPM 10 : 0.0080 (0.0029) Cause of death: SIDS Birth weight: All PM 10 : 0.0138 (0.0038) SO 4 2– : -0.1078 (0.0151) NSPM 10 : 0.0149 (0.0037) Cause of death: SIDS Birth weight: LBW PM 10 : 0.0115 (0.0088) SO 4 2– : -0.1378 (0.0337) NSPM 10 : 0.0146 (0.0085) Cause of death: SIDS Birth weight: normal PM 10 : 0.0137 (0.0042) SO 4 2– : -0.0995 (0.0168) NSPM 10 : 0.0147 (0.0041) Cause of death: All respiratory (ICD9: 460- 519, 769, 770) Birth weight: All PM 10 : 0.0168 (0.0034) SO 4 2– : 0.0706 (0.0146) NSPM 10 : 0.0166 (0.0034) Cause of death: All respiratory (ICD9: 460- 519, 769, 770) Birth weight: LBW PM 10 : 0.0144 (0.0038) SO 4 2– : 0.0821 (0.0158) NSPM 10 : 0.0139 (0.0038) Cause of death: All respiratory (ICD9: 460- 519, 769, 770) Birth weight: normal PM 10 : 0.0177 (0.0091) SO 4 2– : 0.0001 (0.0392) NSPM 10 : 0.0118 (0.0090) Cause of death: Respiratory disease (ICD9: 460-519) Birth weight: All



### December 2009 E-454

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

PM 10 : 0.0133 (0.0089) SO 4 2– : 0.0093 (0.0384) NSPM 10 : 0.0134 (0.0089) Cause of death: Respiratory disease (ICD9: 460-519) Birth weight: LBW PM 10 : 0.0092 (0.0137) SO 4 2– : 0.0434 (0.0580) NSPM 10 : 0.0089 (0.0138) Cause of death: Respiratory disease (ICD9: 460-519) Birth weight: normal PM 10 : 0.0126 (0.0120) SO 4 2– : -0.0177 (0.0509) NSPM 10 : 0.0128 (0.0119) Associations with SIDS by smoking status Smoking status: Yes Birth weight: Normal PM 10 : 0.0202 (0.0073) SO 4 2– : -0.0722 (0.0284) NSPM 10 : 0.0206 (0.0071) Smoking status: No Birth weight: Normal PM 10 : 0.0104 (0.0051) SO 4 2– : -0.114 (0.021) NSPM 10 : 0.0117 (0.005) Smoking status: Yes Birth weight: LBW PM 10 : 0.0322 (0.0130) SO 4 2– : -0.0958 (0.0483) NSPM 10 : 0.0345 (0.0125) Smoking status: No Birth weight: LBW PM 10 : -0.0044 (0.012) SO 4 2– : -0.0172 (0.047) NSPM 10 : -0.0007 (0.012) Mean risks (95%CI) between post neonatal SIDS among normal birth weight babies pollutants regressed one at a time PM 10 : 1.20 (1.02, 1.42) SO 4 2– : 0.43 (0.37, 0.51) NSPM 10 : 1.33 (1.18, 1.50) Reference: Maisonet et al. (2001, 016624 ) Period of Study: 1994-1996

Location: Northeastern U.S. (6 cities: Boston, Hartford, Philadelphia, Pittsburgh, Springfield, Washington DC) Outcome: Low birth weight (LBW): infants with a birth weight <2,500 g and having a gestational age between 37 and 44 wk Age Groups: Term live births (singleton) Study Design: Cross-sectional

N: 89,557 infants Statistical Analyses: Logistic regression (LBW) and linear regression (for reductions in birth weight)

Covariates: Gestational age, gender, birth order, maternal age, race/ethnicity, yr of education, marital status, adequacy of prenatal care, previous induced or spontaneous abortions, weight gain during pregnancy, maternal prenatal smoking, and alcohol consumption

Season

Season: Yes, as covariate Dose-response Investigated? Yes, categorical exposure variables assessed Statistical Package: STATA Pollutant: PM 10 Averaging Time: Trimester avg calculated using 24-h measurements taken every 6 days Range (Min, Max): Ranges for categories of exposure: 1st Trimester <25th: <24.821 25 to <50th: 24.821, 30.996 50 to <75th: 30.997, 36.142 75 to <95th: 36.143, 46.547 ≥ 95th: ≥ 46.548 2nd Trimester <25th: <24.702 25 to <50th: 24.702, 30.294 50 to <75th: 30.295, 35.410 75 to <95th: 35.411, 43.928 ≥ 95th: ≥ 43.929 3rd Trimester <25th: <24.702 25 to <50th: 24.702, 30.162 50 to <75th: 30.163, 35.642 75 to <95th: 35.643, 43.588 ≥ 95th: ≥ 43.589 Monitoring Stations: 3-4 per city Copollutants: CO, SO 2 PM Increment: 10 μg/m 3 for analyses assessing exposures continuously Effect Estimate [Lower CI, Upper CI]: ORs for term LBW by trimester 1st Trimester Crude <25th: 1.00 25 to <50th: 1.02 (0.90, 1.14) 50 to <75th: 0.90 (0.65, 1.24) 75 to <95th: 0.87 (0.58, 1.30) ≥ 95th: 0.89 (0.60, 1.33) Continuous: 0.93 (0.77, 1.13) 1st Trimester Adjusted <25th: 1.00 25 to <50th: 1.02 (0.94, 1.11) 50 to <75th: 0.90 (0.78, 1.03) 75 to <95th: 0.85 (0.73, 1.00) ≥ 95th: 0.83 (0.70, 0.97) Continuous: 0.93 (0.85, 1.00) 2nd Trimester Crude <25th: 1.00 25 to <50th: 1.01 (0.93, 1.10) 50 to <75th: 0.90 (0.66, 1.21) 75 to <95th: 0.92 (0.62, 1.34) ≥ 95th: 0.90 (0.61, 1.33) Continuous: 0.95 (0.78, 1.16) 2nd Trimester Adjusted <25th: 1.00 25 to <50th: 1.06 (0.97, 1.15) 50 to <75th: 0.95 (0.85, 1.07) 75 to <95th: 0.91 (0.79, 1.05) ≥ 95th: 0.77 (0.63, 0.95) Continuous: 0.93 (0.85, 1.02) 3rd Trimester Crude <25th: 1.00



### December 2009 E-455

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 25 to <50th: 0.94 (0.85, 1.05) 50 to <75th: 0.86 (0.58, 1.25) 75 to <95th: 0.86 (0.57, 1.29) ≥ 95th: 0.92 (0.61, 1.38) Continuous: 0.95 (0.75, 1.20) 3rd Trimester Adjusted <25th: 1.00 25 to <50th: 0.98 (0.87, 1.10) 50 to <75th: 0.92 (0.76, 1.11) 75 to <95th: 0.88 (0.75, 1.04) ≥ 95th: 0.91 (0.77, 1.07) Continuous: 0.96 (0.88, 1.06) Adjusted ORs by race/ethnicity Whites: 1st Trimester <25th: 1.00 25 to <50th: 1.13 (0.96, 1.33) 50 to <75th: 1.00 (0.92, 1.08) 75 to <95th: 1.00 (0.91, 1.09) ≥ 95th: 0.92 (0.81, 1.04) Continuous: 0.94 (0.90, 0.98) 2nd Trimester <25th: 1.00 25 to <50th: 0.88 (0.77, 1.02) 50 to <75th: 0.95 (0.89, 1.02) 75 to <95th: 0.95 (0.84, 1.07) ≥ 95th: 0.89 (0.64, 1.26) Continuous: 0.96 (0.89, 1.04) 3rd Trimester <25th: 1.00 25 to <50th: 0.84 (0.64, 1.11) 50 to <75th: 0.91 (0.83, 1.01) 75 to <95th: 0.80 (0.71, 0.90) ≥ 95th: 1.03 (0.86, 1.24) Continuous: 0.95 (0.90, 1.00) African Americans: 1st Trimester <25th: 1.00 25 to <50th: 1.01 (0.98, 1.05) 50 to <75th: 0.88 (0.79, 0.98) 75 to <95th: 0.83 (0.70, 0.97) ≥ 95th: 0.81 (0.67, 0.99) Continuous: 0.93 (0.85, 1.01) 2nd Trimester <25th: 1.00 25 to <50th: 1.10 (0.93, 1.30) 50 to <75th: 0.95 (0.80, 1.12) 75 to <95th: 0.88 (0.69, 1.11) ≥ 95th: 0.75 (0.54, 1.03) Continuous: 0.92 (0.80, 1.05) 3rd Trimester <25th: 1.00 25 to <50th: 1.08 (0.92, 1.27) 50 to <75th: 0.89 (0.70, 1.12) 75 to <95th: 0.94 (0.75, 1.18) ≥ 95th: 0.83 (0.71, 0.97) Continuous: 0.99 (0.87, 1.11) Hispanics: 1st Trimester <25th: 1.00 25 to <50th: 0.83 (0.64, 1.06) 50 to <75th: 0.86 (0.70, 1.05) 75 to <95th: 0.79 (0.68, 0.93) ≥ 95th: 1.36 (1.06, 1.75) Continuous: 0.96 (0.84, 1.09) 2nd Trimester <25th: 1.00 25 to <50th: 1.16 (0.84, 1.61) 50 to <75th: 0.86 (0.63, 1.19) 75 to <95th: 0.98 (0.71, 1.34) ≥ 95th: 0.68 (0.38, 1.21) Continuous: 0.92 (0.81, 1.05) 3rd Trimester <25th: 1.00 25 to <50th: 0.77 (0.55, 1.07) 50 to <75th: 1.12 (0.76, 1.66) 75 to <95th: 0.93 (0.65, 1.31) ≥ 95th: 0.90 (0.55, 1.47)



### December 2009 E-456

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Continuous: 0.96 (0.80, 1.15) Reference: Mannes et al.(2005, 087895 ) Period of Study: Jan 1998-Dec 2000

Location: Metropolitan Sydney, Australia Outcome: Risk of SGA and birth weight Age Groups: All singleton births >20 wk and ≥ 400 grams birth weight and maternal all ages Study Design: Cross-sectional

N: 138,056 singleton births Statistical Analyses: Logistic and linear regression models

Covariates: Sex of child, maternal age, gestational age, maternal smoking, gestational age at first antenatal visit, maternal indigenous status, whether first pregnancy, season of birth, socioeconomic status

Season: All seasons

Included as covariate Dose-response Investigated? No Statistical Package: SAS v8.02 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 16.8 (7.1)

25th: 12.3 50th(Median): 15.7

75th: 19.9 Range (Min, Max): (3.8-104.0) Monitoring Stations: up to 14 Copollutants (correlations): CO: r = 0.26

NO 2 : r = 0.47

O 3 : r = 0.52

PM 2.5 : r = 0.81 PM Increment: 1 μg/m 3

Risk of SGA All births One month before birth: OR = 1.01 (1.00-1.03) Third trimester: OR = 1.00 (0.99-1.013) Second trimester: OR = 1.01 (1.00-1.04) First trimester: OR = 1.00 (0.98-1.02) 5 km births One month before birth: OR = 1.00 (0.99- 1.02) Third trimester: OR = 1.01 (0.99-1.02) Second trimester: OR = 1.02 (1.01-1.03) First trimester: OR = 1.01 (0.99-1.02) Change in birth weight All births One month before birth: ß = -1.21 (-2.31- -0.11) Third trimester: ß = -0.95 (-2.30-0.40) Second trimester: ß = -2.05 (-3.36- -0.74) First trimester: ß = -0.14 (-1.37- 1.09) 5 km births One month before birth: ß = -2.98 (-4.25- -1.71) Third trimester: ß = -3.84 (-5.35- -2.33) Second trimester: ß = -4.28 (-5.79- -2.77) First trimester: ß = -2.57 (-4.04- -1.10) Key second trimester findings Single pollutant model: ß = -4.28 (-5.79- -2.77) 2 pollutant (PM 10 and CO): ß = -3.72 (-6.29- -1.15) 2 pollutant (PM 10 and NO 2 ): ß = -2.65 (-4.32- -0.98) 2 pollutant (PM 10 and O 3 ): ß = -5.47 (-7.06- -3.88) 4 pollutant (PM 10 , NO 2 , CO and O 3 ): ß = - 3.27 (-7.05-0.51) Controlling for exposures in other pregnancy periods: ß = -3.03 (-4.85- -1.21) Reference: Pereira et al. (1998, 007264 ) Period of Study: Jan 1991-Dec 1992

Location: Sao Paulo, Brazil

Notes: Paper does not focus on PM as a pollutant of interest. Outcome: Intrauterine mortality (fetuses over 28 wk of pregnancy) Study Design: Time-series

N: 730 days with PM measures Statistical Analyses: Poisson regression

Covariates: Season, day of the week and weather (temperature and relative humidity)

Season: Assessed by including 24 indicator variables for month and yr Dose-response Investigated? No Statistical Package: NR Lags Considered: Paper focuses on other pollutants (lags for PM not reported) Pollutant: PM 10 Averaging Time: 24 h mean Mean (SD): 65.04 (27.28) Range (Min, Max): (14.80, 192.80) Monitoring Stations: 13 (avgd to provide city-wide pollutant level) Copollutants (correlation): NO 2 (r = 0.45)

SO 2 (r = 0.74) CO (r = 0.41)

O 3 (r = 0.25) PM Increment: NR (reported only regression coefficients for PM) Effect Estimate [Lower CI, Upper CI]: Regression coefficients (standard errors) for pollutants when considered separately and simultaneously in the completed model: Separately: 0.0008 (0.0006) Simultaneously: -0.0005 (0.0010)



### December 2009 E-457

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ritz et al. (2000, 012068 ) Period of Study: 1989-1993

Location: Southern California Outcome: Preterm birth (treated dichotomously as birth at <37 wk gestation Also analyzed continuously) Age Groups: Infants (born vaginally between 26-44 wk of gestation) Study Design: Cross-sectional

N: 97,158 births Statistical Analyses: Logistic and linear regression

Covariates: Maternal age, race, education, parity, interval since the previous live birth, access to prenatal care, infant sex, previous low weight or preterm births, smoking (reported as “pregnancy complications”) To examine effect modification, authors conducted stratified analysis by region, birth and conception seasons, maternal age, race, education, and infant gender

Season: Some models included season of birth or conception

Also assessed as effect modifier in stratified analyses Dose-response Investigated?Examined adequacy of linear or loglinear relation using indicator terms for pollutant-avg quartilesResults presented in Fig 2 (doseresponse demonstrated for last 6 wk exposure period) Statistical Package: NR Pollutant: PM 10 Averaging Time: 24-h avg at 6 day intervals avgd pollutant measures for 1, 2, 4, 6, 8, 12, and 26 wk before birth and the whole pregnancy period Mean (SD): 6 wk before birth: 47.5 (15.0) 1st month of pregnancy: 49.3 (16.9) Range (Min, Max): 6 wk before birth: 12.3-152.3 1st month of pregnancy: 9.5-178.8 Monitoring Stations: 17 stations (PM measured at only 8 stations) Copollutants (correlations):

6 wk before birth: CO (r = 0.43)

NO 2 (r = 0.74)

O 3 (r = 0.20) 1st month of pregnancy: CO (r = 0.37)

NO 2 (r = 0.71)

O 3 (r = 0.23)

Notes: Avgd pollutant measures taken at the air monitoring station closest to the residence PM Increment: 50 μg/m 3 Effect Estimate [Lower CI, Upper CI]:

All 8 stations 6 wk before birth Crude: 1.20 (1.09, 1.33) 2 exposure periods: 1.18 (1.07, 1.31) Other risk factors: 1.15 (1.04, 1.26) Other RFs plus season: 1.15 (1.03, 1.29) Multipollutant model: 1.19 (1.01, 1.40) 1st month of pregnancy Crude: 1.16 (1.06, 1.26) 2 exposure periods: 1.13 (1.04, 1.24) Other risk factors: 1.09 (1.00, 1.19) Other RFs plus season: 1.09 (0.99, 1.20) Multipollutant model: 1.12 (0.97, 1.29) Coastal stations only 6 wk before birth Crude: 1.22 (1.00, 1.49) 2 exposure periods: 1.28 (1.04, 1.56) Other risk factors: 1.13 (0.93, 1.38) Other RFs plus season: 1.18 (0.92, 1.51) Multipollutant model: 1.42 (097, 2.01) 1st month of pregnancy Crude: 1.28 (1.06, 1.54) 2 exposure periods: 1.32 (1.09, 1.59) Other risk factors: 1.17 (0.97, 1.40) Other RFs plus season: 0.99 (0.79, 1.24) Multipollutant model: 1.09 (0.83, 1.41) Inland stations only 6 wk before birth Crude: 1.27 (1.12, 1.44) 2 exposure periods: 1.27 (1.11, 1.44) Other risk factors: 1.19 (1.05, 1.35) Other RFs plus season: 1.27 (1.10, 1.48) Multipollutant model: 1.18 (0.97, 1.43) 1st month of pregnancy Crude: 1.16 (1.04, 1.29) 2 exposure periods: 1.16 (1.04, 1.29) Other risk factors: 1.09 (0.98, 1.21) Other RFs plus season: 1.09 (0.97, 1.24) Multipollutant model: 1.11 (0.93, 1.33) Crude estimates for last 6 wk exposure by season Fall: 1.08 (0.88, 1.31) Summer: 1.06 (0.87, 1.29) Winter: 1.33 (1.07, 1.65) Spring: 1.81 (1.41, 2.31) Reduction in mean gestation length for each increase in PM 10 during last 6 wk before birth (linear regression analysis) Crude: 0.66 (± 0.24) days Adj: 0.90 (± 0.27) days Notes: Effect estimates remain stable when excluding SGA or LBW children or when restricting preterm births to SGA or LBW children only (results not presented)



### December 2009 E-458

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ritz, et al. (2002, 023227 ) Period of Study: 1987-1993

Location: Southern California (Jul 1990-Jul 1993 for Los Angeles, 1989 for Riverside, 1988-1989 for San Bernardino, and 1987-1989 for Orange counties Outcome: 1) Aortic defects 2) Defects of the atrium and atrium Sepum 3) Endocardial and mitral valve defects 4) Pulmonary artery and valve defects 5) Conotruncal defects including tetralogy of Fallot, transposition of great vessels, truncus arteriosus communis, double outlet right ventricle, and aorticopulmonary window and 6) Ventricular Sepal defects not included in the conotruncal category. Age Groups: All live born infants and fetal deaths diagnosed between 20 wk of gestation and 1 yr after birth Study Design: Case-control

N: 10,649 infants and fetuses Statistical Analyses: Hierarchical (twolevel) regression model, polytomous logistic regression, linear model

Covariates: Gender, no prenatal care, multiple births, no siblings, maternal race, maternal age, maternal education, born before 1990, season of conception,

Season: All Dose-response Investigated? Yes, for O 3 and CO, study found a clear doseresponse pattern for aortic Sepum and valve and ventricular Sepal defects and possibly for conotruncal and pulmonary artery and valve defects Statistical Package: SAS Pollutant: PM 10 Averaging Time: 24 h (every 6 days) PM Component: vehicle emissions Monitoring Stations: 11 (for PM 10 ) Copollutants (correlations): CO: r = 0.32

NO 2 (NR)

O 3 (NR) Notes: The authors did not observeconsistently increased risks and doseresponse patterns for PM 10 after controlling for the effects of CO and O 3 on these cardiac defects. (Quantitative results not shown).



### December 2009 E-459

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ritz et al. (2006, 089819 ) Period of Study: 1989-2000

Location: 389 South Coast Air Basin (SoCAB) zip codes Outcome: Total infant deaths during the first yr of life as well as all respiratory causes of death (ICD-9 codes 460-519, 769, 770.4, 770.7, 770.8, and 770.9 and ICD-10 codes J00-J98, P22.0, P22.9, P27.1, P27.9, P28.0, P28.4, P28.5, and P28.9) and sudden infant death syndrome (SIDS) (ICD-9 code 798.0 and ICD-10 code R95). Age Groups: Infants 0-1 yr Study Design: Case-control

N: 2,975,059 births and 19,664 infant deaths Cases, n = 13,146 Controls, n = 151,015 Statistical Analyses: Conditional logistic regression analysis

Covariates: Risk factors available on birth and/or death certificates (maternal age, race/ethnicity, and education, level of prenatal care, infant gender, parity, birth country, and death season)

Season: Death season (spring, summer, fall, winter) Dose-response Investigated? Yes Statistical Package: NR Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 2 wk before death: 46.2 1 month before death: 46.3 2 mo before death: 46.3 6 mo before death: 46.3 Range (Min, Max): 2 wk before death: (21.0-83.5) 1 month before death: ( 25.0-77.2) 2 mo before death: (27.6-74.2) 6 mo before death: (31.3-69.5) Monitoring Stations: maximum of 31 Copollutants (correlation): 2 wk before death CO: r = 0.33 NO 2 : r = 0.48 O 3 : r = 0.12 1 month before death CO: r = 0.33 NO 2 : r = 0.48 O 3 : r = 0.12 2 mo before death CO: r = 0.32 NO 2 : r = 0.48 O 3 : r = 0.12 6 mo before death CO: r = 0.29 NO 2 : r = 0.44 O 3 : r = 0.16 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]:

All-cause death 2 mo before death Single-pollutant model: <25th = 1.04 (1.01-1.06) 25th-75th = 0.96 (0.89-1.04) >75th = 1.14 (1.03-1.27) Multiple-pollutant model: <25th = 1.02 (0.99-1.05) 25th-75th = 0.92 (0.84-1.00) >75th = 1.07 (0.95-1.20) SIDS 2 mo before death: Single-pollutant model: <25th = 1.03 (0.99-1.08) 25th-75th = 0.94 (0.81-1.08) >75th = 1.13 (0.93-1.36) Multiple-pollutant model: <25th = 1.01 (0.95-1.07) 25th-75th = 0.90 (0.76-1.06) >75th = 0.99 (0.80-1.24) Respiratory death 2 wk before death Postneonatal deaths (28 days to 1 y) Single-pollutant model: <25th = 1.05 (1.01-1.10) 25th-75th = 1.13 (1.01-1.10) >75th = 1.46 (1.13-1.88) Multiple-pollutant model: <25th = 1.04 (0.98-1.09) 25th-75th = 1.09 (0.86-1.38) >75th = 1.40 (1.03-1.89) Postneonatal deaths (28 days to 3 mo) Single-pollutant model: <25th = 1.01 (0.95-1.08) 25th-75th = 1.16 (0.82-1.63) >75th = 1.44 (0.96-2.17) Multiple-pollutant model: <25th = 1.00 (0.92-1.09) 25th-75th = 0.97 (0.67-1.42) >75th = 1.23 (0.76-2.00) Post neonatal deaths (4-12 mo) Single-pollutant model: <25th = 1.12 (1.02-1.23) 25th-75th = 1.08 (0.81-1.44) >75th = 1.41 (1.02-1.96) Multiple-pollutant model: <25th = 1.07 (1.00-1.15) 25th-75th = 1.02 (0.75-1.40) >75th = 1.36 (0.92-2.01)



### December 2009 E-460

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Rogers et al. (2006, 091232 ) Period of Study: 1986-1988

Location: Georgia, USA Outcome : VLBW Term, AGA, Preter m AGA, Preterm, SGA Age Groups: Newborns and their mothers (<19 to ≥ 35-yr-old) Study Design: Case-control

N: 325 infants (69 preterm SGA 59 preterm AGA 197 term AGA) and their mothers Statistical Analyses: Logistic regression

Covariates: Maternal age, maternal race, maternal education, active and passive smoking, birth season, prepregnancy weight, pregnancy weight gain, maternal toxemia, anemia, asthma Dose-response Investigated? Yes, used Statistical Package : SUDAAN Cochran-Armitage test for trend to determine whether the observed proportions of cases and controls differed in a linear manner across exposure categories. Pollutant: PM 10 Averaging Time: annual

Preterm SGA: 50th(Median) : 3.38

Preterm AGA: 50th(Median) : 7.84

Term AGA: 50th(Median) : 3.23 Monitoring Stations : NR Percent Mothers Residing In County With Industrial Point Source Preterm SGA: 60.9% Preterm AGA: 79.7% Term AGA: 60.4% Percent Mothers Residing In PM 10 Quartile (based on environmental transport model) Preterm SGA 1st quartile (<1.48): 31.9% 2nd quartile (1.48-3.74): 18.8% 3rd quartile (3.75-15.07): 26.1% 4th quartile (>15.07): 23.2% Preterm AGA 1st quartile (<1.48): 16.9% 2nd quartile (1.48-3.74): 22.1% 3rd quartile (3.75-15.07): 28.8% 4th quartile (>15.07): 32.2% Term AGA 1st quartile (<1.48): 24.7% 2nd quartile (1.48-3.74): 28.4% 3rd quartile (3.75-15.07): 27.9% 4th quartile (>15.07): 19.3% PM Increment: Quartile

Notes: Statistically significant increases in the odds of VLBW and preterm AGA births are associated with living in a county with a PM 10 point source. Preterm AGA births are also associated with living in an area with very high (4th quartile) estimated PM 10 exposure. Delivery of VLBW vs. Term AGA infant County with point source 2.54 [1.46, 4.22] PM 10 quartile 1st quartile: reference 2nd quartile: 0.81 [0.42, 1.55] 3rd quartile: 0.85 [0.45, 1.16] 4th quartile: 1.94 [0.98, 3.83] Delivery of Preterm AGA vs. Term AGA infant County with point source 4.31 [1.88: 9.87] PM 10 quartile 1st quartile: reference 2nd quartile: 1.56 [0.56: 4.35] 3rd quartile: 1.19 [0.44: 3.23] 4th quartile: 3.68 [1.44: 9.44] Delivery of Preterm AGA vs. Preterm SGA infant County with point source 2.07 [0.83: 5.16] PM 10 quartile 1st quartile: reference 2nd quartile: 1.96 [0.59: 6.43] 3rd quartile: 2.10 [0.66: 6.73] 4th quartile: 2.58 [0.78: 8.51]



### December 2009 E-461

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Romieu et al. (2004, 093074 ) Period of Study: 1997-2001

Location: Ciudad Juarez, Mexico Outcome: Respiratory-related infant mortality ICD9 (460-519) ICD10 (J00-J99) Age Groups: 1 month to 1 yr Study Design: Case crossover

N: 216 respiratory-related deaths

N = 412 other causes and N = 628 total deaths Statistical Analyses: The acute effects of air pollution was modeled on both total and respiratory-related mortality as a function of the pollution levels on the same day and preceding days and over 2- and 3-day avg before the date ofdeath. Case-crossover with semisymmetric bidirectional referent selection was the approach used. Data were stratified by day of the week and calendar month. Data were analyzed with conditional logistic regression. Second and third polynomial distributed lag models were used to study lag structure. BIC was used to determine lag length.

Covariate : Temperature, season Dose-response Investigated? Yes Statistical Package: STATA 7.0 Lags Considered: 1-15 days Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 1997: 33.04 (20.67) μg/m 3 1998: 35.25 (17.32) μg/m 3 1999: 45.92 (28.69) μg/m 3 2000: 43.38 (23.77) μg/m 3 2001: 39.46 (29.43) μg/m 3 Monitoring Stations: 5 stations in Ciudad Juarez 2 stations in El Paso (close to U.S.- Mexico border) Copollutant (correlation): O 3 : r = 0.01

Notes: Ciudad Juarez monitors measured PM 10 every 6 days while El Paso monitors measured on a daily basis. PM Increment: 20 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: Total mortality: OR = 1.02 (0.94-1.11) lag 1 OR = 1.03 (0.95-1.12) lag 2 OR = 1.03 (0.94-1.13 ac2 OR = 1.04 (0.95-1.15) ac3 Respiratory mortality OR = 0.95 (0.83-1.09) lag 1 OR = 1.04 (0.91-1.19) lag 2 OR = 0.98 (0.81-1.19) ac2 OR = 0.97 (0.74-1.26) ac3 Higher SES OR = 0.82 (0.59, 1.14) lag 1 OR = 1.08 (0.84, 1.40) lag 2 OR = 0.89 (0.58, 1.35) ac2 OR = 0.97 (0.52, 1.82) ac3 Medium SES OR = 0.99 (0.79, 1.27) lag 1 OR = 1.11 (0.86, 1.43) lag 2 OR = 1.03 (0.73, 1.45) ac2 OR = 1.17 (0.72, 1.90) ac3 Lower SES OR = 1.61 (0.97-2.66) lag 1 OR = 1.07 (0.65, 1.75) lag 2 OR = 2.56 (1.06-6.17) ac2 OR = 1.76 (0.59, 5.23) ac3 Notes: ac2 and ac3 represent cumulative PM 10 ambient levels over 2 or 3 days before death.

Reference: Sagiv et al. (2005, 087468 ) Period of Study: Jan 1997-Dec 2001

Location: Allegheny county, Beaver county, Lackawanna county, Philadelphia county, Pennsylvania, U.S.A. Outcome: Preterm birth (<36 wk) Age Groups: Babies born between 20 and 44 wk Study Design: Time series

N: 3704 observation days, 187,997 births Statistical Analyses: Poisson regression

Multivariable mixed-effects model with a random intercept for each county to incorporate count-level information.

