ii

EPA/600/R-06/063 

July 2006

Provisional Assessment of Recent Studies on 

Health Effects of Particulate Matter Exposure

National Center for Environmental Assessment 

Office of Research and Development 

U.S. Environmental Protection Agency 

Research Triangle Park, NC 27711 
iii

DISCLAIMER 

This document has been reviewed in accordance with U.S. Environmental Protection 

Agency policy and approved for publication. Mention of trade names or commercial 

products does not constitute endorsement or recommendation for use. 
ii

Table of Contents 

 Page

List of Tables ..................................................................................................................... iii 

List of Figures......................................................................................................................v 

Authors............................................................................................................................... vi 

Executive Summary.........................................................................................................E-1 

1. INTRODUCTION AND METHODOLOGY............................................................ 1 

2. OVERVIEW OF RECENT HEALTH STUDY RESULTS...................................... 2 

2.1 Epidemiologic Studies of Long-Term Exposure ........................................... 2 

2.1.1 Mortality ......................................................................................... 2 

2.1.2 Morbidity ...................................................................................... 11 

2.2 Epidemiologic Short-Term Exposure Study Results ................................... 13 

2.2.1 Mortality ....................................................................................... 14 

2.2.1.1 Associations Between Acute Exposure to Fine 

Particles and Mortality................................................ 14 

2.2.1.2 Associations Between Acute Exposure to 

Thoracic Coarse Particles and Mortality..................... 16 

2.2.2 Morbidity ...................................................................................... 17 

2.2.2.1 Associations Between Acute Exposure to Fine 

Particles and Morbidity............................................... 17 

2.2.2.2 Associations Between Acute Exposure to 

Thoracic Coarse Particles and Morbidity ................... 21 

2.2.3 Issues for Interpretation of Epidemiologic Study Results ............ 22 

2.3 Intervention Studies ..................................................................................... 24 

2.4 Health Effects Related to Sources or Components of PM........................... 24 

2.4.1 Epidemiologic Studies Using Source Apportionment .................. 25 

2.4.2 Epidemiologic Studies on Effects of Fine Particle 

Components .................................................................................. 27 

2.4.3 Toxicology Studies—Source Apportionment and Fine 

Particle Components ..................................................................... 28 

2.4.4 Toxicology Studies—Thoracic Coarse Particles .......................... 33 

2.4.5 Toxicology Studies—Comparison of Ambient PM...................... 34 

2.4.6 Studies of Specific Fine Particle Components or 

Characteristics............................................................................... 35 

3. SUMMARY AND CONCLUSIONS ...................................................................... 38 

ABBREVIATIONS AND ACRONYMS......................................................................... 41 

REFERENCES ................................................................................................................. 47 

APPENDIX A................................................................................................................. A-1 

APPENDIX B ..................................................................................................................B-1
iii

List of Tables 

Number Page

1 Mortality and Morbidity Effect Estimates and PM Concentrations from U.S. 

and Canadian Studies with Long-Term Exposures to PM2.5 and PM10-2.5..................3 

2 CAPs Sources and Associated Endpoints: Acute and Subchronic 

Exposures............................................................................................................30 

3 CAPs Components and Associated Endpoints for Acute Studies ......................31 

4 PM Components, Size Fractions, and Associated In Vitro Toxicity ..................35 

A1 Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 

and Mortality and Morbidity............................................................................ A-3 

A2 Associations of Acute PM2.5 Exposure with Mortality.................................. A-13 

A3 Associations of Acute PM10-2.5 Exposure with Mortality .............................. A-20 

A4 Effects of PM2.5 on Daily Hospital Admissions ............................................ A-25 

A5 Effects of PM10-2.5 on Daily Hospital Admissions......................................... A-29 

A6 Effects of PM2.5 on Daily Emergency Department Visits ............................. A-32 

A7 Effects of PM10-2.5 on Daily Emergency Department Visits.......................... A-34 

A8 Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes.................... A-35 

A9 Effects of Acute PM10-2.5 Exposure on Cardiovascular Outcomes ................ A-43 

A10 Effects of Acute PM2.5 Exposure on Various Respiratory Outcomes............ A-44 

A11 Effects of Acute PM10-2.5 Exposure on Various Respiratory Outcomes........ A-49 

A12 Effects of Acute PM2.5 Exposure on Birth Outcomes.................................... A-50 

A13 Results of Epidemiologic “Intervention” Studies.......................................... A-54 

A14 Associations between Source-related Fine Particles and Health 

Outcomes ....................................................................................................... A-59 

A15 Associations of Acute Exposure to Fine Particle Components with 

Health Outcomes............................................................................................ A-62 
iv

List of Tables 

(cont’d) 

Number Page

A16 CAPs Studies with Source Apportionment or Components Analysis ........... A-71

A17 Other Acute CAPs Studies............................................................................. A-76 

A18 Subchronic CAPs Studies .............................................................................. A-81 

A19 Size-fractionated and Collected Ambient PM Studies................................... A-85 

A20 Acid Aerosol Studies ..................................................................................... A-97 
v

List of Figures 

Number Page

1. Relative risk estimates (and 95% confidence intervals) for associations 

between long-term exposure to PM (per 10 PM10-2.5) and mortality.................7 

2 Excess risk estimates for total nonaccidental, cardiovascular, and 

respiratory mortality in single-pollutant models for U.S. and Canadian 

studies, including aggregate results from multicity studies................................15 

3 Excess risk estimates for hospital admissions and emergency department 

visits for cardiovascular and respiratory diseases in single-pollutant 

models for U.S. and Canadian studies, including aggregate results from 

a multicity study..................................................................................................18 
vi

Principal Authors

Dr. Jee Young Kim—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Dennis Kotchmar—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Mary Ross—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Lori White—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Lindsay Wichers—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. William Wilson—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Contributors and Reviewers

Mr. John Bachmann—Office of Air Quality Planning and Standards (C404-04), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. James Brown—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Dan Costa—Office of Research and Development (E205-09), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Robert Devlin—National Health and Environmental Effects Research Laboratory 

(mail code 58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Janice Dye—National Health and Environmental Effects Research Laboratory 

(B143-01), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Kevin Dreher—National Health and Environmental Effects Research Laboratory (B143-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Ian Gilmour—National Health and Environmental Effects Research Laboratory (B143-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 
vii

Contributors and Reviewers

(cont’d) 

Dr. Barbara Glenn—National Center for Environmental Research (8723F), Ariel Rios Building, 

1200 Pennsylvania Ave N.W., U.S. Environmental Protection Agency, Washington, DC 20460 

Dr. Lester Grant—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Ms. Beth Hassett-Sipple—Office of Air Quality Planning and Standards (C539-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Bryan Hubbell—Office of Air Quality Planning and Standards (C539-02), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Mary Johnson—National Health and Environmental Effects Research Laboratory 

(mail code 58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Srikanth Nadadur—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Lucas Neas—National Health and Environmental Effects Research Laboratory 

(mail code 58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. Haluk Ozkaynak—National Exposure Research Laboratory (E205-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Mr. Harvey Richmond—Office of Air Quality Planning and Standards (C539-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. David Svendsgaard—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 

Dr. John Vandenberg—National Center for Environmental Assessment (B243-01), 

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 
E-1

Executive Summary 

In the proposed rule on the National Ambient Air Quality Standards for particulate matter 

(PM), EPA committed to conduct a review and assessment of the numerous studies relevant to 

assessing the health effects of PM that were published too recently to be included in the 2004 

PM Air Quality Criteria Document (AQCD). This report presents the findings of EPA’s survey 

and provisional assessment of such studies. EPA has screened and surveyed the recent literature 

and developed a provisional assessment that places those studies of potentially greatest relevance 

in the context of the findings of the 2004 PM AQCD. The focus is on: (a) epidemiologic studies 

that used PM2.5 or PM10-2.5 and were conducted in the U.S. or Canada, and (b) toxicology or 

epidemiologic studies that compared effects of PM from different sources, PM components, or 

size fractions. Given the limited time available, the provisional assessment presented here does 

not attempt to critically review individual studies or to provide the kind of full integration found 

in a typical AQCD. 

This survey and assessment finds that that the new studies expand the scientific 

information and provide important insights on the relationships between PM exposure and health 

effects of PM. Taken in context, however, the new information and findings do not materially 

change any of the broad scientific conclusions regarding the health effects of PM exposure made 

in the 2004 PM AQCD. In brief, this report finds the following: 

• Recent epidemiologic studies, most of which are follow-ups or extensions of earlier 

work, continue to find that long-term exposure to fine particles is associated with both 

mortality and morbidity, as was stated in the 2004 PM AQCD. Notably, a follow-up to 

the Six Cities study shows that an overall reduction in PM2.5 levels results in reduced 

long-term mortality risk. Both this study and the analysis of the ACS cohort data in Los 

Angeles suggest that previous studies may have underestimated the magnitude of 

mortality risks. Some studies provide more mixed results, including the suggestion that 

higher traffic density may be an important factor. In addition, the California Children’s 

Health Study reported that measures of PM2.5 exposure and PM components and gases 

were associated with reduction in lung function growth in children, increasing the 

evidence for increased susceptibility early in life, as was suggested in the 2004 PM 

AQCD. The results of recent epidemiologic and toxicology studies have also reported 

new evidence linking long-term exposure to fine particles with a measure of 

atherosclerosis development and, in a cohort of individuals with cystic fibrosis, 

respiratory exacerbations. 

• Recent epidemiologic studies have also continued to report associations between acute 

exposure to fine particles and mortality and morbidity health endpoints. These include 

three multi-city analyses, the largest of which (in 204 counties) shows a significant 

association between acute fine PM exposures and hospitalization for cardiovascular and 

respiratory diseases, and suggestions of differential cardiovascular effects in eastern U.S. 

as opposed to western U.S. locations. The new studies support previous conclusions that 

short-term exposure to fine PM is associated with both mortality and morbidity, including 

a substantial number of studies reporting associations with cardiovascular and respiratory 

health outcomes such as changes in heart rhythm or increases in exhaled NO. 
E-2

• New toxicology and epidemiologic studies have continued to link health outcomes with a 

range of fine particle sources and components. Several new epidemiologic analyses and 

toxicology studies have included source apportionment techniques, and the results 

indicated that fine PM from numerous sources, including traffic-related pollution, 

regional sulfate pollution, combustion sources, resuspended soil or road dust, are 

associated with various health outcomes. Toxicology studies continue to indicate that 

various components, including metals, sulfates, and elemental and organic carbon, are 

linked with health outcomes, albeit at generally high concentrations. Recent 

epidemiologic studies have also linked different fine PM components with a range of 

health outcomes; new studies indicate effects of the organic and elemental carbon 

fractions of fine PM that were generally not evaluated in earlier analyses. 

• The recent epidemiologic studies greatly expand the more limited literature on health 

effects of acute exposure to thoracic coarse particles (PM10-2.5). The 2004 PM AQCD 

conclusion that PM10-2.5 exposure was associated with respiratory morbidity is 

substantially strengthened with these new studies; several epidemiologic studies, in fact, 

report stronger evidence of associations with PM10-2.5 than for PM2.5. In two new casecrossover studies, associations with thoracic coarse particles are robust to the inclusion of 

gaseous copollutants. For mortality, many studies do not report statistically significant 

associations, though one new analysis reports a significant association with 

cardiovascular mortality in Vancouver, Canada. 

• Evidence of associations between long-term exposure to thoracic coarse particles and 

either mortality or morbidity remains limited. 

• New toxicology studies have demonstrated that exposure to thoracic coarse particles, or 

PM sources generally representative of this size fraction (e.g., road dust), can result in 

inflammation and other health responses. Clinical exposure of healthy and asthmatic 

humans to concentrated ambient air particles comprised mostly of PM10-2.5 showed 

changes in heart rate and heart rate variability measures. The results are still too limited 

to draw conclusions about specific thoracic coarse particle components and health 

outcomes, but it appears that endotoxin and metals may play a role in the observed 

responses. Two studies comparing toxicity of dust from soils and road surfaces found 

variable toxic responses from both urban and rural locations. 

• Significant associations between improvements in health and reductions in PM and other 

air pollutants have been reported in intervention studies or “found experiments.” One 

new study reported reduced mortality risk with reduced PM2.5 concentrations. In 

addition, several studies, largely outside the U.S., reported reduced respiratory morbidity 

with lowered air pollutant concentrations, providing further support for the 

epidemiological evidence that links PM exposure to adverse health effects. 
1

Provisional Assessment of Recent Studies on Health Effects 

of Particulate Matter Exposure 

1. INTRODUCTION AND METHODOLOGY 

EPA is currently in the final stages of the review of the national ambient air quality 

standards (NAAQS) for particulate matter (PM). As described in more detail in the Federal 

Register Notice of EPA’s proposed rule on the PM NAAQS (71 FR 2620), EPA has prepared the 

Air Quality Criteria for Particulate Matter (hereafter 2004 PM AQCD) that reviewed, 

summarized and integrated the results of studies on PM (EPA, 2004). As noted in the PM 

proposal1, EPA is aware that numerous studies potentially relevant to assessing the health effects 

of ambient PM have been published recently that were not included in the 2004 PM AQCD. The 

proposal notice also indicates the Agency’s intent to conduct a review and assessment of these 

new studies before a final decision is made on the PM NAAQS. This report presents the findings 

of EPA’s survey and provisional assessment of potentially relevant recent studies on the health 

effects of PM exposure. As outlined below, EPA has 1) screened the recently available literature 

to identify potentially relevant studies, 2) surveyed those studies to summarize the key findings, 

and 3) developed a preliminary assessment that places those of potentially greatest relevance in 

the context of the findings of the 2004 AQCD. Given the limited time available, the provisional 

assessment presented here does not attempt to critically review individual studies or to provide 

the kind of full integration found in a typical AQCD. 

The literature search and submissions from public commenters found that hundreds of 

studies have been published in the last few years on the health effects of particulate matter. In an 

initial screen of the literature, more than 700 studies were identified as being potentially relevant 

to this review. In surveying these studies, EPA emphasized studies more likely to be relevant to 

considerations for the PM NAAQS decision. The specific criteria focused on (a) epidemiologic 

studies that used PM2.5 or PM10-2.5 and were conducted in the U.S. or Canada, and (b) toxicology 

or epidemiologic studies that compared effects of PM from different sources, PM components, or 

size fractions. These criteria resulted in a list of over 200 studies that are summarized in tables 

in this report that provide descriptive and quantitative information. The most significant studies 

are discussed in the assessment, and where feasible, quantitative results are compared to those 

from the 2004 PM AQCD. Bibliographies have been attached for studies identified as being 

potentially relevant through the survey effort but not discussed in detail in this report. 

 1

 As stated in the PM NAAQS proposal notice: “The EPA is aware that a number of new scientific studies 

on the health effects of PM have been published since the 2002 cutoff date for inclusion in the Criteria Document. 

As in the last PM NAAQS review, EPA intends to conduct a review and assessment of any significant new studies 

published since the close of the Criteria Document, including studies submitted during the public comment period 

in order to ensure that, before making a final decision, the Administrator is fully aware of the new science that has 

developed since 2002. In this assessment, EPA will examine these new studies in light of the literature evaluated in 

the Criteria Document. This assessment and a summary of the key conclusions will be placed in the rulemaking 

docket.” (71 FR 2625) 
2

The overview in the main body of this report is organized into three main sections: 

(1) epidemiologic studies on effects associated with long-term exposure to PM, focusing on 

U.S. and Canadian studies with measurements of PM2.5 or PM10-2.5; (2) results from time-series 

epidemiologic studies, again focusing on U.S. and Canadian studies with measurements of PM2.5 

or PM10-2.5; and (3) results of recent toxicology and epidemiologic studies that have evaluated 

health effects with exposure to PM from different sources. This last section includes results of 

studies that assessed the effects of a range of sources or components in the same study. Most 

studies have focused on components or sources of fine particles, but information related to 

sources of thoracic coarse particles was also included to the extent available. 

2. OVERVIEW OF RECENT HEALTH STUDY RESULTS 

2.1 Epidemiologic Studies of Long-Term Exposure 

2.1.1 Mortality 

 An extensive discussion of prospective cohort studies was included in Section 8.2.3 of 

the 2004 PM AQCD. These discussions emphasized the results of four U.S. prospective cohort 

studies. The greatest weight was placed on the findings of the American Cancer Society (ACS) 

and the Harvard Six Cities studies which had undergone extensive, independent reanalysis and 

were based on cohorts that were broadly representative of the U.S. population. These studies 

provided strong evidence that long-term exposure to fine particles and sulfates was associated 

with mortality. In addition, results from the Seventh-Day Adventist (AHSMOG) cohort 

provided some suggestive but less conclusive evidence for associations, and results from the 

Veterans Cohort provided inconsistent evidence for associations between long-term exposures to 

PM2.5 and mortality. Overall, the 2004 PM AQCD concluded that there was strong 

epidemiologic evidence for associations between long-term exposures to PM2.5 and mortality 

(p. 9-46). 

In the 2004 PM AQCD, no association was observed between mortality and long-term 

exposure to PM10-2.5 in the ACS study (Pope et al., 2002), and a positive but nonsignificant 

association was reported in males in the AHSMOG cohort (McDonnell et al., 2000). Thus, the 

2004 PM AQCD concluded that there was insufficient evidence for associations between longterm exposure to thoracic coarse particles and mortality. 

Fine Particles: 

Recent studies include results of new analyses for the ACS and Harvard Six Cities 

studies; as highlighted below, the new findings strengthen the evidence linking long-term 

exposure to PM2.5 and mortality. Recent reports have also included analyses from the AHSMOG 

and Veterans study cohorts, as well as a Cystic Fibrosis cohort and a subset of the ACS for 

California. These results, along with those from studies available in the 2004 PM AQCD, are 

shown in Figure 1. The risk estimates and PM concentrations reported in the studies are 

summarized in Table 1, along with results available in the 2004 PM AQCD; further details on 

the studies are presented in Appendix A, Table A1. 
3

Table 1. Mortality and Morbidity Effect Estimates and PM Concentrations from U.S. 

and Canadian Studies with Long-Term Exposures to PM2.5 and PM10-2.5. Adapted from 

Appendix 3B of the 2005 OAQPS Staff Paper. Shaded rows present results from recent 

studies that were not available in the 2004 PM Criteria Document.

Study Indicator Relative Risk (95% CI)

Study 

Concentrations 

(μg/m3

) *

Increased Total Mortality in Adults 

Six CitiesA PM2.5 1.13 (1.04, 1.23) NR (11, 30) 

 SO4

2- (15 μg/m3

) 1.54 (1.15, 2.07) NR (5, 13) 

Six CitiesB

 PM15-2.5 1.43 (0.83, 2.48) 

Six Cities ReanalysisD PM2.5 1.14 (1.05, 1.23) NR (11, 30) 

Six Cities Follow-upAA PM2.5 1.16 (1.07, 1.26) NR (10.2, 22) 

ACS StudyC PM2.5 1.07 (1.04, 1.10) 181 (9, 34) 

 SO4

2- (15 μg/m3

) 1.11 (1.06, 1.16) 111 (4, 24) 

ACS Study Reanalysis PM2.5 1.07 (1.04, 1.10) 20 (10, 38) D

PM15-2.5 1.00 (0.99, 1.02) 7.1 (9, 42) 

ACS Study Extended 

AnalysesE

PM2.5 (1979-83) 

PM2.5 (1999-00) 

PM2.5 (average) 

1.04 (1.01, 1.08) 

1.06 (1.02, 1.10) 

1.06 (1.02, 1.11) 

21 (9, 34) 

14 (5, 20) 

18 (7.5, 30) 

ACS Los AngelesBB PM2.5 1.17 (1.05, 1.30) NR (9, 27) 

AHSMOGH PM2.5 1.09 (0.98, 1.21) (males) 32 (17, 45) 

 PM10-2.5 1.05 (0.92, 1.21) (males) 27 (4, 44) 

Veterans CohortG PM2.5 (1979-81) 0.90 (0.85, 0.95) (males) 24 (6, 42) 

Veterans CohortCC PM2.5 (1999-2001) 1.12 (1.04, 1.20) (males) 14.6 (SD 3.1) 

Veterans CohortCC PM10-2.5 (1989-96) 1.07 (1.01, 1.12) (males) 16.0 (SD 5.1) 

California Cancer 

Prevention StudyDD

PM2.5 (1979-83) 1.04 (1.01, 1.07) 

(deaths 1973-1982) 

1.00 (0.98, 1.02) 

(deaths 1983-2002) 

23.4 (10.6-42.0) 

U.S. Cystic FibrosisEE PM2.5 1.32 (0.91, 1.93) 13.7 (11.8, 15.9) 

Increased Cardiopulmonary Mortality in Adults

Six CitiesA PM2.5 1.18 (1.06, 1.32) NR (11, 30) 

Six Cities ReanalysisD PM2.5 1.19 (1.07, 1.33) NR (11, 30) 
4

Table 1. Mortality and Morbidity Effect Estimates and PM Concentrations from U.S. 

and Canadian Studies with Long-Term Exposures to PM2.5 and PM10-2.5. Adapted from 

Appendix 3B of the 2005 OAQPS Staff Paper. Shaded rows present results from recent 

studies that were not available in the 2004 PM Criteria Document.

Study Indicator Relative Risk (95% CI)

Study 

Concentrations 

(μg/m3

) *

Six Cities Follow-upAA PM2.5 1.28 (1.13-1.44) 

(Cardiovascular) 

1.08 (0.79-1.49) 

(Respiratory) 

NR (10.2, 22) 

ACS StudyC PM2.5 1.12 (1.07, 1.17) 181 (9, 34) 

ACS Study Reanalysis PM2.5 1.12 (1.07, 1.17) 20 (10, 38) D

PM15-2.5 1.00 (0.98, 1.03) 7.1 (9, 42) 

ACS Study Extended 

AnalysesE

PM2.5 (1979-83) 

PM2.5 (1999-00) 

PM2.5 (average) 

1.06 (1.02, 1.10) 

1.08 (1.02, 1.14) 

1.09 (1.03, 1.16) 

21 (9, 34) 

14 (5, 20) 

18 (7.5, 30) 

ACS Cause-specificFF : 

All cardiovascular 

Ischemic heart disease 

Dysrhythmia, et al. 

Hypertensive 

Other atherosclerosis 

Cerebrovascular disease 

Diabetes 

Other cardiovascular 

All Respiratory 

COPD 

Pneumonia 

Other respiratory 

PM2.5 (average) 

1.12 (1.08, 1.15) 

1.18 (1.14, 1.23) 

1.13 (1.05, 1.21) 

1.07 (0.90, 1.26) 

1.04 (0.89, 1.21) 

1.02 (0.95, 1.10) 

0.99 (0.86, 1.14) 

0.84 (0.71, 0.99) 

0.92 (0.86, 0.98) 

0.84 (0.77, 0.93) 

1.07 (0.95, 1.20) 

0.86 (0.73, 1.02) 

17.1 (7.5, 30) 

ACS Los Angeles:BB

Ischemic heart disease 

Cardiopulmonary 

PM2.5

1.39 (1.12, 1.73) 

1.12 (0.97, 1.30) 

NR (9, 27) 

AHSMOG PM2.5 1.23 (0.97, 1.55) (males) 32 (17, 45) H

PM10-2.5 1.20 (0.87, 1.64) (males) 27 (4, 44) 

PM2.5 1.42 (1.06, 1.90) (females) 

1.49 (1.17, 1.89) (postmenopausal) 

0.90 (0.76, 1.05) (males) 

AHSMOG 29 (SD 9.8) GG

Fatal coronary heart disease 

PM10-2.5 1.38 (0.97, 1.95) (females) 

1.61 (1.12, 2.33) (postmenopausal) 

0.92 (0.66, 1.29) (males) 

25.4 (SD 8.5) 

Increased Lung Cancer Mortality in Adults 

Six CitiesA PM2.5 1.18 (0.89, 1.57) NR (11, 30) 
5

Table 1. Mortality and Morbidity Effect Estimates and PM Concentrations from U.S. 

and Canadian Studies with Long-Term Exposures to PM2.5 and PM10-2.5. Adapted from 

Appendix 3B of the 2005 OAQPS Staff Paper. Shaded rows present results from recent 

studies that were not available in the 2004 PM Criteria Document.

Study Indicator Relative Risk (95% CI)

Study 

Concentrations 

(μg/m3

) *

Six Cities ReanalysisD PM2.5 1.21 (0.92, 1.60) NR (11, 30) 

Six Cities Follow-upAA PM2.5 1.27 (0.96, 1.69) NR (10.2, 22) 

ACS StudyC PM2.5 1.01 (0.91, 1.12) 18U (9, 34) 

ACS Study Reanalysis PM2.5 1.01 (0.91, 1.11) 20 (10, 38) D

PM15-2.5 0.99 (0.93, 1.05) 7.1 (9, 42) 

ACS Study Extended 

AnalysesE

PM2.5 (1979-83) 

PM2.5 (1999-00) 

PM2.5 (average) 

1.08 (1.01, 1.16) 

1.13 (1.04, 1.22) 

1.14 (1.05, 1.24) 

21 (9, 34) 

14 (5, 20) 

18 (7.5, 30) 

ACS Los AngelesBB PM2.5 1.44 (0.98, 2.11) NR (9, 27) 

AHSMOG PM2.5 1.39 (0.79, 2.50) (males) 32 (17, 45) H 

M10-2.5 1.26 (0.62, 2.55) (males) 27 (4, 44) 

Increased Bronchitis in Children

Six CitiesI PM2.5 1.3 (0.9, 2.0) NR (12, 37) 

24 CitiesJ SO4

2- (15 μg/m3

) 

PM2.1

3.02 (1.28, 7.03) 

1.31 (0.94, 1.84) 

4.7 (0.7, 7.4) 

14.5 (5.8, 20.7) 

AHSMOGK SO4

2- (15 μg/m3

) 1.39 (0.99, 1.92) — 

12 Southern California 

communitiesM

(children with asthma) 

PM2.5 1.3 (0.9, 1.7) 15.3 (6.7, 31.5) 

12 Southern California 

communitiesHH

(children with asthma) 

PM2.5

PM10-2.5

1.34 (1.11, 1.63) 

1.10 (0.82, 1.49) 

(between communities) 

13.8 (5.5, 28.5) 

17.0 (10.2, 35.0) 

12 Southern California 

communitiesHH

(children with asthma) 

PM2.5

PM10-2.5

2.37 (1.13, 4.94) 

1.21 (0.59, 2.54) 

(within community change) 

13.8 (5.5, 28.5) 

17.0 (10.2, 35.0) 

Increased Cough in Children

12 Southern California 

communitiesM

(children with asthma) 

PM2.5 1.2 (0.8, 1.8) 15.3 (6.7, 31.5) 

Increased Pulmonary Exacerbations in Cystic Fibrosis Patients

U.S. Cystic FibrosisEE PM2.5 1.21 (1.07, 1.33) 13.7 (11.8, 15.9) 
6

Table 1. Mortality and Morbidity Effect Estimates and PM Concentrations from U.S. 

and Canadian Studies with Long-Term Exposures to PM2.5 and PM10-2.5. Adapted from 

Appendix 3B of the 2005 OAQPS Staff Paper. Shaded rows present results from recent 

studies that were not available in the 2004 PM Criteria Document.

Study Indicator Relative Risk (95% CI)

Study 

Concentrations 

(μg/m3

) *

Decreased Lung Function in Children

24 CityJ SO4

2- (15 μg/m3

) 

PM2.1

!6.56% (-9.64, -3.43) FVC 

!2.15% (-3.34, -0.95) FVC 

4.7 (0.7, 7.4) 

14.5 (5.8, 20.7) 

12 Southern California 

communitiesQ

(4th grade cohort) 

PM2.5

PM10-2.5

!0.18 (-0.36, 0.0) FVC % growth 

!0.4 (-0.75, -0.04) MMEF % growth 

!0.22 (-0.47, 0.02) FVC % growth 

!0.54 (-1.0, -0.06) MMEF % growth 

NR (10, 35)3

NR 

12 Southern California 

communitiesQ

(second 4th grade cohort) 

PM2.5 !0.06 (-0.30, 0.18) FVC % growth 

!0.42 (-0.84, 0.0) MMEF % growth 

!0.20 (-0.64, 0.25) PEFR % growth 

NR (5, 30)4

12 Southern California 

communitiesII

(first 4th grade cohort, 8-yr 

follow-up) 

PM2.5 -26.4 (-72.9, 20.1) FVC growth 

-35.0 (-67.1, -2.8) FEV1 growth 

-74.1 (-151.5, 3.4) MMEF growth 

NR (5, 28) 

Lung Function Changes in Adults

AHSMOGT (% predicted 

FEV1, males) 

SO4

2- (1.6 μg/m3

) !1.5% (-2.9, -0.1) FEV1 7.3 (2.0, 10.1) 

* Note: Effect estimates presented using standardized increments of 10 μg/m3

 PM2.5 and PM10-2.5. Concentrations 

are presented as mean (min, max), or mean ("SD); NS Changes = No significant changes (no quantitative results 

reported); NR = not reported. 

1

 Median 

2

 Results only for smoking category subgroups. 

3

 Estimated from Figure 1, Gauderman et al. (2000) 

4

 Estimated from figures available in online data supplement to Gauderman et al. (2002) 

References:

A Dockery et al. (1993) 

B

 EPA (1996a) 

C

 Pope et al. (1995) 

D Krewski et al. (2000) 

E

 Pope et al. (2002) 

F

 Abbey et al. (1999) 

G Lipfert et al. (2000b) 

H McDonnell et al. (2000) 

I

 Dockery et al. (1989) 

J

 Dockery et al. (1996) 

K Abbey et al. (1995a,b,c) 

L

 Peters et al. (1999a) 

M McConnell et al. (1999) 

N Berglund et al. (1999) 

O Raizenne et al. (1996) 

P

 Peters et al. (1999) 

Q Gauderman et al. (2000) 

R

 Gauderman et al. (2002) 

S

 Avol et al. (2001) 

T

 Abbey et al. (1998) 

Recent studies:

AA Laden et al. (2006) BB Jerrett et al. (2005) CC Lipfert et al. (2006) DD Enstrom (2005) EE Goss et al. (2004) FF Pope et al. (2004) GG Chen et al. (2005) HH McConnell et al. (2003) II Gauderman et al. (2004)
7

Figure 1. Relative risk estimates (and 95% confidence intervals) for associations between 

long-term exposure to PM (per 10 PM10-2.5) and mortality. *Note: The second 

result presented for Laden et al. (2006) is for the intervention study results. 
8

Harvard Six Cities: A new study has used updated air pollution and mortality data; an 

additional 1,368 deaths occurred during the follow-up period (1990-1998) and 

1,364 deaths occurred in the original study period (1974-1989). Statistically significant 

associations are reported between long-term exposure to PM2.5 and mortality for data for 

the two periods (RR = 1.16, 95% CI 1.07-1.26 per 10 μg/m3

 PM2.5). Of note, however, 

a statistically significant reduction in mortality risk is reported with reduced long-term 

fine particle concentrations (RR = 0.73, 95% CI 0.57-0.95 per 10 μg/m3

 PM2.5). This is 

equivalent to an RR of 1.27 for reduced mortality risk, suggesting a larger effect than in 

the cross-sectional analysis. This reduced mortality risk was observed for deaths due to 

cardiovascular and respiratory causes, but not for lung cancer deaths. Mean PM2.5

concentrations from the follow-up period range from 10.2 to 22.0 μg/m3 in the six cities. 

The means across the six cities were 18 μg/m3

 in the first period and 14.8 μg/m3 in the 

follow-up period. The PM2.5 concentrations for recent years were estimated from 

visibility data which introduces uncertainty in interpreting the results of this study 

(Laden et al., 2006). Coupled with the results of the original analysis (Dockery et al., 

1993), this study strongly suggests that reduction in fine PM pollution has yielded 

positive health benefits. 

ACS Extended Analyses: One new analysis further evaluated associations between longterm PM2.5 and sulfate exposures in 50 U.S. cities and mortality, adding new information 

about deaths from specific cardiovascular and respiratory causes. Significant 

associations were reported with deaths from specific cardiovascular diseases, particularly 

ischemic heart disease, and a group of cardiac conditions including dysrhythmia, heart 

failure and cardiac arrest (RR for cardiovascular mortality = 1.12, 95% CI 1.08-1.15 per 

10 μg/m3 PM2.5); no associations were reported with respiratory mortality. The mean 

PM2.5 concentration (1979-1983 and 1999-2000) was 17.1 μg/m3

 (Pope et al., 2004). 

ACS, Los Angeles: Much of the exposure gradient in the national-scale ACS studies was 

due to city-to-city differences in regional air pollution. A new analysis using ACS data 

focused on neighborhood-to-neighborhood differences in urban air pollutants, on data 

from 23 PM2.5 monitoring stations in the Los Angeles area and using interpolation 

methods to assign exposure levels to individuals (Jerrett et al., 2005). This resulted in 

both improved exposure assessment and an increased focus on local sources of fine 

particle pollution. Significant associations between PM2.5 and mortality from all causes 

and cardiopulmonary diseases were reported with the magnitude of the relative risks 

being greater than those reported in previous assessments (after adjustment for potential 

confounders including traffic, RR for cardiovascular diseases = 1.17, 95% CI 1.05-1.31, 

per 10 μg/m3

 PM2.5; RR for ischemic heart disease = 1.38, 95% CI 1.11-1.72 per 

10 μg/m3

 PM2.5). The authors suggest that reducing exposure error can result in stronger 

associations between PM2.5 and mortality than generally observed in broader studies 

having less exposure detail. 

California cancer prevention study: In a cohort of elderly people in 11 California 

counties (mean age 73 years in 1983), an association was reported for long-term PM2.5

exposure with all-cause deaths in 1973-1982 (RR = 1.04, 95% CI 1.01-1.07 per 10 μg/m3

PM2.5). No significant associations were reported with deaths in later time periods 
9

(1983-2002) (RR = 1.00, 95% CI 0.98-1.02 per 10 μg/m3

 PM2.5) when PM2.5 levels had 

decreased in the most polluted counties. The PM2.5 data are from the EPA’s Inhalation 

Particle Network, and represent a subset of data used in the 50-city ACS study (Pope 

et al., 1995). The use of average values for California counties as exposure surrogates 

likely leads to significant exposure error as many California counties are large and quite 

topographically variable. The mean PM2.5 concentration (1979-1983) was 23.4 μg/m3

(Enstrom, 2005). 

AHSMOG: In this analysis for the Seventh-Day Adventist cohort in California, positive, 

statistically significant association with coronary heart disease mortality was reported for 

92 deaths among females (RR = 1.42, 95% CI 1.06-1.90 per 10 μg/m3 PM2.5), but not for 

53 deaths among males (RR = 0.90, 95% CI 0.76-1.05 per 10 μg/m3

 PM2.5). Associations 

were strongest in the subset of postmenopausal women (80 deaths; RR=1.49, 95% CI 

1.17, 1.89 per 10 μg/m3

 PM2.5). The authors speculated that females may be more 

sensitive to air pollution-related effects based on differences between males and females 

in dosimetry and exposure, along with the generally lower blood cell levels in females. 

The mean PM2.5 concentration averaged over 1973-1998 was 29.0 μg/m3

 (Chen et al., 

2005). 

Veterans cohort: A recent analysis of the Veterans cohort data focused on exposure to 

traffic-related air pollution (traffic density based on traffic flow rate data and road 

segment length) reported a stronger relationship between mortality with long-term 

exposure to traffic than with PM2.5 mass. A significant association was reported between 

total mortality and PM2.5 in single-pollutant models (RR = 1.12, 95% CI 1.04-1.20 per 

10 μg/m3 PM2.5); the author observes that this risk estimate is larger than results reported 

in a previous study (Lipfert et al., 2000). In multi-pollutant models including traffic 

density, the association with PM2.5 was reduced and lost statistical significance. Traffic 

emissions contribute to PM2.5 so it would be expected that the two would be highly 

correlated, and thus these multi-pollutant model results should viewed with caution. The 

mean PM2.5 level was 14.6 μg/m3 using data from 1997-2001 (Lipfert et al., 2006a). 

In a companion study, Lipfert et al. (2006b, in press) used data from EPA’s fine particle 

speciation network, and reported findings for PM2.5 were similar to those reported in the 

Lipfert et al., 2006a. A positive association was also reported for mortality with sulfates 

using the more recent data, but was not statistically significant. Using 2002 data from the 

fine particle speciation network, significant associations were found between mortality 

and nitrates, EC, Ni and V, as well as traffic density and peak ozone concentrations. In 

multi-pollutant models, associations with traffic density remained significant, as did 

nitrates, Ni and V in some models. The mean PM2.5 level was 13.2 μg/m3

 using data 

from 2002 (Lipfert et al., 2006b, in press). 

U.S. Cystic Fibrosis cohort: A positive, but not statistically significant, association was 

reported in this cohort (RR = 1.32, 95% CI 0.91-1.93 per 10 μg/m3

 PM2.5) in a study that 

primarily focused on evidence of exacerbation of respiratory symptoms (as discussed in 

the following section). Only 200 deaths had occurred in the cohort of over 11,000 people 
10

(average age in cohort was 18.4 years) thus the power of the study to detect associations 

is limited. The mean PM2.5 concentration was 13.7 μg/m3 (Goss et al., 2004). 

Infant mortality: A new study in California has reported statistically significant 

associations between mortality from respiratory causes with exposure to PM2.5, using 

PM2.5 levels averaged over the time between the infant’s birth and death (RR 1.07, 95% 

CI 0.93-1.24 per 10 μg/m3

 PM2.5 for overall mortality and 2.13, 95% CI 1.12-4.05 for 

respiratory mortality). The mean PM2.5 exposure concentrations ranged from 17.3 to 

19.8 μg/m3

 (Woodruff et al., 2006). 

Thoracic coarse particles: 

In the original analyses of the Six Cities and ACS cohort studies, no associations were 

found between long-term exposure to PM10-2.5 and mortality; the extended and follow-up 

analyses that are discussed above for fine particles did not evaluate potential associations with 

PM10-2.5. Two recent reports from the AHSMOG and Veterans study cohorts have provided 

some limited suggestive evidence for associations between long-term exposure to PM10-2.5 and 

mortality, as summarized below. 

AHSMOG: As was found with fine particles, a positive association with coronary heart 

disease mortality was reported for females (RR = 1.38, 95% CI 0.97-1.95 per 10 μg/m3

PM2.5), but not for males (RR = 0.92, 95% CI 0.66-1.29 per 10 μg/m3

 PM2.5); 

associations were strongest in the subset of postmenopausal women (80 deaths). 

The mean PM10-2.5 concentration over 1973-1998 was 25.4 μg/m3 (Chen et al., 2005). 

Veterans cohort: A significant association was reported between long-term exposure to 

PM10-2.5 and total mortality in a single-pollutant model (RR = 1.07, 95% CI 1.01-1.12 per 

10 μg/m3 PM2.5), but the association became negative and not statistically significant in a 

model that included traffic density. As it would be expected that traffic would contribute 

to thoracic coarse particle concentrations, it is difficult to interpret the results of these 

multi-pollutant analyses. The average PM10-2.5 concentration over 1989-1996 was 

16.0 μg/m3

 (Lipfert et al., 2006). 

Conclusions 

 As shown in Figure 1, the pattern of results from the new studies for both fine and 

thoracic coarse particles is generally similar to those available previously. Overall, the recent 

evidence supports associations between long-term PM2.5 exposure and mortality, with key new 

evidence from the Six Cities cohort study showing a relatively large risk estimate for reduced 

mortality risk with decreases in PM2.5 (Laden et al., 2006). The results of new analyses from the 

Six Cities cohort and the ACS study in Los Angeles suggest that previous and current studies 

may underestimate the magnitude of the association (Jerrett et al., 2005). In addition, exposure 

to PM2.5 was associated with increased respiratory mortality in infants in a new study in 

California (Woodruff et al., 2006). New evidence from the Veterans cohort study report 

associations with PM2.5 in single-pollutant models, though the authors report that traffic density 

is a stronger predictor of mortality than PM2.5 (Lipfert et al., 2006a). There is also suggestive 
11

evidence for an association with mortality in the analysis of the Cystic Fibrosis cohort data. 

The new study using Cancer Prevention Study cohort data in Los Angeles, however, indicates 

no association with PM2.5 except when using the first time period in the study (Enstrom et al., 

2005). 

In the 2004 PM AQCD, results from the ACS and Six Cities study analyses indicated that 

thoracic coarse particles were not associated with mortality. The new findings from AHSMOG 

and Veterans cohort studies provide some suggestive evidence of associations between long-term 

exposure to PM10-2.5 and mortality in areas with mean concentrations from 16 to 25 μg/m3

. The 

2004 PM AQCD placed greatest weight on the ACS and Six Cities study findings; further 

evidence will need to be evaluated in the next review of the PM NAAQS on whether long-term 

exposure to thoracic coarse particles is associated with mortality. 

2.1.2 Morbidity 

The 2004 PM AQCD (Section 8.3.3.2) included results from two U.S. and Canadian 

children’s cohort studies that had been available in the 1996 PM AQCD—the Harvard Six Cities 

and Harvard 24-cities studies—that reported significant associations between respiratory 

symptoms and decreased lung function with long-term exposure to fine particles and acid 

aerosols. More recent studies were available, using data from the Children’s Health Study in 

southern California; these studies also indicated that long-term exposure to fine particles was 

associated with decreased lung function growth2

 in children. The results from analyses of data 

from the AHSMOG showed suggestive, but inconsistent findings between long-term exposure to 

PM and respiratory morbidity in adults. Overall, the 2004 PM AQCD concluded that long-term 

exposure to PM, especially fine particles, was associated with respiratory morbidity (2004 PM 

AQCD, p. 8-343). Limited and inconsistent evidence was available on associations between 

long-term exposure to PM10-2.5 and respiratory morbidity. 

Among the recently published studies are longer follow-up analyses of respiratory 

morbidity using data from the Children’s Health Study, as well as a study based on data from the 

U.S. Cystic Fibrosis Cohort. The quantitative results of these studies are included in Table 1, 

and further details presented in Appendix A, Table A1. 

Fine particles:

Children’s Health Study: Significant associations are reported between long-term 

exposure to fine particles, as well as acid vapor and NO2, and reduced lung function 

growth (Gauderman et al., 2004) and increased risk of bronchitic symptoms, prevalence 

of chronic cough, or bronchitis (McConnell et al., 2003). These results expand upon the 

findings available in the 2004 PM AQCD, including assessment of lung function 

measurements in children over an 8-year follow-up period (Gauderman et al., 2004). 

In addition, McConnell et al. (2003) measured respiratory symptom prevalence over a 

 2

 In these studies, lung function measurements were repeated several years apart. Increases in lung 

function measures over this time period are referred to as lung function growth by the authors, with “decreased 

lung function growth” indicating smaller increases in lung function measurements for the children with higher air 

pollution exposure. 
12

4-year period, and reported larger effect estimates with changes in PM2.5 concentration 

over time within the communities than with changes in PM2.5 between communities. 

The mean PM2.5 concentration for the 12 California communities in 1994-2000 was 

13.8 μg/m3

 (McConnell et al., 2003; mean concentrations range from 5 to 28 μg/m3 in 

Gauderman et al., 2004). One additional analysis, based on monthly prevalence of 

respiratory symptoms, reports no significant associations with PM2.5 (Millstein et al., 

2004). 

U.S. Cystic Fibrosis cohort: The risk of experiencing pulmonary exacerbations was 

significantly increased with long-term exposure to PM2.5 (Goss et al., 2004). The mean 

PM2.5 concentration in 2000 was 13.7 μg/m3. 

Cardiovascular clinical studies: One new study has provided insight into the potential 

effect of long-term exposure to PM2.5 on the development of cardiovascular disease; no 

such studies were available in the 2004 PM AQCD. Using data from two clinical trials 

conducted in the Los Angeles area, the authors reported a significant association between 

long-term exposure to PM2.5 and carotid intima-media thickness, a measure of 

atherosclerosis development. The mean PM2.5 concentration was 20.6 μg/m3

 (Kunzli 

et al., 2005). 

Thoracic coarse particles:

Two reports from the Children’s Health Study included results for thoracic coarse 

particles. A significant association was observed between monthly prevalence of wheeze 

and PM10-2.5 during March-August in one new study, but no association was seen in other 

parts of the year (Millstein et al., 2004). No significant associations were reported 

between long-term exposure to PM10-2.5 and incidence of bronchitic symptoms in another 

report in which the mean PM10-2.5 concentration was 17.0 μg/m3 (McConnell et al., 2003). 

 

The recent findings from the southern California Children’s Health Study add support to 

previous conclusions that long-term fine particle exposure is associated with increased incidence 

of respiratory symptoms and decreased lung function growth in children. The new evidence 

from the Cystic Fibrosis Cohort provides additional evidence for associations with pulmonary 

exacerbations, particularly in a cohort of likely more susceptible individuals. These new studies 

also report associations with fine particle concentrations that are somewhat lower than those 

from studies available in the 2004 PM AQCD. These recent findings, however, do not show 

associations between respiratory morbidity and long-term exposure to PM10-2.5; in contrast, one 

earlier analysis from the Children’s Health Study in California had suggested such associations. 

 

No studies available in the 2004 PM AQCD had assessed associations between long-term 

PM exposure and cardiovascular morbidity. A new analysis shows an association between longterm PM2.5 exposure and a measure of atherosclerosis development (Kunzli et al., 2005). 
13

2.2 Epidemiologic Short-Term Exposure Study Results 

 The 2004 PM AQCD included the results of many new epidemiologic studies reporting 

associations between short-term exposure to PM and a range of health outcomes. The larger 

body of evidence from studies of PM10 and other PM indicators provided strong evidence for 

associations between short-term PM exposure and both mortality and morbidity (2004 PM 

AQCD, p. 8-337). 

 

The 2004 PM AQCD concluded that there was strong epidemiological evidence linking 

short-term exposures to PM2.5 with cardiovascular and respiratory mortality and morbidity. 

Positive, often statistically significant associations were observed between PM2.5 and these 

various health endpoints (2004 PM AQCD, p. 9-46). The epidemiological evidence was found 

to support likely causal associations between PM2.5 and both mortality and morbidity from 

cardiovascular and respiratory diseases, based on an assessment of strength, robustness, and 

consistency in results (2004 PM AQCD, p. 9-48). 

 Fewer studies were available to assess associations between PM10-2.5 and health 

outcomes. The magnitude of the effect estimates for associations between PM10-2.5 and mortality 

and morbidity effects (especially respiratory morbidity) was found to be similar to that for PM2.5, 

but the strength of the evidence for PM10-2.5 effects was reduced due to lower precision (AQCD, 

p. 9-46). Despite the reduced strength, the associations were found to be generally robust to 

alternative modeling strategies or consideration of potential confounding by co-pollutants. The 

collective evidence was found to be suggestive of associations for morbidity with short-term 

changes in PM10-2.5 (2004 PM AQCD, p. 9-48). 

Sections 2.2.1 and 2.2.2 highlight results from recent time-series epidemiologic studies. 

Tables A2 through A12 (Appendix A) summarize results of recent epidemiologic studies that 

evaluated relationships between health effects and short-term exposure to PM2.5 and PM10-2.5. 

The discussions below emphasize results of studies conducted in the U.S. and Canada; however, 

some results are also presented from additional international studies or studies using indicators, 

such as PM10, that assess key issues or questions highlighted in the 2004 PM AQCD. 

 The 2004 PM AQCD included a particular focus on results of multicity studies due to 

their evaluation of a wide range of PM exposures and large numbers of observations, which lead 

to generally more precise effects estimates than most smaller scale independent studies of single 

cities. The multicity studies also allowed investigation of homogeneity or heterogeneity of PMhealth relationships, evaluation of confounding by co-pollutants across communities with 

different air pollution mixtures, and assessment of potential effect modifiers. Numerous 

multicity analyses have been published in recent years. Most of the recent multi-city studies 

report statistically significant associations between short-term exposure to PM10 and mortality or 

morbidity and these study results are briefly summarized in Section 2.2.3 as being particularly 

relevant to help address key methodological questions. In addition, 3 new multi-city studies 

have evaluated associations with PM2.5, one of which included PM10-2.5, and these studies are 

highlighted in the following sections. 
14

2.2.1 Mortality 

 Results from multi- and single-city epidemiologic studies on mortality were presented in 

Figure 9-4 of the 2004 PM AQCD. Associations were mostly positive and of similar magnitude 

for both PM2.5 and PM10-2.5. A number of the associations between mortality and short-term 

PM2.5 exposure were statistically significant, while few associations with PM10-2.5 reached 

statistical significance, possibly due to increased measurement error in estimating PM10-2.5

exposure (2004 PM AQCD, p. 9-28). Several recent studies have reported associations between 

mortality and short-term exposure to PM2.5 and PM10-2.5. These findings are included with those 

available from the 2004 PM AQCD in Figure 2, where it can be seen that the new study results 

are generally quite similar to those previously available. Note that Figure 2 presents results from 

single-pollutant models for purposes of comparing results across studies that included different 

mixes of copollutants, as done in the 2004 PM AQCD. 

2.2.1.1 Associations Between Acute Exposure to Fine Particles and Mortality

 A number of recent studies have evaluated associations between fine particles and 

mortality, including two multicity studies (Appendix A; Table A2). Evidence for associations 

between short-term exposure to PM2.5 and all-cause, cardiovascular, and respiratory mortality 

comes from the multi-site study by Ostro et al. (2006) conducted in nine California counties that 

had mean PM2.5 concentrations ranging from 14 to 29 μg/m3. Significant associations were 

reported in single-pollutant models for all-cause, cardiovascular and respiratory mortality for all 

ages, as well as a significant association with all-cause mortality for those aged >65 years. The 

authors observed that in multipollutant models, the PM2.5 effect estimate was attenuated when 

highly correlated pollutants (NO2 and CO) were added to the model, but was not affected by the 

inclusion of O3. However, in those aged >65 yr (who generally experienced stronger 

associations with mortality), adjusting for gaseous pollutants did not affect the PM2.5 coefficient. 

 Burnett et al. (2004) evaluated the relationship between NO2 and mortality in 

12 Canadian cities during the period 1981 to 1999. While the focus of this analysis was on 

associations with NO2, the analysis included other pollutants as well. PM2.5 data were available 

only on 12% of days with mortality data, compared to the other gaseous pollutants that had 

>90% data available, and for most of the study time period, PM2.5 was measured every 6th day. 

In analyses using these data, the association between PM2.5 and all-cause mortality was 

marginally significant (as shown in Figure 2). In two-pollutant models with NO2, the effect 

estimate for PM2.5 became negative (not significant), while the estimate for NO2 remained 

robust. NO2 concentrations were found to be correlated with PM2.5 concentrations (r = 0.48). 

Burnett and colleagues (2004) also report results from a separate analysis using more 

recent data with daily PM2.5 measurements (1998-2000). The authors state that a positive 

association was found between mortality and PM2.5 in this additional analysis (presumably 

significant, but confidence intervals were not provided). In this case, the NO2 association was 

reduced considerably after adjustment for PM2.5, whereas the PM2.5 association remained fairly 

robust with NO2 adjustment. These findings emphasize the difficulty of working with data 

collected every 6th day. The mean PM2.5 concentration for all 12 cities was 12.8 μg/m3

 with 

city-specific means ranging from 8.1 μg/m3

 in St. John to 16.7 μg/m3 in Windsor. 
 15

Figure 2. Excess risk estimates for total nonaccidental, cardiovascular, and respiratory mortality in singl

for U.S. and Canadian studies, including aggregate results from multicity studies (denoted in bo

PM increment used for standardization was 25 μg/m3 for both PM2.5 and PM10-2.5. Results prese

AQCD are marked as ‚ in the figure (studies A through T). Results from recent studies are shaded as × in the figure (studies AA through HH). 

A. Burnett and Goldberg (2003), 8 Canadian cities B. Klemm and Mason (2003), 6 U.S. cities C. Moolgavkar (2003), Los Angeles D. Klemm and Mason (2003), St. Louis E. Klemm and Mason (2003), Boston F. Klemm and Mason (2003), Kingston-Harriman G. Klemm and Mason (2003), Portage H. Ito (2003), Detroit I. Chock et al. (2003) Pittsburgh (age <75 yr) J. Chock et al. (2003) Pittsburgh (age 75+ yr) K. Klemm and Mason (2000), Atlanta 

L. Fairley (2003), Santa Clara County M. Klemm and Mason (2003), Topeka N. Tsai et al. (2000), Newark O. Klemm and Mason (2003), Steubenville P. Tsai et al. (2000), Elizabeth Q. Tsai et al (2000), Camden R. Lipfert et al. (2000), Philadelphia S. Ostro et al. (1995), Southern California T. Mar et al. (2003), Phoenix U. Ostro et al. (2003), Coachella Valley 

AA. Ostro et al. (2006), 9 countieBB. Ostro et al. (2006), 9 countieCC. Burnett et al. (2004), 12 CanDD. Ito et al. (in press), WashingtoEE. Villeneuve et al. (2003), VancFF. Slaughter et al. (2005), SpokaGG. Goldberg et al. (2006), MontrHH. Klemm et al. (2004), Atlanta II. Klemm et al. (2004), Atlanta 
 16 

 Several single-city studies have also been published. Evidence for associations between 

fine particles and mortality was seen in studies in Montreal (Goldberg et al., 2006) and Atlanta 

(Klemm et al., 2004), as well as in studies that focused on source apportionment in Phoenix (Mar 

et al., 2006) and Washington, DC (Ito et al., 2006). No associations were reported in studies in 

Vancouver (Villeneuve et al., 2003) and Spokane (Slaughter et al., 2005); these studies reported 

low PM2.5 concentrations. Finally, one new analysis reports no evidence for associations 

between short-term exposure and death due to sudden infant death syndrome (Dales et al., 2004). 

The mean PM2.5 concentrations in locations where statistically significant associations were 

reported ranged from about 12 to greater than 20 μg/m3

. 

 In Figure 2, the results of the recent time-series studies are presented alongside the 

findings available in the 2004 PM AQCD. In this figure, it can be seen that the results of the 

larger multicity studies are quite consistent with those in earlier studies. The studies have been 

presented in order of decreasing statistical power (based on number of days and number of health 

events per day) from left to right for each group of studies. Some of the recent studies have 

fairly low statistical power which is reflected in the large confidence intervals and more variable 

effect estimate sizes shown in Figure 2. These results, while imprecise, are also generally 

consistent with earlier study results. Collectively, evidence regarding the PM2.5-mortality 

association from the most recent literature appears to be consistent with that available from the 

2004 PM AQCD. 

2.2.1.2 Associations Between Acute Exposure to Thoracic Coarse Particles and Mortality

Several new studies examined the association between PM10-2.5 and mortality in the U.S. 

and Canada (Appendix A; Table A3). The multicity study by Burnett et al. (2004), aimed 

primarily at NO2, also examined the association between PM10-2.5 and all-cause, nonaccidental 

mortality for lag day 1 (i.e., previous day) using data from 12 Canadian cities. The association 

with PM10-2.5 was positive but not significant; there was a significant association with PM10 that 

lost significance with adjustment for NO2. However, particle data were available only on 12% 

of days in this study, as discussed above. The mean PM10-2.5 concentration in this study was 

11.4 μg/m3

 (12 city means range from 5.5 to 15.9 μg/m3). 

Figure 2 includes results from the recent single-pollutant studies and those available in 

the 2004 PM AQCD. Looking across all studies, it can be seen that associations between 

PM10-2.5 and total and cardiovascular mortality are generally positive and a number are 

statistically significant, particularly for cardiovascular mortality. As discussed in the 2004 PM 

AQCD, some studies indicated stronger associations between acute PM10-2.5 exposure and 

cardiovascular mortality than for all-cause mortality. One recent study in Vancouver, Canada, 

also observed a statistically significant relationship with cardiovascular mortality on lag day 0 

(i.e., same day) but not on lag day 1 or 2 or the 3-day average lag periods (i.e., 24-hour average 

concentrations measured 1-, 2- or 3-days prior) (Villeneuve et al., 2003). No associations were 

found for all-cause, respiratory, or cancer mortality in this study. The mean PM10-2.5

concentration in this study was 6.1 μg/m3

 (range 0 to 72 μg/m3). 
 17 

Other recent studies did not report statistically significant associations between PM10-2.5

and total mortality. Slaughter et al. (2005) did not find a significant relationship for PM10-2.5 with 

all-cause, nonaccidental mortality in Spokane, WA, which likely had higher PM10-2.5

concentrations than Vancouver, Canada (data not shown). Neither Slaughter et al. (2005) nor 

Burnett et al. (2004) investigated the relationship with cardiovascular mortality. A recent PM10

study in El Paso (Staniswalis et al., 2005) supports the hypothesis that wind-blown dust coming 

from non-urban areas during high wind speeds (assumed largely coarse-fraction particles) is less 

toxic than particles generated within the urban area. Finally, Klemm and colleagues (2004) 

reported a positive, but not statistically significant association between PM10-2.5 and mortality in 

Atlanta. The mean PM10-2.5 concentration in this study was 9.7 μg/m3

 (range 1.7 to 25.2 μg/m3). 

2.2.2 Morbidity 

 Results from epidemiologic studies on hospital admissions were presented in Figure 9-5 

of the PM AQCD. Associations were all positive and of similar magnitude for both PM2.5 and 

PM10-2.5. Many of the associations with short-term PM2.5 exposure were statistically significant, 

especially for respiratory diseases. Likely due to increased measurement error, some, but not all, 

of the associations with PM10-2.5 reached statistical significance (2004 PM AQCD, p. 9-29). 

Several recent studies have reported associations between short-term exposure to PM2.5 and 

PM10-2.5 and hospitalization or emergency department visits for cardiovascular and respiratory 

diseases. These findings are included with those available from the 2004 PM AQCD in Figure 3. 

2.2.2.1 Associations Between Acute Exposure to Fine Particles and Morbidity

 These new studies substantially expand the evidence for associations between PM2.5 and 

effects on the cardiovascular system (Appendix A; Tables A4, A6 and A8). These include a 

powerful new multi-city study by Dominici et al. (2006) that used data from the Medicare 

National Claims History Files for 11.5 million people living in 204 urban counties in the U.S.; 

the average PM2.5 concentration for 1999-2000 was 13.4 μg/m3. There was only limited 

consideration of other pollutants in this analysis. Hospital admission rates for cause-specific 

cardiovascular and respiratory diseases were significantly associated with short-term PM2.5

exposure in individuals aged >65 yr. The largest association was reported with heart failure. 

Significant associations were also found between short-term PM2.5 exposure and hospital 

admissions for cerebrovascular disease, and positive though not statistically significant 

associations were seen with peripheral vascular disease, ischemic heart disease, and cardiac 

rhythm. When evaluated on a region-specific basis, positive associations with cardiovascular 

disease hospitalization were seen in the Midwest, Northeast, and Southern regions; the authors 

suggest that differences in the sources and composition of fine particles contributes to the 

geographic differences seen in effect estimates. 

