# Annex C. Epidemiology Studies

Table C-1. Studies of CO exposur e and cardiovascular morbidity.

Study Design Concentrations CO Effect Estima tes (95% CI)

CHANGES IN HEART RATE AND HEART RATE VARIABILITY

Author: Chan et al. (2005, 088988 ) Period of Study: December 2001-February 2002

Location: Taipei, Taiwan Health Outcome: Various measures of HRV via ambulatory ECG (Holter system) Study Design: Panel Statistical Analyses: Linear regression (mixed effects) Age Groups Analyzed: 40-75 yr Sample Description: 83 patients from the National Taiwan University Hospital Averaging Time: 1



# - h ma Mean (SD) unit: 1.1 ppm Range (Min, Max): 0.1, 7.7 Copollutant : NR Increment: NR

RR Estimate [Lower CI, Upper CI] Lags examined (-h ma): 1, 2, 3, 4, 5, 6, 7, 8 CO had no statistically significant effect on SDNN, rMSSD, LF, HF.

Author: Chuang (2008, 155731 ) Period of Study: NR Location: Boston, MA Health Outcome: HRV (changes in STsegment) Study Design: Panel Statistical Analyses: Linear additive models; Additive mix ed logistic regression models Age Groups Analyzed: 43-75 Sample Description: 48 patients with documented CAD who had undergone percutaneous coronary intervention for acute coronary syndrome (acute MI or unstable angina pectoris) or who had worsened CAD Averaging Time: 12 h, 24 h Mean (SD) unit: 12 h: 0.48ppm, 24 h: 0.46ppm Range (Min, Max): 12-h: 25th percentile- 0.35, 75th percentile- 0.62, Max- 1.88; 24 h: 25th percentile- 0.37,75th percentile- 0.62, Max1.56 Copollutant : NR Increment: NR

RR Estimate [Lower CI, Upper CI] Lags examined: NR Estimated RR for ST-segment depression ≥ 0.1 mm (ppm): 12-h: 0.70 (0.58-0.84)

24 h: 0.84 (0.68-1.03) Estimated ST-segment change, mm (ppm): 12-h mean: 0.013 (0.003-0.024)

24 h mean: 0.007 (-0.004-0.019) CO not significantly a ssociated with ST-segment depression.

Author: Dales et al. (2004, 099036 ) Period of Study: NR

Location: Toronto, Canada. Health Outcome: Various measures of HRV via Holter system Study Design: Panel Statistical Analyses: Linear regression (mixed effects) Age Groups Analyzed: 51-88 yr (mean 65 yr) Sample Description: 36 subjects with preexisting CAD Averaging Time: 24 h Mean (SD) unit: 2.40 ppm (95th percentile) Personal monitoring Range (Min, Max): 0.4, 16.5 Copollutant: correlation PM 2.5 : r = 0.17 Increment: NR Regression co-efficient [Lower CI, Upper CI] Lags examined: NR CO had no statistically signi ficant effect on LF, HF, HFLFR, SDNN among those taking beta-blockers 

## , whereas CO had a positive effect on SDNN among those not taking beta-blockers. Slope = 0.0111 (0.002-0.020, p = 0.02)

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 litera ture used by U.S. EPA in the process of developing science assessments such as the Integrated Science Assessments (ISAs) and the Integrated Risk Information System (IR IS).



### January 2010 C-1

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Gold et al. (2000, 011432 ) Period of Study: June-September 1997

Location: Boston, MA Health Outcome (ICD9 or ICD10): Heart rate and various measures of HRV via Holter system Study Design: Panel/Cohort Statistical Analyses: Linear regression (fixed effects/random effects) Age Groups Analyzed: 53-87 yr Sample Description: 21 active Boston residents observed up to 12 times. Averaging Time: 24 h Mean (SD) unit: 0.47 ppm Range (Min, Max): 0.12, 0.82 Copollutant: NR Increment: 0.6 ppm % Change [Lower CI, Upper CI] Lags examined: 24 h No significant effect with CO (no results recorded)

Author: Gold et al. (2005, 087558 ) Period of Study: June-September 1999

Location: Boston, MA Health Outcome: ST- segment. Study Design: Panel Statistical Analyses: Linear regression (mixed models) Age Groups Analyzed: 61-88 yr Sample Description: 24 active Boston residents each observed up to 12 times. Averaging Time: 1 h, 24 h Mean (SD) unit: NR Range (Min, Max): (ppm) (personal monitoring) 10th = 0.20 90th = 1.08 Copollutant: NR Increment: NR RR Estimate [Lower CI, Upper CI] Lags examined: 1 24 h Although CO was associ ated with ST-segment depression in single pollutant models, this result did not persist in multiple pollutant models.

Author: Goldberg et al. (2008, 180380 ) Period of Study: July 2002-October 2003

Location: Montreal, Quebec Health Outcome: Oxygen saturation and heart rate Study Design: Panel Statistical Analyses: Mixed regression models Age Groups Analyzed: 50-85 yr Sample Description: 31 subjects with CHF and limits in physical functioning in the Heart Failure and Heart Transplant Center at the McGill University Health Center Averaging Time: 24 h Mean (SD) unit: NR Range (Min, Max): NR Copollutant: PM 2.5 : r = 0.72 NO 2 : r = 0.84 SO 2 and NO 2 : r = 0.43 Increment: NR Adjusted Mean Difference [Lower CI, Upper CI] Lags examined: 0, 1, 2 Oxygen Saturation: Lag 0: 0.004 ppm (-0.060, 0.067) Lag 1: -0.001 ppm (-0.066, 0.065) 3-day: -0.005 ppm (-0.098. 0.088)

Pulse Rate: Lag 0: 0.011 ppm (-0.290, 0.312) Lag 1: 0.227 ppm (-0.080,0.535) 3-day: 0.245 ppm (-0.209, 0.700)

Author: Holguin et al. (2003, 057326 ) Period of Study: February-April 2000

Location: Mexico City, Mexico Health Outcome: Various measures of HRV via ECG Study Design: Panel Statistical Analyses: GEE Age Groups Analyzed: 60-96 yr (mean age 79 yr) Sample Description: 34 patients who were permanent residents of a nursing home in the Northeast metropolitan

area. Averaging Time: 24 h Mean (SD) unit: 3.3 ppm Range (Min, Max): 1.8, 4.8 Copollutant: NR Increment: 10 ppm Regression Coefficients [Lower CI, Upper CI] Lags examined: 0 Lag 0: HF: 0.003 (-0.004 to 0.001) LF: 0.001 (-0.006 to 0.008) LF/HF: 0.001 (-0.005 to 0.002)



### January 2010 C-2

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Ibald-Mulli et al. (2004, 087415 ) Period of Study:

1998-1999

Location: Helsinki, Finland Erfurt, Germany Amsterdam, Netherlands Health Outcome: BP and HR via ECG Study Design: Panel Statistical Analyses: Linear regression Age Groups Analyzed: ≥ 50 yr Sample Description: 131 nonsmokers with coronary heart disease Averaging Time: 24 h Mean (SD) unit: Amsterdam: 0.6 mg/m 3 Erfurt: 0.4 mg/m 3 Helsinki: 0.4 mg/m 3 Range (Min, Max): Amsterdam: 0.4, 1.6 Erfurt: 0.1, 2.5 Helsinki: 0.1, 1.0 Copollutant: Amsterdam PM 2.5 : r = 0.58 μg/m 3 NO 2 : r = 0.76 μg/m 3 SO 2 : r = 0.50 mg/m 3 UFP: r = 0.22 n/cm 3 ACP: r = 0.60 n/cm 3 Erfurt PM 2.5 : r = 0.77 μg/m 3 NO 2 : r = 0.86 μg/m 3 SO 2 : r = 0.68 mg/m 3 UFP: r = 0.72 n/cm 3 ACP: r = 0.78 n/cm 3 Helsinki PM 2.5 : r = 0.40 μg/m 3 NO 2 : r = 0.32 μg/m 3 SO 2 : r = 0.19 mg/m 3 UFP: r = 0.35 n/cm 3 ACP: r = 0.51 n/cm 3 Increment: NR RR Estimate [Lower CI, Upper CI] Lags examined: 0, 1, 2, 3 Results presented graphically

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

Location: Forsyth County, NC; Selected suburbs of Minneapolis, MN; Jackson, MI Health Outcome: Heart rate & various rates of HRV. Study Design: Cohort Statistical Analyses: Linear regression Age Groups Analyzed: 45-64 yr (mean 62 yr) Sample Description: 6,784 study subjects from the atherosclerosis risk in communities study Averaging Time: 24 h Mean (SD) unit: 0.65 ppm (0.44) Range (Min, Max): NR Copollutant: NR Increment: 0.44 ppm Regression coefficients Lags examined: 1 Lag 1: HF (log transformed): -0.033 LF (log transformed): 0.006 SDNN: -0.274 Heart 

# r ate (bpm): 0.404* Confidence 

# i ntervals 

# : not recorded *p < 0.05



### January 2010 C-3

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Min (2009, 199514 ) Period of Study: December 2003 – January 2004

Location: Tae-in island community in South Korea Health Outcome: HRV Study Design: Panel Statistical Analyses: Time-lag model Age Groups Analyzed: 20-87 Sample Description: 986 subjects, 367 with metabolic syndrome (MetS), 619 without MetS Averaging Time: 8 h Mean (SD) unit: 0.454 ppm (0.560) Range (Min, Max): 0.100, 7.200 ppm Copollutant: PM 10 Increment: NR Estimated % Increase in subjects with MetS [Lower CI, Upper CI] Lags examined: 0-1, 1-2, 2-3, 3-4, 4-5, 5-6 Single pollutant: Lag 0-1: Log(SDNN): -0.29 (-0.59, 0.00), p < 0.1 Log(LF): -0.34 (-1.02, 0.33) Log(HF): -0.67 (-1.41, 0.08) 

# , p < 0.1 Lag 1-2: Log(SDNN): -0.45 (-0.81, -0.10), p < 0.05 Log(LF): -0.65 (-1.46, 0.17) Log(HF): -1.04 (-1.94, -0.14), p < 0.05 Lag 2-3: Log(SDNN): -0.28 (-0.57, 0.02), p < 0.1 Log(LF): -0.19 (-0.87, 0.48) Log(HF): -0.82 (-1.57, -0.07), p < 0.05 Lag 3-4: Log(SDNN): -0.18 (-0.47, 0.10) Log(LF): -0.14 (-0.80, 0.51) Log(HF): -0.46 (-1.19, 0.27) Lag 4-5: Log(SDNN): -0.20 (-0.49, 0.09) Log(LF): -0.36 (-1.04, 0.31) Log(HF): -0.42 (-1.17, 0.33) Lag 5-6: Log(SDNN): 0.13 (-0.18, 0.44) Log(LF): 0.50 (-0.21, 1.20) Log(HF): -0.03 (-0.81, 0.76) Co-pollutant (with PM 10 ): Lag 0-1: Log(SDNN): -0.25 (-0.56, 0.05) Log(LF): -0.35 (-1.04, 0.31) Log(HF): -0.67 (-1.44, 0.10), p<0.1 Lag 1-2: Log(SDNN): -0.48 (-0.88, -0.09), p<0.05; Log(LF): -0.72 (-1.63, 0.18); Log(HF): -1.09 (-2.09, -0.09), p<0.05 Lag 2-3: Log(SDNN): -0.35 (-0.67, -0.03), p < 0.05 Log(LF): -0.17 (-0.90, 0.56) Log(HF): -0.78 (-1.59, 0.03), p < 0.1 Lag 3-4: Log(SDNN): -0.22 (-0.55, 0.11) Log(LF): -0.11 (-0.86, 0.63) Log(HF): -0.34 (-1.17, 0.49) Lag 4-5: Log(SDNN): -0.18 (-0.48, 0.12); Log(LF): -0.21 (-0.89, 0.48); Log(HF): -0.37 (-1.14, 0.40) Lag 5-6: Log(SDNN): 0.17 (-0.14, 0.49) Log(LF): 0.54 (-0.18, 1.25) Log(HF): 0.00 (-0.80, 0.80) No significant results for subjects without MetS.



### January 2010 C-4

### Study Design Concentrations CO Effect Estima tes (95% CI)

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

Location: Boston, MA Health Outcome: Various measures of HRV via ECG Study Design: Panel/Cohort Statistical Analyses: Linear regression Age Groups Analyzed: 21-81 yr Sample Description: 497 men from the normat ive aging study in Greater Boston area Averaging Time: 24 h Mean (SD) unit: 0.50 ppm Range (Min, Max): 0.13, 1.8 Copollutant: NR Increment: 0.24 ppm % Change in HRV [Lower CI, Upper CI] Lags examined: 4-h ma, 24-h ma, 48-h ma Lag 4-h ma: SDNN (Log10): 2.0 (-2.9 to 7.3) HF (Log10): 8.8 (-4.6 to 24.1) LF(Log10): 3.2 (-7.0 to 14.6) LF:HF(Log10): -5.1 (-13.5 to 4.1) Lag 24-h ma: SDNN (Log10): -2.2 (-7.7 to 3.6) HF (Log10): -13.2 (-25.4 to 1.0) LF(Log10): -0.6 (-11.9 to 12.1) LF:HF(Log10): 14.5 (2.9-27.5) Lag 48-h ma: SDNN(Log10): -3.4 (-10.2 to 3.9) HF (Log10): -13.8 (-.28.9 to 4.4) LF (Log10): -2.4 (-16.2 to 13.6) LF:HF (Log10): 13.2 (-1.1 to 29.6)

Author: Peters et al. (1999, 011554 ) Period of Study: 1984-1985

Location: Augsburg, Germany Health Outcome: Heart rate Study Design: Cohort Statistical Analyses: Linear regression (GEE) Age Groups Analyzed: 25-64 yr Sample Description: 2681 men and women who participated in the MONICA study Averaging Time: 24 h Mean (SD) unit: During air pollution episode: 4.54 mg/m 3 Outside air pollution episode: 4.51 mg/m 3 Range (Min, Max): During air pollution episode: 2.39, 6.85 Outside air pollution episode: 0.91, 11.51 Copollutant: NR Increment: 6.6 mg/m 3 Mean Change in Heart Rate (beats/min) [Lower CI, Upper CI] Lags examined: 0, 5-day avg

All Lag 0: 0.97 (0.02-1.91) Lag 5-day avg: 0.70 (-0.09 to 1.48) Men Lag 0: 0.95 (-0.37 to 2.27) Lag 5-day avg: 0.91 (-0.25 to 2.07) Women Lag 0: 0.98 (-0.37 to 2.34) Lag 5-day avg: 0.52 (-0.55 to 1.59)

Author: RiojasRodriguez et al. (2006, 156913 ) Period of Study: December 2001-April 2002

Location: Mexico City, Mexico Health Outcome: Various measures of HRV via Holter system Study Design: Panel Statistical Analyses: Linear regression (mixed effects models) Age Groups Analyzed: 25-76 yr (mean 55 yr) Sample Description: 30 patients from the Outpatient Clinic of the National Institute of Cardiology of Mexico Averaging Time: 24 h Mean (SD) unit: 2.9 ppm (personal monitor) Range (Min, Max): 0.1, 18.0 Copollutant: NR Increment: 1 ppm Regression Coefficients [Lower CI, Upper CI] Lags examined (per min): 5, 10 Lag 5 min: HF: -0.006 (-0.023 to 0.010) LF: -0.024 (-0.041 to -0.007) VLF: -0.034 (-0.061 to -0.007) Notes: VLF = Very low frequency

Author: Schwartz et al. (2005, 074317 ) Period of Study: 1999

Location: Boston, MA Health Outcome: Measures of HRV via Holter system Study Design: Panel Statistical Analyses: Linear regression (hierarchical model) Age Groups Analyzed: 61-89 yr Sample Description: 28 subjects living at or near an apartment complex located on the same street as the Harvard School of Public Health Averaging Time: 24 h Mean (SD) unit: NR Range (Min, Max): ppm 25th = 0.38; 75th = 0.54 Copollutant: correlation PM 2.5 : r = 0.61 NO 2 : r = 0.55 SO 2 : r = -0.18 O 3 : r = 0.21 Increment: 0.16 ppm % Change in HRV [Lower CI, Upper CI] Lags examined: 24 h, 1 h Lag 1 h: SDNN: -2.6 (-5.6 to 0.5); rMSSD: -3.9 (-10.6 to 3.3); PNN50: -3.5 (-13.7 to 8.0); LF:HF: 4.5 (-1.2 to10.5) Lag 24 h: SDNN: -4.2 (-0.6 to -7.7); rMSSD: -10.2 (-2.4 to -17.4); PNN50: -14.8 (-3.0 to -25.2); LF:HF: 6.2 (-0.6 to 13.4)



### January 2010 C-5

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Tarkiainen et al. (2003, 053625 ) Period of Study: October 1997-May 1998

Location: Kuopio, Finland Health Outcome: Various measures of HRV via Ambulatory ECG (Holter system) Study Design: Panel Statistical Analyses : ANOVA for repeated errors (GLM) Age Groups Analyzed: 55-68 yr Sample Description: 6 male patients with angiographically- verified CAD Averaging Time: 24 h Mean (SD) unit: 4.6 ppm (max of CO episode) (personal monitoring) Range (Min, Max): 0.5, 27.4 (max of CO episode) Copollutant: NR Increment: NR RR Estimate [Lower CI, Upper CI] Lags examined: 5 min prior to CO episode, 5 min during CO episode CO had no statically significant effect on NN, SDNN or rMSSD. However, during high CO exposure (>2.7 ppm), CO was associated with an increase in rMSSD of 2.4ms (p=0.034).

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

Location: 3 Cities in Europe: Amsterdam, Netherlands; Erfert, Germany; Helsinki, Finland Health Outcome: Stable CAD: Various measures of HRV via ambulatory ECG (Holter system) Study Design: Panel Statistical Analyses: Linear regression (mixed model) Age Groups Analyzed: Mean age across 3 cities; 64-71 yr. Sample Description: 131 subjects with stable CAD followed for 6 mo with biweekly clinical visits. Averaging Time: 24 h Mean (SD) unit: Amsterdam: 0.6 mg/m 3 Erfert: 0.4 mg/m 3 Helsinki: 0.4 mg/m 3 Range (Min, Max): Amsterdam: 0.4, 1.6 Erfert: 0.1, 2.5 Helsinki: 0.1, 1.0 Copollutant: correlation Amsterdam: PM 2.5 : r = 0.58 NO 2 : r = 0.76

Erfert: PM 10 : r = 0.77 NO 2 : r = 0.86

Helsinki: PM 10 : r = 0.40 NO 2 : r = 0.32 Increment: 1 mg/m 3 Regression co-efficient [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3, 5-day avg

SDNN: Lag 0: -1.21 (-4.44 to 2.03); Lag 1: -1.71 (-6.05 to 2.63); Lag 2: -5.69 (-10.7 to -0.72); Lag 3: 0.66 (-3.83 to 5.15); 5-day avg: -3.60 (-9.88 to 2.68) HF: Lag 0: 5.0 (-15.1 to 25.1); Lag 1: -2.0 (-37.1 to 33.1); Lag 2: -30.7 (-59.8 to -1.5); Lag 3: -9.3 (-35.8 to -17.3); 5-day avg: -15.2 (-53.0 to 22.6) LF/HF: Lag 0: -3.6 (-21.8 to 14.5); Lag 1: -28.6 (-52.0 to -5.3); Lag 2: -10.1 (-36.9 to 16.7); Lag 3: 7.7 (-16.5 to 31.9); 5-day avg: -16.9 (-51.2 to 17.3)

Author: Wheeler et al. (2006, 088453 ) Period of Study: 1999-2000

Location: Atlanta, GA Health Outcome: Various measures of HRV via Holter system Study Design: Panel Statistical Analyses: Linear regression (mixed effects models) Age Groups Analyzed: Mean 65 yr;IQR 55-73 yr Sample Description: 18 subjects with COPD and 12 subjects with recent MI. Averaging Time: 1 h Mean (SD) unit: 362.0 ppb Range (Min, Max): 25th = 221.5; 75th = 398.1 Copollutant: correlation PM 2.5 : r = 0.43 Increment: NR RR Estimate [Lower CI, Upper CI] ; lag: Lags examined (h ma): 1, 4, 24 No CO results reported.



### January 2010 C-6

### Study Design Concentrations CO Effect Estima tes (95% CI)

ONSET OF CARDIAC ARRHYTHMIA

Author: Berger et al. (2006, 098702 ) Period of Study: October 2000-April 2001

Location: Erfurt, Germany Health Outcome: Runs of supraventricular and ventricular tachycardia recorded via 24-h ECG. Study Design: Panel Statistical Analyses: Poisson regression (GAM) linear regression Age Groups Analyzed: 52-76 yr (mean 76 yr) Sample Description: 57 men with CHD Averaging Time: 24 h Mean (SD) unit: 0.52 mg/m 3 Range (Min, Max): 0.11, 1.93 Copollutant: correlation NR Increment: All: 0.27 mg/m 3 5-day avg: 0.22 mg/m 3 RR Estimate [Lower CI, Upper CI] Lags examined (h): 0, 0-23, 24-47, 48-71, 72-95, 5-day avg Supraventricular extrasystoles: Lag 0: 1.18 (1.00-1.38) Lag 0-23: 1.16 (1.02-1.31); Lag 24-47: 1.13 (1.00-1.28); Lag 48-71: 1.18 (1.03-1.36); Lag 72-95: 1.08 (0.98-1.20); 5-day avg: 1.18 (1.04-1.35) Mean % Change [Lower CI, Upper CI] Hourly Lags examined: 0, 0-23, 24-47, 48-71 , 72-95, 5-day avg Ventricular extrasystoles: Lag 0: 0.0 (-4.1 to 4.4); Lag 0-23: 1.1 (-3.3 to 5.7); Lag 24-47: 1.9 (-2.6 to 6.6); Lag 48-71: 4.2 (-0.3 to 8.9); Lag 72-95: 2.7 (-1.3 to 6.9); 5-day avg: 3.0 (-1.8 to 8.0)

Author: Dockery et al. (2005, 078995 ) Period of Study: 1995-2002

Location: Boston, MA Health Outcome: Tachyarrhythmias: Study Design: Panel Statistical Analyses: Logistic regression (GEE) Age Groups Analyzed: 19-90 yr; mean 64 yr Sample Description: 203 cardiac patients with ICDs within 40km of air monitoring site at Harvard School of Public Health, Boston Averaging Time: 24 h Mean (SD) unit: NR Range (Min, Max): 25th = 0.53; 75th = 1.02 Copollutant: NR Increment: 0.48 ppm OR for Ventricular Arrhythmia [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3 Lag 2-day ma: 1.14 (0.95-1.29) Among those who had an arrhythmia: within 3 days: 1.65 (1.17-2.33) later than 3 days: 1.04 (0.83-1.29)

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

Location: Atlanta, GA Health Outcome: Cardiac arrhythmia, ICD, ventricular tachyarrhythmia Study Design: Panel Statistical Analyses: Logistic regression (GEE) Age Groups Analyzed: 15-88 yr Sample Description: 518 patients with ICDs with at least one ventricular tachya rrhythmic event Averaging Time: 1 h Mean (SD) unit: 1.7 ppm Range (Min, Max): 0.1, 7.7 Copollutant: NR Increment : 1 ppm

O R for Tachyarrhythmic event [Lower CI, Upper CI] Lags examined (days): 0

Results for all events Lag 0: 0.999 (0.970-1.028) Events resulting in cardiac pacing or defibrillation Lag 0: 1.008 (0.964-1.054) Events resulting defibrillation Lag 0: 1.012 (0.925-1.10.7)



### January 2010 C-7

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Peters et al. (2000, 011347 ) Period of Study: 1995-1997

Location: Eastern Massachusetts Health Outcome: Defibrillated discharges for ventricular tachycardia or fibrillation Study Design: Panel Statistical Analyses: Conditional logistic regression Age Groups Analyzed: Mean 62 yr Sample Description: 100 patients with ICDs Averaging Time: 24 h Mean (SD) unit: 0.58 ppm Range (Min, Max): 25th = 0.43; 75th = 0.66 Copollutant: correlation

PM 10 : r = 0.51 PM 2.5 : r = 0.56 NO 2 : r = 0.71 SO 2 : r = 0.41 O 3 : r = -0.40 Increment: 0.65 ppm (Lags 0, 1, 2, 3); 0.42 ppm (Lag 5-day mean) OR for Defibrillated Discharge [Lower CI, Upper CI] Lags examined (days): 0, 1, 2 ,3, 5-day mean At least one discharge: Lag 0: 1.07 (0.62-1.86); Lag 1: 1.06 (0.61-1.85); Lag 2: 1.05 (0.62-1.77); Lag 3: 0.09 (0.65-1.83); Lag 5-day mean: 1. 23 (0.71- 2.12) At least 10 discharges: Lag 0: 1.12 (0.54-2.32); Lag 1: 1.13 (0.54-2.33); Lag 2: 1.62 (0.85-3.09); Lag 3: 1.98 (1.05-3.72); Lag 5-day mean: 1.94 (1.01-.75)

Author: Rich et al. (2004, 055631 ) Period of Study: February-December 2000

Location: Vancouver, Canada Health Outcome: Cardiac arrhythmia via patients ICD Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: 15-85 yr Sample Description: 34 patients who experienced at least 1 ICD discharge (8,201 person days) Averaging Time: 24 h Mean (SD) unit: 553.8 ppb Range (Min, Max): IQR: 162.7 Copollutant: correlation PM 10 : r = 0.40 SO 2 : r =0.75 NO 2 : r =0.68 O 3 : r = -0.56 Increment: NR RR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3 No significant effect (results not reported in table).

Author: Rich et al. (2005, 079620 ) Period of Study: 1995-1999

Location: Boston, MA Health Outcome: Ventricular arrhythmias via ICD Study Design: Panel/Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 203 patients with implanted ICD at the New England Medical Center Averaging Time: 1 h and 24 h Mean (SD) unit: NR Range (percentiles): 1 h: 25th = 0.46 75th = 1.04

24 h: 25th = 0.52 75th = 1.03 Copollutant: NR Increment: 0.56 ppm; 0.54; 0.51; 0.49 respectively for results shown below OR Estimate [Lower CI, Upper CI] Ventricular arrythmia Hours prior to event: 0-2: 1.01 (0.87-1.18) 0-6: 1.00 (0.85-1.17) 0-23: 1.03 (0.84-1.25) 0-47: 1.11 (0.88-1.40)

Author: Rich et al. (2006, 089814 ) Period of Study: 2001 & 2002

Location: St. Louis, MO Health Outcome: Ventricular arrhythmia Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 60 subjects with at least 1 ICD recorded arrhythmia who lived within 40 km of St. Louis – Midwest supersite. Averaging Time: 24 h Mean (SD) unit: NR Range (Min, Max): 25th = 0.4; 75th = 0.6 Copollutant: NR Increment: 0.2 ppm OR for Ventricular Arrhythmia [Lower CI, Upper CI] Lags examined: 0 to 23-h ma: 0- to 23-h ma: 0.99 (0.80-1.21)



### January 2010 C-8

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Rich et al. (2006, 088427 ) Period of Study: 1995-1999

Location: Boston, MA Health Outcome: ICD episode of atrial fibrillation Study Design: Panel/case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 203 patients with ICDs at the New England Medical Center Averaging Time: 1 h and 24 h Mean (SD) unit: NR Range (Min, Max): 1 h: 25th = 0.46; 75th = 1.04

24 h: 25th = 0.52; 75th = 1.03 Copollutant: NR Increment: Lag (hrs) 0: 0.58 ppm Lag (hrs) 0-23: 0.51 ppm

OR for e pisode of a trial f ibrillation [Lower CI, Upper CI] Lags (h): 0, 0-23 Lag 0: 0.87 (0.56-1.37) Lag 0-23: 0.71 (0.39-1.28)

Author: Sari et al. (2008, 190315 ) Period of Study: June 2007

Location: Gaziantep, Turkey Health Outcome: P-wave dispersion (predictors of atrial fibrillation, ventricular arrhythmias and sudden death) via ECG Study Design: Case control Statistical Analyses: Pearson correlation analysis Age Groups Analyzed: Barbecue workers mean age: 33.66 ± 9.43 yr Control group mean age: 35.15 ± 6.78 yr Sample Description: 48 healthy males working at various indoor barbecue restaurants for at least 3 yr (avg:15.6 ± 7.1 yr), 51 age-matched healthy men for control group Averaging Time: NR Mean (SD) unit: COHb%

Indoor barbecue workers: 6.48% ± 1.43 Control Group: 2.19% ± 1.30 Range (Min, Max): NR Copollutant: NR Increment: NR Correlation coefficient for COHb [p-value] Lags examined: NR Pmin: -0.132 (0.245) Pmax: 0.215 (0.057) Pd: 0.315 (0.005) QTmin: 0.080 (0.454) QTmax: 0.402 (<0.001) QTd: 0.573 (<0.001) cQTd: 0.615 (<0.001)

Author: Sarnat et al. (2006, 090489 ) Period of Study: 24 wk during the summer and fall of 2000

Location: Steubenville, OH Health Outcome: Arrhythmia via ECG measurements Study Design: Panel Statistical Analyses: Logistic regression Age Groups Analyzed: 53-90 yr (mean age 71) Sample Description: 32 nonsmoking older adults Averaging Time: 24 h Mean (SD) unit: 0.02 ppm Range (Min, Max): -0.1, 1.5 Copollutant: correlation PM 2.5 : r = 0.45 SO 2 : r = 0.62 NO 2 : r = 0.66 O 3 : r = -0.37 Increment: 0.2 ppm

RR Estimate [Lower CI, Upper CI] ; lag: Lags examined (days): 1, 2, 3, 4, 5, 5-day ma Lag 5-day ma: Supraventricular ectopy SVE: 0.99 (0.76-1.29) Ventricular ectopy VE: 1.05 (0.75-1.46)

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

Location: Vancouver, Canada Health Outcome: Cardiac arrythmia via patients with ICD Study Design: Panel Statistical Analyses: Logistic regression (GEE) Age Groups Analyzed: Range from 12-77 yr (mean age 53 yr) Sample Description: 50 patients who experienced 1 or more arrhythmia event during the 4yr Averaging Time: 24 h Mean (SD) unit: 0.6 ppm Range (Min, Max): 0.3, 1.6 Copollutant: correlation PM 10 : r = 0.43 SO 2 : r = 0.62 NO 2 : r = 0.74 O 3 : r = -0.52 Increment: 0.2 ppm

RR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3 No significant effect for CO (results shown in plots)



### January 2010 C-9

### Study Design Concentrations CO Effect Estima tes (95% CI)

CARDIAC ARREST

Author: Levy et al. (2001, 017171 ) Period of Study: 1988-1994

Location: Seattle, WA Health Outcome: Out-of-hospital primary cardiac arrest Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: 25-75 yr Sample Description: 362 cases Averaging Time: 24 h Mean (SD) unit: 1.79 ppm Range (Min, Max): 0.52, 5.92 Copollutant: correlation PM 10 : r = 0.81 SO 2 : r = 0.29 Increment: NR

RR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1 Lag 1: 0.99 (0.83-1.18)

Author: Sullivan et al. (2003, 043156 ) Period of Study: 1985-1994

Location: Washington State Health Outcome: Out-of-Hospital cardiac arrest Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 1,542 members of a large health maintenance organization Averaging Time: 24 h Mean (SD) unit: 1.92 ppm Range (Min, Max): 0.52, 7.21 Copollutant: NR Increment: 1.02 ppm

OR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2 Lag 0: 0.95 (0.85-1.05) Lag 1: 0.97 (0.87-1.08) Lag 2: 0.99 (0.89-1.11)



### MYOCARDIAL INFARCTION

Author: Peters et al. (2001, 016546 ) Period of Study: 1995-1996

Location: Boston, MA Health Outcome: Onset of MI Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 772 participants Averaging Time: 24 h Mean (SD) unit: 1.09 Range (percentiles): ppm 5th = 0.49 95th = 1.78 Copollutant: NR Increment: 2 H-1 ppm; 24 h – 0.6 ppm

OR Estimate [Lower CI, Upper CI]

Onset of MI: 2-h prior: 1.22 (0.89-1.67) 24 h prior: 0.98 (0.70-1.36)

Author: Rosenlund et al. (2006, 089796 ) Period of Study: 1992-1994

Location: Stockholm, Sweden Health Outcome: MI Study Design: Case control Statistical Analyses: Logistic regression Age Groups Analyzed: 45-70 yr Sample Description: 1,397 cases;1,870 controls Averaging Time: Mean (SD) unit: 66.8 μg/m 3 (Estimated 30-yr residential exposure) Range (percentiles): 5th = 13.9; 95th = 295.7 Copollutant: NR Increment: 300 μg/m 3

OR Estimate [Lower CI, Upper CI] ; lag: Estimated 30-yr avg exposure All cases: 1.04 (0.89-1.21) Nonfatal cases: 0.98 (0.82-1.16) Fatal cases: 1.22 (0.98-1.52) In-hospital death: 1.16 (0.89-1.51) Out-of-hospital death: 1.36 (1.01-1.84)

Author: Rosenlund et al. (2009, 190309 ) Period of Study: NR

Location: Stockholm County, Sweden Health Outcome: Fatal and nonfatal MI Study Design: Case control Statistical Analyses: Various multiple regression models Age Groups Analyzed: 15-79 yr Sample Description: 43,275 MI cases during 1985-1996; 511,065 controls Averaging Time: 1 yr Mean (SD) unit:

Cases: 64.2 μg/m 3

Controls: 55.8 μg/m 3 Range (percentiles): Cases: 5th = 7.3; 95th =267.4 Controls: 5th =6.1;95th=261.8 Copollutant: PM 10 , NO 2 Increment: NR

OR Estimate [Lower CI, Upper CI] 5-yr avg exposure All subjects (n = 301,273) All cases: 1.01 (0.97-1.05) Nonfatal cases: 0.94 (0.89-1.00) Fatal cases: 1.14 (1.07-1.21) In-hospital death: 1.00 (0.91-1.10) Out-of-hospital death: 1.23 (1.14-1.32) Restriction to subjects who did not move between population census ( n = 80,155) All cases: 1.04 (0.94-1.14) Nonfatal cases: 0.96 (0.87-1.06) Fatal cases: 2.03 (1.59-2.60) In-hospital death: 2.04 (1.35-3.08) Out-of-hospital death: 2.03 (1.50-2.74)



### January 2010 C-10

### Study Design Concentrations CO Effect Estima tes (95% CI)

CHANGES IN BLOOD PRESSURE

Author: Ibalde-Mulli et al. (2001, 016030 ) Period of Study: 1984-1985

Location: Augsburg, Germany Health Outcome: BP–SPB Study Design: Cohort Statistical Analyses: Gaussian regression for repeated measures Age Groups Analyzed: 25-64 yr Sample Description: 2,607 men and women 25-64 yr Averaging Time: 24 h Mean (SD) unit: 4.1 mg/m 3 Range (Min, Max): 1.7, 8.2 Copollutant: NR Increment: Lag 0: 5.6 mg/m 3

5-day prior avg Mean Change [Lower CI, Upper CI] SPB mmHg Lag 0 (days): All: 0.53 (-0.66 to 1.72); M en: 0.68 (-0.94 to 2.31); Women: 0.51 (-1.31 to 2.19) 5-day prior avg: All: 1.06 (-0.17 to 2.29); Men: 0.92 (-0.87 to 2.70); Women: 0.91 (-0.87 to 2.70)

Author: Zanobetti et al. (2004, 087489 ) Period of Study: 1999-2001

Location: Boston, MA Health Outcome: BP Study Design: Cohort/Panel Statistical Analyses: Random effects Age Groups Analyzed: 39-90 yr Sample Description: 62 subjects with 631 total visits Averaging Time: 1 h and 120 h avg Mean (SD) unit: Same h: 0.81 ppm 120-h avg: 0.66 ppm Range (Min, Max): Same h: 10th = 0.48; 90th = 1.22 120-h avg: 10th = 0.48; 90th = 0.86 Copollutant: NR Increment: NR

RR Estimate [Lower CI, Upper CI] CO had no significant effect on BP



### CHANGES IN BLOOD MARKERS OF COAGULATION AND INFLAMMATION

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

Location: Milan, Italy Health Outcome: Prothrombin time (PT) and activated partial throm boplastin time (APTT) Study Design: Panel Statistical Analyses: GAMS Age Groups Analyzed: 11-84 yr (mean 43 yr) Sample Description: 1,218 healthy individuals who were partners or friends of patients with thrombosis who attended the thrombosis center of the University of Milan. Averaging Time: 1 h Mean (SD) unit: NR Range (percentiles): Sept-Nov: 25th = 1.36; 75th = 3.52 Dec-Feb: 25th = 2.00; 75th = 4.31 Mar-May: 25th = 1.03; 75th = 2.14 Jun-Aug: 25th = 0.73; 75th = 1.58 Copollutant: NR Increment: NR Regression co-efficient [Lower CI, Upper CI] Lags examined (time of blood sampling – avg): 0, 7, 30

PT: Lag 0: -0.11 (-0.18 to -0.05); Lag 7: -0.07 (-0.14 to 0.01); Lag 30: -0.05 (-0.13 to 0.02) APTT: Lag 0: 0.03 (-0.04 to 0.10); Lag 7: 0.04 (-0.04 to 0.11); Lag 30: 0.06 (-0.01 to 0.14) Notes: CO had no effect on fibrinogen, functional antithrombin, functional pr otein C, protein C antigen, functional protein S, or free protein S for all lag periods.



### January 2010 C-11

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Delfino et al. (2008, 156390 ) Period of Study:

2005-2006

Location: Los Angeles, CA Health Outcome: Biomarkers of systemic inflammation Study Design: Panel Statistical Analyses:

Linear mixed-effects models Age Groups Analyzed:

≥ 65 yr (mean 85.7 yr) Sample Description: 29 nonsmoking subjects with history of CAD living in retirement communities Averaging Time: 24 h Mean (SD) unit: 0.78 ± 0.30 ppb Range (Min, Max): 0.22, 1.97 Copollutant (Outdoor): EC: r = 0.84 OC: r = 0.69 OCprimary: r = 0.73 NO 2 : r = 0.78 O 3 : r = -0.35 PM 0.25 : r = 0.84 PM 0.25-2.5 : r = 0.14 PM 2.5-10 : r = 0.51 Increment: NR

Estimated coefficient Relationship to outdoor air pollutants: CRP (ng/mL): Lag 0: 847.52 ; 3-day avg: 728.79; 9- day avg: 236.51 IL-6 (pg/mL): Lag 0: 0.52; 3-day avg: 0.51; 9-day avg: 0.50 sTNF-RII (pg/mL): Lag 0: 154.05; 3-day avg: 139.45; 9-day avg: 225.60 Relationship to indoor air pollutants: CRP (ng/mL): Lag 0: 695.39 ; 3-day avg: 527.37; 9- day avg: 760.15 IL-6 (pg/mL): Lag 0: 0.54; 3-day avg: 0.47; 9-day avg: 0.77 sTNF-RII (pg/mL): Lag 0: 114.22; 3-day avg: 107.95; 9-day avg: 273.38 Relationship of sP-selction (ng/mL) to: Indoor air pollutants: Lag 0: 0.77; 5-day avg: 1.40; 9-day avg: 2.19 Outdoor air pollutants: Lag 0: 0.84; 5-day avg: 1.23; 9-day avg: 4.29 Relationship of Cu, Zn-SOD (U/g Hb) to: Indoor air pollutants: Lag 0: -145.54; 5-day avg: -238.72; 9-day avg: -70.10 Outdoor air pollutants: Lag 0: -105.73; 5-day avg: -176.72; 9-day avg: -41.92



### January 2010 C-12

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Delfino et al. (2009, 200844 ) Period of Study: JulmidOct and midOct-Feb of 2005-2006 and 2006-2007

Location: Los Angeles, CA Health Outcome: Biomarkers of inflammation Study Design: Panel Statistical Analyses : Linear mixed effects models adjusted for confounders Age Groups: 65+ (84.1 ± 5.60) yr Sample Description: 60 subjects with confirmed CAD history, nonsmoker, unexposed to environmental tobacco smoke Averaging Time: 24 h Mean (SD) unit: 0.50 (0.25) ppm Range (min, max): 0.11, 1.30 Copollutant: NO 2 , NO X , O 3 , PM 0.25 , PM 0.25-2.5 , PM 2.5-10 , EC, OC, BC, OCpri, SOC, PN/cm 3 Increment: NR Regression coefficients (95% CI) Subjects with pos itive responses: Cu,Zn-SOD (U/g Hb): 1-day avg: 1441 (97, 2786), 3-day avg: 2634 (1416, 3854), 5-day avg: 4227 (2078, 6376), 7-day avg: 3474 (914, 6034), 9-day avg: 2954 (737, 5172) GPx-1 (U/g HB): 1-day av g: -0.97 (-4.45, 2.50), 3-day avg: -2.21 (-6.48, 2.06), 5-day avg: 4.71 (-2.90, 12.33), 7-day avg: 4. 20 (-3.29, 11.68), 9-day avg: 4.76 (-1.58, 11.10) Subjects with negative responses: Cu,Zn-SOD (U/g Hb): 1-day avg: -195 (-338, -52), 3-day avg: -242 (-399, -85) , 5-day avg: -242 (-440, -44), 7-day avg: -315 (- 664, 34), 9-day avg: -176 (-508, 156) GPx-1 (U/g HB): 1-day av g: -0.82 (-1.55, -0.08), 3-day avg: -0.85 (-1.66, -0.04), 5-day avg: -0.84 (-1.88, 0.21), 7-day avg: -1.04 (-2.85, 0.78), 9-day avg: -0.47 (-2.19, 1.26) All subjects: IL-6 (pg/mL): 1-day avg.: 0.35 (0.17, 0.54), 3-day avg.: 0.40 (0.20, 0.61), 5- day avg.: 0.54 (0.27, 0.80), 7-day avg.: 0.34 (-0.06, 0.74), 9-day avg.: 0.31 (- 0.07, 0.70) P-selectin (ng/mL): 1-day avg.: 3.33 (0.94, 5.73), 3-day avg.: 3.65 (1.02, 6. 29), 5-day avg.: 5.28 (1.86, 8.70), 7-day avg.: 11.2 (5.3 9, 17.0), 9-day avg.: 10.4 (4.83, 16.0) TNF-RII (pg/mL): 1-day av g: 112 (13, 211), 3-day avg: 136 (29, 243) , 5-day avg: 229 (88, 371), 7-day avg: 132 (-86, 349), 9-day avg: 220 (19, 421)

TNF- α (pg/mL): 1-day avg: 0. 05 (-0.05, 0.16), 3-day avg: 0.09 (-0.03, 0.20), 5- day avg: 0.14 (-0.01, 0.29), 7-day avg: 0.07 (-0.19, 0.33) , 9-day avg: 0.14 (-0.11, 0.39) CRP (ng/mL): 1-day avg: 780 (343, 1217), 3-day avg: 739 (255, 1222), 5-day avg: 1117 (485, 1749), 7-day avg: 126 (-800, 1052) , 9-day avg: 41 (-840, 923) SOD (U/g Hb): 1-day avg: -62 (-231, 108), 3-day avg: -53 (-244, 138), 5-day avg: -37 (-285, 211), 7-day avg: 98 (-314, 509), 9-day avg: 208 (-173, 590) GPx-1 (U/g Hb): 1-day avg: -0.69 (-1.41, 0.03), 3-day avg: -0.69 (-1.48, 0.11), 5-day avg: -0.56 (-1.60, 0.48), 7-day avg: -0.56 (-2. 34, 1.21), 9-day avg: 0.05 (-1.63, 1.72) Effect modification by medication use: TNF-RII (pg/mL): 1-day av g: All subjects: 125 (11, 239), Statins: 48 (-105, 201), No Statins: 199 (47, 352); 3-day avg: A ll subjects: 161 (39, 283), Statins: 1 (-170, 171), No Statins: 306 (141, 472) ; 5-day avg: All subjects: 257 (100, 413) , Statins: 15 (-210, 240), No Statins: 445 (240, 649); 7- dayay avg: All subjects: 176 (-68, 419), Statins: 43 (-297, 382), No Statins: 283 (-23, 589); 9-dayay avg: 265 (41, 489), Statins: 160 (-158, 478), No Statins: 355 (65, 646) sP-selectin (ng/mL): 1-day avg: All subjects: 1.84 (-0.62, 4.30), Clopidogrel: 0.00 (-2.80, 2.81), No Clopidogrel: 1.72 (-0.42, 3.86); 3-day avg: All subjects: 1.90 (-0.79, 4.60), Clopidogrel: -0.67 (-3.95, 2.60), No Clopidogrel: 1.60 (-0.76, 3.96); 5-day avg: All subjects: 2.97 (-0.47, 6.41), Clopidogrel: -0.18



### January 2010 C-13

### Study Design Concentrations CO Effect Estima tes (95% CI) (-4.38, 4.01), No Clopidogrel: 3.04 (0.06, 6.01); 7-day avg: All subjects : 6.74 (0.75, 12.73), Clopidogrel: 2.24 (-4.22, 8.71), No Clopidogrel: 6.78 (1.60, 3.96); 9-day avg: A ll subjects: 6.96 (1.20, 12.72), Clopidogrel: 2.0 (-4.40, 8.48), No Clopidogrel: 5.54 (0.46, 10.6)

Author: Liao et al. (2005, 088677 ) Period of Study: 1996-1998

Location: Forsyth County, NC; Selected suburbs of Minneapolis, MN; Jackson, MI Health Outcome: Various measures of hemostasis/ inflammation Study Design: Cohort Statistical Analyses: Linear regression Age Groups Analyzed: 45-64 yr Sample Description: 10,208 subjects from the Atherosclerosis Risk in Communities Study Averaging Time: 24 h Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NR Increment: 0.6 ppm Regression coefficients [SE] Lags examined (days): 1 Lag 1: Fibrinogen (mg/dL): -0.16 (0.67) Factor VIII –C (%): 0.45 (0.42) vWF %: -0.29 (0.50) WBC (x 103/mm3): 0.003 (0.017) Albumin (g/dL): -0.018 (0.003)** ** p < 0.01

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

Location: Athens, Greece; Augsberg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; Stockholm, Sweden Health Outcome: Plasma Interleukin-6 (IL6), Fibrinogen Study Design: Panel/Field Statistical Analyses: Linear Mixed Effects Model Age Groups Analyzed: 35-80 yr (mean = 62.2 yr) Sample Description: 955 subjects who had experienced MI between 4 mo and 6 yr before start of the study Averaging Time: 24 h Mean (SD) unit:

Individual cities: 0.29-1.48 mg/m 3

Mean for all cities: 0.78 mg/m 3 Range (percentiles): 25th = 0.56; 75th = 0.90 (for mean of all cities) Copollutant: (mean for all cities)

NO 2 : r = 0.69 PM 10 : r = 0.47 PM 2.5 : r = 0.55 PNC: r = 0.67 Increment: 0.34 mg/m 3 Change of IL-6 % of overall mean per IQ range increase Genotypes: 1 1, 1 2, 2 2

IL6 rs2069832 1 1: 2.0 (0.3, 3.6); 1 2: -0.2 (-1.7, 1.3); 2 2: -2.0 (-4.7, 0.8); p-value: 0.03

IL6 rs2069840 1 1: 2.0 (0.3, 3.8); 1 2: 0.4 (-0.9, 1.7); 2 2: -1.2 (-3.4, 1.1); p-value: 0.04