Covariates: Temperature, dew point temperature, mean 6-week level of copollutants (CO, NO 2 , and SO 2 ), longterm preterm birth trends

Season: All Dose-response Investigated? Yes Statistical Package: NR Lags Considered: 1, 2, 3, 4, 5, 6, 7 Pollutant: PM 10 Averaging Time: Daily used to calculate 6-week period Mean (SD): 6-week period 27.1 (8.3) Daily 25.3 (14.6)

Percentiles: 6-week period 50th (Median): 26.0 Daily 50th (Median): 21.6 Range (Min, Max): 6-week period: 8.7, 68.9 Daily: 2.0, 156.3 Monitoring Stations: NR Copollutant (correlation): Daily PM 10 -daily SO 2 : r = 0.46 Also considered CO, NO 2 and O 3 as copollutants. PM Increment: 1) 50 μg/m 3 2) Quartiles (first quartile is the reference) Exposure period: 6 wk before birth Per 50 μg/m 3 : 1.07 (0.98, 1.18) 2nd quartile: 1.00 (0.95, 1.05) 3rd quartile: 1.04 (0.99, 1.09) 4th quartile: 1.03 (0.98, 1.08) Exposure period: 1-day acute time windows Per 50 μg/m 3 : 2-day lag: 1.10 (1.00, 1.21) 5-day lag: 1.07 (0.98, 1.18) Notes: Within the article, authors provide a Fig 1 displaying a graph of the relative risk (RR) and 95% confidence i ntervals (CI) for 1- to 7-day lags. While the authors report the 2- and 5-day lag RRs and 95% CIs in the text, the others are not specifically reported. However, the Fig shows the approximate RRs per 50 μg/m 3 as indicated below: 1-day lag: 1.05 3-day lag: 1.05 4-day lag: 1.00 6-day lag: 0.97 7-day lag: 1.03



### December 2009 E-462

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Salam et al., 2005, 087885 ) Period of Study: 1975-1987

Location: Southern California Outcome: Birth weight Low birth weight (LBW <2500 g) Intrauterine growth retardation (IUGR) Age Groups: Children born full-term (between 37 and 44 wk) Study Design: Cohort study

N: 3901 children Statistical Analyses: Linear mixedeffects Logistic regression

Covariates: Maternal age, months since last live birth, parity, maternal smoking during pregnancy, SES, marital status at childbirth, gestational diabetes, child’s sex, child’s race/ethnicity, child’s grade in school (4th, 7th, and 10th), Julian day of birth

Season: All Dose-response Investigated? Yes Statistical Package: SAS Pollutant: PM 10 Averaging Time: Monthly Mean (SD): Entire pregnancy: 45.8 (12.9) First trimester: 46.6 (15.9) Second trimester: 45.4 (14.8) Third trimester: 45.4 (15.5) Monitoring Stations: 1 or 3 (See notes) Copollutant (correlation): Entire pregnancy PM 10 -O 3 [10-6]: r = 0.54 PM 10 -O 3 [24 h): r = 0.20 PM 10 -NO 2 : r = 0.55 PM 10 -CO: r = 0.41 First trimester PM 10 -O 3 [10-6]: r = 0.54 PM 10 -O 3 [24 h]: r = 0.34 PM 10 -NO 2 : r = 0.48 PM 10 -CO: r = 0.29 Second trimester PM 10 -O 3 [10-6): r = 0.50 PM 10 -O 3 (24 h): r = 0.27 PM 10 -NO 2 : r = 0.53 PM 10 -CO: r = 0.35 Third trimester PM 10 -O 3 [10-6]: r = 0.52 PM 10 -O 3 [24 h]: r = 0.31 PM 10 -NO 2 : r = 0.52 PM 10 -CO: r = 0.37 Notes: Exposure estimates were calculated by spatially interpolated monthly avg which were based off of three monitoring stations located within 50 km of the ZIP code region of maternal birth residences. PM Increment: IQR (interquartile range) Outcome: birth weight (g) Single-pollutant model Entire pregnancy 18 μg/m 3 : -19.9 (-43.6, 3.8) First trimester 20 μg/m 3 : -3.0 (-22.7, 16.7) Second trimester 19 μg/m 3 : -15.7 (-36.1, 4.7) Third trimester 20 μg/m 3 : -21.7 (-42.2 to -1.1) Multipollutant model (Included O 3 (24 h) in model Third trimester exposure) 20 μg/m 3 : -10.8 (-31.8, 10.2) Outcome: IUGR (ORs) Single-pollutant model Entire pregnancy 18 μg/m 3 : 1.1 (0.9, 1.3) First trimester 20 μg/m 3 : 1.0 (0.9, 1.2) Second trimester 19 μg/m 3 : 1.0 (0.9, 1.2) Third trimester 20 μg/m 3 : 1.1 (0.9, 1.3) Outcome: LBW Single-pollutant model Entire pregnancy 18 μg/m 3 : 1.3 (0.8, 2.2) First trimester 20 μg/m 3 : 1.0 (0.7, 1.5) Second trimester 19 μg/m 3 : 1.2 (0.8, 1.7) Third trimester 20 μg/m 3 : 1.3 (0.9, 1.9) Notes: Numbers reported for birth weight outcome are the effects on birth weight outcome (the change in birth weight in grams) across the IQR (which vary depending on air pollutant and duration of exposure measurement).

Reference: (Sokol et al., 2006, 098539 ) Period of Study: Jan 1996-Dec 1998

Location: Los Angeles, California Outcome: Semen Quality Study Design: Panel Statistical Analysis: Univariate and Multivariate Regression Statistical Package: SAS Age Groups: Males ranging 19-35 in age Pollutant: PM 10 Averaging Time: 0-9d, 10-14d and 70- 90d Mean (SD) Unit: 35.74 ± 13.83 μg/m 3 Copollutant (correlation): O 3 , NO 2 , CO PM 10 specific results are given in Fig 3-. PM 10 was not significantly correlated with sperm quality.

Reference: (Suh et al., 2007, 157028 ) Period of Study: 2001-2004

Location: Seoul, Korea Outcome: Birth weight Age Groups: Prenatal follow-up for newborns Study Design: based prospective cohort study

N: 199 pregnant mothers Statistical Analyses: ANCOVA, generalized linear models

Covariates: infant’s sex, maternal age, maternal and paternal education, parity, presence of illness during pregnancy, delivery month, gestational age (squared) Dose-response Investigated? Yes Statistical Package : SAS Pollutant: PM 10 Averaging Time: 24-h Mean (SD): 1st trimester: 76.41 (28.80) 2nd trimester: 77.84 (31.63) 3rd trimester: 95.61 (26.15)

Percentiles: 1st trimester 25th: 55.28 50th(Median): 71.09 75th: 92.38 2nd trimester 25th: 48.65 50th(Median): 72.36 75th: 108.00 3rd trimester 25th: 77.10 50th(Median): 96.35 75th: 116.68 Range (Min, Max): 1st trimester (21.00, 151.65) 2nd trimester (31.45, 139.13) PM Increment: Trimester ≥ 90th percentile compared to <90thpercentile Least-square (ANCOVA) mean (SE) All Genotypes 1st trimester <90th , N(%): 158 (90.3%): 3253 (37) ≥ 90th percentile, N(%): 17 (9.7%): 2841 (145) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.009 Adjusted, with CO: 0.041 Adjusted, with NO 2 : 0.092 Adjusted, with SO 2 : 0.012 2nd trimester <90th percentile, N(%): 153 (89.5%): 3253 (39) ≥ 90th percentile, N(%): 18 (10.5%): 3026 (157) P-Value for mean birth weight for ≥ 90th



### December 2009 E-463

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 3rd trimester (23.45, 172.75) Monitoring Stations : 27

Copollutant: CO SO 2 NO 2 percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.177 Adjusted, with CO: 0.203 Adjusted, with NO 2 : 0.151 Adjusted, with SO 2 : 0.151 3rd trimester <90th percentile, N(%): 162 (90.5%): 3226 (38) ≥ 90th percentile, N(%): 17 (9.5%): 3122 (140) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.487 Adjusted, with CO: 0.748 Adjusted, with NO 2 : 0.420 Adjusted, with SO 2 : 0.466 Genotype MspI TT 1st trimester <90th percentile, N(%): 60 (34.3%): 3350 (64) ≥ 90th percentile, N(%): 5 (2.9%): 3001 (229) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.147 Adjusted, with CO: 0.186 Adjusted, with NO 2 : 0.430 Adjusted, with SO 2 : 0.155 2nd trimester <90th percentile, N(%): 59 (34.5%): 3335 (66) ≥ 90th percentile, N(%): 6 (3.5%): 3281 (249) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.833 Adjusted, with CO: 0.833 Adjusted, with NO 2 : 0.778 Adjusted, with SO 2 : 0.806 3rd trimester <90th percentile, N(%): 61 (34.1%): 3327 (65) ≥ 90th percentile, N(%): 6 (3.4%): 3227 (300) p-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.749 Adjusted, with CO: 0.980 Adjusted, with NO 2 : 0.635 Adjusted, with SO 2 : 0.687 Genotype MspI TC/CC 1st trimester <90th percentile, N(%): 98 (56.0%): 3193 (48) ≥ 90th percentile, N(%): 12 (6.9%): 2799 (169) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.033 Adjusted, with CO: 0.073 Adjusted, with NO 2 : 0.150 Adjusted, with SO 2 : 0.036 2nd trimester <90th percentile, N(%): 94 (55.0%): 3200 (52) ≥ 90th percentile, N(%): 12 (7.0%): 2933 (176) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.161 Adjusted, with CO: 0.172



### December 2009 E-464

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Adjusted, with NO 2 : 0.152 Adjusted, with SO 2 : 0.158 3rd trimester <90th percentile, N(%): 101 (56.4%): 3165 (49) ≥ 90th percentile, N(%): 11 (6.2%): 3087 (147) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.626 Adjusted, with CO: 0.978 Adjusted, with NO 2 : 0.551 Adjusted, with SO 2 : 0.614 Genotype NcoI IleIle 1st trimester <90th percentile, N(%): 87 (49.7%): 3244 (52) ≥ 90th percentile, N(%): 7 (4.0%): 2983 (232) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.289 Adjusted, with CO: 0.344 Adjusted, with NO 2 : 0.641 Adjusted, with SO 2 : 0.293 2nd trimester <90th percentile, N(%): 82 (48.0%): 3243 (55) ≥ 90th percentile, N(%): 11 (6.4%): 3185 (207) p-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.790 Adjusted, with CO: 0.783 Adjusted, with NO 2 : 0.707 Adjusted, with SO 2 : 0.733 3rd trimester <90th percentile, N(%): 90 (50.3%): 3239 (53) ≥ 90th percentile, N(%): 9 (5.0%): 2944 (198) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.161 Adjusted, with CO: 0.279 Adjusted, with NO 2 : 0.134 Adjusted, with SO 2 : 0.150 Genotype NcoI IleVal/ValVal 1st trimester <90th percentile, N(%): 71 (40.6%): 3262 (56) ≥ 90th percentile, N(%): 10 (5.7%): 2773 (171) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.009 Adjusted, with CO: 0.031 Adjusted, with NO 2 : 0.058 Adjusted, with SO 2 : 0.010 2nd trimester <90th percentile, N(%): 71 (41.5%): 3264 (61) ≥ 90th percentile, N(%): 7 (4.1%): 2862 (208) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.076 Adjusted, with CO: 0.093 Adjusted, with NO 2 : 0.063 Adjusted, with SO 2 : 0.061 3rd trimester <90th percentile, N(%): 72 (40.2%): 3207



### December 2009 E-465

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) (58) ≥ 90th percentile, N(%): 8 (4.5%): 3262 (180) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.777 Adjusted, with CO: 0.607 Adjusted, with NO 2 : 0.843 Adjusted, with SO 2 : 0.791 Reference: Tsai et al. (2006, 090709 ) Period of Study: 1994-2000

Location: Kaohsiung, Taiwan Outcome: Post neonatal mortality Age Groups: Infants more than 27 days and less than 1 yr Study Design: Case-crossover study

N: 207 deaths Statistical Analyses: Conditional logistic regression

Covariates: Temperature, humidity Dose-response Investigated? No Statistical Package: SAS, version 8.2 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 81.45 μg/m 3

Percentiles: 25th: 44.50 50th(Median): 79.20

75th: 111.50 Range (Min, Max): (20.50-232.00) Monitoring Stations: 6 Copollutant: SO 2 NO 2 CO O 3 PM Increment: 67.00 μg/m 3 Effect Estimate [Lower CI, Upper CI]: OR = 1.040 (0.340-3.177)

Note: Air pollution levels at the dates of infant death were compared with air pollution levels 1 week before and 1 week after death A cumulative lag up to 2 previous days was used to assign exposure.

Reference: Wilhelm and Ritz (2005, 088668 ) Period of Study: 1994-2000

Location: Los Angeles County, California, U.S. Outcome: Term low birth weight (LBW) (<2500 g at ≥ 37 completed wk gestation), Vaginal birth <37 completed wk gestation Age Groups: LBW: ≥ 37 completed wk Preterm births: <37 completed wk Study Design: Cross-sectional

N: For LBW: 136,134 For preterm birth: 106,483 Statistical Analyses: Logistic regression

Covariates: Maternal age, maternal race, maternal education, parity, interval since previous live birth, level of prenatal care, infant sex, previous LBW or preterm infant, birth season, other pollutants (CO, NO 2 , O 3 , PM 10 ), gestational age (in birth weight analysis) Dose-response Investigated? Yes Statistical Package: NR Pollutant: PM 10 Averaging Time: 24 h (every 6 days) Entire pregnancy Trimesters of pregnancy Months of pregnancy 6 wk before birth Mean (SD): First trimester: 42.2 Third trimester: 41.5 6 wk before birth: 39.1 Range (Min, Max): First trimester: 26.3, 77.4 Third trimester: 25.7, 74.6 6 wk before birth: 13.0, 103.7 Monitoring Stations: Zip-code-level analysis: 8 Address-level analysis: 6 Copollutant (correlation): First trimester: PM 10 -CO: r = 0.12 PM 10 -NO 2 : r = 0.29 PM 10 -O 3 : r = -0.01 PM 10 -PM 2.5 : r = 0.43 Third trimester: PM 10 -CO: r = 0.32 PM 10 -NO 2 : r = 0.45 PM 10 -O 3 : r = -0.08 PM 10 -PM 2.5 : r = 0.52 6 wk before birth: PM 10 -CO: r = 0.36 PM 10 -NO 2 : r = 0.49 PM 10 -O 3 : r = -0.16 PM 10 -PM 2.5 : r = 0.60 PM Increment: 1) 10 μg/m 3 2) 3 levels: a) <25 percentile (reference) b) 25%-75 percentile c) ≥ 75 percentile Incidence of LBW (third trimester exposure) <32.8 μg/m 3 : 2.0 (1.8, 2.2) 32.8 to <43.4 μg/m 3 : 2.0 (1.9, 2.1) ≥ 43.4 μg/m 3 : 2.2 (2.0, 2.4) Incidence of preterm birth (first trimester exposure) <32.9 μg/m 3 : 8.7 (8.3, 9.2) 32.9 to <43.9 μg/m 3 : 8.8 (8.5, 9.1) ≥ 43.9 μg/m 3 : 8.6 (8.1, 9.0) Incidence of preterm birth (6 wk before birth exposure) <31.8 μg/m 3 : 8.8 (8.4, 9.3) 31.8 to <44.1 μg/m 3 : 8.6 (8.3, 8.9) ≥ 44.1 μg/m 3 : 8.8 (8.4, 9.2)

Outcome: LBW Exposure Period: Third trimester Address-level analysis: Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.22 (1.05, 1.41) 33.4 to <44.7 μg/m 3 : 1.08 (0.76, 1.52) ≥ 44.7 μg/m 3 : 1.48 (1.00, 2.19) Multipollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.36 (1.12, 1.65) 33.4 to <44.7 μg/m 3 : 1.16 (0.77, 1.74) ≥ 44.7 μg/m 3 : 1.58 (0.95, 2.62) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 0.98 (0.90, 1.06) 33.4 to <44.7 μg/m 3 : 0.95 (0.80, 1.13) ≥ 44.7 μg/m 3 : 0.96 (0.78, 1.18) Multipollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.02 (0.92, 1.14) 33.4 to <44.7 μg/m 3 : 0.93 (0.77, 1.12) ≥ 44.7 μg/m 3 : 1.02 (0.79, 1.32) Single-pollutant model:



### December 2009 E-466

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.03 (0.99, 1.08) 33.9 to <45.0 μg/m 3 : 1.04 (0.96, 1.14) ≥ 45.0 μg/m 3 : 1.08 (0.97, 1.20) Multipollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.04 (0.98, 1.09) 33.9 to <45.0 μg/m 3 : 1.02 (0.92, 1.12) ≥ 45.0 μg/m 3 : 1.06 (0.93, 1.21)

Zip-code-level analysis Single-pollutant model: Per 10 μg/m 3 : 1.03 (0.97, 1.09) 33.2 to <43.6 μg/m 3 : 0.98 (0.86, 1.11) ≥ 43.6 μg/m 3 : 1.03 (0.88, 1.21) Multipollutant model: Per 10 μg/m 3 : 1.07 (0.99, 1.15) 33.2 to <43.6 μg/m 3 : 0.97 (0.85, 1.12) ≥ 43.6 μg/m 3 : 1.09 (0.90, 1.31)

Outcome: LBW Exposure Period: Entire pregnancy period Address-level analysis: Multipollutant model: Per 10 μg/m 3 : 1.24 (0.91, 1.70)

Outcome: Preterm Birth Exposure Period: First trimester of pregnancy Address-level analysis : Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.00 (0.93, 1.09) 33.3 to <45.1 μg/m 3 : 1.07 (0.90, 1.26) ≥ 45.1 μg/m 3 : 1.12 (0.91, 1.38) Multipollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.00 (0.90, 1.12) 33.3 to <45.1 μg/m 3 : 1.12 (0.92, 1.36) ≥ 45.1 μg/m 3 : 1.17 (0.90, 1.50) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.01 (0.97, 1.05) 33.7 to <45.3 μg/m 3 : 1.03 (0.95, 1.12) ≥ 45.3 μg/m 3 : 1.07 (0.97, 1.19) Multipollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.04 (0.99, 1.10) 33.7 to <45.3 μg/m 3 : 1.07 (0.98, 1.17) ≥ 45.3 μg/m 3 : 1.13 (1.00, 1.27) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.01 (0.99, 1.03) 34.1 to <45.5 μg/m 3 : 1.03 (0.99, 1.08) ≥ 45.5 μg/m 3 : 1.02 (0.96, 1.07) Multipollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 0.99 (0.97, 1.02) 34.1 to <45.5 μg/m 3 : 0.99 (0.95, 1.04) ≥ 45.5 μg/m 3 : 0.94 (0.89, 1.01)

Zip-code-level analysis Single-pollutant model: Per 10 μg/m 3 : 0.99 (0.96, 1.01) 33.3 to <44.2 μg/m 3 : 1.01 (0.95, 1.08) ≥ 44.2 μg/m 3 : 0.98 (0.90, 1.05) Multipollutant model: Per 10 μg/m 3 : 0.99 (0.96, 1.03) 33.3 to <44.2 μg/m 3 : 1.03 (0.97, 1.11) ≥ 44.2 μg/m 3 : 1.01 (0.92, 1.11)

Outcome: Preterm birth Exposure Period: 6 wk before birth Address-level analysis: Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.02 (0.95, 1.10)



### December 2009 E-467

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 32.5 to <44.8 μg/m 3 : 1.09 (0.92, 1.29) ≥ 44.8 μg/m 3 : 1.12 (0.92, 1.37) Multipollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.06 (0.97, 1.16) 32.5 to <44.8 μg/m 3 : 1.09 (0.90, 1.31) ≥ 44.8 μg/m 3 : 1.17 (0.91, 1.49) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.00 (0.96, 1.03) 32.3 to <45.3 μg/m 3 : 0.99 (0.91, 1.07) ≥ 45.3 μg/m 3 : 0.99 (0.89, 1.10) Multipollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.01 (0.97, 1.06) 32.3 to <45.3 μg/m 3 : 1.00 (0.92, 1.10) ≥ 45.3 μg/m 3 : 1.02 (0.91, 1.16) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 0.99 (0.98, 1.01) 33.1 to <45.3 μg/m 3 : 1.00 (0.96, 1.05) ≥ 45.3 μg/m 3 : 0.98 (0.93, 1.03) Multipollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.00 (0.98, 1.02) 33.1 to <45.3 μg/m 3 : 1.01 (0.96, 1.05) ≥ 45.3 μg/m 3 : 0.98 (0.92, 1.04)

Zip-code-level analysis Single-pollutant model: Per 10 μg/m 3 : 1.02 (0.99, 1.04) 32.1 to <44.3 μg/m 3 : 1.01 (0.95, 1.07) ≥ 44.3 μg/m 3 : 1.04 (0.96, 1.12) Multipollutant model: Per 10 μg/m 3 : 1.02 (0.99, 1.06) 32.1 to <44.3 μg/m 3 : 1.02 (0.95, 1.09) ≥ 44.3 μg/m 3 : 1.04 (0.95, 1.14) Notes: multipollutant model adds CO,NO 2 , and O 3 in addition to the main pollutant of interest, PM 10

. Reference: Woodruff et al. (1997, 084271 ) Period of Study: 1989-1991

Location: 86 Metropolitan Statistical Areas in the U.S. (counties with populations less than 100,000 were excluded) Outcome: Postneonatal mortality (death of an infant between 1 month and 1 yr of age) 1) All post neonatal deaths 2) Normal birth weight (NBW, ≥ 2500 g) SIDS deaths 3) NBW respiratory deaths 4) Low birth weight (LBW) respiratory death Respiratory deaths: ICD9 codes 460- 519

SIDS: ICD9 code 798.0 Age Groups: Infants (1 month-1yr of age) Study Design: Cross-sectional

N: 3,788,079 infants Statistical Analyses: Logistic regression

Covariates: Maternal education, maternal race, parental marital status, maternal smoking during pregnancy Avg temperature during the first 2 mo of life Infant’s month and yr of birthAssessed race as an effect modifier (pval for interaction terms >0.2) Dose-response Investigated? Yes Statistical Package: NR Pollutant: PM 10 Averaging Time: Mean of 1st 2 mo of life analyzed as tertiles of exposure and as continuous exposure Mean (SD): 31.4 (7.8) Range (Min, Max):

Overall: 11.9-68.8 Low category: <28.0 Medium category: 28.1-40.0 High category: >40.0 Monitoring Stations: NR PM Increment: 10 μg/m 3 (for continuous exposure analysis) Adjusted ORs for cause-specific post neonatal mortality by pollution category (tertiles) All causes Low: Ref Medium: 1.05 (1.01, 1.09) High: 1.10 (1.04, 1.16) SIDS, NBW: Low: Ref Medium: 1.09 (1.01, 1.17) High: 1.26 (1.14, 1.39) Respiratory death, NBW: Low: Ref Medium: 1.08 (0.87, 1.33) High: 1.40 (1.05, 1.85) Respiratory death, LBW: Low: Ref Medium: 0.93 (0.73, 1.18) High: 1.18 (0.86, 1.61) All other causes: Low: Ref Medium: 1.03 (0.97, 1.08) High: 0.97 (0.90, 1.04) Adjusted ORs for a continuous 10 μg/m 3 change in exposure All causes: 1.04 (1.02, 1.07) SIDS, NBW: 1.12 (1.07, 1.17) Respiratory death NBW: 1.20 (1.06, 1.36) Respiratory death LBW: 1.05 (0.91, 1.22) All other causes: 1.00 (0.99, 1.00)



### December 2009 E-468

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Woodruff et al. (2008, 098386 ) Period of Study: 1999-2002

Location: U.S. counties with >250,000 residents (96 counties) Outcome: Postneonatal deaths Respiratory mortality (ICD10: J000-99, plus bronchopulmonary dysplasia [BPD] P27.1) SIDS (ICD10: R95) Ill-defined causes (R99);

All other deaths evaluated as a control category Age Groups: Infants aged >28 days and <1 yr Study Design: Cross-sectional

N: 3,583,495 births (6,639 post neonatal deaths) Statistical Analyses: Logistic GEE (exchangeable correlation structure)

Covariates: Maternal race/ethnicity, marital status, age, education, primiparity, county-level poverty and per capita income levels, yr and month of birth dummy variables to account for time trend and seasonal effects, and region of the country Sensitivity analyses performed among only those mothers with smoking information (adjustment for smoking had no effect on the estimates)

Season: Adjusted for yr and month of birth dummy variables to account for time trend and seasonal effects Dose-response Investigated? Evaluated the appropriateness of a linear form from analysis based on quartiles of exposure and concluded that linear form was appropriate (data not shown) Statistical Package: SAS Pollutant: PM 10 Averaging Time: Measured continuously for 24 h once every 6 days exposure assigned by calculating avg concentration of pollutant during first 2 mo of life Median and IQR (25th-75th percentile): Survivors: 28.9 (23.3-34.4) All causes of death: 29.1 (23.9-34.5) Respiratory: 29.8 (24.3-36.5) SIDS: 28.6 (23.5-33.8) SIDS + ill-defined: 28.8 (23.9-33.9) Other causes: 29.2 (23.9-34.5)

Percentiles: see above PM Component: Not assessed, but controlled for region of the country to account for PM composition variation Monitoring Stations: NR Copollutant (correlation): PM 10 PM 2.5 (r = 0.34) CO (r = 0.18)

SO 2 (r = 0.00)

O 3 (r = 0.20)

Notes: Monthly avg calculated if there were at least 3 available measures for PM Assigned exposures using the avg concentration of the county of residence PM Increment: IQR (11 μg/m 3 ) Effect Estimate [Lower CI, Upper CI]: Adjusted ORs for single pollutant models All causes: 1.04 (0.99, 1.10) Respiratory: 1.18 (1.06, 1.31) SIDS: 1.02 (0.89, 1.16) Ill-defined + SIDS: 1.06 (0.97, 1.16) Other causes: 1.02 (0.96, 1.07) Adjusted ORs for multipollutant models (including CO, O 3 , SO 2 ) Respiratory: 1.16 (1.04, 1.30) SIDS: 1.02 (0.90, 1.16) OR for deaths coded as BPD per increase in IQR: 1.19 (0.85, 1.65) OR for respiratory post neonatal death stratified by birth weight NBW only: 1.19 (1.05, 1.36) LBW only: 1.12 (0.95, 1.31) OR for respiratory deaths removing region of U.S. as a confounding variable: 1.30 (1.04, 1.61) OR for respiratory deaths assessing exposure as quartiles Highest vs. Lowest quartile: 1.31 (1.00, 1.71)

OR for respiratory deaths among only those deaths that occurred during the first 90 days (most closely matched exposure metric of the avg over the first 2 mo of life): 1.25 (1.06, 1.47)

Reference: (Suh et al., 2007, 157028 ) Period of Study: 2001-2004

Location: Seoul, Korea Outcome: Birth weight Age Groups: Prenatal follow-up for newborns Study Design: Based prospective cohort study

N: 199 pregnant mothers Statistical Analyses: ANCOVA, generalized linear models

Covariates: Infant’s sex, maternal age, maternal and paternal education, parity, presence of illness during pregnancy, delivery month, gestational age (squared) Dose-response Investigated? Yes Statistical Package : SAS Pollutant: PM 10 Averaging Time: 24-h Mean (SD): 1st trimester: 76.41 (28.80) 2nd trimester: 77.84 (31.63) 3rd trimester: 95.61 (26.15) Percentiles: 1st trimester 25th: 55.28 50th(Median): 71.09 75th: 92.38 2nd trimester 25th: 48.65 50th(Median): 72.36 75th: 108.00 3rd trimester 25th: 77.10 50th(Median): 96.35 75th: 116.68 Range (Min, Max): 1st trimester (21.00, 151.65) 2nd trimester (31.45, 139.13) 3rd trimester (23.45, 172.75) Monitoring Stations : 27 Copollutant: CO SO 2 PM Increment: Trimester ≥ 90th percentile compared to <90th percentile Least-square (ANCOVA) mean (SE) All Genotypes 1st trimester <90th percentile, N(%): 158 (90.3%): 3253 (37) ≥ 90th percentile, N(%): 17 (9.7%): 2841 (145) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.009 Adjusted, with CO: 0.041 Adjusted, with NO 2 : 0.092 Adjusted, with SO 2 : 0.012 2nd trimester <90th percentile, N(%): 153 (89.5%): 3253 (39) ≥ 90th percentile, N(%): 18 (10.5%): 3026 (157) p-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.177 Adjusted, with CO: 0.203 Adjusted, with NO 2 : 0.151 Adjusted, with SO 2 : 0.151 3rd trimester <90th percentile, N(%):



### December 2009 E-469

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

NO 2 162 (90.5%): 3226 (38) ≥ 90th percentile, N(%): 17 (9.5%): 3122 (140) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.487 Adjusted, with CO: 0.748 Adjusted, with NO 2 : 0.420 Adjusted, with SO 2 : 0.466 Genotype MspI TT 1st trimester <90th percentile, N(%): 60 (34.3%): 3350 (64) ≥ 90th percentile, N(%): 5 (2.9%): 3001 (229) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.147 Adjusted, with CO: 0.186 Adjusted, with NO 2 : 0.430 Adjusted, with SO 2 : 0.155 2nd trimester <90th percentile, N(%): 59 (34.5%): 3335 (66) ≥ 90th percentile, N(%): 6 (3.5%): 3281 (249) p-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.833 Adjusted, with CO: 0.833 Adjusted, with NO 2 : 0.778 Adjusted, with SO 2 : 0.806 3rd trimester <90th percentile, N(%): 61 (34.1%): 3327 (65) ≥ 90th percentile, N(%): 6 (3.4%): 3227 (300) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.749 Adjusted, with CO: 0.980 Adjusted, with NO 2 : 0.635 Adjusted, with SO 2 : 0.687 Genotype MspI TC/CC 1st trimester <90th percentile, N(%): 98 (56.0%): 3193 (48) ≥ 90th percentile, N(%): 12 (6.9%): 2799 (169) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.033 Adjusted, with CO: 0.073 Adjusted, with NO 2 : 0.150 Adjusted, with SO 2 : 0.036 2nd trimester <90th percentile, N(%): 94 (55.0%): 3200 (52) ≥ 90th percentile, N(%): 12 (7.0%): 2933 (176) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.161 Adjusted, with CO: 0.172 Adjusted, with NO 2 : 0.152 Adjusted, with SO 2 : 0.158 3rd trimester <90th percentile, N(%): 101 (56.4%): 3165 (49) ≥ 90th percentile, N(%): 11 (6.2%): 3087 (147) P-Value for mean birth weight for



### December 2009 E-470

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.626 Adjusted, with CO: 0.978 Adjusted, with NO 2 : 0.551 Adjusted, with SO 2 : 0.614 Genotype NcoI IleIle 1st trimester <90th percentile, N(%): 87 (49.7%): 3244 (52) ≥ 90th percentile, N(%): 7 (4.0%): 2983 (232) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.289 Adjusted, with CO: 0.344 Adjusted, with NO 2 : 0.641 Adjusted, with SO 2 : 0.293 2nd trimester <90th percentile, N(%): 82 (48.0%): 3243 (55) ≥ 90th percentile, N(%): 11 (6.4%): 3185 (207) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.790 Adjusted, with CO: 0.783 Adjusted, with NO 2 : 0.707 Adjusted, with SO 2 : 0.733 3rd trimester <90th percentile, N(%): 90 (50.3%): 3239 (53) ≥ 90th percentile, N(%): 9 (5.0%): 2944 (198) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.161 Adjusted, with CO: 0.279 Adjusted, with NO 2 : 0.134 Adjusted, with SO 2 : 0.150 Genotype NcoI IleVal/ValVal 1st trimester <90th percentile, N(%): 71 (40.6%): 3262 (56) ≥ 90th percentile, N(%): 10 (5.7%): 2773 (171) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.009 Adjusted, with CO: 0.031 Adjusted, with NO 2 : 0.058 Adjusted, with SO 2 : 0.010 2nd trimester <90th percentile, N(%): 71 (41.5%): 3264 (61) ≥ 90th percentile, N(%): 7 (4.1%): 2862 (208) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.076 Adjusted, with CO: 0.093 Adjusted, with NO 2 : 0.063 Adjusted, with SO 2 : 0.061 3rd trimester <90th percentile, N(%): 72 (40.2%): 3207 (58) ≥ 90th percentile, N(%): 8 (4.5%): 3262 (180) P-Value for mean birth weight for ≥ 90th percentile PM 10 vs. for <90th percentile PM 10 Adjusted: 0.777 Adjusted, with CO: 0.607



### December 2009 E-471

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Adjusted, with NO 2 : 0.843 Adjusted, with SO 2 : 0.791 Reference: Tsai et al. (2006, 098312 ) Period of Study: 1994-2000

Location: Kaohsiung, Taiwan Outcome: Post neonatal mortality Age Groups: Infants more than 27 days and less than 1 yr Study Design: Case-crossover study

N: 207 deaths Statistical Analyses: Conditional logistic regression

Covariates: Temperature, humidity Dose-response Investigated? No Statistical Package: SAS, version 8.2 Pollutant: PM 10 Averaging Time: 24 h Mean (SD): 81.45 μg/m 3

Percentiles: 25th: 44.50 50th(Median): 79.20

75th: 111.50 Range (Min, Max): (20.50-232.00) Monitoring Stations: 6 Copollutant: SO 2 NO 2 CO O 3 PM Increment: 67.00 μg/m 3 Effect Estimate [Lower CI, Upper CI]: OR = 1.040 (0.340-3.177)

Note: Air pollution levels at the dates of infant death were compared with air pollution levels 1 week before and 1 week after death A cumulative lag up to 2 previous days was used to assign exposure.