One recent study reports significant associations between short-term exposure to PM2.5

and emergency department visits for all cardiovascular diseases, congestive heart failure and 

peripheral vascular and cerebrovascular disease in Atlanta (Metzger et al., 2004). Another study 

reports no evidence of associations with cardiovascular visits in Spokane, where the PM2.5

concentrations were low (authors report that 90% of concentrations ranged between 4.2 and 

20.2 μg/m3) (Slaughter et al., 2005). 
 18

Figure 3. Excess risk estimates for hospital admissions and emergency department visits for cardiovascul

diseases in single-pollutant models for U.S. and Canadian studies, including aggregate results fr(denoted in bold print below). PM increment used for standardization was 25 μg/m3 for both PM2

Results presented in the 2004 PM AQCD are marked as ♦‚ in the figure (studies A through H). Resustudies are shaded in grey and marked as × in the figure (studies AA through JJ). (CHF = congestivCOPD = chronic obstructive pulmonary disease; HF = heart failure; IHD = ischemic heart disease; vascular and cerebrovascular disease; RI = respiratory infection; URI = upper respiratory infection
 19 A. Moolgavkar (2003), Los Angeles B. Burnett et al. (1997), Toronto C. Ito (2003), Detroit D. Stieb et al. (2000), St. John E. Sheppard (2003), Seattle F. Thurston et al. (1994), Toronto G. Delfino et al. (1997), Montreal H. Delfino et al. (1998), Montreal AA. Dominici et al. (2006), 204 U.S. counties (age >65 yr) BB. Slaughter et al. (2005), Spokane (age 15+ yr) CC. Metzger et al. (2004), Atlanta DD. Slaughter et al. (2005), Atlanta EE. Chen et al. (2005), Vancouver, Canada (age 65+ yr) FF. Chen et al. (2004), Vancouver, Canada (age 65+ yr) GG. Lin et al. (2002), Toronto, Canada 

HH. Lin et al. (2002), Toronto, Canada II. Peel et al. (2005), Atlanta JJ. Yang et al. (2004), Vancouver, CaKK. Lin et al. (2005), Toronto, Canada LL. Lin et al. (2005), Toronto, Canada 
 20 

Numerous new studies have reported associations between ambient PM2.5 and subtle 

cardiovascular effects such as changes in cardiac rhythm or heart rate variability (Appendix A; 

Table A8). In the 2004 PM AQCD, the data base was characterized as having some studies with 

conflicting results and a note of caution was raised in regard to drawing conclusions relating 

PM2.5 and heart rate variability and other measures of cardiovascular pathophysiological 

alterations. Of about 10 new studies evaluating associations between acute PM2.5 exposure and 

heart rate variability, most reported statistically significant associations with PM2.5. . Two new 

studies showed associations for PM2.5 with ST segment depressions, an indicator of myocardial 

ischemia (Gold et al., 2005). One new study examined PM2.5 effects on bronchial artery 

reactivity (a marker for cardiovascular disease risk) and reported a significant association 

(O’Neill et al., 2005). Noting that many of these studies were conducted over shorter time 

periods, nevertheless, it is reported that mean or median PM2.5 concentrations in a number of 

studies were in the range of 10-11 μg/m3, with maximum levels ranging from about 40 to 

60 μg/m3

. 

For respiratory effects, Dominici et al. (2006) report significant associations between 

PM2.5 and hospitalization for chronic obstructive pulmonary disease (COPD) and respiratory 

infection in the study of 204 U.S. counties mentioned above (Appendix A; Table A4). Less 

regional variation was seen for respiratory hospitalization than for cardiovascular hospital 

admissions; in contrast with the results for cardiovascular diseases, effect estimates for both 

COPD and respiratory infections admissions were larger for the western U.S. than the eastern 

U.S. 

There are also several single-city studies that were conducted in Canada that show no 

associations between hospitalization and acute exposure to PM2.5 (Lin et al., 2002; Lin et al., 

2005; Yang et al., 2004; Chen et al., 2004; Chen et al., 2005). All were studies of hospitalization 

for respiratory diseases, though studies differed in age group and respiratory endpoint, and the 

mean PM2.5 concentrations in the studies ranged from 7.7 to 18 μg/m3

. Another recent study 

reports positive associations with respiratory emergency department visits, although none are 

statistically significant (Peel et al., 2005) (mean concentration of 19.2 μg/m3). Finally, there was 

no evidence of associations with respiratory visits in Spokane, where the PM2.5 concentrations 

were low (90th percentile was 20.2 μg/m3) (Slaughter et al., 2005). 

 There are numerous new studies that examined various respiratory outcomes in relation 

to PM2.5 exposure (Appendix A; Table A10), including one new multicity study that reported a 

significant association between respiratory symptoms and short-term PM2.5 exposure (Gent et al., 

2003) (mean concentration of 13.1 μg/m3

); however, the effect estimate is reduced and not 

statistically significant with adjustment for ozone. Associations have also been reported between 

acute PM2.5 exposure and a new endpoint not previously reported, FENO (fractional exhaled nitric 

oxide, a marker of airway inflammation), in three studies conducted in Seattle, WA (Jansen 

et al., 2005; Koenig et al., 2005; Mar et al., 2005) and one in Steubenville, OH (Adamkiewicz 

et al., 2004). In addition, a study in Seattle reports statistically significant associations with 

lower respiratory symptoms in children with asthma (Mar et al., 2004). One study in Atlanta 

reported no positive associations between PM2.5 and medical visits for various respiratory 

conditions—in fact, some associations were negative in direction—but positive associations 

were reported for several components of PM2.5 (Sinclair and Tolsma, 2004). 
 21 

2.2.2.2 Associations Between Acute Exposure to Thoracic Coarse Particles and Morbidity

A number of new epidemiologic studies are available for assessing associations between 

short-term PM10-2.5 exposure and various morbidity health outcomes, especially related to 

respiratory morbidity (Appendix A; Tables A5, A7, A9, and A11). As shown in Figure 3, a 

number of recent reports have shown significant associations between respiratory hospitalization 

and acute exposure to PM10-2.5. These include associations with hospitalization in Vancouver for 

respiratory illness in children <3 years of age (Yang et al., 2004), COPD in the elderly, (Chen 

et al., 2004) and respiratory illness in the elderly (Chen et al., 2005). Associations were also 

reported with hospitalization for asthma in children (Lin et al., 2002) and respiratory illness in 

children (Lin et al., 2005) in Toronto. These associations with hospital admissions for 

respiratory disease were observed for PM10-2.5 in both time-series and case-crossover analyses, 

and the associations remained significant with adjustment for gaseous co-pollutants in four of the 

five studies (except Chen et al., 2005). The effect estimate increased with longer averaging 

times up to 4-7 days. Slaughter et al. (2005) did not observe significant associations between 

PM10-2.5 and hospitals admissions or emergency room visits in Spokane, WA for all ages taken 

together. Overall, these studies provide evidence for associations between acute PM10-2.5

exposure and respiratory morbidity in locations where reported mean concentrations range from 

5.6 to 12.2 μg/m3, and maximum concentrations from 24.6 to 68 μg/m3. 

One new panel study in Spokane indicated that exposure was associated with several 

upper respiratory tract symptoms in children with asthma, but no association was reported in 

adults (Mar et al., 2004). Peel et al. (2005) reported no significant associations between PM10-2.5

and respiratory emergency department visits in Atlanta; however in another Atlanta study, 

significant associations were reported between acute PM10-2.5 exposure and outpatient medical 

visits for several respiratory conditions (Sinclair and Tolsma, 2004). 

Little evidence was available on associations between cardiovascular morbidity and 

PM10-2.5 in the 2004 PM AQCD. In Atlanta, no significant associations were found between 

acute exposure and cardiovascular emergency department visits (Metzger et al., 2004). 

However, one recent study in Coachella Valley, CA reported significant associations between 

decreases in heart rate variability with short-term exposure to PM10-2.5, but not with PM2.5

(Lipsett et al., 2006). In addition, a panel study in Vancouver (Ebelt, et al., 2005) found 

significant associations between estimates of personal exposure to ambient particles, and to a 

lesser extent, ambient concentrations with decreased FEV1 and increases in systolic blood 

pressure and supraventricular ectopy. However, associations were not significant with measures 

of heart rate variability. No associations were reported with estimates of personal exposure to 

nonambient particles. The mean PM10-2.5 concentrations in the Coachella Valley and Vancouver 

studies range from about 10 to over 20 μg/m3 At the low end of reported concentrations is 

Vancouver, where PM10-2.5 means were 6-7 μg/m3

 and maxima were about 25 μg/m3. Of note, 

correlations reported between PM10-2.5 and combustion-related gaseous co-pollutants (CO, NO2, 

SO2) are generally higher than those reported between PM2.5 and the gases in Vancouver. At the 

high end is Coachella Valley, where PM10 concentrations were quite high, with peak levels 

exceeding the current PM10 standard level. 

Taken together, there is a substantial new body of evidence linking acute exposure to 

PM10-2.5 with morbidity, including associations with respiratory hospitalization, respiratory 
 22 

symptoms, and cardiovascular health outcomes. Of note, several recent studies have reported 

associations for several indicators of morbidity with PM10-2.5, but not with PM2.5. In addition, 

some new studies have used case-crossover methods and reported little evidence for confounding 

by co-pollutants. A key research question that has been identified during the current PM 

NAAQS review is to better understand the sources and components of PM10-2.5 that may be 

responsible for different health effects, and these findings continue to support that research need. 

2.2.3 Issues for Interpretation of Epidemiologic Study Results 

 More than 20 new multicity studies have been published in recent years. Three of these 

studies have included measurements of PM2.5 and one included PM10-2.5 and these studies are 

summarized in more detail above (Burnett et al., 2004; Dominici et al., 2006; Ostro et al., 2006). 

The remaining studies used PM10; the results are summarized briefly in an annotated 

bibliography (Appendix B). Most of these recent studies continue to report associations between 

short-term exposure to PM10 and mortality or morbidity. 

Methodological Issues: The results of the PM10 multicity studies are briefly highlighted 

here due to the importance of multicity studies in being able to evaluate issues that are not 

readily addressed in single-city analyses. The studies are grouped in Appendix B by the general 

issues being evaluated in the analyses. These studies address a range of questions and 

uncertainties that remained in the 2004 PM AQCD, including: 

• Several recent multicity studies reported that associations between PM10 and mortality 

are not likely to be confounded by weather or influenza epidemics (Schwartz 2004a; 

Welty and Zeger, 2005; Analitis et al., 2006; Touloumi et al., 2005). As observed in the 

2004 PM AQCD, assessments of copollutant confounding are complicated when the air 

pollutants are closely correlated, such as pollutants generated from common sources. 

Results from single-pollutant models may overestimate effects from that pollutant; 

however, multi-pollutant model results may be misleading when reporting results for 

correlated pollutants. One new multi-city study used case-crossover design and reported 

no evidence of confounding between PM10 and gaseous co-pollutants in associations with 

mortality in 14 U.S. cities (Schwartz et al., 2004b). Using more traditional time-series 

methods, Ostro et al. (2006) reported attenuation of associations between PM2.5and 

mortality with highly-correlated gaseous pollutants in adults <65 years of age, but not in 

analyses for the elderly. In 12 Canadian studies, PM2.5 and PM10-2.5 were robust to 

adjustment for NO2 in models using only data from the time period when daily PM data 

were available, but effect estimates were not statistically significant in models using data 

from the full time period (Burnett et al., 2004). Dominici et al. (2006) report little 

evidence of effect modification by ozone concentrations in the relationship between 

PM2.5 and hospitalization. 

• Daniels et al. (2004) reported that there was no evidence for a threshold level in the 

PM10-mortality association in analyses of data from the National Morbidity, Mortality 

and Air Pollution Study. 
 23 

• The recent multicity studies continue to report somewhat stronger associations with the 

use of a distributed lag model (Analitis et al., 2006; Zanobetti et al., 2003; Zeka et al., 

2005). In addition, one new analysis shows little evidence that the associations are 

unlikely to represent advancement of death by only a few days (Dominici et al., 2003). 

• The recent studies also report findings that are robust to the use of different analytical 

methods (Roberts and Martin, 2006) and assess the influence of measurement error in 

underestimation of the PM10-mortality association (Zeka and Schwartz, 2004). 

Variation in effects between locations: Numerous new multicity analyses in Europe and 

the U.S. have studied the variation of PM-health associations between locations, and assessed 

factors that may influence heterogeneity in PM-related health effects (Dominici et al., 2003; 

Medina-Ramon et al., 2006; Samoli et al., 2005; Le Tertre et al., 2005; Zeka et al., 2005; Zeka 

et al., 2006). Consistent with the findings available in the 2004 PM AQCD, the recent studies 

highlight exposure differences (e.g., air conditioning use) and the influence of traffic as 

potentially associated with larger effects of PM10. Some recent studies also suggest that 

variability in climate and a number of preexisting health conditions may modify the effects of 

PM. 

New health outcomes: New multicity analyses have also reported associations between 

PM10 and new health outcomes, including emergency admissions for myocardial infarction 

(Zanobetti and Schwartz, 2005), readmission to the hospital for cardiac causes (Von Klot et al., 

2005) and potential changes in physiological cardiac indicators (Ibald-Mulli et al., 2004; 

Timonen et al., 2006)Numerous recent single-city studies also expand of the health endpoints 

that are reported to be associated with PM, generally focusing on PM2.5 exposures. These newly 

reported health endpoints include: (1) indicators of the development of atherosclerosis with longterm PM exposure; (2) indicators of changes in cardiac rhythm, including arrhythmia or 

ST-segment changes; (3) effects on developing children and infants; (4) markers of inflammation 

such as exhaled NO; and (5) effects on organ systems outside the cardiopulmonary systems. 

Numerous new epidemiologic studies have reported associations between PM, primarily using 

PM2.5, and cardiovascular health outcomes such as cardiac arrhythmia, ST segment depression, 

and decreased heart rate variability. New toxicology reports suggest that the brain may be 

affected by exposure to PM, including reports of increases in inflammatory biomarkers and 

neurodegeneration following exposure to CAPs (Campbell et al., 2005; Veronesi et al., 2005). 

Potentially susceptible or vulnerable subpopulations: In the 2004 PM AQCD, people 

with preexisting heart or lung disease, children, and older adults were considered likely to be 

more susceptible to PM-related effects. Recent studies provide increasing evidence that preexisting diseases, particularly diabetes, may increase susceptibility to the cardiovascular effects 

of PM. Goldberg et al. (2006) reported significant associations between PM2.5 and diabetes 

deaths, as well as total mortality in people with previous diagnoses of diabetes. One new 

toxicology study has suggested mechanistic evidence for diabetes-related susceptibility (Proctor 

et al., 2006). Additional research utilizing susceptible animal models of vascular conditions 

(e.g., the Spontaneously Hypertensive rat and the apolipoprotein deficient mouse) have 

demonstrated that exposure to CAPs or surrogate PM can exacerbate symptoms, compromise 

function and potentiate disease states. 
 24 

2.3 Intervention Studies 

The 2004 PM AQCD highlighted the results of several new “intervention” studies or 

“found experiments” that reported associations between reductions in air pollution and 

improvements in public health (2004 PM AQCD, Sections 8.2.3.4 and 9.2.2.6). While few in 

number, these studies were found to provide important support to the epidemiologic evidence 

linking air pollution exposure with adverse health effects. 

One new study reported evidence for reduced mortality risk when ambient pollution 

was decreased (Laden et al., 2006). As discussed briefly above, the authors report a statistically 

significant reduction in mortality risk with reduced long-term fine particle concentrations 

(RR 0.73, 95% CI 0.57-0.95, per 10 μg/m3

 PM2.5). 

Several recent intervention studies have evaluated changes in respiratory health outcomes 

associated with decreased pollution levels; the results of these studies are summarized in 

Table A13 (Appendix A). One U.S. study reported reductions in respiratory medical visits 

with decreased traffic volume that resulted from closure of the Peace Bridge in Buffalo, NY, 

following September 11, 2001 (Lwebuga-Mukasa et al., 2003). Studies conducted in 

Switzerland and East and West Germany have also reported reductions in respiratory symptoms 

or improved lung function with decreases in ambient PM concentrations measured as TSP or 

PM10 (Bayer-Oglesby et al., 2005; Sugiri et al., 2006; Frye et al., 2003; Heinrich et al., 2002). 

In addition, Burr et al. (2003) reported associations between reduced respiratory symptoms and 

reductions in traffic volume. Overall, this group of studies indicates that declining 

concentrations of PM and other pollutants is associated with reduced mortality risk and improved 

respiratory health and thus add substantial support to the evidence available in the 2004 PM 

AQCD. 

2.4 Health Effects Related to Sources or Components of PM 

The current PM NAAQS have been established using PM2.5 and PM10 mass as the 

indicators, as opposed to singling out any particular component or class of particles. This 

decision was based on evidence from epidemiologic studies that reported significant associations 

between various PM components or characteristics, evidence that PM was associated with health 

effects in numerous areas that had differing components or sources of PM, and evidence from 

animal toxicology and controlled human exposure studies that had reported health effects 

associations with high concentrations of numerous fine particle components (e.g., sulfates, 

nitrates, transition metals, organic compounds). 

In the 2004 PM AQCD, epidemiologic and toxicology studies provided evidence for 

effects associated with various fine particle components or size-differentiated subsets of fine 

particles. Toxicology studies reported effects with exposure to different sources or components 

of PM (generally at high levels), such as metals, diesel particles, acid aerosols, and bioaerosols 

(Chapter 7 of the 2004 PM AQCD). The findings of these studies indicated that, for a given 

health response, some fine particle components were more closely linked with that response than 

other components. However, the evidence did not suggest that any component could be singled 

out as potentially the sole contributor to toxicity, or as having no toxic effects. 
 25 

Chapter 8 of the 2004 PM AQCD included a discussion of three new epidemiologic 

studies that reported associations between various health outcomes and different PM 

components. Three new studies that had conducted source-oriented evaluation of PM provided 

new insights into the relationship between fine particles from different sources and mortality. 

While few in number and somewhat preliminary in nature, these studies suggested that a number 

of source types were associated with mortality, including motor vehicle emissions, coal 

combustion, oil burning, and vegetative burning; no associations were reported with the crustal 

factor from fine particles (2004 PM AQCD, Section 8.2.2.5).Considered together, the 2004 PM 

AQCD concluded: “These studies suggest that many different chemical components of fine 

particles and a variety of different types of source categories are all associated with, and 

probably contribute to, mortality, either independently or in combinations” (p. 9-31). 

Conversely, there was no basis to conclude that any individual fine particle component cannot 

be associated with adverse health effects. 

Many new studies have been published in recent years that provide interesting new 

insights into the effects of different sources or types of PM. For the purposes of this provisional 

assessment of new literature published since the release of the 2004 PM AQCD, emphasis has 

been placed on studies that investigated the health effects related to PM sources or comparisons 

of various PM components. To highlight the scientific content of the recent literature while 

focusing on key PM study categories, this section focuses on results of studies that evaluated the 

effects of a range of sources or components. This includes studies that used source 

apportionment, or that compared effects for a range of PM components. Thus, the discussion 

includes: (1) recent epidemiologic studies using source apportionment; (2) epidemiologic 

evidence on effects with PM components; (3) results of new toxicology studies using source 

apportionment with exposures to concentrated ambient particles (CAPs) to provide insight into 

potential effects related to PM from different sources, and comparative toxicology studies using 

fine particle components; and (4) toxicology study results for different surrogates and size 

fractions of PM, including thoracic coarse PM (PM10-2.5). In addition, numerous epidemiologic 

and/or toxicology studies have reported effects of several sources, components, or characteristics 

as discussed in the 2004 PM AQCD. Specific findings for these PM characteristics are not 

discussed in detail; instead, the available new studies are included in reference lists for the 

following categories: 

• ultrafine PM; 

• metals (including residual oil fly ash); 

• traffic; 

• woodsmoke; and 

• endotoxin. 

2.4.1 Epidemiologic Studies Using Source Apportionment 

Some recent epidemiologic studies have employed statistical approaches of source 

contributions from source apportionment analyses in evaluating associations of health effects 

with particular source categories of PM. Since source apportionment analysis is based on 

finding independent groupings of chemical components, the source categories should not 

confound each other. 
 26 

 A workshop was held in May 2003 during which several groups determined source 

category contributions (using multiple techniques) using ambient PM chemical concentration 

data from Washington, D.C. (U.S. Park Service, IMPROVE) and from Phoenix (U.S. EPA). 

An intercomparison of the source apportionment results was also published (Hopke et al., 2006). 

The statistical associations of these source category contributions with total (non-accidental) and 

cardiovascular mortality were then determined by Ito et al. (2006) for Washington and Mar et al. 

(2006) for Phoenix. The results from different groups varied, in part depending on the 

participants’ experience and expertise with source apportionment and time-series epidemiologic 

analyses (Appendix A; Table A14). Although several groups separated the traffic source into 

diesel and gasoline, for the reported analyses, all traffic-related source categories were summed 

into a “traffic” source category. For Washington, DC, the correlations of daily contributions of 

source categories across the various investigators/techniques were fair for crustal, secondary 

sulfate, secondary nitrate, primary residual oil combustion, and incinerator, but poor for traffic, 

wood burning, and salt (correlation not reported for primary coal combustion). In Phoenix, AZ, 

the correlations of daily contributions across the various investigators and analysis techniques 

were high for traffic, secondary sulfate, and sea salt, and low for biomass burning, metals, and 

primary coal burning. 

In Washington, DC, secondary sulfate and primary coal combustion were statistically 

significant with total mortality on lag day 3. PM2.5 had a statistically significant relationship with 

total mortality on lag day 1 and 3 before controlling for temperature, but only on lag day 3 after 

controlling for temperature. For cardiovascular mortality, no source categories were statistically 

significant across all investigators/techniques. However, for one or more analyses, statistically 

significant results were found for soil (lag 2, 3, and 4), traffic (lag 3), secondary sulfate (lag 0 

and 3), residual oil (lag 0), wood smoke (lag 3), and primary coal burning (lag 3). The 

Washington, DC samples were collected on Saturday and Thursday only; so, each lag has a 

different set of mortality days which may introduce some uncertainty into the lag structure. 

 In Phoenix, only sea salt (lag 5) was statistically significant with total mortality for all 

analyses, while 3/5 data sets gave statistically significant results for Cu smelter (lag 0) and 1/8 

for sulfate (lag 0). For cardiovascular mortality, most data sets gave statistically significant (or 

nearly so) associations for traffic (lag 1, 6/9), secondary sulfate (lag 0, 6/8), sea salt (lag 5, 6/6), 

and Cu smelter (lag 0, 3/5). Data sets from both cities show secondary sulfate as the source 

category with the highest statistically significant relative risk (5-95th percentile increments), 

although the lag days and mortality categories differ by city (lag 0 for cardiovascular mortality in 

Phoenix, AZ, and lag 3 for total mortality in Washington, DC, with some Washington, DC, data 

sets reporting lags 0 and 3 for cardiovascular mortality). A generalized traffic source is 

implicated for cardiovascular mortality at lag 1 in Phoenix, AZ and lag 3 in Washington, DC. 

 One study used source apportionment techniques to assess relationships between 

cardiovascular morbidity and acute fine particle exposure in a panel of healthy young male patrol 

officers in Wake County, NC. Riediker et al. (2004) reported the strongest associations between 

a “speed change” factor (Cu, S, and aldehydes) and a number of cardiovascular health indicators. 

There were suggested associations with a gasoline combustion factor, and there was limited 

evidence for associations with fine particles of crustal origin. 
 27 

 Taken together, the results of these new studies are consistent with previously-available 

evidence that link health outcomes with fine particles from a range of sources, including motor 

vehicles and combustion of oil or coal. The use of source categories in community time-series 

epidemiology shows promise but additional work is needed in characterizing the various sources, 

understanding the spatial variability of the different source categories, and obtaining daily 

composition and concentration data for periods of several years in additional cities. 

2.4.2 Epidemiologic Studies on Effects of Fine Particle Components 

As summarized in Section 8.2.2.5 of the 2004 PM AQCD, epidemiologic studies have 

reported generally positive, often statistically significant associations between various fine 

particle components and mortality. Numerous studies have reported associations between shortterm sulfate exposures and mortality and morbidity; the effect estimates reported for mortality 

range from about 1 to 9% increases in mortality per 5 μg/m3

 increase in ambient sulfate 

concentration (as shown in Figure 8-6 of the 2004 PM AQCD). Associations have also been 

reported with other PM components, including carbonaceous components (elemental carbon, 

organic carbon, and coefficient of haze), nitrates, and metals. 

Associations between mortality and long-term exposure to ambient sulfates was reported 

in prospective cohort studies, with effect estimates reported in the range of 11 to 50% increases 

in mortality per 15 μg/m3 increase in sulfates (2004 PM AQCD, Table 8-15). Prospective cohort 

studies have also reported associations between long-term exposure to sulfates and respiratory 

effects, such as prevalence of chronic bronchitis (2004 PM AQCD, section 8.3.3.2). 

Several recent epidemiologic studies have evaluated associations between short-term 

exposure to fine particle components and various health outcomes, as shown in Table A15 

(Appendix A). Overall, this group of studies reports associations between mortality and 

morbidity with several fine particle components. A number of studies report associations with 

sulfates that are generally consistent with those in earlier reports. Several recent studies have 

also shown associations with the organic carbon and elemental carbon components of fine 

particles. 

• For mortality, significant associations were reported with sulfates in a new study in 

Montreal (Goldberg et al., 2006), and a positive, borderline significant, association with 

sulfates was reported in a study of 12 Canadian cities (Burnett et al., 2004). Positive, but 

not statistically significant, associations between mortality and fine particle sulfates was 

reported in Vancouver (Villeneuve et al., 2003). A study in Atlanta also evaluated 

associations with other fine particle components, and reported positive but not significant 

associations between mortality and sulfates and EC, OC, and not association with nitrates 

(Klemm et al., 2004). 

• For emergency department visits, two reports from the ARIES study in Atlanta evaluated 

associations between short-term fine particle component exposures and visits for 

cardiovascular or respiratory diseases (Metzger et al., 2004; Peel et al., 2005). Both 

studies report no significant associations for short-term exposures to either sulfates or 

water-soluble metals with visits for cardiovascular or respiratory diseases. Significant 
 28 

associations were reported between OC and EC and emergency department visits for all 

cardiovascular diseases and congestive heart disease (Metzger et al., 2004). No 

significant associations were reported between any component and respiratory visits, 

except for an association between OC and emergency department visits for pneumonia 

(Peel et al., 2005). 

• For cardiovascular health outcomes, one study that was conducted in Boston, MA 

reported a significant association between short-term sulfate exposure and percent change 

in brachial artery diameter, an indicator of vascular reactivity (O’Neill et al., 2005); other 

components were not evaluated. 

• For respiratory health outcomes, medical visits for asthma in children and lower 

respiratory infections (all ages) were associated with the EC and OC components of fine 

particles in Atlanta, but no associations were reported with sulfates or acidity (Sinclair 

and Tolsma, 2004). Metals were positively associated with medical visits for lower 

respiratory infection, but not for other outcomes. For adult asthma and upper respiratory 

infections, there were no significant positive associations with any of the fine PM 

components; however, sulfates were negatively associated with upper respiratory 

infection visits (Sinclair and Tolsma, 2004). In a panel study of Hispanic children, OC 

and EC (measured in PM10) were significantly associated with asthma symptoms; other 

PM components were not included in this study (Delfino et al. 2003). 

 In addition, one recently published epidemiologic study has also assessed associations 

between mortality and long-term exposure to fine particle components (see Table 1). Mortality 

was significantly associated with long-term exposure to four fine particle components (EC, 

nitrates, nickel, and vanadium), and a positive but not statistically significant association was 

reported with sulfates using the Veterans cohort (Lipfert et al., 2006b, in press). 

2.4.3 Toxicology Studies—Source Apportionment and Fine Particle Components 

There were nine studies in the 2004 PM AQCD that investigated the effects of fine 

particle CAPs exposure in humans and laboratory animals (Sections 7.2.2 and 7.3.1). The results 

of these studies generally showed associations between the CAPs exposure and cardiovascular 

parameters. Effects on the respiratory system were largely absent for pulmonary function, but 

were present for markers of inflammation. Source apportionment was largely absent in the 

previous CAPs studies, although some evidence linked transition metal components in ambient 

PM with lung injury. Additionally, as CAPs composition varies day-to-day, it is difficult to 

establish clear relationships between individual components and adverse health effects. The 

2004 PM AQCD pointed to a “critical need for the systematic conduct of studies in the potential 

respiratory effects of major components of PM from different regions of the U.S., in recognition 

that PM of different composition and from different sources can vary markedly in its potency for 

producing different respiratory effects” (2004 PM AQCD, p. 7-85). 

 Toxicological studies employing CAPs offer a relevant surrogate for atmospheric PM. 

As ambient PM is just one component of a complex mixture that interacts with gases and other 

aerosols, CAPs systems provide a method of exposing subjects to the particle phase. Gases 
 29 

(such as O3 and SO2) are not concentrated and organic PM components in CAPs likely differ 

from components in ambient PM, particularly for ultrafine CAPs systems (Su et al., 2006). 

Similarly, thoracic coarse PM is not enriched (except for the coarse particle concentrator) and 

only certain systems are capable of concentrating ultrafine PM. 

There are three main CAPs exposure systems currently in use. The Harvard Air Particle 

Concentrator (HAPC) uses virtual impactor technology to concentrate particles from 0.15 to 

2.5 μm (Sioutas et al., 1997). The versatile aerosol concentration enrichment system (VACES) 

is also based on virtual impactor technology and concentrates ultrafine particles, as well as those 

in the fine particle range (Sioutas et al., 1999). It is important to note that both ultrafine systems 

(HAPC and VACES) do not uniformly concentrate particles across all size fractions and that the 

enrichment factor has been shown to decrease for PM sized <75 nm (Su et al., 2006). The 

centrifugal concentrator most efficiently concentrates particles in the 0.5–2.5 μm size range 

(Gordon et al., 1998). For the purposes of this provisional assessment, CAPs studies have been 

grouped into those that conducted source apportionment analyses or those that linked PM 

components to health outcomes. Additional CAPs studies that reported linkages between mass 

and toxicity are presented in a subsequent section. 

 Among the recent toxicology studies are 27 new studies reporting effects of CAPs 

exposure. These include several reports from a large study of subchronic exposure to CAPs that 

was carried out using three different mice strains. Four of the acute and one subchronic study 

(with an additional in vitro study) performed complex source apportionment or factor analyses. 

Eight (three human and five animal studies) used regression approaches to estimate the 

relationship between health effects and the concentration of individual PM constituents. 

Additional exposure details, endpoints, and results for all of the CAPs studies are provided in 

Appendix A (Tables A16–A18); the tables present only those findings that were positive in the 

“Results” column. 

Source Apportionment Studies 

Table 2 shows those endpoints which were associated with various source categories 

from humans exposed to Chapel Hill, NC, CAPs (Huang et al., 2003b) and mice exposed 

subchronically to Tuxedo, NY, CAPs (Lippman et al., 2005b). Increases in blood fibrinogen 

levels in healthy humans were correlated with a Cu-Zn-V factor (stated by the authors to be 

linked to combustion, including oil combustion) in the acute exposure study (Huang et al., 

2003b). In addition, elevated polymorphonuclear leukocytes in bronchoalveolar lavage fluid 

(BALF) were observed with CAPs, and this increase was associated with a Fe-Se-sulfate factor; 

the authors considered this factor to represent sulfurous smog and photochemical air pollution. 

There were no other identifiable CAPs factors that were linked to any health outcome. 

Using mouse models, Lippmann et al. (2005b) reported post-exposure decreases in heart 

rate variability (HRV) parameters in subchronic exposures to CAPs for three factors—secondary 

sulfate, residual oil, and motor vehicles—but an increase in HRV parameters with a CAPs factor 

representing resuspended soil. Similar findings were reported for heart rate, with slight increases 

and decreases being observed for different source categories at one interval or another. 
 30 

Table 2. CAPs Sources and Associated Endpoints: Acute and Subchronic Exposures

Source 

Category Endpoint Affected Time Species Reference 

Zn-Cu-V ↑ blood fibrinogen 18 hr post-exposure Human Huang, Y-C.T 

(2003) 

Fe-Se-sulfate ↑ BALF PMN 18 hr post-exposure Human Huang, Y-C.T 

(2003) 

Secondary 

sulfate 

(S, Si, OC) 

↓ HR 

↓ SDNN, ↓ RMSSD 

Afternoon post-exposure 

Night post-exposure 

ApoE-/-mouse Lippmann et al. 

(2005b) 

Resuspended soil 

(Ca, Fe, Al, Si) 

↓ HR 

↑ HR 

↑ SDNN, ↑ RMSSD 

During exposure 

Afternoon post-exposure 

Night post-exposure 

ApoE-/- mouse Lippmann et al. 

(2005b) 

Residual oil 

(V, Ni, Se) 

↓ SDNN, ↓ RMSSD Afternoon post-exposure ApoE-/-mouse Lippmann et al. 

(2005b) 

Motor 

vehicle/other 

↓ RMSSD Afternoon post-exposure C57 mouse Lippmann et al. 

(2005b) 

As shown in Table 2, not all source categories were linked to HR or HRV parameters at 

any given time during or after exposure. 

One in vivo study employed rats and mice (Steerenberg et al., 2006) which were exposed 

to one of five PM types collected from Europe. The traffic, industry/combustion/incinerator, and 

wood smoke source clusters were associated with the adjuvant activity for respiratory allergy, 

whereas the secondary inorganic/long range cluster correlated with systemic allergy (Steerenberg

et al., 2006). The crustal material and sea spray sources were linked to acute inflammation, 

although the endotoxin content also correlated with some of these biomarkers (Steerenberg et al., 

2006). 

In the remaining CAPs studies that included source apportionment, Batalha et al. (2002) 

reported changes in lumen/wall ratio, an indicator of vasoconstriction, with sulfate and Si 

(suggested to be an indicator of road dust) in normal rats and with OC in chronic bronchitic rats. 

Wellenius et al. (2003) also linked a cardiovascular response, ST-segment elevation, with Si and 

other crustal elements derived from Boston CAPs. In the latter study, there were a number of 

tracer elements that were not associated with any electrocardiogram measure, including Ni, S, 

and carbon black. 

Studies of fine particle components in CAPs 

 In addition, six CAPs studies have reported associations between observed cardiovascular 

or respiratory endpoints and specific PM constituents. Table 3 presents more specific results, 

and the overall findings are briefly summarized below: 
 31 

Table 3. CAPs Components and Associated Endpoints for Acute Studies 

Component Endpoint Affected Species Reference

Al lipid peroxidation 

oxidative stress (heart) 

rat 

rat 

Rhoden et al. (2004) 

Gurgueira et al. (2002) 

Si lipid peroxidation 

oxidative stress (heart) 

lumen/wall ratio 

ST-segment elevation 

rat 

rat 

rat 

dog 

Rhoden et al. (2004) 

Gurgueira et al. (2002) 

Batalha et al. (2002) 

Wellenius et al. (2003) 

Fe lipid peroxidation 

oxidative stress (lung) 

oxidative stress (heart) 

rat 

rat 

rat 

Rhoden et al. (2004) 

Gurgueira et al. (2002) 

Gurgueira et al. (2002) 

Zn oxidative stress (lung) 

plasma fibrinogen 

rat 

rat 

Gurgueira et al. (2002) 

Kodavanti et al. (2005) 

Mn oxidative stress (lung) rat Gurgueira et al. (2002) 

Cu oxidative stress (lung) rat Gurgueira et al. (2002) 

Ti oxidative stress (heart) rat Gurgueira et al. (2002) 

Sulfate FEV1 decrements 

FVC decrements 

lumen/wall ratio 

human (+NO2) 

human (+NO2) 

rat 

Gong et al. (2005) 

Gong et al. (2005) 

Batalha et al. (2002) 

OC brachial arterial diameter 

diastolic blood pressure 

lumen/wall ratio 

human 

human 

rat 

Urch et al. (2004) 

Urch et al. (2005) 

Batalha et al. (2002) 

EC brachial arterial diameter 

lumen/wall ratio 

human 

rat 

Urch et al. (2004) 

Batalha et al. (2002) 

Pb lumen/wall ratio rat Batalha et al. (2002) 

• Si—oxidative stress and cardiovascular endpoints; 

• Fe—oxidative stress; 

• OC and EC—cardiovascular effects; 

• Zn—oxidative stress and fibrinogen; and 

• Sulfate—pulmonary and cardiovascular effects. 

Fine Particle CAPs Studies Without Source Apportionment or Identified Components 

 Effects on the cardiovascular system have been reported in a number of human studies. 

Markers of cardiovascular function, such as brachial arterial diameter and blood pressure, have 

been shown to decrease with CAPs exposure (Urch et al., 2004, 2005). Increased occurrence of 

ectopic and abnormal beats has also been reported in healthy and COPD subjects with exposure 

to CAPs (Devlin et al., 2003). Similar to studies cited in the 2004 PM AQCD, elevated blood 

fibrinogen levels were observed in volunteers exposed for two hours to Chapel Hill, NC CAPs 
 32 

(Ghio et al., 2003). Hematological alterations, including increased peripheral basophils (Gong 

et al., 2004a) and decreased white blood cell counts (Ghio et al., 2003), have also been reported. 

Two recent studies measuring heart rate (HR) and heart rate variability (HRV) have 

demonstrated that a single two-hour exposure to CAPs from Los Angeles, CA, or Chapel Hill, 

NC, can result in decreased HRV in human volunteers (Devlin et al., 2003; Gong et al., 2004a). 

Interestingly, in the Los Angeles studies, healthy subjects were reported to have greater 

decreases in HRV compared to compromised individuals with COPD (Gong et al., 2004a). 

 In addition, a few studies have reported some associations with respiratory health 

endpoints. Arterial oxygen saturation decreased in healthy and COPD patients exposed for two 

hours to PM2.5 Los Angeles CAPs (Gong et al., 2005). Elevated polymorphonuclear leukocytes 

in bronchioalveolar lavage fluid were observed in healthy volunteers at 18-hr post-exposure to 

Chapel Hill, NC, CAPs (Ghio et al., 2003). Of the two recent fine CAPs studies that measured 

pulmonary function, only one showed decreased maximal mid-expiratory flow, forced expiratory 

volume and forced vital capacity and the latter two responses were only observed with coexposure to NO2 (Gong et al., 2005); the other study did not report any changes in spirometry or 

respiratory symptoms (Gong et al., 2004a). 

To date, the CAPs animal studies reported in the scientific literature have been of 

relatively short duration (i.e., four weeks or less). There is one large subchronic PM inhalation 

study in the recent literature on toxicological effects of repeated exposures to ambient particles in 

mice exposed to Tuxedo, NY, CAPs for five or six months during the spring and summer of 

2003 (Lippmann et al., 2005a; Sun et al., 2005). Following CAPs exposure, mice models of 

aortic and/or coronary atherosclerosis had altered HR and HRV (Chen and Hwang, 2005; Hwang

et al., 2005; Lippmann et al., 2005b), advanced plaque deposits and lesions in the aorta and heart 

(Chen and Nadziejko, 2005), and changes in vasomotor tone (Sun et al., 2005). Additional 

molecular and biochemical analyses demonstrated altered gene expression post-exposure, 

including those genes involved in the regulation of circadian rhythm, heat shock, inflammation, 

and signal transduction (Gunnison and Chen, 2005). CAPs exposure also induced 

neurodegeneration in the substantia nigra nucleus compacta of ApoE-/- mice (Veronesi et al., 

2005). Interestingly, subchronic CAPs-exposure did not appear to cause pulmonary effects in 

any mouse strain. 

Finally, three reports do not specifically link PM components to health endpoints, but two 

draw inferences that relate the effects seen with a heavy industrial source located near the study 

site (Dvonch et al. 2004; Morishita et al., 2004). One additional study of mice exposed to fine 

CAPs in Los Angeles, downwind of heavily trafficked highways, demonstrated effects on 

biomarkers of inflammation in the brain (Campbell et al., 2005). Additionally, in the one in vitro

study that applied factor analysis to CAPs for cytokine release, the oil-fired power plant emission 

source (comprised of V, Ni, and Se) was linked to the response, but not the regional secondary 

sulfate or resuspended soil factors (Maciejczyk and Chen, 2005). Considered as a group, these 

new studies suggest that many fine particle components can adversely affect health, and that PMassociated cardiovascular and respiratory effects may be linked to resuspended soil, regionally 

transported air pollution, and combustion or industrial sources. 
 33 

2.4.4 Toxicology Studies—Thoracic Coarse Particles 

Few studies examined the effects of thoracic coarse PM on cellular responses prior to the 

release of the 2004 PM AQCD. When considered together, the four in vitro studies discussed in 

Chapter 7 of the 2004 PM AQCD document provided some evidence that exposure to thoracic 

coarse PM may result in proinflammatory effects, as well as cytotoxicity and oxidant generation 

(Section 7.4.2). However, as little data was available at that time on thoracic coarse PM toxicity, 

a very limited evaluation of the literature was conducted. Recent publications include sixteen 

new studies (one human, six in vivo, and nine in vitro) that have specifically focused on the 

thoracic coarse fraction of PM, with the majority of these providing direct comparisons with 

smaller size fractions (i.e., fine and ultrafine). 

In one important new study, healthy and asthmatic humans were exposed to CAPs via a 

high concentration efficiency coarse particle concentrator, in which 80% of the PM mass was 

comprised of the thoracic coarse fraction (Gong et al., 2004b). Exposure to thoracic coarse 

CAPs from Los Angeles also caused lowered HR and HRV. Asthmatics exposed to thoracic 

coarse Los Angeles CAPs had no changes in arterial oxygen saturation (Gong et al., 2004b). 

Healthy subjects were reported to have greater decreases in HRV compared to compromised 

individuals with COPD (Gong et al., 2004b). 

Two in vitro studies evaluated cytokine release and cell viability following exposure to 

PM2.5 soil dusts from a variety of southwestern U.S. locations (Veranth et al., 2004, 2006). The 

responses were quite variable and did not appear to be attributable to sample location category 

(e.g., urban/rural, road surface/open land, military/civilian) or endotoxin content. A multivariate 

analysis of the findings demonstrated a handful of correlations with soil dust constituents 

(Veranth et al., 2006). 

The in vivo rodent studies provide evidence that the observed effects from exposure 

(via non-inhalation routes) to thoracic coarse or fine PM are related to the endotoxin or allergen 

levels, which were often associated with sampling location. These effects included elevated 

cytokine release (Nygaard et al., 2005; Schins et al., 2004) and adjuvant activity (Steerenberg 

et al., 2005). Schins et al. (2004) reported differences between thoracic coarse PM from rural 

and urban areas in The Netherlands, with greater responses for elevated neutrophils and tumor 

necrosis factor-α in BALF from rural PM, but greater induction of macrophage inflammatory 

protein-2 in vitro from urban PM (both PM types contained relatively high levels of endotoxin). 

Otherwise, the thoracic coarse fraction tended to induce similar toxic responses as that observed 

with the fine fraction. In the one study that employed coal fly ash, no differences in effects were 

reported for the thoracic coarse fraction compared to saline control animals (Gilmour et al., 

2004). 

Similar to the in vivo research with surrogate and size-fractionated PM, in vitro studies 

have also shown associations between the induction of inflammatory mediators and PM 

endotoxin content (Huang et al., 2003a; Pozzi et al., 2003), whereas others have found seasonal 

relationships with thoracic coarse PM effects (Becker et al., 2005b; Hetland et al., 2005; Li et al., 

2002). The latter finding could be partially attributable to microbial products or their 

interactions with metals (Hetland et al., 2005). Becker et al. (2005b) further examined possible 

associations between cellular responses and PM components using principal component analysis 
 34 

and reported a Cr/Al/Si/Ti/Fe/Cu factor correlating with IL-6 and IL-8 release. Examination of 

IL-6 induction in alveolar macrophages and IL-8 release in normal human bronchial epithelial 

cells following thoracic coarse PM exposure showed associations with Toll-like receptor 

(TLR) 4 and TLR2 gene expression, respectively (Becker et al., 2005a). Generation of hydroxyl 

radicals has also been recently observed with thoracic coarse PM (Shi et al., 2003). In contrast, 

some studies have also demonstrated greater effects with the fine or ultrafine size fraction 

compared to thoracic coarse PM (Li et al., 2002; Li et al., 2003; Gilmour et al., 2004). 

2.4.5 Toxicology Studies—Comparison of Ambient PM 

There were numerous studies included in the 2004 PM AQCD that employed ambient 

particles collected on filters. These included extracts of collected or stored PM and the majority 

of studies utilized Ottawa (EHC-93) or Provo, Utah PM10. Generally, animals exposed to these 

particles had elevated biomarkers of pulmonary injury and inflammation, as well as systemic and 

cardiovascular responses (Chapter 7). The 2004 PM AQCD stated that studies using collected 

urban PM “have provided evidence indicating that the chemical composition of ambient particles 

can have a major influence on toxicity” (Section 7.10.2.1, pg 7-127). The results of research 

published since 2002 have largely supported and expanded the findings of previous studies cited 

in the 2004 PM AQCD. Five studies are highlighted which evaluated the toxicity of urban PM 

or that collected on filters (one human, two in vivo, and two in vitro). Further details on these 

studies are included in Table A19 (Appendix A). 

Two recent studies investigated the effects of urban (Hettstedt) and rural (Zerbst) 

particles (PM2.5) on lung inflammation and pulmonary function in humans and rodents (Gavett 

et al., 2003; Schaumann et al., 2004). In healthy human volunteers, instillation of either PM 

induced airway inflammation, whereas Hettstedt PM resulted in greater influxes of BALF 

monocytes and increased oxidant radical generation compared Zerbst PM (Schaumann et al., 

2004). In allergic mice, exposure to either PM type induced lung injury and proinflammatory 

cytokines (Gavett et al., 2003). However, aspiration of Hettstedt PM caused heightened airway 

responsiveness and elevated lung inflammatory cells in sensitized mice exposed before allergen 

challenge (Gavett et al., 2003). The endotoxin content was below 0.32 EU/mg in both PM 

samples. 

Two other in vivo toxicology studies examined the cardiovascular and cytogenetic effects 

of urban PM exposure (Rhoden et al., 2005; Soares et al., 2003). Rhoden et al. (2005) compared 

autonomic nervous system (ANS) effects between Boston CAPs (via inhalation) and SRM 1649 

(via intratracheal instillation). Both particles altered ANS function and these changes preceded 

and were required for increased cardiac reactive oxygen species generation (Rhoden et al., 2005). 

Soares et al. (2003) measured micronuclei (MN) in peripheral erythrocytes of mice exposed to 

urban air of Sao Paulo or Atibaia, Brazil (with the latter being a rural location) and reported that 

there were significant increases in MN frequency for mice exposed to the Sao Paulo atmosphere. 

The results of recent studies assessing effects of different components from different 

particle samples or size classes are summarized in Table 4, along with other studies that 

attempted to link in vitro effects with PM components (discussed in the preceding section). 
 35 

Table 4. PM Components, Size Fractions, and Associated In Vitro Toxicity 

Component Endpoint Affected Size Fraction Cell Type Reference

Br IL-8 Fine BEAS-2B Veranth et al. (2006) 

Cr IL-8 

IL-8 

TNF-α

Fine, ultrafine 

Fine 

Ultrafine 

NHBE 

BEAS-2B 

RAW 264.7 

Becker et al. (2005b) 

Huang et al. (2003a) 

Huang et al. (2003a) 

Cu Hydroxyl radical 

8-OHdG formation 

Coarse 

Coarse 

A549 

A549 

Shi et al. (2003) 

Shi et al. (2003) 

Si IL-6 Coarse Human AM Becker et al. (2005b) 

Fe IL-6 

TNF-α

Coarse, fine 

Ultrafine 

Human AM 

RAW 264.7 

Becker et al. (2005b) 

Huang et al. (2003a) 

Mn IL-8 

Cell viability 

Fine 

Fine 

BEAS-2B 

BEAS-2B 

Huang et al. (2003a) 

Veranth et al. (2006) 

Ni IL-6 Fine BEAS-2B Veranth et al. (2006) 

OC Lipid peroxidation 

IL-6 

Hydroxyl radical 

Fine 

Fine 

Ultrafine 

BEAS-2B 

BEAS-2B 

BEAS-2B 

Huang et al. (2003a) 

Veranth et al. (2006) 

Li et al. (2003) 

EC Lipid peroxidation 

IL-6 

Fine 

Fine 

BEAS-2B 

BEAS-2B 

Huang et al. (2003a) 

Veranth et al. (2006) 

 These recent studies continue to show that exposure to different types of surrogate fine 

PM is associated with a range of health outcomes, particularly those related to the cardiovascular 

system. These findings also expand upon the body of evidence related to the effects of thoracic 

coarse particles and PM composition. Exposure to thoracic coarse particles has been linked with 

a number of effects, including inflammatory mediator release and reactive oxygen species 

generation. The results are still too limited to draw conclusions about specific thoracic coarse 

particle components and health outcomes, but it appears that endotoxin and metals potentially 

play roles in the observed responses. While these studies provide interesting new insight into 

potential links between different types of particles and observed effects, it is much too early to 

distinguish any PM components as being primarily responsible for any specific effect or 

conversely, as not involved in any toxicological response. 

2.4.6 Studies of Specific Fine Particle Components or Characteristics 

Toxicological evidence on the effects of different types of particles or particle 

components was discussed in Section 7.10.2 of the 2004 PM AQCD. The particle characteristics 

or sources discussed included acid aerosols, metals, diesel exhaust particles, organic 

components, ultrafine particles and bioaerosols. In addition to the discussions above, EPA 

observes that numerous recent individual toxicology studies have investigated the effects of 

exposure to these particle components or characteristics. For this provisional assessment, 

EPA has not critically reviewed the large number of studies that have assessed effects of 
 36 

individual components, but will highlight below the general nature of the new findings. 

Bibliographies for these groups of particle types or characteristics are included in Attachment B. 

The main overarching conclusion from these groups of studies is that the recent studies 

generally substantiate and support conclusions drawn from earlier work. For example, numerous 

studies had suggested that metals (e.g., transition metals such as V or Ni) contributed to the toxic 

effects observed with PM exposures (albeit at generally high exposure levels). Recentlypublished studies provide more evidence that metal constituents of particles may play important 

roles in PM-related toxicity. 

 Ultrafine Particles: The 2004 PM AQCD had an extensive discussion of the physical 

and chemical properties and behavior of ultrafine particles (diameter <0.1 μm). A growing body 

of evidence from toxicology studies indicated that ultrafine particles were linked with a number 

of health outcomes; however, there was very limited information on the health effects of 

ultrafine particles from epidemiologic studies. The 2004 PM AQCD observed that acute 

exposures to ultrafine particles were associated with slight increases in blood viscosity and with 

respiratory symptoms or decreased lung function, and one study had reported associations with 

mortality. Toxicological studies used various types of ultrafine model particles (e.g., carbon 

black), and reported greater inflammatory responses when compared at the same mass of fine 

particles of the same chemical composition at similar mass doses (2004 PM AQCD, p. 7-221). 

Hence, in the ambient environment where fine particle mass greatly exceeds ultrafine mass, it 

remains to be determined whether this relative difference in potency is reflected in real world 

exposures. 

Since April 2002, about 60 recent studies have evaluated effects of ultrafine particles, and 

over 150 have assessed effects associated with diesel exhaust or traffic-related PM (see 

Attachment B). Diesel and other forms of traffic are considered to be major sources of 

atmospheric ultrafine PM. Recent toxicology studies continue to indicate that ultrafine particles 

have effects and many toxicology studies indicate that, on a mass basis, ultrafine particles are 

more toxic than fine particles. Ultrafine particles have been observed to translocate from the 

olfactory mucosa to the brain and from the lungs to the liver and the systemic circulation. 

However, a number of uncertainties remain regarding the extent of ultrafine particle 

extrapulmonary translocation, including clearance rates and routes (e.g., lymphatic system or 

gastrointestinal tract). Ultrafine particles appear to enter cells and cause mitochondrial damage, 

based on evidence from in vitro studies. Most studies using laboratory-generated carbon 

particles do not demonstrate lung inflammation, but report cardiac and vascular effects. 

Additionally, exposure to ambient ultrafine PM causes lung inflammation that is associated with 

organic carbon carried by the ultrafine particles. A few epidemiologic studies have associated 

health effects with particle number, particle surface area, or active surface area, all variables that 

are thought to be associated more with ultrafine than fine particles. As was true in the 2004 PM 

AQCD, the epidemiologic studies generally do not indicate that ultrafine PM is more strongly 

associated with health effects than fine PM. In general, studies report associations between both 

fine and ultrafine particles, and in a number of cases the associations are reported to be stronger 

for fine than for ultrafine PM. Thus, further evaluation is needed on effects of ultrafine particles 

in the next review of the PM NAAQS. 
 37 

Sulfates and Acid Aerosols: As stated in the 2004 PM AQCD, there is “little new 

information on the effects of acid aerosols.” There was a much more extensive discussion on the 

toxicity of sulfates in Section 11.2 of the previous PM AQCD (U.S. EPA 1996), which 

concluded that human and animal toxicology studies indicated that acid aerosols are associated 

with small changes in pulmonary function, but generally at concentrations greater than those 

measured in ambient air. The results of four recent acid aerosol toxicological studies generally 

agree with conclusions in the 2004 PM AQCD. Three of these studies involve controlled human 

and animal exposures to acid aerosols with or without gaseous co-pollutants such as ozone (O3). 

One study employed in vitro techniques to assess the toxic effects of sulfate on different cell 

types, including alveolar macrophages and blood polymorphonuclear leukocytes. As shown in 

Table A20 the recent studies reported limited evidence for effects with exposure to sulfuric acid 

or sulfate aerosols. One study found that there was some suggestion for interactive effects with 

ozone (Kleinman et al., 2003). There were no new toxicological studies published in the last 

four years that utilized nitrate aerosols (i.e., ammonium nitrate or nitric acid) to examine health 

outcomes. 

Diesel exhaust particles: This source of particles has been the subject of numerous 

studies; the 2004 PM AQCD highlighted findings from the Diesel Health Assessment Document 

along with some additional studies. There are a number of new studies which have investigated 

the toxicity of diesel exhaust by eliminating the particle or gas portion of the exposure 

atmosphere or by separating the organic constituents from the carbonaceous core. Some studies 

have suggested that the gases, organic particle compounds, or particle core are responsible for 

the observed effects, and it is likely that all exhaust components contribute to toxicity. 

Comparison of these results across laboratories or studies is difficult, as the composition of 

diesel exhaust is highly dependent upon the generation method. 

Traffic-related particles: A large body of literature is accumulating on a range of health 

effects that may be associated with exposure to traffic. These exposures include both particulate 

and gaseous pollutants and the reported findings include cardiovascular responses, inflammatory 

changes, allergenic effects, and mutagenicity. Toxicology studies and a partially annotated 

bibliography of epidemiologic studies are included in Attachment B. 

Organic compounds: Little evidence was available on effects of particulate organic 

compounds in the 2004 PM AQCD (Section 7.10.2.5). A number of the recently published 

studies have used fine particle speciation data, along with factor analysis methods, to assess 

potential effects of the organic component of fine PM. Previous studies indicated that PM 

organic compounds (e.g., PAHs) can be mutagenic. However, few studies had provided 

information on potential associations with other health endpoints. Recent study results suggest 

that organic constituents of ambient PM can be linked to a number of biomarker and 

physiological responses, such as lipid peroxidation and oxidative stress generation, cytokine 

release, elevated plasma fibrinogen, and decreased diastolic blood pressure and vessel diameter. 

Metals: As stated in Section 7.10.2.3 in the 2004 PM AQCD, the effects of metals 

leached from ambient filter extracts or residual oil fly ash have been shown to consistently result 

in cell injury and inflammation (albeit often at high concentrations). A number of new studies 

have reported that exposure to metals results in detectable health effects (see Attachment B). 
 38 

These recent studies highlight findings for several metals which may be involved in PM 

toxicological effects, including Fe, Zn, V, and Ni. Furthermore, the activation of select 

pro-inflammatory pathways with metal exposure has been linked to particular cell surface 

receptors. Other research suggests a role for metal-containing PM (including those derived from 

oil or coal combustion sources) in altering cardiovascular parameters, which is consistent with 

the epidemiological findings. 

Conclusions

 Recent analyses continue to indicate that particles related to traffic, residual oil 

combustion, wood smoke, and regional sulfate pollution and primary coal burning are associated 

with increased mortality. A number of new studies continue to indicate that traffic-related PM 

exposures are associated with mortality and morbidity. Recent epidemiologic observations 

continue to support associations between various fine PM components and both mortality and 

morbidity effects. 

3. SUMMARY AND CONCLUSIONS 

The new study results support and expand upon findings in the 2004 PM AQCD and 

provide interesting new insights into relationships between ambient particles and health effects. 

The essential conclusions of this provisional assessment are that the science supporting 

evaluation of the potential health impacts of PM on human health continues to expand and hence 

provides a larger knowledge base for better characterizing the relationships between fine and 

thoracic coarse particles and health effects. The new studies provide important insights on the 

health effects of PM exposure, but the results do not dramatically diverge from previous 

findings. We find that: (a) the new studies generally strengthen the evidence that acute and 

chronic exposures to fine particles and acute exposure to thoracic coarse particles are associated 

with health effects, (b) some of the new epidemiologic studies report effects in areas with lower 

concentrations of PM2.5 or PM10-2.5 than earlier reports; (c) new toxicology and epidemiologic 

studies link various health outcomes with a range of fine particle sources and components, in 

particular from traffic-related pollution; and (d) new toxicology studies report effects of thoracic 

coarse particles, but do not provide evidence to support distinguishing effects from exposure to 

urban and rural particles. This survey and provisional assessment of new studies does not 

materially change any of the broad scientific conclusions regarding the health effects of PM 

exposure made in the 2004 PM AQCD. 

In brief, this provisional assessment found: 

• Recent epidemiologic studies, most of which are follow-ups or extensions of earlier 

work, continue to find that long-term exposure to fine particles is associated with both 

mortality and morbidity, as was stated in the 2004 PM AQCD. Notably, a follow-up to 

the Six Cities study shows that an overall reduction in PM2.5 levels results in reduced 

long-term mortality risk. Both this study and an analysis of the ACS cohort data in Los 

Angeles suggest that previous studies may have underestimated the magnitude of 

mortality risks. Some studies provide more mixed results, including the suggestion that 
 39 

higher traffic density may be an important factor. In addition, the California Children’s 

Health study reported measures of PM2.5 exposure and PM components and gases were 

associated with reduction in lung function growth in children, increasing the evidence for 

increased susceptibility early in life, as was suggested in the 2004 AQCD. In addition, 

one study reported increased infant mortality from respiratory causes with exposure to 

PM2.5. The results of recent epidemiologic and toxicology studies have also reported new 

evidence linking long-term exposure to fine particles with a measure of atherosclerosis 

development and, in a cohort of individuals with cystic fibrosis, respiratory 

exacerbations. 