IL6 rs2069845 1 1: 1.9 (0.2, 3.5); 1 2: -0.1 (-1.5, 1.4); 2 2: -1.6 (-4.3, 1.2); p-value: 0.31

FGA rs2070011 1 1: 1.0 (-0.7, 2.7); 1 2: 0.7 (0.6, 2.0); 2 2: 0.4 (-1.9, 2.7); p-value: 0.64

FGB rs1800790 1 1: -0.2 (-1.8, 1.3); 1 2: 2.1 (0.4, 3.8); 2 2: 4.5 (1.1, 8.0); p-value: 0.02

Author: Pekkanen et al. (2000, 013250 ) Period of Study: 1991-1993

Location: London, England Health Outcome: Fibrinogen Study Design: Cohort Statistical Analyses: Logistic regression Age Groups Analyzed: 35-55 yr Sample Description: 7,205 office workers Averaging Time: 8 h Mean (SD) unit: 1.4 mg/m 3 Range (Min, Max): Min = NR, Max = 9.9 Copollutant correlation: PM 10 : r = 0.57 NO 2 : r = 0.81 SO 2 : r = 0.61 O 3 : r = -0.45 Increment: 1.6 mg/m 3 % Change in fibrinogen concentration [p value] ; Lags examined: 0, 1, 2, 3 Lag 0: 1.43 (<0.01); Lag 1: 1.49 (<0.01); Lag 2: 1.59 (<0.01); Lag 3: 1.26 (<0.01) OR for having Fibrinogen above 3.19 g/l [p value] Lags examined : 0, 1, 2, 3 Lag 0: 1.17 (0.05); Lag 1: 1.09 (0.31); Lag 2: 1.14 (0.11); Lag 3: 1.22 (<0.01)



### January 2010 C-14

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Ruckerl et al. (2006, 088754 )

Period of Study: 2000-2001

Location: Erfert, Germany Health Outcome: Blood markers of inflammation and coagulation Study Design: Panel Statistical Analyses: Linear and logistic regression (fixed effects) Age Groups Analyzed: 51-76 yr (mean = 66 yr) Sample Description: 57 male patients with CHD Averaging Time: 24 h Mean (SD) unit: 0.52 mg/m 3 Range (Min, Max): 0.11, 1.93 Copollutant correlation: NO 2 : r = 0.82 Increment: 0.27 mg/m 3

OR Estimate for blood marker >90th percentile [Lower CI, Upper CI] Lags examined (h): 0-23, 24-47, 48-71, 5-day avg CRP (C-reactive protein) 0-23: 0.9 (0.7-1.2); 24-47: 1.0 (0.7-1.5); 48-71: 1.5 (1.1-2.1); 5-day avg 1.1 (0.8-1.6) ICAM-1 (Intercellular adhesion molecule 1) 0-23: 0.8 (0.6-1.0); 24-47: 1.5 (1.2-1.9); 48-71: 1.7 (1.3-2.3); 5-day avg 1.2 (1.0-1.6) % of change from the mean of blood marker vWF (von Willebrand factor antigen) 0-23: 4.4 (1.4- 7.5); 24-47: 2.7 (-0.8 to 6.1); 48-71: 2.0 (-1.7 to 5.8); 5-day avg: 4.9 (1.0-8.8) FVII (Factor VII) 0-23: -1.4 (-3.8 to 1.1); 24-47: -2.6 (-4.8 to 0.3); 48-71: -2.8 (-5.1 to -0.4); 5-day avg: -3.0 (-5.5 to -0.4)

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

Location: 6 cities across Europe: Athens, Greece; Augsburg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; Stockholm, Sweden Health Outcome: Interleukin-6, C-reactive protein, Fibrinogen Study Design: Panel/Cohort Statistical Analyses: Linear regression (mixed effects) Age Groups Analyzed: 37-81 yr Sample Description: 1,003 MI survivors who had at least 2 valid repeated blood samples Averaging Time: 24 h Mean (SD) unit: Athens: 1.48 mg/m 3 Augsburg: 0.58 mg/m 3 Barcelona: 0.59 mg/m 3 Helsinki: 0.31 mg/m 3 Rome: 1.40 mg/m 3 Stockholm: 0.29 mg/m 3 Range (Min, Max): NR Copollutant: NR Increment: 0.34 mg/m 3 % Change in mean [Lower CI, Upper CI] Lags examined: 0, 1, 2, 5-day avg (Pooled estimates) Interleukin-6 Lag 0: 0.57 (-0.63 to 1.79) Lag 1: 0.44 (-0.79 to 1.68); Lag 2: -2.36 (-4.82 to 0.17) 5-day avg: -0.28 (-2.53 to 2.02) C-reactive protein Lag 0: -0.01 (-1.72 to 1.73 Lag 1: -1.51 (-3.30 to 0.32) Lag 2: -2.35 (-6.84 to 2.36); 5-day avg: -0.85 (-.5.37 to 3.90) Fibrinogen Lag 0: 0.24 (-0.54 to 0.92) Lag 1: 0.32 (-0.35 to 1.00); Lag 2: -0.44 (-1.11 to 0.23) 5-day avg: 0.12 (-0.81 to 1.05)



### January 2010 C-15

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Rudez et al. (2009, 193783 ) Period of Study: January 2005-December 2006

Location: Rotterdam, the Netherlands Health Outcome: Platelet aggregation, thrombin generation, Fi brinogen, C-reactive protein Study Design: Panel Statistical Analyses: Linear regression Age Groups Analyzed: Mean = 41 yr Sample Description: 40 healthy individuals Averaging Time: 24 h Median (SD) unit: 333 μg/m 3 Range (percentiles): 25th = 276; 75th = 412 Copollutant: PM 10 : r >0.6 NO: r >0.6 NO 2 : r >0.6 O 3 : -0.4 ≥ r ≥ -0.6 Increment: NR Estimated Changes [Lower CI, Upper CI] Platelet Aggregation Parameters Maximal Platelat Aggregation: D0-6: -3.6 (-9.3, 2.1); D0-12: -4.7 (-11.0, 1.5); D0-24: -2.6 (-7.9, 2.7); I24-48: -1.1 (-7.2, 4.9); I48-72: 8.4 (2.5, 14.3); I72-96: -0.1 (-5.1, 5.0); D+I0-96: 9.5 (1.6, 17.4) Late Aggregation: D0-6: 10.5 (0.8, 20.3); D0-12: 11.6 (1.2, 21.9); D0-24: 11.2 (1.4, 21.0); I24-48: 7.5 (-2.2, 17.1); I48-72: 18.1 (8.4, 27.8); I72-96: 4.2 (-5.5, 13.9); D+I0-96: 20.4 (8.4, 32.4)

Thrombin Generation ETP D0-6: -1.51 (-3.7, 0.80); D0-12: -1.1 (-3.4, 1.1); D0-24: -1.5 (-3.9, 0.9); I24-48: -0.7 (-3.4, 2.0); I48-72: 0.8 (-1.9, 3.4); I72-96: 3.5 (0.8, 6.2); D+I0-96: 0.8 (-2.7, 4.3)

Peak D0-6: -2.5 (-6.3, 1.3) D0-12: -1.9, (-5.7, 1.9); D0-24: -3.3 (-7.3, 0.7); I24-48; -1.3 (-6.1, 3.6); I48-72: -0.5 (-5.0, 4.0) I72-96: 3.8 (-0.8, 8.4) D+I0-96: -1.7 (-7.5, 4.2) Lag Time D0-6: 1.0 (-0.5, 2.5); D0-12: 1.0 (-0.5, 2.5); D0-24: 1.6 (0.1, 3.1); I24-48; 0.4 (-1.3, 2.2); I48-72: -1.0 (-2.7, 0.7); I72-96: -1.5 (-3.2, 0.2); D+I0-96: 0.1 (-2.1, 2.2) Inflammatory Markers Fibrinogen I24-48; 0.0 (-1.7, 1.8); I48- 72: 0.0 (-1.8, 1.9) I72-96: -0.1 (-1.9, 1.7)

CRP I24-48; 3.2 (-6.4, 12.8); I 48-72: -1.9 (-12.5, 8.7); I72-96: -4.5 (-15.3, 6.3)

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

Location: Tel Aviv, Israel Health Outcome: Various measures of inflammation sensitive biomarkers Study Design: Cohort Statistical Analyses: Linear regression Age Groups Analyzed: Mean = 46 yr Sample Description: 3,659 subjects living within 11 km of monitoring site Averaging Time: 24 h Mean (SD) unit: 0.8 ppm Range (percentiles): 25th = 0.7; 75th = 1.0 Copollutant: correlation PM 10 : r = 0.75 NO 2 : r = 0.857 SO 2 : r = 0.671 O 3 : r = -0.656 Increment: 0.3 ppm Regression co-efficient [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3, 4, 5, 6, 7, last wk avg Fibrinogen: Men Lag 0: -3.3 (-6.1 to -0.6); Lag 1: -2.6 (-5.5 to 0.4); Lag 2: -3.4 (-6.6 to -0.3); Lag 3: -3.4 (-6.5 to -0.2); Lag 4: -5.9 (-8.9 to -2.9); Lag 5: -4.7 (-7.8 to -1.6); Lag 6: -2.0 (-5.1 to 1.0); Lag 7: -2.7 (-5.7 to 0.2); Last wk avg: -7.7 (-12.1 to -3.3)

Notes: No effect on fibrinogen among women. CO had no effect on CRP among men and no effect on CRP and WBC among women for all Lag times examined.



### VARIOUS MEASURES OF CARDIOVASCULAR HEALTH

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

Location: Paris, France Health Outcome: Endothelial function, Reactive Hyperemia Study Design: Case-crossover Statistical Analyses: Multiple regression models Age Groups Analyzed: 18-35 yr Sample Description: 40 healthy white male nonsmokers Averaging Time: 24 h Mean (SD) unit: NR Range (Min, Max): NR Copollutant: PM 2.5 , PM 10 , NO, NO 2 , SO 2 Increment: NR β -Coefficient [Lower CI, Upper CI] Flow-mediated Brachial Artery Dilatation: -0.68 (-1.22, -0.15) Small Artery Reactive Hyperemia: 10.46 (1.73, 19.31)



### January 2010 C-16

### Study Design Concentrations CO Effect Estima tes (95% CI)

Author: Nautiyal et al. (2007, 190301 ) Period of Study: August 1999-May 2000

Location: Mandi Gobindgarh, India Morinda, India Health Outcome: Various measures of cardiovascular health via ECG (Minnesota Code) Study Design: Cross-sectional Statistical Analyses: NR Age Groups Analyzed: +15 yr Sample Description: 200 total survey participants (100/town) Averaging Time: NR Mean (SD) unit: NR Range (Min, Max):

Morinda Pure residential Site: 0-1 ppm GT Road Site: 2-3 ppm Mandi Gobindgarh Mixed Habitat Site: 0-3 ppm GT Road Site: 1-3 ppm

Co pollutant:

PM 2.5 , PM 10 , NO X , SO X Increment: NR

RR Estimate [Lower CI, Upper CI] Lags examined: NR No quantitative results presented

Author: Wellenius et al. (2007, 092830 ) Period of Study: February 2002-March 2003

L ocation: Boston, MA Health Outcome: Congestive heart failure Study Design: Cohort (retrospective) Statistical Analyses: Linear mixed models Age Groups Analyzed: 33-88 yr. Tai Chi Group mean age (n=14): 66 ± 13 yr. Control Group mean age (n=14): 63 ± 14 yr. Sample Description: 28 patients with CHF and impaired systolic function Averaging Time: 24 h Mean (SD) unit: 0.44 ppm Range (IQ): 0.20 ppm Copollutant: PM 2.5 : r = 0.35 NO 2 , SO 2 , O 3 , BC Increment: NR

RR Estimate [Lower CI, Upper CI] Lags examined: 0, 1, 2, 3 Results presented graphically



# Table C-2. Studies of CO exposure and cardio vascular hospital admissions and ED visits.

Study Design Concentrations CO Effect Esti mates (95% CI)

STROKE

Author: Chan et al. (2006, 090193 ) Period of Study: 1997-2002

Location: Taipei, Taiwan ED Visits

Health Outcome (ICD9): Cerebrovascular disease (430-437); Strokes (430-434); Hemorrhagic stroke (430-432); Ischemic stroke (433-434) Study Design: Time-series Statistical Analyses: GAM Age Groups Analyzed: All Sample Description: NR Averaging Time: 8 h Mean (SD) unit: 1.7 ppm Range (Min, Max): 0.6, 4.4 Copollutant: correlation O 3 : r = 0.30 SO 2 :r = 0.63 NO 2 : r = 0.77 PM 2.5 : r = 0.44 PM 10 : r = 0.47 Increment: 0.8 ppm

OR Estimate [Lower CI, Upper CI] Lags (days) examined 0, 1, 2, 3

Cerebrovascular disease: Lag 2, 1.03 (1.01, 1.06) Stroke: Lag 2, 1.03 (1.01, 1.05) Ischemic and Hemorrhagic stroke: not significant. Cerebrovascular 2 pollutant model: CO + O 3 : Lag 2, 1.03 (1.01-1.05) CO + PM 2.5 : Lag 2, 1.02 (1.00-1.04) CO + PM 10 : Lag 2, 1.03 (1.01-1.05)

Author: Henrotin et al. (2007, 093270 ) Period of Study: 1994-2004

Location: Dijon, France Health Outcome (ICD9 or ICD10): Stroke (Ischemic & Hemorrhagic) Study Design: Bidirectional case

crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: ≥ 40 yr Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 683 μg/m 3 Range (Min, Max): 0, 4014 Copollutant: NR Increment: 10 μg/m 3

OR Estimate [Lower CI, Upper CI] Lags (days) examined: 0, 1, 2, 3. Ischemic: Lag 0: 0.999 (0.997-1.001) Lag 1: 0.998 (0.997-1.001) Lag 2: 0.999 (0.998-1.001) Lag 3: 1.000 (0.998-1.001) Hemorrhagic: Lag 0: 1.000 (0.996-1.004) Lag 1: 1.001 (0.997-1.005) Lag 2: 0.999 (0.995-1.004) Lag 3: 0.998 (0.994-1.002) Also not significant w hen stratified by sex.



### January 2010 C-17

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Maheswaran et al. (2005, 090769 ) Period of Study: 1994-1998

Location: Sheffield, UK Health Outcome (ICD9 or ICD10): Stroke deaths (ICD9: 430-438); Stroke Hospital admissions (ICD10: I60-I69) Study Design: Ecological Statistical Analyses: Poisson regression Age Groups Analyzed: ≥ 45 yr Sample Description: 1,030 census districts Averaging Time: NR Mean (SD) unit: Quintiles Range (Min, Max): NR Copollutant: NR Increment: NR – Quintiles of exposure

RR Estimate [Lower CI, Upper CI] Adjusted for sex, age, deprevation, smoking. Quintiles: 2nd: 1.04 (0.94-1.16) 3rd: 1.01 (0.91-1.13) 4th: 1.10 (0.99-1.23) 5th: 1.11 (0.99-1.25) Adjusted for sex, age: 2nd: 1.11 (1.01-1.22) 3rd: 1.15 (1.04-1.27) 4th: 1.29 (1.17-1.42) 5th: 1.37 (1.24-1.52)

Author: Tsai et al. (2003, 080133 ) Period of Study: 1997-2000

Location: Kaohsiung, Taiwan Study Design: Case-crossover Health Outcome (ICD9 or ICD10):

Cerebrovascular diseases: ICD9: 430 to 438 (Subarachnoid hemorrhagic stroke 430, Primary intracerebral hemorrhage (PIH): 431-432, Ischem ic stroke (IS): 433-435). Statistical Analyses: NR Age Groups Analyzed: All Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 0.79 ppm Range (Min, Max): 0.24, 1.72 Copollutant: NR Increment: 0.8 ppm (IQR)

RR Estimate [Lower CI, Upper CI] Lag (days): 0-2 >20oC PIH: OR 1.21 (1.09-1.34) IS: OR 1.21 (1.14-1.28) <20oC PIH: OR 1.18 (0.80-0.72) IS: OR 1.77 (1.31-2.39)

Notes: 2-pollutant models: PIH results persisted when adjusting for SO 2 and O 3 IS results persisted when controlling for PM 10 , SO 2 and O 3 Author: Villeneuve et al. (2006, 090191 ) Period of Study: 1992-2002

Location: Edmonton, Canada ED Visits (within 5 hospitals) Health Outcome (ICD9): Stroke (430- 438); Ischemic (434-436) Hemorrhagic (430-432); Transient Ischemic Attack (435) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: 65+ yr Sample Description: 12,422 visits Averaging Time: 24 h Mean (SD) unit: 0.8 ppm Range (percentiles): 25th = 0.5; 75th = 1.0 Copollutant correlation: O 3 : r = -0.54 PM 2.5 : r = 0.43 PM 10 : r = 0.30 Increment: 0.5 ppm

OR Estimate [Lower CI, Upper CI] Lags (days) examined: 0, 1 & 0-2 Ischemic (April-Sept) Lag 0: 1.16 (1.00, 1.33) Lag 1: 1.17 (1.01, 1.36) Lag 0-2: 1.32 (1.09, 1.60)

Notes: - Not significant for a ll seasons or Oct-Mar. - Hemorrhagic: Not significant for all seasons or Oct- Mar, Apr-Sept. - Transient Ischemic At tack: Not significant for all seasons or Oct-Mar, Apr-Sept.

Author: Wellenius et al. (2005, 088685 ) Period of Study: NR

Location: 9 U.S. cities: Chicago, Detroit, Pittsburgh, Cleveland, Birmingham, New Haven, Seattle, Minneapol is, Salt Lake City ED Visits

Health Outcome: Stroke among Medicare beneficiaries: (Ischemic, hemorrhagic) Study Design: Time-series Statistical Analyses: Logistic regression Age Groups Analyzed: ≥ 65 yr Sample Description: 155,503 visits Averaging Time: NR Mean (SD) unit: NR Range (percentiles): 25th = 0.73; 50th = 1.02; 75th = 1.44 (ppm) Copollutant: correlation

PM 10 : r = 0.43 Increment: 0.71 ppm % Change [Lower CI, Upper CI] Lag: 0 Ischemic: 2.83 (1.23-4.46) Hemorrhagic: -1.61 (-4.79 to 1.68)



### January 2010 C-18

### Study Design Concentrations CO Effect Esti mates (95% CI)

ISCHEMIC HEART DISEASE

Author: D’Ippoliti et al. (2003, 074311 ) Period of Study: 1995-1997

Location: Rome, Italy Hospital Admissions Health Outcome (ICD9): MI (410) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: 18+ yr Sample Description: 6,531 patients. Averaging Time: 24 h Mean (SD) unit: 4.4 mg/m 3 Range (percentiles): 25th = 2.8; 75th = 4.3 Copollutant: correlation TSP: r = 0.35 SO 2 : r = 0.56 NO 2 : r = 0.31 Increment: 1 mg/m 3

OR Estimate [Lower CI, Upper CI] ; lag: Lags examined (days): 0, 1, 2, 3, 4, 0-2 Acute MI Lag 0: 1.021 (0.988-1.054) Lag 1: 1.020 (0.988-1.054) Lag 2: 1.033 (1.001-1.066) Lag 3: 1.010 (0.982-1.040) Lag 4: 1.025 (0.996-1.055) Lag 0-2: 1.044 (1.000- .089

Author: Hosseinpoor et al. (2005, 087413 ) Period of Study: 1996-2001

Location: Tehran, Iran Health Outcome: Angina Pectoris (ICD9: 413; ICD10: I20) Study Design: Time series Statistical Analyses: Poisson regression Age Groups Analyzed: All Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 10.8 mg/m 3 Range (Min, Max): 1.6, 57.8 Copollutant: NR Increment: 1 mg/m 3

RR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3 Lag 1: 1.00957 (1.00600-1.01315)

Author: Lanki et al. (2006, 089788 ) Period of Study: 1994-2000

Location: 5 European cities: Augsburg, Germany Barcelona, Spain Helsinki, Finland Rome, Italy Stockholm, Sweden Health Outcome: First AMI (ICD9: 410; ICD10: I21, I22) Study Design: Time series Statistical Analyses: Poisson regression (GAM) Age Groups Analyzed: 35+ yr Sample Description: 26,854 Hospital Admissions Averaging Time: 24 h Mean (SD) unit: NR Unit: mg/m 3 Range (percentiles): Augsburg, Germany 25th = 0.7; 75th = 1.1 Barcelona, Spain 25th = 0.6; 75th = 1.4 Helsinki, Finland 25th = 0.3; 75th = 0.5 Rome, Italy 25th = 1.7; 75th = 2.9 Stockholm, Sweden 25th = 0.3; 75th = 0.5 Copollutant: correlation PM 10 : r = 0.21 – 0.56 NO 2 : r = 0.43 – 0.75 O 3 : r = -.023 – 020 Increment: 0.2 mg/m 3

RR Estimate [Lower CI, Upper CI] ; lag: Lags examined: 0, 1, 2, 3 All 5 cities: Lag 0: 1.005 (1.000-1.010) Lag 1: 1.002 (0.996-1.007) Lag 2: 1.002 (0.997-1.007) Lag 3: 0.998 (0.992-1.003) 3 cities with Hospital Discharge Register(HDR): Lag 0: 1.007 (1.001-1.012) Lag 1: 1.002 (0.996-1.008) Lag 2: 1.003 (0.998-1.009) Lag 3: 1.004 (0.988-1.020)

3 cities with HDR – ≤ 75years Fatal: Lag 0: 1.027 (1.006-1.048) Lag 1: 1.021 (1.000-1.042) Lag 2: 1.018 (0.997-1.039) Lag 3: 1.015 (0.994-1.037)

Non-Fatal: Lag 0: 1.001 (0.995-1.008) Lag 1: 1.000 (0.994-1.007) Lag 2: 1.004 (0.998-1.011) Lag 3: 0.999 (0.992-1.006)

3 cities with HDR – ≥ 75years Fatal: Lag 0: 1.009 (0.992-1.006) Lag 1: 1.001 (0.985-1.018) Lag 2: 1.006 (0.990-1.023) Lag 3: 1.000 (0.983-1.017)

Non-Fatal: Lag 0: 1.015 (1.004-1.086) Lag 1: 1.006 (0.995-1.017) Lag 2: 0.995 (0.983-1.006) Lag 3: 0.998 (0.987-1.009)



### January 2010 C-19

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Lee et al. (2003, 095552 ) Period of Study: 1997-1999

Location: Seoul, Korea Study Design: Time-series Health Outcome (ICD9 or ICD10): Angina: ICD10: 120 AMI: ICD10: I21-I23 Other Acute IHDs: ICD10: I24 Statistical Analyses: Poisson regression, GAM Age Groups Analyzed: 64+ yr Sample Description: 822 days Averaging Time: Daily max Mean (SD) unit: 1.8 ppm Range (percentiles): 25th = 1.2 75th = 2.2 Copollutant: correlation PM 20 : 0.60 SO 2 : 0.81 NO 2 : 0.79 O 3 : -0.39 Increment: 1 ppm (IQR)

RR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3, 4, 5, 6 All yr: Lag 5: All ages: 0.94 (0.91 0.98) Lag 5: 64+ age: 1.07 (1.01-1.13)

Summer: Lag 5: All ages: 1.19 (1.02-1.38) Lag 5: 64+ age: 1.60 (1.27-2.03) 2-pollutant model: Lag 5: 64+ age: CO + PM 10 : 1.04 (0.98-1.11)

Author: Maheswaran et al. (2005, 090769 ) Period of Study:

1994-1998

Location: Sheffield, UK Emergency Hospital Admission Health Outcome (ICD9): CHD (410-414) Study Design: Ecological Statistical Analyses: Poisson regression Age Groups Analyzed: 45+ yr Sample Description: 11,407 Emergency Hospital Admissions for CHD in patients 45+ yr (within 1,030 census districts) Averaging Time: NR Mean (SD) unit: Quintiles Range (Min, Max): NR Copollutant: NR Increment: NA

RR Estimate [Lower CI, Upper CI] Lowest quintile reference category Adjusted for sex, age, deprivation, smoking: 2nd: 0.97 (0.89-1.07) 3rd: 0.94 (0.86-1.04) 4th: 0.96 (0.97-1.06) 5th: 0.88 (0.79- 0.98) Adjusted for sex, age: 2nd: 1.09 (1.00-1.19) 3rd: 1.15 (1.05-1.26) 4th: 1.19 (1.09-1.30) 5th: 1.20 (1.09-1.32)

Author: Mann et al. (2002, 036723 ) Period of Study: 1988-1995

Location: Southern California Health Outcome (ICD9): IHD (IHD) (410-414); M 

# I (410) Study Design: Time series Statistical Analyses: Poisson regression, GAM Age Groups Analyzed: All Sample Description: 54,863 IHD admissions among Southern California Kaiser- Permanente members (within 20km of monitor) Averaging Time: 8 h Mean (SD) unit: 2.07 ppm Range (Min, Max): 0.30, 11.8 Copollutant: correlation Ranging across 7 regions: NO 2 : r = 0.64, 0.86 O 3 : r = -0.37, 0.28 PM 10 : r = 0.15, 0.40 Increment: 1 ppm % Change [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 2 ma, 3 ma, 4 ma With arrythmia: Lag 0: 2.99 (1.80-4.99) Lag 1: 1.51 (0.37-2.66) Lag 2: 1.26 (0.15-2.38) 2 ma: 2.66 (1.40-3.94) 3 ma: 2.59 (1.27-3.92) 4ma: 2.25 (0.90-3.63) With CHF: Lag 0: 3.60 (1.620-5.63) Lag 1: 3.34 (1.48-5.22) Lag 2: 1.90 (0.11-3.72) 2 ma: 4.23 (2.13-6.37) 3 ma: 4.14 (1.96-6.37) 4 ma: 4.07 (1.81-6.38) Without secondary diagnosis: Lag 0: 1.62 (0.65-2.59) Lag 1: 1.45 (0.54-2.37) Lag 2: 0.92 (0.04-1.82) 2 ma: 1.83 (0.80-2.86) 3 ma: 1.79 (0.72-2.87) 4 ma: 1.82 (0.71-2.94)

Author: Szyszkowicz (2007, 193793 ) Period of Study: 1997-2003

Location: Montreal, Canada Study Design: Time-series Health Outcome (ICD9 or ICD10): ED Visits. IHD: ICD9: 410-414 Statistical Analyses: Poisson regression (GLMM) Age Groups Analyzed: All Sample Description: 4,979 ED Visits Averaging Time: 24 h Mean (SD) unit: 0.5 ppm Range (Min, Max): 0.1, 3.1 Copollutant: NR Increment: 0.2 ppm % Change [Lower CI, Upper CI] ; lag: Lags examined (days): 0, 1 All Patients: Lag 0: 5.4 (2.3-8.5) Males: Lag 0: 7.5 (3.6-11.6) Females: Lag 0: 2.7 (-2.0 to 7.6) Ages ≥ 64 All Patients: Lag 0: 4.9 (1.3-8.7) Males: Lag 0: 7.5 (2.6-12.6) Females: Lag 0: 2.4 (-3.0 to.0) Lag 1 not significant for all results



### January 2010 C-20

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: von Klot et al. (2005, 088070 ) Period of Study: 1992-2001

Location: 5 European cities: Augsburg, Germany Barcelona, Spain Helsinki, Finland Rome, Italy Stockholm, Sweden Health Outcome: Hospital cardiac (mi),angina, dysrythmia, heart failure) readmissions Study Design: Prospective Cohort Statistical Analyses: Poisson regression Age Groups Analyzed: All Sample Description: 22 

# , 006 survivors of first MI Averaging Time: 24 h

Unit: mg/m 3 Mean (SD) unit: Augsburg, Germany: 0.93 Barcelona, Spain: 1.00 Helsinki, Finland: 0.42 Rome, Italy: 2.21 Stockholm, Sweden: 0.43 Range (Min, Max): NR Copollutant: correlation PM 10 : r = 0.21 – 0.57 NO 2 : r = 0.44 – 0.75 O 3 : r = -.027 – 0.47 Increment: 0.2 mg/m 3 (0.172 ppm)

RR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3 Lag 0: MI:1.022 (0.998-.047) Angina: 1.009 (0.992-.02) Cardiac: 1.014 (1.001-.026)



### HEART FAILURE

Author: Lee et al. (2007, 090707 ) Period of Study: 1996-2004

Location: Kaohsiung City, Taiwan Hospital Admissions Health Outcome (ICD9): CHF (428) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 13,475 Hospital Admissions (63 Hospitals) Averaging Time: 24 h Mean (SD) unit: 0.76 ppm Range (Min, Max): 0.14, 1.72 Copollutant: NR Increment: 0.31 ppm

OR Estimate [Lower CI, Upper CI] Lag examined (days): 0-2 ≥ 25°C: 1.19 (1.09-1.31) <25°C: 1.39 (1.24-1.54) Adjusted for PM 10 : ≥ 25°C; 1.15 (1.04-1.27) <25°C; 1.21 (1.206-1.38) Adjusted for SO 2 : ≥ 25°C: 1.23 (1.11-1.36) <25°C: 1.39 (1.24-1.55) Adjusted for NO 2 : ≥ 25°C: 1.22 (1.08-1.39) <25°C: 0.94 (0.81-1.10) Adjusted for O 3 : ≥ 25°C: 1.17 (1.07-1.28) <25°C: 1.36 (1.22-1.51)

Author: Symons et al. (2006, 091258 ) Period of Study: 2002 (April-November)

Location: Johns Hopkins Bayview Medical Center, Baltimore, MD Hospital Admissions

Health Outcome: NR Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 398 Hospital Admissions for CHF Averaging Time: 24 h Mean (SD) unit: 0.4 ppm Range (Min, Max): 0.1, 1.0 Copollutant: NR Increment: 0.2 ppm

OR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3, cum 1, cum 2, cum 3 Lag 0: 0.86 (0.67-1.11) Lag 1: 0.90 (0.70-1.17) Lag 2: 0.96 (0.73-1.26) Lag 3: 0.88 (0.67-1.16) Cum. Lag1: 0.82 (0.60-1.13) Cum. Lag2: 0.80 (0.54-1.17) Cum. Lag3: 0.27 (0.46-1.14)

Author: Wellenius et al. (2005, 087483 ) Period of Study: 1987-1999

Location: Pittsburgh, PA Hospital Admissions Health Outcome (ICD9): CHF (428, 428.1) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: 65+ yr Sample Description: 54,019 Hospital Admissions among Medicare beneficiaries Averaging Time: 24 h Mean (SD) unit: 1.03 ppm Range (percentiles): 25th = 0.68; 75th = 1.23 Copollutant: correlation PM 10 : r = 0.57 NO 2 : r = 0.70 O 3 : r = -0.25 SO 2 : r = 0.54 Increment: 0.55 ppm % Change [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3 Lag 0: Single pollutant model: 4.55 (3.33-5.79) Adjusted for PM 10 : 5.18 (3.49-6.89) Adjusted for NO 2 : 4.84 (3.06-6.66) Adjusted for O 3 : 4.35 (3.08-5.64) Adjusted for SO 2 : 4.51 (3.15-5.90)



### January 2010 C-21

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Yang (2008, 157160 ) Period of Study: 1996-2004

Location: Taipei, Taiwan Hospital Admissions

Health Outcome: CHF Study Design: Case-crossover Statistical Analyses: NR Age Groups Analyzed: NR Sample Description: 24,240 CHF HA from 47 hospitals Averaging Time: 24 h Mean (SD) unit: 1.26 ppm Range (Min, Max): 0.12, 3.66 Copollutant: PM 10 , NO 2 , O 3 , SO 2 Increment: NR

OR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2 Single Pollutant Model Warm days (>20o C): 1.24 (1.16, 1.33) Cool days (<20o C): 1.05 (0.96, 1.15)

Two Pollutant Models Warm days ( ≥ 20 ° C) Adjusted for PM 10 : 1.16 (1.08, 1.26) Adjusted for NO 2 : 1.02 (0.92, 1.13) Adjusted for O 3 : 1.25 (1.17, 1.34) Adjusted for SO 2 : 1.32 (1.22, 1.42) Cool days (<20 ° C) Adjusted for PM 10 : 1.09 (0.97, 1.21) Adjusted for NO 2 : 1.07 (0.92, 1.25) Adjusted for O 3 : 0.89 (0.80, 0.99) Adjusted for SO 2 : 1.03 (0.92, 1.16)



### CARDIOVASCULAR DISEASES – NON-SPECIFIC

Author: Ballester et al. (2001, 013257 ) Period of Study: 1994-1996

Location: Valencia, Spain ED Visits

Health Outcome (ICD9: CVD (390- 459); Heart diseas es (410-414, 427, 428); cerebrovascular disease (430-438) Study Design: Time series Statistical Analyses: Poisson regression Age Groups Analyzed: All Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 6.2 mg/m 3 Range (Min, Max): 0.6, 17.8 Copollutant: correlation BS: r = 0.64 NO 2 : r = 0.03 SO 2 : r = 0.74 O 3 : r = -0.26 Increment: 1 mg/m 3

RR Estimate [Lower CI, Upper CI] ; lag: Lags examined (days): 0, 1, 2, 3, 4, 5 All cardiovascular: Lag 2: 1.0077 (0.9912-1.0138)

Heart Disease: Lag 1: 1.0092 (0.9945-1.0242)

Cerebrovascular Disease: Lag 1: 0.9874 (0.9646-1.0107)

Author: Ballester et al. (2006, 088746 ) Period of Study: 1995-1999

Location: 14 Cities in Spain Health Outcome (ICD9: All CVD (390-459);Heart diseases (410-414, 427, 428) Study Design: Time series Statistical Analyses: GAM Age Groups Analyzed: All Sample Description: NR Averaging Time: 8 h Mean (SD) unit: Range across 14 cities, 1.4-2.8 mg/m 3 Range (percentiles): 10th = 0.4-1.7; 90th = 2.0-3.9 Copollutant: NR Increment: 1 mg/m 3 % Change [Lower CI, Upper CI] Lags examined (days): 0-1 All CVD: Lag 0-1: 2.06 (0.65-3.48) Heart Disease: Lag 0-1: 4.15 (1.31-7.08)

Author: Barnett et al. (2006, 089770 ) Period of Study: 1998-2001

Location: Brisbane, Canberra, Melbourne, Perth, Sydney Australia Auckland & Christchurch, New Zealand Hospital Admissions with CVDs

Health Outcome (ICD9: Arrythmia (247); Cardiac Disease (390-429); Cardiac Failure (428); IHD (410-413); MI (410); Total CVD (390-459) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed : 15-64 yr & ≥ 65 yr Sample Description: NR Averaging Time: 8 h Mean (SD) unit: ppm Brisbane: 1.7 Canberra: 0.9 Melbourne: 1.0 Perth: 1.0 Sydney: 0.8 Auckland: 2.1 Christchurch: 0.5 Range (Min, Max): ppm Brisbane: 0.0, 7.0 Canberra: 0.0, 5.8 Melbourne: 0.1, 8.0 Perth: 0.1, 4.0 Sydney: 0.0, 4.5 Auckland: 0.2, 7.9 Christchurch: 0.0, 5.4 Copollutant NR Increment: 0.9 ppm % Change [Lower CI, Upper CI] Lags examined (days): 0-1 15-64 yr Arrythmia: 2.5 (0.1-4.9) Cardiac: 1.7 (0.5-2.9) Cardiac Failure: 4.2 (0.6-7.8) IHD: 1.6 (-0.6 to 3.9) MI: 1.8 (-0.7 to 4.3) Total CVD: 1.2 (0.3-2.1) ≥ 65 yr Arrythmia: 0.1 (-1.8 to 2.1) Cardiac: 2.8 (1.3-4.4) Cardiac Failure: 6.0 (3.5-8.5) IHD: 2.3 (0.9-3.8) MI: 2.9 (0.8-4.9) Total CVD: 2.2 (0.9-3.4)



### January 2010 C-22

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Bell et al. (2009, 193780 ) Period of Study: 1999-2005

Location: 126 U.S. urban counties Hospital Admissions with CVDs Health Outcome (ICD9): Cardiac failure (428); cerebrovascular events (430- 438); heart rhythm disturbances (426- 427); ihd (410-414,429); peripheral vascular disease (440-448) Study Design: Time series Statistical Analyses: Log-linear overdispersed Poisson regression Age Groups Analyzed: ≥ 65 yr Sample Description: >9.3 million Medicare subjects Averaging Time: 1 h Mean (SD) unit : 1.6 ppm Median (SD) unit: 1.3 ppm Median Range (Min, Max): 0.2, 9.7 Copollutant: PM 2.5 : r = 0.26 NO 2 : r = 0.56 EC: r = 0.48 Increment: 1 ppm % Change [Lower CI, Upper CI] Lags examined (days): 0-2

Lag 0: Single pollutant model: 0.96 (0.79-1.12) Adjusted for PM 2.5 : 0.76 (0.57-0.96) Adjusted for NO 2 : 0.55 (0.36-0.74) Adjusted for EC: 0.97 (0.38-1.57)

Author: Chang et al. (2005, 080086 ) Period of Study: 1997-2001

Location: Taipei, Taiwan Health Outcome (ICD9): CVD Hospital Admissions (410-429) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 74,509 CVD hospital admissions (47 Hospitals) Averaging Time: 24 h Mean (SD) unit: 1.37 ppm Range (Min, Max): 0.37, 3.66 Copollutant: NR Increment: 0.49 ppm

OR Estimate [Lower CI, Upper CI] Lag examined (days): 0-2 ≥ 20°C: 1.090 (1.064-1.118) <20°C: 0.984 (0.927-1.044) Adjusted for PM 10 : ≥ 20°C: 1.171 (1.132-1.211) <20°C: 0.946 (0.892-1.003) Adjusted for SO 2 : ≥ 20°C: 1.232 (1.194-1.272) <20°C: 1.098 (1.034-1.165) Adjusted for NO 2 : ≥ 20°C: 1.048 (1.003-1.095 <20°C: 0.983 (0.914-1.058) Adjusted for O 3 : ≥ 20°C: 1.196 (1.161-1.232) <20°C: 1.092 (1.031-1.157)

Author: Filhol. (2008, 190260 ) Period of Study: January 2001-July 2003

Location: Sao Paulo, Brazil ED Visits Health Outcome (ICD10): Hypertension and Cardiac Ischemic Disease (I10-I25) Study Design: Time series Statistical Analyses: Linear Poisson regression models Age Groups Analyzed: >18 yr Sample Description: 45,000 Cardiovascular emergency room visits from diabetic and non-diabetic patients (tertiary referral teaching hospital) Averaging Time: 8 h Mean (SD) unit: 2.7 ppm Range (Min, Max): 0.7, 12.1 Copollutant: correlation PM 10 : r = 0.69 NO 2 : r = 0.58 SO 2 : r = 0.52 O 3 : r = 0.07 Increment: 1.2 ppm Regression Coefficients [SEM] Lags examined (days): 0, 1, 2

CVD Visits/Diabetes: Lag 0: 0.0575 (0.0410) Lag 1: - 0.0056 (0.0418) Lag 2: -0.0324 (0.0426) 2-day moving avg: 0.0324 (0.0470) 3-day moving avg: 0.0074 (0.0528) 4-day moving avg: -0.0025 (0.0582)

CVD Visits/Non-Diabetes: Lag 0: 0.0286 (0.0095) Lag 1: 0.0098 (0.0091) Lag 2: 0.0102 (0.0089) 2-day moving avg: 0.0271 (0.0108) 3-day moving avg: 0.0281 (0.0120) 4-day moving avg: 0.0306 (0.0131)

Author: Fung et al. (2005, 074322 ) Period of Study: 1995-2000

Location: Windsor, Ontario, Canada Hospital Admissions of CVDs Health Outcome (ICD9): CHF (428); IHD (410-414); dysrythmias (427) Study Design: Time series Statistical Analyses: GLM Age Groups Analyzed: All Sample Description: 11,632 Cardiac hospital admissions Averaging Time: 24 h Mean (SD) unit: 1.3 ppm Range (Min, Max): 0.0, 11.8 Copollutant: correlation PM 10 : r = 0.21 NO 2 : r = 0.38 SO 2 : r = 0.16 O 3 : r = 0.10 Increment: 1.2 ppm % Change [Lower CI, Upper CI] Lags examined (days): 0, 0-1, 0-2 <65 yr Lag 0: -3.1 (-7.4 to 1.4) Lag 0-1: -2.7 (-8.1 to 3.0) Lag 0-2: -0.5 (-6.7 to 6.0) ≥ 65 yr Lag 0: 0.5 (-2.2 to 3.3) Lag 0-1: 2.3 (-1.1 to 5.9) Lag 0-2: 2.8 (-1.1 to 7.0)



### January 2010 C-23

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Jalaludin et al. (2006, 189416 ) Period of Study:

1997-2001

Location: Sydney, Australia ED Visits Health Outcome (ICD9): All cardiovascular (390-459); cardiac disease (390-429) ; IHD (410-413); cerebrovascular or stroke (430-438) Study Design: Time series Statistical Analyses: GLM & GAM Age Groups Analyzed: 65+ yr Sample Description: NR Averaging Time: 8 h Mean (SD) unit: 0.82 ppm Range (Min, Max): 0.02, 4.63 Copollutant: correlation PM 10 : r = 0.31 NO 2 : r = 0.71 SO 2 : r = 0.51 O 3 : r = 0.19 Increment: 0.69 ppm % Change [Lower CI, Upper CI] Lags examined (days): 0, 1, 2, 3, 0-1 All Cardiovascular: Lag 0: 2.32 (1.45-3.19) Lag 1: 1.33 (0.47-2.20) Lag 0-1: 2.35 (1.39-3.32) Cardiac Disease: Lag 0: 2.52 (1.50-3.54) Lag 1: 1.85 (0.83-2.88) Lag 2: 1.11 (0.0-2.15) Lag 0-1: 2.85 (1.71-4.01) IHD: Lag 0: 2.83 (1.22-4.48) Lag 1: 1.58 (0.01-3.19) Lag 0-1: 2.86 (1.07-4.68) Stroke: No results were significant for Stroke.

All CVD: Cool period: Lag 0: 3.26 (2.00-4.53) Cardiac Disease: Cool period: Lag 0: 3.43 (1.95-4.93) IHD: Cool period: Lag 0: 3.64 (1.28-6.06) Warm period: Lag 0: 2.29 (0.01-4.62) Stroke: Cool period: Lag 0: 3.54 (0.78-6.37)

Notes: Cool: May to October Warm: November to April

Author: Koken et al. (2003, 049466 ) Period of Study: 1993-1997

Location: Denver, CO Hospital Admissions for CVD Health Outcome (ICD9: MI (410- 410.92); coronary atherosclerosis (414-414.05); pulmonary heart disease (416-416.9); cardiac dysrythmia (427-427.9); CHF (428) Study Design: Time series Statistical Analyses: GLM Age Groups Analyzed: >65 yr Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 0.9 ppm Range (Min, Max): 0.3, 1.6 Copollutant: correlation PM 10 : r = 0.25 NO 2 : r = 0.73 SO 2 : r = 0.21 O 3 : r = -0.40 Increment: 0.3 ppm % Change [Lower CI, Upper CI] Lags examined (days): 1, 2, 3, 4 CHF: Lag 3: 10.5 (0.1-22.0) CO not significantly associated with other Lag periods.

Author: Linn et al. (2000, 002839 ) Period of Study: 1992-1995

Location: Los Angeles, CA Health Outcome: Hospital Admissions for Cardiovascular, Cerebrovascular, Pulmonary. Study Design: Time series Statistical Analyses: Ordinary least squares regression; Poisson regression Age Groups Analyzed: >30 yr Sample Description: NR Averaging Time: 24 h Mean (SD) unit: Winter: 1.7; Spring: 1.0; Summer: 1.2; Fall: 2.1 Range (Min, Max): Winter: 0.5, 5.3; Spring: 0.4, 2.2; Summer: 0.3, 2.7; Fall: 0.2, 4.3 Copollutant: correlation Winter: PM 10 : r = 0.78; NO 2 : r = 0.89; O 3 : r = -0.43; Spring: PM 10 : r = 0.54; NO 2 : r = 0.92; O 3 : 0.29 Summer: PM 10 : r = 0.72; NO 2 : r = 0.94; O 3 : 0.03 Fall: PM 10 : r = 0.58; NO 2 : r = 0.84; O 3 : r = -0.36 Increment: 1 ppm Co-efficient [SE] Lags examined (lags): 0, 1 Lag 0: Cardiovascular All: 0.032 (0.003)* (e .g. 3.2% increase) Winter: 0.038 (0.006)* Spring: 0.010 (0.015) Summer: 0.035 (0.014)* Fall: 0.027 (0.006)* Cerebrovascular All: 0.009 (0.007) Winter: -0.008 (0.014) Spring: 0.107 (0.033)* Summer: 0.030 (0.033) Fall: 0.008 (0.012) MI All: 0.040 (0.009) * CHF All: 0.025 (0.009)* Cardiac Arrythmia All: 0.023 (0.009)* Stroke All: 0.044 (0.009)* Notes:* p < 0.05



### January 2010 C-24

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Metzger et al. (2004, 044222 ) Period of Study: 1993-2000

Location: Atlanta, GA ED Visits (from 31 hospitals) Health Outcome (ICD9: Cardiovascular: IHD (410-414); Ac ute MI (410); Dysrythmia (427); Cardiac Arrest (427.5); CHF (428); Peripheral Vascular & Cereberovascular Disease (PVCD) (433-437, 440, 443, 444, 451-453); Atherosclerosis (440); Stroke (436) Study Design: Case-crossover Statistical Analyses: Poisson regression (GLM) Age Groups Analyzed: All Sample Description: 4,407,535 visits Averaging Time: 1 h Median (SD) unit: 1.5 ppm Range (percentiles): 10th = 0.5; 90th = 3.4 Copollutant: correlation PM 10 : r = 0.47 NO 2 : r =0.68 SO 2 : r =0.26 O 3 : r =0.20 Increment: 1 ppm RR Estimate [Lower CI, Upper CI] Lags examined (days): 0-2ma All CVD: 1.017 (1.008-1.027) Dysrythmia: 1.012 (0.993-1.031) CHF: 1.010 (0.988-1.032) IHD: 1.016 (0.999-1.034) PVCD: 1.031 (1.010-1.052)

Author: Peel et al. (2007, 090442 ) Period of Study: 1993-2000

Location: Atlanta, GA ED Visits (from 31 hospitals) Health Outcome (ICD9: Cardiovascular: IHD (410-414); Dysrythmia (427); CHF (428); PVCD (433-4 37, 440, 443, 444, 451-453) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 4,407,535 visits Averaging Time: 1-h Mean (SD) unit: 1.8 ppm Range (SD): SD: 1.2 Copollutant: NR Increment: 1.2 ppm OR Estimate [Lower CI, Upper CI] Lags examined (days): 0-2ma IHD: Without Diabetes: 1.023 (1.004-1.420) Without CHF: 1.024 (1.006-1.042) Dysrythmias: With Hypertension: 1.065 (1.015-1.118) PVCD: With Hypertension: 1.038 (1.004-1.074) Without Hypertension: 1.027 (1.002-1.054) With Diabetes: 1.065 (1.012-1.121) Without Diabetes: 1.025 (1.003-1.048) With COPD: 1.113 (1.027-1.205) Without COPD: 1. 026 (1.004-1.047) Without CHF: 1.029 (1.008-1.051) With Dysrythmias: 1.072 (1.011-1.138) Without Dysrythmias: 1.026 (1.004-1.048) CHF: With COPD: 1.058 (1.003-1.115)

Author: Slaughter et al. (2005, 073854 ) Period of Study: 1995-2001

Location: Spokane, WA Health Outcome (ICD9: Cardiac Hospital Admissions: (390-459) Study Design: Time series Statistical Analyses: Poisson regression (GLM & GAM) Age Groups Analyzed: All Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 0.42-1.82 Range (Min, Max): NR Copollutant correlation: PM 10 : r = 0.32 PM 2.5 : r = 0.62 Increment: NR RR Estimate [Lower CI, Upper CI] ; lag: Lags examined (days): 1, 2, 3 No significant association. Results not reported.