Reference: Wilhelm and Ritz (2005, 088668 ) Period of Study: 1994-2000

Location: Los Angeles County, California, U.S. Outcome: Term low birth weight (LBW) (<2500 g at ≥ 37 completed wk gestation), Vaginal birth <37 completed wk gestation Age Groups: LBW: ≥ 37 completed wk Preterm births: <37 completed wk Study Design: Cross-sectional

N: For LBW: 136,134 For preterm birth: 106,483 Statistical Analyses: Logistic regression

Covariates: Maternal age, maternal race, maternal education, parity, interval since previous live birth, level of prenatal care, infant sex, previous LBW or preterm infant, birth season, other pollutants (CO, NO 2 , O 3 , PM 10 ), gestational age (in birth weight analysis) Dose-response Investigated? Yes Statistical Package: NR Pollutant: PM 10 Averaging Time: 24 h (every 6 days) Entire pregnancy Trimesters of pregnancy Months of pregnancy 6 wk before birth Mean (SD): First trimester: 42.2 Third trimester: 41.5 6 wk before birth: 39.1 Range (Min, Max): First trimester: 26.3, 77.4 Third trimester: 25.7, 74.6 6 wk before birth: 13.0, 103.7 Monitoring Stations: Zip-code-level analysis: 8 Address-level analysis: 6 Copollutant (correlation): First trimester: PM 10 -CO: r = 0.12 PM 10 -NO 2 : r = 0.29 PM 10 -O 3 : r = -0.01 PM 10 -PM 2.5 : r = 0.43 Third trimester: PM 10 -CO: r = 0.32 PM 10 -NO 2 : r = 0.45 PM 10 -O 3 : r = -0.08 PM 10 -PM 2.5 : r = 0.52 6 wk before birth: PM 10 -CO: r = 0.36 PM 10 -NO 2 : r = 0.49 PM 10 -O 3 : r = -0.16 PM 10 -PM 2.5 : r = 0.60 PM Increment: 1) 10 μg/m 3 2) 3 levels: a) <25 percentile (reference) b) 25%-75 percentile c) ≥ 75 percentile Incidence of LBW (third trimester exposure) <32.8 μg/m 3 : 2.0 (1.8, 2.2) 32.8 to <43.4 μg/m 3 : 2.0 (1.9, 2.1) ≥ 43.4 μg/m 3 : 2.2 (2.0, 2.4) Incidence of preterm birth (first trimester exposure) <32.9 μg/m 3 : 8.7 (8.3, 9.2) 32.9 to <43.9 μg/m 3 : 8.8 (8.5, 9.1) ≥ 43.9 μg/m 3 : 8.6 (8.1, 9.0) Incidence of preterm birth (6 wk before birth exposure) <31.8 μg/m 3 : 8.8 (8.4, 9.3) 31.8 to <44.1 μg/m 3 : 8.6 (8.3, 8.9) ≥ 44.1 μg/m 3 : 8.8 (8.4, 9.2) Outcome: LBW Exposure Period: Third trimester Address-level analysis: Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.22 (1.05, 1.41) 33.4 to <44.7 μg/m 3 : 1.08 (0.76, 1.52) ≥ 44.7 μg/m 3 : 1.48 (1.00, 2.19) Multipollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.36 (1.12, 1.65) 33.4 to <44.7 μg/m 3 : 1.16 (0.77, 1.74) ≥ 44.7 μg/m 3 : 1.58 (0.95, 2.62) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 0.98 (0.90, 1.06) 33.4 to <44.7 μg/m 3 : 0.95 (0.80, 1.13) ≥ 44.7 μg/m 3 : 0.96 (0.78, 1.18) Multipollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.02 (0.92, 1.14) 33.4 to <44.7 μg/m 3 : 0.93 (0.77, 1.12) ≥ 44.7 μg/m 3 : 1.02 (0.79, 1.32) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.03 (0.99, 1.08) 33.9 to <45.0 μg/m 3 : 1.04 (0.96, 1.14) ≥ 45.0 μg/m 3 : 1.08 (0.97, 1.20) Multipollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.04 (0.98, 1.09) 33.9 to <45.0 μg/m 3 : 1.02 (0.92, 1.12) ≥ 45.0 μg/m 3 : 1.06 (0.93, 1.21)

Zip-code-level analysis Single-pollutant model:



### December 2009 E-472

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Per 10 μg/m 3 : 1.03 (0.97, 1.09) 33.2 to <43.6 μg/m 3 : 0.98 (0.86, 1.11) ≥ 43.6 μg/m 3 : 1.03 (0.88, 1.21) Multipollutant model: Per 10 μg/m 3 : 1.07 (0.99, 1.15) 33.2 to <43.6 μg/m 3 : 0.97 (0.85, 1.12) ≥ 43.6 μg/m 3 : 1.09 (0.90, 1.31)

Outcome: LBW Exposure Period: Entire pregnancy period Address-level analysis: Multipollutant model: Per 10 μg/m 3 : 1.24 (0.91, 1.70)

Outcome: Preterm Birth Exposure Period: First trimester of pregnancy Address-level analysis : Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.00 (0.93, 1.09) 33.3 to <45.1 μg/m 3 : 1.07 (0.90, 1.26) ≥ 45.1 μg/m 3 : 1.12 (0.91, 1.38) Multipollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.00 (0.90, 1.12) 33.3 to <45.1 μg/m 3 : 1.12 (0.92, 1.36) ≥ 45.1 μg/m 3 : 1.17 (0.90, 1.50) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.01 (0.97, 1.05) 33.7 to <45.3 μg/m 3 : 1.03 (0.95, 1.12) ≥ 45.3 μg/m 3 : 1.07 (0.97, 1.19) Multipollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.04 (0.99, 1.10) 33.7 to <45.3 μg/m 3 : 1.07 (0.98, 1.17) ≥ 45.3 μg/m 3 : 1.13 (1.00, 1.27) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.01 (0.99, 1.03) 34.1 to <45.5 μg/m 3 : 1.03 (0.99, 1.08) ≥ 45.5 μg/m 3 : 1.02 (0.96, 1.07) Multipollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 0.99 (0.97, 1.02) 34.1 to <45.5 μg/m 3 : 0.99 (0.95, 1.04) ≥ 45.5 μg/m 3 : 0.94 (0.89, 1.01) Zip-code-level analysis Single-pollutant model: Per 10 μg/m 3 : 0.99 (0.96, 1.01) 33.3 to <44.2 μg/m 3 : 1.01 (0.95, 1.08) ≥ 44.2 μg/m 3 : 0.98 (0.90, 1.05) Multipollutant model: Per 10 μg/m 3 : 0.99 (0.96, 1.03) 33.3 to <44.2 μg/m 3 : 1.03 (0.97, 1.11) ≥ 44.2 μg/m 3 : 1.01 (0.92, 1.11)

Outcome: Preterm birth Exposure Period: 6 wk before birth Address-level analysis: Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.02 (0.95, 1.10) 32.5 to <44.8 μg/m 3 : 1.09 (0.92, 1.29) ≥ 44.8 μg/m 3 : 1.12 (0.92, 1.37) Multipollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.06 (0.97, 1.16) 32.5 to <44.8 μg/m 3 : 1.09 (0.90, 1.31) ≥ 44.8 μg/m 3 : 1.17 (0.91, 1.49) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.00 (0.96, 1.03) 32.3 to <45.3 μg/m 3 : 0.99 (0.91, 1.07) ≥ 45.3 μg/m 3 : 0.99 (0.89, 1.10) Multipollutant model:



### December 2009 E-473

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.01 (0.97, 1.06) 32.3 to <45.3 μg/m 3 : 1.00 (0.92, 1.10) ≥ 45.3 μg/m 3 : 1.02 (0.91, 1.16) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 0.99 (0.98, 1.01) 33.1 to <45.3 μg/m 3 : 1.00 (0.96, 1.05) ≥ 45.3 μg/m 3 : 0.98 (0.93, 1.03) Multipollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.00 (0.98, 1.02) 33.1 to <45.3 μg/m 3 : 1.01 (0.96, 1.05) ≥ 45.3 μg/m 3 : 0.98 (0.92, 1.04)

Zip-code-level analysis Single-pollutant model: Per 10 μg/m 3 : 1.02 (0.99, 1.04) 32.1 to <44.3 μg/m 3 : 1.01 (0.95, 1.07) ≥ 44.3 μg/m 3 : 1.04 (0.96, 1.12) Multipollutant model: Per 10 μg/m 3 : 1.02 (0.99, 1.06) 32.1 to <44.3 μg/m 3 : 1.02 (0.95, 1.09) ≥ 44.3 μg/m 3 : 1.04 (0.95, 1.14) Notes: multipollutant model adds CO,NO 2 , and O 3 in addition to the main pollutant of interest, PM 10

. Reference: Woodruff et al. (1997, 084271 ) Period of Study: 1989-1991

Location: 86 Metropolitan Statistical Areas in the U.S. (counties with populations less than 100,000 were excluded) Outcome: Postneonatal mortality (death of an infant between 1 month and 1 yr of age 1) All post neonatal deaths 2) Normal birth weight (NBW, ≥ 2500 g) SIDS deaths 3) NBW respiratory deaths 4) Low birth weight (LBW) respiratory death Respiratory deaths: ICD9 codes 460-519

SIDS: ICD9 code 798.0 Age Groups: Infants (1 month-1yr of age) Study Design: Cross-sectional

N: 3,788,079 infants Statistical Analyses: Logistic regression

Covariates: Maternal education, maternal race, parental marital status, maternal smoking during pregnancy Avg temperature during the first 2 mo of life Infant’s month and yr of birth

Assessed race as an effect modifier (p-val for interaction terms >0.2) Dose-response Investigated? Yes Statistical Package: NR Pollutant: PM 10 Averaging Time: Mean of 1st 2 mo of life analyzed as tertiles of exposure and as continuous exposure Mean (SD): 31.4 (7.8) Range (Min, Max):

Overall: 11.9-68.8 Low category: <28.0 Medium category: 28.1-40.0 High category: >40.0 Monitoring Stations: NR PM Increment: 10 μg/m 3 (for continuous exposure analysis) Adjusted ORs for cause-specific post neonatal mortality by pollution category (tertiles) All causes Low: Ref Medium: 1.05 (1.01, 1.09) High: 1.10 (1.04, 1.16) SIDS, NBW: Low: Ref Medium: 1.09 (1.01, 1.17) High: 1.26 (1.14, 1.39) Respiratory death, NBW: Low: Ref Medium: 1.08 (0.87, 1.33) High: 1.40 (1.05, 1.85) Respiratory death, LBW: Low: Ref Medium: 0.93 (0.73, 1.18) High: 1.18 (0.86, 1.61) All other causes: Low: Ref Medium: 1.03 (0.97, 1.08) High: 0.97 (0.90, 1.04) Adjusted ORs for a continuous 10 μg/ m 3 change in exposure All causes: 1.04 (1.02, 1.07) SIDS, NBW: 1.12 (1.07, 1.17) Respiratory death, NBW: 1.20 (1.06, 1.36) Respiratory death, LBW: 1.05 (0.91, 1.22) All other causes: 1.00 (0.99, 1.00)



### December 2009 E-474

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Woodruff et al. (2008, 098386 ) Period of Study: 1999-2002

Location: U.S. counties with >250,000 residents (96 counties) Outcome: Postneonatal deaths Respiratory mortality (ICD10: J000-99, plus bronchopulmonary dysplasia [BPD] P27.1) SIDS (ICD10: R95) Ill-defined causes (R99);

All other deaths evaluated as a control category Age Groups: Infants aged >28 days and <1 yr Study Design: Cross-sectional

N: 3,583,495 births (6,639 post neonatal deaths) Statistical Analyses: Logistic GEE (exchangeable correlation structure)

Covariates: Maternal race/ethnicity, marital status, age, education, primiparity, county-level poverty and per capita income levels, yr and month of birth dummy variables to account for time trend and seasonal effects, and region of the country Sensitivity analyses performed among only those mothers with smoking information (adjustment for smoking had no effect on the estimates)

Season: Adjusted for yr and month of birth dummy variables to account for time trend and seasonal effects Dose-response Investigated? Evaluated the appropriateness of a linear form from analysis based on quartiles of exposure and concluded that linear form was appropriate (data not shown) Statistical Package: SAS Pollutant: PM 10 Averaging Time: Measured continuously for 24 h once every 6 days exposure assigned by calculating avg concentration of pollutant during first 2 mo of life Median and IQR (25th-75th percentile): Survivors: 28.9 (23.3-34.4) All causes of death: 29.1 (23.9-34.5) Respiratory: 29.8 (24.3-36.5) SIDS: 28.6 (23.5-33.8) SIDS + ill-defined: 28.8 (23.9-33.9) Other causes: 29.2 (23.9-34.5)

Percentiles: see above PM Component: Not assessed, but controlled for region of the country to account for PM composition variation Monitoring Stations: NR Copollutant (correlation): PM 10 PM 2.5 (r = 0.34) CO (r = 0.18)

SO 2 (r = 0.00)

O 3 (r = 0.20)

Notes: Monthly avg calculated if there were at least 3 available measures for PM Assigned exposures using the avg concentration of the county of residence PM Increment: IQR (11 μg/m 3 ) Effect Estimate [Lower CI, Upper CI]: Adjusted ORs for single pollutant models All causes: 1.04 (0.99, 1.10) Respiratory: 1.18 (1.06, 1.31) SIDS: 1.02 (0.89, 1.16) Ill-defined + SIDS: 1.06 (0.97, 1.16) Other causes: 1.02 (0.96, 1.07) Adjusted ORs for multipollutant models (including CO, O 3 , SO 2 ) Respiratory: 1.16 (1.04, 1.30) SIDS: 1.02 (0.90, 1.16) OR for deaths coded as BPD per increase in IQR: 1.19 (0.85, 1.65) OR for respiratory post neonatal death stratified by birth weight NBW only: 1.19 (1.05, 1.36) LBW only: 1.12 (0.95, 1.31) OR for respiratory deaths removing region of U.S. as a confounding variable: 1.30 (1.04, 1.61) OR for respiratory deaths assessing exposure as quartiles Highest vs. Lowest quartile: 1.31 (1.00, 1.71) OR for respiratory deaths among only those deaths that occurred during the first 90 days (most closely matched exposure metric of the avg over the first 2 mo of life): 1.25 (1.06, 1.47)



### December 2009 E-475

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Jedrychowski, et al., (2007, 156607 ) Period of Study: Jan 2001-Feb 2004

Location: Krakow, Poland Outcome: Birth weight (grams), birth length (cm) Age Groups: Pregnant women 18-35 yr Study Design: Prospective cohort

N: 493 women Statistical Analyses: Linear regression

Covariates: Environmental tobacco smoke (# cigarettes smoked daily in presence of pregnant woman), season of birth, size of mother, parity, gestational age, gender of child, vitamin A intake

Season: All Dose-response Investigated? Yes Statistical Package: NR Lags Considered: Two consecutive days in the second trimester Pollutant: PM 2.5 Averaging Time: 48 h period Percentiles: 50th(Median): 35.3 Range (Min, Max): 10.3, 294.9 Monitoring Stations: No stations, personal monitoring

Notes: PM measured during a 2 day period in the second trimester by Personal Environmental Monitoring Sampler (PEMS) PM Increment: in 1 μg/m 3 and tertiles T1: <27.0 μg/m 3 T2: 27.0-46.2 μg/m 3 T3: ≥ 46.2 μg/m 3

Mean [Lower CI, Upper CI]: Birth weight (g) For ln unit PM: β = -172.39 (p = 0.02) Tertiles: T1: ref T2: β = -16.510 [-94.630, 61.610] T3: β = -109.956 [-196.649 to -23.263] In low Vitamin A group (<1,378 μg) T1: ref T2: β = -68.354 [-165.643, 28.935] T3: β = -185.070 [-293.393 to -76.747] In high Vitamin A group (>1,378 μg) T1: ref T2: β = 64.262 [-70.464, 198.988] T3: β = 38.593 [-109.853, 187.039] Birth length (cm) For ln unit PM: β = -1.39 (p = 0.00) Tertiles: T1: ref T2: β = -0.288 [-0.790, 0.214] T3: β = -0.810 [-1.367 to -0.253] In low Vitamin A group (<1,378 μg) T1: ref T2: β = -0.514 [-1.114, 0.086] T3: β = -1.100 [-1.768 to -0.432] In high Vitamin A group (>1,378 μg) T1: ref T2: β = 0.039 [-0.896, 0.974] T3: β = -0.301 [-1.326, 0.724] Reference : (Lipfert et al., 2000, 004103 ) Period of Study: 1990

Location: U.S. Outcome (ICD9 and ICD10): Infant mortality Including respiratory mortality (traditional definition, ICD9 460-519), expanded definition (adds ICD9 769 and 770) Age Groups: Infants Study Design: Cross-sectional

N: 2,413,762 infants in 180 counties (Ns differ for various models) Statistical Analyses: Logistic regression

Covariates: Mother’s smoking, education, marital status, and race

Month of birth And county avg heating degree days Dose-response Investigated? NR Statistical Package: NR Pollutant: SO 4 2– / NSPM 10 (regressed jointly) Averaging Time: Yearly avg used Mean (SD): 33.1 (9.17) (based on 180 counties) Range (Min, Max): (16.9, 59) Monitoring Stations: NR Copollutant:

PM 10 NSPM 10 CO

SO 2 Notes: TSP-based sulfate was adjusted for compatibility with the PM 10 -based data PM Increment: NR (present regression coefficients) Effect Estimate [Lower CI, Upper CI]: Presented regression coefficients (standard errors) (3 PM exposures regressed jointly) bold = p <0.05 Cause of death: All Birth weight: All SO 4 2– : -0.0002 (0.0061) NSPM : 0.0115 (0.0014) 10 Cause of death: All Birth weight: LBW SO 2– : 0.0265 (0.0080)

4 NSPM 10 : 0.0086 (0.0020) Cause of death: All Birth weight: normal SO 4 2– : -0.0488 (0.0098) NSPM 10 : 0.0096 (0.0024) Cause of death: All neonatal Birth weight: All SO 4 2– : 0.0267 (0.0076) NSPM : 0.0126 (0.0018) 10 Cause of death: All neonatal Birth weight: LBW SO 2– : 0.0388 (0.0088)

4 NSPM 10 : 0.0093 (0.0022) Cause of death: All neonatal Birth wt: normal SO 4 2– : -0.0334 (0.0169) NSPM 10 : 0.0125 (0.0040) Cause of death: All post neonatal Birth wt: All PM 10 : 0.0091 (0.0024) SO 2– : -0.0474 (0.0100)

4 NSPM 10 : 0.0096 (0.0024) Cause of death: All post neonatal Birth wt: LBW SO 4 2– : -0.0247 (0.0173) NSPM 10 : 0.0101 (0.0042) Cause of death: All post neonatal Birth wt: normal SO 4 2– : -0.0569 (0.0121)



### December 2009 E-476

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

NSPM 10 : 0.0080 (0.0029) Cause of death: SIDS Birth weight: All SO 4 2– : -0.1078 (0.0151) NSPM 10 : 0.0149 (0.0037) Cause of death: SIDS Birth weight: LBW SO 4 2– : -0.1378 (0.0337) NSPM 10 : 0.0146 (0.0085) Cause of death: SIDS Birth weight: normal PM 10 : 0.0137 (0.0042) SO 4 2– : -0.0995 (0.0168) NSPM 10 : 0.0147 (0.0041) Cause of death: All respiratory (ICD9: 460- 519, 769, 770) Birth weight: All SO 4 2– : 0.0706 (0.0146) NSPM 10 : 0.0166 (0.0034) Cause of death: All respiratory (ICD9: 460- 519, 769, 770) Birth weight: LBW SO 4 2– : 0.0821 (0.0158) NSPM 10 : 0.0139 (0.0038) Cause of death: All respiratory (ICD9: 460- 519, 769, 770) Birth weight: normal PM 10 : 0.0177 (0.0091) SO 4 2– : 0.0001 (0.0392) NSPM 10 : 0.0118 (0.0090) Cause of death: Respiratory disease (ICD9: 460-519) Birth weight: All PM 10 : 0.0133 (0.0089) SO 4 2– : 0.0093 (0.0384) NSPM 10 : 0.0134 (0.0089) Cause of death: Respiratory disease (ICD9: 460-519) Birth weight: LBW PM 10 : 0.0092 (0.0137) SO 4 2– : 0.0434 (0.0580) NSPM 10 : 0.0089 (0.0138) Cause of death: Respiratory disease (ICD9: 460-519) Birth weight: normal SO 4 2– : -0.0177 (0.0509) NSPM 10 : 0.0128 (0.0119) Associations with SIDS by smoking status Smoking status: Yes Birth weight: Normal SO 4 2– : -0.0722 (0.0284) NSPM 10 : 0.0206 (0.0071) Smoking status: No Birth weight: Normal SO 4 2– : -0.114 (0.021) NSPM 10 : 0.0117 (0.005) Smoking status: Yes Birth weight: LBW SO 4 2– : -0.0958 (0.0483) NSPM 10 : 0.0345 (0.0125) Smoking status: No Birth weight: LBW SO 4 2– : -0.0172 (0.047) NSPM 10 : -0.0007 (0.012) Mean risks (95%CI) between post neonatal SIDS among normal birth weight babies pollutants regressed one at a time SO 4 2– : 0.43 (0.37, 0.51) NSPM 10 : 1.33 (1.18, 1.50)



### December 2009 E-477

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Liu et al., 2007, 090429 ) Period of Study: 1985-2000

Location: 3 Canadian cities: Calgary, Edmonton, and Montreal Outcome: Intrauterine growth restriction (IUGR) Age Groups: Singleton term live births (37-42 wks gestation) Study Design: Retrospective cohort

N: 386,202 singleton live births Statistical Analyses: Multiple logistic regression

Covariates: Maternal age, parity, infant gender, season, and city of residence at time period of birth

Season: All seasons Dose-response Investigated? No Statistical Package: NR Pollutant: PM 2.5 Averaging Time: 24 h (6-day schedule) Mean (SD): 12.2

Percentiles: 25th: 6.3 50th(Median): 9.7

75th: 15 PM Component: metals and organic matter such as polycyclic aromatic hydrocarbons Monitoring Stations: Calgary (4), Edmonton (2), and Montreal (8) Copollutant (correlation): SO 2 : r = 0.44, p < 0.0001 NO 2 : r = 0.41, p < 0.0001 CO: r = 0.31, p < 0.0001 O 3 : r = -0.14, p < 0.0001 PM Increment: 10 μg/m 3

Effect Estimate Single-pollutant mo del [Lower CI, Upper CI]: 1st trimester OR = 1.07 (1.03-1.10) 2nd trimester OR = 1.06 (1.03-1.10) 3rd trimester OR = 1.06 (1.03-1.10)

Effect Estimate multi-pollutant model [Lower CI, Upper CI]: 1st trimester OR= 1.03 (0.99-1.06) 2nd trimester OR= 1.01 (0.98-1.05) 3rd trimester OR= 1.03 (0.99-1.06) Note: ORs and CIs estimated from Fig. 6 and 7

Reference: Loomis et al. (1999, 087288 ) Period of Study: Jan 1993-Jul 1995

Location: Mexico City (southwestern section) Outcome (ICD9 and ICD10): Infant mortality (daily counts of deaths) All ICD9 codes, excluding accidents, poisoning, and violence (ICD9 ≥ 800) Age Groups: Children <1 yr of age Study Design: Time-series

N: 942 deaths (days were the unit of observation) Statistical Analyses: Poisson regression (generalized additive model)

Covariates: Final models controlled for mean temp of 3 days before death and nonparametrically smoothed periodic cycles

Season: Yes (considered) Dose-response Investigated? Loess smoother Statistical Package: NR Lags Considered: 0-5 (also considered lags with avg exposure levels during “windows” of 2 to 4 days) Pollutant: PM 2.5 Averaging Time: 24-h Mean (SD): 27.4 (10.5)

Percentiles: Lower quartile: 20

Median: 26 Upper quartile: 34 Range (Min, Max): 4, 85 Monitoring Stations: 1 Copollutant: O 3 NO 2 NO

NO X SO 2 Notes: Pearson correlation coefficients ranging from 0.52 to 0.71 PM Increment: 10 μg/m 3 Effect Estimate [Lower CI, Upper CI]: %Change in infant mortality Lags 0-5 (single day) presented in Fig 1: Lag0,1,2: No association (results not presented) Lag3: 4.8 (0.97, 8.61) Lag4: 4.2 (0.37, 7.93) %Change in mortality when avg exposure levels during “windows” of 2 to 4 days were considered 2 Days: No lag: -1.36 (-5.51, 2.8) Lag1: -0.95 (-5.10, 3.20) Lag2: 2.78 (-1.33, 6.89) Lag3: 4.93 (0.86, 9.01) 3 Days: No lag: -0.81 (-5.29, 3.67) Lag1: 1.99 (-2.46, 6.45) Lag2: 4.54 (0.12, 8.96) Lag3: 6.87 (2.48, 11.26) 4 Days: No lag: 1.95 (-2.76, 6.66) Lag1: 3.74 (-0.95, 8.42) Lag2: 5.87 (1.21, 10.53) Multipollutant models (3-day mean w/ 3- day lag) 1 pollutant model: 6.87 (2.48, 11.26) 2 pollutant models: w/ O : 6.24 (1.35, 11.14) 3 w/ NO 2 : 5.91 (-0.76, 12.59) 3 Pollutant model (w/ O 3 and NO 2 ): 6.30 (-0.54, 13.15)



### December 2009 E-478

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Mannes et al. (2005, 087895 ) Period of Study: Jan 1998-Dec 2000

Location: metropolitan Sydney, Australia Outcome: Risk of small for gestational age (SGA) and birth weight Age Groups: All singleton births >20 wk and ≥ 400 grams birth weight and maternal all ages Study Design: Cross-sectional

N: 138,056 singleton births Statistical Analyses: Logistic and linear regression models

Covariates: Sex of child, maternal age, gestational age, maternal smoking, gestational age at first antenatal visit, maternal indigenous status, whether first pregnancy, season of birth, and socioeconomic status (SES)

Season: All seasons

included as covariate. Dose-response Investigated? No Statistical Package: SAS System for Windows v8.02 Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD): 9.4 (5.1)

Percentiles: 25th: 6.5 50th(Median): 8.4

75th: 11.2 Range (Min, Max): (2.4- 82.1) Monitoring Stations: up to 14 Copollutant (correlation):

CO: r = 0.53

NO 2 : r = 0.66

O 3 : r = 0.36

PM 10 : r = 0.81 PM Increment: 1 μg/m 3 Risk of SGA All births 1 month before birth: OR = 1.01 (0.99-1.03) Third trimester: OR = 0.99 (0.97-1.02) Second trimester: OR = 1.03 (1.01-1.05) First trimester: OR = 0.99 (0.97-1.01) 5 km births 1 month before birth: OR = 1.01 (0.97-1.04) Third trimester: OR = 1.00 (0.95-1.05) Second trimester: OR = 1.00 (0.96-1.05) First trimester: OR = 0.99 (0.94-1.04) Change in birth weight All births 1 month before birth: ß = -2.48 (-4.58- -0.38) Third trimester: ß = -0.98 (-3.74-1.78) Second trimester: ß = -4.10 (-6.79- -1.41) First trimester: ß = 0.36 (-2.29- 3.01) 5 km births 1 month before birth: ß = -2.70 (-6.80- 1.40) Third trimester: ß = -2.83 (-9.00-3.34) Second trimester: ß = 1.54 (-4.59-7.67) First trimester: ß = 1.89 (-1.99-5.77) Reference: Parker et al. (2005, 087462 ) Period of Study: 1999-2000

Location: California Outcome: Small for gestational age (SGA) and birth weight Age Groups: Infants delivered at 40 wk gestation maternal all ages Study Design: Cross-sectional

N: 18,247 singleton births Statistical Analyses: Linear and logistic regression models

Covariates: Maternal race, maternal Hispanic origin, marital status, parity, maternal education, and maternal age

Season: Season of delivery (covariate) Dose-response Investigated? Yes Statistical Package: STATA Pollutant: PM 2.5 Averaging Time: NR (measurement taken every 6 days) Mean (SD): 15.42 (5.08) PM Component: metals, polycyclic aromatic hydrocarbons Monitoring Stations: 40 Copollutant (correlation):

PM 2.5 -CO: r = 0.6

Notes: Mean calculated for 9-month exposure. The following means (SDs) are calculated for trimester: First: 15.70 (6.26) Second: 15.40 (6.53) Third: 14.29 (6.35) PM categorized into quartiles:

Q1: <11.9

Q2: 11.9-13.9

Q3: 13.9-18.4

Q4: >18.4 PM Increment: <11.9 μg/m 3 |

Referent PM Increment: 11.9-13.9 μg/m 3 Effect Estimate [Lower CI, Upper CI]: First Trimester Birth weight: ß = -5.7 (-27.9-16.5) SGA: OR = 1.02 (0.84-1.23) Second Trimester Birth weight: ß = 11.3 (-12.2-34.9) SGA: OR = 0.89 (0.73-1.09) Third Trimester Birth weight: ß = 8.3 (-13.1-29.8) SGA: OR = 1.00 (0.83-1.19) PM Increment: 13.9-18.4 μg/m 3 Effect Estimate [Lower CI, Upper CI]: First Trimester Birth weight: ß = -2.5 (-24.5-19.5) SGA: OR = 1.12 (0.93-1.34) Second Trimester Birth weight: ß = -17.2 (-39.4-4.9) SGA: OR = 1.05 (0.88-1.26) Third Trimester Birth weight: ß = -8.1 (-30.2-13.9) SGA: OR = 0.98 (0.82-1.18) PM Increment: >18.4 μg/m 3 Effect Estimate [Lower CI, Upper CI]: First Trimester Birth weight: ß = -35.8 (-58.4--13.3) SGA: OR = 1.26 (1.04-1.51) Second Trimester Birth weight: ß = -46.6 (-68.6- -24.6) SGA: OR = 1.24 (1.04-1.49) Third Trimester Birth weight: ß = -31.6 (-52.0- -11.1) SGA: OR = 1.21 (1.02-1.43)



### December 2009 E-479

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Parker and Woodruff (2008, 156846 ) Period of Study: 2001-2003

Location: U.S. Outcome: Low birth weight Study Design: Cohort

N: 785,965 Singleton births delivered at 40 wk gestation Statistical Analyses: GEE regression models linear and logistic regression

Covariates: Race/ethnicity, parity, maternal age

Season: Season of delivery Statistical Package: SUDAAN Pollutant: PM 2.5 Averaging Time: 9 mo Mean (SD): 14.5