• Recent epidemiologic studies have also continued to report associations between acute 

exposure to fine particles and mortality and morbidity health endpoints. These include 

three multi-city analyses, the largest of which (in 204 counties) shows a significant 

association between acute fine PM exposures and hospitalization for cardiovascular and 

respiratory diseases, and suggestions of differential effects in eastern U.S. as opposed to 

western U.S. locations. The new studies support previous conclusions that short-term 

exposure to fine PM is associated with both mortality and morbidity, including a 

substantial number of studies reporting associations with cardiovascular and respiratory 

health outcomes such as changes in heart rhythm or increases in exhaled NO. The fine 

PM concentrations reported in these studies are in some cases lower than in the 

previously-published studies. 

• New toxicology and epidemiologic studies have continued to link health outcomes with a 

range of fine particle sources and components. Source apportionment epidemiologic 

analyses were conducted by teams of analysts for two cities, and the results indicate that 

fine PM from several sources, including regional sulfate and several combustion sources, 

are associated with mortality. Additionally, a number of new studies indicate that trafficrelated PM exposures are associated with mortality and morbidity. A few new toxicology 

studies have used source apportionment techniques to assess effects related to PM from 

different emission categories. While limited in number and preliminary in nature, the 

findings suggest that several PM sources may contribute to toxicity, including 

combustion-related sources and regional sulfate pollution, as suggested in epidemiologic 

studies. Several studies have also indicated that particles from resuspended soils, such as 

road dust, may be associated with health effects. Toxicology studies indicate that various 

components, including metals, sulfates, and elemental carbon and organic carbon, are 

linked with health outcomes, albeit at generally high concentrations. Recent 

epidemiologic studies also report associations between sulfates and mortality and 

morbidity, and provide new evidence that organic or elemental carbon may be linked 

with health effects. 

• The recent epidemiologic studies greatly expand the evidence on health effects of acute 

exposure to thoracic coarse particles. The 2004 PM AQCD conclusion that PM10-2.5

exposure was associated with respiratory morbidity is substantially strengthened with 

these new studies; several epidemiologic studies, in fact, report stronger evidence of 

associations for hospital admissions with thoracic coarse particles than for fine particles. 

Some of the recent morbidity studies were also located in cities with low PM10-2.5
 40 

concentrations. For example, significant associations have been reported with respiratory 

hospital admissions in several Canadian studies, where the reported mean and maximum 

PM10-2.5 concentrations ranged from about 6 to 12 μg/m3 and 25 to 70 μg/m3, 

respectively. For mortality, many studies do not report statistically significant 

associations, though one new analysis reports a significant association with 

cardiovascular mortality in Vancouver, Canada. 

• New toxicology studies have demonstrated that exposure to thoracic coarse particles, or 

PM sources generally representative of this size fraction (e.g., road dust), can result in 

inflammation and other health responses. Clinical exposure of healthy and asthmatic 

humans to concentrated ambient air particles comprised mostly of PM10-2.5 showed 

changes in heart rate and heart rate variability measures. The results are still too limited 

to draw conclusions about specific thoracic coarse particle components and health 

outcomes, but it appears that endotoxin and metals may play a role in the observed 

responses. Two studies comparing toxicity of dust from soils and road surfaces found 

variable toxic responses from both rural and urban locations. 

• Evidence of associations between long-term exposure to thoracic coarse particles and 

either mortality or morbidity remains limited. 

• Significant associations between improvements in health and reductions in PM and other 

air pollutants have been reported in intervention studies or “found experiments.” One 

new study reported reduced mortality risk with reduced PM2.5 concentrations. In 

addition, several studies, largely outside the U.S., reported reduced respiratory morbidity 

with lowered air pollutant concentrations, providing further support for the 

epidemiological evidence that links PM exposure to adverse health effects. 
 41 

PM PROVISIONAL ASSESSMENT—ABBREVIATIONS 

AND ACRONYMS 

A549 human alveolar basal epithelial cell line 

AA arachidonic acid 

ACE angiotensin converting enzyme 

ACS American Cancer Society 

ADMA asymmetric dimethylarginine 

AHSMOG Adventist Health and Smog 

ARIES Aerosol Research and Inhalation and Epidemiology Study 

ALP alkaline phosphatase 

AM alveolar macrophage 

ApoE-/- apolipoprotein deficient (mouse model of atherosclerosis) 

AQS Air Quality System 

$-gluc $-glucuronide

BAD brachial artery diameter 

BALF bronchoalveolar lavage fluid 

BC black carbon 

BEAS-2B human bronchial epithelial cell line 

BN Brown Norway (rat) 

BP blood pressure 

BrdU bromodeoxyuridine 

BS black smoke 

CAPs concentrated ambient particles 

CARB California Air Resources Board 

CB chronic bronchitis 

CBC complete blood count 

CC16 clara-cell 16 protein 

CD11b cell surface receptor 

CI confidence interval 

CL chemiluminescence 

CO carbon monoxide 

CO carbon dioxide 

CoH Coefficient of Haze 

CPC coarse particle concentrator 

CRP C-reactive protein 
 42 

COPD chronic obstructive pulmonary disease 

CVD cardiovascular disease 

DBP diastolic blood pressure 

DD desert dust 

DK double knockout mouse strain (for ApoE and LDL) 

DNA deoxyribonucleic acid 

EC elemental carbon 

ECG electrocardiogram 

eNO exhaled nitric oxide 

eNOS endothelial nitric oxide synthase 

ER emergency room 

ERK extracellular signal-regulated kinase 

ET endothelein 

f breathing frequency 

F344 Fischer 344 (rat) 

FA filtered air 

FENO fractional exhaled nitric oxide 

FEV1 forced expiratory volume in 1 second 

FVC forced vital capacity 

GAM general additive model 

GEE generalized estimating equations 

GGT (-glutamyl transferase 

GLM Generalized Linear Model 

SD geometric standard deviation 

GSH reduced glutathione 

GSH/GSSG reduced glutathione/glutathione disulfide (ratio) 

GSSG glutathione disulfide 

H&E hematoxylin and eosin 

HAPC Harvard ambient fine particle concentrator 

Hb hemoglobin 

Hct hematocrit 

5-HETE 5-hydroxy-eicosatetraenoic acid 

HF high frequency of heart rate variability 

12-HHT 12-hydroxyheptadecatrienoic acid 

HO-1 heme oxygenase 
 43 

HR heart rate 

HRV heart rate variability 

H2SO4 sulfuric acid 

ICAM intercellular adhesion molecules 

ICD Implantable cardioverter defibrillator 

ICP-MS inductively coupled plasma mass spectrometry 

Ig immunoglobulin (e.g., IgA, IgE, IgG, IgM) 

IHD ischemic heart disease 

IL interleukin (e.g., IL-5, IL-6, IL-8, IL-13) 

IMPROVE Interagency Monitoring of Protected Visual Environments (network) 

iNOS inducible nitric oxide synthase 

IPN Inhalable Particle Network 

IQR interquartile range 

IT Intratracheal instillation 

JNK Jun kinase 

LBW low birth weight 

LDH lactate dehydrogenase 

LF low frequency component of heart rate variability 

LDL-/- low-density lipoprotein receptor deficient 

LPS lipopolysaccharide 

LRI lower respiratory infection 

LT leukotriene (e.g., LTB4) 

L/W lumen to wall (ratio) 

MAP mean arterial pressure 

MCh methacholine 

MCT monocrotaline 

MCV Mean cell volume 

MI myocardial infarction 

MIP macrophage inflammatory protein (e.g., MIP-1α, MIP-2) 

MLRA multiple linear regression analysis 

MMD mass median diameter 

MMEF maximal mid-expiratory flow 

MN micronuclei 

mm Hg millimeters of mercury 

MPO myeloperoxidase 
 44 

MV minute ventilation 

n number of observations 

NAC N-acetyl cysteine 

NAG N-acetyl-$-D-glucosaminidase 

NHAPS National Human Activity Pattern Survey 

NHBE normal human bronchial epithelial (cells) 

NF-κB nuclear transcription factor-κB 

NN normal-to-normal (R-R) interval of electrocardiogram 

NO nitric oxide 

NO2 nitrogen dioxide 

NO3 nitrate 

NOI nose-only inhalation 

NR not reported 

O3 ozone 

OC organic carbon 

OHC oxygenated hydrocarbons 

8-OHdG 8-hydroxy-2'-deoxyguanosine 

OR odds ratio 

OVA ovalbumin 

p probability value 

PAF platelet activating factor 

PAH polycyclic aromatic hydrocarbon 

PAU pause 

PE post-exposure 

PEF peak expiratory flow 

PIF peak inspiratory flow 

Penh enhanced pause 

PG prostaglandin (e.g., PGE2) 

PLA2 phospholipase-A2 

PLN popliteal lymph node 

PM particulate matter 

PM2.5 fine particulate matter (mass median aerodynamic diameter #2.5 μm) 

PM10 combination of coarse and fine particulate matter 

PM10-2.5 Thoracic coarse particulate matter 

(mass median aerodynamic diameter between 10 and 2.5 μm) 
 45 

PMN polymorphonuclear leukocyte 

PMR proportionate mortality ratio 

PNC particle number concentration 

PNN50 percentage of NN intervals >50 msec 

(measure of heart rate variability) 

ppb parts per billion 

ppm parts per million 

QAI QA-interval 

R4 range 40 

RAW 264.7 mouse macrophage cell line 

Raw airway resistance 

RBC red blood cell 

RMSSD root mean square of successive differences of adjacent normal-tonormal intervals 

RO residual oil 

ROFA residual oil fly ash 

ROI reactive oxygen intermediates 

ROS reactive oxygen species 

RR risk ratio 

RS resuspended oil 

RTD road tunnel dust 

SaO2 arterial oxygen saturation 

SD Sprague-Dawley (rat) 

SDNN standard deviation of normal-to-normal intervals 

SES socioeconomic status 

SH spontaneously hypertensive 

SIDS sudden infant death syndrome 

SMPS scanning mobility particle sizer 

SO2 sulfur dioxide 

SO4

2! sulfate 

SOD superoxide dismutase 

SRM Standard Reference Material 

SpO2 arterial oxygen saturation 

SS secondary sulfate 

TBARS thiobarbituric acid-reactive species 

TEOM tapered element oscillating microbalance 
 46 

THP-1 human monocytic leukemia cell line 

TLC total lung capacity 

TLR4 toll-like receptor-4 

TNF tumor necrosis factor (e.g., TNF-α) 

TRPV1 transient receptor potential vanilloid 

TSP total suspended particulates 

TWA time-weighted average 

TX tromboxane (e.g., TXB2) 

UA uric acid 

UCPC ultrafine condensation particle counter 

UF ultrafine 

URI upper respiratory infection 

USC University of Southern California 

VT tidal volume 

VACES versatile aerosol concentration enrichment system 

WB whole blood 

WBC white blood cell 

WBI whole body inhalation 

WKY Wistar-Kyoto (rat) 
 47 

REFERENCES 

Adamkiewicz, G.; Ebelt, S.; Syring, M.; Slater, J.; Speizer, F. E.; Schwartz, J.; Suh, H.; Gold, D. R. (2004) 

Association between air pollution exposure and exhaled nitric oxide in an elderly population. Thorax 

59: 204-209. 

Analitis, A.; Katsouyanni, K.; Dimakopoulou, K.; Samoli, E.; Nikoloulopoulos, A. K.; Petasakis, Y.; Touloumi, G.; 

Schwartz, J.; Anderson, H. R.; Cambra, K.; Forastiere, F.; Zmirou, D.; Vonk, J. M.; Clancy, L.; Kriz, B.; 

Bobvos, J.; Pekkanen, J. (2006) Short-term effects of ambient particles on cardiovascular and respiratory 

mortality. Epidemiology 17: 230-233. 

Ballester, F.; Rodriguez, P.; Iniguez, C.; Saez, M.; Daponte, A.; Galan, I.; Taracido, M.; Arribas, F.; Bellido, J.; 

Cirarda, F. B.; Canada, A.; Guillen, J. J.; Guillen-Grima, F.; Lopez, E.; Perez-Hoyos, S.; Lertxundi, A.; 

Toro, S. (2006) Air pollution and cardiovascular admissions association in Spain: results within the 

EMECAS project. J. Epidemiol. Comm. Health 60: 328-336. 

Batalha, J. R.; Saldiva, P H.; Clarke, R. W.; Coull, B. A.; Stearns, R. C.; Lawrence, J.; Murthy, G. G.; Koutrakis, P.; 

Godleski, J. J. (2002) Concentrated ambient air particles induce vasoconstriction of small pulmonary 

arteries in rats. Environ. Health Perspect. 110: 1191-1197. 

Bateson, T. F.; Schwartz, J. (2004) Who is sensitive to the effects of particulate air pollution on mortality? A casecrossover analysis of effect modifiers. Epidemiology 15: 143-149. 

Bayer-Oglesby, L.; Grize, L.; Gassner, M.; Takken-Sahli, K.; Sennhauser, F. H.; Neu, U.; Schindler, C.; BraunFahrlander, C. (2005) Decline of ambient air pollution levels and improved respiratory health in Swiss 

children. Environ. Health Perspect. 113: 1632-1637. 

Beck-Speier, I.; Dayal, N.; Denzlinger, C.; Haberl, C.; Maier, K. L.; Ziesenis, A.; Heyder, J. (2003) Sulfur-related 

air pollutants induce the generation of platelet-activating factor, 5-lipoxygenase- and cyclooxygenaseproducts in canine alveolar macrophages via activation of phospholipases A2. Prostaglandins Other Lipid 

Mediat. 71: 217-234. 

Becker, S.; Dailey, L. A.; Soukup, J. M.; Grambow, S. C.; Devlin, R. B.; Huang, Y. C. (2005a) Seasonal variations 

in air pollution particle-induced inflammatory mediator release and oxidative stress. Environ. Health 

Perspect. 113: 1032-1038. 

Becker, S.; Dailey, L.; Soukup, J. M.; Silbajoris, R.; Devlin, R. B. (2005b) TLR-2 is involved in airway epithelial 

cell response to air pollution particles. Toxicol. Appl. Pharmacol. 203: 45-52. 

Becker, S.; Soukup, J. M.; Sioutas, C.; Cassee, F. R. (2003) Response of human alveolar macrophages to ultrafine, 

fine and coarse urban air pollution particles. Exp. Lung Res. 29: 29-44. 

Bennett, C. M.; McKendry, I. G.; Kelly, S.; Denike, K.; Koch, T. (2006) Impact of the 1998 Gobi dust event on 

hospital admissions in the Lower Fraser Valley, British Columbia. Sci. Total Environ.: in press. 

Biggeri, A.; Baccini, M.; Bellini, P.; Terracini, B. (2005) Meta-analysis of the Italian studies of short-term effects of 

air pollution (MISA), 1990-1999. Int. J. Occup. Environ. Health 11: 107-122. 

Boezen, H. M.; Vonk, J. M.; Van Der Zee, S. C.; Gerritsen, J.; Hoek, G.; Brunekreef, B.; Schouten, J. P.; 

Postma, D. S. (2005) Susceptibility to air pollution in elderly males and females. Eur. Respir. J. 25: 

1018-1024. 

Burnett, R. T.; Stieb, D.; Brook, J. R.; Cakmak, S.; Dales, R.; Raizenne, M.; Vincent, R.; Dann, T. (2004) 

Associations between short-term changes in nitrogen dioxide and mortality in Canadian cities. Arch. 

Environ. Health 59: 228-236. 

Burr, M. L.; Karani, G.; Davies, B.; Holmes, B. A.; Williams, K. L. (2004) Effects on respiratory health of a 

reduction in air pollution from vehicle exhaust emissions Occup. Environ. Med. 61: 212-218. 

Campbell, A.; Oldham, M.; Becaria, A.; Bondy, S. C.; Meacher, D.; Sioutas, C.; Misra, C.; Mendez, L. B.; and 

Kleinman, M. (2005) Particulate matter in polluted air may increase biomarkers of inflammation in mouse 

brain. Neurotoxicology 26:133-40. 

Campen, M. J.; Babu, N. S.; Helms, G. A.; Pett, S.; Wernly, J.; Mehran, R.; McDonald, J. D. (2005) Nonparticulate 

components of diesel exhaust promote constriction in coronary arteries from ApoE -/- mice. Toxicol. Sci. 

88: 95-102. 

Cassee, F. R.; Boere, A. J. F.; Fokkens, P. H. B.; Leseman, D. L. A. C.; Sioutas, C.; Kooter, I. M.; Dormans, J. A. 

M. A. (2005) Inhalation of concentrated particulate matter produces pulmonary inflammation and systemic 

biological effects in compromised rats. J. Toxicol. Environ. Health Part A 68: 773-796. 

Chan, C. C.; Chuang, K. J.; Shiao, G. M.; Lin, L. Y. (2004) Personal exposure to submicrometer particles and heart 

rate variability in human subjects. Environ. Health Perspect. 112: 1063-1067. 
 48 

Chang, C.-C.; Hwang, J.-S.; Chan, C.-C.; Wang, P.-Y.; Hu, T.-H.; Cheng, T.-J. (2004) Effects of concentrated 

ambient particles on heart rate, blood pressure, and cardiac contractility in spontaneously hypertensive rats. 

Inhalation Toxicol. 16: 421-429. 

Chang, C.-C.; Tsai, S.-S.; Ho, S.-C.; Yang, C.-Y. (2005) Air pollution and hospital admissions for cardiovascular 

disease in Taipei, Taiwan. Environ. Res. 98: 114-119. 

Chen, L. C.; Hwang, J. S. (2005) Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. 

IV. Characterization of acute and chronic effects of ambient air fine particulate matter exposures on heartrate variability. Inhalation Toxicol. 17: 209-216. 

Chen, L. C.; Nadziejko, C. (2005) Effects of subchronic exposures to concentrated ambient particles (CAPs) in 

mice. V. CAPs exacerbate aortic plaque development in hyperlipidemic mice. Inhalation Toxicol. 

17: 217-224. 

Chen, Y.; Yang, Q.; Krewski, D.; Shi, Y.; Burnett, R. T.; McGrail, K. (2004) Influence of relatively low level of 

particulate air pollution on hospitalization for COPD in elderly people. Inhalation Toxicol. 16: 21-25. 

Chen, L. H.; Knutsen, S. F.; Shavlik, D.; Beeson, W. L.; Petersen, F.; Ghamsary, M.; Abbey, D. (2005) The 

association between fatal coronary heart disease and ambient particulate air pollution: Are females at 

greater risk? Environ. Health Perspect. 113: 1723-1729. 

Cheng, T.-J.; Hwang, J.-S.; Wang, P.-Y.; Tsai, C.-F.; Chen, C.-Y.; Lin, S.-H.; Chan, C.-C. (2003) Effects of 

concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats. Environ. 

Health Perspect. 111: 147-150. 

Chuang, K.-J.; Chan, C.-C.; Chen, N.-T.; Su, T.-C.; Lin, L.-Y. (2005) Effects of particle size fractions on reducing 

heart rate variability in cardiac and hypertensive patients. Environ. Health Perspect. 113: 1693-1697. 

Claiborn, C. S.; Larson, T.; Sheppard, L. (2002) Testing the metals hypothesis in Spokane, Washington. Environ. 

Health Perspect. 110(suppl. 4): 547-552. 

Dales, R.; Burnett, R. T.; Smith-Doiron, M.; Stieb, D. M.; Brook, J. R. (2004) Air pollution and sudden infant death 

syndrome. Pediatrics 113: 628-631. 

Daniels, M. J.; Dominici, F.; Zeger, S. L.; Samet, J. M. (2004a) The national morbidity, mortality, and air pollution 

study. Part III: PM10 concentration-response curves and thresholds for the 20 largest U.S. cities. Boston, 

MA: Health Effects Institute; research report no. 94(Part 3). 

Daniels, M. J.; Dominici, F.; Zeger, S. (2004b) Underestimation of standard errors in multi-site time series studies. 

Epidemiology. 15: 57-62. 

De Hartog, J. J.; Hoek, G.; Peters, A.; Timonen, K. L.; Ibald-Mulli, A.; Brunekreef, B.; Heinrich, J.; Tiittanen, P.; 

Van Wijnen, J. H.; Kreyling, W.; Kulmala, M.; Pekkanen, J. (2003) Effects of fine and ultrafine particles 

on cardiorespiratory symptoms in elderly subjects with coronary heart disease: the ULTRA study. Am. J. 

Epidemiol. 157: 613-623. 

De Leon, S. F.; Thurston, G. D.; Ito, K. (2003) Contribution of respiratory disease to nonrespiratory mortality 

associations with air pollution. Am. J. Respir. Crit. Care Med. 167: 1117-1123. 

Delfino, R. J.; Zeiger, R. S.; Seltzer, J. M.; Street, D. H.; McLaren, C. E. (2002) Association of asthma symptoms 

with peak particulate air pollution and effect modification by anti-inflammatory medication use. Environ. 

Health Perspect. 110: A607-A617. 

Delfino, R. J.; Gone, H.; Linn, W. S.; Pellizzari, E. D.; Hu, Y. (2003) Asthma symptoms in Hispanic children and 

daily ambient exposures to toxic and criteria air pollutants. Environ. Health Perspect. 111: 647-656. 

Delfino, R. J., Quintana, P. J. E.; Floro, J.; Gastañaga, V. M.; Samimi, B. S.; Kleinman, M. T.; Liu, L.-J. S.; 

Bufalino, C.; Wu, C.-F.; McLaren, C. E. (2004) Association of FEV1 in asthmatic children with personal 

and microenvironmental exposure to airborne particulate matter. Environ. Health Perspect. 112: 932-941. 

DeMeo, D. L.; Zanobetti, A.; Litonjua, A. A.; Coull, B. A.; Schwartz, J.; Gold, D. R. (2004) Ambient air pollution 

and oxygen saturation. Am. J. Respir. Crit. Care Med. 170: 383-387. 

Devlin, R. B.; Ghio, A. J.; Kehrl, H.; Sanders, G.; Cascio, W. (2003) Elderly humans exposed to concentrated air 

pollution particles have decreased heart rate variability. Eur. Respir. J. Suppl. 40: 76S-80S. 

Dockery, D. W.; Luttmann-Gibson, H.; Rich, D. Q.; Link, M. S.; Mittleman, M. A.; Gold, D. R.; Koutrakis, P.; 

Schwartz, J. D.; Verrier, R. L. (2005) Association of air pollution with increased incidence of ventricular 

tachyarrhythmias recorded by implanted cardioverter defibrillators. Environ. Health Perspect. 

113: 670-674. 

Dominici, F.; McDermott, A.; Zeger, S. L.; Samet, J. M. (2003a) Airborne particulate matter and mortality: 

timescale effects in four U.S. Cities. Am. J. Epidemiol. 157: 1055-1065. 

Dominici, F.; McDermott, A.; Zeger, S. L.; Samet, J. M. (2003b) National maps of the effects of particulate matter 

on mortality: exploring geographical variation. Environ. Health Perspect. 111: 39-44. 
 49 

Dominici, F.; Peng, R. D.; Bell, M. L.; Pham, L.; McDermott, A.; Zeger, S. L.; Samet, J. L. (2006) Fine particulate 

air pollution and hospital admission for cardiovascular and respiratory diseases. J. Am. Med. Assoc. JAMA 

295: 1127-1134. 

Dubowsky, S. D.; Suh, H.; Schwartz, J.; Coull, B. A.; Gold, D. R. (2006) Diabetes, obesity, and hypertension may 

enhance associations between air pollution and markers of systemic inflammation. Environ. Health 

Perspect.: 10.1289/ehp.8469. 

Dugandzic, R. Dodds, L.; Stieb, D.; Smith-Doiron, M. (2006) The association between low level exposures to 

ambient air pollution and term low birth weight: a retrospective cohort study. Environ. Health 5: 3. 

Dvonch, J. T.; Brook, R. D.; Keeler, G. J.; Rajagopalan, S.; D'Alecy, L. G.; Marsik, F. J.; Morishita, M.; Yip, F. Y.; 

Brook, J. R.; Timm, E. J.; Wagner, J. G.; Harkema, J. R. (2004) Effects of concentrated fine ambient 

particles on rat plasma levels of asymmetric dimethylarginine. Inhalation Toxicol. 16: 473-480. 

Ebelt, S. T.; Wilson, W. E.; Brauer, M. (2005) Exposure to ambient and nonambient components of particulate 

matter: a comparison of health effects. Epidemiology 16: 396-405. 

Elder, A.; Gelein, R.; Finkelstein, J.; Phipps, R.; Frampton, M.; Utell, M.; Kittelson, D. B.; Watts, W. F.; Hopke, P.; 

Jeong, C. H.; Kim, E.; Liu, W.; Zhao, W.; Zhuo, L.; Vincent, R.; Kumarathasan, P.; Oberdörster, G. (2004) 

On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats. Inhalation Toxicol. 

16(suppl. 1): 41-53. 

Enstrom, J. E. (2005) Fine particulate air pollution and total mortality among elderly Californians, 1973-2002. 

Inhalation Toxicol. 17: 803-816. 

Evans, M. F.; Smith, V. K. (2005) Do new health conditions support mortality-air pollution effects? J. Environ. 

Econ. Manage. 50: 496-518. 

Filleul, L.; Rondeau, V.; Vandentorren, S.; Le Moual, N.; Cantagrel, A.; Annesi-Maesano, I.; Charpin, D.; Declercq, 

C.; Neukirch, F.; Paris, C.; Vervloet, D.; Brochard, P.; Tessier, J. F.; Kauffmann, F.; Baldi, I. (2005) 

Twenty five year mortality and air pollution: results from the French PAARC survey. Occup. Environ. 

Med. 62: 453-460. 

Forastiere, F.; Stafoggia, M.; Picciotto, S.; Bellander, T.; D'Ippoliti, D.; Lanki, T.; Von Klot, S.; Nyberg, F.; Paatero, 

P.; Peters, A.; Pekkanen, J.; Sunyer, J.; Perucci, C. A. (2005) A case-crossover analysis of out-of-hospital 

coronary deaths and air pollution in Rome, Italy. Am. J. Respir. Crit. Care Med. 172: 1549-1555. 

Frye, C.; Hoelscher, B.; Cyrys, J.; Wjst, M.; Wichmann, H. E.; Heinrich, J. (2003) Association of lung function with 

declining ambient air pollution. Environ. Health Perspect. 111: 383-387. 

Gauderman, W. J.; Avol, E.; Gilliland, F.; Vora, H.; Thomas, D.; Berhane, K.; McConnell, R.; Kuenzli, N.; 

Lurmann, F.; Rappaport, E.; Margolis, H.; Bates, D.; Peters, J. (2004) The effect of air pollution on lung 

development from 10 to 18 years of age. N. Engl. J. Med. 351: 1057-1067. 

Gavett, S. H.; Haykal-Coates, N.; Copeland, L B.; Heinrich, J.; Gilmour, M. I. (2003) Metal composition of ambient 

PM2.5 influences severity of allergic airways disease in mice. Environ. Health Perspect. 111: 1471-1477. 

Gent, J. F.; Triche, E. W.; Holford, T. R.; Belanger, K.; Bracken, M. B.; Beckett, W. S.; Leaderer, B. P. (2003) 

Association of low-level ozone and fine particles with respiratory symptoms in children with asthma. 

JAMA J. Am. Med. Assoc. 290: 1859-1867. 

Gerlofs-Nijland, M. E.; Boere, A. J.; Leseman, D. L.; Dormans, J. A.; Sandstrom, T.; Salonen, R. O.; van Bree, L.; 

Cassee, F. R. (2005) Effects of particulate matter on the pulmonary and vascular system: time course in 

spontaneously hypertensive rats. Part Fibre Toxicol. 2005 Mar 24;2(1):2. 

Ghio, A. J.; Hall, A.; Bassett, M. A.; Cascio, W. E.; Devlin, R. B. (2003) Exposure to concentrated ambient air 

particles alters hematologic indices in humans. Inhalation Toxicol. 15: 1465-1478. 

Gilmour, M. I.; O'Connor, S.; Dick, C. A. J.; Miller, C. A.; Linak, W. P. (2004) Differential pulmonary 

inflammation and in vitro cytotoxicity of size-fractionated fly ash particles from pulverized coal 

combustion. J. Air Waste Manage. Assoc. 54: 286-295. 

Girardot, S. P.; Ryan, P. B.; Smith, S. M.; Davis, W. T.; Hamilton, C. B.; Obenour, R. A.; Renfro, J. R.; Tromatore, 

K. A.; Reed, G. D. (2006) Ozone and PM2.5 exposure and acute pulmonary health effects: a study of hikers 

in the Great Smoky Mountains National Park. Environ. Health Perspect.: 10.1289/ehp.8637. 

Gold, D. R.; Litonjua, A. A.; Zanobetti, A.; Coull, B. A.; Schwartz, J.; MacCallum, G.; Verrier, R. L.; Nearing, B. 

D.; Canner, M. J.; Suh, H.; Stone, P. H. (2005) Air pollution and ST-segment depression in elderly 

subjects. Environ. Health Perspect. 113: 883-887. 

Goldberg, M. S.; Burnett, R. T.; Valois, M.-F.; Flegel, K.; Bailar, J. C., III; Brook, J.; Vincent, R.; Radon, K. (2003) 

Associations between ambient air pollution and daily mortality among persons with congestive heart 

failure. Environ. Res. 91: 8-20. 
 50 

Goldberg, M. S.; Burnett, R. T.; Yale, J. F.; Valois, M. F.; Brook, J. R. (2006) Associations between ambient air 

pollution and daily mortality among persons with diabetes and cardiovascular disease. Environ. Res. 

100: 255-267. 

Goldsmith, C.-A. W.; Ning, Y.-Y.; Qin, G.; Imrich, A.; Lawrence, J.; Murthy, G. G., K.; Catalano, P. J.; Kobzik, L. 

(2002) Combined air pollution particle and ozone exposure increases airway responsiveness in mice. 

Inhalation Toxicol. 14: 325-347. 

Gong, H., Jr.; Linn, W. S.; Terrell, S. L.; Anderson, K. R.; Clark, K. W.; Sioutas, C.; Cascio, W. E.; Alexis, N.; 

Devlin, R. B. (2004a) Exposures of elderly volunteers with and without chronic obstructive pulmonary 

disease (COPD) to concentrated ambient fine particulate pollution. Inhalation Toxicol. 16: 731-744. 

Gong, H., Jr.; Linn, W. S.; Terrell, S. L.; Clark, K. W.; Geller, M. D.; Anderson, K. R.; Cascio, W. E.; Sioutas, C. 

(2004b) Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient 

coarse particles. Inhalation Toxicol. 16: 335-343. 

Gong, H. Jr., Linn, W. S.; Clark, K. W.; Anderson, K. R.; Geller, M. D.; Sioutas, C. (2005) Respiratory responses to 

exposures with fine particulates and nitrogen dioxide in the elderly with and without COPD. Inhal. Toxicol. 

17: 123-132. 

Goodman, P. G.; Dockery, D. W.; Clancy, L. (2004) Cause-specific mortality and the extended effects of particulate 

pollution and temperature exposure. Environ. Health Perspect. 112: 179-185. 

Gordon, T.; Gerber, H.; Fang, C. P.; Chen, L. C. (1999) A centrifugal particle concentrator for use in inhalation 

toxicology. Inhalation Toxicol. 11: 71-87. 

Goss, C. H.; Newsom, S. A.; Schildcrout, J. S.; Sheppard, L.; Kaufman, J. D. (2004) Effect of ambient air pollution 

on pulmonary exacerbations and lung function in cystic fibrosis. Am. J. Respir. Crit. Care Med. 

169: 816-821. 

Gunnison, A.; Chen, L. C. (2005) Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. 

VI. Gene expression in heart and lung tissue. Inhalation Toxicol. 17: 225-233. 

Gurgueira, S. A.; Lawrence, J.; Coull, B.; Murthy, G. G. K.; González-Flecha, B. (2002) Rapid increases in the 

steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution 

inhalation. Environ. Health Perspect. 110: 749-755. 

Henneberger, A.; Zareba, W.; Ibald-Mulli, A.; Rückerl, R.; Cyrys, J.; Couderc, J.-P.; Mykins, B.; Woelke, G.; 

Wichmann, H.-E.; Peters, A. (2005) Repolarization changes induced by air pollution in ischemic heart 

disease patients. Environ. Health Perspect. 113: 440-446. 

Hetland, R. B.; Cassee, F. R.; Låg, M.; Refsnes, M.; Dybing, E.; Schwarze, P. E. (2005) Cytokine release from 

alveolar macrophages exposed to ambient particulate matter: heterogeneity in relation to size, city and 

season. Part. Fibre Toxicol. 2: 10.1186/1743-8977-2-4. Available: 

http://www.particleandfibretoxicology.com/content/2/1/4 [14 March, 2006]. 

Holloman, C. H.; Bortnick, S. M.; Morara, M.; Strauss, W. J.; Calder, C. A. (2004) A Bayesian hierarchical 

approach for relating PM2.5 exposure to cardiovascular mortliaty in North Carolina. Environ. Health 

Perspect. 112: 1282-1288. 

Hopke, P. K.; Ito, K.; Mar, T.; Christensen, W. F.; Eatough, D. J.; Henry, R. C.; Kim, E.; Laden, F.; Lall, R.; 

Larson, T. V.; Liu, H.; Neas, L.; Pinto, J.; Stölzel, M.; Suh, H.; Paatero, P.; Thurston, G. D. (2005) PM 

source apportionment and health effects: 1. Intercomparison of source apportionment results. J. Exposure 

Anal. Environ. Epidemiol.: 10.1038/sj.jea.7500458. 

Huang, Y.-C. T.; Ghio, A. J.; Stonehuerner, J.; McGee, J.; Carter, J. D.; Grambow, S. C.; Devlin, R. B. (2003a) The 

role of soluble components in ambient fine particles-induced changes in human lungs and blood. Inhalation 

Toxicol. 15: 327-342. 

Huang, S. L.; Hsu, M. K.; Chan, C. C. (2003b) Effects of submicrometer particle compositions on cytokine 

production and lipid peroxidation of human bronchial epithelial cells. Environ. Health Perspect. 

111: 478-482. 

Hwang, J.-S.; Nadziejko, C.; Chen, L. C. (2005) Effects of subchronic exposures to concentrated ambient particles 

(CAPs) in mice: III. Acute and chronic effects of CAPs on heart rate, heart-rate fluctuation, and body 

temperature. Inhalation Toxicol. 17: 199-207. 

Ibald-Mulli, A.; Timonen, K. L.; Peters, A.; Heinrich, J.; Wolke, G.; Lanki, T.; Buzorius, G.; Kreyling, W. G.; 

De Hartog, J.; Hoek, G.; Ten Brink, H. M.; Pekkanen, J. (2004) Effects of particulate air pollution on blood 

pressure and heart rate in subjects with cardiovascular disease: a multicenter approach. Environ. Health 

Perspect. 112: 369-377. 
 51 

Inoue, K.; Takano, H.; Yanagisawa, R.; Ichinose, T.; Sadakane, K.; Yoshino, S.; Yamaki, K.; Uchiyama, K.; 

Yoshikawa, T. (2004) Components of diesel exhaust particles differentially affect lung expression of 

cyclooxygenase-2 related to bacterial endotoxin J. Appl. Toxicol. 24: 415-418. 

Ito, K.; Christensen, W. F.; Eatough, D. J.; Henry, R. C.; Kim, E.; Laden, F.; Lall, R.; Larson, T. V.; Neas, L.; 

Hopke, P. K.; Thurston, G. D. (2006) PM source apportionment and health effects: 2. An investigation of 

intermethod variability in associations between source-apportioned fine particle mass and daily mortality in 

Washington, DC. J. Exposure Anal. Environ. Epidemiol.: 10.1038/sj.jea.7500464. 

Jansen, K. L.; Larson, T. V.; Koenig, J. Q.; Mar, T. F.; Fields, C.; Stewart J.; Lippmann, M. (2005) Associations 

between health effects and particulate matter and black carbon in subjects with respiratory disease. 

Environ. Health Perspect. 113: 1741-1746. 

Jerrett, M.; Burnett, R. T.; Brook, J.; Kanaroglou, P.; Giovis, C.; Finkelstein, N.; Hutchison, B. (2004) 

Do socioeconomic characteristics modify the short term association between air pollution and mortality? 

Evidence from a zonal time series in Hamilton, Canada. J. Epidemiol. Comm. Health (England) 58: 31-40. 

Jerrett, M.; Burnett, R. T.; Ma, R.; Pope, C. A., III; Krewski, D.; Newbold, K. B.; Thurston, G.; Shi, Y.; Finkelstein, 

N.; Calle, E. E.; Thun, M. J. (2005) Spatial analysis of air pollution and mortality in Los Angeles. 

Epidemiology 16: 727-736. 

Kan, H.-D.; Chen, B.-H.; Fu, C.-W.; Yu, S.-Z.; Mu, L.-N. (2005) Relationship between ambient air pollution and 

daily mortality of SARS in Beijing. Biomed. Environ. Sci. 18: 1-4. 

Karr, C.; Lumley, T.; Shepherd, K.; Davis, R.; Larson, T.; Ritz, B.; Kaufman, J. (2006) A case-crossover study of 

wintertime ambient air pollution and infant bronchiolitis. Environ. Health Perspect. 114: 277-281. 

Kleinman, M. T.; Hyde, D. M.; Bufalino, C.; Basbaum, C.; Bhalla, D. K.; Mautz, W. J. (2003) Toxicity of chemical 

components of fine particles inhaled by aged rats: effects of concentration. J. Air Waste Manage. Assoc. 

53: 1080-1087. 

Kleinman, M.; Phalen, R. (2006) Toxicological interactions in the respiratory system after inhalation of ozone and 

sulfuric acid aerosol mixtures. Inhalat. Toxicol. 18: 295-303. 

Kleinman, M.; Sioutas, C.; Stram, D.; Froines, J.; Cho, A.; Chakrabarti, B.; Hamade, A.; Meacher, D.; Oldham, M. 

(2005) Inhalation of concentrated ambient particulate matter near a heavily trafficked road stimulates 

antigen-induced airway responses in mice. J. Air Waste Manage. Assoc. 55: 1277-1288. 

Klemm, R. J.; Lipfert, F. W.; Wyzga, R. E.; Gust, C. (2004) Daily mortality and air pollution in Atlanta: two years 

of data from ARIES. Inhalation Toxicol. 16(suppl. 1): 131-141. 

Kodavanti, U. P.; Schladweiler, M. C.; Ledbetter, A. D.; McGee, J. K.; Walsh, L.; Gilmour, P. S.; Highfill, J. W.; 

Davies, D.; Pinkerton, K. E.; Richards, J. H.; Crissman, K.; Andrews, D.; Costa, D. L. (2005) Consistent 

pulmonary and systemic responses from inhalation of fine concentrated ambient particles: roles of rat 

strains used and physicochemical properties. Environ. Health Perspect. 113: 1561-1568. 

Koenig, J. Q.; Mar, T. F.; Allen, R. W.; Jansen, K.; Lumley, T.; Sullivan, J. H.; Trenga, C. A.; Larson, T.; Liu, L. J. 

(2005) Pulmonary effects of indoor- and outdoor-generated particles in children with asthma. Environ. 

Health Perspect. 113: 499-503. 

Koike, E.; Kobayashi, T. (2005) Organic extract of diesel exhaust particles stimulates expression of Ia and 

costimulatory molecules associated with antigen presentation in rat peripheral blood monocytes but not in 

alveolar macrophages. Toxicol. Appl. Pharmacol. 209: 277-285. 

Künzli, N.; Jerrett, M.; Mack, W. J.; Beckerman, B.; LaBree, L.; Gilliland, F.; Thomas, D.; Peters, J.; Hodis, H. N. 

(2005) Ambient air pollution and atherosclerosis in Los Angeles. Environ. Health Perspect. 113: 201-206. 

Laden, F.; Schwartz, J.; Speizer, F. E.; Dockery, D. W. (2006) Reduction in fine particulate air pollution and 

mortality: extended follow-up of the Harvard Six Cities study. Am. J. Respir. Crit. Care Med. 

173: 667-672. 

Lanki, T.; De Hartog, J. J.; Heinrich, J.; Hoek, G.; Janssen, N. A. H.; Peters, A.; Stölzel, M.; Timonen, K. L.; 

Vallius, M.; Vanninen, E.; Pekkanen, J. (2006) Can we identify sources of fine particles responsible for 

exercise-induced ischemia on days with elevated pollution? The ULTRA study. Environ. Health Perspect. 

114: 655-660. 

Le Tertre, A.; Schwartz, J.; Touloumi, G. (2005) Empirical Bayes and adjusted estimates approach to estimating the 

relation of mortality to eposure of PM10. Risk Anal. 25: 711-718. 

Lei, Y.C.; Chen, M. C.; Chan, C. C.; Wang, P. Y.; Lee, C. T.; Cheng, T. J. (2004a) Effects of concentrated ambient 

particles on airway responsiveness and pulmonary inflammation in pulmonary hypertensive rats. Inhal. 

Toxicol. 16: 785-792. 
 52 

Lei, Y.-C.; Chan, C.-C.; Wang, P.-Y.; Lee, C.-T.; Cheng, T.-J. (2004b) Effects of Asian dust event particles on 

inflammation markers in peripheral blood and bronchoalveolar lavage in pulmonary hypertensive rats. 

Environ. Res. 95: 71-76. 

Letz, A. G.; Quinn, J. M. (2005) Relationship of basic military trainee emergency department visits for asthma and 

San Antonio air quality. Allergy Asthma Proc. 26: 463-467. 

Lewis, T. C.; Robins, T. G.; Dvonch, J. T.; Keeler, G. J.; Yip, F. Y.; Mentz, G. B.; Lin, X.; Parker, E. A.; Israel, 

B. A.; Gonzalez, L.; Hill, Y. (2005) Air pollution-associated changes in lung function among asthmatic 

children in Detroit. Environ. Health Perspect. 113: 1068-1075. 

Li, N.; Kim, S.; Wang, M.; Froines, J. R.; Sioutas, C.; Nel, A. (2002) Use of a stratified oxidative stress model to 

study the biological effects of ambient concentrated and diesel exhaust particulate matter. Inhalation 

Toxicol. 14: 459-486. 

Li, N.; Sioutas, C.; Froines, J. R.; Cho, A.; Misra, C.; Nel, A. (2003) Ultrafine particulate pollutants induce oxidative 

stress and mitochondrial damage. Environ. Health Perspect. 111: 455-460. 

Liao, D.; Duan, Y.; Whitsel, E. A.; Zheng, Z.-J.; Heiss, G.; Chinchilli, V. M.; Lin, H.-M. (2004) Association of 

higher levels of ambient criteria pollutants with impaired cardiac autonomic control: a population-based 

study. Am. J. Epidemiol. 159: 768-777. 

Lin, M.; Chen, Y.; Burnett, R. T.; Villeneuve, P. J.; Krewski, D. (2002) The influence of ambient coarse particulate 

matter on asthma hospitalization in children: case-crossover and time-series analyses. Environ. Health 

Perspect. 110: 575-581. 

Lin, M.; Stieb, D. M.; Chen, Y. (2005) Coarse particulate matter and hospitalization for respiratory infections in 

children younger than 15 years in Toronto: a case-crossover analysis. Pediatrics 116: 235-240. 

Lipfert, F. W.; Wyzga, R. E.; Baty, J. D.; Miller, J. P. (2006a) Traffic density as a surrogate measure of 

environmental exposures in studies of air pollution health effects: long-term mortality in a cohort of U.S. 

veterans. Atmos. Environ. 40: 154-169. 

Lipfert, F. W.; Baty, J. D.; Wyzga, R. E.; Miller, J. P. (2006b) PM2.5 constituents and related air quality variables as 

predictors of survival in a cohort of U.S. military veterans. Inhalation Toxicol.: in press. 

Lippmann, M.; Gordon, T.; Chen, L. C. (2005a) Effects of subchronic exposures of mice. IX. Integral assessment 

and human health implications of subchronic exposures of mice to CAPs. Inhalation Toxicol. 17: 255-261. 

Lippmann, M.; Hwang, J.; Maclejczyk, P.; Chen, L. (2005b) PM source apportionment for short-term cardiac 

function changes in ApoE-/- mice. Environ. Health Perspect. 113: 1575-1579. 

Lipsett, M. J.; Tsai, F. C.; Roger, L.; Woo, M.; Ostro, B. D. (2006) Coarse particles and heart rate variability among 

older adults with coronary artery disease in the Coachella Valley, California. Environ. Health Perspect.: 

10.1289/ehp.8856. 

Lwebuga-Mukasa, J. S.; Ayirookuzhi, S. J.; Hyland, A. (2003) Traffic volumes and respiratory health care 

utilization among residents in close proximity to the Peace Bridge before and after September 11, 2001. 

J. Asthma 40: 855-864. 

Maciejczyk, P.; Chen, L. C. (2005) Effects of subchronic exposures to concentrated ambient particles (CAPs) in 

mice: VIII. source-related daily variations in in vitro responses to CAPs. Inhalation Toxicol. 17: 243-253. 

Mar, T. F.; Norris, G. A.; Larson, T. V.; Wilson, W. E.; Koenig, J. Q. (2003) Air pollution and cardiovascular 

mortality in Phoenix, 1995-1997. In: Revised analyses of time-series studies of air pollution and health. 

Special report. Boston, MA: Health Effects Institute; pp. 177-182. Available: 

http://www.healtheffects.org/Pubs/TimeSeries.pdf [18 October, 2004]. 

Mar, T. F.; Larson, T. V.; Stier, R. A.; Claiborn, C.; Koenig, J. Q. (2004) An analysis of the association between 

respiratory symptoms in subjects with asthma and daily air pollution in Spokane, Washington. Inhalation 

Toxicol. 16: 809-815. 

Mar, T. F.; Jansen, K.; Shepherd, K.; Lumley, T.; Larson, T. V.; Koenig, J. Q. (2005) Exhaled nitric oxide in 

children with asthma and short-term PM2.5 exposure in Seattle. Environ. Health Perspect. 113: 1791-1794. 

Mar, T. F.; Ito, K.; Koenig, J. Q.; Larson, T. V.; Eatough, D. J.; Henry, R. C.; Kim, E.; Laden, F.; Lall, R.; Neas, L.; 

Stölzel, M.; Paatero, P.; Hopke, P. K.; Thurston, G. D. (2006) PM source apportionment and health effects. 

3. Investigation of inter-method variations in associations between estimated source contributions of PM2.5

and daily mortality in Phoenix, AZ. J. Exposure Anal. Environ. Epidemiol.: 10.1038/sj/jea.7500465. 

Martins, M. C. H.; Fatigati, F. L.; Vespoli, T. C.; Martins, L. C.; Martins, M. A.; Saldiva, P. H. N.; Braga, A. L. F. 

(2004) Influence of socioeconomic conditions on air pollution effects in elderly people an analysis of six 

regions in Sao Paolo, Brazil. J. Epidemiol. Comm. Health 58: 41-46. 
 53 

McConnell, R.; Berhane, K.; Gilliland, F.; Molitor, J.; Thomas, D.; Lurmann, F.; Avol, E.; Gauderman, W. J.; 

Peters, J. M. (2003) Prospective study of air pollution and bronchitic symptoms in children with asthma: 

Online Supplement. Am. J. Respir. Crit. Care Med. 168: 790-797. 

McDonnell, W. F.; Nishino-Ishikawa, N.; Petersen, F. F.; Chen, L. H.; Abbey, D. E. (2000) Relationships 

of mortality with the fine and coarse fractions of long-term ambient PM10 concentrations in nonsmokers. 

J..Exposure Anal. Environ. Epidemiol. 10: 427-436. 

Medina-Ramón, M.; Zanobetti, A.; Schwartz, J. (2006) The effect of ozone and PM10 on hospital admissions for 

pneumonia and chronic obstructive pulmonary disease: a national multicity study. Am. J. Epidemiol. 

163: 579-588. 

Metzger, K. B.; Tolbert, P. E.; Klein, M.; Peel, J. L.; Flanders, W. D.; Todd, K. H.; Mulholland, J. A.; Ryan, P. B.; 

Frumkin , H. (2004) Ambient air pollution and cardiovascular emergency department visits. Epidemiology 

15: 46-56. 

Millstein, J.; Gilliland, F.; Berhane, K.; Gauderman, W. J.; McConnell, R.; Avol, E.; Rappaport, E. B.; Peters, J. M. 

(2004) Effects of ambient air pollutants on asthma medication use and wheezing among fourth-grade 

school children from 12 Southern California communities enrolled in The Children's Health Study. Arch. 

Environ. Health. 59: 505-514. 

Morishita, M.; Keeler, G.; Wagner, J.; Marsik, F.; Timm, E.; Dvonch, J.; Harkema, J. (2004) Pulmonary retention of 

particulate matter is associated with airway inflammation in allergic rats exposed to air pollution in urban 

Detroit. Inhal. Toxicol. 16: 663-674. 

Moshammer, H.; Neuberger, M. (2003) The active surface of suspended particles as a predictor of lung function and 

pulmonary symptoms in Austrian school children. Atmos. Environ. 37: 1737-1744. 

Nadziejko, C.; Fang, K.; Narciso, S.; Zhong, M.; Su, W. C.; Gordon, T.; Nadas, A.; Chen, L. C. (2004) Effect of 

particulate and gaseous pollutants on spontaneous arrhythmias in aged rats. Inhalation Toxicol. 

16: 373-380. 

Neuberger, M.; Moshammer, H.; Kundi, M. (2002) Declining ambient air pollution and lung function improvement 

in Austrian children. Atmos. Environ. 36: 1733-1736. 

Newhouse, C. P.; Levetin, B. S.; Levetin, E. (2004) Correlation of environmental factors with asthma and rhinitis 

symptoms in Tulsa, OK. Ann. Allergy Asthma Immunol. 92: 356-366. 

Nygaard, U. C.; Alberg, T.; Bleumink, R.; Aase, A.; Dybing, E.; Pieters, R.; Lovik, M. (2005) Ambient air particles 

from four European cities increase the primary cellular response to allergen in the draining lymph node. 

Toxicology 207: 241-254. 

O'Neill, M. S.; Veves, A.; Zanobetti, A.; Sarnat, J. A.; Gold, D. R.; Economides, P. A.; Horton, E. S.; Schwartz, J. 

(2005) Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular 

reactivity and endothelial function. Circulation 111: 2913-2920. 

Ostro, B. D.; Broadwin, R.; Lipsett, M. J. (2003) Coarse particles and daily mortality in Coachella Valley, 

California. In: Revised analyses of time-series studies of air pollution and health. Special report. Boston, 

MA: Health Effects Institute; pp. 199-204. Available: http://www.healtheffects.org/Pubs/TimeSeries.pdf 

[18 October, 2004]. 

Ostro, B.; Broadwin, R.; Green, S.; Feng, W.-Y.; Lipsett, M. (2006a) Fine particulate air pollution and mortality in 

nine California counties: results from CALFINE. Environ. Health Perspect. 114: 29-33. 

Park, S. K.; O’Neill, M. S.; Vokonas, P. S.; Sparrow, D.; Schwartz, J. (2005) Effects of air pollution on heart rate 

variability: the VA normative aging study. Environ. Health Perspect. 113: 304-309. 

Peel, J. L.; Tolbert, P. E.; Klein, M.; Metzger, K. B.; Flanders, W. D.; Knox, T.; Mulholland, J. A.; Ryan, P. B.; 

Frumkin, H. (2005) Ambient air pollution and respiratory emergency department visits. Epidemiology 

16: 164-174. 

Pekkanen, J.; Peters, A.; Hoek, G.; Tiittanen, P.; Brunekreef, B.; de Hartog, J.; Heinrich, J.; Ibald-Mulli, A.; 

Kreyling, W. G.; Lanki, T.; Timonen, K. L.; Vanninen, E. (2002) Particulate air pollution and risk of 

ST-segment depression during repeated submaximal exercise tests among subjects with coronary heart 

disease: the exposure and risk assessment for fine and ultrafine particles in ambient air (ULTRA) study. 

Circulation 106: 933-938. 

Penard-Morand, C.; Charpin, D.; Raherison, C.; Kopferschmitt, C.; Caillaud, D.; Lavaud, F.; Annesi-Maesano, I. 

(2005) Long-term exposure to background air pollution related to respiratory and allergic health in 

schoolchildren. Clin. Exp. Allergy 35: 1279-1287. 

Peng, R. D.; Dominici, F.; Pastor-Barriuso, R.; Zeger, S. L.; Samet, J. M. (2005) Seasonal analyses of air pollution 

and mortality in 100 U.S. cities. Am. J. Epidemiol. 161: 585-594. 
 54 

Penttinen, P.; Vallius, M.; Tiittanen, P.; Ruuskanen, J.; Pekkanen, J. (2006) Source-specific fine particles in urban 

air and respiratory function among adult asthmatics. Inhalation Toxicol. 18: 191-198. 

Pierse, N.; Rushton, L.; Harris, R.; Kuehni, C.; Silverman, M.; Grigg, J. (2006) Locally-generated particulate 

pollution and respiratory symptoms in young children. Thorax 61: 216-220. 

Pope, C. A., III; Burnett, R. T.; Thun, M. J.; Calle, E. E.; Krewski, D.; Ito, K.; Thurston, G. D. (2002) Lung cancer, 

cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA J. Am. Med. 

Assoc. 287: 1132-1141. 

Pope, C. A., III; Burnett, R. T.; Thurston, G. D.; Thun, M. J.; Calle, E. E.; Krewski, D.; Godleski, J. J. (2004) 

Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of 

general pathophysiological pathways of disease Circulation 109: 71-77. 

Pozzi, R.; De Berardis, B.; Paoletti, L.; Guastadisengni, C. (2003) Inflammatory mediators induced by coarse 

(PM2.5-10) and fine (PM2.5) urban air particles in RAW 264.7 cells. Toxicology 183: 243-254. 

Proctor, S. D.; Dreher, K. L.; Kelly, S. E.; Russell, J. C. (2006) Hypersensitivity of prediabetic JCR: LA-cp rats to 

fine airborne combustion particle-induced direct and noradrenergic-mediated vascular contraction. Toxicol. 

Sci. 90: 385-391. 

Rabinovitch, N.; Strand, M.; Gelfand, E. W. (2006) Particulate levels are associated with early asthma worsening in 

children with persistent disease. Am. J. Respir. Crit. Care Med. 173: 1098-1105. 

Rhoden, C. R.; Lawrence, J.; Godleski, J. J.; González-Flecha, B. (2004) N-acetylcysteine prevents lung 

inflammation after short-term inhalation exposure to concentrated ambient particles. Toxicol. Sci. 

79: 296-303. 

Rhoden, C. R.; Wellenius, G. A.; Ghelfi, E.; Lawrence, J.; González-Flecha, B. (2005) PM-induced cardiac 

oxidative stress and dysfunction are mediated by autonomic stimulation. Biochim. Biophys. Acta. 

1725: 305-313. 

Rich, K. E.; Petkau, J.; Vedal, S.; Brauer, M. (2004) A case-crossover analysis of particulate air pollution and 

cardiac arrhythmia in patients with implantable cardioverter defibrillators. Inhalation Toxicol. 16: 363-372. 

Rich, D. Q.; Schwartz, J.; Mittleman, M. A.; Link, M.; Luttmann-Gibson, H.; Catalano, P. J.; Speizer, F. E.; 

Dockery, D. W. (2005) Association of short-term ambient air pollution concentrations and ventricular 

arrhythmias. Am. J. Epidemiol. 161: 1123-1132. 

Rich, D. Q.; Mittleman, M. A.; Link, M. S.; Schwartz, J.; Luttmann-Gibson, H.; Catalano, P. J.; Speizer, F. E.; Gold, 

D. R.; Dockery, D. W. (2006) Increased risk of paroxysmal atrial fibrillation episodes associated with acute 

increases in ambient air pollution. Environ. Health Perspect. 114: 120-123. 

Riediker, M.; Cascio, W. E.; Griggs, T. R.; Herbst, M. C.; Bromberg, P. A.; Neas, L.; Williams, R. W.; Devlin, R. 

B. (2004) Particulate matter exposure in cars is associated with cardiovascular effects in healthy young 

men. Am. J. Respir. Crit. Care Med. 169: 934-940. 

Roberts, S. (2005a) An investigation of distributed lag models in the context of air pollution and mortality time 

series analysis. J. Air Waste Manage. Assoc. 55: 273-282. 

Roberts, S. (2005b) Using moving total mortality counts to obtain improved estimates for the effect of air pollution 

on mortality. Environ. Health Perspect. 113: 1148-1152. 

Roberts, S.; Martin, M. A. (2006) Applying a moving total mortality count to the cities in the NMMAPS database to 

estimate the mortality effects of particulate matter air pollution. Occup. Environ. Med. 63: 193-197. 

Romieu, I.; Téllez-Rojo, M. M.; Lazo, M.; Manzano-Patiño, Cortez-Lugo, M.; Julien, P.; Bélanger, M. C.; 

Hernandez-Avila, M. Holguin, F. (2005) Omega-3 fatty acid prevents heart rate variability reductions 

associated with particulate matter. Am. J. Respir. Crit. Care Med. 172: 1534-1540. 

Rückerl, R.; Ibald-Mulli, A.; Koenig, W. Schneider, A.; Woelke, G.; Cyrys, J.; Heinrich, J.; Marder, V.; Frampton, 

M.; Wichmann, H. E.; Peters, A. (2006) Air pollution and markers of inflammation and coagulation in 

patients with coronary heart disease. Environ. Health Perspect. 173: 432-441. 

Sagiv, S. K.; Mendola, P.; Loomis, D.; Herring, A. H.; Neas, L. M.; Savitz, D. A.; Poole, C. (2005) A time-series 

analysis of air pollution and preterm birth in Pennsylvania, 1997-2001. Environ. Health Perspect. 

113: 602-606. 

Salam, M. T.; Millstein, J.; Li, Y.-F.; Lurmann, F. W.; Margolis, H. G.; Gilliland, F. D. (2005) Birth outcomes and 

prenatal exposure to ozone, carbon monoxide, and particulate matter: results from the Children's Health 

Study. Environ. Health Perspect. 113: 1638-1644. 

Samoli, E.; Analitis, A.; Touloumi, G.; Schwartz, J.; Anderson, H. R.; Sunyer, J.; Bisanti, L.; Zmirou, D.; Vonk, 

J. M.; Pekkanen, J.; Goodman, P.; Paldy, A.; Schindler, C.; Katsouyanni, K. (2005) Estimating the 

exposure-response relationships between particulate matter and mortality within the APHEA multicity 

project. Environ. Health Perspect. 113: 88-95. 
 55 

Sandström, T.; Cassee, F. R.; Salonen, R.; Dybing, E. (2005) Recent outcomes in European multicentre projects on 

ambient particulate air pollution. Toxicol. Appl. Pharmacol. 207: 261-268. 