Author: Tolbert et al. (2007, 090316 ) Period of Study: 1993-2004

Location: Atlanta, GA ED Visits (from 41 hospitals) Health Outcome (ICD9): IHD (410- 414), cardiac dysrhythmias (427), CHF (428), peripheral vascular and cerebrovascular diseases (433-437, 440, 443-445 and 451-453) Study Design: Time series Statistical Analyses: Poisson generalized linear model Age Groups Analyzed: NR Sample Description: 10,234,490 ED Visits (238,360 CVD group) Averaging Time: 1 h Mean (SD) unit: 1.6 ppm Range (Min, Max): 0.1, 7.7 Copollutant: PM 10 : r = 0.51 NO 2 : r =0.70 SO 2 : r =0.28 O 3 : r =0.27 PM 2.5 : r = 0.47 Increment: NR RR Estimate [Lower CI, Upper CI] Lags examined (days): 1, 2, 3 Single-Pollutant Model 3-day ma: 1.020 (1.010, 1.030) Results for multi-pollutant models presented graphically



### January 2010 C-25

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Yang et al. (2004, 094376 ) Period of Study: 1997-2000

Location: Kaohsiung City, Taiwan Health Outcome (ICD9: CVDs (410-429) Study Design: Case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Sample Description: 29,661 Cardiovascular hospital admissions (63 hospitals) Averaging Time: 24 h Mean (SD) unit: 0.79 ppm Range (Min, Max): 0.24, 1.72 Copollutant: NR Increment: 0.28 ppm OR Estimate [Lower CI, Upper CI] Lag examined (days): 0-2 ≥ 25°C: 1.264 (1.205-1.326) <25°C: 1.448 (1.357-1.545) Adjusted for PM 10 : ≥ 25°C: 1.206 (1.146-1.270) <25°C: 1.314 (1.213-1.423) Adjusted for SO 2 : ≥ 25°C: 1.406 (1.327-1.489) <25°C: 1.3450 (1.352-1.555) Adjusted for NO 2 : ≥ 25°C: 1.246 (1.166-1.332) <25°C: 0.905 (0.819-0.999) Adjusted for O 3 : ≥ 25°C: 1.250 (1.191-1.311) <25°C: 1.447 (1.356-1.545)



# Table C-3. Studies of CO exposure and neonatal and postneonatal outcomes.

Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Bell et al. (2007, 091059 ) Period of Study: 1999-2002

Location: Connecticut and Massachusetts Health Outcome: Birth weight and LBW Study Design: Retrospective cohort Statistical Analyses: Linear and logistic regression Age Groups Analyzed: NA Sample Description: 358,504 full-term live singleton births (32-44 wk) Averaging Time: 24 h Mean (SD) unit: 0.65 ppm (0.18) Range (Min, Max): NR Copollutant: NR Increment: Interquartile range – 0.30 ppm Regression co-efficient for birth weight (g) [Lower CI, Upper CI] Entire pregnancy: -16.2 (-19.7 to -12.6) Stratified by race. Black mother: -10.9 (-20.2 to -1.6) White mother: -17.5 (-21.3 to -13.7) OR for LBW [Lower CI, Upper CI] Entire pregnancy: 1.028 (0.983-1.074)

Author: Brauer et al. (2008, 156292 ) Period of Study: 1999-2004

Location: Vancouver, Canada Health Outcome: LBW, PTB and SGA Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 70,249 live singleton births Averaging Time: LUR model Mean (SD) unit: 633 μg/m 3 Range (Min, Max): 124, 1409 Copollutant: correlation: PM 10 : r = 0.73 NO 2 : r = 0.75 SO 2 : r = 0.82 O 3 : r = -0.39 Increment: 100 μg/m 3 OR for SGA [Lower CI, Upper CI] ; Entire pregnancy: 1.06 (1.03-1.08) OR for term LBW [Lower CI, Upper CI] ; Entire pregnancy: 1.02 (0.96-1.09) OR PTB [Lower CI, Upper CI] ; Entire pregnancy: 1.16 (1.01-1.33)

Author: Chen et al. (2002, 024945 ) Period of Study: 1991-1999

Location: Northern Nevada Health Outcome: Birth weight & LBW Study Design: Retrospective cohort Statistical Analyses: Linear and logistic regression Age Groups Analyzed: NA Sample Description: 39,338 full term live singleton births (37-44 wk) Averaging Time: 8 h Mean (SD) unit: 0.98 ppm Range (Min, Max): 0.25, 4.87 Copollutant: NR Increment: NR Regression co-efficient for birth weight (g) [SE]

Trimesters: First: -1.02 (6.68) Second: -0.07 (6.58) Third: -3.95 (6.76) Entire pregnancy: -8.28 (14.9)

Notes: CO not associated with LBW



### January 2010 C-26

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Conceicao et al. (2001, 016628 ) Period of Study: 1994-1997

Location: Sao Paulo, Brazil Health Outcome: Child mortality, under 5 yr of age Study Design: Time series Statistical Analyses: Poisson regression (GAM) Age Groups Analyzed: NA Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 4.4 ppm (2.2) Range (Min, Max): NR Copollutant: NR Increment: NR Regression co-efficient for Child mortality – under 5 yr of age [SE] ; Lags examined: 0, 1, 2, 3 Lag 2: 0.0306 (0.0076) (p < 0.01) Lag chosen for best fitting model

Author: Gilboa et al. (2005, 087892 ) Period of Study: 1997-2000

Location: Texas Health Outcome: Birth defects (heart defects and orofacial clefts) Study Design: Case control Statistical Analyses: Conditional Logistic regression Age Groups Analyzed: NA Sample Description: NR Averaging Time: NR Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NR Increment: Exposure categories (ppm):<0.4; 0.4 – 0.5; 0.5 – 0.7; >0.7 OR for Birth Defects [Lower CI, Upper CI] ; Exposure period: wk 3 to 8 of pregnancy

Conotruncal defects: 1.00; 1.38 (0.97-1.97); 1.17 (0.81-1.70); 1.46 (1.03-2.08) Tetralogy of Fallot: 1.00; 0.92 (0.52-1.62); 1.27 (0.75-2.14); 2.04 (1.26-3.29) Notes: CO was not associated with the following defects: Aortic artery and valve, atrial septal, pulmonary artery and valve, ventricular septal, endocardial cushion and mitral valve , cleft lip, cleft palate, aortic valve stenos is, coarctation of the aorta, ostium secundum.

Author: Gouveia et al. (2004, 055613 ) Period of Study: 1997

Location: Sao Paulo, Brazil Health Outcome: Birth weight & LBW Study Design: Retrospective cohort Statistical Analyses: Linear and logistic regression Age Groups Analyzed: NA Sample Description: 179,460 live singleton term births (>37 wk) Averaging Time: 8 h Mean (SD) unit: 3.7 ppm Range (Min, Max): 1.1, 11.4 Copollutant: NR Increment: 1 ppm Regression co-efficient for birth weight (g) [Lower CI, Upper CI]

Trimesters: First: -23.1 (-41.3 to -4.9) Second: 3.2 (-18.2 to 24.5) Third: 1.9 (-18.2 to 22.0) OR for LBW ) [Low er CI, Upper CI] 4th quartile exposure (compa red to lowest quartile): First: 1.02 (0.82-1.27); Se cond: 1.07 (0.88-1.30); Third: 0.93 (0.76-1.12)

Author: Ha et al. (2001, 019390 ) Period of Study: 1996-1997

Location: Seoul, South Korea Health Outcome: LBW Study Design: Retrospective cohort Statistical Analyses: Logistic regression (GAM) Age Groups Analyzed: NA Sample Description: 276 763 full-term live singleton births (>37 wk) Averaging Time: 24 h Mean (SD) unit: NR Range (Min, Max): Percentiles: 25th: 0.99 ppm 75th: 1.41 ppm Copollutant correlation: TSP: r = 0.73 NO 2 : r = 0.75 SO 2 : r = 0.82 O 3 : r = -0.39 Increment: 0.42 ppm RR for LBW [Lower CI, Upper CI]

Trimesters: First: 1.08 (1.04, 1.12) Third: 0.91 (0.87, 0.96)

Author: Ha et al. (2003, 042552 ) Period of Study: 1995-1999

Location: Seoul, South Korea Health Outcome: Post-neonatal mortality (1 mo-1 yr) (also looked at older age groups) Study Design: Time series Statistical Analyses: Poisson regression (GAM) Age Groups Analyzed: NA Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 1.2 ppm Range (Min, Max): 0.39, 3.38 Copollutant correlation: PM 10 : r = 0.63 NO 2 : r = 0.72 SO 2 : r = 0.75 O 3 : r = -0.46 Increment: 0.57 ppm RR for Post–neonatal mortality (1 mo-1 yr) [Lower CI, Upper CI] Lags examined: 0 Total mortality: Lag 0: 1.020 (0.976-1.067) Respiratory mortality: Lag 0: 1.388 (1.009-1.911)



### January 2010 C-27

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Hajat et al. (2007, 093276 ) Period of Study: NR

Location: Birmingham, Bristol, Leeds, Liverpool, London, Manchester, Middlesbrough, Newcastle, Nottingham, Sheffield England Health Outcome: Neonatal and postneonatal mortality Study Design: Time series Statistical Analyses: Poisson regression (GLM) Age Groups Analyzed: NA Sample Description: 22,288 total infant deaths between 1990 and 2000 Averaging Time: 3 days Mean (SD) unit: (mg/m 3 ) Birmingham: 0.64; Bristol: 1.01; Leeds: 0.73; Liverpool: 0.51; London: 0.77; Manchester: 0.63; Middlesbrough: 0.37; Newcastle: 0.67; Nottingham: 0.62; Sheffield: 0.60 Range (Min, Max): Birmingham: 0.4, 0.8; Bristol: 0.6, 1.2; Leeds: 0.5, 0.9; Liverpool: 0.3, 0.6; London: 0.5, 0.9; Manchester: 0.4, 0.7; Middlesbrough: 0.2, 0.4; Newcastle: 0.5, 0.8; Nottingham: 0.4, 0.7; Sheffield: 0.3, 0.7 Copollutant: SO 2 , NO 2 , NO, O 3 , PM 10 Increment: 1 mg/m 3

RR Estimate [Lower CI, Upper CI] Lags examined (days): 0, 1, 2

All infant deaths: 1.02 (0.96, 1.09) Neonatal deaths: 0.99 (0.92, 1.07) Post-neonatal deaths: 1.09 (0.94, 1.25) City-specific results of all infant mortality displayed graphically

Author: Huynh et al. (2006, 091240 ) Period of Study: 1999-2000

Location: California Health Outcome: PTB (24-36 wk gestation) Study Design: Case-control Statistical Analyses: Conditional Logistic regression Age Groups Analyzed: Cases = 24- to 36-wk gestation; Controls = 39- to 44-wk Sample Description: 10,673 PTBs (cases); 32,119 term births (controls) Averaging Time: NR Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NR Increment: 1 ppm Exposure level – Quartiles of exposure for first mo and last two wk of gestation (mg/m 3 ) First: <0.61; Second: 0.61 – 0.82; Third: 0.82 – 1.07; Fourth: >1.07 Quartiles for entire pregnancy and last two wk of pregnancy were similar. OR for PTB [Lower CI, Upper CI] First mo of gestation: Per 1 ppm increase: 1.10 (0.99-1.20) Second quartile: 0.94 (0.88-1.01) Third quartile: 1.04 (0.97-1.11) Fourth quartile: 1.05 (0.96-1.14) Last two wk of gestation: Per 1 ppm increase: 1.00 (0.93-1.09) Second quartile: 1.03 (0.97-1.10) Third quartile: 1.04 (0.97-1.12) Fourth quartile: 0.99 (0.91-1.08) Entire pregnancy: Per 1 ppm increase: 1.06 (0.95-1.18) Second quartile: 0.97 (0.91-1.04) Third quartile: 0.99 (0.92-1.05) Fourth quartile: 1.02 (0.94-1.09) Lowest quartile used as reference group

Author: Hwang and Jaakkola (2008, 193794 ) Period of Study: 2001-2003

Location: Taiwan Health Outcome: Oral clefts (with or without palate) Study Design: Case control Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 6,530 cases from 721,289 newborns Averaging Time: 8 h Mean (SD) unit: 0.69 (0.4) Range (Min, Max): 0.25, 2.7 Copollutant correlation: PM 10 : r = - 0.19 NO X : r = 0.82 SO 2 : r = 0.24 O 3 : r = -0.19 Increment: 100 ppb

RR for oral cleft [Lower CI, Upper CI] Month 1: 1.00 (0.96-1.04) Month 2: 1.00 (0.96-1.03) Month 3: 1.00 (0.96-1.03)

Author: Jalaludin et al. (2007, 156601 ) Period of Study: 1998-2000

Location: Sydney, Australia Health Outcome: PTB Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 123,840 full term live singleton births (<42 wk) Averaging Time: 8 h Mean (SD) unit: 0.9 ppm (0.68) Range (Min, Max): NR Copollutant correlation: PM 10 : r = 0.28 NO 2 : r = 0.60 SO 2 : r = 0.24 O 3 : r = -0.21 Increment: 1 ppm

RR for PTB [Lower CI, Upper CI]

First mo: All of Sydney: 0.89 (0.84-0.95) Within 5km of site: 1.03 (0.68-1.54) First trimester: All of Sydney: 0.77 (0.71-0.83) Within 5km of site: 1.24 (0.81-1.91) 1 mo prior to birth: All of Sydney: 0.96 (0.88-1.04) Within 5km of site: 1.00 (0.86-1.15) 3 mo prior to birth: All of Sydney: 0.99 (0.90-1.09) Within 5km of site: 1.11 (0.94-1.31)



### January 2010 C-28

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Lee et al. (2003, 043202 ) Period of Study: 1996-1998

Location: Seoul, South Korea Health Outcome: LBW Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 388,105 full-term live singleton births (37-44 wk) Averaging Time: 24 h Mean (SD) unit: 1.2 ppm Range (Min, Max): 0.4, 3.4 Copollutant correlation: PM 10 : r = 0.47 NO 2 : r = 0.77 SO 2 : r = 0.79 Increment: 0.5 ppm

OR for LBW [Lower CI, Upper CI] First: 1.04 (1.01-1.07) Second: 1.03 (1.00-1.06) Third: 0.96 (0.93-0.99) Entire pregnancy: 1.05 (1.01-1.09)

Author: Leem et al. (2006, 089828 ) Period of Study: 2001-2002

Location: Incheon, Korea Health Outcome: PTB Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 52,113 live singleton births Averaging Time: Kriging was used to estimate exposure Mean (SD) unit: NR Range (Min, Max): NR Copollutant correlation: PM 10 : r = 0.27 NO 2 : r = 0.63 SO 2 : r = 0.31 Increment: Exposure level – Quartile s of exposure for first trimester (mg/m 3 ) First: 0.47-0.63; Second: 0.6 -0.77; Third: 0.78-0.90; Fourth: 0.91-1.27 - exposure groups for third trimester was similar OR for PTB [Lower CI, Upper CI]

First Trimester: Second quartile: 0.92 (0.81-1.05) Third quartile: 1.14 (1.01-1.29) Fourth quartile: 1.26 (1.11-1.44) Third Trimester: Second quartile: 1.07 (0.95-1.21) Third quartile: 1.07 (0.94-1.22) Fourth quartile: 1.16 (1.01-1.34) Lowest quartile used as reference group.

Author: Lin et al. (2004, 095787 ) Period of Study: 1998-2000

Location: Sao Paulo, Brazil Health Outcome: Neonatal death (within first 28 days of life) Study Design: Time series Statistical Analyses: Poisson regression (GAM) Age Groups Analyzed: NA Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 2.83 ppm Range (Min, Max): 0.54, 10.25 Copollutant correlation: PM 10 : r = 0.71 NO 2 : r = 0.67 SO 2 : r = 0.55 O 3 : r = 0.03 Increment: NR Regression coefficent for neonatal death [SE] Lags examined: 0 Lag 0: 0.0061 (0.0110)

Author: Lin et al. (2004, 089503 ) Period of Study: 1995-1997

Location: Taipei & Kaoshiung, Taiwan Health Outcome: LBW Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 92 

# , 288 full-term live singleton births (>37 wk) within 3 km of monitoring site. Averaging Time: 24 h Mean (SD) unit: Taipei (avg over 5 sites) 0.84-1.31 Kaohsiung (avg over 5 sites) 5.56-10.05 Range (Min, Max): NR Copollutant: NR Increment: Exposure groups M = Median exposure 1.1-14.2 ppm H = High exposure >14.2 ppm OR for LBW [Lower CI, Upper CI]

Trimesters: First: M 1.01 (0.89, 1.16), H 0.90 (0.75, 1.09) Second: M 1.02 (0.90, 1.16), H 1.00 (0.82, 1.22) Third: M 0.88 (0.77, 1.00), H 0.86 (0.71, 1.03) Entire pregnancy: M 0.89 (0.77, 1.01), H 0.77 (0.63, 0.94)

Notes: Cut off for exposures groups for second and third trimester were similar to those presented above.



### January 2010 C-29

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Liu et al. (2003, 089548 ) Period of Study: 1985-1998

Location: Vancouver, BC, Canada Health Outcome: PTB, IUGR, LBW Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 229,085 live singleton births Averaging Time: 24 h Mean (SD) unit: 1.0 ppm Range (Min, Max): 25th: 0.7; 75th: 1.2 Copollutant: NR Increment: 1.0 ppm OR for LBW [Lower CI, Upper CI] Month of pregnancy: First mo: 1.01 (0.93-1.09) Last mo: 0.96 (0.88-1.04) OR for PTB [Lower CI, Upper CI] First mo: 0.95 (0.89-1.01) Last mo: 1.08 (1.01-1.15) OR for IUGR [Lower CI- Upper CI] First mo: 1.06 (1.01-1.10) Last mo: 0.98 (0.94-1.03) Trimester 1: 1.05 (1.00-1.10) Trimester 2: 0.97 (0.92-1.01) Trimester 3: 0.97 (0.93-1.02)

Author: Liu et al. (2007, 090429 ) Period of Study: 1995-2000

Location: Calgary, Edmonton, and Montreal, Canada Health Outcome: IUGR Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 386,202 live singleton births Averaging Time: 24 h Mean (SD) unit: 1.1 ppm Range (Min, Max): 25th: 0.6; 75th: 1.3 Copollutant correlation: PM 2.5 : r = 0.31 NO 2 : r = 0.71 SO 2 : r = 0.21 O 3 : r = -0.42 Increment: 1 ppm

RR for LBW [Lower CI, Upper CI]

Notes: CO was associated with an increased risk of IUGR of approximately 16% and 23% in the first and nine mo of pregnancy. (All results presented in Figures)

Author: Maisonet et al. (2001, 016624 ) Period of Study: 1994-1996

Location: Northeastern USA Health Outcome: Live birth weight Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 89,557 live singleton term births (37-44 wk) Averaging Time: 24 h Mean (SD) unit: NR Range (Min, Max): Percentiles: 25th: 0.93 ppm; 75th: 1.23 ppm Copollutant: NR Increment: 1 ppm OR for LBW [Lower CI, Upper CI]

Trimester: First: 1.08 (0.91-1.28); Se cond: 1.14 (0.83-1.58); Third: 1.31 (1.06-1.62) Stratified results among African-Americans: First: 1.43 (1.18-1.74); Se cond: 1.27 (0.87-1.86); Third: 1.75 (1.50-2.04)

Notes : CO had no effect on whites or Hispanics

Author: Mannes et al. (2005, 087895 ) Period of Study: 1998-2000

Location: Sydney, Australia Health Outcome: Birth weight and SGA Study Design: Retrospective cohort Statistical Analyses: Linear and logistic regression Age Groups Analyzed: NA Sample Description: 138,056 full-term all singleton births (including stillbirths) (at least 20-wk gestation) Averaging Time: 8 h Mean (SD) unit: 0.8 ppm Range (Min, Max): 0.0, 4.6 Copollutant: correlation PM 10 : r = 0.26 NO 2 : r = 0.57 O 3 : r = -0.20 Increment: 1 ppm Regression coefficients for birth weight (g) [Lower CI, Upper CI]

All births: First trimester: 1.86 (-8.31 to 12.03) Second trimester: -10.72 (-23.09 to 1.65) Third trimester: -6 .63 (-18.57 to 5.31) One mo prior to birth: -15.28 (-25.59 to -4.97) Births within 5 km of monitor: First trimester: -8 .56 (-28.60 to 10.68) Second trimester: -28.87 (-50.98 to -6.76) Third trimeste: -22.88 (-44.58 to -1.18) One mo prior to birth: -10.41 (-30.03 to 9.21) OR for SGA [Lower CI, Upper CI]

All births: First trimester: 0.95 (0.88-1.04) Second trimester: 0.99 (0.90-1.10) Third trimester: 1.01 (0.91-1.11) One mo prior to birth: 1.06 (0.98-1.16) Births within 5km of monitor: First trimester 0.99 (0.86-1.14) Second trimester: 1.06 (0.90-1.25) Third trimester: 1.05 (0.90-1.23) One mo prior to birth: 1.10 (0.96-1.27)



### January 2010 C-30

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Medeiros et al. (2005, 089824 ) Period of Study: 1998-2000

Location: Sao Paulo, Brazil Health Outcome: Birth weight and LBW Study Design: Retrospective cohort Statistical Analyses: Linear and logistic regression Age Groups Analyzed: NA Sample Description: 311,735 full-term live singleton births (37-41 wk) Averaging Time: 24 h Mean (SD) unit: Daily mean shown in Figure (see paper) Range (Min, Max): NR Copollutant: NR Increment: 1 ppm Regression coefficient for birth weight (g) [Lower CI, Upper CI]

Trimesters: First: -11.9 (-15.5 to -8.2); Second: 4.9 (0.5-9.3); Third: 12.1 (7.6-16.6) OR for LBW [Lower CI, Upper CI] 4th quartile exposure (compa red to lowest quartile) First: 0.98 (0.91-1.06); Se cond: 0.97 (0.90-1.05); Third: 1.03 (0.96-1.11)

Author: Mortimer et al. (2008, 187280 ) Period of Study: November 2000-April 2005

Location: Central Valley of Californinia Health Outcome: Allergic sensitization Study Design: Cohort Statistical Analyses: Chisquare tests Age Groups Analyzed: 6-11 yrs. Sample Description: 170 children with asthma from the FACES-LiTE study Averaging Time: 8 h Mean (SD) unit: NR Range (Min, Max): NR Copollutant:

Entire Prenatal: PM 10 : r = 0.32 NO 2 : r = 0.74 O 3 : r = -0.40

Trimester 2: PM 10 : r = 0.32 NO 2 : r = 0.68 O 3 : r = -0.26 Increment: NR Trimester specific resu lts presented graphically Single-pollutant Model for “sensitized to at least one outdoor allergen” OR adjusted for yr of birth and sex [Lower CI, Upper CI] Entire Pregnancy 24-h avg: 1.45 (1.02, 2.07) Daily max: 1.53 (1.01, 2.33) 8-h max: 1.55 (1.01, 2.37)

2nd Trimester 24-h avg: 1.52 (0.93, 2.47) Daily max: 1.50 (0.92, 2.45) 8-h max: 1.45 (0.90, 2.35) Coefficient adjusted for yr of birth and sex [SE] Entire Pregnancy 24-h avg: 1.33 (0.68) Daily max:0.54 (0.27) 8-h max: 0.84 (0.42)

2nd Trimester 24-h avg: 0.57 (0.34) Daily max: 0.21 (0.13) 8-h max: 0.32 (0.21)

Author: Parker et al. (2005, 087462 ) Period of Study: 2000

Location: California Health Outcome: Birth weight & SGA Study Design: Retrospective cohort Statistical Analyses: Linear and logistic regression Age Groups Analyzed: NA Sample Description: 18,247 full-term live singleton births (40 wk) within 5 mi of a monitor Averaging Time: 24 h Mean (SD) unit: 0.78 ppm Range (Min, Max): NR Copollutant: NR Increment: Quartiles of exposur e for first trimester First: <0.57; Second: 0.57-0.76 ; Third: 0.76- 0.93; Fourth: >0.93 - exposure groups for other trimesters were similar Regression co-efficient for birth weight (g) [Lower CI, Upper CI]

Trimesters: 4th quartile exposure (compa red to lowest quartile) First: -7.3 (-29.7 to 15.0); Second: 14.2 (-8.9 to 37.3); Third: -8.4 (-32.2 to 15.3); Entire pregnancy: -20.5 (-40.1 to -0.8) OR for SGA [Lower CI, Upper CI] 4th quartile exposure (compa red to lowest quartile) First: 0.91 (0.76-1.09); Se cond: 0.80 (0.66-0.97); Third: 0.90 (0.75-1.10); Entire pregnancy: 0.95 (0.81-1.12)



### January 2010 C-31

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Ritz et al. (2000, 012068 ) Period of Study: 1989-1993

Location: Southern California Health Outcome: PTB Study Design: Retrospective Cohort Statistical Analyses: Logistic regression Age Groups Analyzed: Eligible study subjects were singletons born at 26- to 44-wk gestation Sample Description: 97,518 neonates born in Southern California Averaging Time: 6-9 a.m. Mean (SD) unit: 2.70 ppm Range (Min, Max): 0.36, 9.12 Copollutant correlation: PM 10 : r = 0.37 NO 2 : r = 0.60 O 3 : r = -0.44 Increment: 3 ppm RR for PTB [Lower CI, Upper CI] Adjusted for various risk fa ctors and season of birth and conception 6 wk prior to birth: 1.04 (0.99-1.10) 1st mo of pregnancy: 1.04 (0.99-1.09) Adjusted for various risk factors 6 wk prior to birth: 1.06 (1.02-1.10) 1st mo of pregnancy: 1.01 (0.97-1.04)

Author: Ritz et al. (2002, 023227 ) Period of Study: 1987-1993

Location: Southern California Health Outcome: Birth defects (heart defects and orofacial clefts) Study Design: Case control Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: NR Averaging Time: NR Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NR Increment: Exposure categories: ppm <1.14; 1.14-1.57; 1.57- 2.39; >2.39

OR for Birth defects [Lower CI, Upper CI]: Period of exposure: Second mo of pregnancy. Aortic artery and valve defects: 1.00 (ref group); 1.10 (0. 73-1.66); 1.25 (0.74-2.13); 0.93 (0.47-1.85) Pulmonary artery and valve anomalies: 1.00 (ref group); 1.09 (0. 69-1.73); 0.92 (0.50-1.70); 1.00 (0.46-2.17) Ventricular septal defects: 1.00 (ref group); 1.62 (1. 05-2.48); 2.09 (1.19-3.67); 2.95 (1.44-6.05) Conotruncal defects: 1.00 (ref group); 0.79 (0. 47-1.32); 0.73 (0.36-1.47); 0.95 (0.38-2.38)

Notes: Results also presented for more specific defects, however CO showed no association (see paper Table 3.). CO not associated with orofacial clefts)

Author: Ritz et al. (2006, 089819 ) Period of Study: 1989-2000

Location: Southern California Health Outcome: Postneonatal mortality (28 days to 1 yr); all causes; SIDS Study Design: Case control Statistical Analyses: Conditional Logistic regression Sample Description: Mothers residing within 16 km of monitoring site Averaging Time: 24 h Mean (SD) unit: 1.63 ppm Range (Min, Max): 0.38, 3.44 Copollutant: correlation PM 10 : r = 0.33 NO 2 : r = 0.72 O 3 : r = -0.57 Increment: 1 ppm

OR for Post-neonatal death [Lower CI, Upper CI] Exposure period: 2 wk prior to death, 1 mo prior to death, 2 mo prior to death, 6 mo prior to death All causes: 2 wk prior to death: 1.14 (1.03-1.25) 2 mo prior to death: 1.11 (1.06-1.16) SIDS: 2 mo prior to death: 1.19 (1.10-1.28) Term/normal weight births 2 mo prior to death: All causes: 1. 12 (1.05-1.19) SIDS: 1.17 (1.07-1.29) Respiratory: 1. 14 (0.95-1.36)

Preterm &/or LBW births 2 mo prior to death: All causes: 1. 12 (1.01-1.25) SIDS: 1.46 (1.09-1.94) Respiratory: 1. 03 (0.83-1.27) Notes: These results did not persist in multipollutant models (CO, NO 2 , PM 10 , O 3 )



### January 2010 C-32

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Ritz et al. (2007, 096146 ) Period of Study: January-December 2003

Location: Los Angeles, CA Health Outcome: PTB Study Design: Nested case-control Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: A survey of 2,543 of 6,374 women sampled from a cohort of 58,316 eligible births in Los Angeles county. Averaging Time: 24 h Mean (SD) unit: NR Copollutant correlation: TSP: r = 0.73 NO 2 : r = 0.75 SO 2 : r = 0.82 O 3 : r = -0.39 Increment: Exposure categories (ppm): Less than 0.58: 0.59-0. 91; 0.92-1.25; >1.25 RR for LBW [Lower CI, Upper CI]

First trimester: 1.00 (Ref group); 1.17 (1.08- 1.26); 1.15 (1.05-1.26); 1.25 (1.12-1.38) 6 wk prior to birth 1.00 (Ref group); 1.00 (0.93- 1.08); 1.08 (0.98-1.20); 1.03 (0.93-1.14) Entire pregnancy: 1.00 (Ref group); 0.76 (0.70- 0.82); 0.84 (0.77-0.91); 1.03 (0.91-1.17)

Author: Salam et al. (2005, 087885 ) Period of Study: 1975-1987

Location: California Health Outcome: Birth weight, LBW , IUGR Study Design: Retrospective cohort Statistical Analyses: Linear and logistic regression Age Groups Analyzed: NA Sample Description: 3,901 infants from the California Children’s Health Study Averaging Time: 24-h Mean (SD) unit: 1.8 ppm (0.9) (Entire pregnancy) Range: NR Copollutant: correlation PM 10 : r = 0.41 NO 2 : r = 0.69 O 3 : r = -0.27 Increment: Entire pregnancy 1.2 ppm

Trimesters: Firs t: 1.4 ppm; Second: 1.4 ppm; Third: 1.3 ppm Regression co-efficient for birth weight (g) [Lower CI, Upper CI]

Trimesters: First: -21.7 (-42.3 to -1.1); Second: 11.3 (-9.7 to 32.3); Third: 11.8 (-8.4 to 32.1); Entire pregnancy: 2.2 (-20.1 to 24.4) OR for LBW [Lower CI, Upper CI]

Trimesters: First: 1.0 (0.7-1.5); Second: 0.9 (0.6-1.3); Third: 0.7 (0.5-1.1); Entire pregnancy: 0.8 (0.6-1.3) OR for IUGR [Lower CI, Upper CI]

Trimesters: First: 1.2 (1.0-1.4); Second: 1.0 (0.9-1.1); Third: 1.0 (0.8-1.1); Entire pregnancy: 1.0 (0.9-1.2)

Author: Son et al. (2008, 190323 ) Period of Study: NR

Location: Seoul, Korea Health Outcome: Postneonatal mortality from all causes Study Design: Case crossover and time series Statistical Analyses: Conditional logistic regression Age Groups Analyzed: NA Sample Description: 1,286 first-born birth and infant death records from 1999-2003 (only postneonatal deaths) Averaging Time: 8 h Mean (SD) unit: 1.01 ppm Range (Min, Max): 0.29, 3.54 Copollutant: PM 10 , NO 2 , O 3 , SO 2 Increment : NR

RR Estimate [Lower CI, Upper CI] Lags examined (days): 0-7 Time Series: 1.323 (1.077, 1.625) Case-crossover(1:6): 1.029 (0.833, 1.271) CLR Analyses using differ ent control selection schemes 1:2: 1.076 (0.839, 1.379) 1:4: 0.981 (0.784, 1.228) 1:6: 1.029 (0.833, 1.271)

Author: Strickland et al. (2009, 190324 ) Period of Study: NR

Location: Atlanta, GA Health Outcome: Cardiovascular malformations Study Design: Retrospective cohort Statistical Analyses: Poisson GLM Age Groups Analyzed: NA Sample Description: Pregnancies reaching at least 20-wk gestation that were conceived during January 1, 1986-March 12, 2003 Averaging Time: 24-h Mean (SD) unit: By season of conception: March-May: 0.9 ppm June-August: 0.8 ppm Sept.-Nov.: 0.9 ppm Dec.-Feb.: 0.7ppm By yr of conception: 1986-1991: 0.7 ppm 1992-1997: 0.8 ppm 1998-2003: 0.7 ppm Range (IQR): 0.3 Copollutant: PM 10 (24 h): r = 0.32 NO 2 (24 h): r = 0.41 O 3 (8 h): r = 0.07 SO 2 (24 h): r = 0.23 Increment: NR

RR Estimate [Lower CI, Upper CI] Atrial septal defect, se cundum: 1.16 (0.67, 2.00) Coarctation of the aort a: 1.15 (0.65, 2.06) Hypoplastic left heart syndr ome: 0.82 (0.37, 1.84) Patent ductus arteriosus: 1.39 (0.72, 2.68) Pulmonary stenosis, valvar : 0.97 (0.53, 1.75) Tetralogy of Fallot: 1.09 (0.59, 2.00) Transposition of the great arteries: 1.29 (0.58, 2.85) Ventricular septal defect, muscular: 1.08 (0.77, 1.50) Ventricular septal defect, perimembranous: 1.06 (0.67, 1.68) Conotruncal defect: 1.22 (0.81, 1.85) Left ventricular outflow tract defect: 1.09 (0.70, 1.68) Right ventricular outflow tract defects: 0.73 (0.44, 1.22)



### January 2010 C-33

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Tsai et al. (2006, 090709 ) Period of Study: 1994-2000

Location: Kaoshiung, Taiwan Health Outcome: Postneonatal death (27 days-1 yr old) Study Design: Case

crossover Statistical Analyses: Poisson regression Age Groups Analyzed: NA Sample Description: NR Averaging Time: 24 h Mean (SD) unit: 8.27 ppm x10 Range (Min, Max): 2.26, 17.7 Copollutant : NR Increment: Interquartile range: 0.31 ppm

OR for Post-neonatal morta lity [Lower CI, Upper CI] Lag examined: 0-2 Lag 0-2: 1.051 (0.304-3.630)

Author: Wilhelm et al. (2005, 088668 ) Period of Study: 1994-2000

Location: Los Angeles, CA Health Outcome: Term LBW and PTB Study Design: Retrospective cohort Statistical Analyses: Logistic regression Age Groups Analyzed: NA Sample Description: 518,254 births within 4 mi of a monitoring station. Varied according to analyses. Averaging Time: 24 h Mean (SD) unit : Trimester 1: 1.42 ppm Results for third trimester and 6 wk prior to birth were similar to first trimester Range (Min, Max): 0.26, 2.82 Copollutant correlation: First Trimester: PM 10 : r = 0.12 PM 2.5 : r = 0.57 NO 2 : r = 0.81 SO 2 : r = -0.31 Increment: 1 ppm

RR for PTB [Lower CI, Upper CI]

First trimester: <1 mile: 1.06 (1.00-1.12) 1-2 miles: 1.06 (1.03-1.10) 2-4 miles: 1.08 (1.06-1.09) ZIP code level: 1.04 (1.01-1.07) 6 wk prior to birth: <: 1.04 (0.98-1.09) 1-2 miles: .04 (1.01-1.08) 2-4 miles: 1.01 (0.99-1.02) ZIP code level: 1.03 (1.00-1.06)

Notes: All results above did not persist in multipollutant model (CO, NO 2 , O 3 , PM 10 ) OR for term LBW [Low er CI, Upper CI]

Third trimester: <1 mile: 1.10 (0.98-1.23) 1-2 miles: 1.05 (0.99-1.13) 2-4 miles: 1.06 (1.02-1.10) ZIP code level: 1.12 (1.05-1.19)

Notes: All results above did not persist in multipollutant model (CO, NO 2 , O 3 , PM 10 ) See paper for results based on exposure category groupings.

Author: Woodruff et al. (2008, 098386 ) Period of Study: 1999-2002

Location: U.S. counties with >250,000 residents Health Outcome: Postneonatal deaths all causes; respiratory; SIDS; ill-defined + SIDS; other causes. Study Design: Retrospective cohort Statistical Analyses: Logistic regression (GEE) Age Groups Analyzed: NA Sample Description: NR Averaging Time: 24 h Mean (SD) unit: All causes: 0.70 ppm Range (Min, Max): Percentiles: 25th: 0.48; 75th: 0.87 Copollutant correlation: PM 10 : r = 0.18 SO 2 : r = 0.27 O 3 : r = -0.46 Increment: 0.39 ppm OR for Post-neonatal mortality [Lower CI, Upper CI] Avg exposure over the first 2 mo of life: All causes: 1. 01 (0.95-1.07) Respiratory: 1. 14 (0.93-1.40) SIDS: 0.88 (0.76-1.03) Ill-defined + SIDS : 0.93 (0.84-1.02) Other causes: 1.02 (0.97-1.07)

Author: Yang et al. (2004, 094376 ) Period of Study: 1994-2000

Location: Taipei, Taiwan Health Outcome: Postneonatal mortality (27 days-1 yr old) Study Design: Case

crossover Statistical Analyses: Poisson regression Age Groups Analyzed: NA Sample Description: NR Averaging Time: 24-h Mean (SD) unit: 15.8 ppm x10 Range (Min, Max): 3.20, 48.4 Copollutant: NR Increment: Interquartile range: 0.56 ppm

OR for Post-neonatal morta lity [Lower CI, Upper CI] Lag examined : 0-2 Lag 0-2: 1.038 (0.663-1.624)



### January 2010 C-34

# Table C-4. Studies of short-term CO exposure and resp iratory morbidity

Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Andersen et al. (2008, 096150 ) Period of Study: Dec 1998-Dec 2004

Location: Copenhagen, Denmark Health Outcome: Wheezing symptoms Study Design: Panel Statistical Analyses : Logistic regression (GEE) Age Groups Analyzed: 0-3 yrs Sample Description: 205 children of mothers with asthma Averaging Time: 24h Mean (SD) unit: 0.29 (0.10) ppm Range (percentiles): 25th = 0.22; 75th = 0.34 Copollutant: correlation PM 10 : r = 0.45 PM 2.5 : r = 0.45 UFPNC: r = 0.52 NO 2 : r = 0.75 NO X : r = 0.74 O 3 : r = -0.63 Increment: NR OR Estimate [Lower CI, Upper CI] ; lag: Lags examined: 0, 1, 2, 3, 4, 2-4 Lag 0: 0.96 (0.80, 1.15) Lag 1: 0.92 (0.77, 1.10) Lag 2: 1.08 (0.92, 1.28) Lag 3: 1.07 (0.90, 1.26) Lag 4: 1.02 (0.84, 1.23) 3d mean: 1.07 (0.87, 1.32)

Author: Bhattacharyya et al. (2009, 180154 ) Period of Study: 1997- 2006

Location: NR (National Health Interview Survey as aggregated in the Integrated Health Interview Series served as data source) Health Outcome: Respiratory morbidity Study Design: Cross-sectional study Statistical Analyses: SPSS version 14.0, univariate linear regression analysis Age Groups Analyzed: 18+ yr (avg: 45.2 yr) Sample Description: Hay fever, weak/failing kidneys, sinusitis all in past 12 mo Averaging Time: NR Mean (SD) unit: NR Range (Min, Max): 2.209-4.157ppm (decreased with increasing yr) Copollutant: NR Increment: NR Linear regression analysis for disease condition prevalence: Hayfever: Standardized B- 0.012, p-value- <0.001; Sinusitis: Standardized B- 0.027, p-value- <0.001;Kidney Weak/Failin: Standardized B- -0.001, pvalue- <0.001 Lags examined: NR

Author: Chen et al. (1999, 011149 ) Period of Study: 5/1995-1/1996

Location: 3 Taiwan communities Health Outcome: Lung function (FVC, FEV 1 , FEV 1 /FVC, FEF 25-75%, PEF) Study Design: Cross-sectional survey Statistical Analyses: Multivariate linear model Population: 941 children (Boys: 453; Girls: 488) Age Groups Analyzed: 8-13 yr Pollutant: CO Averaging Time: 1-h max; 24-h avg Mean (SD) unit : NR Range (Min, Max): 1-h max: (0.4, 3.6) Copollutant correlation: NO 2 : r = 0.86 – 0.98

Note: To represent the schoolchildren’s exposure the daytime avg and pe ak concentrations were measured from 0800 to 1800. Increment: NR β Coefficient (SE); lag: FVC (mL) 24-h avg -66.6 (40.73); 1 -147.71 (64.48); 2 2.2 (48.13); 7 1-h max -33.25 (20.74); 1 -16.48 (19.67); 2 -5.18 (16.48); 7

FEV 1 (mL) 24-h avg 20.55 (38.24); 1 -82.42 (60.95); 2 48.23 (45.58); 7 1-h max 1.2 (19.48); 1 -1.44 (18.57); 2 20.96 (15.67); 7

Author: Chen et al. (2000, 011931 ) Period of Study: 8/1996-6/1998

Location: Washoe County, NV Health Outcome: School absenteeism Study Design: Time series Statistical Analyses: Maximum likelihood Population: 1st to 6th grade children: 27,793 Age Groups Analyzed: 1st to 6th grade children Pollutant: CO Averaging Time: 1-h max Mean (SD) unit: 2.73 (1.154) ppm Range (Min, Max): (0.65, 2.73) Copollutant correlation: PM 10 : r = 0.721 O 3 : r = -0.204 Increment: 1.0 ppm % Increase (Lower CI, Upper CI); lag: 3.79% (1.04-6.55); 0



### January 2010 C-35

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: de Hartog et al. (2003, 001061 ) Period of Study: 1998-1999

Location: Amsterdam, Netherlands; Erfurt, Germany; Helsinki, Finland Health Outcome: Respiratory symptoms (shortness of breath, being awakened by breathing problems, phlegm, wheezing, tripping heart) Study Design: Time series Statistical Analyses: Logistic regression Population: Nonsmoking individuals with CHD: Amsterdam: 37 Erfurt: 47 Helsinki: 47 Age Groups Analyzed: ≥ 50 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Amsterdam: 0.6 mg/m 3 Erfurt: 0.4 mg/m 3 Helsinki: 0.4 mg/m 3 Range (Min, Max): Amsterdam: (0.4, 1.6) Erfurt: (0.1, 2.5) Helsinki: (0.1, 1.0) Copollutant: PM 2.5 ; NO 2 Increment: 0.25 mg/m 3 Odds Ratio (Lower CI, Upper CI); lag: Incidence of symptoms Shortness of breath 1 (0.92-1.1); 0 0.96 (0.88-1.05); 1 1 (0.92-1.09); 2 1.07 (0.98-1.16); 3 1.03 (0.9-1.18); 0-4 Being awakened by breathing problems 1.02 (0.92-1.14); 1 1.03 (0.93-1.15); 2 1.11 (1-1.22); 3 1.16 (0.98-1.37); 0-4 Phlegm 1.05 (0.93-1.19); 0 1.02 (0.91-1.14); 1 1.08 (0.96-1.22); 2 1.09 (0.97-1.22); 3 1.13 (0.94-1.35); 0-4 Prevalence of symptoms Shortness of breath 1 (0.94-1.06); 0 0.99 (0.94-1.05); 1 0.99 (0.93-1.05); 2 1.01 (0.95-1.07); 3 0.98 (0.9-1.07); 0-4 Being awakened by breathing problems 1.01 (0.93-1.1); 1 0.99 (0.91-1.08); 2 1.1 (1.02-1.19); 3 1.13 (1-1.29); 0-4

Author: Delfino et al. (2003, 050460 ) Period of Study: 11/1999-1/2000

Location: Los Angeles, CA Health Outcome: Asthma symptoms (Cough, wheeze, sputum production, shortness of breath, chest tight ness) (symptom scores >1, symptoms scores >2); Lung function (PEF) Study Design: Panel study Statistical Analyses: Asthma symptoms: GEE Lung function: Generalized linear mixed model Population: 22 asthmatic Hispanic children Age Groups Analyzed: 10-15 yr Pollutant: CO Averaging Time: 1-h max; 8-h max Mean (SD) unit: 1-h max: 7.7 (3.1) ppb 8-h max: 5.0 (2.0) ppb Range (Min, Max): 1-h max: (2, 17) 8-h max: (1, 10) Copollutant correlation: NO 2 : r = 0.65; O 3 : r = -0.17; Acetaldehyde: r = 0.51; Acetone: r = 0.28; Formaldehyde: r = 0.41; Benzene: r = 0.50; Ethylbenzene: r = 0.62; Tetrachloroethyl ene: r = 0.63; Toluene: r = 0.71; m,p - Xylene: r = 0.72; PM 10 : r = 0.50; EC: r = 0.60; OC: r = 0.55; SO 2 : r = 0.69 Increment: 5.0 ppb & 3.0 ppb Odds Ratio (Lower CI, Upper CI); lag:

1-max Increment: 5.0 ppb Symptom scores >1 0.95 (0.52-1.75); 0 1.11 (0.75-1.65); 1 Symptom scores >2 0.48 (0.07-3.53); 0 .28 (0.53-3.12); 1

8-h max Increment: 3.0 ppb Symptom scores >1 0.95 (0.55-1.62); 0 1.2 (0.77-1.86); 1 Symptom scores >2 0.53 (0.10-2.92); 0 1.43 (0.41-5.00); 1

Author: Estrella et al. (2005, 099124 ) Period of Study: 1/2000-4/2000

Location: Quito, Ecuador Health Outcome: Acute respiratory infection Study Design: Prospective study Statistical Analyses: Logistic regression; Poisson Population: 960 children Age Groups Analyzed: 6-11 yr Pollutant: CO Averaging Time: NR Mean (SD) unit : NR Range (Min, Max): NR Copollutant: NR Increment: NR Odds Ratio (Lower CI, Upper CI); lag: Acute respiratory infection ARI in children COHb >2.5% vs. COHb <2.5%: Adjusted Logistic Regression Model 3.25 (1.65-6.38)

ARI in children COHb >2.5% vs. COHb <2.5%: Crude Logistic Regression Model 2.06 (1.30-3.20) Log-Linear Model (Each Percent Increase in COHb above 2.5%) 1.15 (1.03-1.28)



### January 2010 C-36

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Fischer et al. (2002, 025731 ) Period of Study: NR

Location: Utrecht, Netherlands Health Outcome: Lung function (FVC, FEV 1 , PEF, MMEF) Study Design: Panel study Statistical Analyses: Restricted max likelihood linear model Population: 68 children Age Groups Analyzed: 10-11 Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 921 μg/m 3 Range (Min, Max): (319, 1540) Copollutant: PM 10 ; BS; NO 2 ; NO Increment: 100 μg/m 3 mL (SE); lag: FVC: 0.5 (0.4); 1; 0.1 (0.2); 2 FEV1: -0.4 (0.5); 1; -0.2 (0.2); 2 m/s (SE); lag: PEF: -1.1 (2.8); 1; -0.6 (1.1); 2 MMEF: -0.5 (1.4); 1; -0.3 (0.6); 2