25th: 12.1

75th: 17.6 Copollutant (correlation): SO 2 , NO 2 CO O 3 PM Increment: 10 μg/m 3 Change in Birth weight (9 month exposure): Unadjusted: 19.4 (9.8, 29.0) Adjusted for maternal factors: 18.4 (9.2, 27.7) Stratified by region: Industrial Midwest: -15.3 (-43.4, 12.9) Northeast: -9.8 (-11.9, 26.6) Northwest: 27.5 (5.5, 49.4) Southern CA: 5.5 (-9.6, 20.5) Southeast: 7.3 (-11.9, 26.6) Southwest: 72.3 (34.0, 110.5) Upper Midwest: -0.7 (-62.0, 60.6) Multipollutant models: PM 2.5 +PM 10-2.5 : 14.2 (4.3, 24.1) PM 2.5 +PM 10-2.5 +SO 2 +CO+NO 2 +O 3 : 28.6 (14.2, 43.0)



### December 2009 E-480

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Rich et al. (2009, 180122 ) Period of Study: 1999-2003

Location: New Jersey, United States Outcome: Small for gestational age Study Design: Retrospective Cohort

Covariates: Month and calendar yr of birth, apparent temperature, pregnancy complications Statistical Analysis: Polytomous logistic regression Statistical Package: SAS Age Groups: Gestational age 37-42 wks Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD) Unit: *All values are for first trimester, other trimesters are available in paper Reference Births: 13.8 (2.5) SGA Births: 13.9 (2.5) VSGA Births: 13.9 (2.4) Range (Min, Max): 2.0, 29.0 Copollutant (correlation): *All values are for first trimester, other trimesters are available in paper

NO 2 : 0.01

SO 2 : 0.17

CO: 0.25 *All values are for first trimester, other trimesters are available in paper

Increment: 4 μg/m 3 Percent Change in Risk (95% CI) SGA: 4.5 (0.5-8.7) VSGA: 2.6 (-4.4-10.0) Percent Change in Risk (95% CI) for single and two-pollutant models Single, SGA: 4.6 (-0.3-9.8) Single, VSGA: 4.5 (-4.0-13.4) Two (PM 2.5 & NO 2 ), SGA: 4.5 (-0.4-9.7) Two (PM 2.5 & NO 2 ), VSGA: 3.2 (-5.2-12.4) Percent Change in Risk (95% CI) by pregnancy complication in third trimester SGA Any Complication No: 4.7 (0.6-9.0) Yes: 2.2 (-6.1-11.3) Placental Abruption No: 4.0 (0.3-7.9) Yes: 11.7 (-21.7-59.5) Placental Praevia No: 3.9 (0.2-7.8) Yes: 23.2 (-20.9-91.9) Pre-eclampsia No: 4.2 (0.4-8.2) Yes: 2.7 (-13.8-22.3) Gestational Hypertension No: 4.3 (0.4-8.4) Yes: 3.9 (-7.8-17.1) Premature Rupture of the Membrane No: 3.7 (-0.1-7.7) Yes: 14.6 (-3.3-35.9) Gestational Diabetes No: 4.6 (0.8-8.6) Yes: -9.3 (-24.7-9.3) VSGA Any Complication No: 1.5 (-6.1-9.7) Yes: 12.6 (0.1-26.7) Placental Abruption No: 4.1 (-2.6-11.2) Yes: 7.6 (-29.8-64.9) Placental Praevia No: 4.1 (-2.5-11.2) Yes: 3.2 (-43.0-86.9) Pre-eclampsia No: 4.4 (-2.6-11.9) Yes: 3.9 (-15.7-28.1) Gestational Hypertension No: 3.2 (-4.0-10.9) Yes: 12.9 (-3.3-31.9) Premature Rupture of the Membrane No: 3.3 (-3.5-10.5) Yes: 21.9 (-3.6-54.2) Gestational Diabetes No: 4.3 (-2.5-11.5) Yes: 1.4 (-27.0-40.9)



### December 2009 E-481

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Ritz et al. (2007, 096146 ) Period of Study: Jan 2003-Dec 2003

Location: Los Angeles, California Outcome: Preterm births (infants delivered before 37 wk) Age Groups: Births Study Design: Case-control nested within a birth cohort (cases and controls matched on zip code and birth month) Phase 1: cross-sectional including all birth cohort Phase 2: nested case-control of survey respondents

N: Phase 1: Birth cohort consisted of 58,316 eligible births. Phase II: 2,543 Statistical Analyses: Logistic regression

Covariates: Birth certificate information: maternal age, race/ethnicity, parity, education, season of birth survey information: maternal smoking, alcohol consumption, living with a smoker, and marital status during pregnancy income (imputed) occupation and pregnancy weight gain considered but not included in final models

Season: Yes Dose-response Investigated? Yes, examined categories of exposure Statistical Package: NR Pollutant: PM 2.5 Averaging Time: daily or every 3rd day used to calculate the entire pregnancy, the first trimester, and the last 6 wk before delivery Only reported first trimester exposures for PM Range (Min, Max): NR Ranges for 3 categories reported: Low (ref): ≤ 18.63

Mid: 18.64-21.36 High: >21.36 Monitoring Stations: Each zip code was linked to the nearest monitoring station (number not reported) Copollutant (correlation): CO

NO 2 O 3 Notes: Daily or every 3rd day measurements used for mean calculations PM Increment: Reported analyses using exposure categories Effect Estimate [Lower CI, Upper CI]: Birth cohort (phase I) Crude: Low: 1.0 Mid: 0.96 (0.90, 1.03) High: 1.05 (0.99, 1.12) Adj for birth cert Covariates: Low: 1.0 Mid: 1.01 (0.93, 1.09) High: 1.10 (1.01, 1.20) Survey respondents (phase II) Crude: Low: 1.0’ Mid: 1.11 (0.90, 1.36) High: 1.27 (1.06, 1.53) Adj for birth cert Covariates: Low: 1.0 Mid: 1.14 (0.90, 1.46) High: 1.27 (0.99, 1.64) Adj for all Covariates: Low: 1.0 Mid: 1.15 (0.90, 1.47) High: 1.29 (1.00, 1.67) Two-phase model: * Low: 1.0 Mid: 0.98 (0.84, 1.15) High: 1.07 (0.85, 1.35) *Method to reduce potential selection bias and increase statistical efficiency

Reference: Slama et al. (2007, 093216 ) Period of Study: Jan 1998-Jan 1999

Location: Munich, Germany Outcome: Birth weight offspring at term Study Design: Cohort study

N: 1016 births Statistical Analyses: Poisson model

Covariates: Maternal passive smoking, maternal age, gestational duration, sex of child, parity, maternal education, maternal size, prepregnancy weight, other pollutants (PM 2.5 , PM 2.5 absorbance, NO 2 ), season of conception Dose-response Investigated? Yes Statistical Package: STATA Pollutant: PM 2.5 (estimated based on larger PM size fractions) Averaging Time: Entire pregnancy period and trimesters Mean (SD): 14.4

Percentiles: 25th: 13.5 50th(Median): 14.4

75th: 15.4 Monitoring Stations: Spatial component: 40 Temporal component: 1 Copollutant (correlation): p.a. = pregnancy avg trim. = trimester PM 2.5 (p.a.)-PM 2.5 (1st trim.): 0.85 PM 2.5 (p.a.)-PM 2.5 (2nd trim.): 0.77 PM 2.5 (p.a.)-PM 2 (3rd trim.): 0.87 .5 PM 2.5 (p.a.)-NO 2 (p.a.): 0.45 PM 2.5 (p.a.)-NO 2 (1st trim.): 0.18 PM 2.5 (p.a.)-NO 2 (2nd trim.): 0.32 PM 2.5 (p.a.)-NO 2 (3rd trim.): 0.37 PM 2.5 (1st trim.)-PM 2.5 (2nd trim.): 0.40 PM 2.5 (1st trim.)-PM 2 (3rd trim.): 0.68 .5 PM 2.5 (1st trim.)-NO 2 (p.a.): 0.48 PM 2.5 (1st trim.)-NO 2 (1st trim.): 0.15 PM 2.5 (1st trim.)-NO 2 (2nd trim.): 0.41 PM 2.5 (1st trim.)-NO 2 (3rd trim.): 0.39 PM 2.5 (2nd trim.)-PM 2.5 (3rd trim.): 0.51 PM 2.5 (2nd trim.)-NO 2 (p.a.): 0.23 PM 2.5 (2nd trim.)-NO 2 (1st trim.): -0.03 PM 2.5 (2nd trim.)-NO 2 (2nd trim.): 0.17 PM 2.5 (2nd trim.)-NO 2 (3rd trim.): 0.30 PM Increment: 1) 1 μg/m 3 2) Quartiles: a) 1st (reference) (7.2-13.5 μg/m 3 ) b) 2nd (13.5-14.4 μg/m 3 ) c) 3rd (14.4-15.4 μg/m 3 ) day) 4th (15.41-17.5 μg/m 3 ) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnancy Single-pollutant models Unadjusted models 2nd quartile: 1.07 (0.65, 1.73); 3rd quartile: 1.38 (0.91, 2.09) 4th quartile: 1.45 (0.92, 2.25) Per 1 μg/m 3 : 1.06 (0.95, 1.19) Adjusted models 2nd quartile: 1.08 (0.63, 1.82); 3rd quartile: 1.34 (0.86, 2.13) 4th quartile: 1.73 (1.15, 2.69); Per 1 μg/m 3 : 1.13 (1.00, 1.29)

Multipollutant models Adjusted models 2nd quartile: 1.01 (0.57, 1.85) 3rd quartile: 1.12 (0.64, 1.87) 4th quartile: 1.36 (0.72, 2.45); Per 1 μg/m 3 : 1.07 (0.91, 1.26) Single-pollutant models (restricted analysis to PM 2.5 absorbance below the median) Per 1 μg/m 3 : 1.15 (0.89, 1.52) Prevalence ratios (PRs) of birth weight <3000 g Multipollutant models (simultaneous



### December 2009 E-482

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

PM 2.5 (3rd trim.)-NO 2 (p.a.): 0.39 PM 2.5 (3rd trim.)-NO 2 (1st trim.): 0.33 PM 2.5 (3rd trim.)-NO 2 (2nd trim.): 0.21 PM 2.5 (3rd trim.)-NO 2 (3rd trim.): 0.23 PM 2.5 (p.a.)- PM 2.5 absorbance (p.a.): 0.69 PM 2.5 (p.a.)- PM 2.5 abs (1st trim.): 0.33 PM 2.5 (p.a.)- PM 2.5 abs (2nd trim.): 0.48 PM 2.5 (p.a.)- PM 2.5 abs (3rd trim.): 0.52 PM 2.5 (1st trim.)- PM 2.5 abs (p.a.): 0.68 PM 2.5 (1st trim.)- PM 2.5 abs (1st trim.): 0.27 PM 2.5 (1st trim.)- PM 2.5 abs (2nd trim.): 0.53 PM 2.5 (1st trim.)- PM 2.5 abs (3rd trim.): 0.51 PM 2.5 (2nd trim.)- PM 2.5 abs(p.a.): 0.41 PM 2.5 (2nd trim.)- PM 2.5 abs (1st trim.): 0.08 PM 2.5 (2nd trim.)- PM 2.5 abs (2nd trim.): 0.29 PM 2.5 (2nd trim.)- PM 2.5 abs (3rd trim.): 0.41 PM 2.5 (3rd trim.)- PM 2.5 abs (p.a.): 0.62 PM 2.5 (3rd trim.)- PM 2.5 abs (1st trim.): 0.48 PM 2.5 (3rd trim.)- PM 2.5 abs (2nd trim.): 0.36 PM 2.5 (3rd trim.)- PM 2.5 abs (3rd trim.): 0.37 Adjustment of 3rd trimester PM 2.5 and whole pregnancy PM 2.5 )

PM 2.5 (whole pregnancy) Per 1 μg/m 3 : 0.96 (0.75, 1.19) PM 2.5 (3rd trimester) Per 1 μg/m 3 : 1.17 (0.98, 1.40) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnanc y (adjustment for season of conception) 4th quartile: 1.68 (1.05, 2.75); Per 1 μg/m 3 : 1.12 (0.97, 1.28) Prevalence ratios (PRs) of birth weight <3000 g during exposure over first trimester of pregnancy Each trimester separately 2nd quartile: 1.14 (0.74, 1.96); 3rd quartile: 1.28 (0.84, 2.10) 4th quartile: 1.65 (1.02, 2.60) Per 1 μg/m 3 : 1.10 (0.99, 1.20) All trimesters adjusted simultaneously 2nd quartile: 0.97 (0.60, 1.73); 3rd quartile: 0.98 (0.57, 1.75) 4th quartile: 1.22 (0.71, 2.18) Per 1 μg/m 3 : 1.03 (0.90, 1.17) Prevalence ratios (PRs) of birth weight <3000 g during exposure over second trimester of pregnancy Each trimester separately 2nd quartile: 0.83 (0.52, 1.32); 3rd quartile: 1.08 (0.71, 1.60) 4th quartile: 0.94 (0.61, 1.47) Per 1 μg/m 3 : 1.01 (0.92, 1.12) All trimesters adjusted simultaneously 2nd quartile: 0.75 (0.46, 1.24) 3rd quartile: 0.86 (0.56, 1.30); 4th quartile: 0.75 (0.48, 1.23) Per 1 μg/m 3 : 0.94 (0.84, 1.06) Prevalence ratios (PRs) of birth weight <3000 g during exposure over third trimester of pregnancy Each trimester separately 2nd quartile: 1.30 (0.80, 2.17) 3rd quartile: 1.44 (0.85, 2.27) 4th quartile: 1.90 (1.20, 2.82) Per 1 μg/m 3 : 1.14 (1.02, 1.24) All trimesters adjusted simultaneously 2nd quartile: 1.34 (0.79, 2.30) 3rd quartile: 1.48 (0.86, 2.58) 4th quartile: 1.91 (1.00, 3.20) Per 1 μg/m 3 : 1.14 (0.99, 1.29) Prevalence ratios (PRs) of birth weight <3000 g during exposure over third trimester of pregnancy (adjustment for season of conception) All trimesters adjusted simultaneously Per 1 μg/m 3 : 1.25 (1.04, 1.50) Sensitivity analysis (bootstrapped PR) 2nd quartile: 0.98 (0.63, 1.61); 3rd quartile: 1.22 (0.82, 2.02) 4th quartile: 1.57 (1.02, 2.57) Per 1 μg/m 3 : 1.11 (0.98, 1.27) Estimated increments in prevalence of birth weight of <3000 g during exposure 9 mo after birth Per 1 μg/m 3 : 7% (-7%, 22%)

Reference: (Slama et al., 2007, 093216 ) Period of Study: Jan 1998-Jan 1999 Outcome: Birth weight offspring at term Study Design: Cohort study Pollutant: PM 2.5 absorbance (estimated) Averaging Time: Entire pregnancy period and trimesters PM Increment: 1) 0.5 * 10-5/m 2) Quartiles: a) 1st (reference) (1.29-1.61) b) 2nd (1.61-1.72)



### December 2009 E-483

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Location: Munich, Germany N: 1016 births Statistical Analyses: Poisson model

Covariates: Maternal passive smoking, maternal age, gestational duration, sex of child, parity, maternal education, maternal size, prepregnancy weight, other pollutants (PM 2.5 , PM 2.5 absorbance, NO 2 ), season of conception Dose-response Investigated? Yes Statistical Package: STATA Mean (SD): 1.76 *

Percentiles: 25th: 1.61* 50th(Median): 1.72*

75th: 1.89 * Unit (i.e. μg/ m 3 ): 10-5/m Monitoring Stations: Spatial component: 40 Temporal component: 1 Copollutant (correlation): p.a. = pregnancy avg trim. = trimester abs = absorbance PM 2.5 abs (p.a.)-PM 2.5 abs (1st trim.): 0.54 PM 2.5 abs (p.a.)-PM 2.5 abs (2nd trim.): 0.84 PM 2.5 abs (p.a.)-PM 2.5 abs (3rd trim.): 0.55 PM 2.5 abs (p.a.)-PM 2.5 (p.a.): 0.69 PM 2.5 abs (p.a.)-PM 2.5 (1st trim.): 0.68 PM 2.5 abs (p.a.)-PM 2.5 (2nd trim.): 0.41 PM 2.5 abs (p.a.)-PM 2.5 (3rd trim.): 0.62 PM 2.5 abs (p.a.)-NO 2 (p.a.): 0.67 PM 2.5 abs (p.a.)-NO 2 (1st trim.): 0.34 PM 2.5 abs (p.a.)-NO 2 (2nd trim.): 0.63 PM 2.5 abs (p.a.)-NO 2 (3rd trim.): 0.36 PM 2.5 abs (1st trim.)-PM 2.5 abs (2nd trim.): 0.32 PM 2.5 abs (1st trim.)-PM 2.5 abs (3rd trim.): -0.26 PM 2.5 abs (1st trim.)-PM 2.5 (p.a.): 0.33 PM 2.5 abs (1st trim.)-PM 2.5 (1st trim.): 0.27 PM 2.5 abs (1st trim.)-PM 2.5 (2nd trim.): 0.08 PM 2.5 abs (1st trim.)-PM 2.5 (3rd trim.): 0.48 PM 2.5 abs (1st trim.)-NO 2 (p.a.): 0.29 PM 2.5 abs (1st trim.)-NO 2 (1st trim.): 0.84 PM 2.5 abs (1st trim.)-NO 2 (2nd trim.): 0.16 PM 2.5 abs (1st trim.)-NO 2 (3rd trim.): - 0.39 PM 2.5 abs (2nd trim.)-PM 2.5 abs (3rd trim.): 0.31 PM 2.5 abs (2nd trim.)-PM 2.5 (p.a.): 0.48 PM 2.5 abs (2nd trim.)-PM 2.5 (1st trim.): 0.53 PM 2.5 abs (2nd trim.)-PM 2.5 (2nd trim.): 0.29 PM 2.5 abs (2nd trim.)-PM 2.5 (3rd trim.): 0.36 PM 2.5 abs (2nd trim.)-NO 2 (p.a.): 0.61 PM 2.5 abs (2nd trim.)-NO 2 (1st trim.): 0.19 PM 2.5 abs (2nd trim.)-NO 2 (2nd trim.): 0.85 PM 2.5 abs (2nd trim.)-NO 2 (3rd trim.): 0.17 PM 2.5 abs (3rd trim.)-PM 2.5 (p.a.): 0.52 PM 2.5 abs (3rd trim.)-PM 2.5 (1st trim.): 0.51 PM 2.5 abs (3rd trim.)-PM 2.5 (2nd trim.): 0.41 PM 2.5 abs (3rd trim.)-PM 2.5 (3rd trim.): 0.37 PM 2.5 abs (3rd trim.)-NO 2 (p.a.): 0.40 PM 2.5 abs (3rd trim.)-NO 2 (1st trim.):-0.34 PM 2.5 abs (3rd trim.)-NO 2 (2nd trim.): 0.21 PM 2.5 abs (3rd trim.)-NO 2 (3rd trim.): 0.88 c) 3rd (1.72-1.89) day) 4th (1.89-3.10) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnancy Single-pollutant models Unadjusted models 2nd quartile: 1.19 (0.74, 1.99) 3rd quartile: 1.56 (0.98, 2.50); 4th quartile: 1.52 (0.96, 2.46) Per 0.5 * 10-5/m: 1.25 (0.90, 1.70) Adjusted models 2nd quartile: 1.21 (0.73, 1.97) 3rd quartile: 1.63 (0.98, 2.57); 4th quartile: 1.78 (1.10, 2.70) Per 0.5 * 10-5/m: 1.45 (1.06, 1.87)

Multipollutant models Adjusted models 2nd quartile: 1.19 (0.70, 2.01) 3rd quartile: 1.55 (0.80, 2.80); 4th quartile: 1.46 (0.67, 2.90) Per 0.5 * 10-5/m: 1.33 (0.76, 2.38) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnanc y (adjustment for season of conception) 4th quartile: 1.72 (1.08, 2.73) Per 0.5 * 10-5/m: 1.38 (0.96, 1.86) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnancy Single-pollutant models (Restricted analysis to PM 2.5 below the median) Per 0.5 * 10-5/m: 1.67 (0.66, 3.73) Prevalence ratios (PRs) of birth weight <3000 g during exposure over first trimester of pregnancy Each trimester separately 2nd quartile: 1.15 (0.73, 1.80) 3rd quartile: 1.01 (0.61, 1.53); 4th quartile: 1.04 (0.70, 1.57) Per 0.5 * 10-5/m: 1.03 (0.82, 1.28) All trimesters adjusted simultaneously 2nd quartile: 0.90 (0.52, 1.58) 3rd quartile: 0.82 (0.45, 1.31); 4th quartile: 0.88 (0.53, 1.42) Per 0.5 * 10-5/m: 1.02 (0.77, 1.29) Prevalence ratios (PRs) of birth weight <3000 g during exposure over second trimester of pregnancy Each trimester separately 2nd quartile: 1.33 (0.85, 2.22) 3rd quartile: 1.76 (1.07, 2.91); 4th quartile: 1.83 (1.11, 2.81) Per 0.5 * 10-5/m: 1.27 (1.04, 1.54) All trimesters adjusted simultaneously 2nd quartile: 1.30 (0.77, 2.16) 3rd quartile: 1.63 (0.93, 2.73); 4th quartile: 1.99 (1.12, 3.33) Per 0.5 * 10-5/m: 1.21 (0.93, 1.54) Prevalence ratios (PRs) of birth weight <3000 g during exposure over third trimester of pregnancy Each trimester separately 2nd quartile: 1.30 (0.85, 2.09) 3rd quartile: 0.92 (0.55, 1.50); 4th quartile: 1.50 (1.00, 2.27) Per 0.5 * 10-5/m: 1.20 (0.98, 1.44) All trimesters adjusted simultaneously 2nd quartile: 0.99 (0.64, 1.62) 3rd quartile: 0.71 (0.40, 1.20);



### December 2009 E-484

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) 4th quartile: 1.14 (0.68, 1.91) Per 0.5 * 10-5/m: 1.15 (0.92, 1.42) Prevalence ratios (PRs) of birth weight <3000 g during exposure over first trimester of pregnancy (adjustment for season of conception) All trimesters adjusted simultaneously 4th quartile: 0.73 (0.38, 1.38) Per 0.5 * 10-5/m: 0.93 (0.41, 1.32) Prevalence ratios (PRs) of birth weight <3000 g during exposure over second trimester of pregnancy (adjustment for season of conception) All trimesters adjusted simultaneously 4th quartile: 2.45 (1.22, 4.77) Per 0.5 * 10-5/m: 1.14 (0.70, 1.64) Prevalence ratios (PRs) of birth weight <3000 g during exposure over third trimester of pregnancy (adjustment for season of conception) All trimesters adjusted simultaneously 4th quartile: 1.19 (0.60, 2.48) Per 0.5 * 10-5/m: 1.29 (0.90, 1.75) Sensitivity analysis (bootstrapped PR) 2nd quartile: 1.19 (0.76, 1.91) 3rd quartile: 1.52 (0.99, 2.34); 4th quartile: 1.62 (1.06, 2.55) Per 0.5 * 10-5/m: 1.35 (1.01, 1.83) Estimated increments in prevalence of birth weight <3000 g during exposure 9 mo after birth Per 0.5 * 10-5/m: 18% (-16%, 57%)

Reference: Wilhelm et al. (2005, 088668 ) Period of Study: 1994-2000

Location: Los Angeles County, California, U.S. Outcome: Term low birth weight (LBW) (<2500 g at ≥ 37 completed wk gestation) Vaginal birth <37 completed wk gestation Age Groups: LBW: ≥ 37 completed wk Preterm births: <37 completed wk Study Design: Cross-sectional study

N: For LBW: 136,134 For preterm birth: 106,483 Statistical Analyses: Logistic regression

Covariates: Maternal age, maternal race, maternal education, parity, interval since previous live birth, level of prenatal care, infant sex, previous LBW or preterm infant, birth season, other pollutants (not specified in birth weight analyses, also adjusted for gestational age) Dose-response Investigated? Yes Statistical Package: NR Pollutant: PM 2.5 Averaging Time: 24 h (every 3 days) Entire pregnancy Trimesters of pregnancy Months of pregnancy 6 wk before birth Mean (SD): First trimester: 21.9 Third trimester: 21.0 6 wk before birth: 21.0 Range (Min, Max): First trimester: 11.8-38.9 Third trimester: 11.8-.38.9 6 wk before birth: 9.9-48.5 Monitoring Stations: Zip-code-level analysis: 9 Address-level analysis: 8 Copollutant (correlation): First trimester PM 2.5 -CO: 0.57 PM 2.5 -NO 2 : 0.73 PM 2.5 -O : -0.55 3 PM 2.5 -PM 10 : 0.43 Third trimester: PM 2.5 -CO: 0.67 PM 2.5 -NO 2 : 0.78 PM 2.5 -O 3 : -0.60 PM -PM : 0.52

2.5 10 6 wk before birth: PM 2.5 -CO: 0.63 PM 2.5 -NO : 0.74 2 PM 2.5 -O 3 : -0.60 PM 2.5 -PM 10 : 0.60 PM Increment: 1) 10 μg/m 3 2) 3 levels: a) <25 percentile (reference) b) 25%-75 percentile c) ≥ 75 percentile Incidence of LBW (third trimester exposure) <17.1 μg/m 3 : 2.4 (2.0, 2.8) 17.1 to <24.0 μg/m 3 : 2.2 (2.0, 2.5) ≥ 24.0 μg/m 3 : 2.1 (1.7, 2.4) Incidence of preterm birth (first trimester exposure) <18.0 μg/m 3 : 10.6 (9.6, 11.7) 18.0 to <25.4 μg/m 3 : 8.8 (8.1, 9.5) ≥ 25.4 μg/m 3 : 9.0 (8.1, 10.0) Incidence of preterm birth (6 wk before birth exposure) <16.5 μg/m 3 : 8.2 (7.4, 9.1) 16.5 to <24.7 μg/m 3 : 8.8 (8.2, 9.4) ≥ 24.7 μg/m 3 : 9.6 (8.7, 10.5)

Outcome: Preterm birth Exposure Period: First trimester of pregnancy Address-level analysis: Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 0.85 (0.70, 1.02) 18.1 to <25.2 μg/m 3 : 0.91 (0.72, 1.16) ≥ 25.2 μg/m 3 : 0.83 (0.60, 1.14) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 0.85 (0.74, 0.99) 18.3 to <25.2 μg/m 3 : 0.81 (0.69, 0.94)



### December 2009 E-485

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

≥ 25.2 μg/m 3 : 0.79 (0.65, 0.97) Multipollutant model1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.18 (0.84, 1.65) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 0.83 (0.78, 0.88) 18.5 to <24.9 μg/m 3 : 0.79 (0.74, 0.85) ≥ 24.9 μg/m 3 : 0.76 (0.70, 0.84)

Zip-code-level analysis: Single-pollutant model: Per 10 μg/m 3 : 0.73 (0.67, 0.80) 18.0 to <25.4 μg/m 3 : 0.70 (0.61, 0.80) ≥ 25.4 μg/m 3 : 0.64 (0.53, 0.76)

Outcome: Preterm birth Exposure Period: 6 wk before birth Address-level analysis: Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.09 (0.91, 1.30) 16.8 to <24.1 μg/m 3 : 1.21 (0.97, 1.51) ≥ 24.1 μg/m 3 : 1.25 (0.93, 1.68) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.08 (0.97, 1.21) 17.2 to <24.5 μg/m 3 : 0.94 (0.82, 1.08) ≥ 24.5 μg/m 3 : 1.04 (0.87, 1.24) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.05 (0.99, 1.10) 17.3 to <24.6 μg/m 3 : 1.06 (1.00, 1.13) ≥ 24.6 μg/m 3 : 1.08 (0.99, 1.17)

Zip-code-level analysis Single-pollutant model: Per 10 μg/m 3 : 1.10 (1.00, 1.21) 16.5 to <24.7 μg/m 3 : 1.06 (0.94, 1.20) ≥ 24.7 μg/m 3 : 1.19 (1.02, 1.40) (See Notes) Multipollutant model Per 10 μg/m 3 : 1.12 (0.90, 1.40) ≥ 24.6 μg/m 3 : 1.12 (0.82, 1.52) Notes: In the table, the 75 percentile is noted as 24.7 μg/m 3 . However, the text notes the 75 percentile as 24.3 μg/m 3

.