Schaumann, F.; Borm, P. J. A.; Herbrich, A.; Knoch, J.; Pitz, M.; Schins, R. P. F.; Luettig, B.; Hohlfeld, J. M.; 

Heinrich, J.; Krug, N. (2004) Metal-rich ambient particles (particulate matter 2.5) cause airway 

inflammation in healthy subjects. Am. J. Respir. Crit. Care Med. 170: 898-903. 

Schins, R. P. F.; Lightbody, J. H.; Borm, P. J. A.; Shi, T.; Donaldson, K.; Stone, V. (2004) Inflammatory effects of 

coarse and fine particulate matter in relation to chemical and biological constituents. Toxicol. Appl. 

Pharmacol. 195: 1-11. 

Schwartz, J. (2004a) Is the association of airborne particles with daily deaths confounded by gaseous air pollutants? 

An approach to control by matching. Environ. Health Perspect. 112: 557-561. 

Schwartz, J. (2004b) The effects of particulate air pollution on daily deaths: a multi-city case crossover analysis. 

Occup. Environ. Med. 61: 956-961. 

Schwartz, J.; Litonjua, A.; Suh, H.; Verrier, M.; Zanobetti, A.; Syring, M.; Nearing, B.; Verrier, R.; Stone, P.; 

MacCallum, G.; Speizer, F. E.; Gold, D. R. (2005) Traffic related pollution and heart rate variability in a 

panel of elderly subjects. Thorax 60: 455-461. 

Seagrave, J.; Mauderly, J. L.; Seilkop, S. K. (2003) In vitro relative toxicity screening of combined particulate and 

semivolatile organic fractions of gasoline and diesel engine emissions. J. Toxicol. Environ. Health A 

66: 1113-1132. 

Shi, T.; Knaapen, A. M.; Begerow, J.; Birmili, W.; Borm, P. J.; Schins, R. P. (2003) Temporal variation of hydroxyl 

radical generation and 8-hydroxy-2'-deoxyguanosine formation by coarse and fine particulate matter. 

Occup. Environ. Med. 60: 315-321. 

Silkoff, P. E.; Zhang, L.; Dutton, S.; Langmack, E. L.; Vedal, S.; Murphy, J.; Make, B. (2005) Winter air pollution 

and disease parameters in advanced chronic obstructive pulmonary disease panels residing in Denver, 

Colorado. J. Allergy Clin. Immunol. 115: 337-344. 

Simpson, R.; Williams, G.; Petroeschevsky, A.; Best, T.; Morgan, G.; Denison, L.; Hinwood, A.; Neville, G.; 

Neller, A. (2005) The short-term effects of air pollution on daily mortality in four Australian cities. Aust. 

N. Z. J. Public Health 29: 205-212. 

Sinclair, A. H.; Tolsma, D. (2004) Associations and lags between air pollution and acute respiratory visits in an 

ambulatory care setting: 25-month results from the aerosol research and inhalation epidemiological study. 

J. Air Waste Manage. Assoc. 54: 1212-1218. 

Sioutas, C.; Koutrakis, P.; Godleski, J. J.; Ferguson, S. T.; Kim, C. S.; Burton, R. M. (1997) Fine particle 

concentrators for inhalation exposures–effect of particle size and composition. J. Aerosol Sci. 

28: 1057-1071. 

Sioutas, C.; Kim, S.; Chang, M. (1999) Development and evaluation of a prototype ultrafine particle concentrator. 

J. Aerosol Sci. 30: 1001-1017. 

Slaughter, J. C.; Kim, E.; Sheppard, L.; Sullivan, J. H.; Larson, T. V.; Claiborn, C. (2005) Association between 

particulate matter and emergency room visits, hospital admissions and mortality in Spokane, Washington. 

J. Exposure Anal. Environ. Epidemiol. 15: 153-159. 

Smith, K. R.; Kim, S.; Recendez, J. J.; Teague, S. V.; Ménache, M. G.; Grubbs, D. E.; Sioutas, C.; Pinkerton, K. E. 

(2003) Airborne particles of the California Central Valley alter the lungs of health adult rats. Environ. 

Health Perspect. 111: 902-908. 

Soares, S. R. C.; Bueno-Guimarães, H. M.; Ferreira, C. M.; Rivero, D. H. R. F.; De Castro, I.; Garcia, M. L. B.; 

Saldiva, P. H. N. (2003) Urban air pollution induces micronuclei in peripheral erythrocytes of mice in vivo. 

Environ. Res. 92: 191-196. 

Sørensen, M.; Daneshvar, B.; Hansen, M.; Dragsted, L. O.; Hertel, O.; Knudsen, L.; Loft, S. (2003) Personal PM2.5

exposure and markers of oxidative stress in blood. Environ. Health Perspect. 111: 161-165. 

Staniswalis, J. G.; Parks, N. J.; Bader, J. O.; Maldonado, Y. M. (2005) Temporal analysis of airborne particulate 

matter reveals a dose-rate effect on mortality in El Paso: indications of differential toxicity for different 

particle mixtures. J. Air Waste Manage. Assoc. 55: 893-902. 

Steerenberg, P. A.; Withagen, C. E.; van Dalen, W. J.; Dormans, J. A.; Heisterkamp, S. H.; van Loveren, H.; Cassee, 

F. R. (2005) Dose dependency of adjuvant activity of particulate matter from five European sites in three 

seasons in an ovalbumin-mouse model. Inhalation Toxicol. 17: 133-145. 

Steerenberg, P. A.; Van Amelsvoort, L.; Lovik, M.; Hetland, R. B.; Alberg, T.; Halatek, T.; Bloemen, H. J. T.; 

Rydzynski, K.; Swaen, G.; Schwarze, P.; Dybing, E.; Cassee, F. R. (2006) Relation between sources of 

particulate air pollution and biological effect parameters in samples from four European cities: an 

exploratory study. Inhalation Toxicol. 18: 333-346. 
 56 

Su, Y.; Sipin, M. F.; Spencer, M. T.; Qin, X.; Moffet, R. C.; Shields, L. G.; Prather, K. A.; Venkatachari, P.; Jeong, 

C.-H.; Kim, E.; Hopke, P. K.; Gelein, R. M.; Utell, M. J.; Oberdorster, G.; Bernsten, J.; Devlin, R. B.; and 

Chen, L. C. (2006) Real-time characterization of the composition of individual particles emitted from 

ultrafine particle concentrators. Aerosol Sci. Technol. 40:437-455. 

Sugiri, D.; Ranft, U.; Schikowski, T.; Kramer, U. (2006) The influence of large-scale airborne particle decline and 

traffic-related exposure on children's lung function. Environ. Health Perspect. 114: 282-288. 

Sullivan, J.; Ishikawa, N.; Sheppard, L.; Siscovick, D.; Checkoway, H.; Kaufman, J. (2003) Exposure to ambient 

fine particulate matter and primary cardiac arrest among persons with and without clinically recognized 

heart disease. Am. J. Epidemiol. 157: 501-509. 

Sun, Q.; Wang, A.; Jin, X.; Natanzon, A.; Duquaine, D.; Brook, R. D.; Aguinaldo, J. G.; Fayad, Z. A.; Fuster, V.; 

Lippmann, M.; Chen, L. C.; Rajagopalan, S. (2006) Long-term air pollution exposure and acceleration of 

atherosclerosis and vascular inflammation in an animal model. JAMA J. Am. Med. Assoc. 294: 3003-3010. 

Sunyer, J.; Basagaña, X.; Belmonte, J.; Antó, J. M. (2002) Effect of nitrogen dioxide and ozone on the risk of dying 

in patients with severe asthma. Thorax 57: 687-693. 

Tager, I. B.; Balmes, J.; Lurmann, F.; Ngo, L.; Alcorn, S.; Künzli, N. (2005) Chronic exposure to ambient ozone and 

lung function in young adults. Epidemiology 16: 751-759. 

Timonen, K. L.; Vanninen, E.; De Hartog, J.; Ibald-Mulli, A.; Brunekreef, B.; Gold, D. R.; Henrich, J.; Hoek, G.; 

Lanki, T.; Peters, A.; Tarkiainen, T.; Tiittanen, P.; Kreyling, W.; Pekkanen, J. (2005) Effects of ultrafine 

and fine particulate and gaseous air pollution on cardiac autonomic control in subjects with coronary artery 

disease: the ULTRA study. J. Exposure Anal. Environ. Epidemiol.: 10.1038/sj.jea.7500460. 

Touloumi, G.; Samoli, E.; Quenel, P.; Paldy, A.; Anderson, R. H.; Zmirou, D.; Galan, I.; Forsberg, B.; Schindler, C.; 

Schwartz, J.; Katsouyanni, K. (2005) Short-term effects of air pollution on total and cardiovascular 

mortality: the confounding effect of influenza epidemics. Epidemiology 16: 49-57. 

Tsai, S.-S.; Huang, C.-H.; Goggins, W. B.; Wu, T.-N.; Yang, C.-Y. (2003) Relationship between air pollution and 

daily mortality in a tropical city: Kaohsiung, Taiwan. J. Toxicol. Environ. Health Part A 66: 1341-1349. 

Tunnicliffe W. S.; Harrison, R. M.; Kelly, F. J.; Dunster, C.; Ayres, J. G. (2003) The effect of sulphurous air 

pollutant exposures on symptoms, lung function, exhaled nitric oxide, and nasal epithelial lining fluid 

antioxidant concentrations in normal and asthmatic adults. Occup. Environ. Med. 60: e15. 

U.S. Environmental Protection Agency. (1996) Air quality criteria for particulate matter. Research Triangle Park, 

NC: National Center for Environmental Assessment-RTP Office; report nos. EPA/600/P-95/001aF-cF. 3v. 

U.S. Environmental Protection Agency. (2004) Air quality criteria for particulate matter. Research Triangle Park, 

NC: National Center for Environmental Assessment; report no. EPA/600/P-99/002aF-bF. 2v. Available: 

http://cfpub.epa.gov/ncea/ [9 November, 2004]. 

Urch, B.; Brook, J. R.; Wasserstein, D.; Brook, R. D.; Rajagopalan, S.; Corey, P.; Silverman, F. (2004) Relative 

contributions of PM2.5 chemical constituents to acute arterial vasoconstriction in humans. Inhalation 

Toxicol. 16: 345-352. 

Urch, B.; Silverman, F.; Corey, P.; Brook, J. R.; Lukic, K. Z.; Rajagopalan, S.; Brook, R. D. (2005) Acute blood 

pressure responses in healthy adults during controlled air pollution exposures. Environ. Health Perspect. 

113: 1052-1055. 

Vedal, S.; Brauer, M.; White, R.; Petkau, J. (2003) Air pollution and daily mortality in a city with low levels of 

pollution. Environ. Health Perspect. 111: 45-51. 

Veranth, J. M.; Moss, T. A.; Chow, J. C.; Labban, R.; Nichols, W. K.; Walton, J. C.; Walton, J. G.; Yost, G. S. 

(2006) Correlation of in vitro cytokine responses with the chemical composition of soil-derived particulate 

matter. Environ. Health Perspect. 114: 341-349. 

Veranth, J. M.; Reilly, C. A.; Veranth, M. M.; Moss, T. A.; Langelier, C. R.; Lanza, D. L.; Yost, G. S. (2004) 

Inflammatory cytokines and cell death in BEAS-2B lung cells treated with soil dust, lipopolysaccharide, 

and surface-modified particles. Toxicol. Sci. 82: 88-96. 

Veronesi, B.; Makwana, O.; Pooler, M.; Chen, L. C. (2005) Effects of subchronic exposures to concentrated ambient 

particles. VII. Degeneration of dopaminergic neurons in Apo E-/- mice. Inhalation Toxicol. 17: 235-241. 

Villeneuve, P. J.; Burnett, R. T.; Shi, Y.; Krewski, D.; Goldberg, M. S.; Hertzman, C.; Chen, Y.; Brook, J. (2003) A 

time-series study of air pollution, socioeconomic status, and mortality in Vancouver, Canada. J. Exposure 

Anal. Environ. Epidemiol. 13: 427-435. 
 57 

Von Klot, S.; Peters, A.; Aalto, P.; Bellander, T.; Berglind, N.; D'Ippoliti, D.; Elosua, R.; Hörmann, A.; Kulmala, 

M.; Lanki, T.; Löwel, H.; Pekkanen, J.; Picciotto, S.; Sunyer, J.; Forastiere, F.; Health Effects of Particles 

on Susceptible Subpopulations (HEAPSS) Study Group. (2005) Ambient air pollution is associated with 

increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities. 

Circulation 112: 3073-3079. 

Wellenius, G. A.; Coull, B. A.; Godleski, J. J.; Koutrakis, P.; Okabe, K.; Savage, S. T. (2003) Inhalation of 

concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs. Environ. Health 

Perspect. 111: 402-408. 

Wellenius, G. A.; Schwartz, J.; Mittleman, M. A. (2005) Air pollution and hospital admissions for ischemic and 

hemorrhagic stroke among medicare beneficiaries. Stroke 36: 2549-2553. 

Wellenius, G. A.; Schwartz, J.; Mittleman, M. A. (2006) Particulate air pollution and hospital admissions for 

congestive heart failure in seven United States cities. Am. J. Cardiol. 97: 404-408. 

Welty, L. J.; Zeger, S. L. (2005) Are the acute effects of particulate matter on mortality in the National Morbidity, 

Mortality, and Air Pollution study the result of inadequate control for weather and season? A sensitivity 

analysis using flexible distributed lag models. Am. J. Epidemiol. 162: 80-88. 

Wheeler, A.; Zanobetti, A.; Gold, D. R.; Schwartz, J.; Stone, P.; Suh, H. H. (2006) The relationship between 

ambient air pollution and heart rate variability differs for individuals with heart and pulmonary disease. 

Environ. Health Perspect. 114: 560-566. 

Woodruff, T. J.; Parker, J. D.; Schoendorf, K. C. (2006) Fine particulate matter (PM2.5) air pollution and selected 

causes of postneonatal infant mortality in California. Environ. Health Perspect. 114: 785-790. 

Xia, T.; Korge, P.; Weiss, J. N.; Li, N.; Venkatesen, M. I.; Sioutas, C.; Nel, A. (2004) Quinones and aromatic 

chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine 

particle toxicity. Environ. Health Perspect. 112: 1347-1358. 

Yanagisawa, R.; Takano, H.; Inoue, K.; Ichinose, T.; Sadakane, K.; Yoshino, S.; Yamaki, K.; Kumagai, Y.; 

Uchiyama, K.; Yoshikawa, T.; Morita, M. (2003) Enhancement of acute lung injury related to bacterial 

endotoxin by components of diesel exhaust particles. Thorax 58: 605-612. 

Yang, C.-Y.; Chang, C.-C.; Chuang, H.-Y.; Tsai, S.-S.; Wu, T.-N.; Ho, C.-K. (2004) Relationship between air 

pollution and daily mortality in a subtropical city: Taipei, Taiwan. Environ. Int. 30: 519-523. 

Yin, X. J.; Ma, J. Y. C.; Antonini, J. M.; Castranova, V.; Ma, J. K. H. (2004) Roles of reactive oxygen species and 

heme oxygenase-1 in modulation of alveolar macrophage-mediated pulmonary immune responses to 

listeria monocytogenes by diesel exhaust particles. Toxicol. Sci. 82: 143-153. 

Zanobetti, A.; Schwartz, J. (2005) The effect of particulate air pollution on emergency admissions for myocardial 

infarction: a multicity case-crossover analysis. Environ. Health Perspect. 113: 978-982. 

Zanobetti, A.; Schwartz, J.; Samoli, E.; Gryparis, A.; Touloumi, G.; Peacock, J.; Anderson, R. H.; Le Tertre, A.; 

Bobros, J.; Celko, M.; Goren, A.; Forsberg, B.; Michelozzi, P.; Rabczenko, D.; Hoyos, S. P.; Wichmann, 

H. E.; Katsouyanni, K. (2003) The temporal pattern of respiratory and heart disease mortality in response to 

air pollution. Environ. Health Perspect. 111: 1188-1193. 

Zeka, A.; Schwartz, J. (2004) Estimating the independent effects of multiple pollutants in the presence of 

measurement error: an application of a measurement-error-resistant technique. Environ. Health Perspect. 

112: 1686-1690. 

Zeka, A.; Zanobetti, A.; Schwartz, J. (2005) Short term effects of particulate matter on cause specific mortality: 

effects of lags and modification by city characteristics. Occup. Environ. Med. 62: 718-725. 

Zeka, A.; Zanobetti, A.; Schwartz, J. (2006) Individual-level modifiers of the effects of particulate matter on daily 

mortality. Am. J. Epidemiol. 163: 849-859. 

Zelikoff, J. T.; Schermerhorn, K. R.; Fang, K.; Cohen, M. D.; Schlesinger, R. B. (2002) A role for associated 

transition metals in the immunotoxicity of inhaled ambient particulate matter. Environ. Health Perspect. 

110(suppl. 5): 871-875. 

Zhang, J.; Hu, W.; Wei, F.; Wu, G.; Korn, L. R.; Chapman, R. S. (2002) Children's respiratory morbidity prevalence 

in relation to air pollution in four Chinese cities. Environ. Health Perspect. 110: 961-967. 
 A-1 

APPENDIX A 

Summary Information from Recent Studies on the 

Health Effects of Particulate Matter 
 A-2 

Table A1: Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and 

Mortality and Morbidity 

Table A2. Associations of Acute PM2.5 Exposure with Mortality 

Table A3. Associations of Acute PM10-2.5 Exposure with Mortality 

Table A4. Effects of PM2.5 on Daily Hospital Admissions 

Table A5. Effects of PM10-2.5 on Daily Hospital Admissions 

Table A6. Effects of PM2.5 on Daily Emergency Department Visits 

Table A7. Effects of PM10-2.5 on Daily Emergency Department Visits 

Table A8. Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes 

Table A9. Effects of Acute PM10-2.5 Exposure on Cardiovascular Outcomes 

Table A10. Effects of Acute PM2.5 Exposure on Various Respiratory Outcomes 

Table A11. Effects of Acute PM10-2.5 Exposure on Various Respiratory Outcomes 

Table A12. Effects of Acute PM2.5 Exposure on Birth Outcomes 

Table A13. Results of Epidemiologic “Intervention” Studies 

Table A14. Associations between Source-related Fine Particles and Health Outcomes 

Table A15. Associations of Acute Exposure to Fine Particle Components with Health 

Outcomes

Table A16. CAPs Studies with Source Apportionment or Components Analysis 

Table A17. Other Acute CAPs Studies 

Table A18. Subchronic CAPs Studies 

Table A19. Size-fractionated and Collected Ambient PM Studies 

Table A20. Acid Aerosol Studies 
 A-3 Table A1: Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and Mortality and 

Cohort, Location Study PM Data, Concentrations Cohort Description Quantitative Results CoMortality Studies: Harvard Six Cities follow-up Laden et al. (2006) Initial Harvard impactor data for 1974-1989 (period I). Period II data (1990-1998) based on additional PM2.5 data (a) estimated from visibility and PM10 measurements and (b) measured at AQS monitors w/in 50 miles; r = 0.93 between estimated and measured PM2.5. PM2.5 decreases ranged from <1 μg/m3/decade in Topeka to 7 μg/m3/decade in Steubenville. 

Recent PM2.5 means range from 

10.2 to 22 μg/m3

8096 white participants, 25+ yr, death records through 1998. 

RR (total mortality) for PM2.5 (per 10 μg/m3): 

entire study period: 1.16 (1.07-1.26) period I: 1.17 (1.08-1.26) period II: 1.13 (1.01-1.27) RR with PM2.5 in year of death: 1.14 (1.06-1.22) 

RR for reduced mortality risk with reduction in PM2.5: 0.73 (0.57-0.95). 

Similar results presented for cardiovascular and respiratory deaths. Positive, nonsignificant associations reported for lung cancer deaths in different periods, but no significant association for reduced risk. 

Lowperio

asso25 yleast 
 A-4 Table A1 (cont’d): Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and Mortality 

Cohort, Location Study PM Data, Concentrations Cohort Description Quantitative Results CoMortality Studies (cont’d): AHSMOG Chen et al., 2005 1973-1998 CARB data for PM10 and gases; PM2.5 estimated from visibility; no discussion of PM10- 2.5 determination. Monthly estimates (1973-1998) of PM for each individual. PM2.5 mean = 29.0 μg/m3 PM10-2.5 mean = 25.4 μg/m3 3239 Adventist adults, fatal coronary heart disease (ICD 410-414) (92 cases) Significant associations in females, not males; stronger and statistically significant associations in subset of postmenopausal females (80 of 92 cases). Females: PM2.5 RR = 1.42 (1.06-1.90) and remains significant in 2-pollutant models (increased size with O3 and SO2, no change with NO2) PM10-2.5 RR = 1.38 (0.97-1.95) and increases, becomes significant with O3 and NO2 in 2-pollutant models, little change with SO2. Males: PM2.5 RR = 0.90 (0.76-1.05) 

PM10-2.5 RR = 0.92 (0.66-1.29) (both little change 

with co-pollutants) (all per 10 μg/m3) 

Authwith (200effecdiffefema“we possdiffeerror likelhomNote(e.g.exclu

ACS, Los Angeles Jerrett et al., 2005 

PM2.5 from 23 stations in LA 

basin (and 42 ozone monitors) for year 2000. Kriging and interpolation methods used to assign exposure levels. Also traffic buffers of 500 and 100 m from freeway based on zip code centroids PM2.5 mean = NR, range 9-27 μg/m3

22,905 subjects in 267 zip code areas; death records 1982-2000 

Significant associations between PM2.5 and deaths 

from all causes (RR 1.24, 1.11-1.37 per 10 μg/m3), 

IHD, cardiopulmonary diseases, lung cancer, endocrine disease, digestive disease. No significant associations with digestive and other cancers, diabetes, accidents and other causes. Associations generally decreased with addition of ecologic covariates. After adjustment for 44 covariates and freeways w/in 500 m, significant associations with death from all causes (RR 1.17, 1.05-1.31) and IHD (RR 1.38, 1.11-1.72). 

“Genwith suggexpoassohealtin in
 A-5 Table A1 (cont’d): Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and Mortality 

Cohort, Location Study PM Data, Concentrations Cohort Description Quantitative Results CMortality Studies (cont’d): ACS, cause- specific deaths Pope et al. (2004) Results reported for average PM2.5 exposure levels, using IPN data from 1979-1983 (mean 21.1 μg/m3) and AQS data from 1999-2000 (mean 14.0 μg/m3). 3-digit zip codes at residence used for exposure estimates. PM2.5 mean 17.1 μg/m3 (averaged data) ACS cohort, 16-year follow-up, ~300,000 subjects Significant associations between average PM2.5 and all CV diseases (RR 1.12, 1.08-1.15), IHD (RR 1.18, 1.14-1.23) and dysrhythmias/heart failure/cardiac arrest (RR 1.13, 1.05-1.21). Positive nonsignificant associations with some other CV diseases. Negative association with COPD (RR 0.84, 0.77-0.93) and no associations with diabetes, pneumonia and other respiratory diseases. Whe

statuassobetw

from IHD (nevsmokand hassosmok
 A-6 Table A1 (cont’d): Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and Mortality 

Cohort, Location Study PM Data, Concentrations Cohort Description Quantitative Results CMortality Studies (cont’d): Veterans cohort Lipfert et al. (2006) Traffic density estimated [vehicle-km traveled/county land area] using data from 1985, 1990 and 1997. PM2.5 data restricted to 1999-2001, averaged across period. PM2.5 mean of 14.6 μg/m3 for 1997-2001; sulfate mean 10.7 μg/m3 for 1976-1981; PM10-2.5 mean 16.0 μg/m3 for 1989-1996. Veterans cohort, deaths through 2001, ~25,000 subjects For cohort members dying in 1989-1996 who originally lived in counties with AQ data: significant associations with: traffic density (RR 1.176, 1.100-1.258 per 2.6 106 vehicles km2 in 1999 data) PM2.5 (RR 1.118, 1.038-1.203 per 8 μg/m3 1999 data) PM10-2.5 (RR 1.072, 1.013-1.124 per 12 μg/m3 1999 data) 

nonsulfate PM2.5 (RR 1.091, 1.025-1.161) but not 

sulfates. In 3-poll models, traffic density is little changed, PM2.5 effect reduced and nonsignificant (RR 

1.032) and PM10-2.5 effect negative, nonsignificant.

Significant associations between mortality and traffic density in all time periods (RR’s range from 1.019-1.036). Also significant associations with peak O3 (95th percentile of daily max values). 

“...mrelattimedespreguper v1970other may partiroad psycspatisocio
 A-7 Table A1 (cont’d): Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and Mortality 

Cohort, Location Study PM Data, Concentrations Cohort Description Quantitative Results CMortality Studies (cont’d): Veterans cohort Lipfert et al. (in press) Traffic density and historic air pollution data used as Lipfert et al., 2006, also fine particle speciation data from 2002. Gravimetric PM2.5 mean of 13.2 μg/m3 for 2002 Veterans cohort, deaths through 2001 In single-pollutant models for 1997-2001 mortality and 1999-2001 AQ data and 2002 speciation data, significant associations reported between mortality and traffic density, EC, nitrate, V and Ni. In two- or three-pollutant models, traffic density associations remain significant. Associations with nitrates, V and Ni also remain significant in some multi-pollutant models. Peak ozone concentration also significantly associated with mortality. PM2.5 and sulfates also positively associated with mortality, but not statistically significant. “Tra

consimpopredpollupossaspenoisemost or wpreddensadvameasqualthat markpollugrad
 A-8 Table A1 (cont’d): Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and Mortality 

Cohort, Location Study PM Data, Concentrations Cohort Description Quantitative Results CMortality Studies (cont’d): CA cancer prevention study Enstrom et al. (2005) 1979-1983 IPN data for 11 CA counties, average over time and across stations for each county. overall PM2.5 mean 23.4 μg/m3 (10.6-42.0 range) 35,789 elderly people in 11 CA counties with PM2.5 data (28,441 deaths by 2002) Many results presented. RR’s presented for each county relative to Los Angeles (PM2.5 mean 28.2 μg/m3) and none are significant, many negative. RR’s by decade of death-significant associations for 1973-1982, not for 1983-92 or 1993-2002. For 1973-1982 period, RR reduced somewhat but remains significant with addition of individual potential confounders (e.g., age, sex); for 1973- 2002 and 1983-2002 more marked reduction in 

RR size and loss of significance with addition of covariates. 

“Thedo nrelatpartimortCalifrule partiNotecounas an likelexpo

U.S. cystic fibrosis cohort Goss et al. (2004) 

AQS data for 2000, annual average, subject assigned data from population-oriented monitor closest to zip code centroid. 713 monitors for PM2.5 

PM10 mean 24.9 (20.3-28.9) 

μg/m3

PM2.5 mean 13.7 (11.8-15.9) 

μg/m3

11,484 adults and children >5 yr, enrolled in Cystic Fibrosis Foundation National Patient Registry in 1999-2000. 

Main reported results are respiratory symptoms (below). Also evaluated associations with mortality from 22,303 patients in initial cohort (fewer than 200 deaths in cohort). Positive nonsignificant association reported for PM2.5

(RR 1.32, 0.91-1.93), no associations with PM10, 

O3, NO2, SO2 or CO. 
 A-9 Table A1 (cont’d): Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and Mortality 

Cohort, Location Study PM Data, Concentrations Cohort Description Quantitative Results CMortality Studies (cont’d): California Woodruff et al. (2006) CARB air monitoring data obtained. Birth record data linked to data from monitor w/in 5 miles of mother’s residence; data averaged over time period between birth and death. PM2.5 means ranged from 17.3 to 19.8 μg/m3 for different groups Birth records for infants born in California 1999-2000 (n = 788 infant deaths) Median concentrations of PM2.5 were somewhat higher for infant deaths from all causes or respiratory causes than concentrations for matched survivors; not for SIDS or external causes. OR for all-cause deaths (adjusted for maternal characteristics) 1.07 (0.93-1.24) , and for respiratory deaths 2.13 (1.12-4.05) per 10 μg/m3 PM2.5 Morbidity studies: 2 atheroschlerosis clinical trials, 

Los Angeles CA, Kunzli et al. (2005) 

Using data from 23 monitoring sites in 2000, modeling used to assign exposure at zip code level. Mean PM2.5 exposure level at 20.6 μg/m3, range 

5.2-26.9 μg/m3. 

798 adults in 2 studies in LA basin. 

Outcome measure = CIMT (carotid intimamedia thickness), a measure of atheroschlerosis. Significant associations of 5.9% (1-11%) increase in CIMT per 20 μg/m3 PM2.5 for total study 

population. Effects significant in women, not in men; strongest association for women >60 yr 

CA Children’s Health Study Gauderman et al. (2004) 

Means of annual averages (1994-2000) of measurements from stations in 12 communities, included PM10 (hourly) and 

PM2.5 (2-week integrated filter), 

acid vapor, ED and OC. Mean PM2.5 ranges from 5 to 

28 μg/m3 from figure. 

Recruited 1759 4th grade 

children 

Significant decreases in FEV1 growth with PM2.5, 

acid vapor, ED and NO2. 

Decreases also for FVC and MMEF growth but less often statistically significant. 

“...cupolluadvedevefrom yearsigniFEV

adult
 A-10 Table A1 (cont’d): Associations Between Long-Term Exposure to PM2.5 and PM10-2.5 and Mortality 

Cohort, Location Study PM Data, Concentrations Cohort Description Quantitative Results CMorbidity studies (cont’d): CA Children’s Health Study Millstein et al. (2004) Monthly means of pollutant data (data presented in figures only). 2034 4th grade children, questionnaire in 1995. Monthly prevalence of asthma medication use associated with monthly average O3, HNO3, and acetic acid levels, not with PM2.5 , PM10 or PM10-2.5. Prevalence of wheeze associated with PM10-2.5 during spring and summer months. CA Children’s Health Study McConnell et al. (2003) 4-year means of pollutants for 1996-1999 (same sites from Gauderman et al. (2004); PM10-2.5 determined by subtraction of PM2.5 from PM10 (2-wk integrated). 

Means across communities of 13.8 μg/m3 PM2.5, 17.0 μg/m3

PM10-2.5

475 children with asthma, questionnaire 1996-1999 

Bronchitic symptoms associated with yearly variability of PM2.5 (per μg/m3), OR 1.09 (1.01-

1.17), with OC, OR 1.41 (1.12-1.78), NO2 and O3. 

No significant associations with PM10-2.5. Larger 

OR’s with within-community yearly variability than between-community (per μg/m3 PM2.5 OR = 

1.03, 1.01-1.05). OC and NO2 effects strongest in 

2-pollutant models 

U.S. cystic fibrosis cohort Goss et al. (2004) 

AQS data for 2000, annual average, subject assigned data from population-oriented monitor closest to zip code centroid. 713 monitors for PM2.5PM10 mean 24.9 (20.3-28.9); 

PM2.5 mean 13.7 (11.8-15.9) 

11,484 adults and children >5 yr, enrolled in Cystic Fibrosis Foundation National Patient Registry in 1999-2000. 

Increased odds of having 2 or more pulmonary exacerbations per 10 μg/m3 PM2.5 (21%, 7-33%) 

and PM2.5 (8%, 2-15%) as well as ozone. 

No associations with NO2, SO2, or CO. 

Negative associations with lung function in crosssectional analysis. Decreased FEV1 with PM2.5

and PM10; no clear associations with gaseous 

pollutants. 

“In camb

ozonfor pand ichanthe C
 A-11 

Other studies using PM10 or other PM indicators:

Mortality: 

Evans and Smith (2005) used data from U.S. Health and Retirement Study, a national 

panel survey of birth cohorts 1931-1941 with follow-up in 1992-2004. Long-term (1990-2000) 

PM10 exposure associated with a new heart condition (reported between 1994 and 1996) 

(coefficient = 0.004, t = 1.74) and significantly associated with shortness of breath (coefficient = 

0.017, t = 2.25) but not with new lung conditions. Recent (1994-6) PM10 exposure associated 

with new heart condition (coeff = 0.0004, t = 1.74); also association with shortness of breath, but 

not with new lung condition. Long-term O3 exposure also associated with new lung condition 

and shortness of breath 

Filleul et al. (2005) used data from a respiratory disease survey data of 14,000+ adults in 

24 areas in 7 cities. For 24 areas no association was reported between particles (BS) and 

mortality (RR 0.99, 0.98-1.01). Further analyses excluded data from 6 areas where monitors 

were in an area “heavily influenced by the local traffic and, so, non-representative of the mean 

exposure of the population of the entire area” based on NO/NO2 ratio. For these 18 areas, RR 

with BS of 1.07 (1.03-1.10) for total mortality; nonsignificant RR’s of 1.03 and 1.05 for lung 

cancer and cardiopulmonary diseases. Significant associations also with TSP for total and 

cardiopulmonary diseases. Significant associations also with NO, NO2, but not SO2. No 

consistent modifying effect of gender or education level. BS means ranged from 21 to 152 

μg/m3; “heavy traffic” BS means of 46, 105, 141, 111, and 91 μg/m3. 

Morbidity:

Tager et al. (2005) used data from UC Berkeley students—255 never-smoking students 

from LA and San Francisco areas—and reported consistent inverse associations between O3, 

PM10 and NO2 and FEF75, FEF25-75 in both men and women. O3 associations were more robust 

in co-pollutant models than PM10 or NO2. Mean lifetime PM10 exposure was 48 μg/m3 for men 

and 45 μg/m3

 for women. 

Salam et al. (2005) used birth certificate information obtained for California-born 

children participating in the Children’s Health Study (n = 3901) to test for associations between 

air pollution exposure and birth weight. Air pollution estimates assigned using zip code of 

maternal residence at birth, with spatial interpolation based on data from up to the three nearest 

stations within 50 km of zip code. Exposure estimates calculated as monthly average of 24 hr 

measurements, computed for trimesters and full pregnancy. A nonsignificant association was 

reported between higher PM10 exposures during the third trimester and decreased birth weight. 

Significant associations were reported with first-trimester CO exposure and third-trimester O3

exposure. 

Penard-Morand et al. (2005) uses questionnaire data for 6672 children in six French cities 

with air pollution data collected at children’s schools from 1998-2000. The PM10 mean in high 

and low cities was 23.8 and 18.0 μg/m3, respectively; the overall mean was approximately 21 

μg/m3

 (from figure). Significant associations were reported with PM10 and asthma, atopic 

dermatitis, exercise-induced bronchial reactivity and allergic rhinitis. 
 A-12 

Pierse et al. (2006) reported an association between PM10 and symptoms in children 

surveyed in 1998 and 2001 in Leicester UK. The OR for prevalence of cough without cold in 

1998 and 2001 was 1.21 (1.07-1.38) and 1.56 (1.32-1.84), respectively, PM10 was also associated 

with the incidence of wheeze. 

Zhang et al. (2002) used questionnaire data for 7621 children in four Chinese cities and 

1995-1996 air pollution data. Grand means were PM2.5 = 92 μg/m3

 (not a typo) and PM10-2.5 = 

59 μg/m3

. Significant associations were observed between PM10-2.5 and incidence of bronchitis 

(2.20, 1.14-4.26), persistent cough (1.46, 1.12-1.90) and persistent phlegm (2.83, 1.93-4.16); 

positive nonsignificant association with incidence of asthma, wheeze, and ever-hospitalization 

for respiratory disease. For all six endpoints positive but nonsignificant associations were 

reported with PM2.5. No significant associations (some nonsignificant negative) were observed 

with SO2 and NOx. 

Bayer-Oglesby et al., (2005) used data from a study of 9591 school-children in nine 

Swiss communities with a respiratory questionnaire administered in 1992-2001. A decrease in 

PM10 (per 10 μg/m3

) was associated with a decrease in prevalence of chronic cough (OR 0.65, 

0.54-0.79), bronchitis (OR 0.66, 0.55-0.80), common cold (OR 0.78, 0.6800.89), nocturnal dry 

cough (OR 0.70, 0.60-0.83) and conjunctivitis symptoms. No significant associations were 

reported with wheeze, asthma, sneezing, or hay fever. PM10 decreased 9.8 μg/m3

 between 1993 

and 2000; the decreases in PM10 concentration were three times greater in urban than rural 

communities and ranged from 10-34 μg/m3 in 2000. 
 A-13 Table A2. Associations of Acute PM2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM2.5Ostro et al. (2006) 9 counties in California Jan 1999-Dec 2002 

All nonaccidental, cardiovascular, and respiratory causes, as well as deaths from ischemic heart disease and diabetes; all ages and age >65 yr 

24-h avg PM2.5: Range of means across counties: 14 (Contra Costa and Sacramento) to 29 (Riverside) Range of daily concentrations across counties 0-160 

NO2, CO, O3 2-d lag and 0-1 d 

avg lag 

Time-series study. Poisson regression using penalized and natural spline models. Default model used penalized spine regression. Countyspecific results pooled based on meta-analysis using random-effects model. At least one monitor collected daily PM2.5data in each county. A substantial number of days were missing data, which varied by county and appeared to be generally random. 

% exces

All caus

All agesLag 0-1Age >65 Lag 0-1CardiovAll agesLag 0-1Respirat

All agesLag 0-1In multi

estimate correlate

were adbut was of O3. H

>65 yr, pollutan

coefficieAnalysicategoriindicateassociatmortalitfemalesgraduate
 A-14 Table A2 (cont’d). Associations of Acute PM2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM2.5 (cont’d) Burnett et al. (2004) 12 Canadian cities Jan 1981-Dec 1999 

All nonaccidental, cardiovascular, and respiratory causes 

24-h avg PM2.5: All 12 cities: 12.8 SD not provided. Range of means across cities: 8.1 (St. John) to 16.7 (Windsor) 

PM10-2.5, PM10, 

SO4

2, NO2, SO2, 

CO, O3

0-, 1-, or 2-d lag Time-series study. 

Natural spline functions used to model nonlinear associations. PM2.5 data collected 

every 6th day. PM2.5

data available on 12% of days with mortality data. In 11 of 12 cities, daily PM2.5 data 

collected from Jan 1998 to Dec 2000. 

% exces

All caus

Using aSingle-pLag 1: Two-po

Lag 1: 



SignificNO2 in t

results o

SignificPM10, w

nonsignNO2. 

Only usdaily PM

2000): Single-pLag 1: Two-po

Lag 1: When rewhen dathe NO2 

considerPM2.5, w

fairly ro
 A-15 Table A2 (cont’d). Associations of Acute PM2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM2.5 (cont’d) Dales et al. (2004) 12 Canadian cities Jan 1984-Dec 1999 

SIDS; age <1 yr 24-h avg PM2.5: 

All 12 cities: 12.27 IQR 8.98 Range of means across cities: 8.07 (St. John) to 16.67 (Windsor) 

PM10-2.5, PM10, 

NO2, SO2, CO, 

O3

0-, 1-, 2-, 3-, 4-, or 5-d lag; multiday lags of 2 to 6 d 

Time-series study. Nonlinear randomeffects regression model used. PM2.5 data collected 

every 6th day. 

No assoincidenc

effect esresults o

PM10. 

SignificNO2, SO

Slaughter et al. (2005) Spokane, WA Jan 1995-Jun 2001 

All nonaccidental causes 

24-h avg PM2.5: 

10th%-90th% 4.2-20.2 

PM1, PM10-2.5, PM10, CO 

0-, 1-, 2-, 3-d lag Time-series study. 

Poisson GLM with natural splines. Hourly PM2.5 data 

available. Daily averages calculated. 

RR per 

Lag 1: No assononacci

Similar and PM
 A-16 Table A2 (cont’d). Associations of Acute PM2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM2.5 (cont’d) Mar et al. (in press) Phoenix, AZ Feb 1995-Dec 1997 

All nonaccidental and cardiovascular causes; age 65 yr 

24-h avg PM2.5: Gravimetric sampler: 12.0 SD 6.6 Range 2-39 TEOM sampler: 13.0 SD 7.2 Range 0-42 

Various PM2.5

sources, including soil, traffic, secondary SO4

2

, 

biomass/wood combustion, sea salt, and copper smelter 

0-, 1-, 2-, 3-, 4-d, or 5- lag 

Time-series study. Poisson GLM with natural splines. Daily PM2.5 data 

collected using both gravimetric and TEOM samplers. Focus of study was to assess variability of different methods/ investigators in estimating source apportioned PM2.5

health effects. 

% excesincremeCardiov

Lag 1: Magnituassociatcardiovato those factor. 
 A-17 Table A2 (cont’d). Associations of Acute PM2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM2.5 (cont’d) Ito et al. (in press) Washington, DC Aug1988-Dec 1997 

All nonaccidental, cardiovascular, and cardiorespiratory causes 

24-h avg PM2.5: 17.8 SD 8.7 5th%-95th% 28.7 

Various PM2.5

sources, including soil, traffic, secondary SO4

2

, 

NO3

-, residual 

oil, wood smoke, sea salt, incinerator, and primary coal 

0-, 1-, 2-, 3-, or 

4-d lag 

Time-series study. Poisson GLM with natural splines. PM2.5 data collected every Wednesday and Saturday. Focus of study was to assess variability of different methods/ investigators in estimating source apportioned PM2.5

health effects. 

% exces

All caus

Lag 3: Significcause mobserve

Klemm et al. (2004) Atlanta, GA Aug 1998-July 2000 

All nonaccidental, circulatory, respiratory, cancer, and other causes; age <65 yr and 65 yr 

24-h avg PM2.5: 

19.62 SD 8.32 IQR 11.62 Range 5.29-48.01 

PM10-2.5, SO4

2

, 

EC, OC, NO2, NO3

-, SO2, CO, 

O3, ultrafines, 

hydrocarbons, acid 

Multiday lag of 

0-1 d 

Time-series study. Poisson GLM using natural cubic splines with quarterly, monthly, or biweekly knots. Default model used monthly knots. Daily PM2.5 data 

collected. 

% exces

All caus

Age 65 Lag 0-1Results specificnumber associatNo signin those 
 A-18 Table A2 (cont’d). Associations of Acute PM2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design Ef

PM2.5 (cont’d)Villeneuve et al. (2003) Vancouver, British Columbia, Canada Jan 1986-Dec 1998 

All nonaccidental, cardiovascular, respiratory, and cancer causes; SES status 

24-h avg PM2.5: Daily data from 1995-1998: 7.9 10th%-90th% 4.0-13.0 Range 2.0-32.0 Every 6th day data from 1986-1998: 11.6 10th%-90th% 4.7-20.4 Range 1.8-43.0 

PM10-2.5, PM10, 

TSP, coefficient of haze, SO4

2

, 

SO2, NO2, CO, 

O3

0-, 1-, or 2-d lag; 

multiday lag of 

0-2 d 

Time-series study. Poisson regression using natural spline functions. Daily PM2.5 data 

collected from 1995 to 1998 using TEOM; PM2.5 data collected every 6th day from 1986 to 1998 using a dichotomized sampler. 

% excesResults 

All causLag 0: CardiovLag 0: Respirat

Lag 0: Cancer: Lag 0: 4Collectiassociat

mortalitevidencrisk of camong istatus. Scardiovaobserve

PM10 da
 A-19 Table A2 (cont’d). Associations of Acute PM2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM2.5 (cont’d) Goldberg et al. (2006) Montreal, Canada 1986-1993 

Diabetes, and nonaccidental mortality in subgroups with diabetes diagnosed at least 1 year before death in adults >65 yr. Also considered subgroups with cardiovascular diagnoses. 

24-h avg PM2.5: 17.4 SD 11.4 24-h avg predicted PM2.5: 

17.6 SD 8.8 

PM10, TSP, 

coefficient of haze, SO4

2

, 

predicted SO4

2

, 

SO2, NO2, CO, 

O3

0-, 1-, and average of 0- to 2-day lags (“3-day mean”) 

Time-series study. Poisson regression using natural spline functions. Report results for predicted PM2.5; used 

statistical model to estimate mass when measurements were not available; measured data available on 636 days and predicted data for 3653 days. 

% exces(all 3-damortalit8.37% (nonacciwith dia3.64% (Greater warm seNo signnonacciwith diacardiovadisease. Associanonacciwith diacardiovacoronary 
 A-20 Table A3. Associations of Acute PM10-2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM10-2.5Burnett et al. (2004) 12 Canadian cities Jan 1981-Dec 1999 

All nonaccidental, cardiovascular, and respiratory causes 

24-h avg PM10-2.5: 

All 12 cities: 11.4 SD not provided. Range of means across cities: 5.5 (Vancouver) to 15.9 (Winnipeg) 

PM2.5, PM10, 

SO4

2, NO2, SO2, 

CO, O3

0-, 1-, or 2-d lag Time-series study. 

Natural spline functions used to model nonlinear associations. PM10-2.5 data collected 

every 6th day. PM10-2.5

data available on 12% of days with mortality data. 

% exces

All caus

Single-pLag 1: Two-po

Lag 1: No signfor NO2 

Dales et al. (2004) 12 Canadian cities Jan 1984-Dec 1999 

SIDS; age <1 yr 24-h avg PM10-2.5: 

All 12 cities: 11.28 IQR 8.76 Range of means across cities: 5.46 (St. John) to 15.88 (Winnipeg) 

PM2.5, PM10, 

NO2, SO2, CO, O3

0-, 1-, 2-, 3-, 4-, 

or 5-d lag; 

multiday lags of 

2 to 6 d 

Time-series study. Nonlinear randomeffects regression model used. PM10-2.5 data 

determined by difference. PM2.5 and 

PM10 data collected 

every 6th day. 

No assoincidenc

effect esSignificNO2, SO
 A-21 Table A3 (cont’d). Associations of Acute PM10-2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM10-2.5Klemm et al. (2004) Atlanta, GA Aug 1998-July 2000 

All nonaccidental, circulatory, respiratory, cancer, and other causes; age <65 yr and 65 yr 

24-h avg PM10-2.5: 

9.69 SD 3.94 IQR 5.25 Range 1.71-25.17 

PM2.5, SO4

2, EC, 

OC, NO2, 

NO3

-, SO2, CO, 

O3, ultrafines, 

hydrocarbons, acid 

Multiday lag of 0-1 d 

Time-series study. Poisson GLM using natural cubic splines with quarterly, monthly, or biweekly knots. Default model used monthly knots. Daily PM10-2.5 data 

collected. 

% exces

All caus

Age 65 Lag 0-1Results specificnumber No signin those 
 A-22 Table A3 (cont’d). Associations of Acute PM10-2.5 Exposure with Mortality Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

PM10-2.5 (cont’d) Slaughter et al. (2005) Spokane, WA Jan 1995-Jun 2001 

All nonaccidental causes 

24-h avg PM10-2.5: 

Not reported. 

PM1, PM2.5, 

PM10, CO 

0-, 1-, 2-, 3-d lag Time-series study. 

Poisson GLM with natural splines. PM10-2.5 calculated as 

difference between PM10 and PM2.5

measurements. Hourly PM2.5 and PM10 data available. Daily average values calculated. 

No assononacci

Quantita

Villeneuve et al. (2003) Vancouver, British Columbia, Canada Jan 1986-Dec 1998 

All nonaccidental, cardiovascular, respiratory, and cancer causes; SES status 

24-h avg PM10-2.5: 

Daily data from 1995-1998: 6.1 10th%-90th% 2.0-13.0 Range 0.0-72.0 Every 6th day data from 1986-1998: 8.3 10th%-90th% 3.1-15.0 Range 0.7-35.0 

PM2.5, PM10, 

TSP, coefficient of haze, SO4

2

, 

SO2, NO2, CO, 

O3

0-, 1-, or 2-d lag; 

multiday lag of 

0-2 d 

Time-series study. Poisson regression using natural spline functions. Daily PM10-2.5 data 

collected from 1995 to 1998 using TEOM; PM10-2.5 data collected every 6th day from 1986 to 1998 using a dichotomized sampler. 

% exces

Results 

All caus

Lag 0: CardiovLag 0: Respirat

Lag 0: Cancer: Lag 0: Significcardiovaobserve

data. 
 A-23 

Additional U.S. and Canadian PM-Mortality Studies: 

Staniswalis et al. (2005): This study shows that the effects of airborne PM on daily mortality can 

be underestimated when using daily averages to summarize hourly profiles, because the daily 

average does not capture information about very acute exposures, that is, large exposures 

occurring over very short periods of time. A principal component data analysis is shown to be 

useful for characterizing hourly measurements of air pollution constituents. In addition, it is 

shown that in El Paso, the risk of PM-induced mortality is higher during still-air inversions 

(i.e., at low wind speeds) than it is during sandstorms (i.e., at high wind speeds). These results 

suggest that coarse and fine PM from resuspended fugitive dust is less toxic than fine PM of 

urban type. 

De Leon et al. (2003): The effects of PM10 on circulatory and cancer mortality with and without 

contributing respiratory causes were examined in this study conducted in New York City. 

Among those aged 75 yr, effect estimates were greater for circulatory mortality with contributing 

respiratory causes (6.6% [95% CI: 2.7, 10.6] per 18.16 μg/m3

 increase in PM10) at a 0- to 1-day 

lag compared to that without (2.2% [95% CI: 0.8, 3.5]). Unlike in those aged 75 yr, 

significantly higher risks were not observed with contributing respiratory causes in individuals 

aged <75 yr. 

Bateson and Schwartz (2004): The association between PM10 and all-cause mortality in 

individuals aged 65 yr who were previously admitted to the hospital with a primary or secondary 

diagnosis of heart or lung disease was examined in this case-crossover study in Cook County, IL. 

A 1.14% (95% CI: 0.44, 1.85) excess risk was observed per 10 μg/m3 increase in PM10 at a lag 

of 0 to 1 days. The effect of PM10 on the risk of mortality was higher among those with a prior 

diagnosis of myocardial infarction (1.98%), diabetes (1.49%), and congestive heart failure 

(1.28%). 

Sullivan et al. (2003): In this case-crossover study in King County, WA, the association between 

PM and out-of-hospital sudden cardiac arrest in individuals with and without preexisting 

cardiovascular and respiratory disease was examined. PM2.5 data was estimated using a 

nephelometric measure (PM1). No consistent associations were observed between increased 

levels of PM2.5 or PM10 and risk of primary cardiac arrest. 

Holloman et al. (2004): To examine the association between cardiovascular mortality and 

estimated exposure to PM2.5 in seven counties in North Carolina, a three-level hierarchical 

Bayesian model was used: (1) linking monitor readings to ambient levels over the region; 

(2) linking ambient levels to exposure levels (estimated using NHAPS); and (3) linking exposure 

levels to mortality. Significant associations were observed between cardiovascular mortality and 

PM2.5 at a lag of 2 days. Results obtained by incorporating a simple exposure simulator into the 

model indicated that the effect of increased levels of exposure was not equivalent to that of 

ambient PM2.5 on cardiovascular mortality. 

Vedal et al. (2003): The associations between PM10 and all-cause, cardiovascular, and 

respiratory mortality were examined in Vancouver, Canada (PM10 concentration range 4.1 to 

37.2 μg/m3

). During the summer, statistically significant effects on respiratory mortality were 

observed for PM10, O3, and SO2, and the effects of NO2 and CO were also nearly significant. 

Effects on total and cardiovascular mortality were only seen for O3. During the winter, 

significant effects on total mortality were observed for PM10, NO2, and SO2; NO2 and SO2 also 
 A-24 

were associated with cardiovascular mortality. No significant associations with respiratory 

mortality were observed in the winter. The authors report that these findings may support the 

notion that no threshold pollutant concentrations are present, but they also raise concern that the 

observed effects may not be due to the measured pollutants themselves, but rather of some other 

factors present in the air pollution-meteorology mix. 

Jerrett et al. (2004): Significant associations between CoH and all-cause mortality were 

observed in regions of lower SES status at various lags of exposure. Regions of higher SES 

status displayed no significant associations except at a multiday lag of 0 to 3 days. These 

findings suggest that the effect of PM on mortality may be modified by SES status. Low 

educational attainment and high manufacturing employment significantly and positively 

modified the effects of PM on acute mortality. 

Additional Studies Examining Issues Related to Interpreting the 

PM-Mortality Relationship: 

Forastiere et al. (2005): Using a case-crossover design, the associations between daily ambient 

air pollution levels (particle number concentration [PNC], PM10, CO, NO2, and O3) and the 

occurrence of out-of-hospital fatal coronary events in Rome were examined. The association 

was statistically significant for PNC, PM10, and CO, with the strongest effect observed on the 

same day. An IQR increase in PNC (27,790 particles/cm3) and PM10 (29.7 μg/m3) was 

associated with a 7.6% (95% CI: 2.0, 13.6) and 4.8% (95% CI: 0.1, 9.8) excess risk in mortality, 

respectively. Stronger effects were observed among people aged 65 yr, and possibly in those 

with hypertension and COPD. 

Sunyer et al. (2002): This case-crossover study assessed the acute association between air 

pollution and all-cause mortality in a population-based cohort of subjects with asthma recruited 

from emergency room admissions for asthma exacerbation in Barcelona, Spain. No significant 

associations were observed between PM10 or BS and mortality. Slightly larger effect estimates 

were observed in subjects admitted more than once compared to those admitted only once to the 

emergency department for asthma, but differences were not significant. Stronger associations 

were observed for NO2 and O3. 

Kan et al. (2005): Using time-series Poisson regression, the relationship between daily SARS 

mortality and ambient air pollution in Beijing was examined. An 10 μg/m3

 increase in PM10

(mean 149.1 μg/m3

 [SD 8.1]) over a 5-day moving average corresponded to a RR of 1.06 (95% 

CI: 1.00, 1.12). NO2, but not SO2, also was associated with daily SARS mortality (RRs of 1.22 

[95% CI: 1.01, 1.48] and 0.74 [95% CI: 0.48, 1.13], respectively). 

Goodman et al. (2004): In a Dublin, Ireland study, a constrained (6th order polynomial) 

distributed lag model used to examine BS effects through 40 days. Results were compared to 

effects estimated for a 0 to 2 day lag of BS exposure. Stronger associations with BS were 

consistently observed for all-cause, cardiovascular, and respiratory mortality using the extended 

follow-up period. Analyses suggest that studies on acute effects of air pollution have 

underestimated the total effects of PM on mortality. 

 
 A-25 Table A4. Effects of PM2.5 on Daily Hospital Admissions Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM2.5 Dominici et al. (2006) United States National Database1999-2002 A daily time-series analysis on hospital admission rates (from the Medicare National Claims History Files) for cardiovascular and respiratory outcomes and ambient PM2.5 levels, temperature for 204 U.S. urban counties (population >200,000) with 11.5 million Medicare enrollees (aged >65 years) living an average of 5.9 miles from a PM2.5 monitor. PM2.5 county annual mean: 13.4 μg/m3 IQR (11.3-15.2 μg/m3) 

O3 0-2 Nationally, short-term 

increase in hospital admission rates associated with PM2.5 for 

all health outcomes except injuries. The largest association was for heart failure. Substantial homogeneity of fine particle matter concentration across geographic area. For cardiovascular disease, all estimates in the eastern U.S. were positive and generally statistically significant, while estimates in the western U.S. were close to 0 except for heart failure For respiratory disease, there was greater consistency between regions. The authors noted that they did not find evidence of the effect modification by average concentration of either PM2.5

or O3. 
 A-26 Table A4 (cont=d). Effects of PM2.5 on Daily Hospital Admissions Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM2.5 (cont=d) Lin et al. (2002) Toronto 1981-1993 Both case-crossover and time-series analyses used to assess the associations between various PM measures and asthma hospitalization among children 6-12 years old. PM2.5 mean: 17.99 μg/m3 Min 1.22 Max 89.59 PM10-2.5, PM10, O3, NO2, CO, SO2 1-7 Significant effects were not found for PM2.5, but both analysis methods did find relationships with PM10-2.5 for either sex. Individual PM2.5 results showed some positive association but not after consideration of both weather conditions and gaseous co-pollutants. 

Lin et al. (2005) Toronto 1998-2001 Examined the associations between pollutants and hospitalizations for respiratory infections among children younger 

than 15 years of age. Bi-directional casecrossover design used. 

PM2.5

Mean: SD 9.59 SD 7.06 

PM10-2.5, 

PM10, CO, 

SO2, NO2, O3

 PM2.5 showed no significant 

effects when other pollutants were considered. The effects for PM10-2.5 were pronounced. 
 A-27 Table A4 (cont=d). Effects of PM2.5 on Daily Hospital Admissions Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM2.5 (cont=d) Yang et al. (2004) Vancouver, British Columbia Jun 1, 1995-Mar 31, 1999 Logistic regression was used to estimate the associations between PM and first hospitalization for children less than 3 years of age, a case-control approach. Also, analysis was conducted using bidirectional-case crossover analysis and time-series analysis. PM2.5 Mean 7.7 μg/m3 SD 3.7 Range: 2.0-32.0 PM10, PM10-2.5, CO, 

O3, NO2, SO2

0-7 The data indicated possible 

harmful effects from coarse PM on first hospitalization for respiratory disease. No significant association was found between PM2.5 and first 

hospitalization for respiratory disease. PM2.5 concentrations 

were relatively low. In this study, only the casecontrol and case-crossover approaches support the notion of effect of daily average PM10-2.5 on first 

hospitalization for respiratory disease in early childhood. It is not clear if these two approaches overestimated or if the time-series analysis underestimated. For PM2.5, 

the authors noted that differences in findings may be explained, in part, by TEOM measurements, which may be lower than those of filterbased samples. 
 A-28 Table A4 (cont=d). Effects of PM2.5 on Daily Hospital Admissions Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM2.5 (cont=d) Chen et al. (2004) Vancouver, British Columbia Jun 1995-Mar 1999 A time-series analysis assessing the association between low levels of size- fractionated PM and hospitalization for chronic obstructive pulmonary disease (COPD) in the elderly. GAM and GLM models were used. PM2.5 Mean 7.7 μg/m3 SD (3.7) Range: 2.0-32.0 PM10, PM10-2.5, CO, 

O3, NO2, SO2

1-7 Particle-related measures were 

significantly associated with COPD hospitalizations in the Vancouver area, but the effects are not independent of other air pollutants. 

Chen et al. (2005) Vancouver, British Columbia Jun 1, 1995-Mar 31, 1999 

A time-series analysis was used to evaluate the associations between respiratory admissions and PM, looking at first, second, and overall hospital admission for respiratory disease among the elderly. 8,989 adults, $65 yr. 

PM2.5

Mean 7.7 μg/m3

SD (3.7) Range: 2.0-32.0 

PM10, 

PM10-2.5, CO, 

O3, NO2, SO2

1-7 PM10-2.5 had a larger effect on 

respiratory admissions than PM2.5. For PM10-2.5, the 

second and overall admission rates were higher than the first admission rate. 
 A-29 Table A5. Effects of PM10-2.5 on Daily Hospital Admissions Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM10-2.5 Lin et al. (2002) Toronto 1981-1993 Both case-crossover and time-series analyses used to assess the associations between various PM measures and asthma hospitalization among children 6-12 years old. PM10-2.5 Mean 12.17 Range: 0-68 PM2.5, PM10, 

O3, NO2, CO, 

SO2

1-7 Significant associations with 

PM10-2.5 for either sex; no 

significant associations with PM2.5. 