Author: Ho et al. (2007, 093265 ) Period of Study: Oct 1995-Mar 1996

Location: Taipei, Taiwan Health Outcome: Asthma Study Design: Panel Statistical Analyses: Logistic regression (GEE) Age Groups Analyzed: 10-17 yr Sample Description: A stratified cluster random sample of students (n=69,367) from 1,139,452 students sampled nationwide Averaging Time: 8 h Mean (SD) unit: NR Range (min, max): NR Copollutant: NO, NO 2 , NO X , O 3 , SO 2 , PM 10 , PSI Increment: very high, high, med, low, very low OR Estimate [Lower CI, Upper CI] ; lag: Lags examined: NR Females: 1.984 (1.536, 2.561) Males: 1.780 (1.377, 2.302) Monthly attack rate vs single air pollutant concentrations Estimate (p-value): 0.0750 (0.3336)

Author: Lagorio et al. (2006, 089800 ) Period of Study: 5/1999-6/1999; 11/1999-12/1999

Location: Rome, Italy Health Outcome: Lung function (FVC, FEV 1) Study Design: Time-series panel study Statistical Analyses: Generalized estimating equations (GEE) Population: COPD panel: 11 Asthma panel: 11 IHD panel: 7 Age Groups Analyzed: COPD panel: 50-80 yr Asthma panel: 18-64 yr IHD panel: 40-64 yr

N otes: Asthma panel was restricted to never smokers, while COPD and IHD panels include former smokers if smoking cessation occurred at least 1 yr prior to enrollment. Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Overall: 7.4 (6.2) mg/m 3 Spring: 2.1 (0.3) mg/m 3 Winter: 12.3 (4.9) mg/m 3 Range (Min, Max): Overall: (1.6, 28.9) Copollutant correlation: PM 2.5 : r = 0.67 PM 10-2.5 : r = -0.09 PM 10 : r = 0.55 NO 2 : r = 0.05 O 3 : r = -0.87 SO 2 : r = 0.65 Increment: 1 mg/m 3 β Coefficient (SE); lag: COPD panel FVC (% of predicted) -0.14 (0.15);0 -0.13 (0.18); 0-1 0.15 (0.23); 0-2 FEV1 (% of predicted) -0.05 (0.13); 0 -0.12 (0.16); 0-1 -0.03 (0.2); 0-2 Asthma panel FVC (% predicted) 0.02 (0.12); 0 -0.001 (0.13); 0-1 -0.06 (0.16); 0-2 FEV1 (% predicted) -0.05 (0.14); 0 -0.16 (0.15); 0-1 -0.28 (0.18); 0-2 IHD panel FVC (% of predicted) 0.176 (0.101); 0 0.132 (0.120); 0-1/ 0.132 (0.165); 0-2 FEV1 (% of predicted) 0.204 (0.120); 0 0.114 (0.142); 0-1 0.159 (0.194); 0-2

Author: Moon et al. (2009, 190297 ) Period of Study: Apr 2003-May 2003

Location: Seoul, Incheon, Busan, & Jeju, Korea Health Outcome: Respiratory symptoms Study Design: Panel Statistical Analyses: Logistic regression (GEE) Age Groups Analyzed: < 13 yr Sample Description: 696 children Averaging Time: 24h Mean (SD) unit: NR IQ Range: 0.12ppm Copollutant: PM 10 , SO 2 , NO 2 , O 3 Increment: 0.12 ppm (IQR) OR Estimate [Lower CI, Upper CI] ; lag: Lags examined: lag days 0-3 Lower resp. symptoms: 1.005 (1.003, 1.008), lag 0 Upper resp. symptoms: 1.006 (1.003, 1.008), lag 0-2 Irritation symptoms: 1.004 (1.001, 1.006), lag 1-3



### January 2010 C-37

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Mortimer et al. (2008, 187280 ) Period of Study: Nov 2000-Apr 2005

Location: Fresno, California Health Outcome: Allergic sensitization Study Design: Panel Statistical Analyses: Multistep modeling Age Groups Analyzed: 6-11 yr Sample Description: 170 children with physician diagnosed asthma Averaging Time: 24-h avg, 24-h max, 8-h max Mean (SD) unit: NR IQ Range (24-h avg, 24-h max, 8-h max): 0.28, 0.79, 0.52 Copollutant: entire prenatal correlation NO 2 : r = 0.74 O 3 : r = -0.40 PM 10 : r = 0.32 Increment: IQR OR Estimate [Lower CI, Upper CI] ; lag: Lags examined: NR Entire Pregnancy: CO 24-h avg: 1.45 (1.02, 2.07) CO 24-h max: 1.53 (1.01, 2.33) CO 24-h avg: 1.55 (1.01, 2.37)

Author: Nkwocha et al. (2008, 190304 ) Period of Study: Feb 2005-Jul 2006

Location: Port Harcourt, Nigeria Health Outcome: Respiratory symptoms Study Design: Panel Statistical Analyses: Mixed Effects models Age Groups Analyzed: 0-5 yr Sample Description: 250 children Averaging Time: 8 h Mean (SD) unit: NR Range (min, max): 1.3 μg/m 3 , 1.83 μg/m 3

Copollutant: NO 2 , SO 2 , PM 10 Increment: NR Lags examined: NR

R Estimate: Dry season: 0.13

Wet season: 0.25

Author: O’Connor et al. (2008, 156818 ) Period of Study: Aug 1998-Jul 2001

Location: Boston, MA; the Bronx, NY; Chicago, IL; Dallas, TX; New York, NY; Seattle, WA; Tuscon, AZ Health Outcome: respiratory symptoms Study Design: panel Statistical Analyses: Mixed Effects Models Age Groups Analyzed: 5-12 yr Sample Description: 861 children with persistent asthma and atopy living in low-income census tracts Averaging Time: 8 h Mean (SD) unit: NR Range (10th-90th): 872.1 ppb Copollutant: PM 10 , SO 2 , NO 2 , O 3 Increment: 872.1 ppb Lags examined: NR Change Estimate [Lower CI, Upper CI]:

FEV 1 : -0.56 (-1.31, 0.20) PEFR: -0.49 (-1 .24, 0.27)

Pollution Impact*[Lower CI, Upper CI]: Wheeze-cough: 1.26 (1.03, 1.55) Nighttime asthma: 1.35 (1.07, 1.71) Slow play: 1.28 (1.04, 1.59) OR [Lower CI, Upper CI]: Missed School: 1.08 (0.76, 1.53) *Coefficients from the negative binomial model and indicate the multiplicative effect per unit change

Author: Park et al. (2002, 093798 ) Period of Study: 3/1996-12/1999

Location: Seoul, Korea Health Outcome: School absenteeism Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Population: ~1,264 children (671 Boys, 593 girls) Age Groups Analyzed: 1st through 6th grade students Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.11 (0.40) ppm Range (Min, Max): (0.39, 2.97) Copollutant correlation: PM 10 : r = 0.56; NO 2 : r = 0.70; SO 2 : r = 0.67; O 3 : r = -0.46 Increment: 0.52 ppm Relative Risk (Lower CI, Upper CI); lag:

Total Absences: 0.95 (0.94-0.97); 0 Non-Illness Related Absences: 0.99 (0.96-1.02); 0 Illness-Related Absences: 0.96 (0.94-0.98); 0

Author: Park et al. (2005, 088673 ) Period of Study: 3/2002-6/2002

Location: Incheon, Korea Health Outcome: Lung function (PEF variability (>20%), Mean PEF); Respir atory symptoms (night respirator y symptoms, cough, inhaler use) Study Design: Panel study Statistical Analyses: GEE; Poisson GAM Population: 64 bronchial asthmatics Age Groups Analyzed: 16-75 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Control days: 0.6368 (0.1522) ppm Dust days: 0.6462 (0.0945) ppm Range (Min, Max): NR Copollutant: NR Increment: NR Relative Risk (Lower CI, Upper CI); lag: PEF variability (>20%): 1.43 (0.54-3.75) Night respirator y symptoms: 0.98 (0.51-1.86) β Coefficient (SE); lag: PEF variability (>20 %): 0.9737 (0.3187) Mean PEF (L/min): -10.103 (2.7146) Night respirator y symptoms: -0.018 (0.3654) Cough: 0.0855 (0.1826) Inhaler Use: 0.0796 (0.1733)



### January 2010 C-38

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Penttinen et al. (2001, 030335 ) Period of Study: 11/1996-4/1997

Location: Helsinki, Finland Health Outcome: Lung function (PEF) Study Design: Panel study Statistical Analyses: First order autoregressive linear model Population: 57 nonsmoking adult asthmatics Age Groups Analyzed: NR Pollutant: CO Averaging Time: 24-h avg

Median unit: 0.4 mg/m 3 Range (Min, Max): (0.1, 1.1) mg/m 3

Copollutant correlation: PM 10 : r = -0.03 PM 10-2.5 : r = -0.30 PM 2.5 : r = 0.32 PM 1 : r = 0.39 PNC: r = 0.44 NC0.01-0.1: r = 0.43 NC0.1-1: r = 0.47 NO: r = 0.60 NO 2 : r = 0.44 Increment: 0.2 mg/m 3 β Coefficient (SE); lag: PEF Deviations (L/min) Morning 0.27 (0.38); 0 -1.08 (0.36); 1 0.23 (0.38); 2 -1.11 (1.19); 5-day avg Afternoon -0.4 (0.43); 0 -0.13 (0.41); 1 -0.71 (0.41); 2 -3.03 (1.06); 5-day avg Evening -0.7 (0.45); 0; -0.31 (0.44); 1 0.3 (0.44); 2 -3.62 (1.19); 5-day avg Co-pollutant models with PNC Morning: -0.67 (0.64); 1 Afternoon: -0.46 (0.69); 0 Evening: -0.46 (0.73); 0

Author: Rabinovitch et al. (2004, 096753 ) Period of Study: 11/1999-3/2000; 11/2000-3/2001; 11/2001-3/2002

Location: Denver, CO Health Outcome: Lung function (FEV 1 ); asthma exacerbation; bronchodilator use Study Design: Panel study Statistical Analyses: Pulmonary function: Mixed effects model; Asthma exacerbation and medication use: GLM Population: Urban poor asthmatic children: 1999-2000: 41 2000-2001: 63 2001-2002: 43 Age Groups Analyzed: 6-12 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.0 (0.4) ppm Range (Min, Max): (0.3, 3.5) Copollutant: PM 2.5 ; PM 10 ; NO 2 ; SO 2 ; O 3 Increment: 0.4 ppm β Coefficient (SE); lag: FEV1 AM: -0.001 (0.008); 3-day ma PM: 0.015 (0.01); 3-day ma Odds Ratio (Lower C I, Upper CI); lag:

Asthma exacerbation: 1.012 (0.913-1.123); 3-day ma

Bronchodilator use: 1.065 (1.001-1.133); 3-day ma

Author: Ranzi et al. (2004, 089500 ) Period of Study: 2/1999-5/1999

Location: Emilia-Romagna, Italy Health Outcome: Lung function; respir atory symptoms, medication use Study Design: Panel study Statistical Analyses: GLM Population: 120 “asthma-like” school children Age Groups Analyzed: 6-11 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Urban area: 1.54 mg Rural area: 1.22 mg Range (Min, Max): NR Copollutant: NO2; TSP; PM 2.5 The study did not present quantitative results for CO.

Author: Rodriguez et al. (2007, 092842 ) Period of Study: 1996-2003

Location: Perth, Australia Health Outcome: Respiratory symptoms (body temperature, c ough, wheeze/rattle chest, runny/blocked nose) Study Design: Panel study Statistical Analyses: Logistic regression, GEE Population: 263 children at high risk of developing asthma Age Groups Analyzed: 0-5 yr Pollutant: CO Averaging Time: 8-h avg Mean (SD) unit: 1.408 ppm Range (Min, Max): (0.012, 8.031) Copollutant: NR Increment: NR Odds Ratio (Lower CI, Upper CI); lag: Body Temperature 1.024 (0.911-1.151); 0 1.056 (0.943-1.184); 5 0.991 (0.962-1.021); 0-5 Cough 1.001 (0.996-1.005); 0 1.064 (0.941-1.02); 5 1.028 (0.996-1.061); 0-5 Wheeze/Rattle Chest 1.089 (0.968-1.226); 0 1.136 (1.016-1.26); 5 1.035 (1.005-1.066); 0-5 Runny/Blocked Nose 1.094 (0.824-1.453); 0 1.38 (1.028-1.853); 5 1.101 (1.025-1.183); 0-5



### January 2010 C-39

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Schildcrout et al. (2006, 089812 ) Period of Study: 11/1993-9/1995

Location: 8 North American cities: Albuquerque, NM Baltimore, MD Boston, MA Denver, CO San Diego, CA Seattle, WA St. Louis, MO Toronto, ON, Canada Health Outcome: Asthma symptoms; rescue inhaler use Study Design: Panel study Statistical Analyses: Asthma symptoms: Logistic regression; Rescue Inhaler Use: Poisson regression Population: 990 asthmatic children Age Groups Analyzed: 5-12 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NO 2 ; O 3 ; PM 10 ; SO 2 Increment: 1.0 ppm Odds Ratio (Lower CI, Upper CI); lag: Asthma Symptoms 1.08 (1.01-1.14); 0 1.07 (0.99-1.16); 1 1.08 (1.02-1.15); 2 1.05 (1.01-1.09); 0-2 Asthma Symptoms + 20 ppb increase in NO 2 1.07 (1-1.14); 0 1.04 (0.96-1.11); 1 1.09 (1.02-1.16); 2 1.04 (1-1.08); 0-2 + 25 μg/m 3 increase in 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); 0-2 + 10 ppb increase in SO 2 1.07 (0.99-1.16); 0 1.06 (0.96-1.19); 1 1.1 (1.02-1.18); 2 1.05 (1-1.09); 0-2 Rescue Inhaler Use 1.07 (1.01-1.13); 0 1.05 (0.99-1.1); 1 1.06 (1.01-1.1); 2 1.04 (1.01-1.07); 0-2 Rescue Inhaler Use + 20 ppb increase in NO 2 1.05 (0.99-1.12); 0 1.04 (0.98-1.11); 1 1.07 (1.02-1.12); 2 1.04 (1-1.07); 0-2 + 25 μg/m 3 increase in 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 (1-1.07); 0-2 + 10 ppb increase in SO 2 1.04 (0.96-1.12); 0 1.04 (0.97-1.1); 1 1.08 (1.03-1.13); 2 1.04 (1-1.08); 0-2

Author: Silkoff et al. (2005, 087471 ) Period of Study: 11/11/1999-3/31/2000; 11/1/2000-3/16/2001

Location: Denver, CO Health Outcome: Lung function (FEV1, PEF); recorded symptoms; rescue medication use Study Design: Panel study Statistical Analyses: Rescue medication use and total symptom score: GEE; Lung function: Mixed effects model Population: 1st winter: 16 with a history of more than 10 pack yr of tobacco use, airflow limitation with FEV1 of less than 70% of predicted value, and FEV1/ FVC ratio of less than 60% 2nd winter: 18 with a history of more than 10 pack yr of tobacco use, airflow limitation with FEV1 of less than 70% of predicted value, and FEV1/ FVC ratio of less than 60% Age Groups Analyzed : ≥ 40 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1999-2000: 1.2 (0.555) ppm 2000-2001: 1.1 (0.5) ppm Range (Min, Max): 1999-2000: (0.340, 3.790) 2000-2001: (0.360, 2.810) Copollutant: NR The study did not present quantitative results for CO.



### January 2010 C-40

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: Slaughter et al. (2003, 086294 ) Period of Study: 12/1994-8/1995

Location: Seattle, WA Health Outcome: Asthma severity; medication use Study Design: Panel study Statistical Analyses: Asthma severity: Ordinal logistic regression; Medication use: Poisson Population: 133 mild-to-moderate asthmatic children Age Groups Analyzed: 5-13 yr Pollutant: CO Averaging Time: 24-h avg

Median unit: 1.47 ppm IQR (25th, 75th): (0.23, 1.87) Copollutant: NR Increment: Increased asthma attack severity: 0.67 ppm Increased rescue inhaler use: 1.0 ppm Odds Ratio (Lower CI, Upper CI); lag: Increased asthma attack severity: Without transition: 1.21; 1 With transition: 1.17; 1

Increased rescue inhaler use: Without transition: 1.09 (1.03-1.16); 1 With transition: 1. 06 (1.01-1.1); 1

Author: Steerenberg et al. (2001, 017157 ) Period of Study: NR

Location: Bilthoven and Utrecht, the Netherlands Health Outcome: Lung function (PEF); exhaled nitric oxide; inflammatory nasal markers Study Design: Panel study Statistical Analyses: Restricted max likelihood linear model Population: 126 children Age Groups Analyzed: 8-13 yr

Notes: The study was only conducted for a two mo period: February and March. Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Utrecht: 0.8 mg/m 3 Bilthoven: 0.5 mg/m 3 Range (Min, Max): Utrecht: (0.3, 2.3) Bilthoven: (0.3, 0.9) Copollutant: NR The study did not present quantitative results for CO.

Increment: 0.32 mg/m 3 β Coefficient (SE); lag: Exercise induced responsiveness Author: Timonen et al. (2002, 025653 ) Period of Study: 2/1994-4/1994

Location: Kuopio, Finland Health Outcome: Exercise induced bronchial responsiveness; Lung function (FVC, FEV1, MMEF, AEFV) Study Design: Panel study Statistical Analyses: Linear regression Population: 33 children with chronic respiratory symptoms Age Groups Analyzed: 7-12 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.6 mg/m 3 Range (Min, Max): (0.1, 2.8) Copollutant correlation: PM 10 : r = 0.52 BS: r = 0.80 PNC0.01-0.03: r = 0.81 PNC0.03-0.1: r = 0.87 PNC0.1-0.3: r = 0.71 PNC0.3-1.0: r = 0.60 PNC1.0-3.2: r = 0.84 PNC3.2-10: r = 0.79 NO 2 : r = 0.85 Δ FEV 1 (%) -0.081 (0.647); 0 0.03 (0.262); 1 0.087 (0.26); 2 -0.091 (0.275); 3 0.19 (0.599); 0-3 Δ MMEF (%) 0.442 (1.79); 0 0.52 (0.723); 1 0.313 (0.719); 2 -0.616 (0.75); 3 0.096 (1.64); 0-3 Δ AEFV (%) 0.287 (1.19); 0 0.281 (0.482); 1 0.904 (0.474); 2 0.15 (0.483); 3 1.6 (1.05); 0-3 FVC (mL) 0.064 (10.9); 0 -4.79 (4.51); 1 -9.78 (4.24); 2 -13.9 (4.7); 3 -29.4 (10.1); 0-3 FEV 1 (mL) 19.2 (13.2); 0 -9.04 (5.45); 1 -9.15 (5.21); 2 -11.7 (5.77); 3 -17.5 (12.5); 0-3 MMEF (mL/s) 22.2 (36.9); 0 -23 (15.2); 1 -4.63 (14.7); 2 -30.9 (16); 3 -24.9 (34.8); 0-3 AEFV (L2/s) -0.093 (0.088); 0 -0.068 (0.036); 1 -0.06 (0.035); 2 -0.05 (0.039); 3 -0.076 (0.083); 0-3



### January 2010 C-41

### Study Design Concentrations CO Effect Esti mates (95% CI)

Author: von Klot et al. (2002, 034706 ) Period of Study: 9/1996-3/1997

Location: Erfurt, Germany Health Outcome: Asthma symptoms; medication use Study Design: Panel study Statistical Analyses: Logistic regression Population: 53 adults with asthma or asthma symptoms Age Groups Analyzed: 37-77 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.9 mg/m 3 Range (Min, Max): (0.3, 3.0) Copollutant correlation: NC0.01-0.1: r = 0.66 NC0.1-0.5: r = 0.79 NC0.5-2.5: r = 0.46 MC0.1-0.5: r = 0.66 MC0.01-2.5: r = 0.65 PM 2.5-10 : r = 0.42 PM 10 : r = 0.69 NO 2 : r = 0.82 SO 2 : r = 0.32 Increment: 0 and 5-day avg lag: 0.6 mg/m 3 14-day avg lag: 0.54 mg/m 3 Odds Ratio (Lower CI, Upper CI); lag:

Prevalence: Inhaled β 2-agonist use 0.98 (0.93-1.03); 0 1.04 (0.97-1.12); 0-4 0.93 (0.86-1.01); 0-13 Prevalence: Inhaled corticosteroid use 1.05 (1-1.11); 0 1.25 (1.17-1.34); 0-4 1.06 (0.97-1.15); 0-13 Prevalence: Wheezing 1.03 (0.97-1.08); 0 1.13 (1.05-1.22); 0-4 1.14 (1.05-1.25); 0-13 Co-pollutant models Inhaled β 2-agonist use CO+MC0.01-2.5: 1 (0.91-1.11); 0-4 CO+NC00.01-0.1: 1.01 (0.91-1.11); 0-4

Inhaled corticosteroid use CO+MC0.01-2.5: 0.89 (0.81-0.98); 0-13 CO+NC: 0.01-0. 1: 0.81 (0.72-0.91); 0-13 Wheezing CO+MC0.01-2.5: 1.15 (1.04-1.27); 0-4 CO+NC0.01-0.1: 1.09 (0.98-1.22); 0-4

Author: Yu et al. (2000, 013254 ) Period of Study: 11/1993-8/1995

Location: Seattle, Washington Health Outcome: Asthma symptoms (Wheezing, coughing, chest tight ness, shortness of breath) Study Design: Panel study Statistical Analyses: Repeated measures logistic regression models (GEE) Population: 133 mild-to-moderate asthmatics Age Groups Analyzed : 5-13 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.6 ppm Range (Min, Max) : (0.65, 4.18) Copollutant correlation: PM 1.0 : r = 0.82 PM 10 : r = 0.86 SO 2 : r = 0.31 Increment : 1.0 ppm Odds Ratio (Lower CI, Upper CI); lag: Marginal GEE 1.22 (1.03-1.45); 0 1.3 (1.11-1.52); 1 1.26 (1.09-1.46); 2

Transition GEE 1.18 (1.02-1.37); 0 1.25 (1.1-1.42); 1 1.18 (1.04-1.33); 2



# Table C-5. Studies of short-term CO exposure an d respiratory hospital ad missions and ED visits.

Study Design Concentrations Effect Estimates (95% CI)

Author: Abe et al. (2009, 190536 ) Period of Study: January 1-December 31, 2005

Location: Tokyo, Japan ED Visits

Health Outcome: Asthma Study Design: Time-series Statistical Analyses: Bivariate Pearson correlation coefficitnes, ARIMA model Age Groups Analyzed: Children: ≤ 14 yr, Adults: ≤ 15 yr Sample Description: Data from daily number of ambulance transports to ED for asthma Averaging Time: NR Mean (SD) unit: 11.5ppm Range (Min, Max): 3-44ppm Copollutant: NR Increment: 0.1ppm

ARIMA model for ambulance trans ports to ED for asthma exacerbation among adults: β coefficient: 0.151, SE: 0.098, t statistic: 1. 537, P value: .125

ARIMA model for ambulance trans ports to ED for asthma exacerbation among children: β coefficient: 0.019, SE: 0.034, t statistic: 0. 549, P value: 0.583 Lags examined: 0 On the day with the highest CO the number of transports was 25. The number of transports for adults and CO had significant bivariate correla tions. The fitted ARIMA model had no significant associations.



### January 2010 C-42

### Study Design Concentrations Effect Estimates (95% CI)

Author: Anderson et al. (2001, 017033 ) Period of Study: 10/1994-12/1996

Location: West Midlands; U.K. Hospital Admission Health Outcome (ICD9): Respiratory diseases asthma (493) COPD (490-492, 494-496) Study Design: Time series Statistical Analyses:Regression with quasilikelihood approach and GAM Age Groups Analyzed: All ages 0-14 yr 15-64 yr ≥ 65 yr Pollutant: CO Averaging Time: Max 8-h avg Mean (SD) unit: 0.8 (0.7) ppm Range (Min, Max): (0.2, 10) Copollutant: correlation PM 10 : r = 0.55; PM 2.5 : r = 0.54; PM 2.5-10 : r = 0.10; BS: r = 0.77; SO 4 2- : r = 0.17; NO 2 : r = 0.73; O 3 : r = -0.29; SO 2 : r = 0.49 Increment: 1.0 ppm % Increase (Lower CI, Upper CI); lag: Respiratory Diseases Age Group All ages: 0.3% (-1.10 to 1.70); 0-1 0-14: 1.50% (-0.60 to 3.60); 0-1 15-64: -0.70% (-3.60 to 2.30); 0-1 ≥ 65: 0.00% (-2.10 to 2.10); 0-1

Asthma Age Group 0-14: 3.90% (-0.50 to 8.50); 0-1 15-64: -4.90% (-10.60 to 1.10); 0-1

COPD Age Group ≥ 65: 1.00% (-2.50 to 4.60); 0-1

Author: Andersen et al. (2007, 093201 ) Period of Study: 1/1999-12/2004

Location: Copenhagen, Denmark Hospital Admission Health Outcome (ICD10): Respiratory diseases: chronic bronchitis (J41-42), emphysema (J43), COPD (J44), asthma (j45), status asthmaticus (j46), pediatric asthma (j45), pediatric asthmaticus (j46) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups Analyzed: 5-18 yr; ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.3 (0.1) ppm IQR (25th, 75th): (0.22, 0.34) Copollutant; correlation: PM 10 : r = 0.45 Increment: 0.12 ppm Relative Risk (Lower CI, Upper CI); lag: Respiratory Disease Age Group: ≥ 65 CO: 1.024 (0.997-1.053); 0-4 CO, PM 10 : 1.001 (0.961-1.042); 0-4

Asthma Age Group: 5-18 CO: 1.104 (1.018-1.198); 0-5 CO, PM 10 : 1.023 (0.911-1.149); 0-5

Author: Atkinson et al. (1999, 007882 ) Period of Study: 1/1992-12/1994

Location: London, U.K. ED Visits Health Outcome (ICD9): Respiratory complaints: wheezing, inhaler request, chest infection, chronic obstructive lung disease (COLD), difficulty breathing, cough, other respiratory complaints. e.g., croup, pleurisy, noisy breathing; Asthma (493) Study Design: Time-series Statistical Analyses: Poisson Age Groups Analyzed: All ages 0-14 yr 15-64 yr ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.8 (0.4) ppm Range (Min, Max): (0.2, 5.6) Copollutant; correlation: NO 2 O 3 SO 2 PM 10 BS Increment: 0.8 ppm % Increase (Lower CI, Upper CI); lag : Respiratory complaints Age Group All ages: 0.76% (-0.83, 2.38); 1 0-14: 2.92% (0.60, 5.30); 1 15-64: 2.15% (-0.27, 4.63); 1 ≥ 65: 4.29% (1.15, 7.54); 0

Asthma visits: Single-pollutant model Age Group: All ages: 3.32% (0.56, 6.16); 1 0-14: 4.13% (-0.11, 8.54); 0 15-64: 4.41% (0.46, 8.52); 1 Multi-pollutant model Age Group: 0-14 CO, NO 2 : 2.05% (-2.25, 6.54); 0 CO, O 3 : 4.48% (0, 9.16); 0 CO, SO 2 : 2.34% (-1.94, 6.81); 0 CO, PM 10 : 2.93% (-1.53, 7.58); 0 CO, BS: 4.19% (-0.04, 8.60); 0



### January 2010 C-43

### Study Design Concentrations Effect Estimates (95% CI)

Author: Bedeschi et al. (2007, 090712 ) Period of Study: 1/2001-3/2002

Location: Reggio Emilia, Italy ED Visits Health Outcome (ICD9): Asthma (493); Asthma-like disorders, i.e., asthma, bronchiolitis, dyspnea/ shortness of breath; Other respiratory disorders (i.e., upper and lower respiratory illness including sinusitis, bronchitis, and pneumonia) Study Design: Time series Statistical Analyses: Poisson GAM, penalized splines Age Groups Analyzed: <5 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.4 (0.7) mg/m 3 Range (Min, Max): (0.4, 4.6) Copollutant; correlation: PM 10 : r = 0.61 TSP: r = 0.61 SO 2 : r = 0.71 NO 2 : r = 0.77 The study did not provide quantitative results for CO.

Author: Bell et al. (2008, 091268 ) Period of Study: 1/1995-12/2002

Location: Taipei, Taiwan Hospital Admissions Health Outcome (ICD9): Pneumonia (486); asthma (493) Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SE) unit: 0.9 ppm Range (Min, Max): (0.3, 3.6) Copollutant: NR Increment: 0.5 ppm % Increase (Lower CI, Upper CI); lag Asthma (avg correlation between monitor pairs = 0.75 (13 monitors)) 3.29% (-0.74 to 7.49); 0 .49% (-4.25 to 3.41); 1 -0.84% (-4.43 to 2.88); 2 0.48% (-4.02 to 3.18); 3 0.74% (-4.62 to 6.4); 0-3 Pneumonia (avg correlation between monitor pairs = 0.75 (13 monitors)) 1.91% (-1.97 to 5.95); 0 0.03% (-3.65 to 3.85); 1 0.36% (-3.2 to 4.04); 2 -1.29% (-4.77 to 2.32); 3 0.21% (-5.03 to 5.73); 0-3 Asthma (avg correlation between monitor pairs = 0.88 (5 monitors)) 1.68% (-1.68 to 5.15); 0 -1.19% (-4.29 to 2.01); 1 -0.83% (-3.83 to 2.26); 2 -0.35% (-3.32 to 2.71); 3 -0.31% (-4.9 to 4.5); 0-3 Pneumonia (avg correlation between monitor pairs = 0.88 (5 monitors)) 1.24% (-2.02 to 4.6); 0 -0.01% (-3.06 to 3.13); 1 0.57% (-2.4 to 3.62); 2 -0.85% (-3.78 to 2.16); 3 0.31% (-4.23 to 5.06); 0-3 Asthma (monitors with ≥ 0.75 between monitor correlations (11 monitors), avg correlation between monitor pairs = 0.81) 2.87% (-0.91 to 6.79); 0 -0.71% (-4.2 to 2.91); 1 -0.73% (-4.08 to 2.73); 2 -0.41% (-3.72 to 3.01); 3 0.51% (-4.6 to 5.89); 0-3 Pneumonia (monitors with ≥ 0.75 between monitor correlations (11 monitors) to avg correlation between monitor pairs = 0.81) 0.98% (-1.68 to 5.76); 0 -0.12% (-3.54 to 3.42); 1 0.37% (-2.95 to 3.8); 2 -1.08% (-4.34 to 2.3); 3 0.3% (-4.71 to 5.57); 0-3



### January 2010 C-44

### Study Design Concentrations Effect Estimates (95% CI)

Author: Bellini et al. (2007, 097787 ) Period of Study: 1996-2002

Location: 15 Italian cities Hospital Admissions

Health Outcome: Respiratory conditions Study Design: Time-series; Meta-analysis Statistical Analyses: 1. GLM for city-specific estimates 2. Bayesian random-effects for meta analysis Age Groups Analyzed: All ages Pollutant: CO Averaging Time: NR Mean (SD) unit: NR Range (Min, Max): NR Copollutant: correlation NR Increment: 1 mg/m 3 % Increase (Lower CI, Upper CI); Lag Respiratory conditions All ages: Season: Winter: 0.58%; 0-1 Summer: 3.47%; 0-1 All Season: 1.25%; 0-3

Note: Estimates from Bi ggeri et al. (2004)

Author: Braga et al. (2001, 016275 ) Period of Study: 1/1993-11/1997

Location: Sao Paulo, Brazil Hospital Admissions Health Outcome (ICD9): Respiratory (460-519) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: ≤ 2 yr 3-5 yr 6-13 yr 14-19 yr 0-19 yr Pollutant: CO Averaging Time: Maximum 8-h avg Mean (SD) unit: 4.8 (2.3) ppm Range (Min, Max): (0.6, 19.1) Copollutant: correlation PM 10 : r = 0.60 O 3 : r = -0.07 SO 2 : r = 0.47 Increment: 3 ppm % Increase (Lower CI, Upper CI); lag: Respiratory Age Group: ≤ 2: 5.00% (3.30-6.80); 0-6 3-5: 4.90% (1.40-8.50); 0-6 6-13: 1.00% (-2.50 to4.60); 0-6 14-19: 11.30% (5.90-16.80); 0-6 0-19: 4.90% (3.50-6.40); 0-6

Author: Burnett et al. (1999, 017269 ) Period of Study: 1/1980-12/1994

Location: Toronto, ON, Canada Hospital Admissions Health Outcome (ICD9): Asthma (493); COPD (490-492, 496); respiratory infection (464, 466, 480-487, 494) Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.18 ppm IQR (25th, 75th): (0.9, 1.4) Copollutant: correlation PM 2.5 : r = 0.49 PM 10-2.5 : r = 0.20 PM 10 : r = 0.43 NO 2 : r = 0.55 SO 2 : r = 0.37 O 3 : r = -0.23 Increment: 1.18 ppm % Increase (t-value); lag: Asthma: 5.35% (3.92); 0 COPD: 2.93% (1.48); 0 Respiratory Infection: 5.00% (4.25); 0 Asthma: Multipollutant model CO, SO 2 , O 3 : 5.15% CO, PM 2.5 , SO 2 , O 3 : 4.63% CO, PM 10-2.5 , SO 2 , O 3 : 5.25% CO, PM 10 , SO 2 , O 3 : 4.80% CO, PM 10-2.5 , O 3 : 4.00% COPD: Multipollutant model CO, SO 2 , O 3 : 3.02% CO, PM 2.5 , SO 2 , O 3 : 2.46% CO, PM 10-2.5 , SO 2 , O 3 : 3.00% CO, PM 10 , SO 2 , O 3 : 2.75% CO, PM 10-2.5 , O 3 : 3.00%

Author: Burnett et al. (2001, 093439 ) Period of Study: 1/1980-12/1994

Location: Toronto, ON, Canada Hospital Admissions Health Outcome (ICD9): Asthma (493); Acute bronchitis/ bronchiolitis (466); croup (464.4) ; pneumonia (480-486) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: <2 yr Pollutant: CO Averaging Time: 1-h avg Mean (SD) unit: 1.9 ppm IQR (25th, 75th): (1.3, 2.3) Copollutant: correlation O 3 : r = 0.24 Increment: 1.9 ppm % Increase (Lower CI, Upper CI); lag Respiratory problems CO: 19.20%; 0-1 CO, O 3 : 14.30%; 0-1



### January 2010 C-45

### Study Design Concentrations Effect Estimates (95% CI)

Author: Cakmak et al. (2006, 093272 ) Period of Study: 4/1993-3/2000

Location: 10 Canadian cities Hospital Admissions Health Outcome (ICD9): Actue bronchitis/bronchiolitis (466); pneumonia (480-486); chronic/ unspecified bronchitis (490, 491); emphysema (492); asthma (493); bronchiectasis (494); chronic airway obstruction (496) Study Design: Time series Statistical Analyses: 1. Poisson 2. Restricted Maximum Likelihood Method Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.8 ppm Range (Min, Max): (0.0, 6.5) Copollutant: correlation SO 2 NO 2 O 3 Increment: 0.8 ppm % Increase (Lower CI, Upper CI); lag: Respiratory disease CO: 0.60% (0.20, 1); 2.8 CO, SO 2 , NO 2 , O 3 : -0.20% (-0.70- 0.30); 2.8

Author: Cheng et al. (2007, 093034 ) Period of Study: 1996-2004

Location: Kaohsiung, Taiwan Hospital Admissions Health Outcome (ICD9): Pneumonia (480-486) Study Design: Bidirectional

case-crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.76 ppm Range (Min, Max): (0.14, 1.72) Copollutant: correlation PM 10 SO 2 NO 2 O 3 Increment: 0.31 ppm Odds Ratio (Lower CI, Upper CI); lag: OR for pneumonia and exposure to various pollutants for all ages in areas ≥ 25°C or <25°C Pollutant and Temperature CO, ≥ 25 oC: 1.18 (1.14-1.23); 0-2 CO, <25 oC: 1.47 (1.41-1.53); 0-2 CO, PM 10 , ≥ 25 oC: 1.15 (1.11-1.2); 0-2 CO, PM 10 , <25 oC: 1.28 (1.21-1.35); 0-2 CO, SO 2 , ≥ 25 oC: 1.22 (1.17-1.27); 0-2 CO, SO 2 , <25 oC: 1.49 (1.42-1.56); 0-2 CO, NO 2 , ≥ 25 oC: 1.2 (1.15-1.27); 0-2 CO, NO 2 , <25 oC: 1.01 (0.95-1.08); 0-2 CO, O 3 , ≥ 25 oC: 1.16 (1.12-1.2); 0-2 CO, O 3 , <25 oC: 1.44 (1.38-1.5); 0-2

Author: Chiu et al. (2009, 190249 ) Period of Study: 1996-2004

Location: Taipei, Taiwan Hospital Admissions

Health Outcome: pneumonia HA Study Design: case-crossover Statistical Analyses: Conditional Logistic regression Age Groups Analyzed: All ages Sample Description: 152,594 HA for 47 hospitals in Taipei city Averaging Time: 24h Mean (SD) unit: 1.26 ppm Range (min, max) : 0.12, 3.66 Copollutant: correlation PM 10 : r = 0.34 SO 2 : r = 0.57 NO 2 : r = 0.69 O 3 : r = -0.31 Increment: 0.57 ppm (IQR) OR Estimate [Lower CI, Upper CI] ; lag: Lags examined: one wk before to one wk after

CO: ≥ 23°C: 1.25 (1.21, 1.29) <23°C: 1.12 (1.09, 1.15)

CO + PM 10 : ≥ 23°C: 1.23 (1.19, 1.27) <23°C: 1.05 (1.02, 1.09)

CO + SO 2 : ≥ 23°C: 1.25 (1.21, 1.30) <23°C: 1.27 (1.22,1.31)

CO + NO 2 : ≥ 23°C: 0.97 (0.93, 1.02) <23°C: 1.14 (1.09, 1.20)

CO + O 3 : ≥ 23°C: 1.24 (1.20, 1.28) <23°C: 1.21 (1.17, 1.24)



### January 2010 C-46

### Study Design Concentrations Effect Estimates (95% CI)

Author: Cho et al. (2000, 099051 ) Period of Study: 1/1996-12/1996

Location: 3 South Korea cities: Hospital Admissions Health Outcome (ICD9): Bronchial asthma; COPD; bronchitis Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All Ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Daejeon: 1.424 (0.611) ppm Ulsan: 0.950 (0.211) ppm Suwon: 1.270 (0.549) ppm Range (Min, Max): Daejeon: (.364, 3.504) Ulsan: (.380, 1.675) Suwon: (.250, 3.616) Copollutant: correlation Daejeon SO 2 : r = 0.280; NO 2 : r = 0.041; TSP: r = 0.193; O 3 : r = -0.101; O 3 Max: r = -0.069 Ulsan SO 2 : r = 0.108; NO 2 : r = 0.446; TSP: r = 0.286; O 3 : r = -0.195; O 3 Max: r = -0.107 Suwon SO 2 : r = 0.556; NO 2 : r = 0.291; TSP: r = 0.496; O 3 : r = -0.371; O 3 Max: r = -0.365 Increment: 1,000 ppm Relative Risk (Lower CI, Upper CI); lag: Estimates obtained using dummy variables to apply environmental indicators to the model Daejeon CO: 1.26 (1.08-1.47) TSP, SO 2 , NO 2 , O 3 : 1.21 (1.02-1.44) Ulsan CO: 3.55 (1.65-7.63) TSP, SO 2 , NO 2 , O 3 : 2.51 (1.06-5.93) Suwon CO: 1.24 (0.97-1.59) TSP, SO 2 , NO 2 , O 3 : 1.19 (0.88-1.61) Estimates obtained using actual measured integrated environmental pollution indicator values Daejeon CO: 1.34 (1.14-1.58) Ulsan CO: 1.27 (0.94-1.71) Suwon CO: 3.55 (1.27-9.93)

Author: Delfino et al. (2008, 156390 ) Period of Study: January 1, 2000-December 31, 2003

Location: Orange County, California ED Visits

Health Outcome: Asthma Study Design: Longitudinal, Cohort Statistical Analyses: Proportional hazards models in SAS version 9.2 Age Groups Analyzed: 0-18 yr Sample Description: Various gender, race, insurance status, income, poverty level, residence distance to treating hospital Averaging Time: NR Mean (SD) unit: Cool season: 0.114 (0.052), Warm season: 0.103 (0.048) Range (Min, Max): Cool season: 0.014 -0.378, Warm season: 0.013-0.482 Copollutant: NO X Increment: 0.056 ppm HR (95% CI): Unadjusted: 1.072 (1.016 – 1.131), Adjusted: 1.073 (1.013 – 1.137), Male: 1.054 (0.978 – 1.137), Female: 1.100 (1.011 – 1.197), 0 yr: 1.158 (1.041 – 1.289), 1-5 yr: 1.021 (0.933 – 1. 117), 6-18 yr: 1.076 (0.972 – 1.191), Median or less poverty: 1.054 (0.979 – 1.134), Greater than the median pov erty: 1.094 (1.006 – 1.190), Greater than the median inco me: 1.120 (1.034 – 1.213), Median or less income: 1.041 (0.959 – 1.129), Private insurance: 1.102 (1.006 – 1. 206), Government sponsored or self-pay insurance: 1. 061 (0.989 – 1.138), Unknown insurance: 0.913 (0.591 – 1.412), White: 1.113 (1.027 – 1.205), Hispanic: 1.081 (0. 996 – 1.173), Non-Hispanic nonwhite: 0.804 (0.601 – 1.074) Lags examined: NR The point estimates for CO are stronger in girls than in boy and in infants than in older children. There is little difference in coefficients between adjusted and unadjusted CO models. There were significant increased risks of repeated hospital encounters of 7% to 10% per IQR increase in traffic-related CO exposure.