### December 2009 E-486

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Woodruff et al. (2006, 088758 ) Period of Study: 1999-2000

Location: California Outcome (ICD10): SIDS (R95) Respiratory mortality (J00-J99) Bronchopulmonary dysplasia (P27.1) External accidents (V01-Y98) Ill-defined and unspecified causes of mortality (R99) Age Groups: >28 days old Study Design: Matched case-control (matched on date of birth and birth weight)

N: 3877 infants Statistical Analyses: Conditional logistic regression

Covariates: Maternal race, education, parity, age, marital status Dose-response Investigated? Yes Statistical Package: STATA Pollutant: PM 2.5 Averaging Time: 24 hrs (every 6 days) (time period between birth and post neonatal death for the infant who died and the same period for its four matched surviving infants)

Percentiles: Infants who died of all causes (cases)

25th: 13.4 50th(Median): 19.2

75th: 23.6

Matched controls

25th: 13.5 50th(Median): 18.4

75th: 22.7 Monitoring Stations: 73 (from 39 counties) PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: All-cause mortality: Unadjusted: 1.15 (1.00, 1.32) Adjusted: 1.07 (0.93, 1.24) Cause-specific mortality: Respiratory (all): Unadjusted: 2.15 (1.15, 4.02) Adjusted: 2.13 (1.12, 4.05) Respiratory (excluding deaths due to BPD): Adjusted: 1.42 (0.66, 3.03) Respiratory (BPD alone): Unadjusted: 6.00 (1.40, 27.76) Respiratory (low birth weight infants only): Unadjusted: 3.09 (1.14, 8.40) Respiratory (normal birth weight infants only): Unadjusted: 1.66 (0.74, 3.70) Respiratory (with matched PM 2.5 avgd over all monitors in county) Adjusted: 2.28 (0.94, 5.52) Respiratory (averaging all PM 2.5 measurements in county over the 2-yr study period): Adjusted: 2.26 (0.83, 6.21) SIDS: Unadjusted: 0.86 (0.61, 1.22) Adjusted: 0.82 (0.55, 1.23)SIDS (includes ICD10 code R99: illdefined and unspecified causes of mortality): Adjusted: 1.03 (0.79, 1.35) External causes: Unadjusted: 0.91 (0.56, 1.47) Adjusted: 0.83 (0.50, 1.39) Compare against the lowest quartile, estimates for respiratory-specific mortality were provided: 2nd quartile: 1.28 (0.47, 3.51) 3rd quartile: 1.75 (0.65, 4.72) 4th quartile: 2.35 (0.85, 6.54)



### December 2009 E-487

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Woodruff et al. (2008, 098386 ) Period of Study: 1999-2002

Location: U.S. counties with >250,000 residents (96 counties) Outcome (ICD10): Postneonatal deaths: Respiratory mortality (J000-99, plus bronchopulmonary dysplasia [BPD] P27.1) SIDS (R95) Ill-defined causes (R99)

All other deaths evaluated as a control category Age Groups: Infants aged >28 days and <1 yr Study Design: Cross-sectional

N: 3,583,495 births (6,639 post neonatal deaths) Statistical Analyses: Logistic GEE (exchangeable correlation structure)

Covariates: maternal race/ethnicity, marital status, age, education, primiparity, county-level poverty and per capita income levels, yr and month of birth dummy variables to account for time trend and seasonal effects, and region of the country sensitivity analyses performed among only those mothers with smoking information (adjustment for smoking had no effect on the estimates)

Season: Adjusted for yr and month of birth dummy variables to account for time trend and seasonal effects Dose-response Investigated? Evaluated the appropriateness of a linear form from analysis based on quartiles of exposure and concluded that linear form was appropriate (data not shown) Statistical Package: SAS Pollutant: PM 2.5 Averaging Time: Measured continuously for 24 h once every 6 days exposure assigned by calculating avg concentration of pollutant during first 2 mo of life Median and IQR (25th-75th percentile): Survivors: 14.8 (11.7-18.7) All causes of death: 14.9 (12.0-18.6) Respiratory: 14.8 (11.5-18.5) SIDS: 14.5 (12.0-17.5) SIDS + ill-defined: 14.8 (12.1-18.5) Other causes: 14.9 (12.0-18.6)

Percentiles: See above PM Component: Not assessed, but controlled for region of the country to account for PM composition variation Monitoring Stations: NR Copollutant (correlation): PM 10 (r = 0.34)

PM 2.5 CO (r = 0.35)

SO 2 (r = 0.21)

O 3 (r = -0.10)

Notes: Monthly avg calculated if there were at least 3 available measures for PM Assigned exposures using the avg concentration of the county of residence PM Increment: IQR (7 μg/m 3 ) Effect Estimate [Lower CI, Upper CI]: Adjusted ORs for single pollutant models All causes: 1.04 (0.98, 1.11) Respiratory: 1.11 (0.96, 1.29) SIDS: 1.01 (0.86, 1.20) Ill-defined + SIDS: 1.06 (0.97, 1.17) Other causes: 1.03 (0.96, 1.12) Adjusted ORs for multipollutant models (including CO, O 3 , SO 2 ) Respiratory: 1.05 (0.89, 1.24) SIDS: 1.04 (0.87, 1.23) OR for respiratory deaths assessing exposure as quartiles Highest vs. Lowest quartile: 1.39 (1.04, 1.85)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-488

# E.8. Long-Term Exposure and Mortality

Table E-30. Long-term exposure-mortality - PM 10 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Breitner et al., 2009, 188439 ) Period of Study: Oct 1991-Mar 2002

Location: Efurt, Germany Outcome: Mortality, excluding infants and ICD-9 ≥ 800 Study Design: Time-series

Covariates: Seasonal and weekday variations, influenza epidemics, air temperature, relative humidity Statistical Analysis: Semiparametric Poisson regression, polynomial distributed lag (PDL) Statistical Package: R Age Groups: All Pollutant: PM 10 Averaging Time: Daily Mean (SD) Unit: 1 (10/1/1991-8/31/1995): 50.6 ± 32.2 μg/m 3 2 (9/1/1995-2/28/1998): 41.1 ± 28.4 μg/m 3 3 (3/1/1998-3/31/2002): 24.3 ± 15.4 μg/m 3 Total: 38.0 ±28.3 μg/m 3 Range (Min, Max): NR Copollutant: NO 2 , CO, UFP Increment: IQR Relative Risk (95% CI) Lag New City Limits 6-day IQR: 17.2 PDL: 0.997 (0.972-1.022) Mean of lags 0-5: 0.995 (0.971-1.019) Old City Limits 6-day IQR: 17.2 PDL: 1.004 (0.978-1.031) Mean of lags 0-5: 1.001 (0.976-1.027) New City Limits 15-day IQR: 14.5 PDL: 1.008 (0.982-1.036) Mean of lags 0-14: 1.006 (0.981-1.032) Old City Limits 15-day IQR: 14.5 PDL: 1.019 (0.991-1.048) Mean of lags 0-14: 1.017 (0.990-1.044)

Multiday Ma, 6-day Overall IQR: 24.2 Overall RR (95% CI): 0.998 (0.976-1.021) Period 1: 0.996 (0.969-1.024) Period 2: 1.013 (0.972-1.056) Period 3: 0.949 (0.897-1.004) Multiday Ma, 15-day Overall IQR: 22.3 Overall RR (95% CI): 1.020 (0.993-1.093) Period 1: 1.017 (0.984-1.051) Period 2: 1.012 (0.973-1.071) Period 3: 0.978 (0.911-1.051) Reference: (Slama et al., 2007, 093216 ) Period of Study: Jan 1998-Jan 1999

Location: Munich, Germany Outcome: Birth weight offspring at term Study Design: Cohort study

N: 1016 births Statistical Analyses: Poisson model

Covariates: Maternal passive smoking, maternal age, gestational duration, sex of child, parity, maternal education, maternal size, prepregnancy weight, other pollutants (PM 2.5 , PM 2.5 absorbance, NO 2 ), season of conception Dose-response Investigated? Yes Statistical Package: STATA Pollutant: PM 2.5 (estimated based on larger PM size fractions) Averaging Time: Entire pregnancy period and trimesters Mean (SD): 14.4

Percentiles: 25th: 13.5 50th(Median): 14.4

75th: 15.4 Monitoring Stations: Spatial component: 40 Temporal component: 1 Copollutant (correlation):

p.a. = pregnancy avg trim. = trimester PM 2.5 (p.a.)-PM 2.5 (1st trim.): 0.85 PM 2.5 (p.a.)-PM 2.5 (2nd trim.): 0.77 PM 2.5 (p.a.)-PM 2.5 (3rd trim.): 0.87 PM 2.5 (p.a.)-NO 2 (p.a.): 0.45 PM 2.5 (p.a.)-NO 2 (1st trim.): 0.18 PM 2.5 (p.a.)-NO 2 (2nd trim.): 0.32 PM Increment: 1) 1 μg/m 3 2) Quartiles: a) 1st (reference) (7.2-13.5 μg/m 3 ) b) 2nd (13.5-14.4 μg/m 3 ) c) 3rd (14.4-15.4 μg/m 3 ) day) 4th (15.41-17.5 μg/m 3 ) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnancy Single-pollutant models Unadjusted models 2nd quartile: 1.07 (0.65, 1.73); 3rd quartile: 1.38 (0.91, 2.09) 4th quartile: 1.45 (0.92, 2.25) Per 1 μg/m 3 : 1.06 (0.95, 1.19) Adjusted models 2nd quartile: 1.08 (0.63, 1.82); 3rd quartile: 1.34 (0.86, 2.13) 4th quartile: 1.73 (1.15, 2.69); Per 1 μg/m 3 : 1.13 (1.00, 1.29)

Multipollutant models Adjusted models 2nd quartile: 1.01 (0.57, 1.85) 3rd quartile: 1.12 (0.64, 1.87) 4th quartile: 1.36 (0.72, 2.45); Per 1 μg/m 3 : 1.07 (0.91, 1.26) Single-pollutant models (restricted



### December 2009 E-489

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

PM 2.5 (p.a.)-NO 2 (3rd trim.): 0.37 PM 2.5 (1st trim.)-PM 2.5 (2nd trim.): 0.40 PM 2.5 (1st trim.)-PM 2.5 (3rd trim.): 0.68 PM 2.5 (1st trim.)-NO 2 (p.a.): 0.48 PM 2.5 (1st trim.)-NO 2 (1st trim.): 0.15 PM 2.5 (1st trim.)-NO 2 (2nd trim.): 0.41 PM 2.5 (1st trim.)-NO 2 (3rd trim.): 0.39 PM 2.5 (2nd trim.)-PM 2.5 (3rd trim.): 0.51 PM 2.5 (2nd trim.)-NO 2 (p.a.): 0.23 PM 2.5 (2nd trim.)-NO 2 (1st trim.): -0.03 PM 2.5 (2nd trim.)-NO 2 (2nd trim.): 0.17 PM 2.5 (2nd trim.)-NO 2 (3rd trim.): 0.30 PM 2.5 (3rd trim.)-NO 2 (p.a.): 0.39 PM 2.5 (3rd trim.)-NO 2 (1st trim.): 0.33 PM 2.5 (3rd trim.)-NO 2 (2nd trim.): 0.21 PM 2.5 (3rd trim.)-NO 2 (3rd trim.): 0.23 PM 2.5 (p.a.)- PM 2.5 absorbance (p.a.): 0.69 PM 2.5 (p.a.)- PM 2.5 abs (1st trim.): 0.33 PM 2.5 (p.a.)- PM 2.5 abs (2nd trim.): 0.48 PM 2.5 (p.a.)- PM 2.5 abs (3rd trim.): 0.52 PM 2.5 (1st trim.)- PM 2.5 abs (p.a.): 0.68 PM 2.5 (1st trim.)- PM 2.5 abs (1st trim.): 0.27 PM 2.5 (1st trim.)- PM 2.5 abs (2nd trim.): 0.53 PM 2.5 (1st trim.)- PM 2.5 abs (3rd trim.): 0.51 PM 2.5 (2nd trim.)- PM 2.5 abs(p.a.): 0.41 PM 2.5 (2nd trim.)- PM 2.5 abs (1st trim.): 0.08 PM 2.5 (2nd trim.)- PM 2.5 abs (2nd trim.): 0.29 PM 2.5 (2nd trim.)- PM 2.5 abs (3rd trim.): 0.41 PM 2.5 (3rd trim.)- PM 2.5 abs (p.a.): 0.62 PM 2.5 (3rd trim.)- PM 2.5 abs (1st trim.): 0.48 PM 2.5 (3rd trim.)- PM 2.5 abs (2nd trim.): 0.36 PM 2.5 (3rd trim.)- PM 2.5 abs (3rd trim.): 0.37 Analysis to PM 2.5 absorbance below the median) Per 1 μg/m 3 : 1.15 (0.89, 1.52) Prevalence ratios (PRs) of birth weight <3000 g Multipollutant models (simultaneous adjustment of 3rd trimester PM 2.5 and whole pregnancy PM 2.5 ) PM 2.5 (whole pregnancy) Per 1 μg/m 3 : 0.96 (0.75, 1.19) PM 2.5 (3rd trimester) Per 1 μg/m 3 : 1.17 (0.98, 1.40) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnanc y (adjustment for season of conception) 4th quartile: 1.68 (1.05, 2.75); Per 1 μg/m 3 : 1.12 (0.97, 1.28) Prevalence ratios (PRs) of birth weight <3000 g during exposure over first trimester of pregnancy Each trimester separately 2nd quartile: 1.14 (0.74, 1.96); 3rd quartile: 1.28 (0.84, 2.10) 4th quartile: 1.65 (1.02, 2.60) Per 1 μg/m 3 : 1.10 (0.99, 1.20) All trimesters adjusted simultaneously 2nd quartile: 0.97 (0.60, 1.73); 3rd quartile: 0.98 (0.57, 1.75) 4th quartile: 1.22 (0.71, 2.18) Per 1 μg/m 3 : 1.03 (0.90, 1.17) Prevalence ratios (PRs) of birth weight <3000 g during exposure over second trimester of pregnancy Each trimester separately 2nd quartile: 0.83 (0.52, 1.32); 3rd quartile: 1.08 (0.71, 1.60) 4th quartile: 0.94 (0.61, 1.47) Per 1 μg/m 3 : 1.01 (0.92, 1.12) All trimesters adjusted simultaneously 2nd quartile: 0.75 (0.46, 1.24) 3rd quartile: 0.86 (0.56, 1.30); 4th quartile: 0.75 (0.48, 1.23) Per 1 μg/m 3 : 0.94 (0.84, 1.06) Prevalence ratios (PRs) of birth weight <3000 g during exposure over third trimester of pregnancy Each trimester separately 2nd quartile: 1.30 (0.80, 2.17) 3rd quartile: 1.44 (0.85, 2.27) 4th quartile: 1.90 (1.20, 2.82) Per 1 μg/m 3 : 1.14 (1.02, 1.24) All trimesters adjusted simultaneously 2nd quartile: 1.34 (0.79, 2.30) 3rd quartile: 1.48 (0.86, 2.58) 4th quartile: 1.91 (1.00, 3.20) Per 1 μg/m 3 : 1.14 (0.99, 1.29) Prevalence ratios (PRs) of birth weight <3000 g during exposure over third trimester of pregnancy (adjustment for season of conception) All trimesters adjusted simultaneously Per 1 μg/m 3 : 1.25 (1.04, 1.50) Sensitivity analysis (bootstrapped PR) 2nd quartile: 0.98 (0.63, 1.61); 3rd quartile: 1.22 (0.82, 2.02) 4th quartile: 1.57 (1.02, 2.57) Per 1 μg/m 3 : 1.11 (0.98, 1.27) Estimated increments in prevalence of birth weight of <3000 g during exposure 9 mo after birth



### December 2009 E-490

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI) Per 1 μg/m 3 : 7% (-7%, 22%)

Reference: (Slama et al., 2007, 093216 ) Period of Study: Jan 1998-Jan 1999

Location: Munich, Germany Outcome: Birth weight offspring at term Study Design: Cohort study

N: 1016 births Statistical Analyses: Poisson model

Covariates: Maternal passive smoking, maternal age, gestational duration, sex of child, parity, maternal education, maternal size, prepregnancy weight, other pollutants (PM 2.5 , PM 2.5 absorbance, NO 2 ), season of conception Dose-response Investigated? Yes Statistical Package: STATA Pollutant: PM 2.5 absorbance (estimated) Averaging Time: Entire pregnancy period and trimesters Mean (SD): 1.76 *

Percentiles: 25th: 1.61* 50th(Median): 1.72*

75th: 1.89 * Unit (i.e. μg/ m 3 ): 10-5/m Monitoring Stations: Spatial component: 40 Temporal component: 1 Copollutant (correlation): p.a. = pregnancy avg trim. = trimester abs = absorbance PM 2.5 abs (p.a.)-PM 2.5 abs (1st trim.): 0.54 PM 2.5 abs (p.a.)-PM 2.5 abs (2nd trim.): 0.84 PM 2.5 abs (p.a.)-PM 2.5 abs (3rd trim.): 0.55 PM 2.5 abs (p.a.)-PM 2.5 (p.a.): 0.69 PM 2.5 abs (p.a.)-PM 2.5 (1st trim.): 0.68 PM 2.5 abs (p.a.)-PM 2.5 (2nd trim.): 0.41 PM 2.5 abs (p.a.)-PM 2.5 (3rd trim.): 0.62 PM 2.5 abs (p.a.)-NO 2 (p.a.): 0.67 PM 2.5 abs (p.a.)-NO 2 (1st trim.): 0.34 PM 2.5 abs (p.a.)-NO 2 (2nd trim.): 0.63 PM 2.5 abs (p.a.)-NO 2 (3rd trim.): 0.36 PM 2.5 abs (1st trim.)-PM 2.5 abs (2nd trim.): 0.32 PM 2.5 abs (1st trim.)-PM 2.5 abs (3rd trim.): -0.26 PM 2.5 abs (1st trim.)-PM 2.5 (p.a.): 0.33 PM 2.5 abs (1st trim.)-PM 2.5 (1st trim.): 0.27 PM 2.5 abs (1st trim.)-PM 2.5 (2nd trim.): 0.08 PM 2.5 abs (1st trim.)-PM 2.5 (3rd trim.): 0.48 PM 2.5 abs (1st trim.)-NO 2 (p.a.): 0.29 PM 2.5 abs (1st trim.)-NO 2 (1st trim.): 0.84 PM 2.5 abs (1st trim.)-NO 2 (2nd trim.): 0.16 PM 2.5 abs (1st trim.)-NO 2 (3rd trim.): - 0.39 PM 2.5 abs (2nd trim.)-PM 2.5 abs (3rd trim.): 0.31 PM 2.5 abs (2nd trim.)-PM 2.5 (p.a.): 0.48 PM 2.5 abs (2nd trim.)-PM 2.5 (1st trim.): 0.53 PM 2.5 abs (2nd trim.)-PM 2.5 (2nd trim.): 0.29 PM 2.5 abs (2nd trim.)-PM 2.5 (3rd trim.): 0.36 PM 2.5 abs (2nd trim.)-NO 2 (p.a.): 0.61 PM 2.5 abs (2nd trim.)-NO 2 (1st trim.): 0.19 PM 2.5 abs (2nd trim.)-NO 2 (2nd trim.): 0.85 PM 2.5 abs (2nd trim.)-NO 2 (3rd trim.): 0.17 PM 2.5 abs (3rd trim.)-PM 2.5 (p.a.): 0.52 PM 2.5 abs (3rd trim.)-PM 2.5 (1st trim.): 0.51 PM 2.5 abs (3rd trim.)-PM 2.5 (2nd trim.): 0.41 PM 2.5 abs (3rd trim.)-PM 2.5 (3rd trim.): 0.37 PM 2.5 abs (3rd trim.)-NO 2 (p.a.): 0.40 PM 2.5 abs (3rd trim.)-NO 2 (1st trim.): - PM Increment: 1) 0.5 * 10-5/m 2) Quartiles: a) 1st (reference) (1.29-1.61) b) 2nd (1.61-1.72) c) 3rd (1.72-1.89) day) 4th (1.89-3.10) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnancy Single-pollutant models Unadjusted models 2nd quartile: 1.19 (0.74, 1.99) 3rd quartile: 1.56 (0.98, 2.50); 4th quartile: 1.52 (0.96, 2.46) Per 0.5 * 10-5/m: 1.25 (0.90, 1.70) Adjusted models 2nd quartile: 1.21 (0.73, 1.97) 3rd quartile: 1.63 (0.98, 2.57); 4th quartile: 1.78 (1.10, 2.70) Per 0.5 * 10-5/m: 1.45 (1.06, 1.87)

Multipollutant models Adjusted models 2nd quartile: 1.19 (0.70, 2.01) 3rd quartile: 1.55 (0.80, 2.80); 4th quartile: 1.46 (0.67, 2.90) Per 0.5 * 10-5/m: 1.33 (0.76, 2.38) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnanc y (adjustment for season of conception) 4th quartile: 1.72 (1.08, 2.73) Per 0.5 * 10-5/m: 1.38 (0.96, 1.86) Prevalence ratios (PRs) of birth weight <3000 g during exposure over the whole pregnancy Single-pollutant models (Restricted analysis to PM 2.5 below the median) Per 0.5 * 10-5/m: 1.67 (0.66, 3.73) Prevalence ratios (PRs) of birth weight <3000 g during exposure over first trimester of pregnancy Each trimester separately 2nd quartile: 1.15 (0.73, 1.80) 3rd quartile: 1.01 (0.61, 1.53); 4th quartile: 1.04 (0.70, 1.57) Per 0.5 * 10-5/m: 1.03 (0.82, 1.28) All trimesters adjusted simultaneously 2nd quartile: 0.90 (0.52, 1.58) 3rd quartile: 0.82 (0.45, 1.31); 4th quartile: 0.88 (0.53, 1.42) Per 0.5 * 10-5/m: 1.02 (0.77, 1.29) Prevalence ratios (PRs) of birth weight <3000 g during exposure over second trimester of pregnancy Each trimester separately 2nd quartile: 1.33 (0.85, 2.22) 3rd quartile: 1.76 (1.07, 2.91); 4th quartile: 1.83 (1.11, 2.81) Per 0.5 * 10-5/m: 1.27 (1.04, 1.54) All trimesters adjusted simultaneously 2nd quartile: 1.30 (0.77, 2.16) 3rd quartile: 1.63 (0.93, 2.73); 4th quartile: 1.99 (1.12, 3.33) Per 0.5 * 10-5/m: 1.21 (0.93, 1.54) Prevalence ratios (PRs) of birth weight <3000 g during exposure over third trimester of pregnancy Each trimester separately 2nd quartile: 1.30 (0.85, 2.09) 3rd quartile: 0.92 (0.55, 1.50);



### December 2009 E-491

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

0.34 PM 2.5 abs (3rd trim.)-NO 2 (2nd trim.): 0.21 PM 2.5 abs (3rd trim.)-NO 2 (3rd trim.): 0.88 4th quartile: 1.50 (1.00, 2.27) Per 0.5 * 10-5/m: 1.20 (0.98, 1.44) All trimesters adjusted simultaneously 2nd quartile: 0.99 (0.64, 1.62) 3rd quartile: 0.71 (0.40, 1.20); 4th quartile: 1.14 (0.68, 1.91) Per 0.5 * 10-5/m: 1.15 (0.92, 1.42) Prevalence ratios (PRs) of birth weight <3000 g during exposure over first trimester of pregnancy (adjustment for season of conception) All trimesters adjusted simultaneously 4th quartile: 0.73 (0.38, 1.38) Per 0.5 * 10-5/m: 0.93 (0.41, 1.32) Prevalence ratios (PRs) of birth weight <3000 g during exposure over second trimester of pregnancy (adjustment for season of conception) All trimesters adjusted simultaneously 4th quartile: 2.45 (1.22, 4.77) Per 0.5 * 10-5/m: 1.14 (0.70, 1.64) Prevalence ratios (PRs) of birth weight <3000 g during exposure over third trimester of pregnancy (adjustment for season of conception) All trimesters adjusted simultaneously 4th quartile: 1.19 (0.60, 2.48) Per 0.5 * 10-5/m: 1.29 (0.90, 1.75) Sensitivity analysis (bootstrapped PR) 2nd quartile: 1.19 (0.76, 1.91) 3rd quartile: 1.52 (0.99, 2.34); 4th quartile: 1.62 (1.06, 2.55) Per 0.5 * 10-5/m: 1.35 (1.01, 1.83) Estimated increments in prevalence of birth weight <3000 g during exposure 9 mo after birth Per 0.5 * 10- 5/m: 18% (-16%, 57%)

Reference: Wilhelm et al. (2005, 088668 ) Period of Study: 1994-2000

Location: Los Angeles County, California, U.S. Outcome: Term low birth weight (LBW) (<2500 g at ≥ 37 completed wk gestation) Vaginal birth <37 completed wk gestation Age Groups: LBW: ≥ 37 completed wk Preterm births: <37 completed wk Study Design: Cross-sectional study

N: For LBW: 136,134 For preterm birth: 106,483 Statistical Analyses: Logistic regression

Covariates: Maternal age, maternal race, maternal education, parity, interval since previous live birth, level of prenatal care, infant sex, previous LBW or preterm infant, birth season, other pollutants (not specified in birth weight analyses, also adjusted for gestational age) Dose-response Investigated? Yes Statistical Package: NR Pollutant: PM 2.5 Averaging Time: 24 h (every 3 days) Entire pregnancy Trimesters of pregnancy Months of pregnancy 6 wk before birth Mean (SD): First trimester: 21.9 Third trimester: 21.0 6 wk before birth: 21.0 Range (Min, Max): First trimester: 11.8-38.9 Third trimester: 11.8-.38.9 6 wk before birth: 9.9-48.5 Monitoring Stations: Zip-code-level analysis: 9 Address-level analysis: 8 Copollutant (correlation): First trimester PM 2.5 -CO: 0.57 PM 2.5 -NO 2 : 0.73 PM 2.5 -O 3 : -0.55 PM -PM : 0.43

2.5 10 Third trimester: PM 2.5 -CO: 0.67 PM 2.5 -NO : 0.78 2 PM 2.5 -O 3 : -0.60 PM 2.5 -PM 10 : 0.52 6 wk before birth: PM Increment: 1) 10 μg/m 3 2) 3 levels: a) <25 percentile (reference) b) 25%-75 percentile c) ≥ 75 percentile Incidence of LBW (third trimester exposure) <17.1 μg/m 3 : 2.4 (2.0, 2.8) 17.1 to <24.0 μg/m 3 : 2.2 (2.0, 2.5) ≥ 24.0 μg/m 3 : 2.1 (1.7, 2.4) Incidence of preterm birth (first trimester exposure) <18.0 μg/m 3 : 10.6 (9.6, 11.7) 18.0 to <25.4 μg/m 3 : 8.8 (8.1, 9.5) ≥ 25.4 μg/m 3 : 9.0 (8.1, 10.0) Incidence of preterm birth (6 wk before birth exposure) <16.5 μg/m 3 : 8.2 (7.4, 9.1) 16.5 to <24.7 μg/m 3 : 8.8 (8.2, 9.4) ≥ 24.7 μg/m 3 : 9.6 (8.7, 10.5)

Outcome: Preterm birth Exposure Period: First trimester of pregnancy Address-level analysis: Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 0.85 (0.70, 1.02) 18.1 to <25.2 μg/m 3 :



### December 2009 E-492

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

PM 2.5 -CO: 0.63 PM 2.5 -NO 2 : 0.74 PM 2.5 -O 3 : -0.60 PM 2.5 -PM 10 : 0.60 0.91 (0.72, 1.16) ≥ 25.2 μg/m 3 : 0.83 (0.60, 1.14) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 0.85 (0.74, 0.99) 18.3 to <25.2 μg/m 3 : 0.81 (0.69, 0.94) ≥ 25.2 μg/m 3 : 0.79 (0.65, 0.97) Multipollutant model1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.18 (0.84, 1.65) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 0.83 (0.78, 0.88) 18.5 to <24.9 μg/m 3 : 0.79 (0.74, 0.85) ≥ 24.9 μg/m 3 : 0.76 (0.70, 0.84)

Zip-code-level analysis: Single-pollutant model: Per 10 μg/m 3 : 0.73 (0.67, 0.80) 18.0 to <25.4 μg/m 3 : 0.70 (0.61, 0.80) ≥ 25.4 μg/m 3 : 0.64 (0.53, 0.76)

Outcome: Preterm birth Exposure Period: 6 wk before birth Address-level analysis: Single-pollutant model: Distance ≤ 1 mile Per 10 μg/m 3 : 1.09 (0.91, 1.30) 16.8 to <24.1 μg/m 3 : 1.21 (0.97, 1.51) ≥ 24.1 μg/m 3 : 1.25 (0.93, 1.68) Single-pollutant model: 1 <distance ≤ 2 mile Per 10 μg/m 3 : 1.08 (0.97, 1.21) 17.2 to <24.5 μg/m 3 : 0.94 (0.82, 1.08) ≥ 24.5 μg/m 3 : 1.04 (0.87, 1.24) Single-pollutant model: 2 <distance ≤ 4 mile Per 10 μg/m 3 : 1.05 (0.99, 1.10) 17.3 to <24.6 μg/m 3 : 1.06 (1.00, 1.13) ≥ 24.6 μg/m 3 : 1.08 (0.99, 1.17)

Zip-code-level analysis Single-pollutant model: Per 10 μg/m 3 : 1.10 (1.00, 1.21) 16.5 to <24.7 μg/m 3 : 1.06 (0.94, 1.20) ≥ 24.7 μg/m 3 : 1.19 (1.02, 1.40) (See Notes) Multipollutant model Per 10 μg/m 3 : 1.12 (0.90, 1.40) ≥ 24.6 μg/m 3 : 1.12 (0.82, 1.52) Notes: In the table, the 75 percentile is noted as 24.7 μg/m 3 . However, the text notes the 75 percentile as 24.3 μg/m 3

.