Lin et al. (2005) Toronto 1998-2001 

Examined the associations between pollutants and hospitalizations for respiratory infections among children <15 yr. Bi-directional casecrossover design used. 

PM1-10-2.5

Mean 10.86 (SD 5.37) Range: 0-45 

PM2.5, PM10, 

CO, SO2, 

NO2, O3

 Significant associations with 

PM10-2.5 for either sex; PM2.5

showed no significant effects when other pollutants were considered. 

Chen et al. (2004) Vancouver, British Columbia Jun 1995-Mar 1999 

A time-series analysis assessing the association between low levels of size fractionated PM and hospitalization for chronic obstructive pulmonary disease (COPD) in the elderly. GAM and GLM models were used. 

PM10-2.5

Mean 5.6 μg/m3

Range: 0.1-24.6 

PM10, PM2.5, 

CO, O3, NO2, SO2

1-7 Significant associations for 

PM10-2.5 with COPD 

hospitalizations in the Vancouver area. Also statistically significant associations with PM10, PM2.5, and COH, but the effects are not independent of other air pollutants. 
 A-30 Table A5 (cont=d). Effects of PM10-2.5 on Daily Hospital Admissions Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM10-2.5 (cont=d) Yang et al. (2004) Vancouver, British Columbia Jun 1, 1995-Mar 31, 1999 Logistic regression was used to estimate the associations between PM and first hospitalization for children <3 yr, a case- control approach. Also, analysis was conducted using bidirectional-case crossover analysis and time-series analysis. PM10-2.5 Mean 5.6 μg/m3 Range: 0-24.6 PM10, PM2.5, CO, O3, NO2, SO2 0-7 The data indicated possible harmful effects from coarse PM on first hospitalization for respiratory disease. No significant association was found between PM2.5 and first hospitalization for respiratory disease. PM2.5 concentrations were relatively low. In this study, only the case- control and case-crossover approaches support the notion of effect of daily average PM10-2.5 on first 

hospitalization for respiratory disease in early childhood. It is not clear if these two approaches overestimated or if the time-series analysis underestimated. For PM2.5, 

the authors noted that differences in findings may be explained, in part, by TEOM measurements, which may be lower than those of filterbased samples. 
 A-31 Table A5 (cont=d). Effects of PM10-2.5 on Daily Hospital Admissions Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM10-2.5 (cont=d) Chen et al. (2005) Vancouver, British Columbia Jun 1, 1995-Mar 31, 1999 A time-series analysis was used to evaluate the associations between respiratory admissions and PM, looking at first, second, and overall hospital admission for respiratory disease among the elderly. 8,989 adults, $65 yr. PM10-2.5 Mean 5.6 μg/m3 Range: 0.1-24.6 PM10, PM2.5, CO, O3, NO2, SO2 1-7 PM10-2.5 had a larger effect on respiratory admissions than PM2.5. For PM10-2.5, the second and overall admission rates were higher than the first admission rate. (1) People with a history of respiratory admissions are at a higher risk of respiratory disease in relation to particulate air pollution in urban areas. (2) Analyses based on overall rather than repeated hospital 

admissions lead to lower estimates of the risk of respiratory disease associated with particulate air pollution. 
 A-32 Table A6. Effects of PM2.5 on Daily Emergency Department Visits Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM2.5 Metzger et al. (2004) Atlanta, GA Aug 1998-Aug 2000 Emergency department visits for total and cause- specific cardiovascular diseases by age groups >19 yr and >65 yr. Time-series study. 4, 407, 535, EDV from 31 Atlanta hospitals. PM2.5 μg/m3 Median: 17.8 Range: 8.9 to 32.3 NO2, SO2, CO, 

O3, PM10, 

PM10-2.5, 

ultrafine PM count, SO4

2!

, 

H+, EC, OC, 

metals, oxygenated hydrocarbons 

0-2 Poisson GLM regression used 

for analysis. A priori models specified a lag of 0 to 2 days. Secondary analyses performed to assess alternative pollutant lag structures, seasonal influences, and age effects. Cardiovascular visits were significantly associated with several pollutants, including NO2, CO, and PM2.5, but not O3. 

PM2.5 

All agTotal c3.3% (Dysrh2.1% (Conge5.5% (Ischem2.3% (Periphcerebr5 (0.8, 

Peel et al. (2005) Atlanta, GA Aug 1998-Aug 2000 

Emergency department visits for total and causespecific respiratory diseases by age groups 0-1, 2-18, >19, and >65 yr. Time-series study. 

PM2.5

19.2"8.9 Range: 8.9 to 32.3 

NO2, SO2, CO, 

O3, PM10, 

PM10-2.5, 

ultrafine PM count, SO4

2!

, 

H+, EC, OC, 

metals, oxygenated hydrocarbons 

0-2 Poisson GEE and GLM 

regression used for analysis. A priori models specified a lag of 0 to 2 days. Also performed secondary analyses estimating the overall effect of pollution over the previous 2 wk. Seasonal analyses indicated stronger associations with asthma in the warm months, especially for O3 and PM2.5

organic carbon. Quantitative results not presented for multipollutant, age-specific, and seasonal analyses. 

PM2.5 

All agAll avTotal r1.6% (Upper 1.8 (0, Asthm0.5 (-2Pneum1.1% (COPD1.5 (-3
 A-33 Table A6 (cont=d). Effects of PM2.5 on Daily Emergency Department Visits Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM2.5 (cont=d) Slaughter et al. (2005) Spokane, WA Jan 1995-Jun 2001 Study of hospital and ED visits for respiratory and cardiac condition in relation to PM1, PM2.5, PM10, and PM10-2.5 using a log- linear generalized linear model for lags 0 to 3 and compared results to a log-linear generalized additive model. PM2.5 90% of concentration ranged between 4.2 and 20.2 μg/m3 CO 1-3 No overall association with respiratory ED visits and any size fraction of PM nor with cardiac hospital admissions. PM

incLaAl1% Ac3% Ca0% 
 A-34 Table A7. Effects of PM10-2.5 on Daily Emergency Department Visits Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

PM10-2.5 Metzger et al. (2004) Atlanta, GA Aug 1998-Aug 2000 Emergency department visits for total and cause- specific cardiovascular diseases by age groups >19 yr and >65 yr. Time-series study. 4, 407, 535, EDV from 31 Atlanta hospitals. PM10-2.5 Median: 9.1 μg/m3 Range (10%- 90%): 4.4-16.2 NO2, SO2, CO, 

O3, PM10, PM2.5, 

ultrafine PM count, SO4

2!

, 

H+, EC, OC, 

metals, oxygenated hydrocarbons 

0-2 Poisson GLM regression used for 

analysis. A priori models specified a lag of 0 to 2 days. Secondary analyses performed to assess alternative pollutant lag structures, seasonal influences, and age effects. Cardiovascular visits were significantly associated with several pollutants, including NO2, 

CO, and PM2.5, but not with 

PM10-2.5 or O3. 

PM

3 dCV1.2

Peel et al. (2005) Atlanta, GA Aug 1998-Aug 2000 

Emergency department visits for total and causespecific respiratory diseases by age groups 0-1, 2-18, >19, and >65 yr. Time-series study. 

PM10-2.5

Median: 9.7 μg/m3

Range (10%-90%): 4.4-16.2 

NO2, SO2, CO, 

O3, PM10, PM2.5, 

ultrafine PM count, SO4

2!

, 

H+, EC, OC, 

metals, oxygenated hydrocarbons 

0-2 Poisson GEE and GLM regression 

used for analysis. A priori models 

specified a lag of 0 to 2 days. Also performed secondary analyses estimating the overall effect of pollution over the previous 2 wk. No significant associations with PM10-2.5. Some significant 

associations with gaseous pollutants and PM10. Quantitative 

results not presented for multipollutant, age-specific, and seasonal analyses. 

PM

3 dRe3% 

Slaughter et al. (2005) Spokane, WA Jan 1995-Jun 2001 

Study of hospital and ED visits for respiratory and cardiac condition in relation to PM1, PM2.5, 

PM10, and PM10-2.5 using 

a log-linear generalized linear model for lags 0 to 3 and compared results to a log-linear generalized additive model. 

PM10-2.5 90% 

of concentration ranged between 4.2 and 20.2 μg/m3

CO, PM10, PM2.5 1-3 No overall association with 

respiratory ED visits and any size fraction of PM nor with cardiac hospital admissions. 

PMincLaAl1% Ac3% CO1% 
 A-35 Table A8. Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 Pope et al. (2004) Wasatch Front, UT Winter 1999-2000 and summer in Hawthorne and winter 2000-2001 in Bountiful and Lindon Study of the effects of pollutants on autonomic function measured by changes in HRV and blood markers of inflammation in a panel of 88 elderly subjects using regression analysis. PM2.5 (TEOM) Mean (SD) 18.9"13.4 

C While this study observed statistical 

associations between PM2.5 and HRV and 

C-reactive protein (CRP), most of the relevant variability in the temporal deviation of these physiological endpoints was not explained by PM2.5. These observations 

therefore suggest that PM2.5 may be one of 

multiple factors that influence HRV and CRP. 

Riedker et al. (2004) North Carolina Autumn 2001 

Nine healthy North Carolina Highway Patrol troopers were monitored on 4 successive days for in-vehicle PM2.5, roadside 

PM2.5, and ambient PM2.5.

Ambulatory ECGs performed and various blood indicators measured. 

PM2.5 (ambient) 32.3 μg/m3

Range: 9.9-68.9 

O3, CO, NO2 The troopers showed significant and strong 

increases of HRV, ectopic beats, blood inflammation and coagulation markers, and MCV in association with the in-vehicle exposure to PM2.5 as indication of increase of vagal activity. 
 A-36 Table A8 (cont=d). Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Schwartz et al. (2005b) Boston, MA 12 weeks during the summer of 1999 A panel study of 28 elderly subjects (age 61-89 years). Various HRV parameters were measured for 30 min once a week. Analysis using linear mixed models with log- transformed HRV measurements. To examine heterogeneity of effects, hierarchical model was used. PM2.5 during HRV measurement: Median: 10 μg/m3 BC Median: 1.0 μg/m3 BC,O3, CO, SO2, NO2 HRV parameters examined included: SDNN, r-MSSD, PNN50, and LF/HF ratio. Strongest association seen for BC, an indicator of traffic particles. The random effects model indicated that the negative effect of BC on HRV was not restricted to a few subjects. Subjects with MI experienced greater BC-related decrements in HRV parameters. 

Park et al. (2005) Greater Boston area, MA Nov 2000-Oct 2003 

Cross-sectional study examining the effect of pollutants on HRV in 497 adult males (mean age 72.7 years). Subjects were monitored during a 4-min rest period between 8 a.m. and 1 p.m. Pollutant levels measured at central site 1 km from study site. Exposure averaging times of 4, 24, and 48 h investigated. Modifying effects of hypertension, IHD, diabetes, and use of cardiac/antihypertensive medications also examined. Linear regression analyses. This subject group is from the VA Normative Aging Study. 

PM2.5Mean (SD): 11.4 ("8.0) 

Range: 6.45-62.9 

O3, PNC, BC, 

NO2, SO2, CO 

Of the pollutants examined, only PM2.5 and 

O3 showed significant associations with 

HRV outcomes. The 4-h averaging period was most strongly associated with HRV indices. The PM effect was robust in models including O3. The associations 

between PM and HRV indices were stronger in subjects with hypertension (n = 335) and IHD (n = 142). In addition, calcium-channel blockers significantly influenced the effect of PM on low frequency power. Limitations of this study are the use of a short 4-min period to monitor HRV and the lack of repeated measurements for each subject. 
 A-37 Table A8 (cont=d). Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Wheeler et al. (2006) Atlanta, GA Fall 1999 and spring 2000 Examined pollutant effects on HRV in 18 subjects with COPD and 12 subjects with recent MI. Data collected 7 days in fall and spring. Associations examined using linear-mixed effect model. Age range 49-76 yrs. PM2.5 μg/m2 Mean: 17.8 

O3, CO, SO2, 

NO2

For COPD patients, PM2.5 exposure related 

to an increase in SDNN. The results for MI subjects were positive, but not significant. Effects were modified by medication use, baseline pulmonary function, and health status. The small numbers studied limit the study. 

Rich et al. (2005) Boston, MA Jul 1995-Jul 2002 

In 203 patients with implantable cardioverter defibrillators. Casecrossover study design used to examine association between air pollution and ventricular arrhythmias. For each case period, 3-4 control periods were selected. Various moving average concentrations of exposure considered ! lags 0-2, 

0-6, 0-23, and 0-47 h. Analysis using conditional logistic regression models. 

PM2.5 (μg/m3) 

1-h avg Median: 9.2 PM2.5 (μg/m3) 24-h avg Median: 9.28 IQR: 7.8 

O3, BC, CO, 

NO2, SO2

Associations were observed for PM2.5 and 

O3 with a 24-h moving average, and for 

NO2 and SO2 with a 48-h moving average. In two-pollutant analyses, only PM2.5 and 

O3 appeared to act independently. 

Rich et al., (2006) Boston, MA Jun 1995-Dec 1999 

In 203 patients with implantable cardioverter defibrillators, were 91 episodes of paroxysmal atrial fibrillation (PAF) in 29 subjects. Case-crossover design used to examining association between air pollutants and PAF, with matching control periods on weekday and hour within same calendar month. Conditional logistic regression models used. 

PM2.5 (μg/m3) 

1-h avg Median: 9.2 Max: 84.1 PM2.5 (μg/m3) 24-h avg Median: 9.8 Max: 53.2 

O3, BC, CO, 

NO2, SO2

Positive, but not significant, associations reported with PM2.5, BC and NO2. 

Significant associations reported with O3. 

Authors note reduced statistical power for PM2.5 and BC analyses due to missing data. 

Conclude PAF is associated with exposure to community air pollution. 
 A-38 Table A8 (cont=d). Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Dockery et al. (2005) Boston, MA Jul 1995-Jul 2002 Effect of air pollution on incidence of ventricular arrhythmias was examined in 203 patients with implantable cardioverter defibrillators using time-series methods. Mean follow-up period was 3.1 yr/subject. All subjects located <40 km of air pollution monitoring site. Two-day mean air pollution level used in analysis. Results analyzed by logistic regression using GEE with random effects. Modifying effects of previous arrhythmia 

within 3 days also examined. 

PM2.5

Median: 10.3 μg/m3

IQR: 6.9 μg/m3

O3, BC, SO4

2!

, 

particle number, CO, NO2, SO2

No associations were observed between air pollutants and ventricular arrhythmias when all events were considered. When only examining ventricular arrhythmias within 3 days of a prior event, positive associations were found for most pollutants except for O3. The associations suggest a link with 

motor vehicle pollutants. 
 A-39 Table A8 (cont=d). Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Rich et al. (2004) Vancouver, British Columbia, Canada Feb-Dec 2000 Case-crossover study design used to investigate association between air pollution and cardiac arrhythmia in patients aged 15-85 yr (n = 34) with implantable cardioverter defibrillators. Controls periods were selected 7 days before and after each case day. Analysis using conditional logistic regression. PM2.5 Mean: 8.2 μg/m3 IQR: 5.2 

O3, EC, OC, 

SO4

2!, CO, 

NO2, SO2

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

Gold et al. (2005) Boston, MA Summer of 1999 

Study of associations between ambient pollutants and ST-segment levels in repeated measures involving 269 observations in 24 subjects 61-88 yr; each observed 12 times between June-September involving Holter recording. PM2.5, BC, and CO were 

collected at 5 central sites 0.5 km from residences of subjects. 

PM2.5 12 h Median: 9.8 μg/m3

BC Median: 1.14 μg/m3

CO, O3, NO2, SO2

Elevated BC predicted increased risk of STsegment depression with the strongest association being for the 5-h lagged value. 
 A-40 Table A8 (cont=d). Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Dubowsky et al. (2006) St. Louis, MO Mar-June 2002 Investigation of ambient particles and markers of systemic inflammation among repeated measures from 44 subjects ($60 yr). Trips from senior home in diesel bus into St. Louis. Analyzed using linear mixed model. PM2.5 Mean (SD) μg/m3 16 (6.0) Range 6.5-28 CO, NO2, SO2, O3 Modest positive association found between fine particles and indicators of systemic inflammation with larger association suggested for individuals with diabetes, obesity, and hypertension. Positive associations found for longer moving averages. 
 A-41 Table A8 (cont=d). Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) O=Neill et al. (2005) Boston, MA May 1998-Jan 2000 Baseline period Time trial 2000-2002 

270 patients with diabetes or at risk for diabetes were studied in relation to various pollutant levels and evaluated for association with vascular reactivity. Linear regressions were fit to the percent change in brachial artery diameter (flowmediated and nitroglycerinmediated) into particulate pollutant index and other factors. 

PM2.5

(1998-2002) Mean (SD): 11.5 (6.4) μg/m3Range: 1.1-40.0 

SO4

2!, BC, 

ultrafine 

PM2.5 was associated with nitroglycerinmediated reactivity; an association was also 

reported with ultrafine particles. Effects were stronger in type II than type I diabetes. BC and SO4

2! increases were associated 

with decreased flow-mediated reactivity among those with diabetes. Although the strongest associations were with the 6-day moving avg, similar patterns and quantitatively similar results appear in the other lags. 

Schwartz et al. (2005a) Boston 2000 

Examined the associations between PM2.5 and HF in 497 

subjects in Normative Aging Study (NAS) using linear regression controlling for covariates. 

PM2.5

Mean: 11.4 μg/m3

(8.0 SD) 

C In subjects without the allele (for 

glutathione-S-transferase M1) an increase in PM2.5 during the 48 h before HF (highfrequency component of HRV) 

measurement was associated with a decrease in HF. In subjects with the allele, 

no effect was noted. The effects of PM2.5

on HR appear to be mediated by ROS, which may be a lag pathway for effects of combustion particles. 

Sullivan et al. (2003) Western Washington State 1985-1994 

A case-crossover study of 1,206 out-of-hospital cardiac arrest among persons with (n = 774) and without (n = 432) clinically recognized heart disease and daily measures of PM2.5. 

PM (nephelometry, kmG1 bsp) 

Mean: 0.71 Min: 0.05 Max: 5.99 

SO2, CO There was no consistent association 

between increased levels of fine particular matter and risk of primary cardiac arrest. This differs from results seen in other airsheds. 
 A-42 Table A8 (cont=d). Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Mar et al. (2005) Seattle 1999-2001 Study of pollutants in relation to health parameters in 88 subjects (>75 yrs of age). HR, BP, and arterial oxygen saturation was examined using GEE. PM2.5 outdoor μg/m3 range from 9.0 ("4.61) for healthy to 12.5 ("7.9) for CVD subjects PM10 Healthy subjects had decreases in HR associated with PM2.5. SaO2 does not have a consistent response to PM air pollution. Sample size was a limitation in this study. PM

he!0

DeMeo et al. (2004) Boston July-August 1999 

Investigated the association between PM2.5 and oxygen 

saturation during a 12-wk repeated measures study of 28 older Boston residents using a fixed effects model/GLM. 

PM2.5 μg/m3

IQR (11.45) 

C Demonstrated a statistically significant 

effect of ambient particle air pollution on decreased oxygen saturation at rest in a population of free-living older individuals with a more-significant interaction in those taking β-blockers. These small changes may be related to a pulmonary vascular and/or inflammatory cascade. 

PM

Ox(6-!0

Lipsett et al. (2006) Coachella Valley, CA Feb-May 2000 

Weekly ambulatory ECG=s 

recorded, using Holter monitor, in 19 nonsmoking adults. Mixed linear regression models used with random effects parameters for inter-individual variation. Subjects= residences w/in 5 miles 

of one of two PM monitoring sites. 

PM2.5 μg/m3

mean (range): Indio: 23.2 (6.3-90.4) Palm Springs: 14 (4.7-52) 

PM10, PM10-2.5, 

O3

No significant associations reported with PM2.5; however were significant 

associations with PM10-2.5. 

CoSD24

6h 

4h 2h 

Ebelt et al. (2005) Vancouver, Canada Summer 1998 

Outcomes: FEV1, ectopy, blood 

pressure, heart rate and variability 16 COPD patients, Vancouver, summer 1998, each subject measured 7 days mixed models 

PM2.5

Mean: 11.4 

PM10-2.5, and PM10

Ambient 

concentrations 

and exposures 

PM2.5 significantly associated with 

decreased systolic blood pressure and increased ectopic heart beats Use of ambient exposure instead of ambient concentration yields more meaningful 

results. Suggest that other Panel studies which depend on ambient concentrations or total personal exposure could fail to observe effects that existed. -day 

No repin 
 A-43 Table A9. Effects of Acute PM10-2.5 Exposure on Cardiovascular Outcomes Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

PM10-2.5 Lipsett et al. (2006) Coachella Valley, CA Feb-May 2000 Weekly ambulatory ECG=s recorded, using Holter monitor, in 19 nonsmoking adults. Mixed linear regression models used with random effects parameters for inter-individual variation. Subjects= residences w/in 5 miles of one of two PM monitoring sites. PM10-2.5 μg/m3 Mean (difference between PM10 and PM2.5 ): Indio: 23.2 (6.3-90.4) Palm Springs: 14 (4.7-52) PM10, PM2.5, 

O3

Significant associations between PM10-2.5

(2h, 4h and 6h avg) and SDNN, SDANN. No significant associations reported with PM2.5. 

Ebelt et al. (2005) Vancouver, Canada Summer 1998 

Outcomes: FEV1, ectopy, blood 

pressure, heart rate and variability 16 COPD patients, Vancouver, summer 1998, each subject measured 7 days mixed models 

PM10-2.5

Mean: 5.6 

PM2.5 and PM10

Ambient concentrations and exposures 

Associations between PM10-2.5 and 

decreased systolic blood pressure and increased ectopic heart beats similar to PM2.5 in size, but not statistically significant 

Use of ambient exposure instead of ambient concentration yields more meaningful 

results. Suggest that other Panel studies which depend on ambient concentrations or total personal exposure could fail to observe effects that existed. 
 A-44 Table A10. Effects of Acute PM2.5 Exposure on Various Respiratory Outcomes Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 Gent et al. (2003) Southern New England Apr-Sept 2001 Panel study of 271 children (age <12 years) with active, doctor- diagnosed asthma followed over 183 days for respiratory symptoms. For analysis, cohort split into two groups: 130 who used maintenance medication during follow-up and 141 who did not, on assumption that medication users had more severe asthma. Logistic regression analyses performed. PM2.5 Mean: 13.1 (SD 7.9) μg/m3

O3 Correlation between daily PM2.5

and 1-h max O3 was 0.77 during 

this warm-season study. Significant associations between PM2.5 and symptoms in some 

models, but not significant in two-pollutant models. Significant associations between O3 and symptoms only in 

medication users, a group considered to be more sensitive. 

PM

ShOR pre1.2wi

1.2

Rabinovitch et al. (2006) Denver, CO winters 2001-2002 and 2002-2003 

A school-based cohort study of children aged 6-13 years with physician-diagnosed asthma (n = 92), with data on bronchodilator use, urinary leukotriene E4, and 

reported respiratory infections. Hourly and 24-h avg PM2.5 data 

available from station 2.7 mi from school, using TEOM and FRM monitors. 

PM2.5 (μg/m3) 

TEOM: Daily mean (SD) year 1: 6.5 (3.2) year 2: 8.2 (3.7) Morning mean (SD) year 1: 7.4 (4.7) year 2: 9.1 (5.0) Morning max (SD) year 1:15.5 (9.5) year 2: 18.4 (9.6) FRM: Daily mean (SD) year 1: 11.8 (7.2) year 2: 11.2 (5.5) 

C Peak PM2.5 associated with 

bronchodilator use and urinary LTE4. Stronger associations reported with morning mean or max concentrations than daily mean; also stronger associations for severe asthmatics compared with mild/moderate asthmatics. 

Mo

per 

Incin 8.1In 1.6

Mar et al. (2004) Spokane, WA Mar 1997-Jun 1999 

Evaluated the effects of PM2.5 on 

respiratory symptoms in both adults and children with asthma (16 adults, 9 children) using logistic regression. 

PM2.5

μg/m3

Mean range over three years 8.1 to 11.0 

PM10, PM10-2.5, PM1

In children a strong association was reported between cough and PM10, PM2.5, PM10-2.5, and PM1. 

No association for symptoms in adults. 

PM

(10 

CoLa1.2
 A-45 Table A10 (cont=d). Effects of Acute PM2.5 Exposure on Various Respiratory Outcome

Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Jansen et al. (2005) Seattle 2002-2003 Study of 16 older asthma COPD patients’ exposure to pollutants in relation to various health outcomes from data collected daily for 12 days analyzed using a linear mixed effect model. PM2.5 Outdoor IQR (SD) 10.47 (8.87) μg/m3 BC, PM10 FENO (fractional exhaled nitric oxide) increased in relation to increasing PM2.5. No association was found between PM and changes in spirometry, blood pressure, pulse rate, or SaO2 (oxygen saturation of blood). PM

10 4.2 (95Inc

sub

Koening et al. (2005) Seattle, WA winter 2000 to spring 2001 Examined indoor-generated (Eig) and outdoor generated (Eag) PM pulmonary effects on 19 children with asthma using exhaled nitric oxide (eNO), using a linear model and also by GEE. PM2.5 Outdoor (Eag) Mean: 11.1 μg/m2 Range: 2.8-40.4 

C Based on a recursive model with a 

sample size of 8 children. Eag was 

marginally associated with increases in eNO; no association reported with Eig. Effects were 

only seen in children not using corticosteroid therapy. 

PM

inc5.6 (C

p = 

Mar et al. (2005) Seattle, WA 1999-2001 

Evaluated hourly exposures to PM2.5 and FENO in 19 children with 

asthma using a polynomial distributed lag model, single and lag model taking into account ambient NO levels and use of inhaled corticosteroids. 

PM2.5

1 h avg Ranges from 8.3 μg/m3 at 3-h lag 

to 15.2 at 8-h lag 

C FENO was associated with hourly 

averages of PM2.5 up to 10-12 h 

after exposure. No effects were seen in subjects on inhaled corticosteroids. Similar results were obtained for both analysis methods. 

PM

Sin6.9 (3.
 A-46 Table A10 (cont=d). Effects of Acute PM2.5 Exposure on Various Respiratory Outcome

Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Adamkiewicz et al. (2004) Steubenville, OH Sept-Dec 2000 Breath samples collected weekly in panel of 29 elderly subjects, and analyzed for FENO. Indoor NO measured in study room at time of breath sample collection. Ambient measurements from a central monitoring site. PM2.5 (μg/m3) Mean (max, IQR): 1h: 19.5 (105.8, 17.9) 24h: 19.7 (57.8, 17.7) NO, NO2, O3, SO2 Consistent positive, significant associations reported between FENO and PM2.5, also with ambient and indoor NO levels. No associations reported with NO2, O3, or SO2. In 2- and 3-pollutant models, PM2.5 remains significant, while ambient and indoor NO associations are reduced and lose significance. FE

1h 

1.3241.4

Giradot et al. (2006) Great Smoky Mountains NP, NC-TN Fall 2002, summer 2003 

Investigated lung function in 354 adult-hikers over 71 days in relation to pollutant exposure using multiple linear regression models by ordinary least squares estimation. Hikers averaged 5.0 h of exercise. 

PM2.5

Average daily 13.9"8.2 μg/m3

Range 1.6-38.4 μg/m3

O3 Findings suggest that low levels 

of pollutant exposure over several hours may not result in significant declines in lung function in healthy adults engaged in exercise or work. 

Thpera f

for p = 

Delfino et al. (2004) Alpine, CA Aug-Oct 1999, AprJun 2000 

Panel study of 19 asthmatic children (age 9-17 years) followed daily for 2 weeks to determine relationship between air pollutants and FEV1. Linear mixed model 

used for analysis. Personal PM measurements made with dataRAM, which approximate PM2.5 measurements. 

PM2.5 (24-h) 

Outdoor mean (SD) 10.3 (5.6) μg/m3

Outdoor home: 11.0 (5.4) μg/m3Indoor home: 12.1 (5.4) μg/m3Personal PM: 37.9 (19.9) μg/m3

PM10, O3 Significant declines in FEV1

associated with various PM indices but not ambient O3 levels. 

Stronger associations with multiday moving averages for both personal and stationary-site PM. 

PM

Pe

PM per 

!0per !1per !1per 

!5
 A-47 Table A10 (cont=d). Effects of Acute PM2.5 Exposure on Various Respiratory Outcome

Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Newhouse et al. (2004) Tulsa, OK Sep-Oct 2000 Panel study of 24 subjects aged 9- 64 years with physician diagnosis of asthma. Performed PEF twice daily (morning and afternoon), and reported daily respiratory symptoms and medication use. Forward stepwise regression and Pearson correlation analysis. PM2.5 Mean (range): 13.07 (0.50-29.90) μg/m3

O3, CO, SO2, 

pollen, fungal spores 

Significant associations reported between O3 and FEV1 and various 

respiratory symptoms. In multipollutant models, including pollen and mold spores, maximum PM2.5

negatively associated with cough, wheeze and shortness of breath; no discussion of these findings. 

No 

Sinclair and Tolsma (2004) Atlanta, GA Aug 1998-Aug 2000 

Respiratory medical visit data collected by Kaiser Permanente, including ambulatory care visits for asthma (adult and child), URI and LRI. ARIES air quality data used. Poisson GLM regression used for analysis. A priori models specified a lag of 0 to 2 days (average). Also performed analyses using average lag periods of 3-5 and 6-8 days. 

PM2.5

mean (SD) 17.62 (9.32) μg/m3

NO2, SO2, CO, 

O3, PM10, PM10-2.5, 

ultrafine PM count, SO4

2!

, 

H+, EC, OC, 

metals, oxygenated hydrocarbons (OHC) 

Adult asthma visits associated with ultrafine number count, and negatively associated with PM2.5

mass. Child asthma associated with OHC (0-2 day) and with PM10, PM10-2.5, EC and OC (3-5 

day). LRI associated with PM2.5acidity and SO2 (0-2 day) and 

with PM10, PM10-2.5, EC, OC and 

PM2.5 water soluble metals. For 

URI, significant positive associations with ultrafine PM (0-2) and PM10-2.5 (3-5 day) but 

negative associations with PM2.5, 

SO2 and sulfate. 

PM

QusigAd

RR LREC

RR OC

RR PM

RR PM

per RR 
 A-48 Table A10 (cont=d). Effects of Acute PM2.5 Exposure on Various Respiratory Outcome

Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 (cont=d) Lewis et al. (2005) Detroit Winter 2001 thru Spring 2002 A longitudinal cohort study of primary-school age children with asthma, primarily African American and from low-income families, examined the relationship between lung function and PM and 

O3 using GEE, considered effects 

modification by maintenance corticosteroid use and URI as recorded in diaries of 86 children in six 2-wk seasonal assessments for various lags. 

PM2.5

IQR 12.5 μg/m3

O3 Positive associations between 

PM2.5 and O3 with diurnal 

variability in FEV1, and negative 

associations with lowest daily FEV1; though many not 

statistically significant. Authors conclude that ambient air pollution exposure associated with adverse effects on pulmonary function among at-risk children with asthma in Detroit. 

PM

ChFE

1.6sin

Silkoff et al. (2005) Denver, CO winters 1999-2000 and 2000-2001 

Two panels of adults with COPD (n = 16 and 18 for winters 1 and 2, respectively), with diary of twicedaily PEF and FEV1, symptoms 

and bronchodilator use. 4-month study period included biweekly visits to collect data. 

PM2.5 (μg/m3) 

Mean (SD): winter 1: 9.0 (5.2) winter 2: 14.3 (9.6) 

PM10, CO, NO2 In winter 1, no evidence of 

detrimental effects on lung function; some significant associations between PM10, NO2

and CO with increased lung function. In winter 2, significant associations reported between PM10, NO2 and CO and increased 

medication use or symptoms. No significant associations reported with PM2.5. 

No repfig

Ebelt et al. (2005) Vancouver, Canada Summer 1998 

Outcomes: FEV1, ectopy, blood 

pressure, heart rate and variability 16 COPD patients, Vancouver, summer 1998, each subject measured 7 days mixed models 

PM2.5

Mean: 11.4 

PM10-2.5, and 

PM10

Ambient concentrations and exposures 

Decrease in 

)FEV1 associated 

with ambient exposure for all PM components Use of ambient exposure instead of ambient concentration yields more meaningful results. Suggest that other Panel studies which depend on ambient concentrations or total personal exposure could fail to observe effects that existed. 

No repfig
 A-49 Table A11. Effects of Acute PM10-2.5 Exposure on Various Respiratory Outcomes Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Findings, Interpretation 

PM10-2.5 Sinclair and Tolsma (2004) Atlanta, GA Aug 1998-Aug 2000 Respiratory medical visit data collected by Kaiser Permanente, including ambulatory care visits for asthma (adult and child), URI and LRI. ARIES air quality data used. Poisson GLM regression used for analysis. A priori models specified a lag of 0 to 2 days (average). Also performed analyses using average lag periods of 3-5 and 6-8 days. PM10-2.5 mean (SD) 9.67 (4.74) μg/m3 NO2, SO2, CO, 

O3, PM10, PM2.5, ultrafine PM count, SO4

2!

, 

H+, EC, OC, 

metals, oxygenated hydrocarbons (OHC) 

Adult asthma visits associated with ultrafine number count, and negatively associated with PM2.5

mass. Child asthma associated with OHC (0-2 day) and with PM10, PM10-2.5, EC and OC (3-5 

day). LRI associated with PM2.5

acidity and SO2 (0-2 day) and 

with PM10, PM10-2.5, EC, OC and 

PM2.5 water soluble metals. For 

URI, significant positive associations with ultrafine PM (0-2 day) and PM10-2.5 (3-5 day) but 

negative associations with PM2.5, 

SO2 and sulfate. 

PM

Pe

LRRR ChRR URRR 

Mar et al. (2004) Spokane, WA Mar 1997-Jun 1999 

Evaluated the effects of PM2.5 on 

respiratory symptoms in both adults and children with asthma (16 adults, 9 children) using logistic regression. 

PM10-2.5

Not reported 

PM10, PM2.5, 

PM1

In children a strong association was reported between cough and PM10, PM2.5, PM10-2.5, and PM1. 

No association for symptoms in adults. These findings also suggest that both larger and smaller particles can aggravate asthma symptoms 

PM

(10 

CoLaOR 

Ebelt et al. (2005) Vancouver, Canada Summer 1998 

Outcomes: FEV1, ectopy, blood 

pressure, heart rate and variability 16 COPD patients, Vancouver, summer 1998, each subject measured 7 days mixed models 

PM10-2.5Mean: 5.6 

PM2.5 and PM10

Ambient concentrations and exposures 

Decrease in 

)FEV1 associated 

with ambient exposure for all PM components Use of ambient exposure instead of ambient concentration yields more meaningful results. Suggest that other Panel studies which depend on ambient concentrations or total personal exposure could fail to observe effects that existed. 

No repfig
 A-50 Table A12. Effects of Acute PM2.5 Exposure on Birth Outcomes Reference, Study Location and Period Outcomes and Design Mean PM Levels Copollutants Considered Findings, Interpretation 

PM2.5 Karr et al. (2006) South Coast Air Basin, CA 1995-2000 Linked hospital discharge for bronchiolitis during first year of life with PM2.5 using closest measurements based on zip code. Case-crossover design used, with lag periods of 1-2, 3-5 and 6-8 days. PM2.5 Means range from 23.3 to 24.1 μg/m3, for different lag periods CO, NO2 No significant associations reported for any of the pollutants. PM

1BOR 3-OR 6-OR 
 A-51 

Additional Studies Examining Issues Related to Interpreting the PM-Morbidity 

Relationship: 

U.S. and Canadian studies:

Liao et al. (2004): A population-based cross-sectional study of 5,431 members of the 

Atherosclerosis Risk in Communities cohort study in Minneapolis, MN; Jackson, MS; and 

Forsyth County, NC. Significant associations were reported between PM10 and decreased heart 

rate variability and increased heart rate. The mean PM10 concentration was 24.3 μg/m3. 

Delfino et al. (2002): Panel study of 22 asthmatic children (9-19 years) with diary of symptoms, 

medication use and presence of respiratory infection or hay fever for 61 days. Asthma symptoms 

were significantly associated with 1-h and 8-h PM10 (both lag 0 and 3-day average), but 

association with 24-h PM10 was not significant. Also significant associations were observed 

between asthma symptoms and 1-h ozone (lag 0) and 8-h max NO2 (lag 0). Associations were 

stronger in children not using anti-inflammatory medication than in children on medication. 

Evidence of significant interaction between 1-h PM10 and 8-h max NO2; but in 2-pollutant 

models, both lose significance. 

Dugandzic et al. (2006): Linked 1998-2000 data from Nova Scotia Atlee Perinatal Database 

with air pollution data, using geocoding to link to monitoring site nearest the home. Significant 

associations were reported between LBW and exposures during the first trimester for PM10

(RR = 1.33, 1.02-1.74 for >75th percentile) and SO2 (RR = 1.36, 1.04-1.78 for >75th percentile). 

No associations were reported with pollution exposures during the second and third trimesters. 

The mean PM10 concentration (trimester average) was 17 μg/m3. 

Letz and Quinn (2005): No correlation observed between Air Quality Index values for PM2.5 or 

ozone with emergency department visits (n = 149) for asthma in military trainees. 

Sagiv et al. (2005): Using a time-series analysis, this study investigated the effect of ambient 

outdoor PM10 on risk for preterm delivery counts in three Pennsylvania Counties and the City of 

Philadelphia from Jan 1, 1997-Dec 31, 2001. Results suggest an increase in preterm birth risk 

with exposure to PM10, with a RR of 1.07 (0.98, 1.18) per 50 μg/m3

 PM10 (6 weeks preceding 

birth). The mean PM10 concentration was 25.3 μg/m3

. 

International studies:

Romieu et al. (2005): A randomized double-blind trial, evaluating effect of supplementation with 

omega-3 fatty acids on reduction of PM2.5-related HRV reduction. In 50 subjects living in 

nursing home with 6-month follow-up, HRV high-frequency change associated with 8 μg/m3

PM2.5 was -0.54% (95% CI -72, -24) with supplementation, and -7% (95% CI -20, +7) without 

supplementation. The mean PM2.5 concentration was 19.6 μg/m3.

Sorensen et al. (2003): In Copenhagen, personal exposure to PM2.5 was associated with 

cardiovascular biomarkers (RBC count, hemoglobin) in women, but not men. No significant 

associations were observed with ambient PM2.5 concentrations; however, personal exposure to 

carbon black was associated with plasma protein oxidation. 

Boezen et al. (2005): In a panel of 327 elderly patients, symptom diaries and twice-daily PEF 

were collected for 3 months. Statically significant associations were reported for PM10, BS and 
 A-52 

NO2 with respiratory symptoms in subjects with airway hyperresponsiveness and high IgE levels 

(AHR+

/IgE+). There were no significant associations with the pollutants in the AHR-/IgEsubjects. 

Chan et al. (2004): In Taipei, Taiwan, continuous measurements of ECG and personal exposure 

measurements of ultrafine particles (NC0.02-1) (time period not indicated) were collected for a 

panel of nine young adults (19-29 years) and ten elderly patients (42-79 years). Decreases in 

HRV measures (SDNN, r-MSSD, LF, HF) were reported with personal exposure to NC0.02-1 for 

both age groups. 

Chuang et al. (2005): In Taipei, Taiwan, ECG and PM were measured continuously in a panel of 

26 subjects (ten with coronary heart disease, 16 with hypertension) from November 2002 

through March 2003; HRV measurements were used only for times when the subjects were 

awake. For all PM indicators, there were associations with decreases in several HRV 

measurements—SDNN, r-MSSD, LF, and HF—and positive associations with LF/HF. 

Associations were only significant for PM0.3-1.0; the authors concluded that HRV was associated 

with PM0.3-1.0, but not PM1.0-2.5 or PM2.5-10. 

Lanki et al. (2006): In Helsinki, levels of PM2.5 were related to ST-segment depression in 45 

elderly (mean age 68.2 yrs [6.5]) nonsmoking subjects with stable coronary heart disease. 

Depression of ST-segment indicates a number of conditions including myocardial ischemia. 

The mass of fine particles was apportioned between five sources. ST-segment depression was 

associated with PM2.5 originating from local traffic (RR = 1.53 [1.19-1.97] per 1 μg/m3, at a 

2-day lag) and long-range transport (RR = 1.11 [1.02, 1.20] per 1 μg/m3

). In multipollutant 

models where indicator elements were used for sources, only the absorbance (elemental carbon) 

indicator for local traffic and other combustion was associated with ST-segment depression. 

The mean PM2.5 concentration was 12.8 μg/m3

Penttinen et al. (2006): In a panel study of 57 adult asthmatics in Helsinki, subjects were 

followed for 181 days, and principal component analysis was used to evaluate source 

apportionment based on PM2.5 mass. Decreases in morning PEF was linked to PM2.5 from longrange transport and local combustion sources (1- and 2-day lags). There were no associations 

with PM2.5 derived from oil combustion, soil, or sea salt. 

Ruckerl et al. (2006): Blood parameters were measured in 57 male patients with coronary heart 

disease living in Erfurt, Germany, and positive associations were reported between elevated 

C-reactive protein and all measured pollutants B PM10, PM2.5, accumulation mode particles 

(PM0.1-1), ultrafine particles, ED, OC, NO2 and CO. The authors reported the strongest 

association with accumulation mode particles (3-day lag); significant associations were also 

observed with PM10, ultrafine particles, NO2 and CO (2-day lag strongest). Positive associations 

were also reported between ICAM-1 (indicator of endothelial dysfunction) and PM10, PM2.5, 

accumulation mode particles, EC and OC. No consistent associations were observed with 

various clotting factors. 

Pekkanen et al. (2002): In three panels of elderly subjects in Amsterdam, Erfurt, and Helsinki 

(ULTRA study), biweekly submaximal exercise tests were done for six months. ST-segment 

depression was significantly associated with both PM2.5 mass (OR 2.84, 1.42-5.66, 2-day lag) 

and ultrafine particles (OR 3.14, 1.56-6.32), and also with NO2 and CO. No consistent 

associations were reported with thoracic coarse particles. 
 A-53 

de Hartog et al. (2003): Three panels of elderly (aged 50+ years) subjects in Amsterdam, Erfurt, 

and Helsinki (ULTRA study) were followed for six months, with daily diaries and biweekly 

clinic visits. Prevalence of shortness of breath and phlegm were associated with PM2.5, but not 

with ultrafine particles, CO or NO2. The authors concluded that PM2.5 was more closely 

correlated with cardiorespiratory symptoms than ultrafine particles. 

Timonen et al. (2005): Repeated ECG measurements in panels of elderly subjects in 

Amsterdam, Erfurt, and Helsinki (ULTRA study) over six months. There were no consistent 

associations between HRV measurements and PM2.5, but a pattern of generally positive 

associations between ultrafine particles and HF were reported, along with negative associations 

between ultrafine particles and LF/HF ratio. 

Henneberger et al. (2005): Repeated ECG measurements in a panel of 56 patients with ischemic 

heart disease in Erfurt, Germany. PM2.5 (6h average) was significantly associated with decreased 

T-wave amplitude, increased T-wave complexity and nearly significant with increased variability 

of the T-wave complex. Associations with 6h PM2.5 were stronger than those with 24h PM2.5

averages. Similar associations were seen with 6h ultrafine particles, accumulation mode 

particles, OC and EC, although most were not statistically significant. Significant associations 

were reported between OC and QT duration. 
 A-54 Table A13. Results of Epidemiologic “Intervention” Studies Reference, Study Location and Period Outcome Measure Change in pollution/emissions Reported PM Levels (μg/m3

) Method/Design Effe

U.S. studiesLwebuga-Mukasa et al., 2003 Buffalo, NY 

Hospital admissions and emergency department visits for respiratory illnesses 

50% drop in total traffic at Peace Bridge following 9/11/2001 

 Statistically 

number of por seen in emrespiratory 

European studiesBayer-Oglesby et al., 2005 9 Swiss communities 1991-2001 

Respiratory symptoms via questionnaires, collected in 1992-1993 and 1998-2001 

General air pollution abatement measures in Switzerland resulting in reduced PM10 concentrations 

PM10 concentration declined an average of 9.8 μg/m3 over 

all communities, ranged from 4.0 to 12.7 μg/m3 declines. 

Mean PM10 concentrations in 

1997-2000 ranged from 10 to 38 μg/m3. 

Multivariate logistic regression models used, including adjustment for covariates including indicators for SES, health status, indoor exposure factors, and avoidance behavior. 

OR per 10 μ

chronic cou0.65 (0.54, bronchitis 0.66 (0.55, common co0.78 (0.68, nocturnal dr0.70 (0.60,  conjunctivi0.81 (0.70., No significaasthma, hay 
 A-55 Table A13 (cont’d.). Results of Epidemiologic “Intervention” Studies Reference, Study Location and Period Outcome Measure Change in pollution/emissions Reported PM Levels (μg/m3

) Method/Design Effec

European studies (cont’d) Frye et al., 2003 3 communities in East Germany 1992-1999 

Pulmonary function measurements for 2,493 children 11-14 years of age, in 1992-1993, 1995-1996, and 1998-1999. 

Reduction in air pollution concentrations following German reunification in 1990. 

Mean TSP concentrations fell from 79 to 23 μg/m3, 

while mean SO2

concentration declined from 113 to 6 μg/m3. 

Linear regression using MIXED procedure in SAS, with log-transformed lung function measures and covariates including sex, height, season, lung function equipment, parental education, parental atopy, ETS exposure. 

Percent chaparameter p

TSP: FVC: 4.7% FEV1: 2.9% 

Associationmore often girls than foreported wi

concentratio

Heinrich et al., 2002 3 communities in East Germany 1992-1999 

Respiratory symptom questionnaires for 4,949 children 11-14 years of age, in 1992-1993, 1995-1996, and 1998-1999. 

Reduction in air pollution concentrations following German reunification in 1990. 

In 1991, mean TSP concentrations range from 45 to 79 μg/m3 in the three 

communities; in 1998, range from 25 to 33 μg/m3. Fine 

particle concentrations (NC0.01-2.5) reported for 1993 

(11.7-12.6 μg/m3) and 1999 

(10.6-16.7 μg/m3) 

Two-stage analyses, using repeated-measures in generalized estimating equations. GEE logistic regression model used to compute symptom prevalences, adjusting for age, gender, parental education, parental atopy, and four indoor exposure factors (dampness/mold, gas cooking, ETS, cats); in second stage, logits of prevalence regressed against air pollution variables. 

OR per 50 μ

Bronchitis: 3.02 (1.72, Sinusitis: 2.58 (1.00, Frequent co1.90 (1.17, Otitis media1.45 (0.89, Febrile infe1.79 (0.92, Cough in m1.23 (0.82, Shortness o1.33 (0.83, 
 A-56 Table A13 (cont’d.). Results of Epidemiologic “Intervention” Studies Reference, Study Location and Period Outcome Measure Change in pollution/emissions Reported PM Levels (μg/m3

) Method/Design Effe

European studies (cont’d) Neuberger et al. (2002) Linz, Austria 1985-1990 

Lung function measured 2-8 times in 3,451 children in elementary and high schools, repeated measures over study time period. 

Uniform decreases across districts of Linz for SO2 and 

TSP; some areas report little changes and some dramatic decreases in NO2

concentrations 

NR NR Focus on lu

with reducti

report that T

confounder

Sugiri et al. (2006) East and West Germany 1991-2000 

Lung function measurements in 2,574 children aged 5-7 years 

Dramatic decline in pollution in East Germany; smaller decline in West Germany 

Annual average for TSP in year preceding measurement declined from 74 to 51 μg/m3

in East Germany, from 54 to 44 in West Germany, average on the day of investigation decreased from 133 to 30 μg/m3. 

Linear regression with covariates as for Frye et al. (2003); included test for homogeneity of effects based on proximity to busy streets. 

Lung functiin air pollutEast and Wduring study Stronger assreactive airwTSP exposuwith chroniPer 40 μg/m

Raw: 0.969 per 40 μg/m

TLC: 0.938 Exposure to reduced lun
 A-57 Table A13 (cont’d.). Results of Epidemiologic “Intervention” Studies Reference, Study Location and Period Outcome Measure Change in pollution/emissions Reported PM Levels (μg/m3

) Method/Design Effe

European studies (cont’d) Burr et al., 2003 North Wales, UK 1996-1999 

Repeated questionnaires for respiratory symptom prevalence and PEF measures in 448 adults in congested and uncongested neighborhoods, before (1996-7) and after (1998-9) bypass opened and reduced traffic flow in area 

Heavy goods vehicle counts and air pollution decreases with bypass opening 

PM2.5 mean before and after 

bypass in congested neighborhood : 21.2 μg/m3 and 16.2 μg/m3 

(23.5% reduction) and in uncongested neighborhood: 6.7 μg/m3 and 4.9 μg/m3 (26.6% reduction) For PM10 in congested 

neighborhood : 35.2 μg/m3 and 27.2 μg/m3 

(22.7% reduction) and in uncongested neighborhood: 11.6 μg/m3 and 8.2 μg/m3 (28.9% reduction) 46.9% reduction in heavy goods vehicles per hour 

Percent subjects reporting improvement calculated for congested and uncongested streets and difference expressed as percent improvement. 

% reduction any wheeze # attacks -8No associatconsulted dassociation 10.3 (3.1, 1
 A-58 

Toxicology studies:

Carvalho-Oliveira et al. (2004): Mutagenesis testing of particles collected during and after a bus 

strike in Sao Paulo, Brazil. Significant reduction in damage to DNA was observed, without 

significant changes in overt toxicity to cells, with exposure to PM collected during the strike. 

PM2.5 mass concentrations were high (~40 μg/m3

) during strike; authors note “intense traffic 

jam” during this period. Concentrations of sulfur and BETX were lower on strike than nonstrike days. 

Somers et al. (2004): Study of heritable mutation rates in laboratory mice housed an urbanindustrial area (near a major highway and two integrated steel mills) in Ontario, and mice housed 

in rural area. In both areas, one group of mice exposed to ambient air for 10 weeks and one 

group housed in a chamber with HEPA filtration system to remove 99.97+% of particles. 

HEPA filtration reduced heritable mutations in urban-industrial area, with larger effect on 

paternal mutation rates; no effect in rural area. 
 A-59 Table A14. Associations Between Source-related Fine Particles and Health Outcome

Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

Mar et al. (2006) Phoenix, AZ Feb 1995-Dec 1997 

Mortality: All nonaccidental and cardiovascular causes; age 65 yr 

PM2.5: Estimated mean 

range across 9 independent analyses (24-h avg): SO4

2: 1.3 to 3.6 

Traffic: 4.0 to 7.7 Cu: 0.2 to 0.8 Sea salt: 0.1 to 0.2 Wood: 0.9 to 2.8 Soil: 0.8 to 2.6 Estimated 5th-95th% range across 9 independent analyses (24-h avg): SO4

2: 2.5 to 6.9 

Traffic: 10.3 to 16.1 Cu: 0.5 to 3.5 Sea salt: 0.2 to 0.6 Wood: 2.3 to 6.2 Soil: 2.0 to 7.9 

None 0-, 1-, 2-, 3-, 

4-day, or 5- lag 

Time-series study. Poisson GLM with natural splines. Eight independent analyses performed. Daily PM2.5 data 

collected using both gravimetric and TEOM samplers. Several teams of investigators used different source apportionment methods with PM2.5 data. 

Traffic and secondary sulfate contributions, as estimated by different analyses, were well correlated. 

Results combineMedian 

increme(95% CCardiov

Sulfate, Traffic, Cu smelSea saltBiomasNo assofactor. Among size for observe

by trafficause mVariatioinvestigcomparesource c
 A-60 Table A14 (cont’d). Associations between Source-related Fine Particles and Mortalit

Reference, Study Location and Period Outcome Measure Mean PM Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

Ito et al. (2006) Washington, DC Aug 1988-Dec 1997 

Mortality: All nonaccidental, cardiovascular, and cardiorespiratory causes 

PM2.5: Estimated mean 

range across 9 independent analyses (24-h avg): SO4

2: 5.1 to 10.7 

Traffic: 1.6 to 4.7 NO3

-: 1.6 to 6.7 

Residual oil: 0.3 to 0.6 Wood smoke: 0.2 to 1.9 Incinerator: 0.3 to 1.0 Primary coal: 1.2 to 2.1 Sea salt: 0.2 to 0.9 Soil: 0.3 to 3.7 Estimated 5th% to 95th% range across 9 independent analyses (24-h avg): SO4

2: 10.4 to 22.0 

Traffic: 3.2 to 9.7 NO3

-: 5.0 to 17.9 

Residual oil: 0.9 to 3.3 Wood smoke: 0.6 to 5.7 Incinerator: 0.7 to 1.6 Primary coal: 3.2 to 3.8 Sea salt: 0.7 to 4.3 Soil: 0.9 to 4.8 

None 0-, 1-, 2-, 3-, or 

4-d lag 

Time-series study. Poisson GLM with natural splines. Nine independent analyses performed. PM2.5 gravimetric data collected on Thursday and Saturday only  (U.S. Park Service, IMPROVE). Traffic contributions, as estimated by different analyses, were not well correlated; however, secondary sulfate contributions were fairly well correlated. 

Results combineMedian 

increme(95% CAll caus

Sulfate, Traffic: ResiduaPrimary Soil: 2.1No signreported NO3

-, w

sea salt. Among significamortalitat lag 3 cardioreassociatall-causVariatioinvestigcomparesource c
 A-61 Table A14 (cont’d). Associations Between Source-related Fine Particles and Health Outco

Reference, Study Location and Period Outcomes and Methods Mean PM Levels Copollutants Considered Findings, Interpretation 

Riediker et al. (2004) Wake County, NC Fall 2001 Cardiovascular outcomes: Nine healthy young non-smoking male troopers studied on 4 consecutive days, working 3PM to midnight shift. HRV measured with ambulatory ECG during shift and subsequent sleep phase. Blood parameters from blood sample drawn 15 min after work shift. Mixed effects regression models used. In-vehicle PM2.5 (μg/m3) mean (SD): 23.0 (8.0) — Source apportionment of PM2.5 mass identified 4 components: crustal material (Al, Si, Ca, Ti, Fe), wear of steel automotive components (Ti, Cr, Fe), gasoline combustion (benzene, CO), and speed- changing traffic (Cu, S, aldehydes). The “speed change” factor was significantly associated with increased heart cycle length, increased HRV, decreased % lymphocytes, decreased protein C and increases in von Willebrand factor, % neutrophils, mean red cell volume, and blood urea nitrogen. The “crustal” factor was significantly associated with increased uric acid. 

Nearly significant associations were seen between the “gasoline” factor and mean heart cycle length, decreased protein C and increased von Willebrand factor. 

Nri
 A-62 Table A15. Associations of Acute Exposure to Fine Particle Components with Health Out

Reference, Study Location and Period Outcome Measure Mean Component Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

Burnett et al. (2004) 12 Canadian cities Jan 1981-Dec 1999 

Mortality: All nonaccidental, cardiovascular, and respiratory causes 

24-h avg SO4

2: 

All 12 cities: 2.84 SD not provided. 

PM2.5, PM10-2.5, 

PM10, NO2, SO2, CO, O3

0-, 1-, or 2-d lag Time-series study. 

Natural spline functions used to model nonlinear associations. SO4

2 data determined 

from 75% of PM2.5

filters. SO4

2 data 

available on 9% of days with mortality data. 

% exces

All caus

Single-pLag 1: Two-po

Lag 1: NO2 eff

pollutan
 A-63 Table A15 (cont’d). Associations of Acute Exposure to Fine Particle Components with Health 

Reference, Study Location and Period Outcome Measure Mean Component Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

Goldberg et al. (2006) Montreal, Canada 1986-1993 

Mortality: Diabetes, and nonaccidental mortality in subgroups with diabetes diagnosed at least 1 yr before death in adults >65. Also considered subgroups with cardiovascular diagnoses. 

24-h avg measured SO4

2: 

mean (SD) 3.3 (3.6) 24-h avg predicted SO4

2 (from PM2.5): 

mean (SD) 4.1 (3.6) 

PM10, TSP, 

coefficient of haze, PM2.5, 

predicted PM2.5, 

SO2, NO2, CO, 

O3

0-, 1-, and avg of 0- to 2-day lags (“3-day mean”) 

Time-series study. Poisson regression using natural spline functions. Report results for SO4

2

predicted from PM2.5; 

used statistical model to estimate mass when measurements were not available; measured data available on 2680 days and predicted data for 3653 days. 

Measure% exces

mortalit5.1% (0nonacciwith dia2.31% (Predicte% excesmortalit5.42% (nonacciwith dia2.77% ((all 3-daGreater warm seNo signnonacciwith diacardiovadisease. Associanonacciwith diacardiovacoronary 
 A-64 Table A15 (cont’d). Associations of Acute Exposure to Fine Particle Components with Health 

Reference, Study Location and Period Outcome Measure Mean Component Levels (μg/m3

)

Copollutants 

Considered

Lag Structure 

Examined Method/Design E

Klemm et al. (2004) Atlanta, GA Aug 1998-July 2000 

Mortality: All nonaccidental, circulatory, respiratory, cancer, and other causes; age <65 yr and 65 yr 

24-h avg mean (SD; range): SO4

2: 5.46 (0.79-

19.34) EC: 2.03 (0.45.-9.76) OC: 4.54 (1.41-14.61) nitrates: 1.17 (0.15-5.40) 

PM2.5, PM10-2.5, EC, OC, NO2, 

NO3

-, SO2, CO, 

O3, ultrafines, 

hydrocarbons, acid 

Multiday lag of 

0-1 d 

Time-series study. Poisson GLM using natural cubic splines with quarterly, monthly, or biweekly knots. Default model used monthly knots. Analyses done by individual components, as well as three major PM2.5 fractions: sulfate, 

carbon (OC and EC combined) and “balance” (remaining components combined). 

% excesper 5.46 

All caus

Coefficiknot moSO4

2: 0.

EC: 0.0OC: 0.0NO3

-: -0

For age with PM

monthly biweeklPM2.5 co

Results specificnumber No signthose ag

Villeneuve et al. (2003) Vancouver, British Columbia, Canada Jan 1986-Dec 1998 

Mortality: All nonaccidental, cardiovascular, respiratory, and cancer causes; SES status 

24-h avg SO4

2: 

2.7 10th-90th% 

1.1-4.4 Range 0.4-9.0 

PM2.5, PM10-2.5, 

PM10, TSP, 

coefficient of haze, SO2, NO2, 

CO, O3

0-, 1-, or 2-d 

lag; multiday 

lag of 0-2 d 

Time-series study. Poisson regression using natural spline functions. SO4

2 data collected every 

6th day. 