Author: Farhat et al. (2005, 089461 ) Period of Study: 8/1996-8/1997

Location: Sao Paulo, Brazil Hospital Visits & ED Visits Health Outcome (ICD9): Pneumonia/bronchopneumonia (480-486); asthma (493); bronchiolitis (466) Study Design: Time-series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All ages Pollutant: CO Averaging Time: Max 8-h avg Mean (SD) unit: 3.8 (1.6) ppm Range (Min, Max): (1.1, 11.4) Copollutant: correlation PM 10 : r = 0.72; SO 2 : r = 0.49; NO 2 : r = 0.59; O 3 : r = -0.8 Increment: 1.8 ppm % Increase (Lower CI, Upper CI); lag: Lower Respiratory Tract Disease ED Visits CO, PM 10 : -0.10% (-5.60 to 5.30); 0-2 CO, NO 2 : -1.20% (-6.70 to 4.20); 0-2 CO, SO 2 : 3.70% (-1.00 to 8.40); 0-2 CO, O 3 : 4.80% (0.50-9.10); 0-2 CO, PM 10 , NO 2 , SO 2 , O 3 :- 0.64% (-6.90 to 5.60); 0-2 Pneumonia/ Bronchopneumonia Hospital Admissions CO, PM 10 : 4.40% (-7.90 to 16.70); 0-2 CO, NO 2 : 4.40% (-88.70 to 17.50); 0-2 CO, SO 2 : 7.80% (-2.50 to 18.20); 0-2 CO, O 3 : 9.60% (-0.50 to 19.70); 0-2 CO, PM 10 to NO 2 , SO 2 , O 3 :5.10% (-9.60 to 19.70); 0-2 Asthma/ Bronchiolitis Hospital Admissions CO, PM 10 : 6.10% (-14.90 to 27.10); 0-2 CO, NO 2 : 2.40% (-16.90 to 21.70); 0-2 CO, SO 2 : 10.60% (-6.60 to 27.80); 0-2 CO, O 3 : 12.40% (-3.60 to 28.40); 0-2 CO, PM 10 to NO 2 , SO 2 , O 3 : 8.80% (-15.60 to 33.30); 0-2



### January 2010 C-47

### Study Design Concentrations Effect Estimates (95% CI)

Author: Fung et al. (2006, 089789 ) Period of Study: 6/1995-3/1999

Location: Vancouver, Canada Hospital Admissions Health Outcome (ICD9): Respiratory Illness Study Design: 1. Dewanji and Moolgavkar 2. Time-series 3. Bidirectional case-crossover Statistical Analyses: 1. Dewanji and Moolgavkar 2. Poisson 3. Conditional logistic regression Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.69 0.25) ppm Range (Min, Max): (0.28, 2.03) Copollutant: correlation CoH: r = 0.85; O 3 : r = -0.53; NO 2 : r = 0.74; SO 2 : r = 0.61; PM 10 : r = 0.46; PM 2.5 : r = 0.23; PM 10-2.5 : r = 0.51 Increment: 0.24 ppm Relative Risk (Lower CI, Upper CI); lag Dewanji and Moolgavkar 1.008 (0.997-1.02); 0 1.012 (0.999-1.025); 0-2 1.010 (0.995-1.025); 0-4 1.009 (0.991-1.026); 0-6 Time-series 1.012 (1.000-1.023); 0 1.017 (1.003-1.032); 0-2 1.017 (1.001-1.035); 0-4 1.016 (0.996-1.036); 0-6 Bidirectional case-crossover 1.010 (0.006-1.023); 0 1.012 (0.996-1.027); 0-2 1.012 (0.995-1.03); 0-4 1.010 (0.991 1.031; 0-6

Author: Fusco et al. (2001, 020631 ) Period of Study: 1/1995 10/1997

Location: Rome, Italy Hospital Admissions Health Outcome (ICD9): Respiratory conditions (460- 519, excluding 470-478); acute respiratory infections plus pneumonia (460-466, 480-486); COPD (490-492, 494-496) asthma (493) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages 0-14 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 3.6 (1.2) mg/m 3 IQR (25th, 75th): (2.8, 4.3) Copollutant: correlation All Year SO 2 : r = 0.56 NO 2 : r = 0.31 O 3 : r = -0.57 Cold Season SO 2 : r = 0.37 NO 2 : r = 0.41 O 3 : r = -0.44 Warm Season SO 2 : r = 0.44 NO 2 : r = 0.59 O 3 : r = -0.38 Increment: 1.5 mg/m 3 % Increase (Lower CI, Upper CI); lag: Age Group: All Ages Respiratory conditions 2.80% (1.30-4.30); 0 1.80% (0.20-3.30); 1 0.20% (-1.30 to 1.80); 2 0.50% (-2.00 to 1.10); 3 0.70% (-0.80 to 2.20); 4 CO, NO 2 : 2.30% (0.60-4.00); 0 Acute Respiratory Infections plus pneumonia 2.20% (0.00-4.40); 0 2.10% (-0.10 to 4.40); 0 1.70% (-0.50 to 4.00); 2 -0.90% (-3.00 to 1.30); 3 1.50% (-0.70 to 3.70); 4 CO, NO 2 : 0.00% (-2.30 to 2.40); 0 Asthma 5.50% (0.90-10.40); 0 0.80% (-3.80 to 5.70); 1 -1.30% (-5.90 to 3.50); 2 -3.00% (-7.40 to 1.60); 3 0.60% (-4.00 to 5.30); 4 CO, NO 2 : 4.80% (0.30-9.50); 0 COPD 4.30% (1.60-7.10); 0 -0.20% (-2.90 to 2.50); 1 -0.20% (-2.90 to 2.60); 2 -0.30% (-3.00 to 2.40); 3 -0.10% (-2.80 to 2.60); 4 CO, NO 2 : 4.80% (0.90-7.90); 0 Warm Season Respiratory Conditions: 10.80% (6.70-14.80); 0 Acute respiratory infe ctions plus pneumonia: 8.60% (2.90-14.60); 0 COPD: 13.90% (6.80-21.50); 0 Age Group: 0-14 Respiratory conditions 2.50 (-0.30 to 5.50); 0 0.80 (-2.10 to 3.80); 1; 0.20 (-2.70 to 3.10); 2 -1.00 (-3.70 to 1.90); 3 3.20 (0.40- 6.20); 4 CO, NO 2 : 4.10 (-1.20 to 9.80); 1 Acute Respiratory Infect ions plus Pneumonia 2.50 (-0.80 to 5.80); 0 -0.10 (-3.40 to 3.20); 1 0.90 (-2.30 to 4.30); 2 -2.00 (-5.10 to 1.20); 3 3.20 (0.00-6.60); 4 CO, NO 2 : 6.90 (0.80-13.40); 1 Asthma 6.30 (-0.50 to 13.50); 0 8.20 (1.10-15.70); 1; -0.70 (-7.30 to 6.30); 2



### January 2010 C-48

### Study Design Concentrations Effect Estimates (95% CI) 3.50 (-3.20 to 10.60); 3; 4.80 (-1.90 to 12.00); 4 CO, NO 2 : 3.30 (-4.20 to 11.30); 1

Author: Gouveia and Fletcher (2000, 010436 ) Period of Study: 11/1992-9/1994

Location: Sao Paulo, Brazil Hospital Admissions Health Outcome (ICD9): All respiratory diseases Pneumonia (480-486); asthma (493); bronchitis (466, 490, 491) Study Design: Time-series Statistical Analyses: Poisson Age Groups Analyzed: <1 yr; <5 yr Pollutant: CO Averaging Time: Max 8-h avg Mean (SD) unit: 5.8 (2.4) ppm Range (Min, Max): (1.3, 22.8) Copollutant: correlation PM 10 : r = 0.63 SO 2 : r = 0.65 NO 2 : r = 0.35 Increment: 6.9 ppm Relative Risk (Lower CI, Upper CI); lag: All respiratory diseases Age Group: <5: 1.017 (0.971-1.065); 0

Pneumonia Age Group: <5: 1.015 (0.961-1.071); 0; <1: 1.035 (0.975-1.099); 2

Asthma Age Group: <5: 1.081 (0.98-1.192); 0

Author: Hajat et al. (1999, 000924 ) Period of Study: 1/1992-12/1994

Location: London, U.K. General Practitioner Visits Health Outcome (ICD9): Asthma (493); lower respiratory diseases (464, 466, 476, 480- 483, 485-487, 490-492, 494- 496, 500, 501, 503-505, 510- 515, 518, 519, 786) Study Design: Time-series Statistical Analyses: Poisson Age Groups Analyzed: All ages 0-14 yr 15-64 yr ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: All yr: 0.8 (0.4) ppm Warm Season (April-September): 0.7 (0.3) ppm Cool Season (October-March): 1.0 (0.5) ppm Range (10th, 90th): All Year: (0.5, 1.3) Warm Season: (0.4, 1.0) Cool Season: (0.5, 1.6) Copollutant: correlation All Year NO 2 : r = 0.72; SO 2 : r = 0.51; BS: r = 0.85; O 3 : r = -0.40; PM 10 : r = 0.56 Warm Season NO 2 : r = 0.70; SO 2 : r = 0.32; BS: r = 0.65; O 3 : r = -0.12; PM 10 : r = 0.58 Cool Season NO 2 : r = 0.84; SO 2 : r = 0.58; BS: r = 0.87 Increment: 0.8 & 0.7 ppm % Increase (Lower CI, Upper CI); Lag

All Year: Asthma – Single Day Lags Increment: 0.8 ppm Age Group 0-14: 4.10% (-0.10 to 8.40); 2 15-64: 0.90% (-2.10 to 4.10); 0 ≥ 65: 7.50% (0.50-14.90); 2 All ages: 1.60% (-1.20 to 4.60); 2 Asthma – Cumulative exposure Increment: 0.7 ppm Age Group 0-14: 6.90% (1.30-12.90); 0-3 15-64: 1.00% (-3.20 to 5.40); 0-2 ≥ 65: 8.20% (0.40-16.60); 0-2 All ages: 1.80% (-1. 50 to 5.20); 0-2 Lower Respiratory Diseases – Single Day Lags Increment: 0.8 ppm Age Group 0-14: 4.40 (1.70-7.10); 2 15-64: 1.10 (-0.70 to 3.00); 2 ≥ 65: -2.60 (-4.80 to -0.30); 3 All ages: 2.00 (0.50-3.40); 2 Lower Respiratory Diseases – Cumulative exposure Increment: 0.7 ppm for 0-2 and 0-3; 0.8 for 0-1 Age Group 0-14: 3.00% (-1.00 to 7.20); 0-3 15-64: -0.70% (-2.90 to 1.50); 0-1 ≥ 65: -1.60% (-5.10 to 2.00); 0-3 All ages: 1.80% (0.10-3.60); 0-2 Warm or Cold Seasons: Asthma, Increment: 0.8 ppm Age Group & Season 0-14 & Warm Season: 11 .40% (3.30-20.00); 2 0-14 & Cold Season: 2. 90% (-3.20 to 9.40); 2 15-64 & Warm Season: 4.80% (-0.60 to 10.60); 0 15-64 & Cold Season: -0.30% (-4.80 to 4.50); 0 ≥ 65 & Warm Season: 15.60% (3.10-29.60); 2 ≥ 65 & Cold Season: 4.20% (-6.00 to 15.60); 2 Lower Respiratory Diseas es, Increment: 0.8 ppm Age Group & Season 0-14 & Warm Season: 2.70% (-2.90 to 8.60); 2 0-14 & Cold Season: 6.20% (2.30-10.20); 2 15-64 & Warm Season: 6.20% (2.30-10.20); 2 15-64 & Cold Season: 2.40% (-1.20 to 6.10); 2 ≥ 65 & Warm Season: 1.00% (-1.60 to 3.80); 2 ≥ 65 & Cold Season: -2.20% (-6.50 to 2.40); 3



### January 2010 C-49

### Study Design Concentrations Effect Estimates (95% CI)

Author: Hajat et al. (2002, 030358 ) Period of Study:

1/1992-12/1994

Location: London, U.K. General Practitioner Visits Health Outcome (ICD9): Upper respiratory diseases (URD) Study Design: Time-series Statistical Analyses: Poisson, GAM, LOESS Age Groups Analyzed: 0-14 yr 15-64 yr ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: All yr: 0.8 (0.4) ppm Warm Season (April-September): 0.7 (0.3) ppm Cool Season (October-March): 1.0 (0.5) ppm Range (10th, 90th): All Year: (0.5, 1.3) Warm Season: (0.4, 1.0) Cool Season: (0.5, 1.6) Copollutant: NR Increment: 0.6 ppm, 0.8 ppm, & 1.1 ppm % Increase (Lower CI, Upper CI); lag: Warm Season, Increment: 0.6 ppm Age Group 0-14: 2.90% (-0.60 to 6.40); 1 14-64: 7.90% (4.80-11.10); 1 ≥ 65: 4.90% (-1.80 to 12.10); 3 Cold Season, Increment: 1.1 ppm Age Group 0-14: -2.50% (-4.90 to 0.10); 1 14-64: 0.60% (-1.60 to 2.90); 1 ≥ 65: 5.60% (0.90-10.60); 3 All Year, Increment: 0.8 ppm Age Group 0-14: -2.20% (-4.00 to -0.30); 1 14-64: 2.70% (0.10-5.50); 1 ≥ 65: 5.80% (2.40 to 9.30); 3

Author: Hapcioglu et al. (2006, 093263 ) Period of Study: 1/1997-12/2001

Location: Istanbul, Turkey Hospital Admissions Health Outcome (ICD9): COPD (490-492, 494-496) Study Design: Cross sectional Statistical Analyses: Pearson Correlation Coefficient Age Groups Analyzed: All ages Pollutant: CO Averaging Time: Monthly Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NR Correlation Coefficient: Between CO exposure and COPD: 0.57 Between CO exposure and COPD when controlling for temperature: 0.25

Author: Hinwood et al. (2006, 088976 ) Period of Study: 1/1992-12/1998

Location: Perth, Australia Hospital Admissions Health Outcome (ICD9): COPD (490.00-496.99 excluding asthma); pneumonia/ influenza (480.00-489.99); Asthma (493) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: Max 8-h avg Mean (SD) unit: All Year: 2.3 (1.3) ppm; November-April: 2.2 (1.3) ppm; May-October: 2.4 (1.2) ppm Range (10th, 90th): All Year: (0.9, 4.2) November-April: (0.8, 4.2) May-October: (1.1, 4.2) Copollutant: correlation All Year: NO 2 : r = 0.57 O 3 : r = 0.00 November-April: NO 2 : r = 0.55 O 3 : r = 0.00 May-October: NO 2 : r = 0.57 O 3 : r = 0.16 Increment: 2.3 ppm Odds Ratio (Lower CI, Upper CI); Lag

Pneumonia 0.99999 (0.9737-1.0268); 0 1.00650 (0.9806-1.0331); 1 1.00351 (0.9779-1.0298); 2 1.00424 (0.9790-1.0301); 3 1.00581 (0.9752-1.0374); 0-1 1.01005 (0.9755-1.0458); 0-2 1.00805 (0.9701-1.0474); 0-3

COPD 0.99915 (0.9693-1.0297); 0 1.00205 (0.9727-1.0323); 1 0.98630 (0.9577-1.0158); 2 0.98970 (0.9619-1.0182); 3 0.99960 (0.9647-1.0357); 0-1 0.99260 (0.9538-1.0329); 0-2 0.99160 (0.9493-1.0357); 0-3

Author: Hwang and Chan (2002, 023222 ) Period of Study: 1998

Location: 50 communities in Taiwan Clinic Visits Health Outcome (ICD9): Lower respiratory tract infections (466, 480-486) Study Design: Time series Statistical Analyses: 1. General linear regression 2. Bayesian hierarchical modeling Age Groups Analyzed: All Ages 0-14 yr 15-64 yr ≥ 65 yr Pollutant: CO Averaging Time: Max 8-h avg Mean (SD) unit: 1.00 (0.30) ppm Range (Min, Max): (0.51, 1.71) Copollutant: NR Increment: 0.1 ppm % Increase (Lower CI, Upper CI); Lag Age Group: All Ages 0.80% (0.60-1.00); 0 0.10% (-0.10 to 0.30); 1 0.10% (-0.10 to 0.30); 2 Age Group: 0-14 0.70% (0.50-1.00); 0 0.10% (-0.20 to 0.30); 1 0.20% (-0.10 to 0.40); 2 Age Group: 15-64 0.90% (0.60-1.10); 0 0.20% (0.00-0.50); 1 0.20% (-0.10 to 0.40); 2 Age Group: ≥ 65 1.10% (0.80-1.50); 0 0.60% (0.30-1.00); 1 0.40% (0.10-0.80); 2



### January 2010 C-50

### Study Design Concentrations Effect Estimates (95% CI)

Author: Ito et al. (2007, 091262 ) Period of Study: 1999-2002

Location: New York City, NY ED Visits Health Outcome (ICD9): Asthma (493) Study Design: Time series Statistical Analyses: Poisson GLM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: Max 8-h avg Mean (SD) unit: All Season: 1.31 (0.43) ppm Warm Months (A pril-September): 1.22 (0.32) ppm Cold Months (October-March): 1.41 (0.5) ppm Range (5th, 95th): All season: (0.77, 2.11) Warm months (A pril-September): (0.75, 1.82) Cold months (October-March): (0.78, 2.33) Copollutant: NR Increment: 1.3 ppm Relative Risk (Lower CI, Upper CI); Lag

Warm months: 1.15 (1.07-1.25); 0-1

Author: Jayaraman et al. (2008, 180352 ) Period of Study: 2004-2005

Location: New Delhi, India Hospital Admissions

Health Outcome: respiratory Study Design: time series Statistical Analyses: Poisson regression (GAM) Age Groups Analyzed: All ages Sample Description: daily HA for respiratory unit of Safdarjung hospital Averaging Time: 24-h Mean (SD) unit: 2,379.14 (1,289.18) μg/m 3 Range (min, max): 588, 8458 Copollutant: SO 2 : r = 0.217* NO 2 : r = 0.204* SPM: r = 0.071 RSPM: r = 0.120 O 3 : r = 0.063 *p < 0.05 Increment: 10 μg/m 3 RR Estimate [Lower CI, Upper CI] ; lag: Lags examined: lag days 0-3 Single Pollutant: 0.9989 (0.985, 2.715), 2 Multi-pollutant: 0.998 (0.993, 1.004), 2 Winter, all ages: 1.027 (1.004, 1.051), 2 Winter, males 50-69: 2.625 (1.048, 1.158)

Author: Karr et al. (2007, 090719 ) Period of Study: 1995-2000

Location: South Coast Air Basin, CA Hospital Admissions Health Outcome (ICD9): Acute bronchiolitis (466.1) Study Design: Matched case control Statistical Analyses: Conditional logistic regression Age Groups Analyzed: Infants: 3 wk to 1 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Chronic: 1,770 ppb Subchronic: 1,720 ppb Range (Min, Max): Chronic: (120, 8300) Subchronic: (130, 5070) Copollutant: NR Increment: 910 ppb, 960 ppb Odds Ratio (Lower CI, Upper CI); lag: Increment: 910 ppb Subchronic broncholitis: 1 (0.97-1.03) Increment: 960 ppb Chronic broncholitis: 1 (0.97-1.03)

Author: Karr et al. (2006, 088751 ) Period of Study: 1995-2000

Location: South Coast Air Basin, CA Hospital Admissions Health Outcome (ICD9): Acute bronchiolitis (466.1) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: Infants: 3 wk to1 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1-day lag: Index*: 1,730 ppb Referent*: 1,750 ppb 4-day lag: Index*: 1,760 ppb Referent*: 1,790 ppb Range (Min, Max): Lag 1: Index*: (4, 9600) Referent*: (4, 9600) Lag 4: Index* (4, 8710) Referent* (4, 9600) Copollutant: NR * Index days: days lagged in reference to date of hospitalization of

a case. Referent days: are for each case and includes all days that are the same day of wk and in the same mo as the index day for that case for CO. Increment: 1361, 1400 ppb Odds Ratio (Lower CI, Upper CI); Lag Increment: 1361 ppb Age Group: Overall: 0.99 (0.96-1.02); 1 25-29 wk: 0.86 (0.68-1.1); 1 29 1/7 – 34 wk: 1 (0.86-1.15); 1 34 1/7 – 37 wk: 0.95 (0.87-1.04); 1 37 1/7 – 44 wk: 1 (0.97-1.03); 1 Increment: 1400 ppb Age Group: Overall: 0.97 (0.94-1); 4 25-29 wk: 0.93 (0.72-1.2); 4 29 1/7 – 34 wk: 0.89 (0.77-1.03); 4 34 1/7 – 37 wk: 0.98 (0.90-1.08); 4 37 1/7 – 44 wk: 0.97 (0.94-1); 4



### January 2010 C-51

### Study Design Concentrations Effect Estimates (95% CI)

Author: Kim et al. (2007, 092837 ) Period of Study: 2002

Location: Seoul, Korea Hospital Admissions Health Outcome (ICD10): Asthma (J45 and J46) Study Design: Bidirectional case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All Ages Pollutant: CO Averaging Time: Max 8-h avg Mean (SD) unit: Daily Concentration: 8.6 (4.6) ppm Relevant Concentration: 2.8 (2.8) ppm Range (Min, Max): Daily Concentration: (0.8, 44.0) Relevant Concentration: (0.0, 30.4) Copollutant: NR Relative Risk (Lower CI, Upper CI); lag:

Individual Level SEP Quintile 1: 1.06 (1.02-1.09); 1-3 ma Quintile 2: 1.05 (1.02-1.09); 1-3 ma Quintile 3: 1.05 (1.01-1.08); 1-3 ma Quintile 4: 1.07 (1.03-1.11); 1-3 ma Quintile 5: 1.05 (1.00-1.09); 1-3 ma Regional Level SEP Quintile 1: 0.99 (0.92-1.07); 1-3 ma Quintile 2: 1.06 (1.02-1.11); 1-3 ma Quintile 3: 1.04 (1.02-1.07); 1-3 ma Quintile 4: 1.10 (1.06-1.15); 1-3 ma Quintile 5: 1.06 (1.03-1.09); 1-3 ma Overall: 1.06 (1.04-1.07); 1-3 ma

Relative Effect Modification for SES

Individual Level SEP Quintile 1: 1 Quintile 2: 1 (0.95.1.04); 1-3 ma Quintile 3: 0.99 (0.94-1.03); 1-3 ma Quintile 4: 1.02 (0.97-1.06); 1-3 ma Quintile 5: 0.99 (0.94-1.04); 1-3 ma Regional Level SEP Quintile 1: 1 Quintile 2: 1.05 (0.97-1.14); 1-3 ma Quintile 3: 1.03 (0.96-1.11); 1-3 ma Quintile 4: 1.08 (1-1.16); 1-3 ma Quintile 5: 1.05 (0.97-1.13); 1-3 ma

Author: Kontos et al. (1999, 011326 ) Period of Study: 1/1987-12/1992

Location: Piraeus, Greece Hospital Admissions Health Outcome (ICD9): Respiratory conditions (laryngitis, bronchiolitis, tonsillitis, acute rhinopharyngitis, otitis, bronchopneumonia, pneumonia, asthma) Study Design: Time series Statistical Analyses: Stochastic dynamical system approach Age Groups Analyzed: 0-14 yr Pollutant: CO Averaging Time: 24-h avg Mean Range (SD) unit: 1987: 4.2 mg/m 3 1992: 3.6 mg/m 3 Range (Min, Max): NR Copollutant: correlation 1987-1989 Smoke: r = 0.2979; SO 2 : r = 0.2166; NO 2 : r = 0.1913 1990-1992 Smoke: r = 0.5383; SO 2 : r = 0.43283; NO 2 : 0.5223 This study did not present quantitative results for CO.

Author: Lee et al. (2002, 034826 ) Period of Study: 12/1997-12/1999

Location: Seoul, Korea Hospital Admissions Health Outcome (ICD10): Asthma (J45, J46) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: <5 yr Pollutant: CO Averaging Time: 1-h max Mean Range (SD) unit: 1.8 (0.7) ppm IQR (25th, 75th): (1.2, 2.2) Copollutant: correlation PM 10 : r = 0.598 SO 2 : r = 0.812 NO 2 : r = 0.785 O 3 : r = -0.388 Increment: 1.0 ppm Relative Risk (Lower CI, Upper CI); lag: RR for asthma and exposure to various pollutants for children under 15 yr old

Pollutant: CO: 1.16 (1.10-1.22); 2-3 avg CO, PM 10 : 1.13 (1.07-1.20); 2-3 avg CO, SO 2 : 1.17 (1.08-1.27); 2-3 avg CO, NO 2 : 1.04 (0.95-1.14); 2-3 avg CO, O 3 : 1.16 (1.11-1.22); 2-3 avg CO, O 3 , PM 10 : 1.148 (1.084-1.217); 2-3 avg CO, O 3 , PM 10 , SO 2 : 1.168 (1.075-1.269); 2-3 avg CO, O 3 , PM 10 , SO 2 , NO 2 : 1.098 (0.994-1.214); 2-3 avg



### January 2010 C-52

### Study Design Concentrations Effect Estimates (95% CI)

Author: Lee et al. (2006, 098248 ) Period of Study: 1/2002-12/2002

Location: Seoul, Korea Hospital Admissions Health Outcome (ICD10): Asthma (J45-46) Study Design: Time series Statistical Analyses: GAM with stringent parameters Age Groups Analyzed: <15 yr Pollutant: CO Averaging Time: Maximum 2-h avg Mean (SD) unit: High SES: 6.08 (2.10) ppb Moderate SES: 6.35 (2.44) ppb Low SES: 6.67 (2.59) ppb Range (Min, Max): NR Copollutant: correlation NO 2 : r = 0.55 SO 2 : r = 0.72 PM 10 : r = 0.28 O 3 : r = -0.36 Increment: 3.01 ppb, 0.26 ppb, 4.52 ppb, 3.68 ppb Relative Risk (Lower CI, Upper CI); lag: Increment: 3.01 ppb Overall: 1.07 (0.96-1.20); 0 Increment: 0.26 ppb High SES: 1.06 (0.96-1.17); 0 Increment: 4.52 ppb Moderate SES: 0.96 (0.84-1.10); 0 Increment: 3.68 ppb Low SES: 1.02 (0.85-1.24); 0

Author: Lee et al. (2007, 090707 ) Period of Study: 1996-2003

Location: Kaohsiung, Taiwan Hospital Admissions Health Outcome (ICD9): COPD (490-492, 494, 496) Study Design: Bidirectional

case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.77 ppm Range (Min, Max): (0.23, 1.72) Copollutant: PM 10 SO 2 NO 2 O 3 Increment: 0.29 ppm Odds Ratio (Lower CI, Upper CI); lag:

CO <25°C: 1.398 (1.306-1.496); 0-2 ≥ 25°C: 1.189 (1.123-1.259); 0-2 CO. PM 10 <25°C: 1.257 (1.152-1.371); 0-2 ≥ 25°C: 1.149 (1.079-1.224); 0-2 CO, SO 2 <25°C: 1.396 (1.295-1.504); 0-2 ≥ 25°C: 1.241 (1.161-1.326); 0-2 CO, NO 2 <25°C: 0.973 (0.877-1.080); 0-2 ≥ 25°C: 1.196 (1.104-1.297); 0-2 CO, O 3 <25°C: 1.378 (1.286-1.477); 0-2 ≥ 25°C: 1.170 (1.105-1.239); 0-2

Author: Lin et al. (1999, 040437 ) Period of Study: 5/1991-4/1993

Location: Sao Paulo, Brazil ED Visits Health Outcome (ICD9): Respiratory illness (lower respiratory illness, upper respiratory illness, wheezing) Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: <3 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 5 ppm Range (Min, Max): (1, 12) Copollutant: correlation PM 10 : r = 0.50 NO 2 : r = 0.35 SO 2 : r = 0.56 O 3 : r = 0.04 Increment: NR Relative Risk (Lower CI, Upper CI); lag: Overall Respiratory Illnesses CO: 1.206 (1.066-1.364); 0-5 CO, PM 10 , O 3 , SO 2 , NO 2 : 0.945 (0.808-1.105); 0-5 Lower Respiratory Illness CO: 1.203 (0.867-1.669); 0-5 CO, PM 10 , O 3 , SO 2 , NO 2 : 0.971 (0.641-1.472); 0-5 Upper Respiratory Illness CO: 1.237 (1.072-1.428); 0-5 CO, PM 10 , O 3 , SO 2 , NO 2 : 0.944 (0.785-1.135); 0-5 Wheezing CO: 0.813 (0.606-1.091); 0-5 CO, PM 10 , NO 2 , SO 2 , O 3 : 0.74 (0.505-1.085); 0-5



### January 2010 C-53

### Study Design Concentrations Effect Estimates (95% CI)

Author: Lin et al. (2003, 042549 ) Period of Study: 1/1981-12/1993

Location: Toronto, ON, Canada Hospital Admissions Health Outcome (ICD9): Asthma (493) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: 6-12 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.18 (0.50) ppm Range (Min, Max): (0, 6.10) Copollutant: correlation SO 2 : r = 0.37 NO 2 : r = 0.55 O 3 : r = -0.16 PM 2.5 : r = 0.45 PM 10-2.5 : r = 0.17 PM 10 : r = 0.38 Increment: 0.5 ppm Odds Ratio (Lower CI, Upper CI); lag: Boys: Adjusting for Daily Weather Variables 1.05 (1-1.11); 1 / 1.07 (1.01-1.14); 2 1.08 (1.01-1.16); 3 / 1.08 (1-1.17); 4 1.07 (0.99-1.16); 5 / 1.07 (0.98-1.17); 6 1.07 (0.98-1.17); 7 Adjusting for PM and Daily Weather Variables 1.05 (0.99-1.11); 1 / 1.08 (1.01-1.16); 2 1.09 (1.01-1.18); 3 / 1.10 (1.02-1.20); 4 1.09 (1.00-1.18); 5 / 1.09 (0.99-1.19); 6 1.09 (0.99-1.20); 7 Girls: Adjusting for Daily Weather Variables 1.00 (0.93-1.06); 1 / 1.01 (0.94-1.10); 2 1.00 (0.91-1.09); 3 / 0.98 (0.89-1.09); 4 1.01 (0.91-1.13); 5 / 1.03 (0.92-1.16); 6 1.04 (0.93-1.17); 7 Adjusting for PM and Daily Weather Variables 1.00 (0.93-1.07); 1 / 1.01 (0.92-1.10); 2 0.99 (0.90-1.09); 3 / 0.97 (0.87-1.08); 4 0.99 (0.89-1.11); 5 / 1.02 (0.90-1.15); 6 1.05 (0.93-1.20); 7

Author: Lin et al. (2004, 055600 )

Period of Study: 1/1987-12/1998

Location: Vancouver, BC Canada Hospital Admissions Health Outcome (ICD9): Asthma (493) Study Design: Time series Statistical Analyses: GAM, LOESS Age Groups Analyzed: 6-12 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.96 (0.52) ppm Range (Min, Max): (0.23, 4.90) Copollutant: correlation SO 2 : r = 0.67 NO 2 : r = 0.73 O 3 : r = -0.35 Increment: 0.5 ppm Relative Risk (Lower CI, Upper CI); lag: Boys High SES: 1.06 (0.98-1.14); 1 / 1.06 (0.97-1.15); 2 1.07 (0.97-1.17); 3 / 1.03 (0.93-1.14); 4 1.01 (0.91-1.12); 5 / 1.01 (0.91-1.13); 6 1.06 (0.94-1.18); 7 Low SES: 1.06 (0.99-1.14); 1 / 1.03 (0.95-1.12); 2 1.01 (0.93-1.11); 3 / 0.99 (0.90-1.09); 4 0.96 (0.87-1.06); 5 / 0.98 (0.88-1.08); 6 0.98 (0.88-1.09); 7 Girls High SES: 1.05 (0.94-1.16); 1 / 1.02 (0.90-1.15); 2 0.97 (0.85-1.11); 3 / 0.95 (0.83-1.10); 4 0.93 (0.80-1.08); 5 / 0.95 (0.82-1.11); 6 1.01 (0.87-1.19); 7 Low SES: 1.01 (0.92-1.11); 1 / 0.98 (0.89-1.10); 2 0.99 (0.88-1.11); 3 / 1.05 (0.93-1.19); 4 1.07 (0.94-1.21); 5 / 1.07 (0.94-1.23); 6 1.04 (0.91-1.20); 7

Author: Lin et al. (2005, 087828 ) Period of Study: 1998-2001

Location: Toronto, Canada Hospital Admissions Health Outcome (ICD9): Respiratory infections (464, 466, and 480-487) Study Design: Bidirectional case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: <5 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.16 (0.38) ppm Range (Min, Max): (0.38, 2.45) Copollutant: correlation PM 2.5 : r = 0.10 PM 10-2.5 : r = 0.06 PM 10 : r = 0.10 SO 2 : r = 0.12 NO 2 : r = 0.20 O 3 : r = -0.11 Increment: 0.44 ppm Odds Ratio (Lower CI, Upper CI); Lag Boys No adjustment: 1.11 (1.01-1.22); 0-3 / 1.10 (1.00-1.22); 0-5 Adjustment for weather variables: 1.13 (1.03-1.24); 0-3 / 1.13 (1.02-1.25); 0-5 Adjustment for weather variables and PM: 1.08 (0.98-1.20); 0-3 / 1.08 (0.97-1.20); 0-5 Girls No adjustment: 0.99 (0.89-1.10); 0-3 / 1.00 (0.89-1.13); 0-5 Adjustment for weather variables: 1.02 (0.92-1.14); 0-3: / 1.05 (0.93-1.18); 0-5 Adjustment for weather variables and PM: 1.01 (0.90-1.13); 0-3 / 1.02 (0.90-1.15); 0-5 Total No adjustment: 1.06 (0.98-1.14); 0-3 / 1.06 (0.98-1.15); 0-5 Adjustment for weather variables: 1.09 (1.01-1.17); 0-3 / 1.10 (1.01-1.19); 0-5 Adjustment for weather variables and PM: 1.05 (0.97-1.14); 0-3 / 1.06 (0.97-1.15); 0-5



### January 2010 C-54

### Study Design Concentrations Effect Estimates (95% CI)

Author: Linn et al. (2000, 002839 ) Period of Study: 1992-1995

Location: Los Angeles, CA Hospital Admissions Health Outcome (ICD9): APR-DRG Codes: Pulmonary (75-101); COPD (88) ICD9 Codes: Asthma (493) Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: 0-29 yr; ≥ 30 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Winter 1.7 (0.8) ppm Spring 1.0 (0.3) ppm Summer 1.2 (0.4) ppm Fall 2.1 (0.8) ppm Range (Min, Max): Winter: (0.5, 5.3) Spring: (0.4, 2.2) Summer: (0.3,2.7) Fall: (0.6, 4.3) Copollutant: correlation Winter NO 2 : r = 0.89; PM 10 : r = 0.78; O 3 : r = -0.43 Spring NO 2 : r = 0.92; PM 10 : r = 0.54; O 3 : r = 0.29 Summer NO 2 : r = 0.94; PM 10 : r = 0.72; O 3 : r = 0.03 Fall NO 2 : r = 0.84; PM 10 : r = 0.58; O 3 : r = -0.36 Increment: 1.0 ppm β (SE); lag: Pulmonary Age Group: ≥ 30 All Year: 0.007 Winter: 0.016 Spring: 0.014 Summer: 0.020 Fall: 0.020

Asthma Age Group 0-29 All Year: 0.036

Asthma Age Group: ≥ 30; All Year: 0.028 Winter: 0.045 Fall: 0.039

COPD Age Group: ≥ 30 All Year: 0.019 Winter: 0.035 Fall: 0.029



### January 2010 C-55

### Study Design Concentrations Effect Estimates (95% CI)

Author: Luginaah et al. (2005, 057327 ) Period of Study: 4/1995-12/2000

Location: Windsor, ON, Canada Hospital Admissions Health Outcome (ICD9): Respiratory illness (460-519) Study Design: Time series and case crossover Statistical Analyses: 1. Time-series: Poisson 2. Case-crossover: conditional logistic regression Age Groups Analyzed: All ages 0-14 yr 15-64 yr ≥ 65 yr Pollutant: CO Averaging Time: 1-h max Mean (SD) unit: 1.3 (1.0) ppm Range (Min, Max): (0, 11.82) Copollutant: correlation NO 2 : r = 0.38 SO 2 : r = 0.16 O 3 : r = 0.10 CoH: r = 0.31 PM 10 : r = 0.21 Increment: 1.17 ppm Relative Risk (Lower CI, Upper CI); Lag Females and Case-crossover study design Age Group: All ages: 1.037 (0.968-1.111); 1 1.063 (0.976-1.158); 2 1.087 (0.982-1.203); 3 Age Group: 0-14: 1.147 (1.006-1.307); 1 1.186 (1.020-1.379); 2 1.221 (1.022-1.459); 3 Age Group: 15-64: 1.005 (0.884-1.141); 1 1.007 (0.859-1.181); 2 1.032 (0.858-1.240); 3 Age Group: ≥ 65: 1.014 (0.922-1.116); 1 1.024 (0.907-1.156); 2 1.035 (0.893-1.200); 3 Males and Case-crossover study design Age Group: All Ages: 0.950 (0.884-1.020); 1 0.945 (0.862-1.036); 2 0.965 (0.866-1.075); 3 Age Group: 0-14: 1.003 (0.904-1.113); 1 0.997 (0.871-1.141); 2 0.970 (0.824-1.141); 3 Age Group: 15-64: 1.036 (0.870-1.233); 1 1.033 (0.821-1.299); 2 0.991 (0.760-1.293); 3 Age Group: ≥ 65: 0.867 (0.775-0.970); 1 0.865 (0.752-0.994); 2 0.946 (0.807-1.109); 3 Female and Time-series study design Age Group: All Ages: 1.049 (0.993-1.108); 1 1.032 (0.993-1.188); 2 1.051 (0.993-1.112); 3 Age Group: 0-14: 1.077 (0.979-1.184); 1 1.068 (1.001-1.139); 2 1.100 (0.997-1.213); 3 Age Group: 15-64: 1.072 (0.962-1.195); 1 1.025 ( 0.944-1.112); 2 1.081 (0.963-1.213); 3 Age Group: ≥ 65: 1.029 (0.957-1.118); 1 1.030 (0.928-1.144); 2 1.013 (0.899-1.142); 3 Male and Time-series study design Age Group: All Ages: 0.989 (0.932-1.049); 1 0.986 (0.946-1.029); 2 0.987 (0.929-1.048); 3 Age Group: 0-14: 1.034 (0.949-1.126); 1 0.996 (0.933-1.062); 2 0.968 (0.881-1.064); 3 Age Group: 15-64: 0.994 (0.854-1.157); 1 0.988 (0.884-1.104); 2 0.951 (0.806-1.121); 3 Age Group: ≥ 65: 0.901 (0.817-0.994); 1 0.904 (0.803-1.019); 2 0.963 (0.845-1.098); 3



### January 2010 C-56

### Study Design Concentrations Effect Estimates (95% CI)

Author: Martins et al. (2002, 035059 ) Period of Study: 5/1996-9/1998

Location: Sao Paulo, Brazil ED Visits Health Outcome (ICD10): Chronic lower respiratory disease (CLRD: J40-47) for chronic bronchitis, emphysema, other COPD, asthma, and bronchiectasia Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: >64 yr Pollutant: CO Averaging Time: Max 8-h avg Mean (SD) unit: 3.7 (1.7) ppm Range (Min, Max): (1.0, 12.6) Copollutant: correlation NO 2 : r = 0.62; SO 2 : r = 0.51; PM 10 : r = 0.73; O 3 : r = 0.07 Increment: 1.63 ppm β (SE); lag: Chronic Lower Respiratory Diseases Age Group >64: 0.0489 (0.0274); 2

Author: Masjedi et al. (2003, 052100 ) Period of Study: 9/1997-2/1998

Location: Tehran, Iran ED Visits Health Outcome (ICD9): Total acute respiratory conditions; asthma (493); COPD (490-492, 494, 496) Study Design: Time series Statistical Analyses: Multiple step-wise regression Age Groups Analyzed: Adults Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 8.85 ppm Range (Min, Max): (2.15, 23.8) Copollutant: NR Increment: NR β (p-value); lag; Asthma: -0.779 (0.12) COPD: 0.012 (0.71) Acute Respiratory conditions: -0.086 (0.400)

Correlation coefficients: Mean 3-day CO levels and asthma: -0.300 (0.149) Mean weekly CO level and asthma: -0.14 (0.2) Mean 10-day CO levels and asthma: -0.05 (0.43)

Author: McGowan et al. (2002, 030325 ) Period of Study: 6/1988- 12/1998

Location: Christchurch, New Zealand Hospital Admissions Health Outcome (ICD9): Pneumonia (480-487); acute respiratory infections (460-466); chronic lung diseases (491-492, 494-496); asthma (493) Study Design: Time series Statistical Analyses: Generalized Additive Model Age Groups Analyzed: <15 yr; >64 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.16 (1.51) mg/m 3 Range (Min, Max): (0, 15.7) Copollutant: NR This study did not provide quantitative results for CO.

Author: Migliaretti et al. (2007, 193772 ) Period of Study: 1/1997-12/1999

Location: Turin, Italy Hospital Admissions Health Outcome (ICD9): Respiratory illness (chronic bronchitis, emphysema, and other COPD) (490-496) Study Design: Case control Statistical Analyses: Multiple logistic regression Age Groups Analyzed: ≥ 15 yr 15-64 yr >64 yr Pollutant: CO Averaging Time: 8-h median Median (SD) unit: 3.36 (1.57) mg/m 3 Range (Min, Max): NR Copollutant: correlation TSP Increment: 1 mg/m3 Odds Ratio (Lower CI, Upper CI); lag:

CO Age Group ≥ 15: 1.053 (1.030-1.070) 15-64: 1.040 (0.987-1.085) >64: 1.054 (1.027-1.083) CO , TSP Age Group ≥ 15: 1.058 (1.024-1.096) 15-64: 1.062 (0.993-1.135) >64: 1.054 (1.011-1.099)



### January 2010 C-57

### Study Design Concentrations Effect Estimates (95% CI)

Author: Moolgavkar (2000, 010274 ) Period of Study: 1987-1995

Location: 3 U.S. counties: Los Angeles County,CA Cook County, IL Maricopa County, AZ Hospital Admissions Health Outcome (ICD9): COPD plus asthma (490-496) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All Ages 0-19 yr 20-64 yr ≥ 65 yr Pollutant: CO Averaging Time: 24-h median

Median unit: Cook: 993 ppb LA: 1347 ppb Maricopa: 1240 ppb Range (Min, Max): Cook: (224, 3912) LA:(237,5955) Maricopa: (269, 4777) Copollutant: correlation Cook County: NO 2 : r = 0.63; SO 2 : r = 0.35; O 3 : r = -0.28 LA County: NO 2 : r = 0.80; SO 2 : r = 0.78; O 3 : r = -0.52 Maricopa County: NO 2 : r = 0.66; SO 2 : r = 0.53; O 3 : r = -0.61 Increment: 1.0 ppm % Increase (t-statistic); lag: Age Group: ≥ 65 Cook County CO: 2.60 (1.9); 0; / 3.00 (2.2); 1; / 1.30 (1.0); 2; 1.40 (1.1); 3; / 1.10 (0.8 ); 4; / 2.30 (1.8); 5 Los Angeles County CO: 5.40 (11.3); 0; / 4.90 (10.1); 1; / 5.00 (10.2); 2; 4.90 (10.1); 3; / 4.00 (8.3); 4; / 4.30 (8.6); 5; CO, PM 10 : 4.30 (3.3); 0; / 5.30 (4.2 ); 1; / 5.10 (4.0); 2; 6.80 (5.6); 3; / 6.90 (5.4); 4; / 6.30 (4.7); 5; CO, PM 2.5 : 3.00 (1.9); 0; / 3.90 (2.5 ); 1; / 4.20 (2.6); 2; 6.50 (4.4); 3; / 5.80 (3.8 ); 4; / 5.10 (3.1); 5 Maricopa County CO: 1.40 (1.0); 0; / 0.80 (0.6 ); 1; / 1.20 (0.9); 2; 1.20 (0.9); 3; / 1.50 (1.1 ); 4; / 4.90 (3.8); 5 Age Group: 0-19 Los Angeles County CO: 8.20 (14.4); 0; / 9.00 (15.9) ; 1; / 9.20 (16.4); 2; 8.50 (15.0); 3; / 7.00 (12.1) ; 4; / 4.80 (8.1); 5; CO, PM 10 : 7.50 (14.4); 0; /: 7.40 (5.2 ); 1; / 6.40 (4.3); 2; 8.00 (5.5); 3; / 6.30 (4.0); 4; / 5.30 (3.5); 5; CO, PM 10-2.5 : 5.70 (3.4); 0; / 7.50 (4.9 ); 1; / 5.60 (3.3); 2; 5.40 (3.5); 3; / 4.40 (2.7 ); 4; / 1.80 (1.1); 5 Age Group: 20-64 Los Angeles County CO: 3.70 (8.6); 0; / 3.90 (9.1); 1; / 4.50 (10.6); 2; 3.50 (8.3); 3; / 3.40 (7.9); 4; / 3.50 (7.9); 5; CO, PM 10 : 5.00 (4.6); 0; / 3.00 (2.7); 1; / 3.10 (2.8); 2; 5.20 (4.7); 3; / 5.90 (5.1); 4; / 4.90 (4.4); 5; CO, PM 2.5 : 3.50 (2.5); 0; / 0.60 (0.4); 1; / 1.10 (0.8); 2; 5.70 (4.1); 3; / 4.70 (3.3); 4; / 3.90 (2.8); 5; CO, PM 10-2.5 : 2.80 (2.2); 0; / 2.50 (2.0 ); 1;/ 0.60 (0.5); 2; 3.90 (3.2); 3; / 3.40 (2.8 ); 4; / 4.00 (3.4); 5

Author: Moolgavkar (2003, 042864 ) Period of Study: 1987-1995

Location: 2 U.S. counties: Los Angeles County, CA, and Cook County, IL Hospital Admissions Health Outcome (ICD9): COPD plus asthma (490-496) Study Design: Time series Statistical Analyses: Poisson GAM, Poisson GLM with natural splines Age Groups Analyzed: All Ages; ≥ 65 yr Pollutant: CO Averaging Time: 24-h median

Median unit: Cook: 993 ppb LA: 1347 ppb Maricopa: 1240 ppb Range (Min, Max): Cook: (224, 3912) LA: (237,5955) Copollutant: correlation Cook County: NO 2 : r = 0.63; SO 2 : r = 0.35; O 3 : r = -0.28 Los Angeles County: NO 2 : r = 0.80; SO 2 : r = 0.78; O 3 : r = -0.52 Increment: 1 ppm % Increase (t-statistic); lag: COPD–Los Angeles County CO: GAM-30 (10-8): 5.48 (17.67); 0; / 5.67 (18.22); 1; / 5.90 (19.01); 2; 5.28 (16.94); 3; / 4.59 (14.50); 4; / 4.10 (12.80); 5 GAM-100 (10-8): 2.37 (8.67); 0; / 2.41 (8.73) ; 1; / 2.41 (8.76); 2; 1.81 (6.58); 3; / 1.38 (4.94); 4; / 1.07 (3.82); 5 NS-100: 2.28 (5.65); 0; / 2.29 (5.50) ; 1; / 2.32 (5.33); 2; 1.74 (4.10); 3; / 1.30 (3.16); 4; / 1.00 (2.46); 5 COPD–Cook County CO: GAM-100 (10-8): 2.11 (1.62); 0; / 2.85 (2. 16); 1; / 1.14 (0.86); 2; 1.05 (0.79); 3; / 0.43 (0.33); 4; / 0.34 (0.26); 5



### January 2010 C-58

### Study Design Concentrations Effect Estimates (95% CI)

Author: Neidell et al. (2004, 057330 ) Period of Study: 1992-1998

Location: California Hospital Admissions Health Outcome (ICD9): Asthma (493) Study Design: Time series Statistical Analyses: Linear Regression Age Groups Analyzed: 0-1 yr 1-3 yr 3-6 yr 6-12 yr 12-18 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.777 (1.037) ppm Range (Min, Max): NR Copollutant: correlation O 3 PM 10 NO 2 Increment: NR β (SE); lag; Single-pollutant model Age Group 0-1: -0.007 (0.009); 1-3: 0.027 (0.009); 3-6: 0.053 (0.010); 6-12: 0.047 (0.009); 12-18: 0.025 (0.008) Fixed effect controlling for O 3 , PM 10 , and NO 2 Age Group 0-1: -0.01 (0.01); 1-3: 0.024 (0.011); 3-6: 0.049 (0.011); 6-12: 0.023 (0.011); 12-18: 0.021 (0.009) Fixed effect controlling for O 3 , PM 10 , NO 2 and avoidance behavior Age Group 0-1: -0.010 (0.010); 1-3: 0.027 (0.011); 3-6: 0.051 (0.011); 6-12: 0.025 (0.011); 12-18: 0.021 (0.009)

Author: Norris et al. (1999, 040774 ) Period of Study: 9/1995- 12/1996

Location: Seattle, WA ED Visits Health Outcome (ICD9): Asthma (493) Study Design: Time series Statistical Analyses: Semiparametric Poisson GAM Age Groups Analyzed: <8 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.6 (0.5) ppm Range (Min, Max): (0.6, 4.1) Copollutant: correlation PM 10 : r = 0.74 NO 2 (1-h max): r = 0.47 NO 2 (24-h avg.): r = 0.66 SO 2 (1-h max): r = 0.15 SO 2 (24-h avg.): r = 0.32 Increment: 0.6 ppm Relative Risk (Lower CI, Upper CI); Lag High Utilization: 1.04 (0.93-1.16); 1 Low Utilization: 1.15 (1.05-1.28); 1 All: 1.10 (1.02-1.19); 1

Author: Peel et al. (2005, 056305 ) Period of Study: 1/1993- 8/2000

Location: Atlanta, GA ED Visits Health Outcome (ICD9): Asthma (493, 786.09); COPD (491, 492, 496); URI (460-466, 477); pneumonia (480-486) Study Design: Time series Statistical Analyses: 1. Poisson GEE or asthma, URI, all respiratory 2. Poisson GLM for pneumonia and COPD Age Groups Analyzed: Primary Analysis: All Ages Secondary Analysis: 2-18 yr Pollutant: CO Averaging Time: 1-h max Mean (SD) unit: 1.8 (1.2) ppm Range (10th, 90th): (0.5, 3.4) Copollutant: NR Increment: 1.0 ppm Relative Risk (Lower CI, Upper CI); Lag

Health Condition All respiratory illnesses: 1.011 (1.004-1.019); 0-2 URI: 1.012 (1.003-1.021); 0-2 / 1.066 (1.045-1.087); 0-13 Asthma: 1.010 (0.999-1.022); 0-2 1.076 (1.047-1.105); 0-13 Pneumonia: 1.009 (0.996-1.021); 0-2 1.045 (1.011-1.080); 0-13 COPD: 1.026 (1.004-1.048); 0-2 1.032 (0.975-1.092); 0-13 RR for asthma and exposure to CO for children age 2-18: 1.019 (1.004-1.035); 0-2 RR for all respiratory illnesses and CO exposure for all ages AQS (1/1/93- 8/31/00): 1.011 (1.004-1.019); 0-2 AQS (8/1/98- 8/31/00): 1.010 (1.000-1.021); 0-2 ARIES (8/1/98- 8/31/00): 1.018 (1.003-1.033); 0-2



### January 2010 C-59

### Study Design Concentrations Effect Estimates (95% CI)

Author: Sauerzapf et al. (2009, 180082 ) Period of Study: Jan 2006-Feb 2007

Location: Norfolk county, England Hospital Admissions

Health Outcome: COPD Study Design: Case crossover Statistical Analyses: Logistic Regression Age Groups Analyzed: 18+ yr (90% of patients 60+ yr) Sample Description: 1,050 COPD admissions Averaging Time: 24 h Mean (SD) unit: Control days: 194.46 (80.93) Case days: 204.73 (119.97) Range (min, max): Control days: 105.20, 408.10 Case days: 108.70, 432.20 Copollutant: NO, NO 2 , NO X , O 3 * Control days = 7 days prior to admission; Case days = day of admission Increment: 10 μg/m 3

Lags examined: 0-8 OR Estimate [Lower CI, Upper CI]; lag: Unadjusted: 1.010 (1.001, 1.019); lag 0-7 Adjusted: 1.015 (1.005, 1.025); lag 0-7 Unadjusted: 1.013 (1.001, 1.025); lag 1-8 Adjusted: 1.018 (1.005, 1.031); lag 1-8

Author: Sheppard et al. (1999, 086921 ) Period of Study: 1987-1994

Location: Seattle, WA Hospital Admissions Health Outcome (ICD9): Asthma (493) Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: <65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1831 ppb IQR (25th, 75th): (1277, 2201) Copollutant: correlation PM 10 : r = 0.83; PM 2.5 : r = 0.78; PM 10-2.5 : r = 0.56; O 3 : r = -0.18; SO 2 : r = 0.24 Increment: 924 ppb

% Increase (Lower CI, Upper CI); Lag CO: 6% (3, 9); 3 CO, PM 2.5 : 5% (1, 8); 3

Author: Slaughter et al. (2005, 073854 ) Period of Study: 1/1995-6/2001

Location: Spokane, WA Hospital Admissions & ED Visits Health Outcome (ICD9): Respiratory causes (460-519) Asthma (493); COPD (491, 492, 494, 496) acute respiratory tract infections not including colds and sinusitis (464-466, 490) Study Design: Time series Statistical Analyses: Poisson GLM, Natural Splines Age Groups Analyzed: All ages, Adults Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR Range (5th, 95th): (1.25, 3.05) Copollutant: correlation PM 1 : r = 0.63 PM 2.5 : r = 0.62 PM 10 : r = 0.32 PM 10-2.5 : r = 0.32 Increment: 1.0 ppm Relative Risk (Lower CI, Upper CI); lag:

ED Visits All Respiratory Illnesses Age Group: All Ages: 0.99 (0.96-1.02); 1 / 1.01 (0.98-1.04); 2 1.03 (1.00-1.06); 3 Asthma Age Group: All Ages: 1.00 (0.95-1.06); 1 / 1.01 (0.96-1.07); 2 1.06 (1.00-1.11); 3 COPD Age Group: Adults: 0.92 (0.85-1.00); 1 / 0.99 (0.91-1.08); 2 1.01 (0.93-1.10); 3 Hospital Admissions: All Respiratory Illnesses Age Group: All Ages: 0.99 (0.95-1.02); 1 / 1.00 (0.96-1.04); 2 0.99 (0.96-1.03); 3 Asthma Age Group: All Ages: 1.02 (0.92-1.13); 1 / 1.06 (0.96-1.17); 2 1.00 (0.91-1.11); 3 COPD Age Group: Adults: 0.94 (0.86-1.03); 1 / 1.04 (0.95-1.13); 2 0.97 (0.88-1.06); 3



### January 2010 C-60

### Study Design Concentrations Effect Estimates (95% CI)

Author: Stieb et al. (2000, 011675 ) Period of Study: 7/1992- 3/1996

Location: Saint John, Canada ED Visits Health Outcome (ICD9): Asthma; COPD; respiratory infections; all respiratory illnesses Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg 1-h max Mean (SD) unit: All yr: 0.5 (0.3) ppm May-September: 0.6 (0.3) ppm All yr: 1.6 (1.1) ppm, May-September: 1.7 (0.9) ppm Range (Min, Max): NR Copollutant: correlation H 2 S: r = -0.10; NO 2 : r = 0.68; O 3 : r = -0.05; SO 2 : r = 0.31; TRS: r = 0.07; PM 10 : r = 0.28; PM 2.5 : r = 0.27; H+: r = 0.23; SO 4 2- : r = 0.27; CoH: r = 0.55 Increment: 0.5 & 1.7 ppm Al% Increase (Lower CI, Upper CI); lag: Respiratory Illnesses Increment: 0.5 ppm All Year: -3.40; 7 Increment: 1.7 ppm May- September: -5.70

Author: Sun et al. (2006, 090768 ) Period of Study: 1/2004- 12/2004

Location: Taiwan ED Visits Health Outcome (ICD9): Asthma (493) Study Design: Cross sectional Statistical Analyses: Pearson correlation analysis Age Groups Analyzed: <16 yr; 16-55 yr Pollutant: CO Averaging Time: Monthly Mean (SD) unit : NR Range (Min, Max): NR Copollutant: NR Incre ment: NR

Correlation Coefficient:

Asthma Age Group: <16: 0.653 16-55: 0.425

Author: Tenias et al. (2002, 026077 ) Period of Study: 1/1994- 12/1995

Location: Valencia, Spain ED Visits Health Outcome (ICD9): COPD (491, 492, 494, 496) Study Design: Time series Statistical Analyses: 1. Poisson autoregressive 2. Sensitivity: GAM, LOESS Age Groups Analyzed: >14 yr Pollutant: CO Averaging Time: 24-h avg 1-h max Mean (SD) unit: 24-h avg All yr: 3.1 mg/m 3 Warm Months: 2.5 mg/m 3 Cold Months: 3.7 mg/m 3 1-h avg All yr: 6.7 mg/m 3 Warm Months: 5.4 mg/m 3 Cold Months: 8.0 mg/m 3 Range (Min, Max): 24-h avg: (0.9, 7.1) 1-h max: (1.6, 17.2) Copollutant: correlation SO 2 : r = 0.734; NO 2 : r = 0.180; O 3 : r = -0.517 Increment: 1 mg/m 3 Relative Risk (Lower CI, Upper CI); Lag 24-h avg All Year: 1.074 (0.998- 1156); 1 Cold Months: 1.070 (0.991-1.156); 1 Warm Months: 1.12 9 (0.960-1.329); 1 1-h max All Year: 1.039 (1.014-1.066); 1 Cold Months: 1.037 (1.010-1.064); 1 Warm Months: 1.05 8 (0.994-1.127); 1 All Year: sinusoidal terms: 1.039 (1.010-1.066); 1 All Year: humidity and temperature variables: 1.040 (1.014-1.067); 1 All Year: GAM, LOESS: 1.042 (1.019-1.066); 1

Author: Thompson et al. (2001, 073513 ) Period of Study: 1/1993- 12/1995

Location: Belfast, Northern Ireland ED Visits Health Outcome (ICD9): Asthma (493) Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: Children Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Warm Season: 0.57 (0.41) ppm Cold Season: 0.74 (0.73) ppm IQR (25th, 75th): Warm Season: (0.3, 0.7) Cold Season: (0.4, 0.8) Copollutant: correlation SO 2 (log): r = 0.64; PM 10 (log): r = 0.57; O 3 : r = -0.52; NO X (log): r = 0.74; NO (log): r = 0.71; NO 2 : r = 0.69 Increment: NR Relative Risk (Lower CI, Upper CI); lag: Temperature included in the model: 1.04 (1.00-1.09); 0 / 1. 07 (1.02-1.12); 0-1 1.06 (1.00-1.12); 0-2 / 1.07 (1.00-1.14); 0-3 Warm Season: 1.06 (0.98-1.16); NR Cold Season: 1.07 (1.01-1.14); NR Adjusted for benzene level: 0.92 (0.83-.02); 0-1 avg.