### December 2009 E-493

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Woodruff et al. (2006, 088758 ) Period of Study: 1999-2000

Location: California Outcome (ICD10): SIDS (R95) Respiratory mortality (J00-J99) Bronchopulmonary dysplasia (P27.1) External accidents (V01-Y98) Ill-defined and unspecified causes of mortality (R99) Age Groups: >28 days old Study Design: Matched case-control (matched on date of birth and birth weight)

N: 3877 infants Statistical Analyses: Conditional logistic regression

Covariates: Maternal race, education, parity, age, marital status Dose-response Investigated? Yes Statistical Package: STATA Pollutant: PM 2.5 Averaging Time: 24 h (every 6 days) (time period between birth and post neonatal death for the infant who died and the same period for its four matched surviving infants) Percentiles: Infants who died of all causes (cases)

25th: 13.4 50th(Median): 19.2

75th: 23.6

Matched controls

25th: 13.5 50th(Median): 18.4

75th: 22.7 Monitoring Stations: 73 (from 39 counties) PM Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] lag: All-cause mortality: Unadjusted: 1.15 (1.00, 1.32) Adjusted: 1.07 (0.93, 1.24) Cause-specific mortality: Respiratory (all): Unadjusted: 2.15 (1.15, 4.02) Adjusted: 2.13 (1.12, 4.05) Respiratory (excluding deaths due to BPD): Adjusted: 1.42 (0.66, 3.03) Respiratory (BPD alone): Unadjusted: 6.00 (1.40, 27.76) Respiratory (low birth weight infants only): Unadjusted: 3.09 (1.14, 8.40) Respiratory (normal birth weight infants only): Unadjusted: 1.66 (0.74, 3.70) Respiratory (with matched PM 2.5 avgd over all monitors in county) Adjusted: 2.28 (0.94, 5.52) Respiratory (averaging all PM 2.5 measurements in county over the 2-yr study period): Adjusted: 2.26 (0.83, 6.21) SIDS: Unadjusted: 0.86 (0.61, 1.22) Adjusted: 0.82 (0.55, 1.23)SIDS (includes ICD10 code R99: illdefined and unspecified causes of mortality): Adjusted: 1.03 (0.79, 1.35) External causes: Unadjusted: 0.91 (0.56, 1.47) Adjusted: 0.83 (0.50, 1.39) Compare against the lowest quartile, estimates for respiratory-specific mortality were provided: 2nd quartile: 1.28 (0.47, 3.51) 3rd quartile: 1.75 (0.65, 4.72) 4th quartile: 2.35 (0.85, 6.54)



### December 2009 E-494

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Woodruff et al. (2008, 098386 ) Period of Study: 1999-2002

Location: U.S. counties with >250,000 residents (96 counties) Outcome (ICD10): Postneonatal deaths: Respiratory mortality (J000-99, plus bronchopulmonary dysplasia [BPD] P27.1) SIDS (R95) Ill-defined causes (R99)

All other deaths evaluated as a control category Age Groups: Infants aged >28 days and <1 yr Study Design: Cross-sectional

N: 3,583,495 births (6,639 post neonatal deaths) Statistical Analyses: Logistic GEE (exchangeable correlation structure)

Covariates: Maternal race/ethnicity, marital status, age, education, primiparity, county-level poverty and per capita income levels, yr and month of birth dummy variables to account for time trend and seasonal effects, and region of the country sensitivity analyses performed among only those mothers with smoking information (adjustment for smoking had no effect on the estimates)

Season: Adjusted for yr and month of birth dummy variables to account for time trend and seasonal effects Dose-response Investigated? Evaluated the appropriateness of a linear form from analysis based on quartiles of exposure and concluded that linear form was appropriate (data not shown) Statistical Package: SAS Pollutant: PM 2.5 Averaging Time: Measured continuously for 24 h once every 6 days Exposure assigned by calculating avg concentration of pollutant during first 2 mo of life Median and IQR (25th-75th percentile): Survivors: 14.8 (11.7-18.7) All causes of death: 14.9 (12.0-18.6) Respiratory: 14.8 (11.5-18.5) SIDS: 14.5 (12.0-17.5) SIDS + ill-defined: 14.8 (12.1-18.5) Other causes: 14.9 (12.0-18.6) Percentiles: See above PM Component: Not assessed, but controlled for region of the country to account for PM composition variation Monitoring Stations: NR Copollutant (correlation):

PM 10 (r = 0.34)

PM 2.5 CO (r = 0.35)

SO 2 (r = 0.21)

O 3 (r = -0.10)

Notes: Monthly avg calculated if there were at least 3 available measures for PM Assigned exposures using the avg concentration of the county of residence PM Increment: IQR (7 μg/m 3 ) Effect Estimate [Lower CI, Upper CI]: Adjusted ORs for single pollutant models All causes: 1.04 (0.98, 1.11) Respiratory: 1.11 (0.96, 1.29) SIDS: 1.01 (0.86, 1.20) Ill-defined + SIDS: 1.06 (0.97, 1.17) Other causes: 1.03 (0.96, 1.12) Adjusted ORs for multipollutant models (including CO, O 3 , SO 2 ) Respiratory: 1.05 (0.89, 1.24) SIDS: 1.04 (0.87, 1.23) OR for respiratory deaths assessing exposure as quartiles Highest vs. Lowest quartile: 1.39 (1.04, 1.85)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-495

# E.9. Long-Term Exposure and Mortality

Table E-31. Long-term exposure-mortality - PM 10 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Breitner et al., 2009, 188439 ) Period of Study: Oct 1991-Mar 2002

Location: Efurt, Germany Outcome: Mortality, excluding infants and ICD-9 ≥ 800 Study Design: Time-series

Covariates: Seasonal and weekday variations, influenza epidemics, air temperature, relative humidity Statistical Analysis: Semiparametric Poisson regression, polynomial distributed lag (PDL) Statistical Package: R Age Groups: All Pollutant: PM 10 Averaging Time: Daily Mean (SD) Unit: 1 (10/1/1991-8/31/1995): 50.6 ± 32.2 μg/m 3 2 (9/1/1995-2/28/1998): 41.1 ± 28.4 μg/m 3 3 (3/1/1998-3/31/2002): 24.3 ± 15.4 μg/m 3 Total: 38.0 ±28.3 μg/m 3 Range (Min, Max): NR Copollutant: NO 2 , CO, UFP Increment: IQR Relative Risk (95% CI) lag New City Limits 6-day IQR: 17.2 PDL: 0.997 (0.972-1.022) Mean of lags 0-5: 0.995 (0.971-1.019) Old City Limits 6-day IQR: 17.2 PDL: 1.004 (0.978-1.031) Mean of lags 0-5: 1.001 (0.976-1.027) New City Limits 15-day IQR: 14.5 PDL: 1.008 (0.982-1.036) Mean of lags 0-14: 1.006 (0.981-1.032) Old City Limits 15-day IQR: 14.5 PDL: 1.019 (0.991-1.048) Mean of lags 0-14: 1.017 (0.990-1.044)

Multiday Ma, 6-day Overall IQR: 24.2 Overall RR (95% CI): 0.998 (0.976- 1.021) Period 1: 0.996 (0.969-1.024) Period 2: 1.013 (0.972-1.056) Period 3: 0.949 (0.897-1.004)

Multiday Ma, 15-day Overall IQR: 22.3 Overall RR (95% CI): 1.020 (0.993- 1.093) Period 1: 1.017 (0.984-1.051) Period 2: 1.012 (0.973-1.071) Period 3: 0.978 (0.911-1.051)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-496

# Table E-32. Long-term exposure-mortality - PM 10-2.5 

# .

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: (Chen et al., 2005, 087942 ) Period of Study: 1973-1998

Location: San Francisco, San Diego, Los Angeles, CA Outcome: Mortality: CHD Study Design: Cohort Statistical Analyses: Cox proportion hazards model Age Groups: >25 Pollutant: PM 10-2.5 Averaging Time: 25 yr Mean (SD): 25.4 Range (Min, Max): NR Copollutant: NO 2 O 3 SO 2 Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Males PM 10-2.5 : 0.93 (0.68, 1.29) 0-1 PM 10-2.5 +NO 2 : 0.86 (0.62, 1.20) 0-1 PM 10-2.5 +SO : 0.90 (0.64,1.27) 0-1 2 PM 10-2.5 +O 3 : 1.01 (0.67,1.51) 0-1

Females PM 10-2.5 : 1.20 (0.95, 1.53) 0-1 PM 10-2.5 +NO 2 : 1.19 (0.92, 1.54) 0-1 PM 10-2.5 +SO : 1.31 (1.03,1.68) 0-1 2 PM 10-2.5 +O 3 : 1.47 (1.10,1.96) 0-1 Reference: Goss et al. (2004, 055624 ) Period of Study: 1999-2000

Location: United States Outcome: Mortality Study Design: Cohort Study (Cystic Fibrosis Cohort) Statistical Analyses: Logistic Regression Age Groups: >6 yr Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD) unit: PM 2.5 : 13.7 (4.2)

IQR: PM 2.5 : 11.8-15.9 Copollutant: O 3 NO 2 SO 2 CO Increment: 10 μg/m 3

PM 2.5 : 1.32 (0.91-1.93)

Reference : Lipert et al . (2009, 190271 ) Period of Study: 1989-1996

Location: Various parts of the Untied States Outcome: Mortality Study Design: Retrospective Cohort Statistical Analyses: Cox proportional hazards regression Age Groups: Male U.S. veterans between ages of 39 and 63 (Avg. age: 51) Pollutant: PM 10-2.5 Mean (SD): 16.0 (5.1) Increment: 12 1.07 (1.01, 1.13)

Reference: McDonnell et al. (2000, 010319 ) Period of Study: 1973-1977

Location: California Outcome: Mortality Study Design: Cohort (AHSMOG airport cohort) Statistical Analyses: Cox regression models Age Groups: Males, 27 yr+ Pollutant: PM 10-2.5 Averaging Time: Monthly avg Mean (SD): PM 10-2.5 : 27.3 (8.6)

IQR: 9.7 Copollutant: O 3 : 0.70 SO 2 : 0.31 NO 2 : 0.23 SO 4 : 0.47 Increment: IQR All Cause: 1.05 (0.92-1.20) Resp: 1.19 (0.88, 1.62) Lung Cancer: 1.25 (0.63-2.49)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-497

# Table E-33. Long-term exposure-mortality - PM 2.5 

# (including PM components/sources).

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Reference: Abrahamowicz et al. (2003, 086292 ) Period of Study: 1982-1989

Location: 151 Cities Outcome: Mortality: All-causes Study Design: Case-cohort study Statistical Analyses: Cox proportionhazards model flexible regression spline generalization Age Groups: >18 Pollutant: PM 2.5 Averaging Time: Annual Mean (SD): 18.2 Range (Min, Max): (9.0, 33.5) Copollutant: Sulfates Relative Risk (Min CI, Max CI) Estimated from graph (Fig 1): log HR for a 24.5 μg/m 3 increase in PM 2.5 over time Yr 0: 0.5 (-1.1, 1.6) 2: 0.6 (0.2, 0.9) 4: 0.6 (0.3, 0.8) 6: 0.8 (0.3, 1.1) 8: -1.0 (-1.5, 1.0) Reference: Abrahamowicz et al. (2003, 086292 ) Period of Study: 1982-1989

Location: 151 Cities Outcome: Mortality: All-causes Study Design: Case-cohort study Statistical Analyses: Cox proportionhazards model flexible regression spline generalization Age Groups: >18 Pollutant: Sulfates Averaging Time: Annual Mean (SD): 18.2 Range (Min, Max): (9.0, 33.5) Copollutant: PM 2.5 Relative Risk (Min CI, Max CI) Estimated from graph (Fig 1): Log HR for a 19.9 μg/m 3 increase in Sulfates over time Yr 0: 0.1 (-0.2, 0.7) 2: 0.1 (-0.2, 0.4) 4: 0.0 (-0.4, 0.3) 6: 0.3 (-0.1, 0.5) 8: 0.4 (-0.4, 1.6) Reference: Ballester et al. (2008, 189977 ) Period of Study: 2001-2002

Location: Europe Outcome: Mortality- All-causes Study Design: Health Impact Assessment Statistical Analyses: Aphesis Network Age Groups: >30 Pollutant: PM 2.5 Averaging Time: Annual Mean (SD): NR Range (Min, Max): NR Potential Reduction in the total burden of mortality (min CI, max CI) for four different decreases in annual PM 2.5 using a conservative estimate Reduction to 25 μg/m 3 - 0.4 (0.1, 0.8) Reduction to 20 μg/m 3 - 0.8 (0.2, 1.6) Reduction to 15 μg/m 3 - 1.6 (0.4, 3.1) Reduction to 10 μg/m 3 - 3.0 (0.8, 5.8) Reference: Beelen et al. (2008, 156263 ) Period of Study: 1987-1996

Location: Netherlands Outcome: Mortality: Total (nonaccidental) (<800) Cardio-respiratory (390-448, 490-496, 487, 480-486, 507) Pulmonary (460-519) Cardiovascular (400-440) Lung Cancer (162)

Other-causes Study Design: Case-cohort study and prospective cohort Statistical Analyses: Cox proportionhazards model Age Groups: 55-69 Pollutant: PM 2.5 Averaging Time: Annual Mean (SD): 28.3 (2.1) μg/m 3 Range (Min, Max): (23.0, 36.8) Copollutant (correlation):

NO 2 : (>0.8) BS: (>0.8)

SO 2 : (>0.6) Increment: 11 μg/m 3 Relative Risk (Min CI, Max CI) RR for the association between exposures to PM 2.5 and cause specific mortality Natural Cause: Full cohort: 1.06 (0.97, 1.16) Case cohort: 0.86 (0.66, 1.13) Cardiovascular: Full cohort: 1.04 (0.90, 1.21) Case cohort: 0.83 (0.60, 1.15) Respiratory: Full cohort: 1.07 (0.75, 1.52) Case cohort: 1.02 (0.56, 1.88) Lung Cancer: Full cohort: 1.06 (0.82, 1.38) Case cohort: 0.87 (0.52, 1.47) Other cause: F Ull cohort: 1.08 (0.96, 1.23) Case cohort: 0.85 (0.65, 1.12)

RR for the association between exposures to BS and cause specific mortality Natural Cause: Full cohort: 1.05 (1.00, 1.11) Case cohort: 0.97 (0.83, 1.13) Cardiovascular: Full cohort: 1.04 (0.95, 1.13) Case cohort: 0.98 (0.81, 1.18) Respiratory: Full cohort: 1.22 (0.99, 1.50) Case cohort: 1.29 (0.91, 1.83) Lung Cancer: Full cohort: 1.03 (0.88, 1.20) Case cohort: 1.03 (0.77, 1.38) Other cause: Full cohort: 1.04 (0.97, 1.12) Case cohort: 0.91 (0.78, 1.07)



### December 2009 E-498

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Breitner et al. (2009, 188439 ) Outcome: Mortality, excluding infants and ICD-9 ≥ 800 Pollutant: PM 2.5 Averaging Time: Daily Period of Study: Oct 1991-Mar 2002 Study Design: Time-series Mean (SD) Unit: 1 (10/1/1991-8/31/1995): Location: Efurt, Germany Covariates: Seasonal and weekday variations, influenza epidemics, air temperature, relative humidity 50.6 ± 32.2 μg/m 3 2 (9/1/1995-2/28/1998):

Statistical Analysis: Semiparametric Poisson regression, polynomial distributed lag (PDL) Statistical Package: R Age Groups: All 41.1 ± 28.4 μg/m 3 3 (3/1/1998-3/31/2002): 24.3 ± 15.4 μg/m 3 Total: 38.0 ±28.3 μg/m 3 Range (Min, Max): NR Copollutant: NO 2 , CO, UFP Increment: IQR Relative Risk (95% CI) lag New City Limits 6-day IQR: 13.3 PDL: 1.009 (0.984-1.035) Mean of lags 0-5: 1.004 (0.981-1.027) Old City Limits 6-day IQR: 13.3 PDL: 1.017 (0.990-1.044) Mean of lags 0-5: 1.010 (0.986-1.035) New City Limits 15-day IQR: 11.5 PDL: 1.019 (0.988-1.050) Mean of lags 0-14: 1.017 (0.992-1.042) Old City Limits 15-day IQR: 11.5 PDL: 1.030 (0.997-1.063) Mean of lags 0-14: 1.025 (0.999-1.052)

Multiday Ma, 6-day Overall IQR: 13.3 Overall RR (95% CI): 1.004 (0.981-1.027) Period 1: NR Period 2: 1.017 (0.990-1.044) Period 3: 0.974 (0.937-1.013)

Multiday Ma, 15-day Overall IQR: 11.5 Overall RR (95% CI): 1.017 (0.992-1.042) Period 1: NR Period 2: 1.016 (0.988-1.045) Period 3: 1.016 (0.971-1.063)



### December 2009 E-499

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Brunekreef et al. (2009, 191947 ) Period of Study: 1987-1996

Location: The Netherlands Outcome: All cause mortality (ICD-9 400-440, 460-519, > 800) Study Design: Case-cohort

Covariates: Individual: sex, age, Quetelet index, smoking status, passive smoking status, educational level, occupation, occupational exposure, marital status, alcohol use, intake of vegetables, fruits, energy, saturatured and monounsaturated fatty acids, trans fatty acids, total fiver, folic acid and fish Area-level: Percent of population with income below the 40th percentile and above the 80th percentile Statistical Analysis: Cox proportional hazards Statistical Package: Stata, SPSS, R Age Groups: 120,000 adults aged 55-69 yr at enrollment Pollutant: PM 2.5 , estimated from PM 10 levelsf Averaging Time: 24 h

50th Percentile: 28 μg/m 3 Range (Min, Max): 23-37 Copollutant (correlation):

NO 2 : 0.75

BS: 0.84

NO: 0.69

SO 2 : 0.43 Increment: 10 μg/m 3 Relative Risk (95 % CI) for PM 2.5 concentrations and cause specific mortality Case Cohort Natural Cause: 0.86 (0.66-1.13) Cardiovascular: 0.83 (0.60-1.15) Respiratory: 1.02 (0.56-1.88) Lung Cancer: 0.87 (0.52-1.47) Noncardiopulmonary, non-lung cancer: 0.85 (0.65-1.23) Full Cohort Natural Cause: 1.06 (0.97-1.16) Cardiovascular: 1.04 (0.90-1.21) Respiratory: 1.07 (0.75-1.52) Lung Cancer: 1.06 (0.82-1.38) Noncardiopulmonary, non-lung cancer: 1.08 (0.72-1.19) Relative Risk (95%CI) for PM 2.5 concentrations and cause specific mortality in full cohort analysis by confounder model Natural Cause Mortality Unadjusted: 1.11 (1.04-1.20) Smoking: 1.04 (0.96-1.13) Smoking, area-level income: 1.06 (0.97-1.16) Cardiovascular Mortality Unadjusted: 1.09 (0.97-1.23) Smoking: 1.02 (0.90-1.16) Smoking, area-level income: 1.04 (0.90-1.21) Respiratory Mortality Unadjusted: 1.23 (0.92-1.65) Smoking: 1.10 (0.81-1.50) Smoking, area-level income: 1.07 (0.75-1.52) Lung Cancer Mortality Unadjusted: 1.17 (0.95-1.46) Smoking: 1.06 (0.85-1.33) Smoking, area-level income: 1.06 (0.82-1.38) Noncardiopulmonary, Non-Lung Cancer Mortality Unadjusted: 1.10 (1.00-1.22) Smoking: 1.05 (0.94-1.16) Smoking, area-level income: 1.08 (0.96-1.22) Reference: Chen et al. (2005, 087942 ) Period of Study: 1973-1998

Location: San Francisco, San Diego, Los Angeles, CA Outcome: Mortality: CHD Study Design: Cohort Statistical Analyses: Cox proportion hazards model Age Groups: >25 Pollutant: PM 2.5 Averaging Time: 25 yr Mean (SD): 29.0 Range (Min, Max): NR Copollutant: NO 2 , O 3 , SO 2 Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Males PM 2.5 : 0.89 (0.69, 1.17) 0-1 PM 2.5 +NO 2 : 0.82 (0.61, 1.10); 0-1 PM 2.5 +SO 2 : 0.86 (0.65,1.14) 0-1 PM 2.5 +O 3 : 0.92 (0.65,1.29) 0-1

Females PM 2.5 : 1.19 (0.96, 1.47) 0-1 PM 2.5 +NO 2 : 1.18 (0.95, 1.47); 0-1 PM 2.5 +SO 2 : 1.36 (1.05,1.74) 0-1 PM 2.5 +O 3 : 1.61 (1.17,2.22) 0-1



### December 2009 E-500

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Eftim et al. (2008, 099104 ) Period of Study: 2000-2002

Location: USA, Same cities as six cities and ACS cohorts Outcome (ICD-9): All nonaccidental causes (<800) Study Design: Cross-sectional Statistical Analyses: Log-linear regression, Poisson Age Groups: >65 Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD): | ACS: 13.6 (2.8) SCS: 14.1 (3.1) Range (Min, Max): ACS: (6.0, 25.1); SCS: (9.6, 19.1) Increment: 10 μg/m 3 % Increase in Mortality for overall exposure period and individual yr (95%CI Min, 95%CI Max): ACS (adjusted for age, sex) Overall: 10.8 (8.6, 13.0) 2000: 10.9 (7.3, 14.6) 2001: 9.1 (5.3, 12.7) 2002: 10.1 (6.0, 14.3) SCS (adjusted for age, sex) Overall: 20.8 (14.8, 27.1) 2000: 17.8 (9.8, 26.4) 2001: 16.5 (7.4, 25.0) 2002: 33.5 (19.2, 49.3) Reference: Enstrom et al. (2005, 087356 ) Period of Study: 1973-2002

Location: 25 California Colonies 11 California Colonies (EPA IPN study) Outcome: Mortality: Cardiovascularrespiratory (390-448) (480-486, 487, 490-496, 507) Study Design: Retrospective cohort Statistical Analyses: Cox proportional hazards regression model, SAS PHREG Age Groups: 35 or older Pollutant: PM 2.5 Averaging Time: Annual Mean (SD): 23.4 Range (Min, Max): (13.1 μg/m 3 , 36.1) Relative Risk (Lower CI, Upper CI) RR from causes for both sexes by county from 1973-2002 Alameda: 0.962 (0.926,0.999) Butte: 0.999 (0.910,1.096) Contra Costa: 0.999 (0.943,1.058) Fresno: 0.935 (0.872,1.002) Humboldt: 0.992 (0.900,1.092) Kern: 0.944 (0.872,1.023) Marin: 0.939 (0.867,1.016) Napa: 0.949 (0.868,1.038) Orange: 0.990 (0.948,1.034) Riverside: 0.959 (0.906,1.015) Sacramento: 0.998 (0.944,1.055) San Bernardino: 0.992 (0.938,1.049) San Diego: 0.992 (0.954, 1.033) San Francisco: 0.963 (0.914,1.014) San Joaquin: 0.925 (0.816,1.049) San Mateo: 0.949 (0.899, 1.003) Santa Barbara: 0.968 (0.878,1.068) Santa Clara: 0.955 (0.910,1.003) Santa Cruz: 0.890 (0.793,0.999) Solano: 0.901 (0.815,0.995) Sonoma: 0.968 (0.884,1.060) Stanislaus: 0.984 (0.904,1.072) Tulare: 1.047 (0.979,1.119) Ventura: 0.967 (0.872,1.072)

RR from all causes for 11 counties for both sexes (EPA IPN study) Santa Barbara: 0.968 (0.878,1.068) Contra Costa: 0.999 (0.943,1.058) Alameda: 0.962 (0.926,0.999) Butte: 0.999 (0.910,1.096) San Francisco: 0.963 (0.914,1.014) Santa Clara: 0.955 (0.910,1.003) Fresno: 0.935 (0.872,1.002) San Diego: 0.992 (0.954,1.033) Kern: 0.944 (0.872,1.023) Riverside: 0.959 (0.906,1.015) Reference: Filleul et al. (2005, 087357 ) Period of Study: 1974-1976

Location: 7 cities in France Outcome: Nonaccidental causes (<800), cardiopulmonary disease (401- 440 and 460-519), lung cancer (162) Age Groups: 25-59 yr Study Design: Cohort

N: 14,284 people Statistical Analyses: Cox proportional hazard, regression

Covariates: Sex, smoking habits, educational level, body-mass index (BMI), occupational exposure Statistical Package: Proc Phreg SAS Pollutant: Total suspended particles (TSP) Averaging Time: NR Mean (SD): NR Range (Min, Max): (45, 243) PM Component: NR Monitoring Stations: 1 station Copollutant (correlation): BS r = 0.87 SO 2 r = 0.17 NO r = 0.84 NO 2 r = 0.60 Increment: 10 μg/m 3 Adjusted mortality rate ratios: 24 areas: All nonaccidental causes: 1.00[0.99, 1.01] Lung cancer: 0.97[0.94, 1.01] Cardiopulmonary disease: 1.01[0.99, 1.03]

18 areas: All nonaccidental causes: 1.05[1.02, 1.08] Lung cancer: 1.00[0.92, 1.10] Cardiopulmonary disease: 1.06[1.01, 1.12]



### December 2009 E-501

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Fuentes et al. (2006, 097647 ) Period of Study: Jun 2000

Location: Conterminous U.S. Outcome: Mortality: Study Design: Time-series Statistical Analyses: Generalized Poisson Regression Age Groups: 0-14, 15-64, >65

Covariates: Temperature, pressure, dew point, wind speed, elevation, age, ethnicity Pollutant: PM 2.5 Averaging Time: Monthly Mean (SD): 6.60 (0.76) Copollutant: PM 10 , O 3 Increment: 10 μg/m 3

PM 2.5 : 1.066 (1.064, 1.069)

PM 10 : 1.030 (1.028, 1.032)

Reference: Janes et al. (2007, 090927 ) Period of Study: 2000-2002

Location: 113 U.S. counties Outcome: Mortality: Study Design: Time-series Statistical Analyses: Cox proportional hazards model Age Groups: 65-74

75-84

85+ Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD): NR Range (Min, Max): NR Increment: 1 μg/m 3 % Increase (Lower CI, Upper CI) lag: Overall % Increase by age-sex stratum Age Category 65-74: Male: 1.48 (0.93,2.03) Female: 0.83 (0.24,1.43) 75-84: Male: 0.85 (0.34,1.35) Female: 0.77 (0.28,1.27) 85+: Male: 0.70 (0.03,1.38) Female: 0.59 (0.05,1.12) National Trend % Increase by age-sex stratum Age Category 65-74: Male: 3.55 (2.77,4.34) Female: 1.97 (1.12,2.83) 75-84: Male: 2.48 (1.83,3.14) Female: 2.29 (1.66,2.93) 85+: Male: 1.38 (0.52,2.26) Female: 1.65 (1.01,2.29) Local Trend % Increase by age-sex stratum Age Category 65-74: Male: 0.04 (-0.58,0.67) Female: -0.03 (-0.71,0.66) 75-84: Male: -0.34 (-0.87,0.19) Female: -0.31 (-0.82, 0.21) 85+: Male: <0.01 (-0.71,0.73) Female: -0.22 (-0.74,0.31) *Local trends are county specific deviations from national trends

Reference: Jerrett et al. (2003, 087380 ) Period of Study: 1982

Location: 151 cities from ACS Outcome: Mortality Study Design: Multilevel, individualecologic analysis Statistical Analysis: Cox proportional hazards model

Covariates: Smoking, education, occupational exposures, BMI, marital status, alcohol consumption, gender Pollutant: Sulfates Mean (SD): 10.6 Range (Min, Max): 3.6,23.5 Increment: 19.9 (Range) All Cause: SO 4 : 1.17 (1.07, 1.27) SO 4 + CO: 1.16 (1.10, 1.23) SO 4 + NO 2 : 1.16 (1.08, 1.24) SO 4 + O 3 : 1.17 (1.11, 1.24) SO 4 + SO 2 : 1.05 (0.98, 1.12) CPD: SO 4 : 1.25 (1.16, 1.35) SO 4 + CO: 1.28 (1.18, 1.39) SO 4 + NO 2 : 1.29 (1.17, 1.42) SO 4 + O 3 : 1.27 (1.17, 1.38) SO 4 + SO 2 : 1.13 (1.03, 1.24) Lung Cancer: SO 4 : 1.31 (1.09, 1.58) SO 4 + CO: 1.26 (1.03, 1.53) SO 4 + NO 2 : 1.31 (1.05, 1.65) SO 4 + O 3 : 1.30 (1.07, 1.59) SO 4 + SO 2 : 1.37 (1.08, 1.73)



### December 2009 E-502

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Jerrett et al. (2005, 087600 ) Period of Study: 1982-2000

Location: Los Angeles, California Outcome: Mortality: Non- accidental (<800) IHD (410-414) Cardiopulmonary (400-440, 460-519) Lung Cancer (162) Other Cancers (140-149,160, 161, 163- 239)

Other causes Study Design: Retrospective Cohort Statistical Analyses: Cox regression hazards model kriging, radial basis function multiquadric interpolator Age Groups: All ages Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD): NR Range (Min, Max): NR Copollutant: O 3 Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) All Causes - PM 2.5 Only: 1.24 (1.11,1.37) 44 Ind. Covariates together+PM 2.5 : 1.17 (1.03,1.32) 44 Ind. Covariates together+ PM 2.5 +O 3 : 1.20 (1.07,1.34) 44 Ind. Covariates together+intersection within freeways within 500 m+ PM 2.5 +O 3 : 1.17 (1.05,1.31) IHD - PM 2.5 Only: 1.49 (1.20,1.85) 44 Ind. Covariates together+PM 2.5 : 1.39 (1.12,1.73) 44 Ind. Covariates together+PM 2.5 +O 3 : 1.45 (1.15,1.82) 44 Ind. Covariates together+intersection within freeways within 500 m+ PM 2.5 +O 3 : 1.38 (1.11,1.72) Cardiopulmonary - PM 2.5 Only: 1.20 (1.04,1.39) 44 Ind. Covariates together+ PM 2.5 +O 3 : 1.19 (1.02,1.38) 44 Ind. Covariates together+intersection within freeways within 500 m+ PM 2.5 +O 3 : 1.13 (0.97,1.31) Lung Cancer - PM 2.5 Only: 1.60 (1.09,2.33) 44 Ind. Covariates together+PM 2.5 : 1.44 (0.98,2.11) 44 Ind. Covariates together+intersection within freeways within 500 m+ PM 2.5 +O 3 : 1.46 (0.99,2.16) Other Cancers - PM 2.5 Only: 1.09 (0.85,1.40) 44 Ind. Covariates together+ PM 2.5 +O 3 : 1.08 (0.83,1.39) 44 Ind. Covariates together+intersection within freeways within 500 m+ PM 2.5 +O 3 : 1.08 (0.83,1.39) All Other Causes - PM 2.5 Only: 1.11 (0.74,1.67) 44 Ind. Covariates together+ PM 2.5 +O 3 : 0.95 (0.64,1.39) 44 Ind. Covariates together+intersection within freeways within 500 m+ PM 2.5 +O 3 : 1.02 (0.71,1.48)



### December 2009 E-503

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Laden et al. (2006, 087605 ) Period of Study: 1974-1998

Period 1: 1974-1989

Period 2: 1990-1998

Location: Nine U.S. Cities Watertown, MA Kingston, TN Harriman, TN St. Louis, MO Steubenville, OH Portage, WI |Wyocena, WI Pardeeville, WI Topeka, KS Outcome: Total mortality Nonaccidental (<800) Cardiovascular (400-440) Respiratory (485-496) Lung Cancer (162)

Other Study Design: Prospective Cohort Statistical Analyses: Cox proportional hazards regression Age Groups: 25-74 Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD): Period 1 Portage: 11.4 Topeka: 12.4 Watertown: 15.4 Harriman: 20.9 St Louis: 19.2 Steubenville: 29.0 Period 2 Portage: 10.2 Topeka: 13.1 Watertown: 12.1 Harriman: 18.1 St. Louis: 13.4 Steubenville: 22.0 Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) lag: Period 1: Portage: 1.00 Topeka: 1.06 (0.86, 1.31) Watertown: 1.06 (0.87, 1.28) Harriman: 1.19 (0.98, 1.44) St Louis: 1.15 (0.96, 1.38) Steubenville: 1.31 (1.10, 1.57) Period 2: Portage: NR Topeka: 1.01 (0.83, 1.22) Watertown: 0.82 (0.67, 1.00) Harriman: 1.10 (0.91, 1.33) St Louis: 0.96 (0.80, 1.15) Steubenville: 1.06 (0.89, 1.27) Complete Period: Portage: 1.00 Topeka: 1.03 (0.89, 1.19) Watertown: 0.95 (0.83, 1.08) Harriman: 1.15 (1.01, 1.32) St. Louis: 1.05 (0.93, 1.20) Steubenville: 1.18 (1.04, 1.34) RR for complete follow up avg PM 2.5 Total Mortality: 1.16 (1.07, 1.26) Cardiovascular: 1.28 (1.13, 1.44) Respiratory: 1.08 (0.79, 1.49) Lung Cancer: 1.27 (0.96, 1.69) Other: 1.02 (0.90, 1.17) RR for Period 1 avg PM 2.5 Total Mortality: 1.18 (1.09, 1.27) Cardiovascular: 1.28 (1.14, 1.43) Respiratory: 1.21 (0.89, 1.66) Lung Cancer: 1.20 (0.91, 1.58) Other: 1.05 (0.93, 1.19) Decrease in avg PM 2.5 over the 2 periods Total Mortality: 0.73 (0.57, 0.95) Cardiovascular: 0.69 (0.46, 1.01) Respiratory: 0.43 (0.16, 1.13) Lung Cancer: 1.06 (0.43, 2.62) Other: 0.85 (0.56, 1.27) Reference: Lipfert et al. (2006, 088756 ) Period of Study: 1989-1996

Location: Various parts of the Untied States Outcome: Mortality Study Design: Retrospective Cohort Statistical Analyses: Cox proportional hazards regression Age Groups: Male U.S. veterans between ages of 39 and 63 (Avg. age: 51) Pollutant: Sulfate Mean (SD) from 1976-81: 10.7 (3.6) Increment: 8 1.045 (0.944, 1.157)

Reference: Lipfert et al. (2006, 088756 ) Period of Study: 1989-1996

Location: Various parts of the Untied States Outcome: Mortality Study Design: Retrospective Cohort Statistical Analyses: Cox proportional hazards regression Age Groups: Male U.S. veterans between ages of 39 and 63 (Avg age 51) Pollutant: PM 2.5 Mean (SD): 14.3 (3.2) Increment: 8 1.118 (1.038, 1.203)



### December 2009 E-504

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Lipfert et al. (2006, 088218 ) Period of Study: 1997-2002

Location: Various parts of the Untied States Outcome: Mortality: Non- accidental (<800) Study Design: Retrospective cohort Statistical Analyses: Cox proportional hazards regression

AIC Age Groups: Male U.S. veterans between ages of 39 and 63 (Avg. age: 51) Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD): 15.02 (4.80) μg/m 3 (2000- 2003) Range (Min, Max): (3.29, 24.96) Copollutant (correlation):

As: r = 0.443

Cr: r = 0.379

Cu: r = 0.530 Fe: r = 0.379;

Pb: r = 0.489 Mn: r = 0.389;

Ni: r = 0.140 Se: r = 0.312;

V: r = 0.197 Zn: r = 0.420;