% exces

SO4

2: 

All causLag 0: CardiovLag 0: Respirat

Lag 0: Cancer: Lag 0: 
 A-65 Table A15 (cont’d). Associations of Acute Exposure to Fine Particle Components with Health 

Reference, Study Location and Period Outcomes and Design Mean Component Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

(Re

Metzger et al. (2004) Atlanta, GA Aug 1998-Aug 2000 Emergency department visits for total and cause- specific cardiovascular diseases by age groups >19 yr and >65 yr. Time-series study. 4, 407, 535, EDV from 31 Atlanta hospitals. Components included acidity (H+), EC, OC, water-soluble (WS) metals, sulfates Median (μg/m3) (10-90% Range) SO4

2: 4.5 (1.9-10.7) 

WS metals: 0.021 (0.006-0.061) OC: 4.1 (2.2-7.1) EC: 1.6 (0.8-3.7) 

NO2, SO2, CO, 

O3, PM10, 

PM10-2.5, PM2.5, 

ultrafine PM count, oxygenated hydrocarbons 

0-2 Poisson GLM regression 

used for analysis. A priori models specified a lag of 0 to 2 days. Secondary analyses performed to assess alternative pollutant lag structures, seasonal influences, and age effects. Cardiovascular visits were significantly associated with several pollutants, including NO2, CO, and PM2.5, but 

not O3 or sulfates 

Relative SO4

2 pe

WS met

OC per 

EC per 

All agesTotal caSO4

2 1.0

WS metOC 1.02EC 1.02CongestSO4

2 1.0

WS metOC 1.04EC 1.03IschemiSO4

2 0.9

WS metOC 1.02EC 1.01PeriphercerebrovSO4

2 1.0

WS metOC 1.02EC 1.02
 A-66 Table A15 (cont’d). Associations of Acute Exposure to Fine Particle Components with Health 

Reference, Study Location and Period Outcomes and Design Mean Component Levels Copollutants Considered Lag Structure Examined Method, Findings, Interpretation 

(Re

Peel et al. (2005) Atlanta, GA Aug 1998-Aug 2000 Emergency department visits for total and cause- specific respiratory diseases by age groups 0-1, 2-18, >19, and >65 yr. Time-series study. Components included acidity (H+), EC, OC, water-soluble (WS) metals, sulfates Median (μg/m3) (10-90% Range) SO4

2: 5.5 (1.9-10.7) 

WS metals: 0.028 (0.006-0.061) OC: 4.5 (2.2-7.1) EC: 2.0 (0.8-3.7) 

NO2, SO2, CO, 

O3, PM10, PM10-

2.5, PM2.5, 

ultrafine PM count, oxygenated hydrocarbons oxygenated hydrocarbons 

0-2 Poisson GEE and GLM 

regression used for analysis. A priori models specified a lag of 0 to 2 days. Also performed secondary analyses estimating the overall effect of pollution over the previous 2 weeks. Seasonal analyses indicated stronger associations with asthma in the warm months, especially for O3 and 

PM2.5 organic carbon. 

Quantitative results not presented for multipollutant, agespecific, and seasonal analyses. 

All ages SO4

2 pe

WS met

OC per 

EC per 

All avaiTotal reSO4

2 0.9

WS metOC 1.01EC 0.99Upper rSO4

2 1.0

WS metOC 1.01EC 0.99AsthmaSO4

2 0.9

WS metOC 1.00EC 0.99PneumoSO4

2 1.0

WS metOC 1.02EC 1.00COPD: SO4

2 1.0

WS metOC 0.99EC 0.98
 A-67 Table A15 (cont’d). Associations of Acute Exposure to Fine Particle Components with Health 

Reference, Study Location and Period Outcomes and Methods Mean Component Levels Copollutants Considered Findings, Interpretation 

O’Neill et al. (2005) Boston, MA May 1998-Jan 2000 Baseline period Time trial 2000-2002 Cardiovascular Outcomes: 270 patients with diabetes or at risk for diabetes were studied in relation to various pollutant levels and evaluated for association with vascular reactivity. Linear regressions were fit to the percent change in BAD (flow-mediated and nitroglycerin-mediated) into particulate pollutant index and other factors. SO4

2

mean: 3.3 μg/m3

Range: 0.3 to 12.9 

PM2.5, BC, 

ultrafine 

PM2.5 was associated with nitroglycerinmediated reactivity; an association was also reported with ultrafine particles. Effects were stronger in type II than type I diabetes. Black carbon and SO4

2 increases 

were associated with decreased flowmediated reactivity among those with diabetes. Although the strongest associations were with the 6-day morning average, similar patterns and quantitatively similar results appear in the other lags. 

E

6N6
 A-68 Table A15 (cont’d). Associations of Acute Exposure to Fine Particle Components with Health 

Reference, Study Location and Period Outcomes and Methods Mean Component Levels Copollutants Considered Findings, Interpretation 

Sinclair and Tolsma (2004) Atlanta, GA Aug 1998-Aug 2000 Respiratory medical visit data collected by Kaiser Permanente, including ambulatory care visits for asthma (adult and child), URI and LRI. ARIES air quality data used. Poisson GLM regression used for analysis. A priori models specified a lag of 0 to 2 days (avg). Also performed analyses using avg lag periods of 3-5 and 6-8 days. Fine particle components included SO4

2, H+, 

EC, OC, water-soluble (WS) metals.

mean (SD) in μg/m3: 

SO4

2: 5.52 (3.5) 

H+: 0.02 (0.02) 

EC: 2 (1.38) OC: 4.49 (2.2) WS metals: 0.03 (0.03) 

NO2, SO2, CO, 

O3, PM10, 

PM2.5, 

PM10-2.5, 

ultrafine PM count, oxygenated hydrocarbons (OHC) 

Adult asthma visits associated with ultrafine number count, and negatively associated with PM2.5 mass. Child asthma 

associated with OHC (0-2 day) and with PM10, PM10-2.5, EC and OC (3-5 day). LRI 

associated with PM2.5 acidity and SO2 (0-2 

day) and with PM10, PM10-2.5, EC, OC and 

PM2.5 WS metals. For URI, significant 

positive associations with ultrafine PM (0-2 day) and PM10-2.5 (3-5 day) but negative 

associations with PM2.5, SO2 and sulfate. 

RA

H

EOW

C

H

EOWL

H

EOW

U

H

EOW

Qo
 A-69 Table A15 (cont’d). Associations of Acute Exposure to Fine Particle Components with Health O

Reference, Study Location and Period Outcomes and Methods Mean Component Levels Copollutants Considered Findings, Interpretation 

Delfino et al. (2003) Los Angeles, CA Nov 1999-Jan 2000 Respiratory outcomes: Panel study of 22 Hispanic children (10-15 yr) with asthma, living in the Huntington Park region of LA. Daily diary with symptoms, inhaler use, and PEF measurements made three times daily. GEE regression methods used. Mean (range) in μg/m3: EC: 5.09 (1.79-9.42) IQR = 2.91 OC: 9.47 (4.29-17.05) IQR = 4.64 (Measured in PM10) NO2, SO2, CO, O3, PM10, numerous air toxics Significant associations reported between increased asthma symptoms and PM10, EC, OC, NO2 and SO2, acetaldehyde, benzene, ethylbenzene and tetrachloroethylene. Associations with PM10, EC, and OC generally decreased in size and lose significance in 2-pollutant models with air toxics. Authors conclude that their findings support the view that air toxics in the pollutant mix from traffic and industrial sources may have adverse effects on asthma in children. O

EllOll
 A-70

Additional U.S. and Canadian Studies:

Bennett et al. (2006): Assessed relationship between Asian dust event in April 1998 and hospital 

admissions. No statistically significant difference in hospital admissions rates for either 

respiratory or cardiovascular diseases between 4-day period in 1998 and corresponding 4-day 

period in 1997; methods include graphical display and chi-square test for difference. 

Clairborn et al. (2002): This report includes discussion of ongoing research in Spokane, WA, that 

will examine relationships between health outcomes and particle sizes and fine and thoracic 

coarse particle metal concentrations. In addition, results of previous publications from this 

research group are discussed, and it is suggested that fine particulate metals, particularly Zn, are 

significantly associated with asthma hospital admissions. 

Henneberger et al. (2005): Repeated ECG measurements in a panel of 56 patients with ischemic 

heart disease in Erfurt, Germany. PM2.5 (6 h avg) was significantly associated with decreased 

T-wave amplitude, increased T-wave complexity and nearly significant with increased variability 

of T-wave complex. Associations with 6 h PM2.5 were stronger than those with 24 h PM2.5. 

Similar associations were observed with 6 h ultrafine particles, accumulation mode particles, 

OC and EC, although most were not statistically significant. A significant association was 

reported between OC and QT duration. 

Moshammer and Neuberger (2003): In a panel of 78 children, biweekly lung function tests and 

daily symptom diaries were collected for 4 weeks. Ambient monitoring was conducted to 

determine “active surface” of particles by unipolar diffusion charging. The results of this study 

demonstrated that active surface correlates with PAH levels of particles. Significant associations 

reported between active surface of particles and evening cough, shortness of breath and wheeze. 
 A-71 Table A16: CAPs Studies with Source Apportionment or Components Analysis Reference Species CAPs Exposure CAPs Characterization Endpoints Results Factor or Principal Component Analysis Huang, Y-C.T et al. (2003) Human, M (n = 35), F (n = 2) 26.2±0.7 yr 2 h with 15 min alternating rest and exercise ~50 L/min; assessed 18 h PE Chapel Hill, NC air; HAPC; 72.2 μg/m3 (range 0–311 μg/m3) Median soluble components (μg/m3): sulfate 17.6; V 2.1; Fe 42.6; Zn 66.4; Cu 13.1; As 2.2; Ni 1.2; Se 6.0; Pb 3.4 BALF: Cell counts Cell differential protein Cytokines PGE2 Protein Fibrinogen NO Fibronectin Venous blood: CBC Ferritin Fibrinogen Factor 1 (sulfate/Fe/Se) cor

BALF PMN. Factor 2 (Cu/Zn/V) correlafibrinogen levels. BALF fibronectin correlatePMN. Factor 1 correlated highly w

Batalha et al. (2002) 

Rat, M, SD, 200–250 g; CB induced with SO2

5 h/day for 3 consecutive days in 6 experimental sets; assessed 24 h PE 

Boston, MA; HAPC; mean mass conc. 262.21±213 μg/m3 (range 

73.5–733) Elemental composition (μg/m3); sulfate 66.9; EC 11.45; OC 57.73; Al 1.22; Si 4.62; S 25.61; Cl 0.68; K 1.68; Ca 1.82; Ti 0.20; V 0.05; Cr 0.01; Mn 0.09; Fe 3.47; Ni 0.05; Cu 0.10; Zn 0.26; As 0.01; Se 0.02; Br 0.07; Cd 0.02; Ba 0.73; Pb 0.12 

Histopathology Morphometry for L/W ratios (muscular hypertrophy and constriction of vessels) 

CAPs caused vasoconstrictarteries. Exposure to CAPs in normdecreased L/W ratio that wmass, Si, Pb, sulfate, EC anIn normal rats exposed to Cwas associated with sulfate In CB rats, decreases in L/W with Si and OC. No significant associations L/W ratio and Day 1 of exponly to Days 2 and 3). 
 A-72 Table A16 (cont’d): CAPs Studies with Source Apportionment or Components Analysis Reference Species CAPs Exposure CAPs Characterization Endpoints Results Factor or Principal Component Analysis (cont’d) Goldsmith et al. (2002) Mice, Balb/c; sensitized to OVA on days 7 and 14, pretreated with OVA via inhalation on days 21, 22, and 23 5 h/day for 3 days (21, 22, and 23); exposure to CAPs only, O3 only (0.3 ppm), or CAPs+O3; assessed 24 or 48 h PE Boston, MA; HAPC; mean mass conc. 302±58 μg/m3; range 63.3– 1569 μg/m3 Elemental composition (μg/m3): Al nd–17.2, Si 0.9–35.1, S 3.5–187, Cl nd–7.9, K 0.4–5.7, Ca 0.6–12.5, Ti nd–1.9, V nd–0.26, Cr nd–0.05, Mn 0.01–0.43, Fe 1.4–21.9. Ni nd–0.16, Cu 0.02–0.43, Zn 0.06–1.1, Br 0.01–0.24, Ba 0.04–0.83, Pb 0.001– 0.34, As nd–0.31, Se nd–0.06, Cd nd Pulmonary function BALF: Cell viability Cell counts Cell differentials CAPs alone caused increas

airway responsiveness) immexposure, although the magsmall (approximately 0.9% 

in CAPs). CAPs+O3 exposure resulte

sensitized animals were chmethacholine. An Al/Si component for daconcentrations was associaOVA animals exposed to C

A S component was associnon-OVA mice exposed to 

Wellenius et al. (2003) 

Dog, F, retired mongrel; implanted balloon occluder on left anterior descending coronary artery 

6 h/day; immediately PE a 5 min preconditioning occlusion followed 20 min later by a 5 min study occlusion 

Boston CAPs; HAPC; mean mass conc. 345±194 (range 161–957) Elemental composition (μg/m3): sulfate 77.90; BC 9.78; EC 21.48; OC 66.71; Al 2.13; As 0.028; Br 0.09; Ca 4.31; Cr 0.03; Cu 0.19; Fe 8.26; K 2.15; Mn 0.18; Ni 0.16; Pb 0.15; S 27.41; Se 0.02; Si 8.17; Ti 0.41; V 0.16; Zn 0.58 

ECG: Peak and integrated ST-segment elevation Peak HR Incidence of arrhythmias 

CAPs enhanced occlusion-elevation. HR was not affected by CAST-segment elevation was other crustal elements. CAPs mass or particle numwith any endpoint. 
 A-73 Table A16 (cont’d): CAPs Studies with Source Apportionment or Components Analysis Reference Species CAPs Exposure CAPs Characterization Endpoints Results Components (Elements, sulfate, nitrate, organic/elemental carbon) Gong et al. (2005) Human, healthy (4F, 2M, 68±11 yr) and COPD (9F,9M, 72±7 yr); exposures were on separate days followed by at least 2 wks 2 h with 15 min alternating rest and exercise; assessed during, at 0h PE, 4 h PE, and day 2 (~22h PE) Los Angeles, CA; HAPC Exposures to: (a) FA (b) 0.4 ppm NO2 (c) CAPs - predominantly PM2.5 at ~200 μg/m3 collected with HAPC (d) CAPs + NO2 <0.1 μm contributed ~6 μg/m3 in all exp; >2.5 μm contributed ~6 μg/m3 in FA or NO2 exp and 12 μg/m3 in CAPs and CAPs +NO2 exp; CAPs and CAPs+NO2 (1–2.5 μm) ~170 μg/m3 Elemental composition (μg/m3): 

Si 4.0; Fe 2.9; EC 10.1; Al 1.6; Ca 2.3; Na 2.0; K 1.1; Cl 2.5; NO2 42 

ppb 

ECG SaO2

Pulmonary function BP HR Sputum: Cell counts Cell differentials 

For all exposure groups, thsymptoms, spirometry, or dIn subjects exposed to CAPdecrements in MMEF and 

than COPD) were observedof columnar epithelial cells reported. For subjects exposed to CA

decreases were associated wmass did not correlate with HR increased for both CAPfor COPD subjects, the tenlower with increasing massThere was a decrease in selduring CAPs+NO2 that we

Fe concentration. 

Urch et al. (2004) 

Human, healthy (14M, 10F; 35±10 yr) 

2 h CAP + O3

(crossover design); O3 conc. 

120 ppb 

Toronto CAPs; HAPC; mean mass conc.148 μg/m3 (range 102–257) 

Major constituents (μg/m3): C 22.7 

(OC 19.7, EC 2.5), sulfate 14.2, nitrate 14.0, ammonium 5.4, Ca 0.78 

BAD A decrease in OC or EC co

with changes in BAD. When multiple linear regrewas conducted on the dose ventilation, exposure duratconcentration), elevated OCwith change in BAD (althosulfate in the MLRA). Sulfate was not associated alone. 
 A-74 Table A16 (cont’d): CAPs Studies with Source Apportionment or Components Analysis Reference Species CAPs Exposure CAPs Characterization Endpoints Results Components (Elements, sulfate, nitrate, organic/elemental carbon) (cont’d) Urch et al. (2005) Human, healthy (13M, 10F; 35±10 yr) 1 h CAP + O3 (crossover design); O3 conc. 121 ppb Toronto CAPs; HAPC; mean mass conc.147±27 μg/m3 (range 102–214); C 28.4 μg/m3 BP HR DBP increased an average of 6 

exposure. A nonlinear relationDBP change and estimated expa similar correlation was obser

Dvonch et al. (2004) Rat, BN, M; 7 rats/group 8 h/day for 3 consecutive days (22–24 July 2004); assessed 24 h PE Urban Detroit CAPs; HAPC; mean mass conc. 354 μg/m3 Elemental composition ranges (ng/m3): sulfur 1393–26839, Mg 173–487; Ca 1137–2125; V 2–15; Fe 1035–2377; Ni 4.3–11.5; Cu 101–152; Cd 0.44–1.75; La 0.3–9.7; Ce 0.6–18.5; Sm 0.03–0.21; Pb 48.6–57.5 Plasma ADMA Elevated levels of ADMA we

rats. CAPs mass concentration was exposure (4–5 times greater thIncreased PM mass was associV, La, Ce, and Sm. An industrial complex (coal coovens, iron/steel mills, sewage located SW of the study locati

Gurgueira et al. (2002) 

Rat, SD, 250–300g 1, 3, or 5 h Boston, MA; HAPC; conc. mass range 

100–956 μg/m3; mean mass conc. 

300±60 μg/m3

Organ CL (for ROS concentration); organ water content; LDH; SOD; catalase 

Exposure to CAPs for 5 h resustress in the lung, that was ass

Fe, Mn, Cu, and Zn. Oxidative following exposure was associCAPs. Organ water content and LDH Elevated levels of the antioxidalso reported following exposu

Kodavanti et al. (2005) 

Rat, WKY and SH, 10–12 wk old 

SH one 4 h exp, assessed 1–3 h PE; SH and WKY 4h/day or 2 days, assessed 1 day PE 

Research Triangle Park, NC; HAPC 1-day exp: 1138–1765 μg/m3, size range 

1.07–1.19, mean 1.12 μm 2-day exposure 144-2758 μg/m3, 

size range 1.27–1.48, mean 1.39 μm 

Pulmonary function BALF: Cell count Cell differentials Total protein, albumin, LDH, NAG, GGT, glutathione, ascorbic acid, cytokines Blood: CBC Plasma fibrinogen ACE activity CRP 

In the 1-day exposure, no bioloIn the 2-day exposure, WKY rdecreased total cells and AM aFibrinogen levels were also eleIn the 2-day exposure, SH rats increased total protein, GGT aPMN. Decreases in albumin wFor SH rats exposed to CAPs, with Zn and OC when express
 A-75 Table A16 (cont’d): CAPs Studies with Source Apportionment or Components Analysis Reference Species CAPs Exposure CAPs Characterization Endpoints Results Components (Elements, sulfate, nitrate, organic/elemental carbon) (cont’d) Morishita et al. (2004) Rat, BN, M; some sensitized to OVA (days 1-3) and challenged (days 14-16), n = 6/group 4 days after challenge; 10 h/day for either 4 days (July) or 5 days (Sept); assessed 24 h PE Urban Detroit; HAPC; mean mass conc. 676 μg/m3 (July), 313 μg/m3 (Sept) Elemental composition (TWA in ng/m3 in July): La 1.2; S 77716; V 17; Mn 206 Elemental composition (TWA in ng/m3 in Sept): La 1.5; S 19272; V 46; Mn 309 BALF (left lung): Cell counts Cell differentials Leukocytes Total protein Right lung: trace elements by ICP-MS CAPs caused increases in BAL

allergenic rats. Increased levelnormal rats and greater increascolocalized with eosinophilic iFor the September allergic CAeosinophils and protein were rIncreased levels of La were repboth CAPs groups in SeptembIncreased levels of V and S werats in the OVA/CAPs group iHeavy industrial source complof exposure site in September. Rhoden et al. (2004) Rat, SD, M, 250-300 g; control 

and NAC-pretreated 

5 h, assessed 24 h PE 

Boston, MA; HAPC; 1060300 μg/m3

(range 150–2520 μg/m3) 

Elemental composition (μg/m3): 

Na 2.54; Mg 1.93; Al 5.21; Si 14.03; S 141.9; Cl 0.18; K 4.32; Ca 4.59; Ti 0.67; V 0.08; Cr 0.02; Mn 0.69; Fe 10.91; Ni 0.05; Cu 0.18; Zn 1.58; Br 0.20; Cd 0.01; Ba 0.83; Pb 0.10 

TBARS Carbonyl BALF: Cell counts Cell differentials Edema 

CAPs caused increases in TBAand edema. No change in BALNAC pretreatment attenuated iand PMNs. Component analysis: Al, Si, and Fe correlated with Cr and NA trended with carboCr, Zn, and Na trended with P
 A-76 Table A17: Other Acute CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Humans Devlin et al. (2003) Human, M&F (66.9±1.0 yr); healthy elderly subjects (n = 10) 2 h, alternating 15 min exercise and rest; HRV assessed pre-and post-exposure and 24 h PE; cross-over design Chapel Hill, NC; HPAC; mean mass conc. 40.5 ± 8.6 μg/m3 (range 21.2– 80.3 μg/m3) HRV CAPs caused significant decre

domain HRV parameters (PNNIndividual subjects (n = 5) exp(premature atrial contractions Source apportionment not don

Ghio et al. (2003) Human, M (n = 14), F (n = 6), 25.3±0.8 yr; 5 to FA, 15 to CAPs 2 h alternating 15 min rest and exercise ~50L/min; assessed 0 or 24 h PE Chapel Hill, NC; HAPC; mean mass 121±14.0 μg/m3, range 15.0 to 358 μg/m3 Venous blood: CBC Biochemical indices (total protein, albumin, UA, LDH, CRP) Cytokines ET-1 Fibrinogen and other clotting factors CAPs caused decreases in WB

other changes CRC values. CAPs caused decreases in LDH changes in blood chemistries. CAPs caused increases in fibrifactors and inflammatory medSource apportionment not don

Gong et al. (2004a) 

Human, M and F; healthy (68"11 yr, n = 6) and COPD (73±8 yr, n = 13) 

2 h, alternating 15 min exercise and rest; assessed just PE, at 4h, and at day 2. ECG before, during and after exposure 

Los Angeles, CA; HAPC; mean mass conc. 194±26 μg/m3; range 135–229 

μg/m3

>2.5 μm: 20±7 μg/m3; range 7 –31 

μg/m3

0.1–2.5 μm: 167±27 μg/m3; range 104–

201 μg/m3

<0.1 μm: 8±5 μg/m3; range 3–23 μg/m3

Mass percentages: 25% nitrate; 10% sulfate; 6% elemental carbon. Element composition (μg/m3): 

silicon 4.1; iron 3.1; chlorine 2.7; sodium 2.4; calcium 2.3; aluminum 1.7; potassium 1.2 

Pulmonary function SaO2

BP Exhaled NO HRV Ectopic beat incidence Venous blood: WBC, platelet, and clotting factors Sputum: Cell counts 

CAPS had no effect on symptosputum. Decreased SaO2 and i

in healthy subjects. Modest inCOPD subjects. HRV was lowCOPD subjects. Source apportionment not don
 A-77 Table A17 (cont’d): Other Acute CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Animals Gong et al. (2004b) Human, M&F (19-51 yr); healthy (4) and mild asthmatics (12) 2 h, alternating 15 min exercise and rest; assessed immediately PE, at 4h, and at day 2. ECG before, during and after exposure Los Angeles, CA; CPC; 80% coarse (2.5-10 μm), 20% fine (<2.5 μm); 157 μg/m3 (range 56–218 μg/m3 ) Elemental composition (%): silicon 19; sodium 18; iron 15; chlorine 11; sulfur 9; aluminum 7; potassium 4; magnesium 2; titanium 1; 16 others <1 Pulmonary function BP Exhaled NO HRV Sputum: Cell counts CAPs caused reduction in ove

4-24 h PE. Greater responses changes in inflammation, spiroor SaO2. Source apportionment not don

Campbell et al. (2005) Mice, M, Balb/c (6 wk); 9 mice/group; pretreated daily with OVA (50 μg) via intranasal instillation prior to CAPs exposure; OVA challenge 1 and 2 wk PE, assessed 1 day 

after challenge 

4 hr/day, 5 day/wk for 2 wk in whole body chambers 

Los Angeles, CA; 150 m downwind of heavily trafficked highways; VACES UF (#180 nm) or F (#2.5 μm) UF: mass 282.5 μg/m3; elemental 

composition (%): EC 5.7, OC 47.8, total metals 15.9, nitrate 8.8, sulfate 8.8 F: mass 441.7 μg/m3; elemental 

composition (%): EC 2.8, OC 16.1, total metals 24.6, nitrate 17.0, sulfate 14.7 

Brain: IL-1α

TNF-α

NF-κB 

Elevated NF-κB in brain nucleUF or F CAPs. Increased amount of IL-1α in cmice exposed to UF or F CAPmice exposed to F CAPs only. 

Cassee et al. (2005) 

Rat, M, SH (8–12 wk) or WKY (7 wk); a subset were preexposed to ozone for 8 h 1 day before CAPs 

6 h, assessed 2 h PE 

The Netherlands: Bilthoven (suburban), Utrecht (industrial), and freeway; HAPCFor Wistar exposures: mean mass conc. 1104 μg/m3; range 36–2085 μg/m3

For SH exposures: mean mass conc. 1234 μg/m3; range 270–3660 μg/m3

BrdU for cell proliferation BALF: LDH NAG ALP UA Total protein Blood: WBC Fibrinogen CC16 

In Wistar rats pretreated with oprotein, albumin and NAG actHb, Hct, and RBC in CBC. Adecreased. No observed effectantioxidants or cytotoxicity. In SH rats, CAPs caused increwere observed in BALF biochcaused no changes in hematolocause increases in fibrinogen aFor both strains, no robust conwas observed for CAPS as a c
 A-78 Table A17 (cont’d): Other Acute CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Animals (cont’d) Chang et al. (2004) Rat, M, SH, ~200 g, implanted with radiotelemetry transmitters 5 h/day in nose-only exposure chambers in spring (4 days total) and summer (6 days total) Taipei suburb; VACES; mean mass conc. 202±68.8 μg/m3 (spring) and 141±54.9 μg/m3 (summer); particle number 2.30 × 105 particles/cm3 (spring) and 2.78 × 105 particles/cm3 (summer) HR BP QAI HR and BP significantly incre

exposure (maximum ↑52 bpm 

QAI decreased throughout the maximum of 1.6 msec. Chang et al. (2005) Rat, M, SH, ~200 g, implanted with radiotelemetry transmitters 5 h/day in nose-only exposure chambers in spring (4 days total) Taipei suburb; VACES; mean mass conc. 202±68.8 μg/m3; particle number 2.30 × 105 particles/cm3 HRV Statistically significant decrea

baseline period) were observed The effects of CAPs on RMSSalthough there was a trend tow

Cheng et al. (2003) 

Rat, M,. SD, MCT-treated; implanted with telemetry transmitters 

6 h/day in nose-only exposure chambers for 3 consecutive days, then rested 4 days; exposed to CAPs on wk 2,3, and 4 and to FA wk 1 and 5 

Taipei suburb; VACES; mean mass conc. 240±77 μg/m3; range 108 to 338 

μg/m3

Elemental composition (μg/m3): Al 26.5; 

Mg 6.8; S 2.8; Si 2.7; Fe 1.4; Ga 0.7; P 0.5; Zn 0.2; Ni 0.07; Mn 0.03; Cu 0.02; Co 0.01; V 0.01 

HR BP core temperature 

An early decrease in HR (↓14.

followed by a gradual increase maximum observed 11 h after BP initially decreased (↓3.3 mexposure, then returned to normNo changes in core temperatur

Kleinman et al. (2005) 

Mice, Balb/c, M; pretreated with OVA via nasal instillation and challenge one and two weeks after exposure 

WBI; 4 h/day for 5 day/wk for 2 wk; assessed 24 h after second OVA challenge; 4 experiments (July and October 2001, June and August 2002) 

Los Angeles, CA; 50 or 150 m downwind of heavily trafficked roadway; VACES UF (#150 nm) or F 

(#2.5 μm) UF ranges: mass 283–442 μg/m3; count 

2.9–5.9×105 particles/cm3; elemental 

composition (μg/m3): EC 16–18, OC 

135–189, total metals 45–51, nitrate 24.7–53.7, sulfate 25.0–35.5 F ranges: mass 313–498 μg/m3; count 

1.6–2.85×105 particles/cm3; elemental 

composition (μg/m3): EC 8.5–13, OC 

86.0–253.8, total metals 10–109, nitrate 75.0–107, sulfate 25.3–76.9

BALF: Cell counts Cell differentials Cytokines Plasma: Cytokines IgE IgG1 

Mice exposed to fine CAPs in elevated eosinophils and cytokIgG1 in blood plasma compareMice exposed to UF CAPs in 2elevated IL-5 in BALF and incSignificant interactions were olocation for IL-5, eosinophils, to CAPs at 50-m had higher lebiomarkers than mice exposed of the freeway). 
 A-79 Table A17 (cont’d): Other Acute CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Animals (cont’d) Lei et al. (2004a) Rat, SD, M, 60 days old; 318.7±8.3 g; pretreated with single 60 mg/kg ip injection of MCT 6 h/day for 3 days; pulmonary function assessed 5 h PE; blood, lung and BALF 2 days PE Taipei, Taiwan; VACES; mean mass conc. 371.7 μg/m3 Elemental composition (μg/m3): K 33.7;S 25.5; Al 6.1; Fe 4.7; P 2.7; Ca 2.3; Si 2.1; Zn 1.7; Mo 0.5; Ti 0.4; Cu 0.3; Mn 0.2; Pt 0.07; V 0.06; Co 0.04 Pulmonary function BALF: Cell counts Cell differentials Total protein LDH Cytokines CAPs caused decreased 

f and i

CAPs caused increased BALF protein, IL-6, and LDH. MCh challenge following expo

Lei et al. (2004b) 

Rat, SD, M, 300–350 g; pretreated with single 60 mg/kg ip injection of MCT; 4 rat/group 

Low - 6h; high - 4.5 h; assessed 36 h PE 

Taiwan, Asian dust event particles; ACES Low: mean mass conc 315.6 μg/m3; 

elemental composition (μg/m3): Si 53.3; 

Al 14.0; S 6.25; Ca 6.1; K 3.1; Mg 2.7; Fe 2.1; As 2.1; Ni 0.09; W 0.9; V 0.2 High: mean mass conc 684.5 μg/m3; 

elemental composition: Si 41.6; Al 10.7; K 3.6; As 2.9; Mg 1.2; Ca 1.7; W 1.4; V 0.1 

BALF: Cell counts Cell differentials Total protein LDH IL-6 Blood: CBC 

A dose-dependent increase in exposure; no other blood paramDose-dependent increases in toprotein, LDH and IL-6 were obor lymphocytes. 

Nadziejko et al. (2004) 

Rat, M, F344, 18 mo; 6 rats/group, crossover design 

4 h/day for 1 day; NOI; repeated twice for CAPs and ultrafine C (500 and 1280 μg/m3) and 4 

times for SO2

(1.2 ppm) 

Tuxedo, NY; centrifugal concentrator; 161 and 200 μg/m3

HR Body temperature Activity Arrhythmia 

Increases were observed in the following CAPs exposure. No frequency were observed follo

exposure. 

Smith et al. (2003) 

Rat, M, SD, 9–10 wk; 6 rats/group 

4 h/day for 3 consecutive days in 6 experimental sets (3 weeks in fall, 3 weeks in winter); assessed immediately after exposure on day 3 

Fresno, CA; VACES; fall mean mass conc. 260–847 μg/m3 (number 1.1–

1.2×105 particles/cm3), winter mean 

mass conc. 190–815 μg/m3 (number 0.9–

1.2×105 particles/cm3); largest 

contributors to PM mass were ammonium nitrate and OC (60–80%) Elemental composition ranges (μg/m3); 

sulfate 13–51; nitrate 58–527; OC 61–141; EC 4–59; metals 8–38 (mostly Al, Si, S, Ca, and Fe); unexplained 30–174 

BALF: Cell counts Cell differential Cell viability 

Elevated PMN were observed first week of fall and the first wlevels of PM mass, nitrate, and these two weeks. The most consistent particle chwere particle number, OC, Cl, The particle characteristics thathe exposure periods were maselements (EC, Al, Si, S, K, Ca
 A-80 Table A17 (cont’d): Other Acute CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Animals (cont’d) Zelikoff et al. (2002) Rat, F-344, M, 7–9 mo, infected with Streptococcus pneunoniae (15– 20 × 106) via IT; 4 rats/group 5 h/day for 1 day; NOI; assessed 4.5, 9, 18, 24, and 120 h PE NYC; centrifugal concentrator; 65– 90 μg/m3 Lungs (affected rats): Absolute levels of bacteria Bacteria per g lung Rats exposed to NYC CAPs h

at 9 h (10% above control), 18 24 h (70% above control), and 
 A-81 Table A18: Subchronic CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Factor Analysis Lippman et al. (2005c) Mice, M, C57, ApoE-/- 6 h/day, 5 day/wk for 5 mo. Tuxedo, NY CAPs; VACES; mean mass conc. 113 μg/m3 Source categories: 1. Secondary sulfate (SS)—high S, Si, and OC 2. Resuspended soil (RS)—high Ca, Fe, Al, and Si 3. Residual oil (RO)—V, Ni, and Se 4. Motor vehicle (MV) emissions and other HR HRV (SDNN, RMSSD); data analyzed from 1600–1800 (afternoon) and 130–430 (night) SS was the largest contributor to 

(12%); MV/other were 30.9% anRS (and PM mass) were associaCAPs exposure in ApoE-/- mice. SS (but not PM mass) was assoc

in HR in the afternoons followinwas associated with short-term iperiod. MV traffic/other source category decreases in RMSSD in the afterexposures in C57. RO was associated with short-teRMSSD in the afternoons follow

mice. SS was associated with short-terRMSSD (also PM mass) in nighin ApoE-/- mice. RS was associated with short-terRMSSD at night following CAP

Maciejczyk et al. (2005) 

BEAS-2B; 0, 100, 300, 500 μg/mL for 24 h 9 104 cells/well 

Ambient (12.6"9.3 μg/m3) 

and CAPs (108.6"177.5 μg/m3) filter 

samples collected 3/4–9/5/2003 M-F (900-1500) 

Tuxedo, NY; VACES Source categories: 1. Secondary sulfate (SS)—S, Si, P,  EC, and OC 2. Resuspended soil (RS)—K, Ca, Mn,  Zn, Fe, Al, and Si 3. Residual oil (RO)—V and Ni 4. Motor vehicle (MV) emissions and  other—Zn, Se, Br, Pb, nitrate 

NF-κB The NF-κB response was correl

category. SS contributed on average 65% contributed 20%, and RO contrimass was unaccounted for and iZn, Se, and nitrate. S and OC correlated well with e
 A-82 Table A18 (cont’d): Subchronic CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Other Chen and Hwang (2005) Mice, C57 and ApoE-/-; 3–10 rats/group 6 h/day, 5 day/wk for 5 mo (4/11–9/5/2003) Tuxedo, NY; VACES; mean mass conc. 110 μg/m3 HR HRV (SDNN, RMSSD); data analyzed from 1600– 1800 and 130–430 For ApoE-/- mice, SDNN grad

of CAPs exposure, then slightand progressively increased at and 130–430). No changes in evening HR or mice. Slight increases in SDNafter 6 wk of CAPs exposure. No lag effects were observed. There was no clear pattern betestimated acute effects (48 h). Chen and Nadziejko (2005) Mice, C57, ApoE-/-, M&F ApoE-/- + LDL-/- (DK); 

4–12 rats/group 

6 h/day, 5 day/wk for up to 6 mo (3/10–9/5/2003); C57 6 mo, ApoE-/- 5 mo, 

DK 4 mo 

Tuxedo, NY; VACES ; mean mass conc. 110±79, 120±90, and 131±99 μg/m3

Heart: histopathology Aorta roots: total atherosclerotic lesion area, lipid contents, cellularity 

20 DK mice died (lesions werinfarction) during air or CAPs mice seemed to die earlier than females were more susceptibleNo abnormal lipid deposition ApoE-/- mice. 

More mice in the CAPs group (7/10) compared to the air (3/1mice in the CAPs group had cin the coronary artery (3/10) c(0/13). All DK mice developed extenregions; plaque lesion cellularCAPs-exposed mice (28%). ApoE-/- and DK mice had seve>40% of lumenal surface of aosignificantly greater for CAPs
 A-83 Table A18 (cont’d): Subchronic CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Other (cont’d) Gunnison and Chen (2005) Mice, M&F ApoE-/- + LDL- /- (DK); 3 rats/group 6 h/day, 5 day/wk for 4 mo (5/12–9/5/ 2003); sacrifice 3 or 4 days PE Tuxedo, NY; VACES; median size of 4 exposure days 389±2 nm; mean mass conc. 131±99 μg/m3 (range 13–441 μg/m3) Heart gene expression Lung gene expression Many genes were up- or down

to CAPs. The largest functionwere heat shock proteins and oOther genes related to DNA btranscription, defense responseresponse, and signal transductwere changed. The Dbp gene associated with upregulated. Hwang et al. (2005a) Mice, C57 and ApoE-/-; 3–10 rats/group 6 h/day, 5 day/wk for 5 mo (4/11–9/5/2003) Tuxedo, NY; VACES; median size of 4 exposure days 389±2 nm; mean mass conc. 133 μg/m3 (range 5–627 μg/m3) HR Core temperature Activity data analyzed from 130–430 (night) and 1100-1300 (morning) Chronic CAPs exposure was a

decreased HR (~34 bpm), bodactivity (2.4 count/min) in Ap

exposure began. There were few changes obseror activity at night in C57 micApoE-/- mice had increased bo

during exposure (1100–1300) CAPs (chamber effect). Decreassociated with mean CAPs coFluctuation of HR in ApoE-/- m

intervals (4–7 h) increased 1.3fluctuation within short term i0.7 fold. 

Lippmann et al. (200b) 

Mice, C57, ApoE-/-, M&F 

ApoE-/- + LDL-/- (DK) 

Whole-body inhalation, 6 h/day, 5 day/wk up to 6 mo.; sacrifice 3 days after last exposure day 

Tuxedo, NY; VACES Same as Lippmann et al. (I) Summary of results. 

No inflammation was observeby BALF. 
 A-84 Table A18 (cont’d): Subchronic CAPs Studies Reference Species CAPs Exposure CAPs Characterization Endpoints Results Other (cont’d) Veronesi et al. (2005) Mice, C57 and ApoE-/-; 5-9 rats/group 6 h/day, 5 day/wk for 4 mo; sacrifice 3 or 4 days PE Tuxedo, NY; VACES Dopamine-containing neurons Astrocytes In ApoE-/- mice exposed to CA

hydroxylase-stained neurons (region of the brain were obserIncreased glial fibrillary acidic (8%) in nucleus compacta werApoE-/- mice. There were no effects of CAP

C57 mice exposed to CAPs. Sun et al. (2005) Mice, M, ApoE- /- fed normal and high fat chow 6 h/day, 5 day/wk for 6 mo Tuxedo, NY; VACES; mean mass conc. 85 μg/m3 Composite atherosclerotic plaque in thoracic and abdominal aorta, vasomotor tone changes The peak constriction due to s

enhanced in high fat chow michalf-maximal dose for dilation in the same group. The mean percentage positive iNOS in aortic sections was obchow mice exposed to CAPs ccontrols; there were no differeMice fed high fat chow and exlipid content in the aortic archThere was increased hydrogen aorta of mice exposed to CAP
 A-85 Table A19: Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results Humans Schaumann et al. (2004) Humans, 12 healthy subjects (8 F, 4 M); avg 27 yr Instillation into lingula, 100 μg/10 mL; BALF collected 24 h PE Ambient PM from Zerbst, Germany (agricultural sources) or Hettstedt, Germany (industrial and domestic sources); collected in 1999; PM2.5 BALF: Cell counts Cell differentials AM surface markers Cytokines Total protein Albumin CL Exposure to He

numerous respPM. Endotoxin levesamples. In Vivo Gavett et al. (2003) Mice, Balb/c, F, 1–21 g; OVA sensitized, 2– 12 mice/group OA, 100 μg total in 50 μL saline (1 or 2 doses); assessed 18 h, 2 and 7 days after challenge 2 exposure protocols: 1) 10 μg OVA on Days 

0 and 2 for sensitization 2 h prior to PM exposure on both days and 20 μg OVA on Day 14 for challenge 2) 20 μg OVA on Day 0 and PM exposure on Day 14 with OVA challenge 2 h later 

Ambient PM from Zerbst, Germany (agricultural sources) or Hettstedt, Germany (industrial and domestic sources); collected in 1999; PM2.5

Pulmonary function after MCh challenge Serum OVA-specific IgE BALF: Cell counts Total protein Albumin LDH NAG Cytokines 

Allergic mice eelevated penh aBALF markers challenge. Mice exposed televated penh, 2 days post-chaZerbst PM had Hettstedt had mCu, Cd, Sn, and Neither Hettstebefore sensitizaresponses (excmice). 
 A-86 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vivo (cont’d) Corey et al. (2006) Mice, ApoE-/-, 11-12 mo, 2-3 mice/group Nasal instillation, 1.5 mg/kg; assessed through 4 day PE Seattle, WA PM2.5 collected in close proximity to a freeway and industrial area HR HRV (SDNN, RMSSD, HF, LF) Activity Increased HR i

exposure; decrDecreased SDNdecreased RMSLowered LF/H

Gerlofs-Nijland et al. (2005) Rats, SH, M, 250–350 g, 4–6 rats/group IT, 0.3, 1, 3, and 10 mg/kg; assessed 4, 24, or 48 h PE Road tunnel dust (RTD) collected outside a traffic tunnel in Netherlands; coarse and fine fractions were combined together prior to exposure BrdU BALF (right lung); Cell counts Cell differentials MPO activity LDH NAG ALP UA 

Albumin Total protein CC16 GSH, GSSG Cytokines Fibrinogen Hematology ET-1 Histopathology (left lung) 

Increased PMN rats exposed to dose. Increases in fibrats exposed to 48 h. A number of Bincreased with points. There was a donumber of inflain rats exposed 

Gilmour et al.

(2004) 

Mice, F, CD1, 20–25 g, 5 mice/group 

IT, 25 and 100 μg/mouse (approx. 1.25 and 5 mg/kg); assessed at 18 h PE 

Coal fly ash derived from Montana (low-sulfur subbituminous; 0.83% sulfur, 11.72% ash content) or Western Kentucky (highsulfur bituminous; 3.11% sulfur, 8.07% ash content); thoracic coarse, fine, and UF fractions 

BALF: Cell counts Cell differentials Cell viability Cytokines 

There were no either coarse pasaline. The UF fractioinduced greater and cytokine prcoarse or fine PThe fine fractiofine PM caused and protein. 
 A-87 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vivo (cont’d) Nygaard et al. (2005) Mice, BALB/cA, F, 5–9 mice/group Subcutaneous injection of particles (100 μg) with or without OVA (50 μg) into hind footpads; 20 μL solution; assessed 5 days PE Ambient PM from Oslo, Rome, Lodz, Amsterdam; spring, summer, and winter 2001/2002; thoracic coarse and fine fractions Popliteal lymph node (PLN): Cell count Cell surface molecules Cell cytokines Histology There was no o

most of the coainduction of ILLodz coarse PM were statisticalthe Lodz fine PAllergic mice eexacerbated effalone or PM alExposure to Roincreased cytokExposure to OsPLN cell countExposure to OVexpression of slymphocytes. 

Rhoden et al.

(2005) 

Rat, SD, M, 300 g; pretreated with 1) atenolol or glycopyrrolate or 2) NAC 

CAPs: WBI, 700 μg/m3, 5 h; assessed 

immediately PE SRM 1649: IT, 750 μg; assessed 30 min PE 

Boston CAPs Urban air particles; SRM 1649 

Heart CL SDNN HR TBARS (heart) Wet/dry heart ratios 

CAPs caused inwet/dry heart rSRM 1649 expTBARS, CL, aPretreatment win heart rate, SDCL in SRM 16Administration prior to SRM 1prevented chan
 A-88 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vivo (cont’d) Schins et al. (2004) Rat, Wistar, F, 350–550 g; 5 rats/group IT, 0.35 mg/rat (0.6–1 mg/kg); assessed 18 h PE Ambient PM from Duisburg (D) and Borken (B) Germany collected in weekly intervals Feb–May 2000; thoracic coarse and fine fractions D: heavily-industrialized area; endotoxin 0.3 EU/mg for fine, 5 EU/mg for coarse B: Rural area; endotoxin 0.6 EU/mg for fine, 6.6 EU/mg for coarse BALF: Cell differentials GSH, GSSG LDH Total protein Cytokines In vitro whole blood (WB) assay: Cytokines Rats exposed to 

location) had inBALF and TNF

blood assay. Only rats expodepleted GSH BALF. Rats exposed to increased MIP-

Soares et al. (2003) Mice, Balb/c, 8–10 weeks; 20 mice/group WBI, 31–47 μg/m3 (monthly average) for 

120 days; for Sao Paulo SO2 ranged from 12-20 

μg/m3, CO (8 h) ranged 

from 2.4–3.2 ppm, and NO2 ranged from 97-108 μg/m3

Urban air of Sao Paulo, Brazil (including gases) Urban air of Atibaia (AT) in rural Brazil, 65 km from Sao Paulo 

Blood from tail vein: Micronuclei (MN) in peripheral erythrocytes 

The greatest M90 days. Significant incrobserved for SaAT mice, with interaction. A positive assopollution meas

and MN frequefor the previou
 A-89 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vivo (cont’d) Steerenberg et al. (2005) Mice, Balb/cByJ.ico, M; 6–8 weeks; OVA sensitization (0.4 mg/ml) at days 0 and 14, challenge +/- PM on days 35, 38, and 41 IN, 0, 3, or 9 mg/mL PM with OVA (150-450 μg PM /mouse); assessed on day 42 Ambient PM collected during spring, winter, and summer from: (1) Oslo (near road), (2) Lodz (near heavy traffic), (3) Rome (rail station), (4) Amsterdam (near busy roadway), or (5) De Zilk (low traffic and natural allergens); thoracic coarse and fine fractions Serum from abdominal aorta: IgE IgG1 IgG2a BALF: Total cells Cell differentials LDH Cytokines Lung histopathology Spring and win

potent than sumThe order of mIgG2a, and eosRome$Oslo>AThe coarse fracactivity for De fraction. The coarse and Rome with OVof effects incluPMN, and monThe adjuvant awas greater witfraction. In general, the PM was responadjuvant activi
 A-90 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vivo (cont’d) Steerenberg et al. (2006) Rat, Wistar, M, 8 rats/group (also mice, but data reported in other studies—Nygaard et al. 2005 and Steerenberg et al. 2005) IT, 1 or 2.5 mg PM/rat; assessed 24-h PE Ambient PM collected during spring, winter, and summer from: 1) Oslo (near road), 2) Lodz (near heavy traffic), 3) Rome (rail station), 4) Amsterdam (near busy roadway); thoracic coarse and fine fractions combined in the analysis BALF: Albumin CC16 Cytokines Correlations be

industry/combucluster and pathincreased IgE wrespiratory alleThe combustiocoal/wood smowith albumin in score in the resCrustal materiawith CC16 in rMIP-2 in macr(in vitro). 

Secondary inorsource cluster csystemic allergSea spray sourcCC16 in rats an(in vitro); the C

with endotoxin
 A-91 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vitro (cont’d) Becker et al. (2003) Human AM (3 × 105 cell/mL) 50 μg/mL; 18–20 h PM downwind of Utrecht (background site; collected March 1999) and west of Utrecht, Netherlands (influenced by light industrial activities and freeway traffic, esp. diesel; collected June 1999); thoracic coarse, fine, and UF fractions Cytokines Phagocytosis CL Cell surface receptor expression Increased IL-6

and decreased expression wercoarse fraction other size fractEndotoxin was thoracic coarse 

Becker et al. (2005) Human AM (2–3 × 105 cells/cm2) and normal bronchial epithelial (NHBE) cells (1 × 105 cells/cm2) AM: 50 μg/mL; NHBE: 11 μg/mL; 18–24 h Chapel Hill, NC PM; collected Oct 2001, Jan 2002, Apr 2002, Jul 2002; thoracic coarse, fine, and UF fractions Cytokines ROS CL Thoracic coars

inducing IL-6 athoracic coarse response. The July thoracgreatest producAM. Thoracic coarsassociated with 
 A-92 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vitro (cont’d) Becker et al. (2005b) Human AM (2–3×105 cells/cm2) and normal bronchial epithelial (NHBE) cells (1×105 cells/cm2) AM: 50 μg/mL; NHBE: 25, 50, 100, 250 

μg/mL; 18–24 h 

Chapel Hill, NC PM; collected for 72 h; thoracic coarse, fine, and UF fractions 

Cytokines Gene expression 

Thoracic coarsinducing IL-8 rresponse was bTLR2 was addIL-6 release in addition of TLRbinding protein Expression of TNHBE cells exonly. Expression of Texposed to all tthe largest incrthoracic coarse TLR4 expressiexposed to thorThoracic coarsinducer of Hspalso stimulated expression. 
 A-93 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vitro (cont’d) Hetland et al. (2005) WKY rat AM; 1.5×106 cells/mL 10, 20, 50, or 100 

μg/mL; 20 h 

Ambient PM collected during spring, winter, and summer 2001/2002 from: 1) Oslo (near road), 2) Lodz (near heavy traffic), 3) Rome (rail station), 4) Amsterdam (near busy roadway); thoracic coarse and fine fractions 

Cytokines Thoracic coars

and summer frofor IL-6 releaseOslo. Thoracic coarsAmsterdam had for the winter cPM from other The spring thorand Lodz induc

The fine fractioincrease in TNany season. The thoracic coCu, and Al conEndotoxin levethoracic coarse was similar whendotoxin-bind
 A-94 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vitro (cont’d) Huang et al. (2003) Human BEAS-2B and mouse RAW 264.7; 5 × 105 cells/mL 100 μg/mL; 8–16 h PM from 4 different sites in Taiwan-background (B), urban (U), traffic (T), or industrial (I); thoracic coarse, fine, and UF fractions BEAS-2B: IL-8 Lipid peroxidation RAW 264.7: TNF-α Cell viability Increase

exposure 

although attributaFor thorsignificaand lipid and Fe wthoracic the other For the fIL-8 corincreaseassociateCu and ZPM1.0 - 2.

There wand Cr a

Li et al. (2002) RAW 264.7 and THP-1 

cells 

10–200 μg/mL; 8 h CAPs from Downey, CA 

in Los Angeles basin using VACES from Mar 15-Dec 7 2000; thoracic coarse and fine fractions 

HO-1 MnSOD JNK Β-actin GSH/GSSG Apoptosis 

The fine effect thendpoinCoarse Presulted expressihighest lin DecemThoracic Jan–Feb expressicontent tcoarse s
 A-95 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vitro (cont’d) Li et al. (2003) Human BEAS-2B and mouse RAW 264.7 8–100 μg/mL (12.3 or 21.1 for coarse, 17.3 or 20.9 for fine, and 1.9 or 3.9 μg/m3 for ultrafine); 16 h CAPs from Los Angeles basin (USC as a typical urban site with vehicular traffic and Claremont as a receptor site) using VACES from Nov 2001– March 2002; thoracic coarse, fine, and UF fractions HO-1 GSH/GSSG ROS UF PM 

inducing associateThoracic toxic effThoracic large cyt264.7 ceinside m

Pozzi et al. (2003) Mouse RAW 264.7 30 or 120 μg/mL (13.6 or 54.5 μg/cm2); 5 or 24 h Ambient PM from Rome, Italy (mainly traffic- derived) collected for 15 days in Sept 1999; 

thoracic coarse and fine fractions Endotoxin: Thoracic coarse = 7.68 EU/mg Fine = 1.92 EU/mg 

LDH AA Cytokines 

At 120 μ

induced and fine change iThoracic slightly AA and fraction Thoracic 30 μg/mTNF-α p
 A-96 Table A19 (cont’d): Size-fractionated and Collected Ambient PM Studies Reference Species (in vivo)/ Cell Type (in vitro) Exposure PM Characterization Endpoints Results In Vitro (cont’d) Shi et al. (2003) Human A549; 1.2×105 cells/ chamber 50 μg/mL; 2 h Ambient PM from Dusseldorf, Germany from Jul–Dec 1999; coarse and fine fractions Hydroxyl radical formation (using electron spin resonance) 8-Hydroxyde- oxyguanosine (8-OHdG) in A549 DNA or calf thymus DNA Coarse P

generate OHdG cmass. Cradical acoarse PFor coarsamples hydroxysummer Both coainduced 

Vernanth et al. (2004) BEAS-2B; 2.0×104 cells/cm2 10, 20, 40, 80, 160 μg/cm2; 

(≈25–400 μg/mL), 24 h 

Dust PM2.5 (0.3–3 μm): 

DD: desert dust (unpaved road) WM: west mesa (windgenerated dust area) R4: range 40 (unpaved road) UN: Uinta (wind and recreation activity) 

Cell viability Cytokines TRPV1 receptor ROS 

The cytofollows: The IL-6 the highHeating IL-6 respLPS indrelease wthat from 

Veranth et al.(2006) 

BEAS-2B; 3.5 × 104

cells/cm2

10, 20, 40 or 80 μg/cm2

(≈25–200 μg/mL); 24 h 

Urban and rural surface soils (32) from the Southwestern U.S.; PM2.5

Cell viability Cytokines 

Rank orat low anCoal fly IL-6 comStrongesIL-8 werOC. 
 A-97 Table A20. Acid Aerosol Studies Reference Species Exposure Exposure Characterization Endpoints Sulfate Effect

Controlled human study Tunnicliffe et al. (2003) Humans, healthy (7F, 5M; avg 34.5 yr) and mild asthmatics (5F, 7M; avg 35.7 yr; all using short-acting β agonists); double blind, random order design; prior to exposure subjects brushed teeth and gargled with mouthwash to reduce oral ammonia levels 1 h; head-only exposure system; measured during, pre- and/or post- exposure, or 5.5–6 h later Six exposures: 1) FA 2) SO2 (200 ppb) 3) sulfuric acid (200 μg/m3; low) 4) sulfuric acid (2000 μg/m3; high) 5) NH4HSO4 (200 μg/m3; low) 6) NH4HSO4 (2000 μg/m3; high) Particle exposures target MMD 0.3 μm, count mode 

≈30 nm. 

Self-reported symptoms Ventilation (breaths/min, VT) 

Lung function Exhaled NO Nasal lavage (AA and UA) 

Asthmatics ex

increased respAsthmatics exconcentrations 

increased exhaHealthy subjeconcentrations NH4HSO4 had 

nasal lavage. 

Animal toxicology studies Kleinman et al. (2003) 

Rat, F344, 22–24 mo; 10–12 rats/group 

4 h/day, 3 consecutive day/wk, 4 wk; NOI; 12 h PE 

Four exposures: (1) FA (2) O3 (0.2 ppm) (3) Low conc. particle mixture (50 μg/m3 EC + 70 μg/m3

NH4HSO4) +O3 (0.2 ppm)–0.3 

μm MMAD, 2.5 GSD (4) High conc. particle mixture (100 μg/m3 EC + 140 

μg/m3 NH4HSO4) + O3 (0.2 

ppm)–0.3 μm MMAD, 2.3 GSD 

Lung histology Cell replication in lung epithelial and interstitial cells BALF: Albumin mucus glycoprotein total protein AM Fc receptor binding AM function 

Exposure to eiparticle mixtureplication (29AM Fc receptburst activity. Greater cell rethe interstitial epithelial regiAt the end of eactivated but bdepressed. Increases in toin the low conmixture group 
 A-98 Table A20 (cont’d). Acid Aerosol Studies Reference Species Exposure Exposure Characterization Endpoints Sulfate Effect

In Vitro Kleinman et al. (2006) Rat, SD, M, 200 g; 5–15 rats/group 4 h; NOI; assayed 42 h post-exposure Nine exposures: (1) FA (2) O3–0.3 ppm (3) O3–0.6 ppm (4) H2SO4–0.5 mg/m3 (5) H2SO4–1.0 mg/m3 (6) O3 + H2SO4–0.3 ppm + 0.5 mg/m3 (7) O3 + H2SO4–0.3 ppm + 1.0 mg/m3 (8) O3 + H2SO4–0.6 ppm + 0.5 mg/m3 (9) O3 + H2SO4–0.6 ppm + 1.0 mg/m3 Aerosol MMD 0.23–0.28 μm (GSD 2.1–2.3). Lung histology DNA synthesis in nose, trachea, and lung AM Fc receptor binding AM function Exposure to O

lesions in the 0.6 ppm; co-ex

attenuated this interaction). O3 and H2SO4 

in this study. 

Beck-Speieret al. (2003) 

Dog, AM (1 × 106/mL) and 

blood PMN 

Sulfite and sulfate at pH 6 or pH 7; 30 min. 

1.0 mM PAF 

LTB4

5-HETE 12-HHT TXB2

PGE2

PLA2

Sulfite at pH 7 

for release of synthesis of PSulfite activat

through signalpathway. 
 B-1

APPENDIX B 

Bibliographies and Annotated Bibliographies for Recent Studies 

on the Health Effects of Particulate Matter Exposure 

Recent Multicity Epidemiologic Studies 

Epidemiologic Studies on Health Effects Associated with Exposure to Traffic 

Toxicology Studies of Traffic, Diesel, or Vehicle Exhaust 

Toxicology and Epidemiology Studies of Ultrafine Particles 

Toxicology and Epidemiology Studies of Metals or Metal-Containing Particles 

Toxicology Studies of Traffic, Diesel, or Vehicle Exhaust 

Epidemiologic Studies on Health Effects Associated with Exposure to Traffic 

Toxicology Studies of Endotoxin/LPS or Endotoxin/LPS-Containing Particles 

Toxicology and Epidemiology Studies of Wood Smoke 
 B-2

Recent Multicity Epidemiologic Studies 

 The following three studies are described in detail in Tables 1 and 2. The remaining 

studies are grouped by the general issues being evaluated. 

Ostro B, Broadwin R, Green S, Feng W-Y, Lipsett M. 2006. Fine particulate air 

pollution and mortality in nine California counties: results from CALFINE. Environ 

Health Perspect 114: 29-33. 

Burnett RT, Stieb D, Brook JR, Cakmak S, Dales R, Raizenne M, Vincent R, Dann T. 

2004. Associations between short-term changes in nitrogen dioxide and mortality in 

Canadian cities. Arch Environ Health 59:2280236. 

Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, Samet JM. 2006. 