Note: The increment the study us es to calculate effect estimates is a doubling in CO levels, but The study did not provide this value.



### January 2010 C-61

### Study Design Concentrations Effect Estimates (95% CI)

Author: Tolbert et al. (2007, 090316 ) Period of Study: 1/1993- 12/2004

Location: Atlanta, GA ED Visits Health Outcome (ICD9): Respiratory disease: asthma (493, 786.07, 786.09); COPD (491, 492, 496); URI (460-465, 460.0, 477); pneumonia (480- 496); bronchiolitis (466.1, 466.11, 466.19)) Study Design: Time series Statistical Analyses: Poisson GLM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 1-h max Mean (SD) unit: 1.6 ppm Range (Min, Max): (0.1, 7.7) Copollutant: correlation PM 10 : r = 0.51; O 3 : r = 0.27; NO 2 : r = 0.70; SO 2 : r = 0.28; Coarse PM: r = 0.38; PM 2.5 : r = 0.47; SO 4 : r = 0.14;EC: r = 0.66; OC: r = 0.59; TC: r = 0.63; OHC: r = 0.29 Increment: 1.22 ppm Relative Risk (Lower CI, Upper CI); lag: Respiratory Diseases: 1.016 (1.009-1.022); 3

Note: The study only provides resu lts of the multi-pollutant models in figures, not quantitatively.

Author: Trapasso and Keith (1999, 180127 ) Period of Study: 1/1994- 12/1994

Location: Bowling Green, KY Hospital Admissions Health Outcome (ICD9): Asthma (493) Study Design: Time series Statistical Analyses: Spearman Rank Correlation Coefficient Age Groups Analyzed: All ages Pollutant: CO Averaging Time: NR Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NR Increment: NR Correlation Coefficient (lag) CO Mean: r = 0.19;0 CO Mean: r = 0.27; 1 CO Mean: r = 0.21; 2 CO Max: r = 0.26; 0 CO Max: r = 0.36; 1 CO Max: r = 0.24; 2

Author: Tsai et al. (2006, 089768 ) Period of Study: 1996-2003

Location: Kaohsiung, Taiwan Hospital Admissions Health Outcome (ICD9): Asthma (493) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.77 ppm Range (Min, Max): (0.23, 1.72) Copollutant: PM 10 SO 2 NO 2 O 3 I ncrement: 0.29 ppm Odds Ratio (Lower CI, Upper CI); lag OR for getting asthma and ex posure to various pollutants for all ages at either <25°C or ≥ 25°C

CO <25°C: 1.414 (1.300-1.537); 0-2 ≥ 25°C: 1.222 (1.138-1.312); 0-2 CO, PM 10 <25°C: 1.251 (1.125-1.393); 0-2 ≥ 25°C: 1.178 (1.088-1.274); 0-2 CO, SO 2 <25°C: 1.207 (1.076-1.354); 0-2 ≥ 25°C: 1.290 (1.188-1.400); 0-2 CO, NO 2 <25°C: 0.916 (0.807-1.039); 0-2 ≥ 25°C: 1.249 (1.127-1.384); 0-2 CO, O 3 <25°C: 1.396 (1.282-1.520); 0-2 ≥ 25°C: 1.195 (1.113-1.284); 0-2

Author: Vigotti et al. (2007, 090711 ) Period of Study: 1/2000- 12/2000

Location: Pisa, Italy ED Visits Health Outcome (ICD9): Respiratory disease: asthma (493); dry cough (468); acute bronchitis (466) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: <10 yr; >65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.5 (0.7) ug/m 3 Range (Min, Max): (0.3, 3.5) Copollutant: correlation NO 2 : r = 0.62 PM 10 : r = 0.70 Increment: 1mg/m 3 % Increase (Lower CI, Upper CI); lag Age Group <10: 18.60% (-6.90 to 51.10); 1 >65: 26.50% (3.40-54.80); 4



### January 2010 C-62

### Study Design Concentrations Effect Estimates (95% CI)

Author: Villeneuve et al. (2006, 091179 ) Period of Study: 1995-2000

Location: Toronto, ON, Canada Physician Visits Health Outcome (ICD9): Allergic rhinitis (177) Study Design: Time series Statistical Analyses: Poisson GLM Age Groups Analyzed: >65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.1 (0.4) ppm Range (Min, Max): (0.0, 2.2) Copollutant: PM 2.5 PM 10 PM 10-2.5 SO 2 NO 2 O 3 Increment: 0.4 ppm Odds Ratio (Lower CI, Upper CI); Lag The study did not present quantitative results for CO.

Author: Xirasagar et al. (2006, 093267 ) Period of Study: 1998- 2001

Location: Taiwan Hospital Admissions Health Outcome (ICD9): Asthma (493) Study Design: Cross sectional Statistical Analyses: Spearman Rank Correlations Age Groups Analyzed: 0-14 yr; <2 yr; 2-5 yr; >5 yr Pollutant: CO Averaging Time: Monthly Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NR Increment: NR Correlation Coefficient (Lag) Age Group: <2: r = -0.208 2-5: r = -0.281 >5: r = -0.134

Author: Yang et al. (2007, 092848 ) Period of Study: 1996-2003

Location: Taipei, Taiwan Hospital Admissions Health Outcome (ICD9): Asthma (493) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.33 ppm Range (Min, Max): (0.32, 3.62) Copollutant: PM 10 SO 2 NO 2 O 3 Increment: 0.53 ppm Odds Ratio (Lower CI, Upper CI); Lag

CO <25°C: 1.076 (1.019-1.136); 0-2 ≥ 25°C: 1.277 (1.179-1.383); 0-2 CO, PM 10 <25°C: 1.050 (0.983-1.122); 0-2 ≥ 25°C: 1.332 (1.216-1.459); 0-2 CO, SO 2 <25°C: 1.131 (1.059-1.207); 0-2 ≥ 25°C: 1.278 (1.174-1.392); 0-2 CO, NO 2 <25°C: 0.915 (0.839-0.997); 0-2 ≥ 25°C: 1.177 (1.049-1.320); 0-2 CO, O 3 <25°C: 1.169 (1.102-1.240); 0-2 ≥ 25°C: 1.275 (1.177-1.382); 0-2

Author: Yang et al. (2007, 092847 ) Period of Study: 1996-2003

Location: Taipei, Taiwan Hospital Admissions Health Outcome (ICD9): COPD: (490-492, 494, 496) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.33 ppm Range (Min, Max): (0.32, 3.66) ppm Copollutant: PM 10 SO 2 NO 2 O 3 Increment: 0.53 ppm Odds Ratio (Lower CI, Upper CI); Lag

CO <20°C: 0.975 (0.921,1.033); 0-2 ≥ 20°C: 1.227 (1.178-1.277); 0-2 CO, PM 10 <20°C: 0.925 (0.863-0.992); 0-2 ≥ 20°C: 1.177 (1.123-1.235); 0-2 CO, SO 2 <20°C: 0.895 (0.832-0.962); 0-2 ≥ 20°C: 1.274 (1.219-1.331); 0-2 CO, NO 2 <20°C: 1.000 (0.910-1.099); 0-2 ≥ 20°C: 1.061 (0.998-1.129); 0-2 CO, O 3 <20°C: 0.935 (0.875-0.999); 0-2 ≥ 20°C: 1.234 (1.185-1.285); 0-2



### January 2010 C-63

### Study Design Concentrations Effect Estimates (95% CI)

Author: Yang et al. (2005, 090184 ) Period of Study: 1/1994- 12/1998

Location: Vancouver, Canada Hospital Admissions Health Outcome (ICD9): COPD (490-492, 494, 496) Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: .71 (0.28) ppm Range (Min, Max): (0.30, 2.48) Copollutant: correlation O 3 : r = -0.56 NO 2 : r = 0.73 SO 2 : r = 0.67 PM 10 : r = 0.50 Increment: 0.3 ppm Relative Risk (Lower CI, Upper CI); lag

CO 1.03 (1.00-1.06); 0 / 1. 04 (1.01-1.08); 0-1 1.05 (1.01-1.09); 0-2 / 1.05 (1.00-1.10); 0-3 1.06 (1.01-1.11); 0-4 / 1.07 (1.02-1.12); 0-5 1.08 (1.02-1.13); 0-6

MultiPollutant: CO, O 3 : 1.11 (1.04-1.18); 0-6 CO, NO 2 : 1.04 (0.95-1.14); 0-6 CO, SO 2 : 1.11 (1.01-1.22); 0-6 CO, PM 10 : 1.02 (0.93-1.12); 0-6 CO, PM 10 , O 3 , NO 2 , SO 2 : 1.08 (0.96-1.22); 0-6 CO, O 3 , NO 2 , SO 2 : 1.10 (0.98-1.23); 0-6

Author: Yang et al. (2003, 055621 ) Period of Study: 1/1986- 12/1998

Location: Vancouver, BC, Canada Hospital Admissions Health Outcome (ICD9): Respiratory diseases (460-519) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: <3 yr; ≥ 65 yr Pollutant : CO Averaging Time: 24-h avg Mean (SD) unit : 0.98 (0.54) ppm IQR (25th, 75th): (0.62, 1.16) Copollutant: correlation O 3 : r = -0.52 CoH NO 2 SO 2 Increment: 0.54 ppm Odds Ratio (Lower CI, Upper CI); lag OR for respiratory diseas es and exposure to various pollutants for people <3 and ≥ 65 Age Group: <3 CO alone: 1.04 (1.01-1.07); 1 CO, O 3 : 1.04 (1.01-1.07); 1 CO, O 3 , CoH, NO 2 , SO 2 : 1.02 (0.96-1.08); 1 Age Group: ≥ 65 CO alone: 1.02 (1.00-1.04); 1 CO, O 3 : 1.02 (1.00-1.04); 1 CO, O 3 , CoH, NO 2 , SO 2 : 0.96 (0.93-1.00); 1

Author: Yang et al. (2004, 087488 ) Period of Study: 6/1/1995-3/31/1999

Location: Vancouver, Canada Hospital Admissions Health Outcome (ICD9): Respiratory diseases (460- 519); pneumonia (480-486); asthma (493) Study Design: Case control Statistical Analyses: Pearson’s correlation coefficient Age Groups Analyzed: <3 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.70 (0.30) ppm IQR (25th, 75th): (0.50, 0.80) Copollutant: correlation PM 10 : r = 0.46; PM 2.5 : r = 0.24; PM 10-2.5 : r = 0.33; O 3 : r = -0.53; NO 2 : r = 0.74; SO 2 : r = 0.61 This study did not present quantitative results for CO.

Author: Zanobetti and Schwartz (2006, 090195 ) Period of Study: 1995-1999

Location: Boston, MA Hospital Admissions Health Outcome (ICD9): Pneumonia (480-487) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR IQR (25th, 75th): (0.39, 0.60) Copollutant: correlation PM 2.5 : r = 0.52; BC: r = 0.82; NO 2 : r = 0.67; O 3 : r = -0.30 Increment: 0.475 ppm % Increase (Lower CI, Upper CI); lag: 5.45 (1.10, 9.51); 0 5.12 (0.83, 9.16); 0-1



### January 2010 C-64

# Table C-6. Studies of long-term CO exposure and respir atory morbidity.

Study Design Concentrations Effect Estimates (95% CI)

Author: Goss et al. (2004, 055624 ) Period of Study: 1999-2000

Location: U.S. Health Outcome: Lung function (FEV 1 , cystic fibrosis pulmonary exacerbation) Study Design: Cohort Statistical Analyses: Logistic regression Population: 11,484 cystic fibrosis patients Age Groups Analyzed: >6 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit: 0.692 (0.295) ppm IQR (25th, 75th): (0.48, 0.83) Copollutant: NR Increment: 1.0 ppm Odds Ratio (Lower CI, Upper CI); lag: Two or more pulmonary exacerbations during 2000 1.02 (0.85-1.22)

Author: Guo et al. (1999, 010937 ) Period of Study: 10/1995-5/1996

Location: Taiwan Health Outcome: Asthma Study Design: Cohort Statistical Analyses: Logistic regression Population: 331,686 nonsmoking children Age Groups Analyzed: Middle-school children (mean age = 13.8 yr) Pollutant: CO Averaging Time: Annual avg Mean (SD) unit: 853 (277) ppb Range (Min, Max): (381, 1610) Copollutant: NR Increment: 326 ppb % Increase (Lower CI, Upper CI); lag: Boys Physician-diagnosed asthma: 1.17% (0.63-1.72) Questionnaire-diagnosed asthma: 1.10% (0.45-1.75) Girls Physician-diagnosed asthma: 0.84% (0.45-1.22) Questionnaire-diagnosed asthma: 1% (0.44-1.56)



### January 2010 C-65

### Study Design Concentrations Effect Estimates (95% CI)

Author: Hirsch et al. (1999, 003537 ) Period of Study: Population: 9/1995-6/1996 Air: 4/1994-4/1995

Location: Dresden, Germany Health Outcome: Asthma symptoms in the past 12 mo (wheeze, morning cough); Doctor's diagnosis (asthma, bronchitis); Lung function (bronchial hyperresponsiveness (BHR), FEV 1 <85% pred., FEF 25-75% <70% pred.) Study Design: Cross sectional Statistical Analyses: Multiple logistic regression Population: 5-7: 2,796; 9-11: 2,625 Age Groups Analyzed: 5-7 and 9-11 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit: 0.69 mg/m 3 Range (Min, Max): (0.32, 1.54) Copollutant: NR Increment: 0.2 μg/m 3 Prevalence Odds Ratio (Lower CI, Upper CI); lag: Symptoms in the past 12 mo: Wheeze Home Exposure Age Groups: 5-7; 9-11: 1.05 (0.93-1.18) Home/School Exposure Age Groups: 9-11: 1.02 (0.85-1.22) Morning Cough Home Exposure Age Groups: 5-7; 9-11: 1.12 (1.01-1.23) Age Group: 9-11: 1.13 (0.98-1.3) Doctor’s diagnosis: Asthma Home Exposure Age Groups: 5-7; 9-11: 1.07 (0.94-1.21) Age Groups: 9-11: 1.16 (0.97-1.38) Doctor’s diagnosis: Bronchitis Age Groups: 5-7; 9-11: 1.19 (1.11-1.27) Age Group: 9-11: 1.24 (1.12-1.38) Lung function: BHR Age Groups: 5-7; 9-11: 0.79 (0.63-0.99) Age Group: 9-11: 0.77 (0.6-0.99) Lung function: FEV1 <85% pred. Age Groups: 5-7; 9-11: 1.09 (0.81-1.47) Age Group: 9-11: 1.01 (0.73-1.41) Lung function: FEV25- 75% <70% pred. Age Groups: 5-7; 9-11: 1.15 (0.94-1.39) Age Group: 9-11: 1.07 (0.86-1.34) Symptoms in the past 12 mo: Wheeze Age Groups: 5-7; 9-11 Atopic children: 1 (0.81-1.24) Nonatopic children: 1.05 (0.83-1.31) Morning cough Age Groups: 5-7; 9-11 Atopic children: 1.03 (0.82-1.29) Nonatopic children: 1.22 (1.05-1.41) Doctor’s diagnosis: Asthma Atopic children: 1.05 (0.83-1.32) Nonatopic children: 1.29 (1.05-1.59) Doctor’s diagnosis: Bronchitis Age Groups: 5-7; 9-11 Atopic children: 1 (0.86-1.16) Nonatopic children: 1.21 (1.1-1.33) Notes: Atopic Children were defined as those children with specific IgE to aeroallergens >0.7 kU-L-1; Nonatopic Children were defined as those children with specific IgE to aeroallergens ≤ 0.7 kU-L-1.

Author: Hwang et al. (2006, 088971 ) Period of Study: 2001

Location: Taiwan Health Outcome: Allergic rhinitis Study Design: Cross sectional Statistical Analyses: Two-stage hierarchical model (logistic and linear regression) Population: 32,143 Taiwanese school children Age Groups Analyzed: 6-15 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit : 664 (153) ppb Range (Min, Max): (416, 964) Copollutant: correlation NO X : r = 0.88 O 3 : r = -0.37 PM 10 : r = 0.27 SO 2 : r = 0.40 Increment: 100 ppb Adjusted Odds Ratio (Lower CI, Upper CI); lag: Physician-diagnosed allergic rhinitis 1.05 (1.04-1.07) CO, SO 2 : 1.04 (1.02-1.06) CO, PM 10 : 1.05 (1.03-1.07) CO, O 3 : 1.07 (1.05-1.09) Male: 1.06 (1.03-1.08); Female: 1.05 (1.02-1.08) Parental atopy: Yes: 1.05 (1.02-1.08) Parental atopy: No : 1.06 (1.03-1.08) Parental Education: <6: 1 (0.91-1.09) Parental Education: 6- 8: 1.07 (1.02-.12) Parental Education: 9-11: 1.05 (1.02-1.08) Parental Education: ≥ 12: 1.06 (1.03-1.09) ETS: Yes: 1.06 (1.03-1.08); ETS: No: 1.05 (1.02-1.08) Visible Mold: Yes: 1.07 (1.03-1.11) Visible Mold: No: 1.05 (1.03-1.07)



### January 2010 C-66

### Study Design Concentrations Effect Estimates (95% CI)

Author: Hwang et al. (2005, 089454 ) Period of Study: 2001

Location: Taiwan Health Outcome: Asthma Study Design: Cross sectional Statistical Analyses: Two-stage hierarchical model (logistic and linear regression) Population: 32,672 Taiwanese school children Age Groups Analyzed: 6-15 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit: 664 (153) ppb Range (Min, Max): (416, 964) Copollutant: correlation NO X : r = 0.88 O 3 : r = -0.37 PM 10 : r = 0.27 SO 2 : r = 0.40 Increment: 100 ppb Adjusted Odds Ratio (Lower CI, Upper CI); lag: Physician-diagnosed asthma: 1.045 (1.017-1.074) CO, SO 2 : 1.066 (1.034-1.099) CO, PM 10 : 1.079 (1.047-1.112) CO, O 3 : 1.063 (1.1-1.474) CO, SO 2 , O 3 : 1.111 (1.074-1.15) CO, PM 10 , O 3 : 1.119 (1.084-1.155) Male: 1.49 (1.37-1.63); Female: 1 Parental atopy: Yes: 1 Parental atopy: No: 2.72 (2.5-2.97)

Parental Education: <6: 1 Parental Education: 6-8: 1.17 (0.9-1.52) Parental Education: 9-11: 1.61 (1.26-2.05) Parental Education: ≥ 12: 2.43 (1.9-3.09) ETS: Yes: 0.85 (0.7 8-0.92); ETS: No: 1 Visible Mold: Yes: 1.27 (1. 16-1.4); Visible Mold: No: 1 Maternal smoking during pregnancy: Yes: 1.18 (0.89-1.56) Maternal smoking during pregnancy: No: 1 Cockroaches noted monthly: Yes: 1.15 (1.03-1.29) Cockroaches noted monthly: No: 1 Water damage: Yes: 0.96 (0.81-1.12) Water damage: No: 1

Author: Lee et al. (2003, 049201 ) Period of Study: 10/1995-5/1996

Location: Taiwan Health Outcome: Allergic rhinitis Study Design: Cohort Statistical Analyses: Multiple logistic regression Population: 331,686 nonsmoking children Age Groups Analyzed: 12-14 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit: 853 (277) ppb Range (Min, Max): (381, 1610) Copollutant: NR The study did not present quantitative results for CO.

Author: Meng et al. (2007, 093275 ) Period of Study: 11/2000-9/2001

Location: Los Angeles County and San Diego County, California Health Outcome: Asthma Study Design: Cohort Statistical Analyses: Logistic regression Population: 1,609 physician-diagnosed asthmatics Age Groups Analyzed: ≥ 18 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: correlation Traffic: r = -0.04; O 3 : r = -0.55; PM 10 : r = 0.42; PM 2.5 : r = 0.52; NO 2 : r = 0.55 The study did not present quantitative results for CO.



### January 2010 C-67

### Study Design Concentrations Effect Estimates (95% CI)

Author: Mortimer et al. (2008, 122163 ) Period of Study: 1989-2000

Location: San Joaquin Valley, CA Health Outcome: Lung function (FVC, FEV 1 , PEF, FEF25-75, FEV 1 /FVC, FEF25-75/FVC, FEF25, FEF75) Study Design: Cohort Statistical Analyses: 1. DSA algorithm 2. GEE Population: 232 asthmatic children Age Groups Analyzed: 6-11 yr Pollutant: CO Averaging Time: 8-h max monthly mean Mean (SD) unit: NR Range (Min, Max): NR Copollutant; correlation:

Lifetime NO 2 (24-h avg): r = 0.68 O 3 (8-h max): r = -0.40 PM 10 (24-h avg): r = 0.05

Prenatal CO (8-h max): r = 0.52 NO 2 (24-h avg): r = 0.37 O 3 (8-h max): r = -0.16 PM 10 (24-h avg): r = -0.05 Increment: NR Effect Size per IQR Increase in Pollutant (SE):

FEF25-75: 24-h avg CO exposure during 1st trimester 0.90% (0.0113) FEV 1 /FVC Daily max CO exposure during ages 0 to 3 -2.50% (0.0016) FEF25-75/FVC 24-h avg CO exposure during ages 0 to 6 and diagnosed with asthma <2 yr old -4.80% (0.0446) FEF25 24-h avg CO exposure during ages 0 to 6 and diagnosed with asthma <2 yr old plus 24-h avg PM 10 exposure during 2nd trimes ter and mother smoked when pregnant -6.70% (0.015) Coefficient (SE): FVC 24-h avg CO exposure during 2nd trimester -0.0878 (0.0415) FEF25-75 Lifetime 24-h avg CO exposure -0.94454 (0.3975) FEF25-75/FVC -0.1090 (0.0303) FEV 1 /FVC Prenatal 8-h max CO exposure: 0.1711 (0.0653) Lifetime 1-h max CO exposure: -0.3242 (0.0919) 24-h avg CO exposure dur ing ages 0-3 and diagnosed with asthma <2 yr old: -0.1814 (0.0599)

FEF25 24-h avg CO exposure dur ing ages 0-6 and diagnosed with asthma <2 yr old: -1.0460 (0.1953)

FEF75 Lifetime 8-h max CO exposure: -0.4214 (0.1423)

Author: Singh et al. (2003, 052686 ) Period of Study: NR

Location: Jaipur, India Health Outcome: Lung function Study Design: Panel study Statistical Analyses: Parametric statistical methods Population: Campus panel: 142 Commuter panel: 158 Age Groups Analyzed: ~20 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit : Roadside: 3,175 μg/m 3 Campus: 2,150 μg/m 3 Range (Min, Max): NR Copollutant: NR The study did not present quantitative results for CO.



### January 2010 C-68

### Study Design Concentrations Effect Estimates (95% CI)

Author: Sole et al. (2007, 090706 ) Period of Study:

Location: Sao Paulo West, Sao Paulo South, Santo Andre, Curitba, & Porto Alegre, Brazil Health Outcome: Symptoms of asthma, rhinitis, and eczema Study Design: Panel Statistical Analyses: Logistic Regression Age Groups Analyzed: 13-14 yr Averaging Time: Annual Mean (SD) unit: Sao Paulo West: 7.70 ppm Sao Paulo South: 7.50 ppm Santo Andre: 9.80 ppm Curitba: 7.90 ppm Porto Alegre: 1.51 ppm Range (min, max): NR Copollutant: NO 2 , SO 2 , O 3 Increment: Risk in relation to center w/ lowest annual mean (Porto Alegre = ref) OR Estimate [Lower CI, Upper CI]: Lags examined: NR Current Wheezing: Sao Paulo West: 1.26 (1.11, 1.42) Sao Paulo South: 1.03 (0.91, 1.18) Santo Andre: 1.36 (1.20, 1.56) Curitba: 1.05 (0.93, 1.19) Severe Asthma: Sao Paulo West: 1.20 (0.95, 1.50) Sao Paulo South: 0.59 (0.45, 0.78) Santo Andre: 0.62 (0.48, 0.81) Curitba: 0.64 (0.50, 0.82) Nighttime Coughing: Sao Paulo West: 1.06 (0.95, 1.17) Sao Paulo South: 0.93 (0.84, 1.03) Santo Andre: 0.91 (0.82, 1.02) Curitba: 0.99 (0.89, 1.10) Rhinoconjunctivitis: Sao Paulo West: 1.31 (1.15, 1.15) Sao Paulo South: 0.73 (0.64, 0.85) Santo Andre: 0.85 (0.74, 0.97) Curitba: 1.10 (0.96, 1.25) Severe Rhinits: Sao Paulo West: 1.01 (0.91, 1.49) Sao Paulo South: 0.68 (0.59, 0.77) Santo Andre: 0.73 (0.64, 0.83) Curitba: 1.03 (0.91, 1.16) Eczema: Sao Paulo West: 1.45 (1.20, 1.74) Sao Paulo South: 1.03 (0.85, 1.25) Santo Andre: 1.03 (0.85, 1.25) Curitba: 0.90 (0.75, 1.10) Flexural Eczema: Sao Paulo West: 1.42 (1.15, 1.76) Sao Paulo South: 0.71 (0.56, 0.91) Santo Andre: 0.68 (0.53, 0.87) Curitba: 0.73 (0.57, 0.92) Severe Eczema: Sao Paulo West: 1.08 (0.86, 1.35) Sao Paulo South: 0.42 (0.31, 0.56) Santo Andre: 0.38 (0.28, 0.51) Curitba: 0.30 (0.22, 0.41) Author: Wang et al. (1999, 008105 ) Period of Study: 10/1995-6/1996

Location: Kaohsiung and Pintong, Taiwan Health Outcome: Asthma Study Design: Cross sectional Statistical Analyses: Multiple logistic regression Population: 165,173 high school students Age Groups Analyzed: 11-16 yr Pollutant: CO Averaging Time: Annual median Median (SD) unit: 0.80 ppm Range (Min, Max): NR Copollutant: NR Increment: NR Adjusted Odds Ratio (Lower CI, Upper CI); lag: CO Concentrations: <0.80 ppm: 1.0

CO Concentrations ≥ 0.80 ppm: 1.23 (1.19-1.28) Multivariate analysis with variables for exercise, smoking, alcohol, incense us e, ETS: 1.15 (1.1-1.2)

Author: Wilhelm et al. (2008, 191912 ) Period of Study: 2000-2001

Location: Los Angeles County or San Diego County, California Health Outcome: Asthma symptoms/ED visit/HA Study Design: Panel Statistical Analyses: Logistic regression Age Groups Analyzed: 0-17 yr Sample Description: 612 children who reported a physician diagnosis of asthma at some point in their lives Averaging Time: annual Mean (SD) unit: 1.0 ppm Range (min, max): 0.34, 1.8 Copollutant: correlation O 3 : r= -0.67 PM 10 : r= 0.41 PM 2.5 : r= 0.60 NO 2 : r= 0.57 traffic density: r= 0.02 Increment: NR OR Estimate [Lower CI, Upper CI] ; lag: Lags examined: NR No associations observed between asthma symptom outcome measures (no results shown)



### January 2010 C-69

# Table C-7. Studies of short-te rm CO exposure and mortality.

Study Design Concentrations Effect Estimates (95% CI)

Author: Anderson et al. (2001, 017033 ) Period of Study: 10/1994-12/1996

Location: West Midlands, United Kingdom Health Outcome (ICD9): Mortality: All-cause (nonaccidental) (<800); cardiovascular (390-459); respiratory (460-519) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: Max 8-h ma Mean (SD) unit: 0.8 (0.7) ppm Range (Min, Max): (0.2, 10.0) Copollutant correlation: PM 10 : r = 0.55; PM 2.5 : r = 0.54; PM 10-2.5 : r = 0.10; BS: r = 0.77; SO 4 2- : r = 0.17; NO 2 : r = 0.73; O 3 : r = -0.29; SO 2 : r = 0.49 Increment: 1.0 ppm % Increase (Lower CI, Upper CI); lag:

All-cause 0.8% (-0.6 to 2.2); 0-1

Cardiovascular 2.5% (0.4-4.6); 0-1 Respiratory 1.2% (-2.1 to 4.6); 0-1

Author: Bellini et al. (2007, 097787 ) Period of Study: 1996-2002

Location: 15 Italian cities Health Outcome (ICD9): Mortality: All-cause (nonaccidental) (<800); cardiovascular (390-459); respiratory (460-519) Study Design: Meta-analysis Statistical Analyses: Poisson GLM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: SO 2 NO 2 O 3 PM 10 Increment: 1 mg/m 3 % Increase (Lower CI, Upper CI); lag:

All-cause 1.19% (0.61-1.72); 0-1 Respiratory 0.66% (-1.46 to 2.88); 0-1

Cardiovascular 0.93% (-0.10 to 1.77); 0-1

Author: Berglind et al. (2009, 190068 ) Period of Study: 1992-2002

Location: Augsburg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; Stockholm, Sweden Health Outcome: Mortality Study Design: Cohort Statistical Analyses: Poisson regression analysis Age Groups Analyzed: ≥ 35 yr Sample Description: Firsttime MI patients Averaging Time: 24 h Mean (SD) unit: Median calculated from daily 24-h means: Augsburg: 0.85 Barcelona: 0.75 Helsinki: 0.36 Rome: 1.66 Stockholm: 0.38 Range (IQR): Augsburg: 0.43 Barcelona: 0.75 Helsinki: 0.36 Rome: 1.11 Stockholm: 0.38 Copollutant: NR Increment: 0.2 mg/m 3 % Change in Daily Nontraum a Deaths [Lower CI, Upper CI]: Mean of Lag 0 and 1: 2.61 (-0.26-5.56) Mean of Lag 0-4: 3.82 (1.00-6.72) Mean of Lag 0-14: 4.92 (2.11-7.81) Lags examined: 0, 1, 4, 14 CO had a trend towards or positive associations with all cities for 2-day mean effects on daily mortality. CO was associated with ri sk for the 5-day avg. The strongest association was observed for the 15-day avg.



### January 2010 C-70

### Study Design Concentrations Effect Estimates (95% CI)

Author: Biggeri et al. (2005, 087395 ) Period of Study: 1990-1999

Location: 8 Italian Cities (Turin, Milan, Verona, Bologna, Ravenna, Florence, Rome, and Palermo) Health Outcome (ICD9): Mortality: All-cause (nonaccidental) (<800); cardiovascular (390-459);respiratory (460-519); cardiorespiratory Study Design: Meta-analysis Statistical Analyses: Poisson GLM, cubic splines Age Groups Analyzed: All ages Pollutant: CO Averaging Time: Max 8-h ma Mean (SD) unit: Turin, 1991-1994: 5.8 mg/m 3 Turin, 1995-1998: 4.0 mg/m 3 Milan, 1990-1994: 5.9 mg/m 3 Milan, 1995-1997: 4.0 mg/m 3 Verona, 1995-1999: 2.5 mg/m 3 Ravenna, 1991-1995: 1.8 mg/m 3 Bologna, 1996-1998: 2.4 mg/m 3 Florence, 1996-1998: 2.7 mg/m 3 Rome, 1992-1994: 6.5 mg/m 3 Rome, 1995-1997: 5.4 mg/m 3 Palermo, 1997- 1999: 2.1 mg/m 3 Range (Min, Max): Turin, 1991-1994: (NR, 24.7) Turin, 1995-1998: (NR, 19.8) Milan, 1990-1994: (NR, 26.5) Milan, 1995-1997: (NR, 12.3) Verona, 1995-1999: (NR, 10.2) Ravenna, 1991-1995: (NR, 7.0) Bologna, 1996-1998: (NR, 11.1) Florence, 1996-1998: (NR, 8.7) Rome, 1992-1994: (NR, 22.3) Rome, 1995-1997: (NR, 18.5) Palermo, 1997- 1999: (NR, 8.0) Copollutant: NR Increment: 1.0 mg/m 3 % Increase (Lower CI, Upper CI); lag:

Non-accidental Fixed: 0.93 (0.50-1.36); 0-1 Random: 0.93 (0.50-1.36); 0-1

Cardiovascular Fixed: 1.29 (0.62-1.96); 0-1 Random: 1.29 (0.62-1.96); 0-1 Respiratory Fixed: 2.44 (0.74-4.17); 0-1 Random: 2.47 (0.14-4.85); 0-1

Author: Botter et al. (2002, 011922 ) Period of Study: 1991-1993

Location: São Paulo, Brazil Health Outcome (ICD9): Mortality Study Design: Longitudinal study Statistical Analyses: State space model Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: TSP; NO 2 ; O 3 ; SO 2 Increment: NR β (SE): Model 1: 0.0053 (0.0036) Model 2: 0.0046 (0.0028) Model 3: 0.0040 (0.0028) Model 4: 0.0032 (0.0028)

Author: Bremner et al. (1999, 007601 ) Period of Study: 1/1992–12/1994

Location: London, U.K. Health Outcome (ICD9): Mortality: All-cause (nonaccidental) (<800); cardiovascular (390-459); respiratory (460-519) Study Design: Time series Statistical Analyses: Poisson, cubic splines Age Groups Analyzed: All ages 0-64 yr ≥ 65 yr 65-74 yr ≥ 75 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit : 0.8 (0.4) ppm Range (Min, Max): (0.2, 5.6) Copollutant: NO 2 ; O 3 ; SO 2 ; PM 10 ; BS Increment: 0.8 ppm % Increase (Lower CI, Upper CI); lag:

All-cause Age Group: All ages: 0.9% (-0.2 to 2.0); 1 0-64: 1.2% (-1.0 to 3.5); 1 ≥ 65: 0.8% (-0.4 to 1.9); 2 65-74: 0.8% (-1.2 to 2.8); 3 ≥ 75: 0.9% (-0.4 to 2.2); 2 Respiratory Age Group: All ages: 2.0% (-0.3 to 4.5); 3 0-64: 7.8% (0.2-15.9); 3 ≥ 65: 0.7% (-1.7 to 3.2); 3 65-74: 7.5% (2.1-13.2); 3 ≥ 75: 2.3% (-0.5 to 5.3); 0 Multipollutant: CO, SO 2 : 1.90% (0.18-3.64); 3 CO, PM 10 : 1.25% (0.04-2.47); 3 CO, BS: 2.41% (-0.65 to 5.57); 3 Cardiovascular Age Group: All ages: 1.4% (-0.1 to 3.0); 1 0-64: 2.1% (-1.7 to 6.0); 2 ≥ 65: 1.1% (-0.4 to 2.8); 2 65-74: 2.4% (-0.6 to 5.5); 2 ≥ 75: 1.9% (0.0-3.9); 2 Multipollutant: CO, NO 2 : 2.55% (0.40-4.75); 1 CO, O 3 : 3.98% (0.85-7.21); 1 CO, PM 10 : 0.62% (-0.59 to 1.85); 1 CO, BS: 1.29% (-1.53 to 4.19); 1



### January 2010 C-71

### Study Design Concentrations Effect Estimates (95% CI)

Author: Burnett et al. (2000, 010273 ) Period of Study: 1986-1996

Location: 8 Canadian cities Health Outcome (ICD9): Mortality: All-cause (nonaccidental) (<800) Study Design: Time series Statistical Analyses: 1. Single-pollutant models: Poisson GAM, LOESS 2. Multi-pollutant models: Principal component regression analysis Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.9 ppm Range (Max): 7.2 ppm Copollutant: correlation O 3 : r = -0.05 SO 2 : r = 0.42 PM 2.5 : r = 0.44 PM 10-2.5 : r = 0.29 PM 10 : r = 0.45 Increment: 0.9 ppm % Increase (t-value); lag: Temporally filtered daily nonaccidental mortality (days in which PM 10 data available) CO: 0.4 (0.4); 0; 2.0 (2.3); 1 CO, PM 2.5 : -0.7 (-0.7); 0; 1.1 (1.1); 1 CO, PM 10-2.5 : 0.1 (0.2); 0; 1.8 (2.1); 1 CO, PM 10 : -0.5 (-0.6); 0; 1.2 (1.3); 1 Daily filtered non-accidental mortality Single-pollutant model: 2.1 (2.1) Multi-pollutant models: Model 1: CO, PM 2.5 , PM 10-2.5 , O 3 , NO 2 , SO 2 : 0.7 (1.9) Model 2: CO, SO 4 , Ni, Fe, Zn, O 3 , NO 2 : 0.7 (1.7)

Author: Burnett et al. (2004, 086247 ) Period of Study: 1981-1999

Location: 12 Canadian cities Health Outcome (ICD9): Mortality: All-cause (nonaccidental) (<800) Study Design: Time series Statistical Analyses: 1. Poisson, natural splines 2. Random effects regression model Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.02 ppm Range (Min, Max): NR Copollutant: NO 2 ; O 3 ; SO 2 ; PM 2.5 ; PM 10-2.5 Increment: 1.02 ppm % Increase (t-value); lag: 0.68% (3.12); 1 CO, NO 2 : 0.07% (0.30); 1

Author: Cakmak et al. (2007, 091170 ) Period of Study: 1/1997-12/2003

Location: Chile-7 cities Health Outcome (ICD9): Mortality: All-cause (nonaccidental) (<800); CVDs (390-459); respiratory diseases (460-519) Study Design: Time series Statistical Analyses: Poisson; Random effects regression model Age Groups Analyzed: All ages ≤ 64 yr 65-74 yr 75-84 yr ≥ 85 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.29 ppm Range (Min, Max): NR Copollutant correlation: O 3 : r = -0.55 to -0.01 SO 2 : r = 0.31 to 0.67 PM 10 : r = 0.49 to 0.82

Note: Correlations are between pollutants for seven monitoring stations. Increment: 1.29 ppm % Increase (t-value); lag:

Nonaccidental: 5.88% (6.42); 1; 9.39% (6.89); 0-5 CO+PM 10 +O 3 +SO 2 : 6.13% (4.34); 1 Age Group: ≤ 64 4.10% (2.52); 1; / 4.76% (2.19); 0-5 Age Group: 65-74 6.24% (3.17); 1; / 8.12% (3.88); 0-5 Age Group: 75-84 8.64% (4.82); 1; / 13.12% (5.12); 0-5 Age Group: ≥ 85 8.58% (4.45); 1; / 13.20% (4.82); 0-5 April-September 7.09% (4.02); 1; / 9.65% (4.50); 0-5 October-March 5.45% (1.14); 1; / 7.80% (1.89); 0-5 Cardiac 7.79% (4.56); 1; / 11.22% (4.8); 0-5 Respiratory 12.93% (5.78); 1; / 21.31% (6.34); 0-5

Author: Chock et al. (2000, 010407 ) Period of Study: 1989-1991

Location: Pittsburgh, PA Health Outcome (ICD9): Mortality: Respiratory (480-486, 490-496, 507); cardiovascular (390-448); influenza (487) Study Design: Time series Statistical Analyses: Poisson GAM; Cubic B-spline basis functions Age Groups Analyzed: All ages <75 yr >75 yr Pollutant: CO Averaging Time: 1-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: PM 10 ; PM 2.5 ; O 3 ; SO 2 ; NO 2 Increment: NR β (SE); lag: Age Group: <75 CO alone: 0.0080 (1.56); 0 PM 10 , CO: 0.0030 (0.48); 0 PM 10 , NO 2 , CO: 0.0079 (1.14); 0 PM 10 , O 3 , SO 2 , NO 2 , CO: 0.072 (1.02); 0 CO -0.00738 (-1.42); -3; / 0.00133 (0.23); -2; -0.00219 (-0.38); -1; / 0.00809 (1.48); 0; -0.00129 (-0.22); 1; / 0.00512 (0.90); 2; -0.00974 (-1.87); 3 CO, PM 10 , O 3 , SO 2 , NO 2 -0.01103 (-1.48); -3; / -0.00097 (-0.13); -2; 0.00514 (0.67); -1; / 0.00853 (1.15); 0; -0.00404 (-0.52); 1; / -0.00296 (-0.39); 2; -0.00346 (-0.46); 3 Season CO Winter: 0.00539 (0.78); 0 Spring: 0.01655 (1.90); 0 Summer: 0.00155 (0.14); 0 Fall: 0.00797 (1.14); 0



### January 2010 C-72

### Study Design Concentrations Effect Estimates (95% CI) CO, PM 10 Winter: -0.00563 (-0.50); 0 Spring: 0.01233 (0.99); 0 Summer: -0.00712 (-0.48); 0 Fall: 0.00661 (0.73); 0 CO, PM 10 , O 3 , SO 2 , NO 2 Winter: -0.01326 (-0.95); 0 Spring: 0.02501 (1.54); 0 Summer: 0.01874 (0.92); 0 Fall: 0.01011 (0.88); 0 Age Group:>75 CO Alone: -0.0035 (-0.67); 0 CO, PM 10 : -0.0104 (-1.67); 0 CO, PM 10 , NO 2 : -0.0128 (-1.80); 0 CO, PM 10 , O 3 , SO 2 , NO 2 : -0.0144 (-1.99); 0 CO -0.00025 (-0.05); -3; / -0.00242 (-0.42); -2; -0.00238 (-0.41); -1; / -0.00302 (-0.54); 0; -0.00116 (-0.20); 1; / -0.00508 (-0.88); 2; -0.00251 (-0.48); 3 CO, PM 10 , O 3 , SO 2 , NO 2 -0.00123 (-0.17); -3; / -0.00876 (-1.13); -2; -0.00682 (-0.88); -1; / -0.01248 (-1.66); 0; -0.00672 (-0.86); 1; / -0.00181 (-0.23); 2; -0.00515 (-0.69); 3 Season CO Winter: -0.00304 (-0.43); 0 Spring: 0.00482 (0.54); 0 Summer: 0.01178 (1.07); 0 Fall: -0.01011 (-1.43); 0 CO, PM 10 Winter: -0.02303 (-2.03); 0 Spring: -0.00517 (-0.40); 0 Summer: 0.00735 (0.50); 0 Fall: -0.01042 (-1.14); 0 CO, PM 10 , O 3 , SO 2 , NO 2 Winter: -0.03370 (-2.41); 0 Spring: -0.00652 (-0.39); 0 Summer: 0.01258 (0.61); 0 Fall: -0.01250 (-1.07); 0



### January 2010 C-73

### Study Design Concentrations Effect Estimates (95% CI)

Author: Cifuentes et al. (2000, 010351 ) Period of Study: 1988-1996

Location: Santiago, Chile Health Outcome (ICD9): Mortality: All causes (nonaccidental) (<800) Study Design: Time series Statistical Analyses: Poisson GAM, GAM with filtered variables & GLM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 1-h avg Mean (SD) unit: 2.5 ppb Range (5th, 95th): (0.6, 6.2) Copollutant correlation: PM 2.5 : r = 0.80 PM 10-2.5 : r = 0.47 SO 2 : r = 0.62 NO 2 : r = 0.65 O 3 : r = -0.01 Increment: All yr: 2.5 ppm Winter: 3.6 ppm Summer: 1.3 ppm Relative Risk (t-ratio); Lag All Year CO: 1.041 (7.2); 0-1 CO, PM 2.5 : 1.025 (3.5); 0-1 CO, PM 10-2.5 : 1.035 (4.9); 0-1 CO, SO 2 : 1.038 (6.0); 0-1 CO, NO 2 : 1.026 (3.9); 0-1 CO, O 3 : 1.036 (4.8); 0-1 Winter CO: 1.052 (5.9); 0-1 CO, PM 2.5 : 1.025 (2.1); 0-1 CO, PM 10-2.5 : 1.049 (4.3); 0-1 CO, SO 2 : 1.049 (5.0); 0-1 CO, NO 2 : 1.027 (2.6); 0-1 CO, O 3 : 1.051 (4.4); 0-1 Summer CO: 1.053 (6.0); 0-1 CO, PM 2.5 : 1.053 (5.3); 0-1 CO, PM 10-2.5 : 1.053 (5.3); 0-1 CO, SO 2 : 1.050 (5.2); 0-1 CO, NO 2 : 1.047 (5.2); 0-1 CO, O 3 : 1.042 (3.6); 0-1

All Year GAM model CO: 1.041 (7.2); 0-1 CO, PM 2.5 , PM 10-2.5 , SO 2 , NO 2 , O 3 : 1.032 (4.6); 0-1 GAM Filtered Variables CO: 1.030 (4.3); 0-1 CO, PM 2.5 , PM 10-2.5 , SO 2 , NO 2 , O 3 : 1.022 (2.4); 0-1 GLM CO: 1.023 (2.4); 0-1 CO, PM 2.5 , PM 10-2.5 , SO 2 , NO 2 , O 3 : 1.013 (1.1); 0-1

Author: Conceicao et al. (2001, 016628 ) Period of Study: 1994-1997

Location: Sao Paulo, Brazil Health Outcome (ICD9): Mortality: Respiratory diseases (460-519) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: <5 yr Pollutant: CO Averaging Time: Max 8-h ma Mean (SD) unit: Total: 4.4 (2.2) ppm 1994: 5.1 (2.4) ppm 1995: 5.1 (2.4) ppm 1996: 3.9 (2.0) ppm 1997: 3.7 (1.6) ppm Range (Min, Max): NR Copollutant: PM 10 ; SO 2 ; O 3 Increment: NR β (SE); lag: CO: 0.0306 (0.0076); 2 CO, SO 2 , PM 10 , O 3 : 0.0259 (0.0116); 2

Model 1: Pollutant concentration: 0.0827 (0.0077); 2 Model 2: 1+loess(time): 0.0285 (0.0074); 2 Model 3: 2+loess(tem perature)+humidity: 0.0309 (0.0076); 2 Model 4: 3+nonrespiratory counts: 0.0306 (0.0076); 2 Model 5: 4+autoregressive parameters: 0.0292 (0.0118); 2

Author: De Leon et al. (2003, 055688 ) Period of Study: 1/1985-12/1994

Location: New York, NY Health Outcome (ICD9): Mortality: Circulatory (390-459); cancer (140-239) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages <75 yr >75 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 2.45 ppm IQR (25th, 75th): (1.80, 2.97) Copollutant: PM 10 ; O 3 ; SO 2 ; NO 2 The study did not present quantitative results for CO.