OC: r = 0.620 EC: r = 0.544; |

SO 4 : r = 0.827

NO 3 : r = 0.649

NO 2 : r = 0.641

Peak CO: r = 0.040

Peak O 3 : r = 0.222

Peak SO 2 : r = 0.714 Increment: 10 μg/m 3 % Increase per 10 μg/m 3 increase in PM 2.5 Single-Pollutant Model As: -5.23% Cr: -2.11% Cu: 2.12% Fe: 2.81% Pb: -2.40% Mn: -1.20% Ni: 3.75% Se: -0.30% V: 5.08% Zn: 1.52% OC: -0.02% EC: 9.16% SO 4 : 3.04% NO 3 : 6.60% NO 2 : 6.92% Peak CO: -0.61% Peak O 3 : 4.95% Peak SO 2 : -4.20%

Multiple Pollutants model- Pollutant with traffic density NO 3 : 3.42% SO 4 : -2.73% EC: 6.27% Ni: 2.51% V: 3.27%

Pollutant with NO 3 EC: 5.93% Ni: 2.31% V: 3.11%

Pollutant with Peak O 3 Traffic density: 2.40% EC: 10.79% Fe: 5.94% NO 3 : 7.57% PM 2.5 : 8.97% V: 4.93% Ni: 3.65% SO 4 : 6.75% Cu: 1.55% OC: 0.21%



### December 2009 E-505

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Death Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR

Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3 Range (Min, Max):

1979-1983: 10.77-30.01

1999-2000: 5.80-22.20 Copollutant:

SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 10 μg/m 3 Hazard Ratio (95% CI) MSA & DIFF Increment Change: 10.78 (1.043-1.115) Change 5-15 μg/m 3 : 1.128 (1.077-1.183) Change 10-20 μg/m 3 : 1.079 (1.048-1.112) HR (95% CI) Los Angeles Parsimonious ecologic covariates: 1.126 (1.014-1.251) HR (95% CI) 15-yr time window Group A: 0.98 (0.92-1.06) Group B: 1.01 (0.99-1.02) HR (95% CI) Third follow-up, 7 Ecologic Variables 1979-1983: 1.044 (1.028-1.060) 1999-2000: 1.057 (1.036-1.079) HR (95% CI) Nationwide analysis, 1999-2000 Standard Cox: 1.03 (1.01-1.05) Random Effects Cox: 1.06 (1.04-1.08) Increment: 1.5 μg/m 3 HR (95% CI) 28 County, 3-yr model All 7 ecologic covariates: 0.977 (0.932-1.025) Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Death from cardiopulmonary disease Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR

Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3 Range (Min, Max):

1979-1983: 10.77-30.01

1999-2000: 5.80-22.20 Copollutant:

SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 10 μg/m 3 Hazard Ratio (95% CI) MSA & DIFF Increment Change: 1.078 (1.077-1.182) Change 5-15 μg/m 3 : 1.208 (1.132-1.290) Change 10-20 μg/m 3 : 1.127 (1.081-1.174) HR (95% CI) Los Angeles Parsimonious ecologic covariates: 1.086 (0.939-1.285) HR (95% CI) 15-yr time window Group A: 1.00 (0.90-1.11) Group B: 1.05 (1.03-1.07) HR (95% CI) Third follow-up, 7 Ecologic Variables 1979-1983: 1.094 (1.070-1.118) 1999-2000: 1.138 (1.106-1.172) HR (95% CI) Nationwide analysis, 1999-2000 Standard Cox: 1.09 (1.06-1.12) Random Effects Cox: 1.13 (1.10-1.16) Increment: 1.5 μg/m 3 HR (95% CI) 28 County, 3-yr model All 7 ecologic covariates: 0 .940 (0.875-1.011)



### December 2009 E-506

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Death from ischemic heart disease Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR

Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3 Range (Min, Max):

1979-1983: 10.77-30.01

1999-2000: 5.80-22.20 Copollutant:

SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 10 μg/m 3 Hazard Ratio (95% CI) MSA & DIFF Increment Change: 1.196 (1.177-1.407) Change 5-15 μg/m 3 : 1.484 (1.311-1.680) Change 10-20 μg/m 3 : 1.283 (1.186-1.387) HR (95% CI) Los Angeles Parsimonious ecologic covariates: 1.263 (10.22-1.563) HR (95% CI) Third follow-up, 7 Ecologic Variables 1979-1983: 1.184 (1.146-1.222) 1999-2000: 1.242 (1.191-1.295) HR (95% CI) Nationwide analysis, 1999-2000 Standard Cox: 1.15 (1.11-1.20) Random Effects Cox: 1.24 (1.19-1.29) Increment: 1.5 μg/m 3 HR (95% CI) 28 County, 3 yr model All 7 ecologic covariates: 1.072 (0.980-1.172) Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Death from lung cancer Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR

Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3 Range (Min, Max):

1979-1983: 10.77-30.01

1999-2000: 5.80-22.20 Copollutant:

SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 10 μg/m 3 Hazard Ratio (95% CI) MSA & DIFF Increment Change: 1.142 (1.057-1.234) Change 5-15 μg/m 3 : 1.236 (1.114-1.372) Change 10-20 μg/m 3 : 1.143 (1.071-1.221) HR (95% CI) Los Angeles Parsimonious ecologic covariates: 1.311 (0.897-1.915) HR (95% CI) 15-yr time window Group A: 1.08 (0.87-1.35) Group B: 1.07 (1.02-1.13) HR (95% CI) Third follow-up, 7 Ecologic Variables 1979-1983: 1.092 (1.033-1.154) 1999-2000: 1.138 (1.057-1.225) HR (95% CI) Nationwide analysis, 1999-2000 Standard Cox: 1.11 (1.04-1.18) Random Effects Cox: 1.14 (1.06-1.23) Increment: 1.5 μg/m 3 HR (95% CI) 28 County, 3-yr model All 7 ecologic covariates: 0.985 (0.832-1.166) Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Death from diabetes Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3

Range (Min, Max): 1979-1983: 10.77-30.01 1999-2000: 5.80-22.20

Copollutant: SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 1.5 μg/m 3 HR (95% CI) 28 County, 3 yr model All 7 ecologic covariates: 1.083 (0.723-1.621)



### December 2009 E-507

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Death from endocrine disease Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3

Range (Min, Max): 1979-1983: 10.77-30.01 1999-2000: 5.80-22.20

Copollutant: SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 1.5 μg/m 3 HR (95% CI) 28 County, 3-yr model All 7 ecologic covariates: 1.143 (0.835-1.564)

Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Death from digestive cancer Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3

Range (Min, Max): 1979-1983: 10.77-30.01

1999-2000: 5.80-22.20 Copollutant: SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 10 μg/m 3 HR (95% CI) Los Angeles Parsimonious ecologic covariates: 1.199 (0.817-1.758)

Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Death cancers other than lung and digestive Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3

Range (Min, Max): 1979-1983: 10.77-30.01 1999-2000: 5.80-22.20 Copollutant: SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 10 μg/m 3 HR (95% CI) Los Angeles Parsimonious ecologic covariates: 1.012 (0.788-1.299)

Reference: Krewski et al. (2009, 191193 ) Period of Study: 1979-2000

Location: 48 contiguous states U.S. Outcome: Deaths from causes other than CPD, IHD and lung cancer Study Design: Cohort

Covariates: Demographic, socioeconomic and ecologic characteristics Statistical Analysis: Cox proportionalhazards model Statistical Package: NR Age Groups: Adults of at least 30 yr Pollutant: PM 2.5 Averaging Time: NR Mean Unit: 1979-1983: 21.20 μg/m 3 1999-2000: 14.02 μg/m 3

Range (Min, Max): 1979-1983: 10.77-30.01 1999-2000: 5.80-22.20

Copollutant: SO 4 2– , SO 2 , PM 15 , TSP, O 3 , NO 2 , CO Increment: 10 μg/m 3 Hazard Ratio (95% CI) MSA & DIFF Increment Change: 1.010 (0.968-1.055) Change 5-15 μg/m 3 : 1.026 (0.970-1.085) Change 10-20 μg/m 3 : 1.016 (0.981-1.053) HR (95% CI) Third follow-up, 7 Ecologic Variables 1979-1983: 0.983 (0.960-1.007) 1999-2000: 0.953 (0.923-0.984) Reference: McDonnell et al. (2000, 010319 ) Period of Study: 1973-1977

Location: California Outcome: Mortality Study Design: Cohort (AHSMOG airport cohort) Statistical Analyses: Cox regression models Age Groups: Males, 27 yr+ Pollutant: PM 2.5 Averaging Time: Monthly avg Mean (SD): 31.9 (10.7)

IQR: 24.3 Copollutants (correlation): O 3 : 0.68 SO 2 : 0.18 NO 2 : -0.08; SO 4 : 0.33 Increment: IQR All Cause: 1.22 (0.95-1.58) Resp: 1.64 (0.93-2.90) Lung Cancer: 2.23 (0.56-8.94)



### December 2009 E-508

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Miller et al. (2007, 090130 ) Period of Study: 1994-1998

Location: 36 U.S. Metropolitan Areas Outcome: CVD Mortality Study Design: Prospective Cohort (WHI) Statistical Analyses: Cox proportional hazards regression Age Groups: Postmenopausal women ages 50-79 Pollutant: PM 2.5 Averaging Time: Annual avg (2000) Mean (SD): 13.4

IQR: 11.6, 18.3 Range: 3.4, 28.3 Increment: 10 μg/m 3 CVD Death: 1.76 (1.25, 2.47) CHD Death: 2.21 (1.17, 4.16) CV Death: 1.83 (1.11, 3.00)

Reference: Naess et al. (2007, 090736 ) Period of Study: 1992-1998

Location: Oslo, Norway Outcome: Mortality: Nonaccidental (<800) Lung cancer (162) COPD (490-496) Cardiovascular (390-459) Study Design: Prospective Cohort Statistical Analyses: Cox proportional hazards regression model Age Groups: 51-70, 71-90 Pollutant: PM 2.5 Averaging Time: 4-yr avg Mean (SD): PM 2.5 : 15 Range (Min, Max): PM 2.5 : (7, 22) Copollutant (correlation):

NO 2 : r = 0.95 Relative Risk (CI min, CI max)

RR for deaths from all causes Men (ages 51-70) PM 2.5 exposure (in μg/m 3 ) 6.56-11.45: 1.00 11.46-14.25: 0.96 (0.89, 1.04) 14.26-18.43: 1.12 (1.03, 1.22) 18.44-22.34: 1.48 (1.36, 1.60) Men (ages 71-90) PM 2.5 exposure (in μg/m 3 ) 6.56-11.45: 1.00 11.46-14.25: 0.99 (0.93, 1.06) 14.26-18.43: 1.10 (1.03, 1.17) 18.44-22.34: 1.19 (1.12, 1.27) Women (ages 51-70) PM 2.5 exposure (in μg/m 3 ) 6.56-11.45: 1.00 11.46-14.25: 0.96 (0.87, 1.07) 14.26-18.43: 1.08 (0.98, 1.20) 18.44-22.34: 1.44 (1.30, 1.59) Women (ages 71-90) PM 2.5 exposure (in μg/m 3 ) 6.56-11.45: 1.00 11.46-14.25: 1.03 (0.97, 1.09) 14.26-18.43: 1.07 (1.01, 1.12) 18.44-22.34: 1.11 (1.05, 1.16)

Increment: 10 μg/m 3 RR for death from CVD and lung cancer Men (ages 51-70) CVD- PM : 1.11 (1.06, 1.16) 2.5 COPD- PM 2.5 : 1.32 (1.17, 1.49) Lung Cancer- PM 2.5 : 1.07 (0.98, 1.17) Women (ages 51-70) CVD: PM 2.5 : 1.16 (1.09, 1.24) COPD: PM 2.5 : 1.18 (1.03, 1.34) Lung Cancer: PM 5 : 1.23 (1.10, 1.37) 2. Men (ages 71-90) CVD: PM 2.5 : 1.06 (1.03, 1.09) COPD: PM : 1.13 (1.04, 1.24) 10 PM 2.5 : 1.14 (1.04, 1.24) Lung Cancer: PM 2.5 : 1.08 (0.98, 1.19) Women (ages 71-90) CVD: PM 2.5 : 1.02 (1.00, 1.05) COPD: PM 2.5 : 1.09 (1.00, 1.18) Lung Cancer: PM 2.5 : 1.16 (1.03, 1.31) Reference: Naess et al. (2007, 090736 ) Period of Study: 1992-1998

Location: Oslo, Norway Outcome: Mortality: Lung cancer (162) COPD (490-496) Cardiovascular (390-459) Psychiatric causes (290, 292-302, 304, 306-319) Stomach cancer (151) Violence (800-999) Study Design: Multilevel cohort Statistical Analyses: WinBUGS Age Groups: 50-74 Pollutant: PM 2.5 Averaging Time: (Mo-yr) avg Range Mean (SD): 14.2 (3.6) IQ Range (1st, 4th): (6.6, 22.3) Copollutant (correlation):

PM 10 : r = 0.95|

NO 2 : r = 0.87 Relative Risk (CI min, CI max) RR on All-cause mortality of PM 2.5 in Men Age 50-74 Primary Education: PM 2.5 : 1.06 (1.00, 1.11) Individual: 1.34 (1.24, 1.43) Neighborhood: 1.22 (1.16, 1.28) Manual Class: PM 2.5 : 1.06 (1.01, 1.12) Individual: 1.28 (1.20, 1.37) Neighborhood: 1.20 (1.14, 1.26) Income below median: PM 2.5 : 1.05 (1.00, 1.12) Individual: 1.44 (1.35, 1.53) Neighborhood: 1.16 (1.11, 1.21) Not owner occupied: PM 2.5 : 1.06 (1.00, 1.13) Individual: 1.24 (1.12, 1.36) Neighborhood: 1.11 (1.05, 1.17) Lives in flat dwelling:



### December 2009 E-509

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

PM 2.5 : 1.04 (0.98, 1.11) Individual: 1.19 (1.09, 1.31) Neighborhood: 1.10 (1.04, 1.17) More than one person per room in dwelling: PM 2.5 : 1.10 (1.02, 1.18) Individual: 1.05 (0.98, 1.13) Neighborhood: 1.01 (0.96, 1.05) RR on All-cause mortality of PM 2.5 in Women Age 50-74 Primary Education Only: PM 2.5 : 1.05 (1.00, 1.11) Individual: 1.32 (1.23, 1.42) Neighborhood: 1.18 (1.12, 1.24) Manual Class: PM 2.5 : 1.07 (1.01, 1.13) Individual: 1.27 (1.18, 1.36) Neighborhood: 1.18 (1.12, 1.24) Income below median: PM 2.5 : 1.05 (1.01, 1.10) Individual: 1.52 (1.41, 1.63) Neighborhood: 1.13 (1.09, 1.18) Not owner occupied: M 2.5 : 1.07 (1.01, 1.14) Individual: 1.24 (1.12, 1.38) Neighborhood: 1.08 (1.02, 1.14) Lives in a flat dwelling: PM 2.5 : 1.05 (0.99, 1.11) Individual: 1.21 (1.09, 1.34) Neighborhood: 1.09 (1.02, 1.15) More than one person per room in dwelling: PM 2.5 : 1.11 (1.04, 1.19) Individual: 1.07 (0.99, 1.14) Neighborhood: 1.01 (0.96, 1.05) RR for Interquartile Increase (MI) in PM 2.5 for different causes of death CVD: Age and sex adjusted: 1.11 (1.07, 1.15) Primary education only: M1+ Individual: 1.07 (1.04, 1.11) M1+ Neighborhood: 1.03 (1.00, 1.07) Manual Class: M1+ Individual: 1.08 (1.04, 1.11) M1+ Neighborhood: 1.06 (1.02, 1.10) Income below Median: M1+ Individual: 1.07 (1.03, 1.11) M1+ Neighborhood: 1.02 (0.98, 1.05) Not owner occupied: M1+ Individual: 1.05 (1.01, 1.09) M1+ Neighborhood: 1.03 (0.99, 1.07): Living in a Flat dwelling M1+ Individual: 1.04 (1.00, 1.08) M1+ Neighborhood: 1.01 (0.97, 1.05) Crowded household: M1+ Individual: 1.10 (1.05, 1.14) M1+Neighborhood: 1.10 (1.06, 1.15) Pulmonary Cancer: Age and sex adjusted: 1.12 (1.05, 1.19) Primary education only: M1+ Individual: 1.09 (1.01, 1.17) M1+ Neighborhood: 1.05 (0.98, 1.13) Manual Class: M1+ Individual: 1.09 (1.01, 1.17) M1+ Neighborhood: 1.10 (1.06, 1.13) Income below Median: M1+ Individual: 1.09 (1.01, 1.17) M1+ Neighborhood: 1.02 (0.95, 1.10) Not owner occupied: M1+ Individual: 1.07 (1.00, 1.15) M1+ Neighborhood: 1.04 (0.97, 1.12) Living in a Flat dwelling: M1+ Individual: 1.03 (0.96, 1.11) M1+ Neighborhood: 1.00 (0.92, 1.08) Crowded household: M1+ Individual: 1.10 (1.03, 1.14) M1+Neighborhood: 1.11 (1.04, 1.20) COPD: Age and sex adjusted: 1.17 (1.09, 1.25)



### December 2009 E-510

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI) Primary education only: M1+ Individual: 1.13 (1.05, 1.22) M1+ Neighborhood: 1.09 (1.01, 1.19) Manual Class: M1+ Individual: 1.14 (1.05, 1.23) M1+ Neighborhood: 1.12 (1.04, 1.22) Income below Median: M1+ Individual: 1.13 (1.04, 1.22) M1+ Neighborhood: 1.06 (0.97, 1.15) Not owner occupied: M1+ Individual: 1.10 (1.02, 1.19) M1+ Neighborhood: 1.07 (0.99, 1.16) Living in a Flat dwelling: M1+ Individual: 1.08 (1.00, 1.18) M1+ Neighborhood: 1.03 (0.95, 1.13) Crowded household: M1+ Individual: 1.16 (1.07, 1.26) M1+Neighborhood: 1.16 (1.07, 1.26) Estimates for psychiatric diseases, genetic cancer and violent death

Reference: Nerriere et al. (2005, 088630 ) Period of Study: Grenoble (2001) Paris (2002) Rouen (2002-2003) Strasbourg (2003) Location: Four French CitiesGrenoble, Rouen, Paris, and Strasbourg Outcome: Mortality: Lung Cancer (162) Study Design: Time-series Statistical Analyses: GIS Age Groups: 30-71 yr old nonsmoking adults Pollutant: PM 2.5 Averaging Time: 48-h avg Mean Range: 17 to 49 μg/m 3 Increment: 10 μg/m 3 % Increase (Lower CI, Upper CI) % increase in lung cancer deaths attributable to PM 2.5 exposure France: 8 (1, 16) Grenoble: 10 (3, 19) Rouen: 10 (2, 19) Strasbourg: 24 (4, 40)

Reference: Ozkaynak and Thurston (1987, 072960 ) Period of Study: 1980

Location: U.S. Outcome: Total Mortality Study Design: Cross-sectional Statistical Analyses: Multiple regression analysis Pollutant: Sulfate Averaging Time: Annual avg Mean Range: Sulfate: 11.1 (3.5) Range of estimated total mortality effects of air pollutions:

Sulfate: 4-9% “Sulfate concentration was consistently found to be a significant predictor of mortality in the models considered. Fine particle mass coefficients were also often found to be statistically significant in the mortality regressions.”

Reference: Pope et al. (2004, 055880 ) Period of Study: 1982-2000

Location: Metropolitan areas in all 50 states in the U.S. Outcome: Mortality: Cardiovascular Diseases (390-459) Diabetes (250) Respiratory Disease (460-519) Study Design: Prospective Cohort Statistical Analyses: Cox proportional hazards regression Age Groups: >30 Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD): 17.1 (3.7) Range (Min, Max): NR Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) All cardiovascular disease plus diabetes: PM 2.5 : 1.12 (1.08, 1.15) Former Smoker: 1.26 (1.23, 1.28) Current Smoker: 1.94 (1.90, 1.99) Ischemic Heart Disease: PM 2.5 : 1.18 (1.14, 1.23) Former Smoker: 1.33 (1.29, 1.37) Current Smoker: 2.03 (1.96, 2.10) Diabetes: PM 2.5 : 0.99 (0.86, 1.14) Former Smoker: 1.05 (0.94, 1.16) Current Smoker: 1.35 (1.20, 1.53) All other Cardiovascular Diseases: PM : 0.84 (0.71, 0.99)

2.5 Former Smoker: 1.22 (1.09, 1.38) Current Smoker: 1.78 (1.56, 2.04) Diseases of the respiratory system: PM 2.5 : 0.92 (0.86, 0.98) Former Smoker: 2.16 (2.04, 2.28) Current Smoker: 3.88 (3.66, 4.11) COPD: PM 2.5 : 0.84 (0.77, 0.93) Former Smoker: 4.93 (4.48, 5.42) Current Smoker: 9.85 (8.95, 10.84) All other respiratory diseases: PM 2.5 : 0.86 (0.73, 1.02) Former Smoker: 1.54 (1.36, 1.74) Current Smoker: 1.83 (1.57, 2.12)



### December 2009 E-511

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Pope et al. (2007, 091256 ) Period of Study: 1960-1975

Location: New Mexico, Arizona, Utah, and Nevada Outcome (ICD7&8): Mortality: Cardiovascular (ICD 7: 400- 468, 331, 332 ICD 8: 390-458) Respiratory (ICD 7: 470-527 ICD 8: 460-519) Influenza/ pneumonia (ICD 7: 480-483, 490-493, ICD 8: 470-474, 480-486) Study Design: Retrospective Cohort Statistical Analyses: Poisson regression model

GAM

SAS Age Groups: All smelter workers >18 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): NR Range (Min, Max): NR The study does not present quantitative results Results are presented in figures. The References found that the strike-related estimated percent decrease in mortality was 2.5% (1.1-4.0),

Reference: Pope et al. (2009, 190107 ) Period of Study: 1978-1982, 1997-2001

Location: 211 U.S. counties and 51 metropolitan areas Outcome: Increased life expectancy Study Design: Cross-sectional Statistical Analysis: Cross-sectional regression Age Groups: Adults ≥ 45 yr Pollutant: PM 2.5 Averaging Time: Daily, quarterly and annual Mean (SD) Unit: 1979-1983: 20.61 ± 4.36 μg/m 3 1999-2000: 14.10 ± 2.86 μg/m 3 Range (Min, Max): NR Copollutant (correlation): NR Increment: 10 μg/m 3 Regression Coefficient ± SD 211 County Units Intercept: 1.75 ± 0.27 Reduction in PM 2.5 : 0.61 ± 0.20 Change in Income: 0.13 ± 0.01 Change in Population: 0.06 ± 0.02 Change in Black Population: -2.70 ± 0.64 Change in Lung Cancer Mortality Rate: -0.06 ± 0.02 Change in COPD Mortality Rate: -0.08 ± 0.02 R: 0.53 51 Metropolitan Areas Intercept: 2.09 ± 0.36 Reduction in PM 2.5 : 0.95 ± 0.23 Change in Income: 0.11 ± 0.02 Change in Population: 0.05 ± 0.02 Change in Black Population: -5.98 ± 1.99 Change in Lung Cancer Mortality Rate: 0.02 ± 0.03 Change in COPD Mortality Rate: -0.19 ± 0.05 R: 0.74



### December 2009 E-512

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Rainham et al. (2005, 088676 ) Period of Study: 1981-1999

Location: Toronto, Canada Outcome: Total deaths (ICD9 <800),cardiorespiratory (390-459), noncardiorespiratory (ICD9-NR) Study Design: Time-series Statistical Analyses: Generalized linear models were used

Season: Winter (Dec-Feb) Summer (Jun-Aug) Statistical Package: S-Plus 6.1 Pollutant: PM 2.5 Averaging Time: NR Mean (SD): All yr: 17.0 (8.7) μg/m 3 Winters: 17.2 (6.8) Summers: 18.8 (10.2) Avg Winter values: Dry Moderate: 17.0 (1.0) Dry Polar: 17.5 (0.5) Dry Tropical: No Comparison Moist Moderate: 17.1 (0.8) Moist Polar: 17.5 (0.6) Moist Tropical: 16.5 (3.6) Transition: 16.7 (1.0) Avg summer values: Dry Moderate: 18.4 (0.9) Dry Polar: 19.0 (1.2) Dry Tropical: 18.5 (2.4) Moist Moderate: 19.2 (1.2) Moist Polar: 17.5 (2.0) Moist Tropical: 19.8 (1.1) Transition: 17.6 (1.5) Mortality risk for winter season and within winter synoptic weather categories RR Estimate [Lower CI, Upper CI]: Winter: Total: 0.998[0.997, 1.000] Cardioresp: 0.998[0.996, 1.000] Other: 0.998 [0.996, 1.000] Dry Moderate: Total: 1.001[0.996, 1.007] Cardioresp: 1.005[0.998, 1.011] Other: 1.002 [0.998, 1.005] Dry Polar: Total: 0.998[0.995, 1.001] Cardioresp: 0.995[0.991, 0.999] Other: 1.002 [0.998, 1.005] Dry Tropical: NA Moist Moderate: Total: 0.998[0.993, 1.002] Cardioresp: 1.003[0.995, 1.010] Other: 0.997 [0.991, 1.004] Moist Polar: Total: 1.001[0.998, 1.005] Cardioresp: 1.002[0.997, 1.007] Other: 1.003 [0.999, 1.007] Moist Tropical: Total: 1.007[0.965, 1.203] Cardioresp: 1.123[1.031, 1.224] Other: 1.248 [1.123, 1.387] Transition Total: 1.003[0.996, 1.009] Cardioresp: 0.996[0.987, 1.004] Other: 0.997 [0.990, 1.004] Mortality risk for summer season and within summer synoptic weather categories RR Estimate [Lower CI, Upper CI]: Summer: Total: 1.000[1.000, 1.001] Cardioresp: 1.001[1.000, 1.002] Other: 1.001[1.000, 1.002] Dry Moderate: Total: 1.001[0.999, 1.002] Cardioresp: 1.002[0.999, 1.004] Other: 0.999[0.997, 1.002] Dry Polar: Total: 1.002[0.999, 1.005] Cardioresp: 0.996[0.991, 1.000] Other: 1.003[ 0.999, 1.007] Dry Tropical: Total: 1.016[1.006, 1.027] Cardioresp: 1.017[1.005, 1.030] Other: 1.017 [1.003, 1.031] Moist Moderate: Total: 1.002[1.000, 1.004] Cardioresp: 1.003[0.999, 1.006] Other: 1.004 [1.001, 1.006] Moist Polar: Total: 1.005[0.998, 1.011] Cardioresp: 1.008[0.997, 1.018] Other: 1.003 [0.995, 1.011] Moist Tropical: Total: 0.999[0.997, 1.001] Cardioresp: 0.996[0.993, 1.000] Other: 0.998 [0.995, 1.001] Transition: Total: 1.005[0.996, 1.014] Cardioresp: 1.007[0.994, 1.020] Other: 1.002 [0.996, 1.008] Reference: Roman et al. (2008, 156921 ) Period of Study: 2006

Location: U.S. Outcome: Mortality Study Design: Expert Judgment Study Statistical Analyses: Standard best practices for expert elicitation Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD): 4-30 Quantitative results are not presented in the text, but can be found graphically in Fig 3. “Most of the experts’ central estimates fall at or above the 2002 ACS median (0.6% per μg/m 3 ) and below the original Six Cities median (1.2% per μg/m 3 ).”



### December 2009 E-513

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Schwartz, et al. (2008, 156921 ) Period of Study: 1979-1988

Location: Six U.S. metropolitan areas: Boston, Massachusetts Knoxville, Tennessee St. Louis, Missouri Steubenville, Ohio Madison, Wisconsin and Topeka, Kansas Outcome: Mortality Study Design: Poisson regression with GAM Statistical Analyses: Weighted linear regression

Season: all Dose-response Investigated? No Statistical Package: S-plus Pollutant: PM 2.5 Averaging Time: Daily Mean (SD): Boston-16.5 Knoxville-21.1 St. Louis-19.2 Steubenville-30.5 Madison-11.3 Topeka-12.2 SD not reported Range (Min, Max): (0,35) Monitoring Stations: 6 PM Increment: 10 μg/m 3

The difference between mean PM 2.5 concentrations of 10 μ g/m 3 and 20 μ g/m 3 is associated with about a 1.5% increase in deaths.