Fine particulate air pollution and hospital admission for cardiovascular and respiratory 

diseases. JAMA 295:1127-1134. 

Confounding by co-pollutants, weather, influenza epidemics:

Schwartz J. (2004a): Potential confounding of associations between PM10 and mortality by 

weather and season was assessed in 14 U.S. cities. A 0.36% (95% CI: 0.22, 0.50) excess risk in 

mortality per 10 μg/m3 increase in PM10 was estimated using symmetrical sampling of control 

days. Results were little changed when control days were matched on temperature, the time 

stratified method was applied, or more lags of winter time temperatures were used. These results 

indicated that associations between PM10 and mortality risk are unlikely to be confounded by 

weather and season, and are robust to the analytical method. 

Schwartz J. (2004b): Uses case-crossover design to assess potential confounding of associations 

between PM10 and mortality by gaseous co-pollutants in 14 U.S. cities. Significant associations 

reported with case-crossover matching for each of the 4 gaseous co-pollutants; effect estimate 

sizes range from 0.45% to 0.81% increases per 10 μg/m3 PM10. 

Welty LJ, and Zeger SL. (2005): Used two flexible versions of distributed lag models to control 

for weather and season in 100 cities (1987-2000), with a 0-, 1- or 2-day lag for PM10. Results 

were consistent with previous analyses, with effect estimates of approximately 0.2% increase in 

mortality per 10 μg/m3

 PM. 

Touloumi G et al. (2005): Used data from 7 APHEA-2 cities and found that adjustment for 

influenza epidemics increased effect estimate for PM10-mortality associations in most cases. 

Concentration-response function and threshold evaluation: 

Daniels MK et al. (2004): Applied flexible modeling strategies to daily time-series data for 

20 U.S. cities (1987-1994). Spline model showed a linear relation without indicating a threshold 

for relative risks of death from all causes and for cardiovascular-respiratory cases with shortterm PM10 exposure.
 B-3

Evaluation of factors influencing heterogeneity:

Dominici F et al. (2003): City-specific and regional effect estimates provided for the 88-city 

analysis (1987-1994). The authors report “some modest variation in the relative risks across the 

nation . . . we were unable to explain the heterogeneity using descriptors of the population, air 

pollution characteristics, and reliability of the PM10 measurement data.” 

Martins et al. (2004): Significant associations were observed between PM10 and respiratory 

mortality in the elderly ($60 yr) in the combined analysis for six regions in Sao Paulo, Brazil, 

with an effect estimate of 5.4% (2.3, 8.6) excess risk per 10 μg/m3 increase in PM10 at a multiday 

lag of 0 to 2 days. The greatest effect (14.2% [95% CI: 0.4, 28.0]) was found in the region with 

the highest % of slums, and the lowest % with college education and high monthly income. The 

effect of PM10 on respiratory mortality was strongly and negatively correlated with two SES 

indicators: % with college education and family income, and positively correlated with greater 

% living in slums. 

Le Tertre A, et al. (2005): Used data from 21 cities (includes one non-APHEA city), reporting 

heterogeneity in associations between PM10 and mortality and calculates Bayesian estimates. 

A meta-regression method was then used to adjust for the identified sources of the heterogeneity. 

The authors state that the heterogeneity present in the data could be better taken into account 

by deriving an estimated underlying distribution that represents the dispersion observed 

between cities. 

Medina-Ramon M, et al. (2006): Uses case-crossover design to evaluate effects of ozone and 

PM10 on respiratory hospital admissions and evaluate city characteristics that may explain 

heterogeneity in data from 36 U.S. cities. Significant associations found for both pollutants with 

pneumonia and COPD hospital admissions (effect estimates per 10 μg/m3 PM10 of 1.47% and 

0.84%, respectively). Effect estimates for PM10 reduced with greater air conditioning use in 

cities; little difference based on percentage of PM10 from traffic. 

Samoli E, et al. (2005): Using data from 22 cities, found that association between PM10 or BS 

and mortality could be adequately estimated using a linear model. Tested thresholds at 10 and 

20 μg/m3

 PM10 and found that linear models had better fit. The authors also report heterogeneity 

in associations between cities that is partly explained by several factors, with increased effect 

estimates associated with hotter climates, mean NO2 concentration as an indicator of traffic 

emissions, and lower standard mortality rates (more elderly people in population). 

Zeka A, et al. (2005): Using case-crossover design, significant associations were reported 

between PM10 and both cardiovascular and respiratory mortality in 20 U.S. cities that were 

stronger using 3-day cumulative distributed lag model. Associations were increased in size with 

increasing percent PM10 from traffic and with increasing summer temperature variability. 

Zeka A, et al. (2006): Using data from 20 U.S. cities with case-crossover design, reported 

significant associations between PM10 and mortality from all causes, respiratory, and heart 

disease, and positive but not significant associations with MI and stroke deaths. Substantial 

effect modification was found for some sociodemographic factors (larger with >75 years, little 

difference for gender or race), location of death (larger for out-of-hospital), season (larger in 
 B-4

spring and fall) and coexisting medical conditions (e.g., secondary diagnoses of pneumonia, 

diabetes, heart failure). 

Lag Structure:

Analitis A, et al. (2006): Used 2-stage hierarchical model with data from 29 APHEA-2 cities, 

and report significant associations with cardiovascular mortality (0.76% per 10 μg/m3 PM10) and 

respiratory deaths (0.58% per 10 μg/m3

 PM10) using 0-1 day average lag. With distributed lag 

model effect sizes increase, particularly for respiratory mortality. The associations are 

independent of ozone, but reduced in size with adjustment for SO2 and NO2. 

Roberts, S. (2005): This investigation finds that distributed lag models return particulate air 

pollution mortality effect estimates that are more robust and less prone to negative bias than 

single- and multi-day moving average exposure measures. The author concludes that distributed 

lag models should be preferred in future air pollution mortality time series studies and helps 

quantify the negative bias that can result from using single or multi-day moving average 

exposure measures. 

Zanobetti A, et al. (2003): Using distributed lag models in 10 cities from the APHEA-2 project, 

effect estimate size for association with PM10 doubles for cardiovascular deaths and is five times 

higher for respiratory disease deaths compared with 1-day lag models. 

Zeka A, et al. (2005): Using case-crossover design, significant associations were reported 

between PM10 and both cardiovascular and respiratory mortality in 20 U.S. cities that were 

stronger using 3-day cumulative distributed lag model. Associations were increased in size with 

increasing percent PM10 from traffic and with increasing summer temperature variability. 

Mortality displacement:

Dominici F, et al. (2003): Used decomposed time series of PM10 data for 4 U.S. cities for which 

daily data were available (1987-1994), and reported larger relative rates of mortality associated 

with PM10 using longer timescale (14 days to 2 months) than shorter timescale (1 to 4 days), 

indicating that association does not represent advancement of death by just a few days for frail 

individuals. 

Seasonal variation:

Peng RD, et al. (2005): Bayesian semiparametric hierarchical models for estimating timevarying effects of pollution on mortality in multisite time series studies. Effect estimates for 

winter, spring, summer, and fall were, respectively, 0.15%, 0.14%, 0.36% and 0.14% increases 

per 10 μg/m3

 PM10 (1-d lag), with an all-year estimate of 0.19% per 10 μg/m3 PM10. Effects were 

stronger in the summer for the Northeast and Industrial Midwest, but little difference across 

seasons in the southern regions and northwest. 

New health outcomes:

Ballester et al. (2006): Significant associations reported between PM10 (lag 0-1 day) and 

emergency admissions for cardiovascular diseases and heart diseases. Significant associations 
 B-5

were also reported with ozone and CO, while associations with SO2 and NO2 were more 

sensitive in two-pollutant models. 

Ibald-Mulli A, et al. (2004): Study of 131 adults in Helsinki, Erfurt and Amsterdam with 

biweekly clinic visits for 6 months. Results suggest decreased blood pressure (diastolic and 

systolic) and in heart rate. 

Timonen KL, et al. (2006): Same cohort as above with analysis of heart rate variability (5-min 

measurement). Ultrafine particles associated with decreased LF/HF in pooled analysis; PM2.5

associated with decreased HF and reduced LF/HF in Helsinki but opposite association in Erfurt, 

and no clear association in Amsterdam. Suggest that effects may be modified by location and 

characteristics of individual. 

von Klot S, et al. (2005): In cohort of 22,000+ first MI survivors in Augsburg, Barcelona, 

Helsinki, Rome and Stockholm, significant associations were reported for cardiac hospital 

readmissions with PM10, ultrafine particle number count, CO, NO2 and O3. 

Wellenius et al. (2006a): Using case-crossover analysis, a significant association was reported 

between PM10 and hospital admissions for congestive heart failure in the elderly in 7 U.S. cities 

(7% increase [95% CI 0.35 to 1.10%] per 10 μg/m3

 PM10 [0-day lag]). Effect seemed to be 

smaller in those with secondary diagnosis of hypertension. No consistent effect modification 

observed for age, gender, race or other secondary diagnoses. 

Wellenius et al. (2006b): Using case-crossover analysis, a significant association was reported 

between PM10 (3-day distributed lag) and hospital admissions for ischemic stroke (1.03% 

increase [95% CI 0.04 to 2.04%] per 10 μg/m3

 PM10). No association was found for 

hemorrhagic stroke admissions. 

Zanobetti A, and Schwartz J. (2005): Case-crossover analysis showed significant association 

between PM10 and emergency hospitalization for myocardial infarction in elderly people (0.65% 

[0.3-1.0] per 10 μg/m3 PM10) in 21 U.S. cities. Effect size doubled for subjects with previous 

admission for COPD or secondary diagnosis of pneumonia (difference in size not statistically 

significant). 

Analytical methods:

Biggeri et al. (2005): A meta-analysis was conducted to examine the associations between PM10

and all-cause, cardiovascular, and respiratory mortality in six Italian cities. Daily PM10 data 

were collected in 2 cities; in the other cities, daily TSP collected. Conversion factors, estimated 

through validation studies, were applied to convert TSP to PM10. Significant associations with 

PM10 were observed for all-cause (0.90% [95% CI: 0.21, 1.66] excess risk per 10 μg/m3 increase 

in PM10 at a 0- to 1-day lag) and cardiovascular (1.11% [95% CI: 0.22, 2.19]) mortality. All 

other pollutants examined (NO2, SO2, CO, O3) also were significantly associated with all-cause 

mortality. The effect of PM10 on mortality was greater during the warm season and for those 

aged 65 yr. 
 B-6

Daniels MJ, et al. (2004): Investigated impact of variance underestimation in both a simulation 

study and using NMMAPS data; report that underestimation as large as 40% had little effect on 

the national average relative risk of mortality. 

Roberts S. (2005): Introduces model that uses information available in daily mortality time 

series to infer otherwise lost information about the effect of PM on mortality, considering that 

PM measurements may only be available every sixth day while the effect of PM on mortality 

may be spread over multiple days. Analyses use data from NMMAPS, a simulated data set, and 

daily PM measurements from Cook County, IL and Allegheny County, PA. New model 

produces more precise effect estimates compared with standard model. 

Roberts S, and Martin, MA. (2006): New model tested use of moving total mortality time series 

that “allows inference on the information about the effect of PM on mortality that is lost when 

daily PM data is unavailable.” Using the 100-city database (1987-2000), report results that are 

“consistent with those found in the NMMAPS analysis” with effect estimates of 0.12% increase 

in total mortality and 0.17% increase in cardiovascular and respiratory mortality per 10 μg/m3

PM10. 

Simpson et al. (2005): Using three statistical methods—GLM, R, and a two-stage Poisson 

GAM with stringent convergence criteria—PM-related excess risks of total nonaccidental, 

cardiovascular, and respiratory mortality in Brisbane, Sydney, Melbourne, and Perth were 

estimated. Daily PM2.5 data were collected using nephelometers in all four cities. Daily PM2.5

data were available in all four cities, but Brisbane was excluded from the analysis as more than 

40% of data was missing. Daily PM10 data were only available in Brisbane, Sydney, and 

Melbourne. Melbourne, which was included in all analyses, was missing ~30% of PM2.5 and 

PM10 data. Significant associations were observed for all cause and cardiovascular mortality 

using the nephelometric data, but no associations were found with PM2.5 or PM10. Results using 

different statistical methods were similar. Mean PM2.5 levels ranged from 9.00 μg/m3 (Sydney 

and Perth) to 9.30 μg/m3

 (Melbourne) across the 3 cities. 

Measurement error:

Zeka A and Schwartz J. (2004): Used 90-city database (1987-1994) and approach developed by 

Schwartz and Coull (2003) to test associations between pollutants and mortality, correcting for 

measurement error in the other pollutants. Effect estimates from models adjusting for the 

gaseous pollutants ranged from 0.14 to 0.35% increases in mortality per 10 μg/m3

 PM10, with an 

overall effect of 0.24% per 10 μg/m3

 PM10. 

Review article:

Sandstrom T et al. (2005): Review article, concludes “The PM investigated generally induced 

significant biological responses, with both coarse (2.5-10 μm) and fine (0.1-2.5 μm) PM being 

able to induce toxic effects.” Three studies briefly described: HEPMEAP (health effects of 

particles from motor engine exhaust and ambient air pollution) RAIAP (respiratory allergy and 

inflammation due to ambient particles) PAMCHAR (chemical and biological characterization of 

ambient air coarse, fine and ultrafine particles for human health risk assessment in Europe). 
 B-7

Epidemiologic Studies on Health Effects Associated 

with Exposure to Traffic 

Mortality

Finkelstein MM, Jerrett M, Sears MR. (2004) Traffic air pollution and mortality rate 

advancement periods. Am J Epidemiol 160:173-177. 

Firestone Institute pulmonary function cohort (5228 adults), using residence w/in 50 m or 

major urban road or w/in 100 m of a highway as traffic index. CVD mortality 

significantly associated with pollution index [RR 1.06 (1.00-1.13)]; stronger association 

with deprivation index (RR 1.15) and traffic indicator (RR 1.40). In 2- and 3-variable 

models, pollution index reduced (RR 1.04 and nonsignificant) with little change in traffic 

indicator and some reduction for deprivation index. Deprivation and pollution indices 

were highly collinear, so created a combined (sum) index; both traffic and 

deprivation/pollution index were significantly association with CVD mortality 

(RR 1.05, 1.01-1.10) 

Finkelstein MM, Jerrett M, DeLuca P, Finkelstein N, Verma DK, Chapman K, Sears MR. (2003) 

Relationship between income, air pollution and mortality: a cohort study. Can Med Assoc J 

169(5):397-402. 

Firestone Institute pulmonary function cohort (5228 adults), using residence w/in 50 m or 

major urban road or w/in 100 m of a highway as traffic index. Significant association 

between mortality and residence w/in a road/highway buffer: RR 1.18 (1.02-1.38) for all 

subjects. By interpolation from Ontario life tables, estimated “rate advancement period” 

associated with traffic pollution of 2.5 years (0.2-4.8). 

Finkelstein MM, Jerrett M, Sears MR (2005) Environmental inequality and circulatory disease 

mortality gradients. J Epidemiol Community Health 59:481-486. 

Hart JE, Laden F, Schenker MB, Garshick E. (2006) Chronic obstructive pulmonary disease 

mortality in diesel exposed railroad workers. Environ Health Perspect 114:(in press) 

Hoek G, Brunekreef B, Goldbohm S, Fischer P, van den Brandt PA. (2002) Association between 

mortality and indicators of traffic-related air pollution in the Netherlands: a cohort study. 

Lancet 360(9341):1203-1209. 

Jerrett M, Burnett RT, Ma R, Pope CA III, Krewski D, Newbold KB, Thurston G, Shi Y, 

Finkelstein M, Calle EE, Thun MJ. (2005) Spatial analysis of air pollution and mortality in 

Los Angeles. Epidemiology 16:727-736. 

American Cancer Society cohort, using traffic buffers of 500 and 100 m from freeway based on 

zip code centroids (22,905 subjects in 267 zip code areas). Significant association between 
 B-8

PM2.5 and deaths from all causes; after adjustment for 44 covariates and freeways w/in 

500 m, significant associations were reported with death from all causes (RR 1.17, 

1.05-1.31) and IHD (RR 1.38, 1.11-1.72). 

Lipfert FW, Wyzga RE, Baty JF, Miller JP. (2006) Traffic density as a surrogate measure of 

environmental exposures in studies of air pollution health effects: long-term mortality in a 

cohort of U.S. veterans. Atmos Environ 40:154-169. 

Veterans cohort; traffic volume estimated from [vehicle-km traveled/county land area] 

using data from 1985, 1990 and 1997. Significant association with traffic (RR 1.176, 

1.100-1.258 per 2.6 in 1999 data). In 3-pollutant models, traffic effect was little changed, 

with the PM2.5 effect estimate reduced and not significant (RR 1.032) and PM10-2.5 effect 

negative and nonsignificant. 

Lipfert FW, Baty JD, Wyzga RE, Miller JP. (2006) PM2.5 constituents and related air quality 

variables as predictors of survival in a cohort of U.S. military veterans. Inhal Toxicol (in press). 

Veterans cohort; traffic volume estimated from [vehicle-km traveled/county land area], 

also PM2.5 speciation data. Significant associations between mortality and traffic density, 

EC, nitrates, V and Ni, with the strongest effects for traffic density and EC. Positive, 

nonsignificant associations with PM2.5 mass and sulfates. Negative nonsignificant 

associations with elements association with crustal particles (Al, Ca, Si). 

Maheswaran R, Elliott P. (2003) Stroke mortality associated with living near main roads in 

England and Wales: a geographical study. Stroke 34(12):2776-2780. 

Zeka A, Zanobetti A, Schwartz J. (2005) Short term effects of particulate matter on cause 

specific mortality: effects of lags and modification by city characteristics. Occup Environ Med 

62:718-725. 

Multicity study, associations for PM10 with cause-specific mortality in 20 U.S. cities. 

Heterogeneity in effect estimates partially explained by differences in city characteristics, 

including increased % PM10 from traffic. 

Respiratory morbidity: 

Brauer M, Hoek G, Van Vliet P, Meliefste K, Fishcer PH, Wijga A, Koopman LP, Neijens HJ, 

Gerritsen J, Kerkhof M, Heinrich J, Bellander T, Brunekreef B. (2002) Air pollution from traffic 

and the development of respiratory infections and asthmatic and allergic symptoms in children. 

Am J Respir Crit Care Med 166(8):1092-8. 

The Netherlands: respiratory symptoms for 4,135 in birth cohort, 3,730 reassessed at 

2 yr; numerous cities. Associations with NO2, PM2.5, soot; long-term average based on 

2-wk samples. Positive, borderline significantly associations between all three pollutants 

and prevalence of wheeze, E, N, T infections, and flu/serious colds 

Brunekreef B, Janssen NAH, de Hartog J, Harssema H, Knape M, van Vliet P. (1997) Air 

pollution from truck traffic and lung function in children living near motorways. Epidemiol 

8(3): 298-303. 
 B-9

Buckeridge D, Gozdyra P, Ferguson K, Schrenk M, Skinner J, Tam T, Amrhein C. (1998) 

A study of the relationship between vehicle emissions and respiratory health in an urban area. 

Geogr Environ Modeling 2:17-36. 

Buckeridge DL, Glazier R, Harvey BJ, Escobar M, Amrhein C, Frank J. (2002) Effect of motor 

vehicle emissions on respiratory health in an urban area. Environ Health Perspect 

110(3):293-300. 

Three year hospitalization rates determined in SE Toronto; PM2.5 emissions estimated 

from traffic data; modeled exposures. Hospitalization rate for subset of respiration 

diseases (asthma, bronchitis, COPD, pneumonia, URI) significantly increased with PM2.5 

emission density (RR 1.24, 1.05-1.45) 

Burr ML, Karani G, Davies B, Holmes BA, Williams KL. (2004) Effects on respiratory health of 

a reduction in air pollution from vehicle exhaust emissions. Occupational and Environmental 

Medicine 61:212-218. 

PM10, PM2.5 via dichot, daily for 3-wk and 2-wk periods, before and after bypass; 

respiratory symptoms in 448 adults living in congested and uncongested neighborhoods. 

PM2.5 means decreased between before/after bypass by 23.5% in congested and 26.6% 

in uncongested neighborhoods. Reduction in symptoms with decreased traffic for any 

wheeze -6.5% (-14.9, 2.0) and number of attacks -8.5% (-18.2, 1.2). No association with 

cough, phlegm, consulted doctor, rhinitis. Positive association with “affects activities” 

10.3 (3.1, 17.3). 

De Marco R, Poli A, Ferrari M, Accordini S, Giammanco G, Bugiani M, Villani S, Ponzio M, 

Bono R, Carrozzi L, Cavallini R, Cazzoletti L, Dallari R, Ginesu F, Lauriola P, Mandrioli P, 

Perfetti L, Pignato S, Pirina P, Struzzo P; ISAYA study group. (2002) Italian Study on Asthma 

in Young Adults. The impact of climate and traffic-related NO2 on the prevalence of asthma 

and allergic rhinitis in Italy. Clin Exp Allergy 32(10):1405-1412. 

Delfino RJ, Gong H, Linn WS, Pellizzari ED, Hu Y. (2003) Asthma symptoms in Hispanic 

children and daily ambient exposures to toxic and criteria air pollutants. Environ Health 

Perspect 111(4):647-656. 

Los Angeles, CA, community with high traffic density. Positive associations with both 

criteria pollutants and VOCs; two-pollutant models showed stronger association with EC 

or OC fractions of PM10 than PM10 mass. Suggest air toxics from traffic and industrial 

sources may have adverse effects on asthma in children. 

Delfino RJ, Gong H, Linn WS, Hu Y, Pellizzari E. (2003) Respiratory symptoms and peak 

expiratory flow in children with asthma in relation to volatile organic compounds in exhaled 

breath and ambient air. J Expos Analysis Environ Epidemiol 13:348-363. 

Los Angeles, CA, community with high traffic density. Ambient VOCs, NO2 and SO2

associated with decreased peak flow in Hispanic children. 

Fritz GJ, Herbarth O. (2004) Asthmatic disease among urban preschoolers: an observational 

study. Int J Hyg Environ Health 207:23-30. 
 B-10

Garshick E, Laden F, Hart JE, Caron A. (2003) Residence near a major road and respiratory 

symptoms in U.S. Veterans. Epidemiol 14(6):728-736. 

U.S. male veterans in SE Massachusetts: persistent wheeze increased in men living w/in 

50 m of major roadway, compared with those living >400 m away. 

Gauderman WJ, Avol E, Lurmann, F, Kuenzli N, Gilliland F, Peters J, McConnell R. (2005) 

Childhood asthma and exposure to traffic and nitrogen dioxide. Epidemiology 16(6):737-743. 

Children’s Health Study in southern California; NO2 (from 2000) as indicator of freewayrelated pollutants and 3 traffic metrics: proximity to freeway, number of vehicles/day, 

modeling of traffic-related air pollution. Significant association between asthma history 

and distance to freeway (OR 1.89, 1.19-3.02) and model-based freeway pollution (OR 

2.22, 1.36-3.63); positive nonsignificant association with traffic volume and model-based 

pollution from other roads. 

Gehring U, Cyrys J, Sedlmeir G, Brunedreef B, Belander T, Fischer T, Bauer CP, Reinhardt D, 

Wichmann HE, Heinrich J. (2002) Traffic-related air pollution and respiratory health during the 

first 2 yrs of life. Eur Respir J 19(4):690-698. 

Gordian ME, Hanuese S, Wakefield J. (2006) An investigation of the association between traffic 

exposure and the diagnosis of asthma in children. J Expo Sci Environ Epidemiol 16(1):49-55. 

Anchorage, AK, survey of parents of children in kindergarten and 1st grade, traffic index 

based on GIS mapping of traffic density w/in 100 m of home. Increased risk of asthma 

diagnosis with medium and high exposure; significant for high-exposure group (OR 

2.84, 1.23-6.51). 

Heinrich J, Topp R, Gehring U, Thefeld W. (2005) Traffic at residential address, respiratory 

health, and atopy in adults: the National German Health Survey 1998. Environmental Research 

98:240-249. 

Heinrich, J.; Wichmann, H-E. (2004) Traffic related pollutant in Europe and their effect on 

allergic disease. Current Opin Clinical Epidemiol 4: 341-348. 

Hirsch T, Weiland SK, von Mutius E, Safeca AF, Grafe H, Csaplovics E, Duhme H, Keil U, 

Leupold W. (1999) Inner city air pollution and respiratory health and atopy in children. Eur 

Respir J 14(3):669677. 

Hirsch T, Neumeister V, Weiland SK, von Mutius E, Hirsch D, Grafe H, Duhme H, Leupold W. 

(2000) Traffic exposure and allergic sensitization against latex in children. J Allergy Clin 

Immunol. 106(3):573-8. 

Ising H, Lange-Asschenfieldt H, Lieber GF, Weinhold H, Eilts M. (2003) Respiratory and 

dermatological diseases in children with long-term exposure to road traffic emissions. Noise 

Health 5:41-50. 

Janssen NAH, Brunekreef B, van Vliet P, Aarts F, Meliefste K, Harssema H, Fishcer P. (2003) 

The relationship between air pollution from heavy traffic and allergic sensitization, bronchial 
 B-11

hyper responsiveness and respiratory symptoms in Dutch school children. Environ Health 

Perspect 111(12):1512-1518. 

Kim JJ, Smorodinsky S, Ostro B, Lipsett M, Singer BC, Hogdson AT. (2002) Traffic-related air 

pollution and respiratory health: the East Bay Children’s Respiratory Health Study. Epidemiol 

13(4):S100. 

Kim JJ, Smorodinsky S, Lipsett M, Singer BC, Hogdson AT, Ostro B. (2004) Traffic-related air 

pollution near busy roads: the East Bay Children’s Respiratory Health Study. American Journal 

of Respiratory Critical Care Medicine. Am J Respir Crit Care Med 170:520-526. 

Respiratory symptoms for 1109 children in 10 schools, grades 3-5. Authors state 

positive, generally larger effect estimates for BC, NOx and NO suggest effects of primary 

emissions more than regional pollutants for these outcomes. 

Lee YL, Shaw CK, Su HJ, Lai JS, Ko YC, Huang SL, Sung FC, Guo YL. (2003) Climate, 

traffic-related air pollutants and allergic rhinitis prevalence in middle-school children in Taiwan. 

Eur Respir J 21(6):964-70. 

Lewis SA. Antoniak M. Venn AJ. Davies L. Goodwin A. Salfield N. Britton J. Fogarty AW. 

2005. Secondhand smoke, dietary fruit intake, road traffic exposures, and the prevalence of 

asthma: a cross-sectional study in young children. American Journal of Epidemiology. 

161(5):406-11. 

UK study, 11,562 children 4-6 years of age, questionnaire at school on respiratory 

symptoms. Traffic index of living w/in 30, 60, 90, 120 or 150 m of main road; asthma 

prevalence not associated with proximity of home to main road. 

Lin S, Munsie JP, Hwang SA, Fitzgerald E, Cayo MR. (2002) Childhood asthma hospitalization 

and residential exposure to state route traffic. Environ Res 88(2):73-81. 

Livingstone AE, Shaddick G, Grundy C, Elliott P. (1996) Do people living near inner city main 

roads have more asthma needing treatment? Case-control study. BMJ 312:676-677. 

Lwebuga-Mukasa JS, Ayirookuzhi SJ, Hyland A. (2003) Traffic volumes and respiratory health 

are utilization among residents in close proximity to the Peace Bridge before and after September 

11, 2001. J Asthma 40(8):855-864. 

Buffalo, NY: Decrease in traffic on Peace Bridge (50%) after Sept 11, 2001 was 

associated with decreased hospital admissions or emergency department visits for 

respiratory illnesses. 

Lwebuga-Mukasa JS, Oyana T, Thenappan A, Ayirookuzhi SJ. (2004) Association between 

traffic volume and health care use for asthma among residents at a U.S.-Canadian border 

crossing point. J Asthma 41(3):289-304. 

Buffalo, NY: Data on commercial traffic volume across Peace Bridge, and hospital 

discharges and outpatient visits for asthma. Highest asthma prevalence rates and health 

care use rates were in the two zip codes that surround the Peace Bridge. 
 B-12

Lwebuga-Mukasa JS, Oyana TJ, Johnson C. (2005) Local ecological factors, ultrafine 

particulate concentrations, and asthma prevalence rates in Buffalo, New York. J Asthma 

42:337-348. 

Buffalo, NY: Cross-sectional survey of 2000 households, OR of 2.57 (1.85-3.57) for 

having at least one person with asthma in households on west side compared to east side. 

Ultrafine particle levels also higher in communities downwind of Peace Bridge. 

McConnell R, Birhane K, Yao L, Jerrett M, Lurmann F, Gilliland F, Kunzli N, Gauderman J, 

Avol E, Thomas D, Peters J. (2006) Traffic, susceptibility, and childhood asthma. Environ 

Health Perspect 114:766-772. 

13 Southern California communities: Cohort study of kindergarten and first grade 

children in 13 communities. Risk of asthma and wheeze was increased with residence 

within 75 m of a major road, also with exposure to nonfreeway traffic pollution 

(modeled) but not to freeway or total traffic pollution. 

Montnemery P, Popovic M, Andersson M, Greiff L, Nybert P, Lofdahl CG, Svensson C, Persson 

CG. (2003) Influence of heavy traffic, city dwelling and socio-economic status on nasal 

symptoms assessed in a postal population survey. Respir Med 97(8):970-977. 

Nicolai T, Carr K, Weiland SK, Duhme H, von Ehrenstein O. (2003) Urban traffic and pollutant 

exposure related to respiratory outcomes and atopy in a large sample of children. Eur Respir J. 

21(6):956-63. 

Oftedal B, Nafstad P, Magnus P, Bjorkly S, Skrondal A. (2003) Traffic related air pollution and 

acute hospital admission for respiratory diseases in Drammen, Norway 1995-2000. Eur J 

Epidemiol. 18(7):671-675. 

Oyana TJ, Lwebuga-Mukasa JS. (2004) Spatial relationships among asthma prevalence, health 

care utilization, and pollution sources in neighborhoods of Buffalo, New York. J Environ Health 

67:25-37. 

Buffalo, NY: Statistically significant association between proximity to source and 

diagnosed asthma. Asthma clusters located along major roadways, in communities near 

Peace Bridge, and in the west side of city. 

Penttinen P, Vallius M, Tiittanen P, Ruuskanen J, Pekkanen J. (2006). Source-specific 

fine particles in urban air and respiratory function among adult asthmatics. Inhal Toxicol 

18:191-198. 

EPIC, European multi-city study, deviation of peak expiratory flow in 78 adult 

asthmatics, during winter and spring seasons, 1996-1997. Used PM2.5 data with source 

apportionment (long-range transport, local combustion, soil, heavy fuel oil, sea salt). 

Most consistent association with PM2.5 from local combustion sources; significant 

association between decreased morning aPEF and PM2.5 from long range transport; 

positive nonsignificant association with PM2.5 from soil. 
 B-13

Ryan, P.H.; LeMasters, G.; Biagnini, J.; Bernstein, D.; Grinshpun, S.A.; Shukla, R.; Wilson, 

M.S.; Villareal, M.; Burkle, J.; Lockey, J. (2005) Is it traffic type, volume, or distance? 

Wheezing in infants living near truck and bus traffic. J Allergy Clin Immunol 116: 279-284. 

Cincinnati allergy and air pollution study cohort: GIS and traffic classification used to 

categorize traffic exposures based on type (bus, truck), traffic volume and distance from 

road. Significant increase in prevalence of wheeze in infants living very near (<100 m) 

stop-and-go bus and truck traffic; no increase in infants living <400 m from high volume 

moving traffic; also greater risk for nonwhite infants compared with white infants. 

Salam MT, Yi Y-F, Langholz B, Gilliand FD. (2004) Early life environmental risk factors for 

asthma: findings from the Children’s Health Study. Environ Health Perspect 112(6): 760-725. 

Sekine K, Shima M, Nitta Y, Adachi M. (2004) Long term effects of exposure to automobile 

exhaust on the pulmonary function of female adults in Tokyo, Japan. Occup Environ Med. 

61:350-357. 

Shima M, Nitta Y, Adachi M. (2003) Traffic-related air pollution and respiratory symptoms in 

children living along trunk roads in Chiba Prefecture, Japan. J Epidemiol 13(2): 108-19. 

Sugiri D, Ranft U, Schikowski T, Kramer U. (2006) The influence of large-scale airborne 

particle decline and traffic-related exposure on children’s lung function. Environ Health 

Perspect 114:282-288. 

Lung function measures in 2574 children, 5-7 years of age, living at least 2 years at their 

residence, with measurements of TSP and SO2 in 1991, 1994, 1997 and 2000; also < or 

> 50 m from busy street. Lung function improved with decreasing TSP; traffic-related 

exposure was linked with decreased lung function; for children living close to busy roads, 

the beneficial changes in lung function associated with reduced TSP were smaller 

Tamura K, Jinsart W, Yano E, Karita K, Boudoung D. (2003) Particulate air pollution and 

chronic respiratory symptoms among traffic policemen in Bangkok. Arch Environ Health 

58:201-207. 

Venn A., Yemaneberhan H., Lewis S., Parry E., Britton J. 2005. Proximity of the home to roads 

and the risk of wheeze in an Ethiopian population. Occupational and Environmental Medicine. 

62:376-380. 

Volpino P, Tomei F, La Valle C, Tomao E, Rosati MV, Ciarrocca M, De Sio S, Cangemi B, 

Vigliarolo R, Fedele F. (2004) Respiratory and cardiovascular function at rest and during 

exercise testing in a healthy working population: effects of outdoor traffic air pollution. 

Occup Med (Lond.) 54:475-482. 

Yang CY, Yu ST, Chang CC. (2002) Respiratory symptoms in primary schoolchildren living 

near a freeway in Taiwan. J Toxicol Environ Health A 65(10):747-55. 
 B-14

Zmirou D, Gauvin S, Pin I, Momas I, Sahraoui F, Just J, Le Moullec Y, Bremont F, Cassadou S, 

Reungoat P, Albertini M, Lauvergne N, Chiron M, Labbe A. (2004) Traffic related air pollution 

and incidence of childhood asthma: results of the Vesta case-control study. J Epidemiol 

Community Health 58(1):18-23. 

Cancer: 

Cordier S, Monfort C, Filippini G, Preston-Martin S, Lubin F, Mueller BA, Holly EA, PerisBonet R, McCredie M, Choi W, Little J, Arslan A. (2004) Parental exposure to polycyclic 

aromatic hydrocarbons and the risk of childhood brain tumors. Am J Epidemiol. 159:1109-1116. 

Crosignani P, Tittarelli A, Borgini A, Codazzi T, Rovelli A, Porro E, Contiero P, Bianchi N, 

Tagliablue G, Fissi R, Rossitto F, Berrino F. (2004) Childhood leukemia and road traffic: 

A population-based case-control study. Int J Cancer 108(4):596-599. 

Feychting M, Svensson D, Ahlbom A. (1998) Exposure to motor vehicle exhaust and childhood 

cancer. Scand. J. Work Environ. Health 24: 8-11. 

Ippen M, Fehr R, Krasemann EO. (1989) Cancer in residents of heavy traffic areas. 

Versicherungsmedizin 41(2):39-42. 

Knox EG. (2005) Childhood cancers and atmospheric carcinogens. J Epidemiol Community 

Heath 59:101-105. 

Knox EG. (2005) Oil combustion and childhood cancers. J Epidemiol Community Health 

59:755-560. 

Langholz B, Ebi KL, Thomas DC, et al. (2002) Traffic density and the risk of childhood 

leukemia in a Los Angeles case-control study. Ann Epidemiol 12(7):482-7. 

Mannes T, Jalaludin B, Morgan G, Lincoln D, Sheppeard V, Corbett S (2005) Impact of ambient 

air pollution on birth weight in Sydney, Australia. Occup Environ Med 62:524-530. 

Nafstad P, Haheim LL, et al. (2003) Lung cancer and air pollution: a 27 year follow up of 

16,209 Norwegian men. Thorax 58(12):1071-1076. 

Perera FP, Tang D, Tu Y-H, Cruz LA, Borjas M, Bernert T, Whyatt RM. (2004) Biomarkers in 

maternal and newborn blood indicate heightened fetal susceptibility to procarcinogenic DNA 

damage. Environ Health Perspect. 112(10):1133-1136. 

Reynolds P, von Behren J, Gunier RB, Goldberg DE, Hertz A, Smith D. (2002) Traffic patterns 

and childhood cancer incidence rates in California, United States. Cancer Causes and Control 

13:665-673. 

Reynolds P, von Behren J, Gunier RB, Goldberg DE, Hertz A. (2004) Residential exposure to 

traffic in California and childhood cancer. Epidemiol 15(1):6-12. 
 B-15

Steffen C, Auclere MF, Auvrignon A, Baruchel A, Kebaili K, Lambilliotte A, Leverger G, 

Sommelet D, Vilmer E, Hemon D, Clavel J. (2004) Acute childhood leukaemia and 

environmental exposure to potential sources of benzene and other hydrocarbons; a case-control 

study. Occup Environ Med 61(9):773-778. 

Vincents PS, Moller P, Sorensen M, Knudsen LE, Herte LQ, Jensen FP, Schibye B, Loft S. 

(2005) Personal exposure to ultrafine particles and oxidative DNA damage. Environ Health 

Perspect 113:1485-1490. 

Other morbidity:

Brauer M. Gehring U, Brunekreef B, de Jongste J, Gerritsen J, Rovers M, Wichmann H-E, 

Wijga A, Heinrich J. (2006) Traffic-related air pollution and otitis media. Environ Health 

Perspec 114: (in press) 

De Rosa M, Zarrilli S, Paesano L, Carbone U, Boggia B, Petretta M, Maisto A, Cimmino F, 

Puca G, Coalo A, Lombardi G. (2003) Traffic pollutants affect fertility in men. Human Reprod 

18(5):1055-1061. 

Gunier RB, Hertz A, von Behren J, Reynolds P. (2003) Traffic density in California: 

socioeconomic and ethnic differences among potentially exposed children. J Exposure Anal 

Environ Epidemiol 13:240-246 

O’Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz 

J. (2005) Diabetes enhances vulnerability to particulate air pollution-associated impairment in 

vascular reactivity and endothelial function. Circulation 111:2913-2920. 

Parker JD, Woodruff TJ, Basu R, Schoendorf KC. (2005) Air pollution and birth weight among 

term infants in California. Pediatrics 115:121-128. 

Pedersen CB, Raaschou-Nielsen O, Hertel O, Mortensen PB. (2004) New directions: air 

pollution from traffic and schizophrenia risk. Atmos Environ 38:3733-3734. 

Peters A, von Klot S, Heier M, Trentinaglia I, Hormann A, Wichmann E, Lowel H (2004) 

Exposure to traffic and the onset of myocardial infarction. The New England J of Med 

351:1721-

1730. 

Rich DQ, Mittleman MA, Link MS, Schwartz J, Luttmann-Gibson H, Catalano PJ, Speizer FE, 

Gold DR, Dockery DW. (2006) Increased risk of paroxysmal atrial fibrillation episodes 

associated with acute increases in ambient air pollution. Environ Health Perspect 114:120-123. 

Riediker M, Cascio WE, Griggs TR, Herbst MC, Bromber PA, Neas L, Williams R, Devlin RB. 

(2004) Particulate matter exposure in cars is associated with cardiovascular effects in healthy, 

young men. Am J Respir Crit Care Med 169:934-940. 

Riediker M, Devlin RB, Griggs TR, Herbst MC, Bromberg PA, Williams RW, Cascio WE. 

(2004) Cardiovascular effect in patrol officers are associated with fine particulate matter from 

brake wear and engine emissions. Particle Fiber Toxicol 1:2-11. 
 B-16

Riediker M, Devlin RB, Griggs TR, Herbst MC, Bromberg PA, Williams RW, Cascio WE. 

(2004) Health effects in highway patrol troopers are associated to traffic source of particulate 

matter. In Press. 

Santos U de Paula, Braga ALF, Giorgi DMA, Pereira LAA, Grupi CJ, Lin CA, Bussacos MA, 

Zanetta DMT, Saldiva PHdN, Filho MT. (2005) Effects of air pollution on blood pressure and 

heart rate variability: a panel study of vehicular traffic controllers in the city of Sao Paulo, Brazil. 

European Heart Journal 26:193-200. 

Schwartz J, Litonjua L, Suh H, Verrier M, Zanobetti A, Syring M, Nearing B, Verrier R, 

Stone P, MacCallum G, Speizer FE, Gold DR (2005) Traffic related pollution and heart rate 

variability in a panel of elderly subjects. Thorax 60:455-461. 

Sharman JE, Cockcroft JR, Coombes JS. (2004) Cardiovascular implications of exposure to 

traffic air pollution during exercise. Q J M 97:637-643. 

Tomai F, Ciarrocca M, Rosati MV, Baccolo TP, Grimaldi F, Tomao E. (2004) Exposure to urban 

pollutants and plasma vasopressin in traffic policement. Ind Health (Japan) 42:246-251. 

Wang X, King H, Ryan L, Xu X (1997) Association between air pollution and low birth weight: 

a community-based study. Environ Health Perspect 105:514-520. 

Wilhelm M, Ritz B. (2003) Residential proximity to traffic and adverse birth outcomes in 

Los Angeles County, California, 1994-1996. Env Health Perspect 111:207-216. 

Yamazaki S, Sokejima S, Nitta H, Nakayama T, Fukuhara S. (2005) Living close to automobile 

traffic and quality of life in Japan: A population-based survey. International Journal of 

Environmental Health Research 15(1):1-9. 
 B-17

Toxicology Studies of Traffic, Diesel, or Vehicle Exhaust

Arimoto, T.; Kadiiska, M. B.; Sato, K.; Corbett, J.; Mason, R. P. (2005) Synergistic production 

of lung free radicals by diesel exhaust particles and endotoxin. Am. J. Respir. Crit. Care 

Med. 171: 379-387. 

Aust, A. E.; Ball, J. C.; Hu, A. A.; Lighty, J. S.; Smith, K. R.; Straccia, A. M.; Veranth, J. M.; 

Young, W. C. (2002) Particle characteristics responsible for effects on human lung 

epithelial cells. Boston, MA: Health Effects Institute; HEI research report no. 110. 

Available at: http://www.healtheffects.org/ (28 January 2003). 

Bayram H, Ito K, Issa R, Ito M, Sukkar M, Chung KF. (2006) Regulation of human lung 

epithelial cell numbers by diesel exhaust particles. Eur. Respir. J. 27: 705-713. 

Becker, S.; Mundandhara, S.; Devlin, R. B.; Madden, M. (2005) Regulation of cytokine 

production in human alveolar macrophages and airway epithelial cells in response to 

ambient air pollution particles: further mechanistic studies. Toxicol. Appl. Pharmacol. 

207(2 Suppl): 269-275. 

Becker, S.; Soukup, J. (2003) Coarse (PM2.5-10), fine (PM2.5), and ultrafine air pollution 

particles induce-increase immune costimulatory receptors on human blood-derived 

monocytes but not on alveolar macrophages. J. Toxicol. Environ. Health Part A 

66: 847-859. 

Becker, S.; Soukup, J. M.; Sioutas, C.; Cassee, F. R. (2003) Response of human alveolar 

macrophages to ultrafine, fine and coarse urban air pollution particles. Exp. Lung Res. 

29: 29-44. 

Becker, S.; Soukup, J. M.; Gallagher, J. E. (2002) Differential particulate air pollution induced 

oxidant stress in human granulocytes, monocytes and alveolar macrophages. Toxicol. in 

Vitro 16: 209-218. 

Behndig, A. F.; Mudway, I. S.; Brown, J. L.; Stenfors, N., Helleday, R., Duggan, S. T.; Wilson, 

S. J.; Boman, C., Cassee, F. R.; Frew, A. J.; Kelly, F. J.; Sandstrom, T., Blomberg, A. 

(2006) Airway antioxidant and inflammatory responses to diesel exhaust exposure in 

healthy humans. Eur. Respir. J. 27: 359-365. 

 

Blanchet, S.; Ramgolam, K.; Baulig, A.; Marano, F.; Baeza-Squiban, A. (2004) Fine particulate 

matter induces amphiregulin secretion by bronchial epithelial cells. Am. J. Respir. Cell 

Mol. Biol. 230: 421-427. 

 

Block, M. L.; Wu, X.; Pei, Z.; Li, G.; Wang, T.; Qin, L.; Wilson, B.; Yang, J.; Hong, J. S.; 

Veronesi, B. (2004) Nanometer size diesel exhaust particles are selectively toxic to 

dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase. 

FASEB J. 18: 1618-1620. 
 B-18

Campen, M. J.; Babu, N. S.; Helms, G. A.; Pett, S.; Wernly, J.; Mehran, R.; McDonald, J. D. 

(2005) Nonparticulate components of diesel exhaust promote constriction in coronary 

arteries from ApoE -/- mice. Toxicol. Sci. 88: 95-102. 

Carvalho-Oliveira, R.; Pozo, R. M. K.; Lobo, D. J. A.; Lichtenfels, A. J. F. C.; Martins-Junior, 

H. A.; Bustilho, J. O. W. V.; Saiki, M.; Sato, I. M.; Saldiva, P. H. N. (2005) Diesel 

emissions significantly influence composition and mutagenicity of ambient particles: 

a case study in Sao Paulo, Brazil. Environ. Res. 98: 1-7. 

Dagher Z, Garcon G, Gosset P, Ledoux F, Surpateanu G, Courcot D, Aboukais A, Puskaric E, 

Shirali P. (2005) Pro-inflammatory effects of Dunkerque city air pollution particulate 

matter 2.5 in human epithelial lung cells (L132) in culture. J Appl Toxicol. 2005 MarApr;25(2):166-75. 

Dai, H.; Song, W.; Gao, X.; Chen, L. (2004) [Study on relationship between ambient PM10, 

PM2.5 pollution and daily mortality in a district in Shanghai]. J. Hyg. Res. 33: 293-297. 

De Kok, T. M.; Hogervorst, J. G.; Briede, J. J.; van Herwijnen, M. H.; Maas, L. M.; Moonen, 

E. J.; Driece, H. A.; Kleinjans, J. C. (2005) Genotoxicity and physicochemical 

characteristics of traffic-related ambient particulate matter. Environ. Mol. 

Mutagen.46: 71-80. 

DeMarini, D. M.; Brooks, L. R.; Warren, S. H.; Kobayashi, T.; Gilmour, M. I.; Singh, P. (2004) 

Bioassay-directed fractionation and Salmonella mutagenicity of automobile and forklift 

diesel exhaust particles. Environ. Health Perspect. 112: 814-819. 

Dong, C. C.; Yin, X. J.; Ma, J. Y. C.; Millecchia, L.; Wu, Z.-X.; Barger, M. W.; Roberts, J. R.; 

Antonini, J. M.; Dey, R. D.; Ma, J. K. H. (2005) Effect of diesel exhaust particles on 

allergic reactions and airway responsiveness in ovalbumin-sensitized Brown Norway 

Rats. Toxicol. Sci. 88: 202-212. 

Elder, A.; Gelein, R.; Finkelstein, J.; Phipps, R.; Frampton, M.; Utell, M.; Kittelson, D. B.; 

Watts, W. F.; Hopke, P.; Jeong, C. H.; Kim, E.; Liu, W.; Zhao, W.; Zhuo, L.; 

Vincent, R.; Kumarathasan, P.; Oberdorster, G. (2004) On-road exposure to highway 

aerosols. 2. Exposures of aged, compromised rats. Inhalation Toxicol. 

16(suppl. 1): 41-53. 

Farraj, A. K.; Haykal-Coates, N.; Ledbetter, A. D.; Evansky, P. A.; Gavett, S. H. (2006) 

Inhibition of pan neurotrophin receptor p75 attenuates diesel particulate-induced 

enhancement of allergic airway responses in C57/B16J mice. Inhal. Toxicol. 18: 483-491. 

Gong, H., Jr.; Linnx, W. S.; Terrell, S. L.; Clark, K. W.; Geller, M. D.; Anderson, K. R.; Cascio, 

W. E.; Sioutas, C. (2004) Altered heart-rate variability in asthmatic and healthy 

volunteers exposed to concentrated ambient coarse particles. Inhalation Toxicol. 

16: 335-343. 
 B-19

Hiramatsu, K.; Saito, Y.; Sakakibara, K.; Azuma, A.; Takizawa, H.; Sugawara, I. (2005) The 

effects of inhalation of diesel exhaust on murine mycobacterial infection. Exp. Lung Res. 

31: 405-415. 

Holgate, S. T.; Sandstrom, T.; Frew, A. J.; Stenfors, N.; Nordenhall, C.; Salvi, S.; Blomberg, A.; 

Helleday, R.; Soderberg, M. (2003) Health effects of acute exposure to air pollution. Part 

I: healthy and asthmatic subjects exposed to diesel exhaust. Boston, MA: Health Effects 

Institute; research report no. 112. Available: 

http://www.healtheffects.org/Pubs/Holgate.pdf. 

Huang, S. L.; Hsu, M. K.; Chan, C. C. (2003) Effects of submicrometer particle compositions on 

cytokine production and lipid peroxidation of human bronchial epithelial cells. Environ. 

Health Perspect. 111: 478-482. 

Inoue, K.; Takano, H.; Yanagisawa, R.; Ichinose, T.; Sadakane, K.; Yoshino, S.; Yamaki, K.; 

Uchiyama, K.; Yoshikawa, T. (2004) Components of diesel exhaust particles 

differentially affect lung expression of cyclooxygenase-2 related to bacterial endotoxin J. 

Appl. Toxicol. 24: 415-418. 

Jaspers, I.; Ciencewicki, J. M.; Zhang, W.; Brighton, L. E.; Carson, J. L.; Beck, M. A.; Madden, 

M. C. (2005) Diesel exhaust enhances influenza virus infections in respiratory epithelial 

cells. Toxicol. Sci. 85: 990-1002. 

Jalava, P.; Salonen, R. O.; Halinen, A. I.; Sillanpaa, M.; Sandell, E.; Hirvonen, M. R. (2005) 

Effects of sample preparation on chemistry, cytotoxicity, and inflammatory responses 

induced by air particulate matter. Inhal. Toxicol. 17: 107-117. 

Karlsson, H. L.; Nilsson, L.; Moller, L. (2005) Subway particles are more genotoxic than street 

particles and induce oxidative stress in cultured human lung cells. Chem. Res. Toxicol. 

18: 19-23. 

Kleinman MT, Sioutas C, Chang MC, Boere AJ, Cassee FR. (2003) Ambient fine and coarse 

particle suppression of alveolar macrophage functions. Toxicol Lett. 2003 Feb 

3;137(3):151-8. 

 

Kleinman, M.; Sioutas, C.; Stram, D.; Froines, J.; Cho, A.; Chakrabarti, B.; Hamade, A.; 

Meacher, D.; Oldham, M. (2005) Inhalation of concentrated ambient particulate matter 

near a heavily trafficked road stimulates antigen-induced airway responses in mice. J. 

Air. Waste Manag. Assoc. 55: 1277-1288. 

Koike, E.; Hirano, S.; Furuyama, A.; Kobayashi, T. (2004) cDNA microarray analysis of rat 

alveolar epithelial cells following exposure to organic extract of diesel exhaust particles. 

Toxicol. Appl. Pharmacol. 201: 178-185. 
 B-20

Koike, E.; Kobayashi, T. (2005) Organic extract of diesel exhaust particles stimulates expression 

of Ia and costimulatory molecules associated with antigen presentation in rat peripheral 

blood monocytes but not in alveolar macrophages. Toxicol. Appl. Pharmacol. 

209: 277-285. 

Kristovich, R.; Knight, D. A.; Long, J. F.; Williams, M. V.; Dutta, P. K.; Waldman, W. J. (2004) 

Macrophage-mediated endothelial inflammatory responses to airborne particulates: 

impact of particulate physicochemical properties. Chem. Res. Toxicol. 17: 1303-1312. 

Kubatova, A.; Steckler, T. S.; Gallagher, J. R.; Hawthorne, S. B.; Picklo, M. J. Sr. (2004) 

Toxicity of wide-range polarity fractions from wood smoke and diesel exhaust particulate 

obtained using hot pressurized water. Environ. Toxicol. Chem. 23: 2243-2250. 

Lei, Y.C.; Chen, M. C.; Chan, C. C.; Wang, P. Y.; Lee, C. T.; Cheng, T. J. (2004) Effects of 

concentrated ambient particles on airway responsiveness and pulmonary inflammation in 

pulmonary hypertensive rats. Inhal. Toxicol. 16: 785-792. 

Li, N.; Hao, M.; Phalen, R. F.; Hinds, W. C.; Nel, A. E. (2003) Particulate air pollutants and 

asthma. A paradigm for the role of oxidative stress in PM-induced adverse health effects. 

Clin. Immunol. 109: 250-265. 

Li, N.; Kim, S.; Wang, M.; Froines, J. R.; Sioutas, C.; Nel, A. (2002) Use of a stratified oxidative 

stress model to study the biological effects of ambient concentrated and diesel exhaust 

particulate matter. Inhalation Toxicol. 14: 459-486. 

Li, N.; Wang, M.; Oberley, T. D.; Sempf, J. M.; Nel, A. E. (2002) Comparison of the prooxidative and proinflammatory effects of organic diesel exhaust particle chemicals in 

bronchial epithelial cells and macrophages. J. Immunol. 169: 4531-4541. 

Lippmann, M.; Hwang, J.; Maclejczyk, P.; Chen, L. (2005) PM source apportionment for 

short-term cardiac function changes in ApoE-/-mice. Environ. Health Perspect. 

113: 1575-1579. 

Ma, C.; Wang, J.; Luo, J. (2004) Activation of nuclear factor kappa B by diesel exhaust particles 

in mouse epidermal cells through phosphatidylinositol 3-kinase/Akt signaling pathway. 

Biochem. Pharmacol. 67: 1975-1983. 

McDonald, J. D.; Harrod, K. S.; Seagrave, J.; Seikop, S. K.; Mauderly, J. L. (2004) Effects of 

low sulfur fuel composition and a catalyzed particle trap on the composition and toxicity 

of diesel emissions. Environ. Health Perspect. 112: 1307-1312. 

McDonald, J. D.; Eide, I.; Seagrave, J.; Zielinska, B.; Whitney, K.; Lawson, D. R.; Mauderly, 

J. L. (2004) Relationship between composition and toxicity of motor vehicle emission 

samples. Environ. Health Perspect. 112: 1527-1538. 
 B-21

Mills, N. L.; Tornqvist, H.; Robinson, S. D.; Gonzalez, M.; Darnley, K.; MacNee, W.; Boon, 

N. A.; Donaldson, K.; Blomberg, A.; Sandstrom, T.; Newby, D. E. (2005) Diesel exhaust 

inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 

112: 3930-3936. 

Moreno, T.; Merolla, L.; Gibbons, W.; Greenwell, L.; Jones, T.; Richards, R. (2004) Variations 

in the source, metal content and bioreactivity of technogenic aerosols: a case study from 

Port Talbot, Wales, UK Sci. Tot. Environ. 333: 59-73. 

Nemmar, A.; Hoet, P. H.; Vermylen, J.; Nemery, B.; Hoylaerts, M. F. (2004) Pharmacological 

stabilization of mast cells abrogates late thrombotic events induced by diesel exhaust 

particles in hamsters. Circulation 110: 1670-1677. 

Nemmar, A.; Hoylaerts, M. F.; Hoet, P. H. M.; Nemery B. (2004) Possible mechanisms of the 

cardiovascular effects of inhaled particles: systemic translocation and prothrombotic 

effects. Toxicol. Lett. 149: 243-253. 

Nygaard, U. C.; Alberg, T.; Bleumink, R.; Aase, A.; Dybing, E.; Pieters, R.; Lovik, M. (2005) 

Ambient air particles from four European cities increase the primary cellular response to 

allergen in the draining lymph node. Toxicology. 207: 241-254. 

Nygaard, U. C.; Samuelsen, M.; Aase, A.; Lovik, M. (2004) The capacity of particles to increase 

allergic sensitization is predicted by particle number and surface area, not by particle 

mass. Toxicol. Sci. 82: 515-524. 

 

Nygaard, U. C.; Ormstad, H.; Aase, A.; Lovik, M. (2005) The IgE adjuvant effect of particles: 

characterisation of the primary cellular response in the draining lymph node. 

Toxicology.206: 181-193. 

Oh, S. M.; Chung, K. H. (2006) Identification of mammalian cell genotoxins in respirable diesel 

exhaust particles by bioassay-directed chemical analysis. Toxicol. Lett. 161: 226-235. 

Pan, C.-J. G.; Schmitz, D. A.; Cho, A. K.; Froines, J.; Fukuto, J. M. (2004) Inherent redox 

properties of diesel exhaust particles: catalysis of the generation of reactive oxygen 

species by biological reductants. Toxicol. Sci. 81: 225-232. 

Pourazar, J.; Mudway, I. S.; Samet, J. M.; Helleday, R.; Blomberg, A.; Wilson, S. J.; Frew, A. J.; 

Kelly, F. J.; Sandstrom, T. (2005) Diesel exhaust activates redox-sensitive transcription 

factors and kinases in human airways. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: 

L724-L730. 

Rao, K. M.; Ma, J. Y.; Meighan, T.; Barger, M. W.; Pack, D.; Vallyathan, V. (2005) Time course 

of gene expression of inflammatory mediators in rat lung after diesel exhaust particle 

exposure. Environ. Health Perspect. 113: 612-617. 

 
 B-22

Riediker, M.; Williams, R.; Devlin, R.; Griggs, T.; Bromberg, P. (2003) Exposure to particulate 

matter, volatile organic compounds, and other air pollutants inside patrol cars. Environ. 

Sci. Technol. 37: 2084-2093. 

 

Riediker, M.; Cascio, W. E.; Griggs, T. R.; Herbst, M. C.; Bromberg, P. A.; Neas, L.; 

Williams, R. W.; Devlin, R. B. (2004) Particulate matter exposure in cars is associated 

with cardiovascular effects in healthy young men. Am. J. Respir. Crit. Care Med. 

169: 934-940. 

Saber, A. T.; Jacobsen, N. R.; Bornholdt, J.; Kjaer, S. L.; Dybdahl, M.; Risom, L.; Loft, S.; 

Vogel, U.; Wallin, H. (2006) Cytokine expression in mice exposed to diesel exhaust 

particles by inhalation. Role of tumor necrosis factor. Part. Fibre. Toxicol. 3: 4. 

 

Sandstrom, T.; Cassee, F. R.; Salonen, R.; Dybing, E. (2005) Recent outcomes in European 

multicentre projects on ambient particulate air pollution. Toxicol. Appl. Pharmacol. 

207: 261-268. 

Seagrave, J.; Knall, C.; McDonald, J. D.; Mauderly, J. L. (2004) Diesel particulate material binds 

and concentrates a proinflammatory cytokine that causes neutrophil migration. Inhalation 

Toxicol. 16(suppl. 1): 93-98. 