### January 2010 C-74

### Study Design Concentrations Effect Estimates (95% CI)

Author: Dominici et al. (2003, 056116 ) Period of Study: 1987-1994

Location: 90 U.S. cities (NMMAPS) Health Outcome (ICD9): Mortality: All-cause (nonaccidental); cardiovascular; respiratory Study Design: Time series Statistical Analyses: 1. GAM with S-PLUS default convergence criteria 2. GAM with more stringent convergence criteria 3. Poisson GLM with natural cubic splines Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: O 3 ; NO 2 ; SO 2 ; CO Increment: 1 ppm % Increase (Lower CI, Upper CI); Lag

CO 0.08% (-0.18 to 0.34); 0 0.46% (0.18-0.73); 1 0.16% (-0.12 to 0.45); 2

Author: Fairley et al. (1999, 000896 ) Period of Study: 1989-1996

Location: Santa Clara, CA Health Outcome (ICD9): Mortality: Respiratory; cardiovascular Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg; Max 8-h avg Median (SD) unit: 24-h avg: 1.4 (1.0) ppm Max 8-h avg: 2.1 (1.6) ppm Range (Min, Max): 24-h avg: (0.0, 7.6) Max 8-h avg: (0.2, 2.5) Copollutant: correlation PM 10 : r = 0.609; PM 2.5 : r = 0.435; PM 10-2.5 : r = 0.326; COH: r = 0.736; NO 3 : r = 0.270; SO 4 : r = 0.146; O 3 : r = -0.215 Increment: 2.2 ppm Relative Risk (Lower CI, Upper CI); lag:

1980-1986 CO: 1.04; 0; CO: 1.05; 1; CO, COH: 1.00; 1; CO, NO 3 : 1.03; CO, NO 3 , O 3 , COH: 1.00

1989-1996 CO: 1.02; 0; CO: 1.04; 1; CO, PM 2.5 : 0.98; CO, NO 3 : 1.01; CO, NO 2 , O 3 , NO 3 : 1.06 Respiratory mortality: CO: 1.08; 1 Cardiovascular mortality: CO: 1.04; 1

Author: Fischer et al. (2003, 043739 ) Period of Study: 1986-1994

Location: The Netherlands Health Outcome (ICD9): Mortality: Nonaccidental (<800); pneumonia (480-486); COPD (490-496); cardiovascular (390-448) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: <45 yr 45-64 yr 65-74 yr ≥ 75 yr Pollutant: CO Averaging Time: 24-h avg Median (SD) unit: 406 μg/m 3 Range (Min, Max): (174, 2620) Copollutant: PM 10 ; BS; O 3 ; NO 2 ; SO 2 Increment: 1,200 μg/m 3 Relative Risk (Lower CI, Upper CI); lag:

Cardiovascular Age Group: <45: 0.965 (0.750-1.240); 0-6 45-64: 1.029 (0.941-1.125); 0-6 65-74: 1.038 (0.972-1.108); 0-6 ≥ 75: 1.024 (0.984-1.065); 0-6 COPD Age Group: <45: 1.710 (0.852-3.435); 0-6 45-64: 1.181 (0.850-1.640); 0-6 65-74: 1.377 (1.147-1.654); 0-6 ≥ 75: 1.072 (0.963-1.193); 0-6 Pneumonia Age Group: <45: 0.927 (0.463-1.856); 0-6 45-64: 2.691 (1.509-4.800); 0-6 65-74: 1.118 (0.743-1.683); 0-6 ≥ 75: 1.230 (1.090-1.389); 0-6

Author: Forastiere et al. (2005, 086323 ) Period of Study: 1998-2000

Location: Rome, Italy Health Outcome (ICD9): Mortality: IHD (410-414) Study Design: Time-stratified case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: >35 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 2.4 (1.0) mg/m 3 IQR (25th, 75th): (1.7, 2.9) Copollutant correlation: PNC: r = 0.89; PM 10 : r = 0.34; NO 2 : r = 0.54; SO 2 : r = 0.52; O 3 : r = 0.01 Increment: 1.2 mg/m3 % Increase (Lower CI, Upper CI); lag: 6.5% (1.0-12.3); 0 4.7% (-0.9 to 10.7); 1 2.6% (-3.0 to 8.5); 2 -0.1% (-5.5 to 5.5); 3 7.0% (0.8-13.7); 0-1



### January 2010 C-75

### Study Design Concentrations Effect Estimates (95% CI)

Author: Forastiere et al. (2007, 090720 ) Period of Study: 1998-2001

Location: Rome, Italy Health Outcome (ICD9): Mortality: Malignant neoplasms (140-208); diabetes mellitus (250); hypertens ive (401-405); previous AMI (410, 412); IHD (410-414); conduction disorders of the heart (426); dysrhythmia (427); heart failure (428); cerebrovascular (430- 438); peripherical artery disease (440-448); COPD (490-496) Study Design: Time-stratified

case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: >35 yr Pollutant: CO Averaging Time: 24-h avg

Mean (SD) unit: NR IQR (25th, 75th): NR Copollutant: PM 10 ; PM 2.5 ; NO X ; Benzene This study did not present quantitative results for CO.

Author: Goldberg et al. (2001, 016548 ) Period of Study: 1984-1993

Location: Montreal, Quebec, Canada Health Outcome (ICD9): Mortality: Upper respiratory diseases (472-478); acute upper respiratory diseases (460-465); acute lower respiratory (466, 480-487, 512, 513, 518, 519) Study Design: Time series Statistical Analyses: Poisson GAM; LOESS Age Groups Analyzed: <65 yr; ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg

M ean (SD) unit: 0.8 (0.5) ppm Range (Min, Max): (0.1, 5.1) Copollutant: TSP; PM 10 ; PM 2.5 ; Sulfates; COH; SO 2 ; NO 2 ; NO; O 3 The study did not present quantitative results for CO.

Author: Goldberg et al. (2003, 035202 ) Period of Study: 1984-1993

Location: Montreal, Quebec, Canada Health Outcome (ICD9): Mortality: CHF (428) Study Design: Time-series Statistical Analyses: Poisson GLM, natural splines Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.8 (0.5) ppm Range (Min, Max): (0.1, 5.1) Copollutant: PM 2.5 ; Sulfate; SO 2 ; NO 2 ; O 3 Increment: 0.50 ppm % Increase (Lower CI, Upper CI); lag: Daily mortality from CHF -0.99% (-6.31 to 4.63); 0 0.12% (-5.29 to 5.84); 1 -1.38% (-8.81 to 6.66); 0-2 Daily mortality among persons classified as having CHF before death 2.10% (-0.24 to 4.49); 0 2.28% (-0.09 to 4.72); 1 2.86% (-0.46 to 6.29); 0-2

Author: Goldberg et al. (2006, 088641 ) Period of Study: 1984-1993

Location: Montreal, Quebec, Canada Health Outcome (ICD9): Mortality: Diabetes (250) Study Design: Time series Statistical Analyses: Poisson, natural splines Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.8 (0.5) ppm Range (Min, Max): (0.1, 5.1) Copollutant: PM 2.5 ; Sulfate; SO 2 ; NO 2 ; O 3 Increment: 0.50 ppm % Increase (Lower CI, Upper CI); lag: Daily mortality from diabetes 2.64% (-2.56 to 8.12); 0 6.54% (1.31-12.03); 1 8.08% (1.03-15.62); 0-2 Daily mortality among persons classified as having diabetes before death 1.15% (-1.69 to 4.07) ; 0 1.30% (-1.58 to 4.27) ; 1 2.63% (-1.42 to 6.85) ; 0-2

Author: Gouveia et al. (2000, 012132 ) Period of Study: 1991-1993

Location: Sao Paulo, Brazil Health Outcome (ICD9): Mortality: Respiratory; cardiovascular; all other causes Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: All ages >65 yr <5 yr Pollutant: CO Averaging Time: Maximum 8-h moving avg

Mean (SD) unit: 5.8 (2.1) ppm Range (Min, Max): (1.3, 16.2) Copollutant: PM 10 ; SO 2 ; NO 2 ; O 3 Increment: 5.1 ppm Relative Risk (Lower CI, Upper CI); lag: Age Group: All ages: All-causes 1.012 (0.994-1.031); 0 Age Group: >65 All-causes: 1.020 (0.996-1.046); 0 Respiratory: 0.981 (0.927-1.037); 2 CVD: 1.041 (1.007-1.076); 0 Age Group: <5 Respiratory: 1.086 (0.950-1.238); 0 Pneumonia: 1.141 (0.962-1.321); 2



### January 2010 C-76

### Study Design Concentrations Effect Estimates (95% CI)

Author: Gwynn et al. (2000, 074109 ) Period of Study: 5/1988-10/1990

Location: Buffalo, NY Health Outcome (ICD9): Mortality: Respiratory (466, 480-486); Circulatory (401-405,410-414, 415-417); All nonaccidental causes (<800) Study Design: Time-series Statistical Analyses: Poisson GLM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant correlation: H+: r =0.15; SO 4 2- : r = 0.24; O 3 : r = -0.23; SO 2 : r = 0.11; NO 2 : r = 0.65 Increment: NR β (SE); lag: Respiratory mortality: 0.032466 (0.053802); 0 Circulatory mortality: 0.039216 (0.026544); 3 Total mortality: 0.040214 (0.015205); 3

Author: Hoek et al. (2001, 016550 ) Period of Study: 1986-1994

Location: The Netherlands Health Outcome (ICD9): Mortality: Heart failure (428); arrhythmia (427); cerebrovascular (430-436); thrombocytic (433, 434, 444, 452, 453); cardiovascular (390- 448) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: O 3 ; BS; PM 10 ; SO 2 ; NO 2 Increment: 120 μg/m 3 Relative Risk (Lower CI, Upper CI); Lag Total CVD mortality: 1.026 (0.993-1.060); 0-6 MI and other IHD mortality: 1.050 (1.004-1.099); 0-6 Arrhythmia: 1.062 (0.937-1.203); 0-6 Heart failure mortality: 1.109 (1.012-1.216); 0-6 Cerebrovascular mortality: 1.066 (1.029-1.104); 0-6 Embolism, thrombosis: 1.065 (0.926-1.224); 0-6

Author: Hoek et al. (2000, 010350 ) Period of Study: 1986-1994

Location: The Netherlands Health Outcome (ICD9): Mortality: Pneumonia (480-486); COPD (490-496); CVDs (CVD) (390-448) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Netherlands: 457 μg/m 3 Four Major Cities: 589 μg/m 3 Range (Min, Max): Netherlands: (174, 2620) Four Major Cities: (202, 4621) Copollutant correlation: PM 10 : r = 0.64; BS: r = 0.89; O 3 : r = -0.48; NO 2 : r = 0.89; SO 2 : r = 0.65; SO 4 2- : r = 0.55; NO 3 -: r = 0.58 Increment: Single-day lag (1): 1,500 μg/m 3 Weekly avg (0-6): 1200 μg/m 3 Relative Risk (Lower CI, Upper CI); Lag

CO Four Major Cities: 1.022 (0.995-1.050); 1 Four Major Cities: 1.044 (1.008-1.082); 0-6 Netherlands w/o Major Cities: 1.040 (1.020-1.060); 1 Netherlands w/o Major Cities: 1.051 (1.026-1.076); 0-6 avg Entire Netherlands: 1.035 (1.018-1.052); 1 Entire Netherlands: 1.046 (1.025-1.068); 0-6 CVD: 1.044 (1.012-1.077); 0-6 COPD: 1.194 (1.099-1.298); 0-6 Pneumonia: 1.276 (1.143-1.426); 0-6 Winter: 1.038 (1.013-1.063); 0-6 Summer: 1.199 (1.108-1.296); 0-6 Multi-pollutant model CO, PM 10 Total mortality: 0.969 (0.914-1.028); 0-6 CVD: 1.005 (0.918-1.101); 0-6 BS, CO Total mortality: 0.980 (0.933-1.030); 0-6 CVD: 0.927 (0.860-0.999); 0-6 CO, SO 4 2- Total mortality: 0.990 (0.951-1.030); 0-6 CVD: 0.999 (0.939-1.063); 0-6

Author: Honda et al. (2003, 193774 ) Period of Study: 1976-1990

Location: Tokyo, Japan Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800) Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Median (SD) unit: 1.6 ppm Range (Min, Max): (0, 6.8) Copollutant correlation: NO: r = 0.403; NO 2 : r = 0.415; Oxidant: r = 0.396; SO 2 : r = 0.675 Increment: NR Rate Ratio (Lower CI, Upper CI); lag:

CO concentration <1.1 ppm: 1.00 (reference category) 1.1-1.6 ppm: 1.017 (1.009, 1.026) 1.6-2.2 ppm: 1.031 (1.020, 1.041) >2.2 ppm: 1.051 (1.039, 1.063)



### January 2010 C-77

### Study Design Concentrations Effect Estimates (95% CI)

Author: Hong et al. (2002, 035060 ) Period of Study: 1/1991-12/1997

Location: Seoul, Korea Health Outcome (ICD9): Mortality: Hemorrhagic and ischemic stroke (431-434) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.44 (0.70) ppm Range (Min, Max): (0.430, 5.14) Copollutant: TSP; SO 2 ; NO 2 ; O 3 Increment: 0.76 ppm Relative Risk (Lower CI, Upper CI); lag: 1.06 (1.02, 1.09); 1 Multipollutant: CO, TSP: 1.07 (1.03, 1.11); 1 CO, NO 2 : 1.06 (1.00, 1.11); 1 CO, SO 2 : 1.05 (1.01, 1.10); 1 CO, O 3 : 1.09 (1.05, 1.13); 1

Author: Hong et al. (1999, 011195 ) Period of Study: 1/1995-12/1995

Location: Inchon, Korea Health Outcome (ICD9): Mortality: Cardiovascular (400- 440); respiratory (460-519); nonaccidental causes (<800) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.7 (0.8) ppm Range (Min, Max): (0.3, 5.1) Copollutant: SO 2 ; NO 2 ; O 3 Increment : 1 ppm Relative Risk (Lower CI, Upper CI); lag: Total mortality: 0.993 (0.950, 1.037); 0-4 Cardiovascular mortality: 0.965 (0.892, 1.044); 0-4

Author: Hong et al. (2002, 024690 ) Period of Study: 1/1995-12/1998

Location: Seoul, Korea Health Outcome (ICD9): Mortality: Stroke (160-169) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.2 (0.5) ppm Range (Min, Max): (0.4, 3.4) Copollutant: correlation PM 10 : r = 0.22; NO 2 : r = 0.64; SO 2 : r = 0.90; O 3 : r = -0.35 Increment: 0.3 ppm % Increase (Lower CI, Upper CI); lag: CO: 2.2% (0.4, 4.1); 2 CO (stratified by PM 10 concentration): <median concentration of PM 10 : 1.1; 2 ≥ median concentration of PM 10 : 3.6; 2

Author: Hong et al. (1999, 008087 ) Period of Study: 1/1995-8/1996

Location: Inchon, South Korea Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); respiratory; cardiovascular Study Design: Time series Statistical Analyses: Poisson GAM; LOESS Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 15.2 (7.1) ppb Range (Min, Max): (2.9, 51.2) Copollutant: PM 10 ; NO 2 ; SO 2 ; O 3 Increment: 100 ppb β (SE); lag: Total Mortality CO 0.0019 (0.0015); 1 0.0024 (0.0041); 0-4 CO, PM 10 , NO 2 , SO 2 , O 3 -0.0009 (0.0019); 1 -0.0018 (0.0043); 0-4 Cardiovascular Mortality CO 0.0019 (0.0073); 1 -0.0008 (0.0028); 0-4 CO, PM 10 , NO 2 , SO 2 , O 3 -0.0053 (0.0078); 1 -0.0037 (0.0033); 0-4 Respiratory Mortality CO 0.0148 (0.0065); 1 0.0063 (0.0171); 0-4 CO, PM 10 , NO 2 , SO 2 , O 3 0.0121 (0.0079); 1 -0.0034 (0.0183); 0-4

Author: Keatinge et al. (2001, 017063 ) Period of Study: 1976-1995

Location: London, England Health Outcome (ICD9): Mortality: Nonaccidental causes (<800) Study Design: Time series Statistical Analyses: Singleand multiple-delay regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit : NR Range (Min, Max): NR Copollutant: SO 2 ; PM 10 The study did not present quantitative results for CO.



### January 2010 C-78

### Study Design Concentrations Effect Estimates (95% CI)

Author: Kettunen et al. (2007, 091242 ) Period of Study: 1998-2004

Location: Helsinki, Finland Health Outcome (ICD10): Mortality: Stroke (I60-I61, I63-I64) Study Design: Time series Statistical Analyses:Poisson GAM, penalized thinplate splines Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time : Max 8-h ma Median (SD) unit: Cold Season: 0.5 mg/m 3 Warm Season: 0.4 mg/m 3 Range (Min, Max): Cold Season: (0.1, 2.4) Warm Season: (0.1, 1.1) Copollutant: correlation Cold Season: PM 2.5 : r = 0.32; UFP: r = 0.47 Warm Season: PM 2.5 : r = 0.24; UFP: r = 0.39 Increment: 0.2 mg/m 3 % Increase (Lower CI, Upper CI); lag:

Cold Season 0.47 (-3.29 to 4.39); 0; / -0.63 (-4.39 to 3.28); 1; -2.69 (-6.46 to 1.24); 2; / -0.19 (-3.93 to 3.69); 3

Warm Season 3.95 (-3.78 to 12.30); 0; / 8.33 (0.63 to 16.63); 1; 6.97 (-0.59 to 15.11); 2; / 7.54 (-0.05 to 15.71); 3

Author: Klemm et al. (2004, 056585 ) Period of Study: 8/1998-7/2000

Location: Fulton County and DeKalb County, GA (ARIES) Health Outcome (ICD9): 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 Analyzed: <65 yr; ≥ 65 yr Pollutant: CO Averaging Time: 1-h max Median (SD) unit: 1,310 (939.13) ppb Range (Min, Max ): (303.58, 7400) Copollutant: PM 2.5 ; PM 10-2.5 ; O 3 ; NO 2 ; SO 2 ; Acid; EC; OC; SO 4 ; Oxygenated HCs; NMHCs; NO 3 Increment: NR β (SE); lag: Quarterly Knots: 0.00002 (0.00001); 0-1 Monthly Knots: 0.00002 (0.00001); 0-1 Biweekly Knots: 0.00001 (0.00002); 0-1

Author: Knox et al. (2008, 193776 ) Period of Study: 1996-2004

Location: 352 English local authorities Health Outcome: Mortality Study Design: Cross sectional Statistical Analyses: Linear regression Age Groups Analyzed: NR Sample Description: Data from Oxford Cancer Intelligence Unit Averaging Time: NR Meuan (SD) nit: NR Range (Min, Max): NR Copollutant: NR Increment: NR Significant (p<0.01) correlations (r) between CO and diseases: Lung cancer: 0.28, Stomach cancer: 0.20, Oesophagus cancer: -0.20, Pr ostate cancer: -0.25, Brain cancer: -0.24, Mel anoma: -0.24, Hodgkin’s: - 0.19, Peripheral vascular disease: 0.15, Stroke: 0.16, Rheumatic heart diseas e: 0.27, Peptic ulcer: 0.28, Diabetes: 0.17, COPD: 0.25, Asthma: 0.14, Pneumonia: 0.44, Multip le sclerosis: -0.16, Motorneurone disease: -0.24, Parkinsons disease: - 0.15 Significant (p<0.01) socially standardized correlations between dis eases and exposures: Lung cancer: 0.25, Stomach c ancer: 0.18, RHD: 0.19, Pneumonia: 0.37, COPD: 0.17, Peptic ulcer: 0.16 Lags examined: NR



### January 2010 C-79

### Study Design Concentrations Effect Estimates (95% CI)

Author: Kwon et al. (2001, 016699 ) Period of Study: 1994-1998

Location: Seoul, Korea Health Outcome (ICD9): Mortality: CHF (428); cardiovascular (390-459) Study Design: 1. Time-series 2. Bi-directional case-crossover Statistical Analyses: 1. Poisson GLM, LOESS 2. Conditional logistic regression Age Groups Analyzed: <55 yr 55-64 yr 65-74 yr 75-84 yr ≥ 85 yr Pollutant: CO Averaging Time: 1-h avg Mean (SD) unit: 12.4 ppb Range (Min, Max): (4.1, 38.0) Copollutant correlation: PM 10 : r = 0.713; NO 2 : r = 0.744; SO 2 : r = 0.843; O 3 : r = -0.367 Increment: 0.59 ppm Odds Ratio (Lower CI, Upper CI); lag: From GAM approach CHF patients: 1.054 (0.991-1.121); 0; 0 General Population: 1. 022 (1.017- 1.029); 0 From case-crossover design CHF patients: 1.033 (0.946-1.127); 0 General Population: 1.007 (0.997- .016); 0 Modifiers and CHF patients (case-crossover design) Gender Male: 1.025 (0.890-1.180); 0 Female: 1.035 (0.925-1.157); 0 Age Group: <75: 0.948 (0.890-1.180); 0 ≥ 75: 1.116 (0.989-1.258); 0

Time from admission to death 4 or less wk: 1.088 (0.907-1.306); 0 >4 wk: 1.017 (0.920-1.124); 0 Total mortality: 1.033 (0.946-1.127); 0 Cardiovascular mortality: 1.033 (0.920-1.160); 0 Cardiac death: 1.052 (0.919-1.204); 0Two-pollutant model in CHF patients (casecrossover design) CO alone: 1.054 (0.991-1.121); 0 CO, PM 10 : 1.096 (0.981-1.224); 0 CO, NO 2 : 1.022 (0.932-1.122); 0 CO, SO 2 : 1.014 (0.909-1.131); 0 CO, O 3 : 1.056 (0.992-1.124); 0

Author: Lee et al. (2007, 093042 ) Period of Study: 1/2000-12/2004

Location: Seoul, Korea Health Outcome (ICD10): Mortality: Nonaccidental (A00- R99) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: Max 8-h ma Mean (SD) unit: w/ Asian dust days: 0.92 (0.42) ppm w/o Asian dust days:0.92 (0.41) ppm Asian dust days only: 1.00 (0.47) ppm Range (Min, Max): NR Copollutant: PM 10 ; NO 2 ; SO 2 ; O 3 Increment : 0.54 ppm % Increase (Lower CI, Upper CI); lag:

Model with Asian Dust Da ys: 3.3% (2.5-4.1); 1 Model without Asian dust days: 3.3% (2.5-4.2); 1

Author: Lipfert et al. (2000, 004088 ) Period of Study: 5/1992-9/1995

Location: Philadelphia, PA, three nearby suburban Pennsylvania counties, and three nearby New Jersey counties Health Outcome (ICD9): Mortality: Respiratory (460-519); cardiac (390-448); Cancer; other causes (<800) Study Design: Time series Statistical Analyses: Step-wise regression Age Groups Analyzed: <65 yr ≥ 65 yr Pollutant: CO Averaging Time : 24-h avg; 1-h max Mean (SD) unit: Camden: 24-h avg: 0.75 (0.40) ppm Philadelphia: 24-h avg: 0.63 (0.40) ppm 1-h max: 1.44 (1.04) Range (Min, Max): Camden: (0.10, 3.8) Philadelphia: 24-h avg: (0.10, 3.3) 1-h max: (0.0, 7.8) Copollutant: NO; NO 2 ; O 3 ; SO 2 ; SO 4 2- ; PM 10 ; PM 2.5 Increment: NR Attributable Risk; lag:

Peak CO All-cause Philadelphia: 0.0054; 0-1 4 Pennsylvania Counties: 0.0081; 0-1 Pennsylvania + NJ: 0.0085; 0-1 CO All seven counties in Pennsylvania and New Jersey All ages Respirator y: -0.0067; Cardiac: 0.0131; Other: 0.0078 All-cause: <65: 0.0148; 0-1; ≥ 65: 0.0054; 0-1

Joint model with CO Philadelphia: 0.0059; 0-1 4 Pennsylvania Counties: 0.0089; 0-1 Pennsylvania + NJ: 0.0096; 0-1 Cardiac: 0.0135; 0-1;

Other causes: 0.0084 <65: 0.0154; 0-1; ≥ 65: 0.0060; 0-1



### January 2010 C-80

### Study Design Concentrations Effect Estimates (95% CI)

Author: Lippmann et al. (2000, 011938 ) Period of Study: 1985-1990 1992-1994

Location: Detroit, MI and Windsor, ON Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); circulatory (390-459); respiratory (460-519) Study Design: Time series Statistical Analyses: Poisson GLM Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1985-1990: 0.9 ppm 1992-1994: 0.72 ppm Range (5th, 95th): 1985-1990: (.46, 1.61) 1992-1994: (0.36, 1.2) Copollutant correlation: 1985-1990 PM 10 : r = 0.35; TSP: r = 0.28; TSP-PM 10 : r = 0.02; TSP-SO 4 2- : r = 0.18; O 3 : r = -0.22; SO 2 : r = 0.36; NO 2 : r = 0.58

1992-1994 PM 10 : r = 0.38; PM 2.5 : r = 0.38; PM 10-2.5 : r = 0.24; H+: r = 0.16; SO 4 2- :r = 0.32; O 3 : r = 0.16; SO 2 : r = 0.42; NO 2 : r = 0.68 Increment: 1985-1990: 11.5 ppm; 1992-1994: 8.4 ppm Relative Risk (Lower CI, Upper CI); lag:

1985-1990 Total Mortality: 0.9842 (0.9667-1.002); 0 1.0103 (0.9926-1.0284); 1 1.0075 (0.9898-1.0254); 2 1.0145 (0.9967-1.0326); 3 0.9968 (0.9789-1.0151); 0-1 1.0105 (0.9925-1.0288); 1-2 1.0134 (0.9954-1.0317); 2-3 1.0003 (0.9823-1.0187); 0-2 1.0152 (0.9971-1.0336); 1-3 1.0053 (0.9873-1.0236); 0-3 Circulatory Mortality: 0.9818 (0.9574-1.0068); 0 0.9991 (0.9745-1.0243); 1 0.9980 (0.9735-1.0232); 2 1.0088 (0.9841-1.0341); 3 0.9888 (0.9640-1.0144); 0-1 0.9981 (0.9732-1.0237); 1-2 1.0042 (0.9792-1.0298); 2-3 0.9900 (0.9650-1.0157); 0-2 1.0029 (0.9777-1.0287); 1-3 0.9944 (0.9692-1.0202); 0-3 Respiratory Mortality; 0.9644 (0.9042-1.0287); 0 1.0142 (0.9518-1.0808); 1 1.0483 (0.9845-1.1164); 2 1.0468 (0.9828-1.1149); 3 0.9868 (0.9248-1.053); 0-1 1.0372 (0.9730-1.1056); 1-2 1.0554 (0.9904-1.1246); 2-3 1.0088 (0.9457-1.0762); 0-2 1.0466 (0.9817-1.1158); 1-3 1.0205 (0.9569-1.0884); 0-3 Total minus respiratory and circulatory mortality: 0.9939 (0.9668-1.0217); 0 1.0278 (1.0001-1.0562); 1 1.0178 (0.9902-1.0461); 2 1.0227 (0.9948-1.0514); 3 1.0127 (0.9860-1.0412); 0-1 1.0269 (0.9989-1.0556); 1-2 1.0249 (0.9968-1.0538); 2-3 1.0172 (0.9893-1.0458); 0-2 1.0322 (1.0041-1.0612); 1-3 1.0229 (0.9950-1.0516); 0-3

1992-1994 Total Mortality 0.9933 (0.9636-1.024); 0 1.0162 (0.9860-1.0473); 1 1.0116 (0.9816-1.0426); 2 0.9947 (0.9648-1.0254); 3 1.0056 (0.9756-1.0366); 0-1 1.0165 (0.9864-1.0476); 1-2 1.0038 (0.9739-1.0476); 2-3 1.0098 (0.9796-1.0409); 0-2 1.0104 (0.9862-1.0414); 1-3 1.0064 (0.9755-1.0382); 0-3 Circulatory Mortality 1.0076 (0.9640-1.0531); 0 1.0307 (0.9865-1.0768); 1 1.0142 (0.9705-1.0598); 2 0.9523 (0.9102-0.9964); 3 1.0229 (0.9788-1.0688); 0-1 1.0267 (0.9827-1.0727); 1-2 0.9802 (0.9375-1.0248); 2-3 1.0243 (0.9801-1.0726); 0-2 0.9987 (0.9553-1.0441); 1-3 1.0019 (0.9573-1.0487); 0-3



### January 2010 C-81

### Study Design Concentrations Effect Estimates (95% CI)

Respiratory Mortality 0.9894 (0.8912-1.0984); 0 0.9474 (0.8521-1.0533); 1 0.9652 (0.8682-1.0732); 2 0.9931 (0.8934-1.1040); 3 0.9626 (0.8668-1.0691); 0-1 0.9485 (0.8535-1.0541); 1-2 0.9752 (0.8775-1.0838); 2-3 0.9555 (0.8802-1.0615); 0-2 0.9567 (0.8607-1.0635); 1-3 0.9584 (0.9604-1.0675); 0-3 Total minus respiratory and circulatory mortality: 0.9769 (0.9332-1.0227); 0 1.0135 (0.9682-1.0609); 1 1.0195 (0.9747-1.0664); 2 1.0429 (0.9974-1.0905); 3 0.9940 (0.9494-1.0406); 0-1 1.0197 (0.9746-1.0670); 1-2 1.0371 (0.9918-1.0845); 2-3 1.0045 (0.9596-1.0515); 0-2 1.0353 (0.9896-1.0831); 1-3 1.0215 (0.9749-1.0702); 0-3

Author: Maheswaran et al. (2005, 090769 ) Period of Study: 1994-1998

Location: Sheffield, United Kingdom Health Outcome (ICD9): Mortality: CHD (410-414) Study Design: Ecological Statistical Analyses: Poisson Age Groups Analyzed: ≥ 45 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NO X ; PM 10 Notes: Quintiles represent the following mean CO concentrations and category limits: 5: 482 μg/m 3 ( ≥ 455) 4: 443 μg/m 3 ( ≥ 433 to <455) 3: 426 μg/m 3 ( ≥ 419 to <433) 2: 405 μg/m 3 ( ≥ 387 to <419) 1: 360 μg/m 3 (<387) Increment: NR Rate Ratios (Lower CI, Upper CI):

CO Adjusted for sex and age Quintile: 5 (highest): 1.24 (1.14, 1.36) 4: 1.30 (1.19, 1.41) 3: 1.15 (1.05, 1.25) 2: 1.08 (0.99, 1.17) 1: (lowest): 1.00

CO Adjusted for sex, age, deprivation, and smoking Quintile: 5 (highest): 1.05 (0.95, 1.16); 4: 1.16 (1.06, 1.28); 3: 1.04 (0.95, 1.14); 2: 1.03 (0.94, 1.13); 1 (lowest): 1.00

CO Adjusted for sex, age, deprivation, and smoking (spatially smoothed using a 1 km radius) Quintile: 5 (highest): 1.07 (0.96, 1.18); 4: 1.13 (1.03, 1.24); 3: 1.04 (0.95, 1.14); 2: 1.01 (0.92, 1.10); 1 (lowest): 1.00



### January 2010 C-82

### Study Design Concentrations Effect Estimates (95% CI)

Author: Maheswaran et al. (2005, 088683 ) Period of Study: 1994-1998

Location: Sheffield, United Kingdom Health Outcome (ICD9): Mortality: Stroke deaths (430-438) Study Design: Ecological Statistical Analyses: Poisson Age Groups Analyzed: ≥ 45 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Quintile: 5: 482 μg/m 3 ; 4: 443 μg/m 3 ; 3: 426 μg/m 3 ; 2: 405 μg/m 3 ; 1: 360 μg/m 3 Range (Min, Max): NR Copollutant correlation: PM 10 : r = 0.88; NO X : r = 0.87

Notes: Quintiles represent the following mean CO concentrations and category limits: 5: 482 μg/m 3 ( ≥ 455) 4: 443 μg/m 3 ( ≥ 433 to <455) 3: 426 μg/m 3 ( ≥ 419 to <433) 2: 405 μg/m 3 ( ≥ 387 to <419) 1: 360 μg/m 3 (<387) Increment: NR Rate Ratios (Lower CI, Upper CI); lag: RR for mortality and CO modeled outdoor air pollution Adjusted for sex and age Quintile: 5 (highest): 1.35 (1.19, 1.53); 4: 1.40 (1.24, 1.58); 3: 1.08 (0.95, 1.23); 2: 1.10 (0.97, 1.24); 1 (lowest): 1.00 Adjusted for sex, age, deprivation, and smoking Quintile: 5 (highest): 1.26 (1.10, 1.46); 4: 1.32 (1.15, 1.50); 3: 1.07 (0.93, 1.22); 2: 1.12 (0.99, 1.28); 1 (lowest): 1.00 Not spatially smoothed CO outdoor air pollution Quintile: 5 (highest): 1.26 (1.10, 1.46); 4: 1.32 (1.15, 1.50); 3: 1.07 (0.93, 1.22); 2: 1.12 (0.99, 1.28); 1 (lowest): 1.00 Spatially smoothed using a 1-km radius Quintile: 5 (highest): 1.16 (1.01, 1.34); 4: 1.22 (1.07, 1.39); 3: 0.95 (0.83, 1.09); 2: 0.97 (0.85, 1.11); 1 (lowest): 1.00

Author: Mar et al. (2000, 001760 ) Period of Study: 1995-1997

Location: Phoenix, AZ Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); cardiovascular (390- 449) Study Design: Time series Statistical Analyses: Poisson Age Groups Analyzed: >65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.5 (0.8) ppm Range (Min, Max): 1995: (0.5, 4.0) ppm 1996: (0.3, 4.0) ppm 1997: (0.3, 3.7) ppm Copollutant correlation: PM 2.5 : r = 0.85; PM 10 : r = 0.53; PM 10-2.5 : r = 0.34; NO 2 : r = 0.87; O 3 : r =-0.40; SO 2 : r =0.53 Increment: 1.19 ppm Relative Risk (Lower CI, Upper CI); lag: Total Mortality (CO exposure): 1.06 (1.02, 1.09); 0; 1.05 (1.01, 1.09); 1 Cardiovascular Mortality (CO exposure): 1.05 (1.00, 1.11); 0; 1.10 (1.04, 1.15); 1; 1.07 (1.02, 1.12); 2; 1.07 (1.02, 1.12); 3; 1.08 (1.03, 1.13); 4



### January 2010 C-83

### Study Design Concentrations Effect Estimates (95% CI)

Author: Moolgavkar et al. (2000, 012054 ) Period of Study: 1987-1995

Location: Cook County, IL Los Angeles County, CA Maricopa County, AZ Health Outcome (ICD9): Mortality: Circulatory (390-448); cardiovascular (390-429); cerebrovascular (430-448); COPD (490-496); asthma (493) Study Design: Time series Statistical Analyses: Poisson GAM, spline smoother Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg

Median unit: Cook county: 993 ppb Los Angeles: 1347 ppb Maricopa: 1240 ppb Range (Min, Max): Cook county: (224, 3912) Los Angeles: (237, 5955) Maricopa: (269, 4777) Copollutant correlation:

PM 10 : Cook: r = 0.30; LA: r = 0.45; Maricopa: r = 0.20 NO 2 : Cook: r = 0.63; LA: r = 0.80; Maricopa: r = 0.66 SO 2 : Cook: r = 0.35; LA: r = 0.78; Maricopa: r = 0.53 O 3 : Cook: r = -0.28; LA: r = -0.52; Maricopa: r = -0.61 Increment: 1 ppm % Change (Lower CI, Upper CI); lag: CVD Mortality Cook County CO -1.07 (-2.67, 0.54); 0; / 1. 25 (-0.36, 2.87); 1; 1.49 (-0.09, 3.07); 2; / 1. 90 (0.32, 3.48); 3; 1.44 (-0.16, 3.03); 4; / 0.72 (-0.89, 2.32); 5 Los Angeles County CO 3.47 (2.94, 4.00); 0; / 3.93 (3.41, 4.46); 1; 4.08 (3.56, 4.60); 2; / 3.76 (3.24, 4.28); 3; 2.91 (2.37, 3.44); 4; / 2.63 (2.09, 3.17); 5 CO, PM 10 2.27 (0.88, 3.66); 0; / 4.33 (2.96, 5.69); 1; 4.72 (3.38, 6.05); 2; / 4.26 (2.90, 5.63); 3; 2.49 (1.10, 3.88); 4; / 5.93 (4.60, 7.27); 5

CO and PM 2.5 0.43 (-1.35, 2.20); 0; / 2. 88 (1.16, 4.60); 1; 4.65 (2.93, 6.37); 2; / 5.93 (4.20, 7.65); 3; 3.88 (2.13, 5.63); 4; / 5.85 (4.12, 7.58); 5 Maricopa County CO 0.81 (-0.79, 2.39); 0; / 2. 20 (0.61, 3.79); 1; 3.05 (1.49, 4.61); 2; / 3.78 (2.27, 5.28); 3; 3.73 (2.27, 5.19); 4; / 2.25 (0.76, 3.72); 5 COPD Mortality Cook County CO -2.65 (-7.05, 1.75); 0; / 2. 80 (-1.60, 7.19); 1; 0.98 (-3.34, 5.31); 2; / 2. 20 (-2.12, 6.53); 3; 1.31 (-3.06, 5.68); 4; / 1.59 (-2.78, 5.97); 5 Los Angeles County CO 3.78 (2.31, 5.25); 0; / 5.23 (3.78, 6.69); 1; 5.71 (4.26, 7.17); 2; / 5.42 (3.95, 6.89); 3; 4.01 (2.51, 5.50); 4; / 3.82 (2.31, 5.33); 5 Maricopa County CO 1.29 (-2.19, 4.76); 0; / 4. 63 (1.17, 8.09); 1; 0.07 (-3.36, 3.50); 2; / 3. 00 (-0.30, 6.30); 3; 6.21 (3.02, 9.40); 4; / 3.27 (0.04, 6.50); 5 Cerebrovascular Disease Mortality Cook County -0.41 (-3.30, 2.47); 0; / 3.13 (0.23, 6.02); 1; 2.12 (-0.73, 4.97); 2; / 1. 00 (-1.85, 3.86); 3; 2.50 (-0.36, 5.37); 4; / 1.88 (-1.00, 4.76); 5 Los Angeles County 3.31 (2.32, 4.31); 0; / 3.88 (2.89, 4.87); 1; 3.23 (2.25, 4.22); 2; / 2.65 (1.66, 3.65); 3; 2.11 (1.11, 3.12); 4; / 2.04 (1.02, 3.06); 5 Maricopa County 0.26 (-2.65, 3.16); 0; / 3. 50 (0.60, 6.41); 1; 3.52 (0.66, 6.38); 2; / 4.61 (1.85, 7.37); 3; 4.78 (2.10, 7.46); 4; / 5.15 (2.45, 7.84); 5

Notes: Total Mortality effect estimates were not presented quantitatively.