Reference: (Schwartz et al., 2008, 156963 ) Period of Study: 1979-1998

Location: Watertown, MA Kingston and Harriman, TN St Louis, MO Steubenville, OH Portage, Wyocena

Pardeeville WI Topeka, KS Outcome: Mortality: Nonaccidental (<800) Study Design: Cross-sectional Statistical Analyses: Cox proportional hazards regression penalized splines Bayesian Model Averaging Age Groups: >18 Pollutant: PM 2.5 Averaging Time: Annual avg Mean (SD): 17.5 (6.8) Range (Min, Max): (8, 40) Increment: 10 μg/m 3 Relative Risk (Lower CI, Upper CI) Estimated from Fig 4: All Cause Mortality - Year before Death 0: 1.10 (1.00, 1.21) 1: 1.03 (0.98, 1.08) 2: 1.01 (1.00, 1.02) 3: 1.00 (0.99, 1.01) 4: 1.00 (0.99, 1.01) 5: 1.00 Lung Cancer Mortality - Year Before Death Estimated from Fig 5 0: 1.18 (1.00, 1.48) 1: 1.12 (0.98, 1.33) 2: 1.08 (0.92, 1.22) 3: 1.02 (1.01, 1.03) 4: 1.01 (1.00, 1.02) 5: 1.01 RR per 10 μg/m 3 increase of PM 2.5 exposure Level Of Increase Estimated from Fig 3 10 μg/m 3 : 1.15 20 μg/m 3 : 1.29 30 μg/m 3 : 1.46 40 μg/m 3 : 1.64 Reference: Tainio et al. (2005, 087444 ) Period of Study: 1997-Present

Location: Helsinki, Finland Outcome (ICD10): Mortality: Cardiopulmonary (I11-I70 and J15-J47) Lung Cancer (C34)

Other causes Study Design: Time-series simulation Statistical Analyses: Monte Carlo Simulation Age Groups: All ages Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): 10.7 Range (Min, Max): NR Estimated Deaths Per Year (Min CI, Max CI) Associated with Primary PM 2.5 Emissions from buses in Helsinki in 2020 for different bus strategies Cardiopulmonary Mortality Current Fleet: 15.9 (0, 46.6) Modern Diesel: 7.9 (0, 23.0) Diesel with particle trap: 3.9 (0, 12) Natural gas bus: 2.3 (0, 6.8) Lung Cancer Mortality Current Fleet: 2.2 (0, 6.1) Modern Diesel: 1.1 (0, 3.0) Diesel with particle trap: 0.6 (0, 1.6) Natural gas bus: 0.3 (0, 0.9) Total Mortality Current Fleet: 18.1 (0, 55.0) Modern Diesel: 9.0 (0, 27.0) Diesel with particle trap: 4.4 (0, 14.1) Natural Gas Bus: 2.6 (0, 8.0)



### December 2009 E-514

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Villeneuve et al. (2002, 042576 ) Period of Study: 1974-1991

Location: Six U.S. Cities: Steubenville, OH, St. Louis, MO, Portage, WI, Topeka, KS, Watertown, MA, Kingston/ Harriman, TN Outcome (ICD10): Mortality: Nonaccidental (<800) Study Design: Prospective Cohort Statistical Analyses: Poisson, EPICURE Age Groups: All ages

<60

≥ 60 Pollutant: PM 2.5 Averaging Time: 24-h avg Mean (SD): Portage: 10.9 (7.2) Topeka: 12.1 (7.1) Harriman: 20.7 (9.4) Watertown: 14.9 (8.4) St. Louis: 18.7 (10.6) Steubenville: 28.6 (21.0)

Overall: 18.6 Range (Min, Max): NR Increment: 18.6 μg/m 3 Relative Risk (Min CI, Max CI) RR of all cause mortality for exposure of PM 2.5 by age group Exposure to PM 2.5 remained fixed over entire study period <60: 1.89 (1.32, 2.69) >60: 1.21 (1.02, 1.43) Total: 1.31 (1.12, 1.52) Exposure to PM 2.5 was defined according to 13 calendar periods* (no smoothing) <60: 1.52 (1.15, 2.00) >60: 1.11 (0.95, 1.29) Total: 1.19 (1.04, 1.36) Exposure to PM 2.5 was defined according to 13 calendar periods* (smoothed) <60: 1.43 (1.10, 1.85) >60: 1.09 (0.93, 1.26) Total: 1.16 (1.02, 1.32) Time dependent estimate of PM 2.5 received during the previous 2 yr <60: 1.42 (1.09, 1.82) >60: 1.08 (0.94, 1.25) Total: 1.16 (1.02, 1.31) Time dependent estimate of PM 2.5 received 3-5 yr before current yr <60: 1.35 (1.08, 1.67) >60: 1.08 (0.95, 1.22) Total: 1.14 (1.02, 1.27) Time dependent estimate of PM 2.5 received >5 yr before current yr <60: 1.34 (1.11, 1.59) >60: 1.09 (0.99, 1.20) Total: 1.14 (1.05, 1.23) * The calendar periods used were: 1970-1978, 1979, 1980, 1981, 1982, 1983, 1984, 1985, 1986, 1987, 1988, 1989, and 1990+. RR of all cause mortality and PM 2.5 exposure by city Portage: 1.16 (0.96, 1.39) Topeka: 1.06 (0.89, 1.27) Harriman Men: 1.04 (0.79, 1.36) Women: 0.96 (0.69, 1.31) All: 1.13 (0.95, 1.35) Watertown Men: 1.20 (0.95, 1.51) Women: 1.06 (0.78, 1.43) All: 1.32 (1.11, 1.51) St. Louis Men: 0.97 (0.76, 1.24) Women: 1.13 (0.86, 1.49) Steubenville Men: 1.39 (1.11, 1.74) Women: 1.22 (0.93, 1.61) Reference: Willis et al. (2003, 089922 ) Period of Study: 1982-1989

Location: U.S. Metropolitan areas in all 50 states Outcome: Mortality: All causes Lung Cancer (162) Cardiopulmonary (401-440, 460-519) Study Design: Prospective Cohort Statistical Analyses: Cox proportional hazards model Age Groups: All ages Pollutant: Sulfates Averaging Time: Annual avg Mean (SD): 10.6 μg/m 3 Range (Min, Max): 3.6, 23.5 Copollutant: CO, NO 2 , O 3 , SO 2 All Cause, Metropolitan Scale: 1.25 (1.13, 1.37) All Cause, County Scale: 1.50 (1.30, 1.73) CPD, Metropolitan Scale: 1.29 (1.15, 1.46) CPD, County Scale: 1.75 (1.48, 2.08)

Reference: Zanobetti and Schwartz (2009, 188462 ) Period of Study: 1999-2005

Location: 112 U.S. Cities Outcome: Mortality, all causes, excluding ICD codes S00-U99 Study Design: Time-series

Covariates: Region, season Pollutant: PM 2.5 Averaging Time: 24 h Mean (SD) Birmingham AL - 16.5 Phoenix AZ - 11.4 LittleRock AR - 14.3 Increment: 10 μg/m 3 Percent Increase (95% CI) in mortality by increment of PM 2.5 , combined by season All Cause Mortality Overall: 0.98 (0.75-1.22)



### December 2009 E-515

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Statistical Analysis: Poisson regression Age Groups: All Fresno CA - 19.4 Bakersfield CA - 21.7 Los Angeles CA - 19.9 Anaheim CA - 16.3 Rubidoux CA - 24.9 Sacramento CA - 13.0 El Cajon CA - 13.5 Denver CO - 10.3 Hartford CT - 11.6 New Haven CT - 13.7 Wilmington DE - 15.1 Davie FL - 8.4 Miami FL - 9.4 Jacksonville FL - 10.6 Pensacola FL - 12.4 Tampa FL - 11.9 Orlando FL - 10.3 Palm beach FL - 7.9 Pinellas FL - 10.4 Atlanta GA - 17.6 Chicago IL - 15.9 Gary IN - 15.3 Indianapolis IN - 16.3 Cedar Rapids IA - 11.0 Des Moines IA - 10.5 Davenport IA - 12.3 Louisville KY - 15.9 Baton Rouge LA - 13.4 Avondale LA - 12.3 New Orleans LA - 12.6 Baltimore MD - 15.6 Springfield MA - 12.3 Boston MA - 12.4 Worcester MA - 11.3 Holland MI - 12.1 Grand Rapids MI - 13.6 Detroit MI - 16.2 Minneapolis MN - 11.1 Kansas MO - 12.0 St Louis MO - 14.5 Omaha NE - 10.4 Elizabeth NJ - 14.7 Albuquerque NM - 6.7 New York NY - 14.8 Bath NY - 9.6 Durham NC - 14.3 Winston NC - 14.7 Greensborough NC - 14.2 Charlotte NC - 15.3 Raleigh NC - 14.3 Middletown OH - 16.4 Youngstown OH - 15.6 Cleveland OH - 16.4 Columbus OH - 16.2 Cincinnati OH - 17.1 Steubenville OH - 17.0 Toledo OH - 14.9 Dayton OH - 16.2 Akron OH - 16.0 Warren OH - 15.3 Oklahoma OK - 9.9 Tulsa OK - 11.1 Bend OR - 7.8 Medford OR - 9.9 Klamath OR - 10.6 Eugene OR - 8.0 Portland OR - 8.8 Gettysburg PA - 13.4 Pittsburgh PA - 15.7 State College PA - 13.2 Carlisle PA - 15.1 Harrisburg PA - 15.5 Erie PA - 13.1 Scranton PA - 11.8 Allentown PA - 14.2 Wilkes Barre PA - 12.8 Mercer PA - 14.1 Easton PA - 14.0 Winter: 0.56 (0.17-0.94) Spring: 2.57 (1.96-3.19) Summer: 0.25 (-0.13-0.63) Fall: 0.95 (0.56-1.34) CVD Overall: 0.85 (0.46-1.24) Winter: 0.70 (0.04-1.36) Spring: 2.18 (1.22-3.15) Summer: -0.03 (-0.75-0.69) Fall: 0.92 (0.17-1.68) MI Overall: 1.18 (0.48-1.89) Winter: 1.29 (-0.14-2.75) Spring: 2.12 (0.53-3.74) Summer: -0.03 (-1.46-1.42) Fall: 1.24 (0.12-2.36) Stroke Overall: 1.78 (0.96-2.62) Winter: 1.93 (0.34-3.54) Spring: 2.04 (-0.02-4.13) Summer: 1.64 (0.05-3.26) Fall: 1.69 (0.06-3.35) Respiratory Overall: 1.68 (1.04-2.33) Winter: 0.86 (-0.16-1.88) Spring: 4.62 (3.08-6.18) Summer: 0.78 (-0.49-2.06) Fall: 1.45 (0.19-2.72) Percent Increase (95% CI) in mortality by increment in PM 2.5 combined by region All Cause Mortality Humid Subtropical and Maritime: 1.02 (0.65-1.38) Warm Summer Continental: 1.19 (0.73-1.64) Hot Summer Continental: 1.14 (0.55-1.73) Dry: 1.18 (-0.70-3.10) Dry, Continental: 1.26 (-0.21-2.76) Mediterranean: 0.50 (0.00-1.01) CVD Humid Subtropical and Maritime: 0.78 (0.05-1.51) Warm Summer Continental: 1.43 (0.67-2.19) Hot Summer Continental: 0.43 (-0.53-1.40) Dry: 3.11 (-0.02-6.33) Dry, Continental: 1.67 (-0.75-4.16) Mediterranean: 0.16 (-0.46-0.79) MI Humid Subtropical and Maritime: 0.97 (-0.29-2.26) Warm Summer Continental: 1.50 (0.05-2.97) Hot Summer Continental: 0.64 (-0.96-2.28) Dry: 4.25 (-2.38-11.33) Dry, Continental: 0.60 (-7.42-9.32) Mediterranean: 1.85 (-0.66-4.41) Stroke Humid Subtropical and Maritime: 2.94 (1.59-4.32) Warm Summer Continental: 1.85 (0.04-3.69) Hot Summer Continental: 0.77 (-1.77-3.38) Dry: 1.82 (-6.98-11.45) Dry, Continental: 2.49 (-2.32-7.53) Mediterranean: 0.95 (-0.66-2.59) Respiratory Humid Subtropical and Maritime: 0.91 (-0.25-2.08) Warm Summer Continental: 2.12 (0.89-3.36) Hot Summer Continental:



### December 2009 E-516

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI) Philadelphia PA - 14.5 Washington PA - 14.7 Providence RI - 11.5 Charleston SC - 12.1 Taylors SC - 15.3 Columbia SC - 14.0 Spartanburg SC - 14.2 Nashville TN - 14.0 Knoxville TN - 16.0 Memphis TN - 13.5 San Antonio TX - 9.4 Dallas TX - 12.9 El Paso TX - 9.2 Houston TX - 12.9 Port Arthur TX - 11.5 Ft Worth TX - 12.2 Austin TX - 10.4 Salt Lake UT - 11.5 Provo UT - 9.5 WDC VA - 15.2 Annandale VA - 14.0 Dumbarton VA - 13.6 Chesapeake VA - 12.7 Norfolk VA - 12.7 Richmond VA - 14.3 Seattle WA - 10.1 Tacoma WA - 11.2 Spokane WA - 9.1 Dodge WI - 11.1 Milwaukee WI - 13.2 Waukesha WI - 13.2 Range (Min, Max): NR Copollutant (correlation): NR 3.36 (1.95-4.79) Dry: 5.81 (-0.04-12.00) Dry, Continental: -0.31 (-5.89-5.61) Mediterranean: 1.06 (-0.36-2.50)

Reference: Zeger et al. (2007, 157176 ) Period of Study: 2000-2002

Location: 250 largest U.S. counties Outcome: Mortality Study Design: Retrospective Cohort (MCAPS) Statistical Analyses: Log-linear regression models (GAM)

Covariates: Age, gender, race, countylevel SES, education and COPD SMR Age Groups: 65+ 65-74, 75-84, 85+ Pollutant: PM 2.5 Averaging Time: 3-yr avg Increment: 10 μg/m 3 65+: 1.076 (1.044, 1.108) Eastern U.S.: 1.125 (1.091, 1.159) Central U.S.: 1.196 (1.115, 1.277) Western U.S.: 1.029 (0.994, 1.064) 65-74: 1.156 (1.117, 1.196) 75-84: 1.081 (1.042, 1.121) 85+: 0.995 (0.956, 1.035)



### December 2009 E-517

### Concentrations 1 

### Study Design & Methods Effect Estimates (95% CI)

Reference: Zeger et al. (2008, 191951 ) Period of Study: 2000-2005

Location: 4568 zip codes in urban

areas Outcome: Mortality Study Design: Retrospective Cohort Statistical Analysis: Log-linear regression model Age Groups: ≥ 65 Pollutant: PM 2.5 Averaging Time: Annual Median (SD) Unit: Eastern: 14.0 μg/m 3 Central: 10.7 μg/m 3 Western: 13.1 μg/m 3 All: 13.2 μg/m 3 Range (IQR):

Eastern: 12.3-15.3

Central: 9.8-12.2

Western: 10.4-18.5

All: 11.1-14.9 Copollutant (correlation): NR Increment: 10 μg/m 3 Relative Risk (Min CI, Max CI) lag Risk estimate for increase in mortality per increase in PM 2.5 , all ages Eastern Region Age: 1.155 (1.130-1.180) Age + SES: 1.105 (1.084-1.125) Age + SES + COPD: 1.068 (1.049-1.087) Central Region Age: 1.178 (1.133-1.222) Age + SES: 1.089 (1.052-1.125) Age + SES + COPD: 1.132 (1.095-1.169) Western Region Age: 1.003 (0.981-1.025) Age + SES: 0.997 (0.978-1.016) Age + SES + COPD: 0.989 (0.970-1.008) Risk estimate for increase in mortality per increase in PM 2.5 , ages 65-74 Eastern Region Age: 31.1 (26.8-35.5) Age + SES: 17.3 (14.6-20.0) Age + SES + COPD: 11.4 (8.8-14.1) Central Region Age: 39.0 (29.7-48.2) Age + SES: 16.5 (10.9-22.1) Age + SES + COPD: 20.4 (15.0-25.8) Western Region Age: 6.0 (2.3-9.6) Age + SES: -2.1 (-5.0-0.8) Age + SES + COPD: -1.5 (-4.2-1.1) Risk estimate for increase in mortality per increase in PM 2.5 , ages 75-84 Eastern Region Age: 17.6 (14.9-20.4) Age + SES: 12.4 (10.1-14.6) Age + SES + COPD: 8.9 (6.8-11.0) Central Region Age: 17.5 (12.7-22.2) Age + SES: 8.8 (4.6-13.0) Age + SES + COPD: 12.0 (7.6-16.4) Western Region Age: 0.4 (-2.0-2.7) Age + SES: 0.3 (-1.8-2.5) Age + SES + COPD: -0.2 (-2.2-1.9) Risk estimate for increase in mortality per increase in PM 2.5 , aged ≥ 85 Eastern Region Age: -1.4 (-3.5-0.8) Age + SES: 1.4 (-0.7-3.5) Age + SES + COPD: 1.7 (-0.3-3.7) Central Region Age: -2.1 (-5.9-1.6) Age + SES: -0.7 (-4.2-2.8) Age + SES + COPD: -0.3 (-4.0-3.3) Western Region Age: -5.2 (-7.2-3.2) Age + SES: 0.9 (-0.8-2.7) Age + SES + COPD: -0.5 (-2.5-1.5)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-518

# Table E-34. Long-term exposure - central nervous system outcomes - PM.

Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Author: Calderón-Garcidueñas et al. (2008, 192369 ) Period of Study: NR

Location: Mexico City (polluted city) and Tlaxcala and Veracruz (control cities), Mexico Outcome (ICD9 and ICD10): COX2 (cyclooxygenase), IL-1 β , CD14 in lungs, OB (olfactory bulb), frontal cortex, hippocampus, substantia nigrae, periaqueductal gray and vagus nerves Age Groups Analyzed: Subjects 2-45 yr of age mean=25.1 ± 1.5 yr Study Design:

Cross-sectional

N: 47 deceased subjects with complete autopsies and neuropathological examinations (each subject had to be considered clinically healthy and cognitively and neurologically intact prior to death) (primarily cause of death: accidents resulting in immediate death) Statistical Analyses: NR likely used T-tests in addition, stated using “parametric procedure that considers the differences among variances of the variables of interest”

Covariates: Age, gender, place of birth, place of residency, occupation, smoking habits, clinical histories, cause of death, and time between death and autopsy

Season: NR Dose-response Investigated? (Yes/No): No Statistical package: Stata PM Size: No measure of PM used Mexico City as the “polluted city” and Tlaxcala and Veracruz as the “control cities” Averaging Time: NA Mean (SD): NA

Percentiles: NA Range (Min, Max): NA Unit (i.e. μg/ m 3 ): NA Number of Monitoring Stations: NA Co-pollutant (correlation):

NA PM Increment: NA Effect Estimate [Lower CI, Upper CI]: RT-PCR sample results from Control and Mexico City (MC) lung, CNS, PNS (peripheral nervous system) tissues and p-value for the difference between the

means Concentrations are normalized to the amount of GAPDH cDNA COX2 (cyclooxygenase-2) lung Controls: 15.9± 6.7 x 106 MC residents: 42.3± 7.4 x 106 P-value: 0.015 IL-1 β lung Controls: 3.08±1.87 x 106 MC residents: 4.51± 2.6 x 106 P-value: 0.60 COX2 OB (olfactory bulb) Controls: 12.9± .0 x 105 MC residents: 38.7± 5.5 x 105 P-value: 0.0002 IL-1 β OB Controls: 3.4± 0.8 x 104 MC residents: 7.7± 1.0 x 104 P-value: 0.003 CD14 OB Controls: 0.01± 0.001 MC residents: 0.04± 0.01 P-value: 0.04 COX2 frontal Controls: 2.6± 0.4 x 105 MC residents: 5.0± 0.7 x 105 P-value: 0.008 IL-1 β frontal Controls: 0.6± 0.2 x 104 MC residents: 6.2± 1.3 x 104 P-value: 0.0002 COX2 hippocampus Controls: 1.9± 0.5 x 105 MC residents: 1.6± 8.7 x 105 P-value: 0.1 IL-1 β hippocampus Controls: 1.8±0.2 x 104 MC residents: 3.0±0.5 x 104 P-value: 0.06 COX2 substantia nigrae Controls: 0.16± 0.06 MC residents: 0.97± 0.2 P-value: 0.03 IL-1 β substanita nigrae Controls: 0.01± 0.005 MC residents: 0.09± 0.03 P-value: 0.06 CD14 substantia nigrae Controls: 0.02± 0.005 MC residents: 0.03± 0.007 P-value: 0.7 COX2 periaqueductal gray Controls: 0.10± 0.03 MC residents: 0.45± 0.12 P-value: 0.12 IL-1 β periaqueductal gray Controls: 0.009± 0.003 MC residents: 0.07± 0.02 P-value: 0.09 COX2 left vagus Controls: 0.65± 0.18 MC residents: 2.68± 0.82 P-value: 0.03 COX2 right vagus Controls: 0.43± 0.09



### December 2009 E-519

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

MC residents: 3.68± 0.8 P-value: 0.0002 IL-1 β left vagus Controls: 0.1± 0.03 MC residents: 1.3± 0.73 P-value: 0.06 IL-1 β right vagus Controls: 0.15± 0.09 MC residents: 0.87± 0.53 p-value: 0.66 CD14 left vagus Controls: 0.07± 0.01 MC residents: 0.79± 0.41 P-value: 0.01 CD14 right vagus Controls: 0.05± 0.01 MC residents: 0.31± 0.1 P-value: 0.02 Distribution of subjects with expression of A β 42 as a function of age and residency Groups: No (%) with A β 42 expression Controls <25yr APOE 3/3 (n=6): 0 (0) Controls >25yr APOE 3/3 (n=3): 0 (0) MC E2 or E3 <25yr (n=17): 10 (58.82) MC E2 or E3 >25yr (n=10): 8 (80) MC E4 (n=8): 8 (100) Controls E4 (n=3): 2 (66) Distribution of subjects with expression of α -synuclein as a function of age and Residency Groups: No (%) with α -synuclein expression Controls <25yr APOE 3/3 (n=6): 0 (0) Controls >25yr APOE 3/3 (n=3): 0 (0) MC E2 or E3 <25yr (n=17): 4 (23.5) MC E2 or E3 >25yr (n=10): 3 (30) MC E4 (n=8): 2 (25) Controls E4 (n=3): 0 (0) Reference: Chen and Schwartz (2009, 179945 ) Period of Study: 1989-1991

Location: U.S. Outcome: Change in central nervous system function Study Design: Panel

Covariates: Age, sex, race/ethnicity, individual socioeconomic position, lifestyle factors, household and neighborhood characteristics, conventional CVD risk factors Statistical Analysis: Pearson Chisquare tests and t-tests, as appropriate Statistical Package: STATA Age Groups: 20-59 yr Pollutant: PM 10 Averaging Time: 1 yr Mean (SD) Unit: 37.2 ± 12.8 μg/m 3 Copollutant: O 3 Increment: 10 μg/m 3 Regression Coefficient β (95% CI) Crude SRTT: 2.14 (-0.08-4.36) SDST: 0.08 (0.04-0.13) SDLT Trials: 0.22 (0.13-0.31) SDLT Total: 0.44 (0.23-0.65) Model 1: adjusted for age, sex, race/ethnicity SRTT: 2.03 (-0.15-4.20) SDST: 0.10 (0.05-0.15) SDLT Trials: 0.23 (0.14-0.32) SDLT Total: 0.48 (0.27-0.68) Model 2: Model 1 + socioeconomic factors SRTT: -0.11 (-2.38-2.16) SDST: 0.01 (-0.04-0.06) SDLT Trials: 0.01 (-0.08-0.10) SDLT Total: -0.07 (-0.27-0.13) Model 3: Model 2 + lifestyle factors SRTT: -0.36 (-2.58-1.85) SDST: 0.00 (-0.04-0.05) SDLT Trials: 0.09 (0.00-0.17) SDLT Total: 0.12 (-0.07-0.31)



### December 2009 E-520

### Study Design & Methods Concentrations 1 

### Effect Estimates (95% CI)

Author: Suglia et al. (2008, 157027 ) Period of Study: 1986-2001

Location: Boston, Massachusetts Outcome (ICD9 and ICD10): Cognition: Kaufman Brief Intelligence Test, K-BIT (vocabulary and matrices subscales and composite IQ score) Wide Range Assessment of Memory and Learning, WRAML (psychometric instrument with subscales on verbal memory, visual memory, learning, and overall general index scale) All cognition scores have a mean of 100 and SD=15. Age Groups Analyzed: Cognitive tests administered when children were 8-11 yr of age Study Design: Cross-sectional

N: 202 children Statistical Analyses: Linear regression

Covariates: Child’s age at cognitive assessment, gender, primary language spoken at home, and maternal education (model 1 “Demographic factors”) Sensitivity analyses performed with further adjustment for in-utero and postnatal secondhand tobacco smoke exposure (via questionnaire during follow-ups and urinary cotinine levels) (model 2) Birth weight (model 3) and blood lead level (model 4)

Season: Separate land-use regression models were fit for the warm (May-Oct) and cold (Nov-Apr) seasons Used avg of two seasons as measure of avg lifetime BC exposure Dose-response Investigated? (Yes/No): No Statistical package: SAS (v9.0) PM Size: Black carbon (BC) Averaging Time: Lifetime exposure

Estimated 24 h measures of traffic using a spatiotemporal land-use regression model using data from >80 locations in Greater Boston (6021 pollution measurements from 2127 unique exposure days) Predictors in the land-use regression analysis were the BC level at a central station (to capture avg concentrations on that day), meteorological conditions, weekday/weekend, and measure of traffic activity (GIS-based measures of cumulative traffic density within 100m, population density, distance to nearest major roadway, % urbanization) Used the avg of the cold and warm seasons as the measure of avg lifetime BC exposure Mean (SD): 0.56 (0.13) μ g/m 3

Percentiles: NR Range (Min, Max): NR Unit (i.e. μg/ m 3 ): Number of Monitoring Stations: >80 locations Co-pollutant (correlation): NA PM Increment: 0.4 μg/m 3 Effect Estimate [Lower CI, Upper CI]: Change in subscale score (95%CI) per IQR (0.4 μ g/m 3 ) increase in log BC level K-BIT Vocabulary: Adj for demographic factors: -2.0 (-5.3, 1.3) Adj for above factors + secondhand smoke: -2.0 (-5.3, 1.4) Adj for above factors + birth weight: - 2.0 (-5.4, 1.3) Adj for above factors + blood lead level: -2.2 (-5.5, 1.1) Matrices: Adj for demographic factors: -4.2 (-7.7, -0.7) Adj for above factors + secondhand smoke: -4.0 (-7.5, -0.4) Adj for above factors + birth weight: -4.0 (-7.6, -0.5) Adj for above factors + blood lead level: -4.0 (-7.6, -0.5) Composite: Adj for demographic factors: -3.4 (-6.6, -0.3) Adj for above factors + secondhand smoke: -3.3 (-6.4, -0.1) Adj for above factors + birth weight: -3.3 (-6.5, -0.2) Adj for above factors + blood lead level: -3.4 (-6.6, -0.3) WRAML Verbal: Adj for demographic factors: -1.1 (-4.6, 2.3) Adj for above factors + secondhand smoke: -1.2 (-4.7, 2.3) Adj for above factors + birth weight: -1.3 (-4.7, 2.2) Adj for above factors + blood lead level: -1.3 (-4.8, 2.2) Visual: Adj for demographic factors: -5.2 (-8.6, -1.7) Adj for above factors + secondhand smoke: -5.3 (-8.8, -1.8) Adj for above factors + birth weight: -5.3 (-8.8, -1.8) Adj for above factors + blood lead level: -5.4 (-8.9, -1.9) Learning: Adj for demographic factors: -2.7 (-6.5, 1.1) Adj for above factors + secondhand smoke: -2.6 (-6.5, 1.2) Adj for above factors + birth weight: -2.6 (-6.5, 1.3) Adj for above factors + blood lead level: -2.8 (-6.6, 1.1) General: Adj for demographic factors: -3.7 (-7.2, -0.2) Adj for above factors + secondhand smoke: -3.7 (-7.3, -0.1) Adj for above factors + birth weight: -3.8 (-7.4, -0.2) Adj for above factors + blood lead level: -3.9 (-7.5, -0.3)

1 All units expressed in μg/m 3 unless otherwise specified.



### December 2009 E-521

# Annex E References

Abbey DE; Nishino N; McDonnell WF; Burchette RJ; Knutsen SF; Beeson WL; Yang JX (1999). Long-term inhalable particles and other air pollutants related to mortality in nonsmokers. Am J Respir Crit Care Med, 159: 373-382. 047559 Abrahamowicz M; Schopflocher T; Leffondre K; Du Berger R; Krewski D (2003). Flexible modeling of exposure-response relationship between long-term average levels of particul ate air pollution and mortality in the American Cancer Society study. J Toxicol Environ Health A Curr Iss, 66: 1625-1654. 086292 Ackermann-Liebrich U; Leuenberger P; Schwartz J; Schi ndler C; Monn C; Bolognini B; Bongard JP; Brandli O; Domenighetti G; Elsasser S; Grize L; Karrer W; Keller R; Keller-Wossidlo H; Kunzli N; Martin BW; Medici TC; Pliger B; Wuthrich B; Zellweger JP; Zemp E (1997). L ung function and long term exposure to air pollutants in Switzerland. Am J Respir Cr it Care Med, 155: 122-129. 077537 Adamkiewicz G; Ebelt S; Syring M; Slater J; Speizer FE; Schwartz J; Suh H; Gold DR (2004). Association between air pollution exposure and exhaled nitric oxide in an elderly population. Thorax, 59: 204-209. 087925

Adar SD; Adamkiewicz G; Gold DR; Schwartz J; Coull BA ; Suh H (2007). Ambient and micr oenvironmental particles and exhaled nitric oxide before and after a group bus trip. Environ Health Perspect, 115: 507-512. 098635

Adar SD; Gold DR; Coull BA; Schwartz J; Stone PH; Suh H (2007). Focused exposures to airborne traffic particles and heart rate variability in the elderly. Epidemiology, 18: 95-103. 001458 Aekplakorn W; Loomis D; Vichit-Vadakan N; Shy C; Plungc huchon S (2003). Acute effects of SO2 and particles from a power plant on respiratory symptoms of children, Thai land. Southeast Asian J Trop Med Public Health, 34: 906- 914. 089908 Aga E; Samoli E; Touloumi G; Anderson HR; Cadum E; Forsberg B; Goodman P; Goren A; Kotesovec F; Kriz B; Macarol-Hiti M; Medina S; Paldy A; Schindler C; Sunyer J; Tittanen P; Wojtyniak B; Zmirou D; Schwartz J; Katsouyanni K (2003). Short-term effects of ambient particles on mortality in the elderly: results from 28 cities in the APHEA2 project. Eur Respir J, 40: 28s-33s. 054808 Agarwal R; Jayaraman G; Anand S; Marimuthu P (2006). A ssessing respiratory morbidity through pollution status and meteorological conditions for Delhi. Environ Monit Assess, 114: 489-504. 099086 Allen RW; Criqui MH; Diez Roux AV; Allison M; Shea S; Detrano R; Sheppard L; Wong N; Hinckley Stukovsky K; Kaufman JD (2009). Fine particulate air pollution, proximity to traffic, and aortic atherosclerosis: The multi-ethnic study of atherosclerosis. Epidemiology, 20: 254-264. 156209 Allen RW; Mar T; Koenig J; Liu LJ; Gould T; Simpson C; Larson T (2008). Changes in lung function and airway inflammation among asthmatic children residing in a woods moke-impacted urban area. I nhal Toxicol, 20: 423-433. 156208 Analitis A; Katsouyanni K; Dimakopoulou K; Samoli E; Nikoloulopoulos AK; Petasakis Y; Touloumi G; Schwartz J; Anderson HR; Cambra K; Forastiere F; Zmirou D; Vonk JM; Clancy L; Kriz B; Bobvos J; Pekkanen J (2006). Short-term effects of ambient par ticles on cardiovascular and respiratory mortality. Epidemiology, 17: 230-233. 088177 Andersen ZJ; Wahlin P; Raaschou-Nielsen O; Ketzel M; Scheike T; Loft S (2008). Size distribution and total number concentration of ultrafine and accumulation mode particles and hospital admissions in children and the elderly in Copenhagen, Denmark. Occup Environ Med, 65: 458-66. 189651

Andersen ZJ; Wahlin P; Raaschou-Nielsen O; Scheike T; Lo ft S (2007). Ambient particle source apportionment and daily hospital admissions among children and elderly in C openhagen. J Expo Sci Environ Epidemiol, 17: 625-636. 093201 Anderson HR; Atkinson RW; Bremner SA; Marston L (2003). Particulate air pollution and hospital admissions for cardiorespiratory diseases: are the elderly at greater risk? Eur Respir J, 40: 39s-46s. 054820

Note: Hyperlinks to the reference citations throughout this doc ument will take you to the NCEA HERO database (Health and Environmental Research Online) at http: //epa.gov/hero . HERO is a database of scientific literature used by U.S. EPA in the process of developing science assessments such as the Integrated Science Assessments (ISA) and the Integrated Risk Information System (IRIS)

.



### December 2009 E-522

### Anderson ME; Bogdan GM (2007). Environments, indoor air qua lity, and children. Pediatr Clin North Am, 54: 295-307. 156214

Annesi-Maesano, I.; Forastiere, F.; Kunzli, N.; Brunekref , B.; Environment and Health Committee of the European Respiratory Society.. (2007). Particulate matter, sc ience and EU policy. Eur Respir J, 29: 428-431. 091348

Arbex MA; Martins LC; De Oliveira RC; Pereira LA; Arbex FF; Cancado JE; Saldiva PH; Braga AL (2007). Air pollution from biomass burning and asthma hospital admissions in a sugar cane plantation area in Brazil. J Epidemiol Community Health, 61: 395-400. 091637

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