Seagrave, J.; Mauderly, J. L.; Seilkop, S. K. (2003) In vitro relative toxicity screening of 

combined particulate and semivolatile organic fractions of gasoline and diesel engine 

emissions. J. Toxicol. Environ. Health A 66: 1113-1132. 

Seagrave, J. C.; Gigliotti, A.; McDonald, J. D.; Seilkop, S. K.; Whitney, K. A.; Zielinska, B.; 

Mauderly, J. L. (2005) Composition, toxicity, and mutagenicity of particulate and 

semivolatile emissions from heavy-duty compressed natural gas-powered vehicles. 

Toxicol. Sci. 87: 232-241. 

 

Seagrave, J.; McDonald, J. D.; Reed, M. D.; Seilkop, S. K.; Mauderly, J. L. (2005) Responses to 

subchronic inhalation of low concentrations of diesel exhaust and hardwood smoke 

measured in rat bronchoalveolar lavage fluid. Inhalation Toxicol. 17: 657-670. 

Sheesley, R. J.; Schauer, J. J.; Hemming, J. D.; Geis, S.; Barman, M. A. (2005) Seasonal and 

spatial relationship of chemistry and toxicity in atmospheric particulate matter using 

aquatic bioassays. Environ. Sci. Technol. 39: 999-1010. 

 

Shima, H.; Koike, E.; Shinohara, R.; Kobayashi, T. (2006) Oxidative ability and toxicity of 

n-hexane insoluble fraction of diesel exhaust particles. Toxicol. Sci. 91: 218-226. 

Shimada, H.; Oginuma, M.; Hara, A.; Imamura, Y. (2004) 9,10-phenanthrenequinone, a 

component of diesel exhaust particles, inhibits the reduction of 4-benzoylpyridine and alltrans-retinal and mediates superoxide formation through its redox cycling in pig heart. 

Chem. Res. Toxicol. 17: 1145-1150. 

 
 B-23

Singh, P.; DeMarini, D. M.; Dick, C. A.; Tabor, D. G.; Ryan, J. V.; Linak, W. P.; Kobayashi, T.; 

Gilmour, M. I. (2004) Sample characterization of automobile and forklift diesel exhaust 

particles and comparative pulmonary toxicity in mice. Environ. Health Perspect. 112: 

820-825. 

Singh, P.; Madden, M.; Gilmour, M. I. (2005) Effect of diesel exhaust particles and carbon black 

on induction of dust mite allergy in Brown Norway rats. J. Immunotoxicol. 2: 41-49. 

Steerenberg, P.; Verlaan, A.; De Klerk, A.; Boere, A.; Loveren, H.; Cassee, F. (2004) Sensitivity 

to ozone, diesel exhaust particles, and standardized ambient particulate matter in rats with 

a listeria monocytogenes-induced respiratory infection. Inhalation Toxicol. 16: 311-317. 

 

Stinn, W.; Teredesai, A.; Anskeit, E.; Rustemeier, K.; Schepers, G.; Schnell, P.; Haussmann, 

H. J.; Carchman, R. A.; Coggins, C. R.; Reininghaus, W. (2005) Chronic nose-only 

inhalation study in rats, comparing room-aged sidestream cigarette smoke and diesel 

engine exhaust. Inhal. Toxicol. 17: 549-576. 

 

Sureshkumar, V.; Paul, B.; Uthirappan, M.; Pandey, R.; Sahu, A. P.; Lal, K.; Prasad, A. K.; 

Srivastava, S.; Saxena, A.; Mathur, N.; Gupta, Y. K. (2005) Proinflammatory and antiinflammatory cytokine balance in gasoline exhaust induced pulmonary injury in mice. 

Inhalation Toxicol. 17: 161-168. 

Takano, H.; Yanagisaw, R.; Ichinose, T.; Sadakane, K.; Yoshino, S.; Yoshikawa, T.; Morita, M. 

(2002) Diesel exhaust particles enhance lung injury related to bacterial endotoxin through 

expression of proinflammatory cytokines, chemokines, and intercellular adhesion 

molecule-I. Am. J. Respir. Crit. Care Med. 165: 1329-1335. 

 

Takeda, K.; Tsukue, N.; Yoshida, S. (2004) Endocrine-disrupting activity of chemicals in diesel 

exhaust and diesel exhaust particles. Environ. Sci. (Japan) 11: 33-45. 

 

Takizawa, H. (2004) Diesel exhaust particles and their effect on induced cytokine expression in 

human bronchial epithelial cells. Curr. Opin. Allergy Clin. Immunol. 4: 355-359. 

Taneda, S.; Mori, Y.; Kamata, K.; Hayashi, H.; Furuta, C.; Li, C.; Seki, K.-I.; Sakushima, A.; 

Yoshino, S.; Yamaki, K.; Watanabe, G.; Taya, K.; Suzuki, A. K. (2004) Estrogenic and 

anti-androgenic activity of nitrophenols in diesel exhaust particles (DEP). Biol. Pharm. 

Bull. (Japan) 27: 835-837. 

Urch, B.; Silverman, F.; Corey, P.; Brook, J. R.; Lukic, K. Z.; Rajagopalan, S.; Brook, R. D. 

(2005) Acute blood pressure responses in healthy adults during controlled air pollution 

exposures. Environ. Health Perspect. 113: 1052-1055. 

Veranth, J. M.; Reilly, C. A.; Veranth, M. M.; Moss, T. A.; Langelier, C. R.; Lanza, D. L.; Yost, 

G. S. (2004) Inflammatory cytokines and cell death in BEAS-2B lung cells treated with 

soil dust, lipopolysaccharide, and surface-modified particles. Toxicol. Sci. 82: 88-96. 
 B-24

Vinzents, P. S.; Moller, P.; Sorensen, M.; Knudsen, L. E.; Herte, L. Q.; Jensen, F. P.; Schibye, 

B.; Loft, S. (2005) Personal exposure to ultrafine particles and oxidative DNA damage. 

Environ. Health Perspect. 113: 1485-1490. 

Vogel, C. F. A.; Sciullo, E.; Wong, P.; Kuzmicky, P.; Kado, N.; Matsumura, F. (2005) Induction 

of proinflammatory cytokines and C-reactive protein in human macrophage cell line 

U937 exposed to air pollution particulates. Environ. Health Perspect. 113: 1536-1541. 

 

Watanabe, N. (2005) Decreased number of sperms and Sertoli cells in mature rats exposed to 

diesel exhaust as fetuses. Toxicol. Lett. 155: 51-58. 

 

Witten, M. L.; Wong, S. S .; Sun, N. N.; Keith, I.; Kweon, C.; Foster, D. E.; Schauer, J. J.; 

Sherrill, D. L. (2005) Neurogenic responses in rat lungs after nose-only exposure to 

diesel exhaust. Boston, MA: Health Effects Institute; research report no. 128. Available: 

http://www.healtheffects.org/Pubs/Witten.pdf [9 January, 2006]. 

 

Xia, T.; Korge, P.; Weiss, J. N.; Li, N.; Venkatesen, M. I.; Sioutas, C.; Nel, A. (2004) Quinones 

and aromatic chemical compounds in particulate matter induce mitochondrial 

dysfunction: implications for ultrafine particle toxicity. Environ. Health Perspect. 

112: 1347-1358. 

Yanagisawa, R.; Takano, H.; Inoue, K.; Ichinose, T.; Sadakane, K.; Yoshino, S.; Yamaki, K.; 

Kumagai, Y.; Uchiyama, K.; Yoshikawa, T.; Morita, M. (2003) Enhancement of acute 

lung injury related to bacterial endotoxin by components of diesel exhaust particles. 

Thorax 58: 605-612. 

 

Yin, X. J.; Dong, C. C.; Ma, J. Y. C.; Antonini, J. M.; Roberts, J. R.; Barger, M. W.; Ma, J. K. H. 

(2005) Sustained effect of inhaled diesel exhaust particles on T-lymphocyte-mediated 

immune responses against Listeria monocytogenes. Toxicol. Sci. 88: 73-81. 

 

Yin, X. J.; Ma, J. Y. C.; Antonini, J. M.; Castranova, V.; Ma, J. K. H. (2004) Roles of reactive 

oxygen species and heme oxygenase-1 in modulation of alveolar macrophage-mediated 

pulmonary immune responses to listeria monocytogenes by diesel exhaust particles. 

Toxicol. Sci. 82: 143-153. 

 

Yun, Y. P.; Joo, J. D.; Lee, J. Y.; Nam, H. Y.; Kim, Y. H.; Lee, K. H.; Lim, C. S.; Kim, H. J.; 

Lim, Y. G.; Lim, Y. (2005) Induction of nuclear factor-kappaB activation through TAK1 

and NIK by diesel exhaust particles in L2 cell lines. Toxicol. Lett. 155: 337-342.
 B-25

Toxicology and Epidemiology Studies of Ultrafine Particles 

Asgharian, B.; Price, O.; Oberdorster, G. (2006) A modeling study of the effect of gravity on 

airflow distribution and particle deposition in the lung. Inhal. Toxicol. 18: 473-481. 

 

Avogbe, P. H.; Ayi-Fanou, L.; Autrup, H.; Loft, S.; Fayomi, B.; Sanni, A.; Vinzents, P.; 

Moller, P. (2005) Ultrafine particulate matter and high-level benzene urban air pollution 

in relation to oxidative DNA damage. Carcinogenesis 26: 613-620. 

Becker, S.; Dailey, L. A.; Soukup, J. M.; Grambow, S. C.; Devlin, R. B.; Huang, Y. C. (2005) 

Seasonal variations in air pollution particle-induced inflammatory mediator release and 

oxidative stress. Environ. Health Perspect. 113: 1032-1038. 

Becker, S.; Mundandhara, S.; Devlin, R. B.; Madden, M. (2005) Regulation of cytokine 

production in human alveolar macrophages and airway epithelial cells in response to 

ambient air pollution particles: further mechanistic studies. Toxicol. Appl. Pharmacol. 

207(2 Suppl): 269-275. 

Becker, S.; Soukup, J. (2003) Coarse (PM2.5-10), fine (PM2.5), and ultrafine air pollution 

particles induce-increase immune costimulatory receptors on human blood-derived 

monocytes but not on alveolar macrophages. J. Toxicol. Environ. Health Part A 

66: 847-859 

Becker, S.; Soukup, J. M.; Sioutas, C.; Cassee, F. R. (2003) Response of human alveolar 

macrophages to ultrafine, fine and coarse urban air pollution particles. Exp. Lung Res. 

29: 29-44. 

Campbell, A.; Oldham, M.; Becaria, A.; Bondy, S. C.; Meacher, D.; Sioutas, C.; Misra, C.; 

Mendez, L. B.; Kleinman, M. (2005) Particulate matter in polluted air may increase 

biomarkers of inflammation in mouse brain. Neurotoxicology 26: 133-140. 

Cho, A. K.; Sioutas, C.; Miguel, A. H.; Kumagai, Y.; Schmitz, D. A.; Singh, M.; EigurenFernandez, A.; Froines, J. R. (2005) Redox activity of airborne particulate matter at 

different sites in the Los Angeles Basin. Environ. Res. 99: 40-47. 

Churg, A.; Brauer, M.; del Carmen Avila-Casado, M.; Fortoul, T. I.; Wright, J. L. (2003) 

Chronic exposure to high levels of particulate air pollution and small airway remodeling. 

Environ. Health Perspect. 111: 714-718. 

Cozzi, E.; Hazarika, S.; Stallings I.H.W.; Cascio, W.E.; Devlin, R.B.; Lust, R.M.; Windard C.J.; 

Van Scott, M. R. (2006) Ultrafine Particulate Matter Exposure Augments Ischemia 

Reperfusion in Mice. Am. J. Physiol Heart Circ. Physiol. (in press). 
 B-26

De Hartog, J. J.; Hoek, G.; Peters, A.; Timonen, K. L.; Ibald-Mulli, A.; Brunekreef, B.; 

Heinrich, J.; Tiittanen, P.; Van Wijnen, J. H.; Kreyling, W.; Kulmala, M.; Pekkanen, J. 

(2003) Effects of fine and ultrafine particles on cardiorespiratory symptoms in elderly 

subjects with coronary heart disease: the ULTRA study. Am. J. Epidemiol. 157: 613-623. 

Delfino, R. J.; Sioutas, C.; Malik, S. (2005) Potential role of ultrafine particles in associations 

between airborne particle mass and cardiovascular health. Environ. Health Perspect. 

113: 934-946. 

Donaldson, K.; Stone, V. (2003) Current hypotheses on the mechanisms of toxicity of ultrafine 

particles. Ann. Ist. Super. Sanita 39: 405-410. 

Elder, A. C. P.; Gelein, R.; Azadniv, M.; Frampton, M.; Finkelstein, J.; Oberdorster, G. (2004) 

Systemic effects of inhaled ultrafine particles in two compromised, aged rat strains. 

Inhalation Toxicol. 16: 461-471. 

Elder, A.; Gelein, R.; Finkelstein, J.; Phipps, R.; Frampton, M.; Utell, M.; Kittelson, D. B.; 

Watts, W. F.; Hopke, P.; Jeong, C. H.; Kim, E.; Liu, W.; Zhao, W.; Zhuo, L.; Vincent, 

R.; Kumarathasan, P.; Oberdorster, G. (2004) On-road exposure to highway aerosols. 2. 

Exposures of aged, compromised rats. Inhalation Toxicol. 16(suppl. 1): 41-53. 

Elder, A. C. P.; Gelein, R.; Finkelstein, J. N.; Cox, C.; Oberdorster, G. (2000) Pulmonary 

inflammatory response to inhaled ultrafine particles is modified by age, ozone exposure, 

and bacterial toxin. In: Grant, L. D., ed. PM2000: particulate matter and health. 

Inhalation Toxicol. 12(suppl. 4): 227-246. 

Fiedler, N.; Laumbach, R.; Kelly-McNeil, K.; Lioy, P.; Fan, Z.-H.; Zhang, J.; Ottenweller, J.; 

Ohman-Strickland, P.; Kipen, H. (2005) Health effects of a mixture of indoor air volatile 

organics, their ozone oxidation products, and stress. Environ. Health Perspect. 113: 1542-

1548. 

Forastiere, F.; Stafoggia, M.; Picciotto, S.; Bellander, T.; D'Ippoliti, D.; Lanki, T.; Von Klot, S.; 

Nyberg, F.; Paatero, P.; Peters, A.; Pekkanen, J.; Sunyer, J.; Perucci, C. A. (2005) A casecrossover analysis of out-of-hospital coronary deaths and air pollution in Rome, Italy. 

Am. J. Respir. Crit. Care Med. 172: 1549-1555. 

Frampton, M. W.; Stewart, J. C.; Oberdorster, G.; Morrow, P. E.; Chalupa, D.; Pietropaoli, A. P.; 

Frasier, L. M.; Speers, D. M.; Cox, C.; Huang, L. S.; Utell, M. J. (2006) Inhalation of 

ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. 

Environ. Health Perspect. 114: 51-58. 

Frampton, M. W.; Utell, M. J.; Zareba, W.; Oberdorster, G.; Cox, C.; Huang, L. S.; Morrow, 

P. E.; Lee, F. E.; Chalupa, D.; Frasier, L. M.; Speers, D. M.; Stewart, J. (2004) Effects of 

exposure to ultrafine carbon particles in healthy subjects and subjects with asthma. 

Boston, MA: Health Effects Institute; research report no. 126. Available: 

http://www.healtheffects.org/Pubs/Frampton2004.pdf [20 December, 2005]. 
 B-27

Geiser, M.; Rothen-Rutishauser, B.; Kapp, N.; Schurch, S.; Kreyling, W.; Schulz, H.; Semmler, 

M.; Im Hof, V.; Heyder, J.; Gehr, P. (2005) Ultrafine particles cross cellular membranes 

by nonphagocytic mechanisms in lungs and in cultured cells. Environ. Health Perspect. 

113: 1555-1560. 

Ghio, A. J.; Cohen, M. D. (2005) Disruption of iron homeostasis as a mechanism of biologic 

effect by ambient air pollution particles. Inhal. Toxicol. 17: 709-716. 

Gilmour, M. I.; O'Connor, S.; Dick, C. A. J.; Miller, C. A.; Linak, W. P. (2004) Differential 

pulmonary inflammation and in vitro cytotoxicity of size-fractionated fly ash particles 

from pulverized coal combustion. J. Air Waste Manage. Assoc. 54: 286-295. 

Gilmour, P. S.; Ziesenis, A.; Morrison, E. R.; Vickers, M. A.; Drost, E. M.; Ford, I.; Karg, E.; 

Mossa, C.; Schroeppel, A.; Ferron, G. A.; Heyder, J.; Greaves, M.; MacNee, W.; 

Donaldson, K. (2004) Pulmonary and systemic effects of short-term inhalation exposure 

to ultrafine carbon black particles. Toxicol. Appl. Pharmacol. 195: 35-44. 

Hahn, F. F.; Barr, E. B.; Menache, M. G.; Seagrave, J. (2005) Particle sze and composition 

related to adverse health effects in aged, sensitive rats. Boston, MA: Health Effects 

Institute; research report no. 129. Available: http://www.healtheffects.org/Pubs/Hahn.pdf 

[13 December, 2005]. 

Harder, V.; Gilmour, P.; Lentner, B.; Karg, E.; Takenaka, S.; Ziesenis, A.; Stampfl, A.; 

Kodavanti, U.; Heyder, J.; Schulz, H. (2005) Cardiovascular responses in unrestrained 

WKY rats to inhaled ultrafine carbon particles. Inhalation Toxicol. 17: 29-42. 

Henneberger, A.; Zareba, W.; Ibald-Mulli, A.; Ruckerl, R.; Cyrys, J.; Couderc, J.-P.; Mykins, B.; 

Woelke, G.; Wichmann, H.-E.; Peters, A. (2005) Repolarization changes induced by air 

pollution in ischemic heart disease patients. Environ. Health Perspect. 113: 440-446. 

Hunt, A.; Abraham, J. L.; Judson, B.; Berry, C. L. (2003) Toxicologic and epidemiologic clues 

from the characterization of the 1952 London smog fine particulate matter in archival 

autopsy lung tissues. Environ. Health Perspect. 111: 1209-1214. 

Inoue, K.; Takano, H,; Yanagisawa, R.; Sakurai, M.; Ichinose, T.; Sadakane, K.; Yoshikawa, T. 

(2005) Effects of nano particles on antigen-related airway inflammation in mice. Respir. 

Res. 16:106. 

Khandoga, A.; Stampfl, A.; Takenaka, S.; Schulz, H.; Radykewicz, R.; Kreyling, W.; 

Krombach, F. (2004) Ultrafine particles exert prothrombotic but not inflammatory effects 

on the hepatic microcirculation in healthy mice in vivo. Circulation 109: 1320-1325. 

Kleinman, M.; Sioutas, C.; Stram, D.; Froines, J.; Cho, A.; Chakrabarti, B.; Hamade, A.; 

Meacher, D.; Oldham, M. (2005) Inhalation of concentrated ambient particulate matter 

near a heavily trafficked road stimulates antigen-induced airway responses in mice. 

J. Air. Waste Manag. Assoc. 55: 1277-1288. 
 B-28

Kreyling, W. G.; Semmler, M.; Moller, W. (2004) Dosimetry and toxicology of ultrafine 

particles. J. Aerosol Med. 17: 140-152. 

Laskin, D. L.; Morio, L.; Hooper, K.; Li, T.-H.; Buckley, B.; Turpin, B. (2003) Peroxides and 

macrophages in the toxicity of fine particulate matter in rats. Boston, MA: Health Effects 

Institute; research report no. 117. 

Li, N.; Sioutas, C.; Froines, J. R.; Cho, A.; Misra, C.; Nel, A. (2003) Ultrafine particulate 

pollutants induce oxidative stress and mitochondrial damage. Environ. Health Perspect. 

111: 455-460. 

Lwebuga-Mukasa, J. S.; Oyana, T. J.; Johnson, C. (2005) Local ecological factors, ultrafine 

particulate concentrations, and asthma prevalence rates in Buffalo, New York, 

neighborhoods. J. Asthma 42: 337-348. 

McNee, W.; Donaldson, K. (2003) Mechanism of lung injury caused by PM10 and ultrafine 

particles with special reference to COPD. Eur. Respir. J. Suppl. 40: 47-S-51S. 

Mills, N. L., Amin, N., Robinson, S. D., Anand, A., Davies, J., Patel, D., de la Fuente, J. M., 

Cassee, F. R., Boon, N. A., Macnee, W., Millar, A. M., Donaldson, K., and Newby, D. E. 

(2006). Do inhaled carbon nanoparticles translocate directly into the circulation in 

humans? Am J Respir Crit Care Med 173, 426-31. 

Molinelli, A. R.; Madden, M. C.; McGee, J. K.; Stonebuerner, J. G.; Ghio, A. J. (2002) Effect of 

metal removal on the toxicity of airborne particulate matter from the Utah Valley. 

Inhalation Toxicol. 14: 1069-1086. 

Moshammer, H; Neuberger, M. (2003) The active surface of suspended particles as a predictor 

of lung function and pulmonary symptoms in Austrian school children. Atmospheric 

Environment 37: 1737–1744 

Nadziejko, C.; Fang, K.; Nadziejko, E.; Narciso, S. P.; Zhong, M.; Chen, L. C. (2002) Immediate 

effects of particulate air pollutants on heart rate and respiratory rate in hypertensive rats. 

Cardiovasc. Toxicol. 2: 245-252. 

Nadziejko, C.; Fang, K.; Narciso, S.; Zhong, M.; Su, W. C.; Gordon, T.; Nadas, A.; Chen, L. C. 

(2004) Effect of particulate and gaseous pollutants on spontaneous arrhythmias in aged 

rats. Inhalation Toxicol. 16: 373-380. 

Nemmar, A.; Hoylaerts, M. F.; Hoet, P. H. M.; Nemery B. (2004) Possible mechanisms of the 

cardiovascular effects of inhaled particles: systemic translocation and prothrombotic 

effects. Toxicol. Lett. 149: 243-253. 

Nemmar, A.; Hoylaerts, M. F.; Hoet, P. H. M.; Vermylen, J.; Nemery, B. (2003) Size effect of 

intratracheally instilled particles on pulmonary inflammation and vascular thrombosis. 

Toxicol. Appl. Pharmacol. 186: 38-45. 
 B-29

Nemmar, A.; Nemery, B.; Hoylaerts, M. F.; Vermylen, J. (2002) Air pollution and thrombosis: 

an experimental approach. Pathophysiol. Haemostasis Thromb. 32: 349-350. 

Oberdorster, G.; Oberdorster, E.; Oberdorster, J. (2005) Nanotoxicology: an emerging discipline 

evolving from studies of ultrafine particles. Environ. Health Perspect. 113: 823-839. 

Oberdorster, G.; Sharp, Z.; Atudorei, V.; Elder, A.; Gelein, R.; Kreyling, W.; Cox, C. (2004) 

Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicol. 16: 437-445. 

Pekkanen, J.; Peters, A.; Hoek, G.; Tiittanen, P.; Brunekreef, B.; de Hartog, J.; Heinrich, J.; 

Ibald-Mulli, A.; Kreyling, W. G.; Lanki, T.; Timonen, K. L.; Vanninen, E. (2002) 

Particulate air pollution and risk of ST-segment depression during repeated submaximal 

exercise tests among subjects with coronary heart disease: the exposure and risk 

assessment for fine and ultrafine particles in ambient air (ULTRA) study. Circulation 

106: 933-938. 

Penn, A.; Murphy, G;. Barker, S.; Henk, W.; Penn, L. (2005) Combustion-derived ultrafine 

particles transport organic toxicants to target respiratory cells. Environ. Health Perspect. 

113: 956-963. 

Penttinen, P.; Vallius, M.; Tiittanen, P.; Ruuskanen, J.; Pekkanen, J. (2006) Source-specific fine 

particles in urban air and respiratory function among adult asthmatics. Inhalation Toxicol. 

18: 191-198. 

Pinkerton, K. E.; Zhou, Y.; Teague, S. V.; Peake, J. L.; Walther, R. C.; Kennedy, I. M.; Leppert, 

V. J.; Aust, A.E. (2004) Reduced lung cell proliferation following short-term exposure to 

ultrafine soot and iron particles in neonatal rats: key to impaired lung growth? Inhalation 

Toxicol. 16(suppl. 1): 73-81. 

Ramage, L.; Guy, K. (2004) Expression of C-reactive protein and heat-shock protein-70 in the 

lung epithelial cell line A549, in response to PM10 exposure. Inhalation Toxicol. 

16: 447-452. 

Sinclair, A. H.; Tolsma, D. (2004) Associations and lags between air pollution and acute 

respiratory visits in an ambulatory care setting: 25-month results from the aerosol 

research and inhalation epidemiological study. J. Air Waste Manag. Assoc. 

54: 1212-1218. 

Sioutas, C.; Delfino, R. J.; Singh, M. (2005) Exposure assessment for atmospheric ultrafine 

particles (UFPs) and implications in epidemiologic research. Environ. Health Perspect. 

113: 947-955. 

Smith, K. R.; Kim, S.; Recendez, J. J.; Teague, S. V.; Menache, M. G.; Grubbs, D. E.; Sioutas, 

C.; Pinkerton, K. E. (2003) Airborne particles of the California Central Valley alter the 

lungs of health adult rats. Environ. Health Perspect. 111: 902-908. 
 B-30

Timonen, K. L.; Hoek, G.; Heinrich, J.; Bernard, A.; Brunekreef, B.; de Hartog, J.; Hameri, K.; 

Ibald-Mulli, A.; Mirme, A.; Peters, A.; Tiittanen, P.; Kreyling, W. G.; Pekkanen, J. 

(2004) Daily variation in fine and ultrafine particulate air pollution and urinary 

concentrations of lung Clara cell protein CC16. Occup. Environ. Med. 61: 908-914. 

Tin-Tin-Win, S.; Shoji, Y.; Sohel, A.; Masaki, K.; Takahiro, K.; Hidekazu, F. (2006) Hydroxylradical-dependent DNA damage by ambient particulate matter from contrasting sampling 

locations. Environ. Res. 101:18-24. 

Tin-Tin-Win, S.; Yamamoto, S.; Ahmed, S.; Kakeyama, M.; Kobayashi, T.; Fujimaki, H. (2006) 

Brain cytokine and chemokine mRNA expression in mice induced by intranasal 

instillation with ultrafine carbon black. Toxicol. Lett. 63: 153-160. 

Tong, S.; Colditz, P. (2004) Air pollution and sudden infant death syndrome: a literature review. 

Paediatr. Perinatal. Epidemiol. 18: 327-335. 

Vinzents, P. S.; Moller, P.; Sorensen, M.; Knudsen, L. E.; Herte, L. Q.; Jensen, F. P.; Schibye, 

B.; Loft, S. (2005) Personal exposure to ultrafine particles and oxidative DNA damage. 

Environ. Health Perspect. 113: 1485-1490. 

Von Klot, S.; Peters, A.; Aalto, P.; Bellander, T.; Berglind, N.; D'Ippoliti, D.; Elosua R, 

Hormann A, Kulmala M, Lanki T, Lowel H, Pekkanen J, Picciotto S, Sunyer, J.; 

Forastiere, F.; Health Effects of Particles on Susceptible Subpopulations (HEAPSS) 

Study Group. (2005) Ambient air pollution is associated with increased risk of hospital 

cardiac readmissions of myocardial infarction survivors in five European cities. 

Circulation. 112: 3073-3079. 

Warheit, D. B.; Webb, T. R.; Sayes, C. M.; Colvin, V. L.; Reed, K. L. (2006) Pulmonary 

instillation studies with nanoscale TiO2 rods and dots in rats: toxicity is not dependent 

upon particle size and surface area. Toxicol. Sci. 91: 227-236. 

Wiebert, P.; Sandhez-Crespo, A.; Seitz, J.; Philipson, K.; Kreyling, W.G.; Moller, W.; 

Sommerer, K.; Larsson, S.; Svartengren, M. (2006) Negligible clearance of ultrafine 

particles retained in healthy and affected human lungs. Eur Respir J (in press). 

Wottrich, R.; Diabate, S.; Krug, H. F. (2004) Biological effects of ultrafine model particles in 

human macrophages and epithelial cells in mono- and co-culture. Int. J. Hyg. Environ. 

Health 207: 353-361. 

Xia, T.; Korge, P.; Weiss, J. N.; Li, N.; Venkatesen, M. I.; Sioutas, C.; Nel, A. (2004) Quinones 

and aromatic chemical compounds in particulate matter induce mitochondrial 

dysfunction: implications for ultrafine particle toxicity. Environ. Health Perspect. 

112: 1347-1358. 
 B-31

Zhou, Y.-M.; Zhong, C.-Y.; Kennedy, I. M.; Pinkerton, K. E. (2003) Pulmonary responses of 

acute exposure to ultrafine iron particles in healthy adult rats. Environ. Toxicol. 

18: 227-235. 
 B-32

Toxicology and Epidemiology Studies of Metals or Metal-Containing Particles3

Adamson, I. Y. R.; Vincent, R.; Bakowska, J. (2003) Differential production of 

metalloproteinases after instilling various urban air particle samples to rat lung. 

Exp. Lung Res. 29: 375-388. 

Anseth, J. W.; Goffin, A. J.; Fuller, G. G.; Ghio, A. J.; Kao, P. N.; Upadhyay, D. (2005) Lung 

surfactant gelation induced by epithelial cells exposed to air pollution or oxidative stress. 

Am. J. Respir. Cell Mol. Biol. 33: 161-168. 

Bagate, K.; Meiring, J. J.; Gerlofs-Nijland, M. E.; Vincent, R.; Cassee, F. R.; Borm, P. J. A. 

(2004) Vascular effects of ambient particulate matter instillation in spontaneous 

hypertensive rats. Toxicol. Appl. Pharmacol. 197: 29-39. 

Baulig, A.; Poirault, J. J.; Ausset, P.; Schins, R.; Shi, T.; Baralle, D.; Dorlhene, P.; Meyer, M.; 

Lefevre, R.; Baeza-Squiban, A.; Marano, F. (2004) Physicochemical characteristics and 

biological activities of seasonal atmospheric particulate matter sampling in two locations 

of Paris. Environ. Sci. Technol. 38: 5985-5992. 

Becker, S.; Soukup, J. M.; Gallagher, J. E. (2002) Differential particulate air pollution induced 

oxidant stress in human granulocytes, monocytes and alveolar macrophages. Toxicol. 

In Vitro 16: 209-218. 

Bennett, C. M.; McKendry, I. G.; Kelly, S.; Denike, K.; Koch, T. (2006) Impact of the 1998 

Gobi dust event on 

hospital admissions in the Lower Fraser Valley, British Columbia. Sci. Total Environ.: in press. 

Brits, E.; Schoeters, G.; Verschaeve, L. (2004) Genotoxicity of PM10 and extracted organics 

collected in an 

industrial, urban, and rural area in Flanders, Belgium. Environ. Res. 96: 109-118. 

Burchiel, S. W.; Lauer, F.T.; Dunaway, S. L.; Zawadzki, J.; McDonald, J. D.; Reed, M. D. 

(2005) Hardwood smoke alters murine splenic T cell responses to mitogens following a 

6-month whole body inhalation exposure. Toxicol. Appl. Pharmacol. 202: 229-236. 

Carvalho-Oliveira, R.; Pozo, R. M. K.; Lobo, D. J. A.; Lichtenfels, A. J. F. C.; Martins-Junior, 

H. A.; Bustilho, J. O. W. V.; Saiki, M.; Sato, I. M.; Saldiva, P. H. N. (2005) Diesel 

emissions significantly influence composition and mutagenicity of ambient particles: 

a case study in Sao Paulo, Brazil. Environ. Res. 98: 1-7. 

 

3

 Studies which include “metals” in the abstract or those that highlight particular metals (i.e., V, Zn, etc.) in the 

abstract. 
 B-33

Churg, A.; Brauer, M.; del Carmen Avila-Casado, M.; Fortoul, T. I.; Wright, J. L. (2003) 

Chronic exposure to high levels of particulate air pollution and small airway remodeling. 

Environ. Health Perspect. 111: 714-718. 

Claiborn, C. S.; Larson, T.; Sheppard, L. (2002) Testing the metals hypothesis in Spokane, 

Washington. Environ. Health Perspect. 110(suppl. 4): 547-552. 

Costa, D. L.; Lehmann, J. R.; Winsett, D.; Richards, J.; Ledbetter, A. D.; Dreher, K. L. (2006) 

Comparative pulmonary toxicological assessment of oil combustion particles following 

inhalation or instillation exposure. Toxicol. Sci. 91: 237-246. 

De Kok, T. M.; Hogervorst, J. G.; Briede, J. J.; van Herwijnen, M. H.; Maas, L. M.; Moonen, 

E. J.; Driece, H. A.; Kleinjans, J. C. (2005) Genotoxicity and physicochemical 

characteristics of traffic-related ambient particulate matter. Environ. Mol. 

Mutagen.46: 71-80. 

Fernandez, A.; Wendt, J. O. L.; Cenni, R.; Young, R. S.; Witten, M. L. (2002) Resuspension of 

coal and coal/municipal sewage sludge combustion generated fine particles for inhalation 

health effects studies. Sci. Total Environ. 287: 265-274. 

Fernandez, A.; Wendt, J. O.; Wolski, N.; Hein, K. R.; Wang, S.; Witten, M. L. (2003) Inhalation 

health effects of fine particles from the co-combustion of coal and refuse derived fuel. 

Chemosphere 51: 1129-1137. 

Gabelova, A.; Valovicova, Z.; Horvathova, E.; Slamenova, D.; Binkova, B.; Sram, R. J.; Farmer, 

P. B. (2004) Genotoxicity of environmental air pollution in three European cities: Prague, 

Kosice and Sofia. Mutat. Res. 563: 49-59. 

Gardner, S. Y.; McGee, J. K.; Kodavanti, U. P.; Ledbetter, A.; Everitt, J. I.; Winsett, D. W.; 

Doerfler, D. L.; Costa, D. L. (2004) Emission-particle-induced ventilatory abnormalities 

in a rat model of pulmonary hypertension. Environ. Health Perspect. 112: 872-878. 

Gao, F.; Barchowsky, A.; Nemec, A. A.; Fabisiak, J. P. (2004) Microbial stimulation by 

Mycoplasma fermentans synergistically amplifies IL-6 release by human lung fibroblasts 

in response to residual oil fly ash (ROFA) and nickel. Toxicol. Sci. 81: 467-479. 

Gavett, S. H.; Haykal-Coates, N.; Copeland, L B.; Heinrich, J.; Gilmour, M. I. (2003) Metal 

composition of ambient PM2.5 influences severity of allergic airways disease in mice. 

Environ. Health Perspect. 111: 1471-1477. 

Ghio, A. J.; Cohen, M. D. (2005) Disruption of iron homeostasis as a mechanism of biologic 

effect by ambient air pollution particles. Inhal. Toxicol. 17: 709-716. 
 B-34

Ghio, A. J.; Piantadosi, C. A.; Wang, X.; Dailey, L. A.; Stonehuerner, J. D.; Madden, M. C.; 

Yang, F.; Dolan, K. G.; Garrick, M. D.; Garrick, L. M. (2005) Divalent metal transporter1 decreases metal-related injury in the lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 

289: L460-L467. 

Gilmour PS, Nyska A, Schladweiler MC, McGee JK, Wallenborn JG, Richards JH, Kodavanti 

UP. (2006) Cardiovascular and blood coagulative effects of pulmonary zinc exposure. 

Toxicol. Appl. Pharmacol. 211: 41-52. 

Gilmour, P. S.; Schladweiler, M. C.; Richards, J. H.; Ledbetter, A. D.; Kodavanti, U. P. (2004) 

Hypertensive rats are susceptible to TLR4-mediated signaling following exposure to 

combustion source particulate matter. Inhalation Toxicol.16(suppl. 1): 5-18. 

Graff, D. W.; Cascio, W. E.; Brackhan, J. A.; Devlin, R. B. (2004) Metal particulate matter 

components affect gene expression and beat frequency of neonatal rat ventricular 

myocytes. Environ. Health Perspect. 112: 792-798. 

Grahame, T.; Hidy, G. (2004) Using factor analysis to attribute health impacts to particulate 

pollution sources. Inhalation Toxicol. 16 (suppl. 1): 143-152. 

Gurgueira, S. A.; Lawrence, J.; Coull, B.; Murthy, G. G. K.; Gonzalez-Flecha, B. (2002) Rapid 

increases in the steady-state concentration of reactive oxygen species in the lungs and 

heart after particulate air pollution inhalation. Environ. Health Perspect. 110: 749-755. 

Hahn, F. F.; Barr, E. B.; Menache, M. G.; Seagrave, J. (2005) Particle size and composition 

related to adverse health effects in aged, sensitive rats. Boston, MA: Health Effects 

Institute; research report no. 129. Available: 

http://www.healtheffects.org/Pubs/Hahn.pdf [13 December, 2005]. 

Hetland, R. B.; Cassee, F. R.; Lag, M.; Refsnes, M.; Dybing, E.; Schwarze, P. E. (2005) 

Cytokine release from alveolar macrophages exposed to ambient particulate matter: 

heterogeneity in relation to size, city and season. Part. Fibre Toxicol. 2: 10.1186/1743-

8977-2-4. Available: http://www.particleandfibretoxicology.com/content/2/1/4 

[14 March, 2006]. 

Huang, S. L.; Hsu, M. K.; Chan, C. C. (2003) Effects of submicrometer particle compositions on 

cytokine production and lipid peroxidation of human bronchial epithelial cells. Environ. 

Health Perspect. 111: 478-482. 

Huang, Y.-C. T.; Ghio, A. J.; Stonehuerner, J.; McGee, J.; Carter, J. D.; Grambow, S. C.; Devlin, 

R. B. (2003) The role of soluble components in ambient fine particles-induced changes in 

human lungs and blood. Inhalation Toxicol. 15: 327-342. 

Huang, Y.-C. T.; Li, Z.; Harder, S. D.; Soukup, J. M. (2004) Apoptotic and inflammatory effects 

induced by different particles in human alveolar macrophages. Inhalation Toxicol. 

16: 863-878. 
 B-35

Hunt, A.; Abraham, J. L.; Judson, B.; Berry, C. L. (2003) Toxicologic and epidemiologic clues 

from the characterization of the 1952 London smog fine particulate matter in archival 

autopsy lung tissues. Environ. Health Perspect. 111: 1209-1214. 

Karlsson, H. L.; Nilsson, L.; Moller, L. (2005) Subway particles are more genotoxic than street 

particles and induce oxidative stress in cultured human lung cells. Chem. Res. Toxicol. 

18: 19-23. 

Kim, J. Y.; Chen, J.-C.; Boyce, P. D.; Christiani, D. C. (2005) Exposure to welding fumes is 

associated with acute systemic inflammatory responses. Occup. Environ. Med. 

62: 157-163. 

Kim, Y. M.; Reed, W.; Wu, W.; Bromberg, P. A.; Graves, L. M.; Samet, J. M. (2005) Zn2+-

induced IL-8 expression involves AP-1, JNK, and ERK activities in human airway 

epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 290: L1028-1035. 

Kodavanti, U. P.; Schladweiler, M. C.; Ledbetter, A. D.; McGee, J. K.; Walsh, L.; Gilmour, P. 

S.; Highfill, J. W.; Davies, D.; Pinkerton, K. E.; Richards, J. H.; Crissman, K.; 

Andrews, D.; Costa, D. L. (2005) Consistent pulmonary and systemic responses from 

inhalation of fine concentrated ambient particles: roles of rat strains used and 

physicochemical properties. Environ. Health Perspect. 113: 1561-1568. 

Kristovich, R.; Knight, D. A.; Long, J. F.; Williams, M. V.; Dutta, P. K.; Waldman, W. J. (2004) 

Macrophage-mediated endothelial inflammatory responses to airborne particulates: 

impact of particulate physicochemical properties. Chem. Res. Toxicol. 17: 1303-1312. 

Laskin, D. L.; Morio, L.; Hooper, K.; Li, T.-H.; Buckley, B.; Turpin, B. (2003) Peroxides and 

macrophages in the toxicity of fine particulate matter in rats. Boston, MA: Health Effects 

Institute; research report no. 117. 

Li, Z.; Carter, J. D.; Dailey, L. A.; Huang, Y. C. (2005) Pollutant particles produce 

vasoconstriction and enhance MAPK signaling via angiotensin type I receptor. Environ. 

Health Perspect. 11: 1009-1014. 

Long, J. F.; Waldman, W. J.; Kristovich, R.; Williams, M.; Knight, D.; Dutta, P. K. (2005) 

Comparison of ultrastructural cytotoxic effects of carbon and carbon/iron particulates on 

human monocyte-derived macrophages. Environ. Health Perspect. 113: 170-174. 

 

Maciejczyk, P.; Chen, L. C. (2005) Effects of subchronic exposures to concentrated ambient 

particles (CAPs) in mice: VIII. source-related daily variations in in vitro responses to 

CAPs. Inhalation Toxicol. 17: 243-253. 

Magari, S. R.; Schwartz, J.; Williams, P. L.; Hauser, R.; Smith, T. J.; Christiani, D. C. (2002) 

The association of particulate air metal concentrations with heart rate variability. 

Environ. Health Perspect. 110: 875-880. 
 B-36

Merolla, L.; Richards, R. J. (2005) In vitro effects of water-soluble metals present in UK 

particulate matter. Exp. Lung Res. 31:671-683. 

 

Moreno, T.; Merolla, L.; Gibbons, W.; Greenwell, L.; Jones, T.; Richards, R. (2004) Variations 

in the source, metal content and bioreactivity of technogenic aerosols: a case study from 

Port Talbot, Wales, UK Sci. Tot. Environ. 333: 59-73. 

Morishita, M.; Keeler, G.; Wagner, J.; Marsik, F.; Timm, E.; Dvonch, J.; Harkema, J. (2004) 

Pulmonary retention of particulate matter is associated with airway inflammation in 

allergic rats exposed to air pollution in urban Detroit. Inhal. Toxicol. 16: 663-674. 

Moyer, C. F.; Kodavanti, U. P.; Haseman, J. K.; Costa, D. L.; Nyska, A. (2002) Systemic 

vascular disease in male B6C3F1 mice exposed to particulate matter by inhalation: 

studies conducted by the national toxicology program. Toxicol. Pathol. 30: 427-434. 

Nurkiewicz, T. R.; Porter, D. W.; Barger, M.; Castranova, V.; Boegehold, M. A. (2004) 

Particulate matter exposure impairs systemic microvascular endothelium-dependent 

dilation. Environ. Health Perspect. 112: 1299-1306. 

Nurkiewicz, T. R.; Porter, D. W.; Barger, M.; Millecchia, L.; Rao, K. M.; Marvar, P. J.; Hubbs, 

A. F.; Castranova, V.; Boegehold, M. A. (2006) Systemic microvascular dysfunction and 

inflammation after pulmonary particulate matter exposure. Environ. Health 

Perspect.114: 412-419. 

Obot, C. J.; Morandi, M. T.; Beebe, T. P.; Hamilton, R. F.; Holian, A. (2002) Surface 

components of airborne particulate matter induce macrophage apoptosis through 

scavenger receptors. Toxicol. Appl. Pharmacol. 184: 98-106. 

Okeson, C. D.; Riley, M. R.; Fernandez, A.; Wendt, J. O. L. (2003) Impact of the composition of 

combustion generated fine particles on epithelial cell toxicity: influences of metals on 

metabolism. Chemosphere 51: 1121-1128. 

 

Okeson, C. D.; Riley, M. R.; Riley-Saxton, E. (2004) In vitro alveolar cytotoxicity of soluble 

components of airborne particulate matter: effects of serum on toxicity of transition 

metals. Toxicol. In Vitro 18: 673-680. 

Paoletti, L.; De Berardis, B.; Arrizza, L. (2003) Inquinamento da polveri e da particolato fino in 

siti con differenti caratteristiche ambientali [Inhalable airborne particulate pollution in 

sites characterized by dissimilar environmental conditions]. Ann. Ist. Super. Sanita 

39: 381-385. 

Pastorkova, A.; Cerna, M.; Smid, J.; Vrbikova, V. (2004) Mutagenicity of airborne particulate 

matter PM10. Cent. Eur. J. Public Health 12(suppl.): S72-S75. 
 B-37

Penn, A.; Murphy, G;. Barker, S.; Henk, W.; Penn, L. (2005) Combustion-derived ultrafine 

particles transport organic toxicants to target respiratory cells. Environ. Health Perspect. 

113: 956-963. 

Pinkerton, K. E.; Zhou, Y.; Teague, S. V.; Peake, J. L.; Walther, R. C.; Kennedy, I. M.; Leppert, 

V. J.; Aust, A. E. (2004) Reduced lung cell proliferation following short-term exposure to 

ultrafine soot and iron particles in neonatal rats: key to impaired lung growth? Inhalation 

Toxicol. 16(suppl. 1): 73-81. 

 

Pozzi, R.; De Berardis, B.; Paoletti, L.; Guastadisegni, C. (2005) Winter urban air particles from 

Rome (Italy): effects on the monocytic-macrophagic RAW 264.7 cell line. Environ. Res. 

99: 344-354. 

Proctor, S. D.; Dreher, K. L.; Kelly, S. E.; Russell, J. C. (2006) Hypersensitivity of prediabetic 

JCR: LA-cp rats to fine airborne combustion particle-induced direct and noradrenergicmediated vascular contraction. Toxicol. Sci. 90: 385-391. 

Rhoden, C. R.; Lawrence, J.; Godleski, J. J.; Gonzalez-Flecha, B. (2004) N-acetylcysteine 

prevents lung inflammation after short-term inhalation exposure to concentrated ambient 

particles. Toxicol. Sci. 79: 296-303. 

Riediker, M.; Williams, R.; Devlin, R.; Griggs, T.; Bromberg, P. (2003) Exposure to particulate 

matter, volatile organic compounds, and other air pollutants inside patrol cars. Environ. 

Sci. Technol. 37: 2084-2093. 

Riley, M. R.; Boesewetter, D. E.; Kim, A. M.; Sirvent, F. P. (2003) Effects of metals Cu, Fe, Ni, 

V, and Zn on rat lung epithelial cells. Toxicology 190: 171-184. 

 

Salnikow, K.; Li, X.; Lippmann, M. (2004) Effect of nickel and iron co-exposure on human lung 

cells. Toxicol. Appl. Pharmacol. 196: 258-265. 

 

Schaumann, F.; Borm, P. J. A.; Herbrich, A.; Knoch, J.; Pitz, M.; Schins, R. P. F.; Luettig, B.; 

Hohlfeld, J. M.; Heinrich, J.; Krug, N. (2004) Metal-rich ambient particles (particulate 

matter 2.5) cause airway inflammation in healthy subjects. Am. J. Respir. Crit. Care Med. 

170: 898-903. 

Schins, R. P. F.; Lightbody, J. H.; Borm, P. J. A.; Shi, T.; Donaldson, K.; Stone, V. (2004) 

Inflammatory effects of coarse and fine particulate matter in relation to chemical and 

biological constituents. Toxicol. Appl. Pharmacol. 195: 1-11. 

Schneider JC, Card GL, Pfau JC, Holian A. (2005) Air pollution particulate SRM 1648 causes 

oxidative stress in RAW 264.7 macrophages leading to production of prostaglandin E2, 

a potential Th2 mediator. Inhal Toxicol. 17(14):871-7. 
 B-38

Sheesley, R. J.; Schauer, J. J.; Hemming, J. D.; Geis, S.; Barman, M. A. (2005) Seasonal and 

spatial relationship of chemistry and toxicity in atmospheric particulate matter using 

aquatic bioassays. Environ. Sci. Technol. 39: 999-1010. 

Shi, T.; Knaapen, A. M.; Begerow, J.; Birmili, W.; Borm, P. J.; Schins, R. P. (2003) Temporal 

variation of hydroxyl radical generation and 8-hydroxy-2'-deoxyguanosine formation by 

coarse and fine particulate matter. Occup. Environ. Med. 60: 315-321. 

Smith, K. R.; Kim, S.; Recendez, J. J.; Teague, S. V.; Menache, M. G.; Grubbs, D. E.; Sioutas, 

C.; Pinkerton, K. E. (2003) Airborne particles of the California Central Valley alter the 

lungs of health adult rats. Environ. Health Perspect. 111: 902-908. 

Sorensen, M.; Schins, R. P. F.; Hertel, O.; Loft, S. (2005) Transition metals in personal samples 

of PM2.5 and oxidative stress in human volunteers. Cancer Epidemiol. Biomarkers Prev. 

14: 1340-1343. 

 

Wesselkamper, S. C.; Chen, L. C.; Gordon, T. (2005) Quantitative trait analysis of the 

development of pulmonary tolerance to inhaled zinc oxide in mice. Respir. Res. 6: 73. 

Wichers, L. B.; Nolan, J. P.; Winsett, D. W.; Ledbetter, A. D.; Kodavanti, U. P.; Schladweiler, 

J.; Costa, D. L.; Watkinson, W. P. (2004) Effects of instilled combustion-derived 

particles in spontaneously hypertensive rats. Part 1: cardiovascular responses. Inhalation 

Toxicol. 16: 391-405. 

Wichers, L. B.; Nolan, J. P.; Winsett, D. W.; Ledbetter, A. D.; Kodavanti, U. P.; Schladweiler, 

M. C. J.; Costa, D. L.; Watkinson, W. P. (2004) Effects of instilled combustion-derived 

particles in spontaneously hypertensive rats. Part 2: pulmonary responses. Inhalation 

Toxicol. 16: 407-419. 

 

Zelikoff, J. T.; Schermerhorn, K. R.; Fang, K.; Cohen, M. D.; Schlesinger, R. B. (2002) A role 

for associated transition metals in the immunotoxicity of inhaled ambient particulate 

matter. Environ. Health Perspect. 110(suppl. 5): 871-875. 

Zhou, Y.-M.; Zhong, C.-Y.; Kennedy, I. M.; Pinkerton, K. E. (2003) Pulmonary responses of 

acute exposure to ultrafine iron particles in healthy adult rats. Environ. Toxicol. 

18: 227-235. 
 B-39

Toxicology Studies of Endotoxin/LPS or Endotoxin/LPS-Containing Particles

Archer, A. J.; Cramton, J. L.; Pfau, J. C.; Colasurdo, G.; Holian, A. (2004) Airway 

responsiveness after acute exposure to urban particulate matter 1648 in a DO11.10 

murine model. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L337-L343. 

Arimoto, T.; Kadiiska, M. B.; Sato, K.; Corbett, J.; Mason, R. P. (2005) Synergistic production 

of lung free radicals by diesel exhaust particles and endotoxin. Am. J. Respir. Crit. Care 

Med. 171: 379-387. 

Bagate, K.; Meiring, J. J.; Gerlofs-Nijland, M. E.; Vincent, R.; Cassee, F. R.; Borm, P. J. A. 

(2004) Vascular effects of ambient particulate matter instillation in spontaneous 

hypertensive rats. Toxicol. Appl. Pharmacol. 197: 29-39. 

Becker, S.; Soukup, J. M.; Gallagher, J. E. (2002) Differential particulate air pollution induced 

oxidant stress in human granulocytes, monocytes and alveolar macrophages. Toxicol. in 

Vitro 16: 209-218. 

Becker, S.; Mundandhara, S.; Devlin, R. B.; Madden, M. (2005) Regulation of cytokine 

production in human alveolar macrophages and airway epithelial cells in response to 

ambient air pollution particles: further mechanistic studies. Toxicol. Appl. Pharmacol. 

207(2 Suppl): 269-275. 

 

Becker, S.; Dailey, L.; Soukup, J. M.; Silbajoris, R.; Devlin, R. B. (2005) TLR-2 is involved in 

airway epithelial cell response to air pollution particles. Toxicol. Appl. Pharmacol. 203: 

45-52. 

Elder, A. C. P.; Gelein, R.; Azadniv, M.; Frampton, M.; Finkelstein, J.; Oberdorster, G. (2004) 

Systemic effects of inhaled ultrafine particles in two compromised, aged rat strains. 

Inhalation Toxicol. 16: 461-471. 

Elder, A.; Gelein, R.; Finkelstein, J.; Phipps, R.; Frampton, M.; Utell, M.; Kittelson, D. B.; 

Watts, W. F.; Hopke, P.; Jeong, C. H.; Kim, E.; Liu, W.; Zhao, W.; Zhuo, L.; Vincent, 

R.; Kumarathasan, P.; Oberdorster, G. (2004) On-road exposure to highway aerosols. 2. 

Exposures of aged, compromised rats. Inhalation Toxicol. 16(suppl. 1): 41-53. 

Gilmour, P. S.; Morrison, E. R.; Vickers, M. A.; Ford, I.; Ludlam, C. A.; Greaves, M.; 

Donaldson, K.; MacNee, W. (2005) The procoagulant potential of environmental 

particles (PM10). Occup. Environ. Med. 62: 164-171. 

Harkema, J. R.; Wagner, J. G. (2005) Epithelial and inflammatory responses in the airways of 

laboratory rats coexposed to ozone and biogenic substances: enhancement of toxicantinduced airway injury. Exp. Toxicol. Pathol. 57(suppl. 1): 129-141. 
 B-40

Hetland, R. B.; Cassee, F. R.; Lag, M.; Refsnes, M.; Dybing, E.; Schwarze, P. E. (2005) 

Cytokine release from alveolar macrophages exposed to ambient particulate matter: 

heterogeneity in relation to size, city and season. Part. Fibre Toxicol. 2: 10.1186/1743-

8977-2-4. Available: http://www.particleandfibretoxicology.com/content/2/1/4 [14 

March, 2006]. 

Huang, S. L.; Hsu, M. K.; Chan, C. C. (2003) Effects of submicrometer particle compositions on 

cytokine production and lipid peroxidation of human bronchial epithelial cells. Environ. 

Health Perspect. 111: 478-482. 

Inoue, K.; Takano, H.; Yanagisawa, R.; Ichinose, T.; Sadakane, K.; Yoshino, S.; Yamaki, K.; 

Uchiyama, K.; Yoshikawa, T. (2004) Components of diesel exhaust particles 

differentially affect lung expression of cyclooxygenase-2 related to bacterial endotoxin J. 

Appl. Toxicol. 24: 415-418. 

Kleinman MT, Sioutas C, Chang MC, Boere AJ, Cassee FR. (2003) Ambient fine and coarse 

particle suppression of alveolar macrophage functions. Toxicol Lett. 2003 Feb 

3;137(3):151-8. 

Laskin, D. L.; Morio, L.; Hooper, K.; Li, T.-H.; Buckley, B.; Turpin, B. (2003) Peroxides and 

macrophages in the toxicity of fine particulate matter in rats. Boston, MA: Health Effects 

Institute; research report no. 117. 

Schins, R. P. F.; Lightbody, J. H.; Borm, P. J. A.; Shi, T.; Donaldson, K.; Stone, V. (2004) 

Inflammatory effects of coarse and fine particulate matter in relation to chemical and 

biological constituents. Toxicol. Appl. Pharmacol. 195: 1-11. 

Takano, H.; Yanagisaw, R.; Ichinose, T.; Sadakane, K.; Yoshino, S.; Yoshikawa, T.; Morita, M. 

(2002) Diesel exhaust particles enhance lung injury related to bacterial endotoxin through 

expression of proinflammatory cytokines, chemokines, and intercellular adhesion 

molecule-I. Am. J. Respir. Crit. Care Med. 165: 1329-1335. 

Veranth, J. M.; Reilly, C. A.; Veranth, M. M.; Moss, T. A.; Langelier, C. R.; Lanza, D. L.; Yost, 

G. S. (2004) Inflammatory cytokines and cell death in BEAS-2B lung cells treated with 

soil dust, lipopolysaccharide, and surface-modified particles. Toxicol. Sci. 82: 88-96. 

Yanagisawa, R.; Takano, H.; Inoue, K.; Ichinose, T.; Sadakane, K.; Yoshino, S.; Yamaki, K.; 

Kumagai, Y.; Uchiyama, K.; Yoshikawa, T.; Morita, M. (2003) Enhancement of acute 

lung injury related to bacterial endotoxin by components of diesel exhaust particles. 

Thorax 58: 605-612. 
 B-41

Toxicology and Epidemiology Studies of Wood Smoke

Bhattacharyya, S. N.; Dubick, M. A.; Yantis, L. D.; Enriquez, J. I.; Buchanan, K. C.; Batra, S. 

K.; Smiley, R. A. (2004) In vivo effect of wood smoke on the expression of two mucin 

genes in rat airways. Inflammation 28: 67-76. 

Boman, B. C.; Forsberg, A. B.; Jarvholm, B. G. (2003) Adverse health effects from ambient air 

pollution in relation to residential wood combustion in modern society. Scand. J. Work 

Environ. Health 29: 251-260. 

Burchiel, S. W.; Lauer, F.T.; Dunaway, S. L.; Zawadzki, J.; McDonald, J. D.; Reed, M. D. 

(2005) Hardwood smoke alters murine splenic T cell responses to mitogens following a 

6-month whole body inhalation exposure. Toxicol. Appl. Pharmacol.202: 229-236. 

Guggisberg, M.; Hessel, P. A.; Michaelchuk, D.; Ahmed, I. (2003) Respiratory symptoms and 

exposure to wood smoke in an isolated northern community. Can. J. Public Health 94: 

372-376. 

Kubatova, A.; Steckler, T. S.; Gallagher, J. R.; Hawthorne, S. B.; Picklo, M. J. Sr. (2004) 

Toxicity of wide-range polarity fractions from wood smoke and diesel exhaust particulate 

obtained using hot pressurized water. Environ. Toxicol. Chem. 23: 2243-2250. 

Liu, P. L.; Chen, Y. L.; Chen, Y. H.; Lin, S. J.; Kou, Y. R. (2005) Wood smoke extract induces 

oxidative stress-mediated caspase-independent apoptosis in human lung endothelial cells: 

role of AIF and EndoG. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: L739-L749. 

Seagrave, J.; McDonald, J. D.; Reed, M. D.; Seilkop, S. K.; Mauderly, J. L. (2005) Responses to 

subchronic inhalation of low concentrations of diesel exhaust and hardwood smoke 

measured in rat bronchoalveolar lavage fluid. Inhalation Toxicol. 17: 657-670. 

Steerenberg, P.; Withagen, C.; Dalen, W.; Dormans, J.; Loveren, H. (2004) Adjuvant Activity of 

Ambient Particulate Matter in Macrophage Activity-Suppressed, N-AcetylcysteineTreated, iNOS- and IL-4-Deficient Mice. Inhal. Toxicol. 16: 835-843. 

Zelikoff, J. T.; Chen, L. C.; Cohen, M. D.; Schlesinger, R. B. (2002) The toxicology of inhaled 

woodsmoke. J. Toxicol. Environ. Health Part B 5: 269-282.