### January 2010 C-84

### Study Design Concentrations Effect Estimates (95% CI)

Author: Moolgavkar et al. (2003, 051316 ) Period of Study: 1987-1995

Location: Cook County, Illinois & Los Angeles County, California Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); circulatory (390-448) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All Ages Pollutant: CO Averaging Time: 24-h avg

Median unit: Cook County: 993 ppb LA County: 1347 ppb Range (Min, Max): Cook County: (224, 3912) ppb LA County: (237, 5955) ppb Copollutant correlation: Cook County: NO 2 : r = 0.63; O 3 : r = -0.22; SO 2 : r = 0.35; PM 10 : r = 0.30 LA County: NO 2 : r = 0.80; O 3 : r = -0.52; SO 2 : r = 0.78; PM 10 : r = 0.45; PM 2.5 : r = 0.58 Increment: 1 ppm % Increase (t-statistic); lag Total Mortality Cook County CO: 0.6% (1.2); 0; / 2.5% (5.4); 1; / 1.2% (2.6); 2; 1.5% (3.2); 3; / 1.1% (2.5); 4; / 0.6% (1.3); 5 CO, PM 10 : -0.5% (-1.0); 0; / 2.2% (4.3); 1; / 1.1% (2.2); 2; 1.0% (1.9); 3; / 1.1% (2.1); 4; / 1.4% (2.7); 5 Total Mortality Los Angeles County CO: 1.3% (7.4); 0; / 1.9% (10. 5); 1; / 1.6% (8.9); 2; 1.4% (8.1); 3; / 1.0% (5.9); 4; / 0.7% (4.1); 5 CO, PM 10 : 0% (0); 0; / 2.2% (4.8); 1; / 1.4% (3.1); 2; 0.8% (1.8); 3; / 0.7% (1.6); 4; / 1.3% (3.0); 5 CO, PM 2.5 : -0.1% (-1.5); 0; / 1.5% (2.5); 1; / 2.4% (3.8); 2; 0.3% (0.5); 3; / 1.6% (2.8); 4; / 1.5% (2.6); 5 Total Mortality (Season-specific) Cook County Spring (CO): 0.8% (0.9); 0; / 2.4% (2.9); 1; / 0% (0); 2; 1.2% (1.5); 3; / 0.8% (1.0); 4; / -0.1% (-0.2); 5 Summer (CO): 1.2% (1.0); 0; / 3.6% (3.0); 1; / 4.2% (3.6); 2; -0.3% (-0.2); 3; / -1.1% (-1.0); 4; /-0.7% (-0.6); 5 Fall (CO): 1.2% (1.5); 0; / 2.1% (2.7); 1; / 0% (0); 2; 0% (0); 3; /-0.5% (-0.6); 4; / -0.7% (-0.9); 5 Winter (CO): -0.7% (-1.0); 0; / 1.8% (2.3); 1; / -0.2% (-0.3); 2; 0.5% (0.6); 3; / 1.2% (1.5); 4; / 1.0% (1.3); 5 Los Angeles County Total Mortality (Season-specific) Spring (CO): 3.6% (6.3); 0; / 3.5% (6.2); 1; / 1.9% (3.4); 2; 0.6% (1.0); 3; / -0.5% (-0.8); 4; / -0.7% (-1.2); 5 Summer (CO): 3.0% (3.0); 0; / 4.7% (4.6); 1; / 5.2% (5.1); 2; 4.1% (3.8); 3; / 1.9% (1.8); 4; / 1.4% (1.3); 5 Fall (CO): 1.8% (4.6); 0; / 2.0% (5.1); 1; / 1.0% (2.6); 2; 0.6% (1.5); 3; / 0.4% (1.2); 4; / 0.2% (0.6); 5 Winter (CO): 0% (0); 0; / 0.8% (2.5); 1; / 0.9% (3.1); 2; 1.0% (3.4); 3; / 0.5% (1.7); 4; / 0.5% (1.6); 5 CVD Mortality Cook County CO: -1.1% (-1.5); 0; / 1.8% (2.5); 1; / 1.5% (2.2); 2; 1.6% (2.4); 3; / 1.4% (2.1); 4; / 0.7% (1.0); 5 CO, PM 10 : -2.1% (-2.6); 0; / 1.5% (1.8); 1; / 1.4% (1.7); 2; 0.1% (1.1); 3; / 1.4% (1.9); 4; / 1.6% (2.1); 5 CVD Mortality Los Angeles County CO: 1.6% (6.3); 0; / 1.9% (7.6); 1; / 1.6% (6.6); 2; 1.9% (8.2); 3; / 1.6% (7.1); 4; / 1.4% (6.1); 5 CO, PM 10 : -0.8% (-1.2); 0; / 1.9% (3.0); 1; / 2.7% (4.3); 2; 1.3% (2.2); 3; / 0.5% (0.9); 4; / 2.8% (4.7); 5 CO, PM 2.5 : -2.2% (-2.7); 0; / 1.5% (1.8); 1; / 1.9% (2.0); 2; 1.9% (2.2); 3; / 2.1% (2.6); 4; / 3.7%(4.5); 5



### January 2010 C-85

### Study Design Concentrations Effect Estimates (95% CI)

CVD Mortality (Season Specifid) Cook County Spring (CO): 0.7% (0.5); 0; / 1.4% (1.1); 1; / 0.3% (0.3); 2; 1.1% (0.9); 3; / 0.4% (3.1); 4; / 0.1% (0.6); 5 Summer (CO): -2.6% (-1.4); 0; / 2.5% (1.4); 1; / 6.5% (3.7); 2; 0.9% (0.5); 3; / -1.9% (-1.1); 4; / -1.0% (-0.6); 5 Fall (CO): 0% (0); 0; / 2.9% (2.5); / 1; 0% (0); 2; 0% (0); 3; /-0.8% (-0.7); / 4; 0% (0); 5

Winter (CO): -2.5% (-2.2); 0; / 0.7% (0.6); 1; / 0% (0); 2; 1.3% (1.1); 3; / 0.8% (0.7); 4; / 0.4% (0.4); 5 Los Angeles County CVD Mortality (Season-specific) Spring (CO): 3.0% (3.7); 0; / 3.3% (4.1); 1; / 2.3% (2.9); 2; 0.7% (0.9); 3; / -1.2% (-1.6); 4; / 0% (0); 5 Summer (CO): 4.0% (2.8); 0; / 5.2% (3.5); 1; / 6.3% (4.3); 2; 5.0% (3.3); 3; / 3.1% (2.0); 4; / 3.6% (2.3); 5 Fall (CO): 2.3% (4.2); 0; / 2.1% (3.7); 1; / 1.1% (1.9); 2; 1.2% (2.2); 3; / 1.5% (2.9); 4; / 1.0% (1.8); 5 Winter (CO): 0.3% (0.8); / 0; 0.7% (1.7); 1; / 0.8% (2.0); 2; 1.4% (3.4); 3; / 1.0% (2.3); 4; / 1.1% (2.5); 5

Author: Ostro et al. (1999, 006610 ) Period of Study: 1989-1992

Location: Coachella Valley, California Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); respiratory (460-519); cardiovascular (393-440) Study Design: Time series Statistical Analyses: Poisson GAM; LOESS Age Groups Analyzed: >50 yr Pollutant: CO Averaging Time: 1-h max Mean (SD) unit: 1.35 ppm Range (Min, Max): (0, 6.0) Copollutant correlation: PM 10 : r = -0.18; O 3 : r = -0.47; NO 2 : r = 0.65 Increment: NR β (SE); lag: CO: 0.0371 (0.0157); 2 CO, PM 10 : 0.0300 (0.0194); 2

Author: Penttinen et al. (2004, 087432 ) Period of Study: 1988-1996

Location: Helsinki, Finland Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); respiratory (460-519); cardiovascular (393-440) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All ages 15-64 yr 65-74 yr ≥ 75 Pollutant: CO Averaging Time: Max 8-h avg

Median unit: 1.2 mg/m 3 Range (Min, Max): (0, 12.4) Copollutant correlation: O 3 : r = -0.46; NO 2 : r = 0.59; SO 2 : r = 0.55; PM 10 : r = 0.45; TSP: r = 0.26; TSP Blackness: r = 0.26 Increment: 1 mg/m 3 % Increase (Lower CI, Upper CI); lag: Total Mortality -1.50% (-2.78, -0.22); 0 0.15% (-1.09, 1.39); 1 -1.00% (-2.80, 0.81); 0-3 Cardiovascular Mortality -2.48% (-4.30, -0.66); 0 -0.84% (-2.61, 0.93); 1 -1.87% (-4.43, 0.69); 0- Respiratory Mor 

# t ality -0.48% (-4.84, 3.87); 0 -0.14% (-4.43, 4.15); 1 -1.49% (-7.73, 4.74); 0-3

Author: Peters et al. (2000, 001756 ) Period of Study: 1982-1994

Location: Northern Bavaria (Rural Germany) and the Coal Basin of the Czech Republic Health Outcome (ICD9): Mortality: Total (non-accidental) (<800); Cardiovascular (390- 459); Respiratory (460-519); Cancer (140-239) Study Design: Time-series Statistical Analyses: (1) Poisson Regression Models by logistic regression analyses with a cubic function; (2) Poisson GAM, natural splines Age Groups Analyzed: All Ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Coal Basin: 0.58 (0.39) mg/m 3 Northeast Bavaria: 0.88 (0.69) mg/m 3 Range (Min, Max): Coal Basin: (-0.1, 2.88) Northeast Bavaria: (0.1, 6.2) Copollutant correlation: SO 2 : r = 0.37; TSP: r = 0.37; NO 2 : r = 0.32; O 3 : r = -0.57; PM 10 : r = 0.44; PM 2.5 : r = 0.42 Increment: 1 mg/m 3 Relative Risk (Lower CI, Upper CI); lag: Coal Basin of the Czech Republic Total Mortality: 1.016 (0.998, 1.035); 0; / 1.016 (0.998, 1.034); 1; 1.013 (0.996, 1.030); 2; / 1.012 (0.995, 1.028); 3 Northeast Bavaria Total Mortality: 1.014 (0.994, 1.034); 0; / 1.023 (1.005, 1.041); 1; 1.013 (0.995, 1.031); 2; / 1.003 (0.985, 1.021); 3 CVD Mortality: 1.018 (0.994, 1.044); 0; / 1.012 (0.987, 1.038); 1; 1.016 (0.991, 1.041); 2; / 1.004 (0.980, 1.029); 3



### January 2010 C-86

### Study Design Concentrations Effect Estimates (95% CI)

Author: Rainham et al. (2003, 053202 ) Period of Study: 1980-1996

Location: Toronto, ON, Canada Health Outcome (ICD9): Mortality: Cardiac (390-459); Respiratory (480-519); Total (non-accidental) (<800) Study Design: Time-series Statistical Analyses: Poisson GAM, natural cubic splines Age Groups Analyzed: <65 ≥ 65 Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.0 (0.4) ppm Range (Min, Max): (0.0, 4.0) Copollutant: O 3 ; NO 2 ; SO 2 The study did not present quantitative results for CO.

Author: Roemer et al. (2001, 019391 ) Period of Study: 1/1987-11/1998

Location: Amsterdam Health Outcome (ICD9): Mortality: Total (non-accidental) (<800) Study Design: Time-series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Air pollution background: 836 μg/m 3 Air pollution traffic: 1805 μg/m 3 Range (10th, 90th): Air pollution background: (448, 1315) μg/m 3 Air pollution traffic: (727, 3192) μg/m 3

Copollutant: BS; PM 10 ; SO 2 ; NO 2 ; NO; O 3 Increment: Lag 1 and 2: 100 μg/m 3 Lag 0-6: 50 μg/m 3 Relative Risk (Lower CI, Upper CI); lag: Total Population using Background sites 1.002 (1.000-1.004); 1; 1.001 (0.999-1.003); 2; 1.001 (1.000-1.003); 0-6 Traffic Population using Background Sites 1.003 (0.997-1.008); 1; 1.008 (1.003-1.013); 2; 1.003 (0.999-1.007); 0-6 Total population using Traffic Sites 1.000 (1.000-1.001); 1; 1.000 (0.999-1.001); 2; 1.000 (1.000-1.001); 0-6



### January 2010 C-87

### Study Design Concentrations Effect Estimates (95% CI)

Author: Samet et al. (2000, 013132 ) Period of Study: 1987-1994

Location: 20 U.S. Cities: Los Angeles, CA; New York, NY; Chicago, IL; Dallas, TX; Houston, TX; San Diego, CA; Anaheim, CA; Phoenix, AZ; Detroit, MI; Miami, FL; Philadelphia, PA; Minneapolis, MN; Seattle, WA; San Jose, CA; Cleveland, OH; San Bernardino, CA; Pittsburgh, PA; Oakland, CA; Atlanta, GA; San Antonio, TX Health Outcome (ICD9): Mortality: Cardiovascular (390- 459); Respiratory(460-519); Other (nonaccidental) (<800) Study Design: Time-series Statistical Analyses: Two-stage log linear regression model Age Groups Analyzed: <65 65-74 ≥ 75 Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Los Angeles: 15.1 ppm New York: 20.4 ppm Chicago: 7.9 ppm Dallas: 7.4 ppm Houston: 8.9 ppm San Diego: 11.0 ppm Anaheim: 12.3 ppm Phoenix: 12.6 ppm Detroit: 6.6 ppm Miami: 10.6 ppm Philadelphia: 11.8 ppm Minneapolis: 11.8 ppm Seattle: 17.8 ppm San Jose: 9.4 ppm Cleveland: 8.5 ppm San Bernardino: 10.3 ppm Pittsburgh: 12.2 ppm Oakland: 9.1 ppm Atlanta: 8.0 ppm San Antonio: 10.1 ppm Range (10th, 90th): Los Angeles: (5.9, 28.3) New York: (14.8, 27.6) Chicago: (4.5, 11.9) Dallas: (3.6, 12.0) Houston: (4.0, 14.2) San Diego: (4.5, 20.5) Anaheim: (3.7, 25.2) Phoenix: (5.4, 22.6) Detroit: (3.2, 11.1) Miami: (6.5, 15.9) Philadelphia: (7.0, 17.2) Minneapolis: (7.0, 17.0) Seattle: (10.5, 26.4) San Jose: (1.7, 21.3) Cleveland: (3.7, 13.8) San Bernardino: (4.0, 17.5) Pittsburgh: (6.1, 19.8) Oakland: (2.9, 17.0) Atlanta: (3.2, 14.3) San Antonio: (4.1, 17.3) Copollutant correlation: PM 10 : r = 0.45; O 3 : r = -0.19; NO 2 : r = 0.64; SO 2 : r = 0.41 This study did not provide quantitative results for CO.

Author: Samoli et al. (2007, 098420 ) Period of Study: 1990-1997

Location: 19 European Cities (APHEA2) Health Outcome (ICD9): Mortality: Total (non-accidental) (<800); Cardiovascular (390- 459) Study Design: Time-series Statistical Analyses: Poisson and two-stage hierarchical model Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean Range (unit–mg/m3): Athens: 6.1; Barcelona: 0.9; Basel: 0.6; Birmingham: 1. 0; Budapest: 5.1; Geneva: 1.5; Helsinki: 1.2; Ljubljana: 1.6; London: 1.4; Lyon: 3.8; Milano: 5.4; Netherlands: 0.6; Prague: 0.9; Rome: 4.1; Stockholm: 0.8; Teplice: 0.7; Torino: 5.5; Valencia: 4.1; Zurich: 1.2 Range (10th, 90th): Athens: (3.5, 9.2) Barcelona: (0.4, 1.7) Basel: (0.4, 1.1) Birmingham: (0.5, 1.6) Budapest: (3.3, 7.4) Geneva: (0.8, 2.6) Helsinki: (0.7, 1.9) Ljubljana: (0.6, 3.0) London: (0.7, 2.2) Lyon: (2.0, 6.0) Milano: (2.9, 8.7) Netherlands: (0.4, 1.2) Prague: (0.5, 1.5) Increment: 1 mg/m 3 % Increase (Lower CI, Upper CI); lag: Non-accidental mortality 8 Degrees of Freedom per yr Fixed Effects: CO: 0.59% (0.41-0.78); 0-1 CO, BS: 0.35% (-0.03 to 0.72); 0-1 CO, PM 10 : 0.48% (0.24-0.72); 0-1 CO, SO 2 : 0.44% (0.21-0.67); 0-1 CO, O 3 : 0.66% (0.46-0.86); 0-1 CO, NO 2 : 0.27% (0.03-0.51); 0-1 Random Effects: CO: 0.66% (0.27-1.05); 0-1 CO, BS: 0.45% (-0.01 to 0.92); 0-1 CO, PM 10 : 0.58% (0.12-1.04); 0-1 CO, SO 2 : 0.46% (0.07-0.85); 0-1 CO, O 3 : 0.76% (0.45-1.06); 0-1 CO, NO 2 : 0.30% (-0.11 to 0.71); 0-1 PACF: (Partial Autocorrelation Function) Plot Fixed Effects: CO: 1.00% (0.83-1.18); 0-1 CO, BS: 0.67% (0.30-1.04); 0-1 CO, PM 10 : 0.78% (0.55-1.00); 0-1 CO, SO 2 : 0.68% (0.47-0.90); 0-1 CO, O 3 : 1.12% (0.93-1.31); 0-1 CO, NO 2 : 0.72% (0.50-0.95); 0-1



### January 2010 C-88

### Study Design Concentrations Effect Estimates (95% CI) Rome: (2.5, 5.9) Stockholm: (0.5, 1.2) Teplice: (0.3, 1.2) Torino: (2.8, 9.1) Valencia: (2.4, 5.9) Zurich: (0.7, 2.0) Copollutant correlation: PM 10 : r = 0.16 to 0.70 BS: r = 0.67 to 0.82 SO 2 : r = 0.35 to 0.82 NO 2 : r = 0.03 to 0.68 O 3 : r = -0.25 to -0.65 Random Effects: CO: 1.20% (0.63-1.77); 0-1 CO, BS: 0.77% (0.28-1.26); 0-1 CO, PM 10 : 1.09% (0.36-1.83); 0-1 CO, SO 2 : 0.75% (0.26-1.26); 0-1 CO, O 3 : 1.37% (0.81-1.95); 0-1 CO, NO 2 : 0.88% (0.22-1.55); 0-1 Cardiovascular Mortality 8 Degrees of Freedom per Year Fixed Effects: CO: 0.80% (0.53-1.07); 0-1 CO, BS: 0.49% (-0.04 to 1.02); 0-1 CO, PM 10 : 0.73% (0.39-1.07); 0-1 CO, SO 2 : 0.72% (0.39-1.04); 0-1 CO, O 3 : 0.91% (0.62-1.20); 0-1 CO, NO 2 : 0.44% (0.10-0.79); 0-1 Random Effects: CO: 0.81% (0.36-1.26); 0-1 CO, BS: 0.49% (-0.04 to 1.02); 0-1 CO, PM 10 : 0.73% (0.39-1.07); 0-1 CO, SO 2 : 0.68% (-0.03 to 1.40); 0-1 CO, O 3 : 1.02% (0.58-1.46); 0-1 CO, NO 2 : 0.43% (-0.06 to 0.93); 0-1 PACF (Partial Autocorrelation Function) Fixed Effects: CO: 1.06% (0.80-1.32); 0-1 CO, BS: 0.83% (0.31-1.35); 0-1 CO, PM 10 : 0.95% (0.62-1.27); 0-1 CO, SO 2 : 0.91% (0.59-1.22); 0-1 CO, O 3 : 1.28% (1.01-1.56); 0-1 CO, NO 2 : 0.68% (0.35-1.00); 0-1 Random Effects: CO: 1.25% (0.30-2.21); 0-1 CO, BS: 0.83% (0.31-1.35); 0-1 CO, PM 10 : 1.13% (0.60-1.67); 0-1 CO, SO 2 : 0.86% (0.06-1.66); 0-1 CO, O 3 : 1.62% (0.72-2.52); 0-1 CO, NO 2 : 0.84% (-0.03 to 1.71); 0-1 Effect Modifiers Non-accidental Mortality 8 Degrees of Freedom per Year Number of CO monitors: 25th Percentile: 0.71 % (0.48-0.94); 0-1 75th Percentile: 0.54 % (0.34-0.74); 0-1 Mean PM 10 Levels: 25th Percentile: 0.37 % (0.08-0.66); 0-1 75th Percentile: 0.49 % (0.28-0.69); 0-1 Standardized Mortality Rate: 25th Percentile: 0.79 % (0.55-1.03); 0-1 75th Percentile: 0.44 % (0.22-0.66); 0-1 Western cities: 0.75% (0.47-1.03); 0-1 Southern cities: 0.61% (0.32-0.91); 0-1 Eastern cities: 0.03% (-0.47 to 0.53); 0-1 PACF (Partial Autocorrelation Function)

Number of CO monitors: 25th Percentile: 1.18 % (0.96-1.39); 0-1 75th Percentile: 0.92% (0.73-1.11); 0-1 Mean PM 10 Levels: 25th Percentile: 0.74 % (0.46-1.02); 0-1 75th Percentile: 1.07 % (0.87-1.27); 0-1 Standardized Mortality Rate: 25th Percentile: 1.29 % (1.06-1.52); 0-1 75th Percentile: 0.77 % (0.56-0.98); 0-1 Western cities: 1.15% (0.90-1.40); 0-1 Southern cities: 1.08% (0.79-1.38); 0-1 Eastern cities: 0.27% (-0.20 to 0.74); 0-1 Cardiovascular Mortality 8 Degrees of Freedom per Year Mean O 3 : 25th Percentile: 1.04 % (0.67-1.41); 0-1 75th Percentile: 0.82 % (0.55-1.10); 0-1 Standardized Mortality Rate: 25th Percentile: 1.06 % (0.71-1.42); 0-1 75th Percentile: 0.61 % (0.30-0.93); 0-1



### January 2010 C-89

### Study Design Concentrations Effect Estimates (95% CI)

Population >75 yr of age (%): 25th Percentile: 0.58 % (0.25-0.92); 0-1 75th Percentile: 0.94 % (0.64-1.24); 0-1 Western cities: 1.06% (0.67-1.46); 0-1 Southern cities: 0.70% (0.26-1.14); 0-1 Eastern cities: 0.21% (-0.48 to 0.90); 0-1 PACF (Partial Autocorrelation Function) Mean O 3 : 25th Percentile: 1.32 % (0.96-1.68); 0-1 75th Percentile: 1.09 % (0.83-1.14); 0-1 Standardized Mortality Rate: 25th Percentile: 1.40 % (1.06-1.75); 0-1 75th Percentile: 0.85 % (0.55-1.14); 0-1 Population >75 yr of age (%): 25th Percentile: 0.74 % (0.41-1.06); 0-1 75th Percentile: 1.25 % (0.96-1.54); 0-1 Western cities: 1.38% (1.00-1.76); 0-1 Southern cities: 0.90% (0.47-1.33); 0-1 Eastern cities: 0.48% (-0.14 to 1.11); 0-1

Author: Schwartz et al. (1999, 017915 ) Period of Study: 1989-1995

Location: Spokane, WA Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 1-h avg Mean (SD) unit: Dust Storm Days: 09/08/1990: 6.37 ppm 09/12/1990: 3.40 ppm 10/04/1990: 3.15 ppm 11/09/1990: 2.45 ppm 11/23/1990: 2.50 ppm 09/13/1991: 4.60 ppm 10/16/1991: 2.10 ppm 10/21/1991: 2.20 ppm 09/04/1992: 3.43 ppm 09/12/1992: 1.80 ppm 09/13/1992: 1.65 ppm 09/25/1992: 2.95 ppm 09/26/1992: 4.30 ppm 10/08/1992: 3.85 ppm 09/11/1993: 1.88 ppm 11/3/1993: 5.33 ppm 07/24/1994: 2.10 ppm 08/30/1996: 2.85 ppm Range (Min, Max): NR Copollutant: PM 10 The study did not present quantitative results for CO.

Author: Sharovsky et al. (2004, 156976 ) Period of Study: 1996-1998

Location: Sao Paulo, Brazil Health Outcome (ICD10): Mortality: MI (I.21) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: 35-109 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 3.7 (1.6) ppm Range (Min, Max): (1.0, 11.8) Copollutant: correlation SO 2 : r = 0.73; PM 10 : r = 0.51 Increment: NR β x 100 (SE); lag: CO: 1.42 (1.01) CO, SO 2 , PM 10 : 0.97 (1.27)

Notes: The study did not present the lag used for CO.

Author: Slaughter et al. (2005, 073854 ) Period of Study: 1/1995-6/2001

Location: Spokane, WA Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); respiratory (460-519); asthma (493); COPD (491, 492, 494, 496); pneumonia (480-487); acute upper respirator y tract infections (464-466, 490); cardiac outcomes (390-459) Study Design: Time series Statistical Analyses: Log-linear Poisson GLM, natural splines for calendar time Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: Areas in Spokane Hamilton St: 1.73 (0.46) ppm Backdoor Tavern: 1.29 (0.23) ppm Spokane Club: 1.41 (0.32) ppm Third and Washington: 1.82 (0.33) ppm Rockwood: 0.42 (0.15) ppm Range (Min, Max): NR Copollutant correlation: PM 1 : r = 0.63; PM 2.5 : r = 0.62; PM 10 : r = 0.32; PM 10-2.5 : r = 0.32 The study did not present quantitative results for CO.



### January 2010 C-90

### Study Design Concentrations Effect Estimates (95% CI)

Author: Stieb et al. (2003, 056908 ) Period of Study : 1985-2000

Location: All locations Health Outcome (ICD9): Mortality: Nonaccidental Study Design: Meta-analysis Statistical Analyses: NR Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: NR IQR (25th, 75th): NR Copollutant: NR Increment: 1.1 ppm % Excess Mortality (Lower CI, Upper CI); lag: Non-GAM: Single-pollutant model (4 studies): 4.7% (1.1-8.4) Multi-pollutant model (1 study): 0.0% (-3.8 to 3.8) GAM: Single-pollutant model (18 studies): 1.6% (1.1-2.1) Multi-pollutant model (11 studies): 0.7% (-0.1 to 1.5)

Author: Stölzel et al. (2007, 091374 ) Period of Study: 9/1995-8/2001

Location: Erfurt, Germany Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); cardio-respiratory (390- 459, 460-519, 785, 786) Study Design: Time series Statistical Analyses: Poisson GAM Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.47 (0.39) mg/m 3 IQR (25th, 75th): (0.23, 0.57) Copollutant correlation: MC0.1-0.5: r = 0.58; MC0.01-2.5: r = 0.57; PM 10 : r = 0.50; NO: r = 0.70; NO 2 : r = 0.71 Increment: 0.34 mg/m 3 Relative Risk (Lower CI, Upper CI); lag: Total (non-accidental) 1.000 (0.977-1.023); 0; 1.002 (0.980-1.024); 1; 1.013 (0.991-1.035); 2; 1.007 (0.986-1.029); 3; 1.012 (0.990-1.034); 4; 0.995 (0.974-1.017); 5

Author: Sunyer et al. (2001, 019367 ) Period of Study: 1990-1995

Location: Barcelona, Spain Health Outcome (ICD9): Mortality: COPD (491, 492, 494, 496) Study Design: Bidirectional case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: >35 yr Pollutant: CO Averaging Time: 8-h avg Mean (SD) unit: NR Range (Min, Max): NR Copollutant: PM 10 ; NO 2 ; O 3 Increment: 4.5 μg/m 3 Odds Ratio (Lower CI, Upper CI); lag: CO: 1.052 (0.990-1.117); 0-2 CO, PM 10 : 1.017 (0.947-1.091); 0-2

Author: Sunyer et al. (2002, 034835 ) Period of Study: 1985-1995

Location: Barcelona, Spain Health Outcome (ICD9): Mortality: Respiratory mortality Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: >14 yr Study population: Asthmatic individuals: 5,610 Pollutant: CO Averaging Time: 24-h avg Median (SD) unit: 7.7 μg/m 3 Range (Min, Max): (0.6, 66.0) Copollutant: PM 10 ; BS; NO 2 ; O 3 ; SO 2 Increment: 7.2 μg/m 3 Odds Ratio (Lower CI, Upper CI); lag:

Asthmatic individuals with 1 ED visit 1.127 (0.895-1.418); 0-2

Asthmatic individuals with >1 ED visit 1.125 (0.773-1.638); 0-2

Asthma/COPD individuals with >1 ED visit 0.815 (0.614-1.082); 0-2

Author: Tsai et al. (2003, 050480 ) Period of Study: 1994-2000

Location: Kaohsiung, Taiwan Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); respiratory (460-519); circulatory (390-459) Study Design: Bidirectional case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.827 ppm Range (Min, Max): (0.226, 1.770) Copollutant: PM 10 ; SO 2 ; NO 2 ; O 3 Increment: 0.313 ppm Odds Ratio (Lower CI, Upper CI); lag: Total (nonaccidental): 1.003 (0.968-1.039); 0-2 Respiratory: 1.011 (0.883-1.159); 0-2 Circulatory: 0.986 (0.914-1.063); 0-2

Author: Tsai et al. (2006, 090709 ) Period of Study: 1994-2000

Location: Kaohsiung, Taiwan Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800) Study Design: Case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: 27 days old to <1 yr of age Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit : 8.27 ppm Range (Min, Max): (2.26, 17.70) Copollutant: PM 10 ; SO 2 ; O 3 ; NO 2 Increment: 0.31 ppm Odds Ratio (Lower CI, Upper CI); lag: Postneonatal Mortality 1.051 (0.304-3.630); 0-2



### January 2010 C-91

### Study Design Concentrations Effect Estimates (95% CI)

Author: Vedal et al. (2003, 039044 ) Period of Study: 1/1994-12/1996

Location: Vancouver, BC, Canada Health Outcome (ICD9): Mortality: Total (nonaccidental) (<800); respiratory (460-519); cardiovascular (390-459) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.6 (0.2) ppm Range (Min, Max): (0.3, 1.9) Copollutant correlation: Summer: PM 10 :r = 0.71; O 3 : r = 0.12; NO 2 : r = 0.81; SO 2 : r = 0.67 Winter: PM 10 : r = 0.76; O 3 : r = -0.65; NO 2 : r = 0.78; SO 2 : r = 0.83 The study did not present quantitative results for CO.

Author: Villeneuve et al. (2003, 055051 ) Period of Study: 1986-1999

Location: Vancouver, BC, Canada Health Outcome (ICD9): Mortality: Nonaccidental (<800); cardiovascular (401-440); respiratory (460-519); cancer (140-239) Study Design: Time series Statistical Analyses: Poisson, natural splines Age Groups Analyzed: ≥ 65 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.0 ppm Range (Min, Max): (0.2, 4.9) Copollutant: PM 2.5 ; PM 10 ; PM 10-2.5 ; TSP; SO 4 ; CO; COH; O 3 ; NO 2 ; SO 2 Increment: 1.1 ppb % Increase (Lower CI, Upper CI); lag:

Non-accidental 0.5% (-1.9 to 2.9); 0-2; / -0.3% (-2.2 to 1.7); 0; 0.6% (-1.3 to 2.6); 1; / 0.5% (-1.4 to 2.5); 2 Cardiovascular 2.3% (-1.6 to 6.3); 0-2; / 1.6% (-1.5 to 4.7); 0; 1.2% (-2.0 to 4.5); 1; / 1.5% (-1.5 to 4.4); 2 Respiratory -1.0% (-7.3 to 5.8); 0-2; / 1.3% (-4.4 to 7.3); 0; -0.1% (-5.3 to 5.4); 1; -/ 2.8% (-7.8 to 2.6); 2 Cancer -2.8% (-7.6 to 2.4); 0-2; / -3.0% (-6.9 to 1.1); 0; -1.6% (-5.6 to 2.4); 1; / -0.5% (-4.7 to 3.8); 2

Author: Wang et al. (2008, 179974 ) Period of Study: Daily CO content: 2000-2005 (data from Beijing Environment Protection Bureau), Death rate: 2000-2003

Location: Beijing, China Health Outcome: Mortality Study Design: Time series, Granger causality, Back propagation neural network model, MIV Statistical Analyses: Eviews 3.1, SAS 9.0, Matlab 7.0 Age Groups Analyzed: NR Sample Description: Death rate of respiratory diseases in Beijing from China Centers for Disease Control and Prevention Averaging Time: NR Mean (SD) unit: NR Range (Min, Max): NR Copollutant: NR Increment: NR Granger causality: Acute respiratory diseases probability: 0.03122 COPD probability: 0.00047 Change of death rate of ac ute respiratory diseases: Increasing 10%: +0.437, Decreasing 10%: -0.386 Change of death rate of COPD: Increasing 10%: +0.181, Decreasing 10%: -0.316 Lags examined: 10



### January 2010 C-92

### Study Design Concentrations Effect Estimates (95% CI)

Author: Wichmann et al. (2000, 013912 ) Period of Study: 9/1995-12/1998

Location: Erfurt, Germany Health Outcome (ICD9): Mortality: Nonaccidental (<800); cardiovascular (401-440); respiratory (460-519) Study Design: Time series Statistical Analyses: Poisson GAM, LOESS Age Groups Analyzed: <70 70-79 ≥ 80 Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 0.6 (0.5) mg/m 3 Range (Min, Max): (0.10, 2.50) Copollutant: correlation PM 2.5 : r = 0.62; PM 10 : r = 0.58; TSP: r = 0.57; SO 2 : r = 0.59; NO 2 : r = 0.71 Increment: 0.5 ppm Relative Risk (Lower CI, Upper CI); lag: Single-Day Lag CO: 1.055 (1.003-1.110); 4 Polynomial Distributed Lag Multi-pollutant model: 1.076 (1.017-1.138); 4 Total Mortality CO: 1.012 (0.977-1.049); 0 Log-transformed: 1.016 (0.962-1.073); 0 1.004 (0.969-1.040); 1 Log-transformed: 1.027 (0.973-1.083); 1 1.020 (0.984-1.057); 2 Log-transformed: 1.024 (0.970-1.081); 2 1.019 (0.984-1.055); 3 Log-transformed: 1.037 (0.984-1.093); 3 1.029 (0.995-1.063); 4 Log-transformed: 1.055 (1.003-1.110); 4 0.997 (0.965-1.031); 5 Log-transformed: 1.014 (0.966-1.065); 5 Total Mortality (Season-specific): Log-transformed Winter: 1.002 (0.922-1.088); 4 Spring: 1.019 (0.942-1.102); 4 Summer: 1.085 (1.018-1.156); 4 Fall: 1.111 (1.039-1.188); 4 Winter-specific: Log-transformed 10/95-3/96: 1.046 (0.949-1.153); 4 10/96-3/97: 1.091 (0.998-1.193); 4 10/97-3/98: 1.028 (0.966-1.095); 4 One-pollutant Model: Log-transformed CO: 1.055 (1.003-1.110); 4

Author: Yang et al. (2004, 055603 ) Period of Study: 1994-1998

Location: Taipei, Taiwan Health Outcome (ICD9): Mortality: Nonaccidental (<800); circulatory (390-459); respiratory (460-519) Study Design: Bidirectional case crossover Statistical Analyses: Conditional logistic regression Age Groups Analyzed: All ages Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1.16 ppm Range (Min, Max): (0.24, 4.42) Copollutant: PM 10 ; SO 2 ; NO 2 ; O 3 Increment: 0.52 ppm Odds Ratio (Lower CI, Upper CI); lag: Non-accidental: 1.005 (0.980-1.031); 0-2 Respiratory: 1.014 (0.925-1.110); 0-2 Circulatory: 0.996 (0.948-1.046); 0-2



### January 2010 C-93

# Table C-8. Studies of long-ter m CO exposure and mortality.

Study Design Concentrations Effect Estimates (95% CI)

Author: Krewski et al. (2009, 191193 ) Period of Study: 1983-2000

Location: United States Health Outcome: Mortality Study Design: Cohort Statistical Analyses: Random effects Cox model Age Groups Analyzed: 30+ yrs Sample Description: 508,538 adults living in large US cities Averaging Time: 1980 annual avg Mean (SD) unit: 1.68 (0.66) ppm Range (min, max): 0.19, 3.95 Copollutant: PM 15 , PM 2.5 , SO 2 , SO 4 , TSP, O 3 , NO 2 Increment: 1ppm HR Estimate [Lower CI, Upper CI]: Lags examined: NR

All Causes: 1.00 (0.99, 1.01) Cardiopulmonary: 1.00 (0.99, 1.01) IHD: 1.01 (0.99, 1.03) Lung Cancer: 0.99 (0.97, 1.03) All Other Causes: 0.99 (0.98, 1.01)

Author: Lipfert et al. (2000, 004087 ) Period of Study: 1975-1996

Location: 32 Veterans Hospitals, USA Mortality Health Outcome (ICD9): Nonaccidental Study Design: Cohort Study Population: ~90,000 hypertensive male U.S. veterans Statistical Analyses: Staged regression Age Groups Analyzed: NR Pollutant: CO Averaging Time: 95th Percentile Annual avg Mean (SD) unit: 1960-1974: 10.82 (5.15) ppm 1975-1981: 7.64 (2.94) ppm 1982-1988: 3.42 (0.95) ppm 1989-1996: 2.36 (0.67) ppm Range (Min, Max): 1960-1974: (0.94, 35.30) 1975-1981: (0.43, 22.38) 1982-1988: (0.30, 15.20) 1989-1996: (0.30, 7.10) Copollutants; correlation: 1960-1974: O 3 : r = 0.004; NO 2 : r = 0.690; SO 4 2- : r = 0.469

1975-1981: O 3 : r = 0.109; NO 2 : r = 0.249; SO 4 2- : r = -0.155; IP SO 4 2- : r = 0.356; PM 2.5 : r = 0.634; PM 10-2.5 : r = 0.498; PM 15 : r = 0.626

1982-1988 O 3 : r = 0.158; NO 2 : r = 0.413; SO 4 2- : r = -0.518; IP SO 4 2- : r = 0.075; PM 2.5 : r = 0.296; PM 10-2.5 : r = 0.135 PM 15 : r = 0.284

1989-1996 O 3 : r = 0.397; NO 2 : r = 0.492; SO 4 2- : r = -0.551 Increment: NR

Coefficient: Baseline Model Exposure Period: up to 1975 Single Period: -0.000 Deaths, 1976-81: 0.0043 Deaths, 1982-88: -0.0002 Deaths after 1988: -0.0041 Exposure Period: 1975-81 Single Period: -0.013 Deaths, 1976-81: -0.0170 Deaths, 1982-88: -0.0217 Deaths after 1988: -0.0240 Exposure Period: 1982-88 Single Period: -0.028 Deaths, 1976-81: -0.0294 Deaths, 1982-88: -0.0484 Deaths after 1988: -0.0424 Exposure Period: 1989-96 Single Period: -0.046 Deaths, 1976-81: -0.0590 Deaths, 1982-88: -0.0581 Deaths after 1988: -0.0536 Final Model w/ Ecological Variables Exposure Period: up to 1975 Single Period: -0.001 Deaths, 1976-81: 0.0013 Deaths, 1982-88: -0.0022 Deaths after 1988: -0.0061 Exposure Period: 1975-81 Single Period: -0.008 Deaths, 1976-81: -0.0128 Deaths, 1982-88: -0.0186 Deaths after 1988: -0.0203 Exposure Period: 1982-88 Single Period: -0.009 Deaths, 1976-81: -0.0007 Deaths, 1982-88: -0.0246 Deaths after 1988: -0.0216 Exposure Period: 1989-96 Single Period: -0.009 Deaths, 1976-81: -0.0106 Deaths, 1982-88: -0.0136 Deaths after 1988: -0.0078

Notes: Mortality risks based on mean concentrations of pollutants less estimated background weighted by the number of subjects in each county, but The study did not present this value for each pollutant.



### January 2010 C-94

### Study Design Concentrations Effect Estimates (95% CI)

Author: Lipfert and Morris (2002, 019217 ) Period of Study: 1960-1997

Location: U.S. counties Mortality Health Outcome (ICD9): Nonaccidental Study Design: Ecological/ cross sectional Statistical Analyses: Staged regression Age Groups Analyzed: 15-44 yr 45-64 yr 65-74 yr 75-84 yr ≥ 85 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit: 1960-1969: 13.81 (8.47) ppm 1970-1974:9.64 (5.63) ppm 1979-1981:5.90 (3.54) ppm 1989-1991:2.69 (1.22) ppm 1995-1997:1.72 (0.76) ppm

R ange (Min, Max): NR Copollutant: TSP SO 4 2- SO 2 NO 2 O 3 Increment: NR Attributable risk (SE): Attributable Risks of mortality (1960-4) Peak CO 1960-1964, All locations Ages 15-44: 0.1299 (0.0341) Ages 45-64: 0.0340 (0.0280) Ages 65-74: -0.0058 (0.0220) Ages 75-84: 0.0121 (0.0188) Ages ≥ 85: 0.0374 (0.0225) Log Mean: 0.0365 (0.0149) Attributable Risks of mortality (1970-4) Peak CO 1970-1974, All locations Ages 15-44: 0.0553 (0.0240) Ages 45-64: 0.0181 (0.0148) Ages 65-74: -0.0146 (0.0134) Ages 75-84: -0.0128 (0.0098) Ages ≥ 85: -0.0151 (0.0093) Log Mean: 0.0038 (0.0086) Attributable Risks of mortality (1979-81) Peak CO 1979-1981, All locations Ages 15-44: 0.0054 (0.0174) Ages 45-64: -0.0060 (0.0141) Ages 65-74: -0.0251 (0.0105) Ages 75-84: -0.0331 (0.0086) Ages ≥ 85: -0.0123 (0.0079) Log Mean: -0.0183 (0.0077) Peak CO 1970-1974, All locations Ages 15-44: 0.0218 (0.0200) Ages 45-64: 0.0327 (0.0161) Ages 65-74: -0.0136 (0.0119) Ages 75-84: -0.0250 (0.0105) Ages ≥ 85: -0.0202 (0.0085) Log Mean: -0.0048 (0.0077) Peak CO 1960-1969, All locations Ages 15-44: 0.0506 (0.0478) Ages 45-64: 0.0704 (0.0337) Ages 65-74: 0.0100 (0.0211) Ages 75-84: -0.0124 (0.0143) Ages ≥ 85: 0.0187 (0.0135) Log Mean: 0.0084 (0.0149) Peak CO 1979-1981, CO 1970-1974 Ages 15-44: 0.0244 (0.0209) Ages 45-64: 0.0016 (0.0181) Ages 65-74: -0.0183 (0.0128) Ages 75-84: -0.0382 (0.0108) Ages ≥ 85: -0.0201 (0.0089) Log Mean: -0.0165 (0.0089) Peak CO 1979-1981, CO 1960-1969 Ages 15-44: 0.0748 (0.0679) Ages 45-64: 0.0844 (0.0496) Ages 65-74: 0.0144 (0.0259) Ages 75-84: -0.0158 (0.0168) Ages ≥ 85: -0.0073 (0.0170) Log Mean: 0.0109 (0.0218) Peak CO 1979-1981, CO 1960-1969 Ages 15-44: 0.1191 (0.0709) Ages 45-64: 0.1163 (0.0491) Ages 65-74: 0.0177 (0.0310) Ages 75-84: -0.0120 (0.0212) Ages ≥ 85: -0.0040 (0.0202) Log Mean: 0.0211 (0.0231) Attributable Risks of mortality (1989-91) Peak CO 1989-1991, All locations Ages 15-44: 0.0404 (0.0322) Ages 45-64: -0.0262 (0.0162) Ages 65-74: -0.0397 (0.0115) Ages 75-84: -0.0464 (0.0097) Ages ≥ 85: -0.0209 (0.0073) Log Mean: -0.0178 (0.0098) Peak CO 1979-1981, All locations



### January 2010 C-95

### Study Design Concentrations Effect Estimates (95% CI) Ages 15-44: 0.0522 (0.0227) Ages 45-64: -0.0047 (0.0121) Ages 65-74: -0.0165 (0.0078) Ages 75-84: -0.0268 (0.0068) Ages ≥ 85: -0.0027 (0.0055) Log Mean: -0.0020 (0.0065) Peak CO 1970-1974, All locations Ages 15-44: 0.0685 (0.0274) Ages 45-64: 0.0022 (0.0148) Ages 65-74: -0.0051 (0.0091) Ages 75-84: -0.0158 (0.0079) Ages ≥ 85: -0.0069 (0.0060) Log Mean: 0.0038 (0.0077) Peak CO 1960-1969, All locations Ages 15-44: 0.0578 (0.0713) Ages 45-64: 0.0583 (0.0347) Ages 65-74: 0.0007 (0.0174) Ages 75-84: -0.0245 (0.0130) Ages ≥ 85: -0.0138 (0.0113) Log Mean: 0.0041 (0.0176) Attributable Risks of mortality (1995-97) Peak CO 1995-1997, All locations Ages 15-44: 0.0344 (0.0256) Ages 45-64: -0.0203 (0.0198) Ages 65-74: -0.0346 (0.0146) Ages 75-84: -0.0378 (0.0161) Ages ≥ 85: -0.0283 (0.0119) Log Mean: -0.0188 (0.0103) Peak CO 1989-1991, All locations Ages 15-44: 0.0289 (0.0248) Ages 45-64: -0.0192 (0.0192) Ages 65-74: -0.0466 (0.0140) Ages 75-84: -0.0497 (0.0147) Ages ≥ 85: -0.0301 (0.0108) Log Mean: -0.0240 (0.0096) Peak CO 1979-1981, All locations Ages 15-44: 0.0336 (0.0176) Ages 45-64: -0.0037 (0.0135) Ages 65-74: -0.0298 (0.0096) Ages 75-84: -0.0301 (0.0105) Ages ≥ 85: -0.0087 (0.0078) Log Mean: -0.0094 (0.0071) Peak CO 1970-1974, All locations Ages 15-44: 0.0464 (0.0202) Ages 45-64: 0.0202 (0.0155) Ages 65-74: -0.0032 (0.0112) Ages 75-84: -0.0157 (0.0122) Ages ≥ 85: -0.0142 (0.0084) Log Mean: 0.0007 (0.0077) Peak CO 1960-1969, All locations Ages 15-44: 0.0679 (0.0441) Ages 45-64: 0.0772 (0.0405) Ages 65-74: 0.0059 (0.0173) Ages 75-84: -0.0085 (0.0213) Ages ≥ 85: -0.0158 (0.0162) Log Mean: 0.0162 (0.0149)



### January 2010 C-96

### Study Design Concentrations Effect Estimates (95% CI)

Author: Lipfert et al. (2006, 088218 ) Period of Study: 1976-2001

Location: 32 Veterans Hospitals, USA Mortality Health Outcome (ICD9): Nonaccidental Study Design: Cohort Study Population: ~70,000 hypertensive male U.S. veterans Statistical Analyses: Cox proportional-hazards model Age Groups Analyzed: NR Pollutant: CO Averaging Time: 95th Percentile Annual avg Mean (SD) unit: 1976-1981: 7.6 (2.9) ppm 1982-1988: 3.4 (9.5) ppm 1989-1996: 2.4 (0.67) ppm 1997-2001: 1.6 (5.6) ppm Range (Min, Max): NR Copollutants correlation: ln(VKTA): r = -0.06 Avg NO 2 : r = 0.43 Peak O 3 : r = 0.08 Peak SO 2 : r = -0.05 PM 2.5 : r = 0.08 SO 4 2- : r = -0.16

Note: VKTA = annual vehicle-km traveled/km 2 Increment : 2 ppm Relative risk (Lower CI, Upper CI): CO: 1.032 (0.954-1.117) CO, lnVKTA: 0.999 (0.923-1.081) CO, lnVKTA, NO 2 : 1.012 (0.923-1.110) CO, lnVKTA, NO 2 +O 3 : 1.023 (0.939-1.115)

Author: Lipfert et al. (2006, 088756 ) Period of Study: 1997-2002

Location: 32 Veterans Hospitals, USA Mortality Health Outcome (ICD9): Nonaccidental Study Design: Cohort Study Population: ~18,000 hypertensive male U.S. veterans Statistical Analyses: Cox proportional-hazards model Age Groups Analyzed: NR Pollutant: CO Averaging Time: 95th Percentile Annual avg Mean (SD) unit: 1999-2001: 1.63 (0.84) ppm 1999-2001 (STN sites only): 1.73 (0.77) Range (Min, Max): 1999-2001: (0.40, 6.7) 1999-2001 (STN sites only): (0.47, 4.2) Copollutants correlation: ln(traffic density): r = -0.199 PM 2.5 : r = 0.040; As: r = 0.148 Cr: r = 0.448; Cu: r = 0.177 Fe: r = -0.138; Pb: r = 0.420 Mn: r = 0.357; Ni: r = 0.090 Se: r = -0.110; V: r = 0.230 Zn: r = 0.472; OC: r = 0.470 EC: r = 0.234; SO 4 2- : r = -0.123 NO 3 -: r = -0.088 PM 2.5 comp.: r = 0.133 NO 2 : r = 0.418 Peak O 3 : r = 0.172 Peak SO 2 : r = 0.405 Increment: NR β coefficient (SE); t-statistic: -0.00000536 (0.0000324); -0.165

Author: Jerrett et al. (2003, 087380 ) Period of Study: 1982-1989

Location: 107 U.S. cities Mortality Health Outcome (ICD9): Cardiovascular; CHD; Cerebrovascular disease Study Design: Cohort Study Population: 65,893 postmenopausal women without previous CVD Statistical Analyses: Cox proportional-hazards model Age Groups Analyzed: ≥ 30 yr Pollutant: CO Averaging Time: Annual avg

M ean (SD) unit: 1.56 ppm Range (Min, Max): (0.19, 3.95) Copollutants correlation: Sulfates: r = -0.07 NO 2 O 3 SO 2 Increment: 1 ppm Relative risk (Lower CI, Upper CI): CO: 0.98 (0.92-1.03) CO, Sulfates: 0.97 (0.92-1.03)



### January 2010 C-97

### Study Design Concentrations Effect Estimates (95% CI)

Author: Miller et al. (2007, 090130 ) Period of Study: 1994-1998

Location: 36 U.S. cities Mortality Health Outcome (ICD9): Cardiovascular; CHD; Cerebrovascular disease Study Design: Cohort Study Population: 65,893 postmenopausal women without previous CVD Statistical Analyses: Cox proportional-hazards model Age Groups Analyzed: 50-79 yr Pollutant: CO Averaging Time: Annual avg Mean (SD) unit : NR Range (Min, Max): NR Copollutants: PM 2.5 PM 10-2.5 SO 2 NO 2 O 3 Increment: 1 ppm Hazard ratio (Lower CI, Upper CI): All subjects CO: 1.0 (0.81-1.22) Only subjects with non-missing exposure data CO: 0.92 (0.71-1.21) CO, PM 2.5 , PM 10-2.5 , SO 2 , NO 2 , O 3 : 0.93 (0.67, 1.30)

Author: Pope et al. (2002, 024689 ) Period of Study: 1980-1998

Location: All 50 States, Washington DC, and Puerto Rico (ACS-CPS-II) Mortality

Health Outcome (ICD9): Total (nonaccidental) (<800); lung cancer (162); cardiopulmonary (401-440, 460-519) Study Design: Prospective cohort Statistical Analyses: Cox proportional hazards model Age Groups Analyzed: ≥ 30 yr Pollutant: CO Averaging Time: 24-h avg Mean (SD) unit: 1980: 1.7 (0.7) ppm 1982-1998: 1.1 (0.4) ppm Range (Min, Max): NR Copollutant: PM 2.5 ; PM 10 ; TSP; SO 2 ; NO 2 ; O 3 The study presents results for CO graphically.



### January 2010 C-98

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