December 2012
EPA/600/R-12/056F
vvEPA
United States
Environmental Protection
Agency
Provisional Assessment of Recent
Studies on Health Effects of
Particulate Matter Exposure
National Center for Environmental Assessment RTF Division
Office of Research and Development
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
-------
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.
-------
Table of Contents
List of Tables iv
List of Figures v
Authors, Contributors, Reviewers vi
Executive Summary viii
1. INTRODUCTION AND METHODOLOGY 1
2. OVERVIEW OF RECENT HEALTH STUDIES RESULTS 2
2.1. Epidemiologic Studies of Long-Term Exposure 3
2.1.1. Mortality 4
2.1.2. Morbidity - Cardiovascular Effects 12
2.1.3. Morbidity - Respiratory Effects 14
2.1.4. Morbidity - Reproductive and Developmental Effects 16
2.2. Epidemiologic Studies of Short-Term Exposure 16
2.2.1. Mortality 17
2.2.2. Morbidity 21
2.3. Health Effects Related to Sources or Components of PM 30
2.3.1. Epidemiologic Studies Using Source Apportionment 30
2.3.2. Epidemiologic Studies on Effects of Fine PM Components and Sources 31
2.3.3. Toxicology Studies- Source Apportionment and Fine PM Components 35
3. SUMMARY AND CONCLUSIONS 40
APPENDIX A. Studies Included in the PM Provisional Science Assessment 42
References 57
in
-------
List of Tables
Table 2.1. Causal Determinations for Short-and Long-Term Exposure to PM25 3
Table 2.2.Association between mortality outcomes and PM2 5 components using a 30-km buffer
(n=43,220) (adapted from Ostroetal. (2011)) 34
Table 2.3. CAPs Sources and Associated Endpoints 36
Table A.I. Characterization of Studies of Long-term Exposure to PM2.5 and Mortality 42
Table A.2. Characterization of Studies of Long-term Exposure to PM10-2.5 and Mortality 43
Table A.3. Characterization of Studies of Long-term Exposure to PM2.5 and Cardiovascular Effects.... 44
Table A.4. Characterization of Studies of Long-term Exposure to PM2.5 and Respiratory Effects 45
Table A.5. Characterization of Studies of Long-term Exposure to PM2.5 and Reproductive and
Developmental Effects 47
Table A.6. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5 and
Mortality 49
Table A.7. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5 and
Respiratory Hospital Admissions and Emergency Department Visits 50
Table A.8. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM10-2.5 and
Respiratory Hospital Admissions and Emergency Department Visits 53
Table A.9. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5 and
Cardiovascular Hospital Admissions and Emergency Department Visits 53
Table A.10. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5 and
Out of Hospital Cardiac Arrests 56
Table A.ll. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5 and
Time of Stroke Symptom Onset 56
IV
-------
List of Figures
Figure 2.1. All-cause mortality risk estimates, long-term exposure to PM25 in recent cohort studies 6
Figure 2.2. Cardiovascular mortality risk estimates, long-term exposure to PM2 5 in recent cohort
studies 7
Figure 2.3. Respiratory mortality risk estimates, long-term exposure to PM2 5 in recent cohort
studies 8
Figure 2.4. Percent increase in non-accidental and cause-specific mortality for a 10 (ig/m3 increase in
24-h average PM2 5 concentrations in single-pollutant models from U.S. and Canadian studies 20
Figure 2.5. % Increase in respiratory-related hospital admissions and ED visits for a 10 (ig/m3
increase in 24-h average PM2 5 concentrations in single-pollutant models from U.S. and Canadian
studies 25
Figure 2.6. Percent increase in cardiovascular-related hospital admissions and ED visits for a 10
(ig/m3 increase in 24-h average PM2 5 concentrations in single-pollutant models from U.S. and
Canadian studies 29
-------
Authors, Contributors, Reviewers
Executive Direction
Dr. John Vandenberg (Director) - National Center for Environmental Assessment-RTF Division,
U.S. Environmental Protection Agency, Research Triangle Park, NC
Ms. Debra Walsh (Deputy Director) - National Center for Environmental Assessment-RTF
Division, U.S. Environmental Protection Agency, Research Triangle Park, NC
Dr. Mary Ross (Branch Chief) - National Center for Environmental Assessment, U.S.
Environmental Protection Agency, Research Triangle Park, NC
Principal Authors
Mr. Jason Sacks (Team Lead) - National Center for Environmental Assessment, U.S.
Environmental Protection Agency, Research Triangle Park, NC
Dr. Ellen Kirrane - National Center for Environmental Assessment, U.S. Environmental
Protection Agency, Research Triangle Park, NC
Dr. Thomas Luben - National Center for Environmental Assessment, U.S. Environmental
Protection Agency, Research Triangle Park, NC
Dr. Elizabeth Oesterling Owens - National Center for Environmental Assessment, U.S.
Environmental Protection Agency, Research Triangle Park, NC
Contributors
Ms. Laura Datko-Williams - Oak Ridge Institute for Science and Education Research Fellow,
National Center for Environmental Assessment, U.S. Environmental Protection Agency,
Research Triangle Park, NC
Reviewers
Dr. Dan Costa, Air, Climate, and Energy Research Program, Office of Research and
Development, U.S. Environmental Protection Agency, Research Triangle Park, NC
Dr. Aimen Farraj, National Health and Environmental Effects Research Laboratory, U.S.
Environmental Protection Agency, Research Triangle Park, NC
Dr. Ian Gilmour, National Health and Environmental Effects Research Laboratory, U.S.
Environmental Protection Agency, Research Triangle Park, NC
Ms. Beth Hassett-Sipple, Office of Air Quality Planning and Standards, U.S. Environmental
Protection Agency, Research Triangle Park, NC.
VI
-------
Dr. Karen Martin, Office of Air Quality Planning and Standards, U.S. Environmental Protection
Agency, Research Triangle Park, NC.
Dr. Lucas Neas, National Health and Environmental Effects Research Laboratory, U.S.
Environmental Protection Agency, Research Triangle Park, NC
Mr. Steven Silverman, Office of General Council, U.S. Environmental Protection Agency,
Washington, D.C.
Dr. Lindsay Wichers Stanek, National Exposure Research Laboratory, U.S. Environmental
Protection Agency, Research Triangle Park, NC
vn
-------
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 2009
PM Integrated Science Assessment (ISA). 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 to
the current PM NAAQS review in the context of the findings of the 2009 PM ISA. The focus is
on: (a) epidemiologic studies that used PM2.5 (i.e., fine PM) or PMio-2.s (i.e., coarse PM) and were
conducted in the U.S. or Canada, and (b) toxicological or epidemiologic studies that compared
effects of PM from different sources, PM components, or size fractions. The provisional
assessment is not intended to critically review individual studies or integrate the scientific
findings to draw causal conclusions as is done for an ISA.
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. 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 2009 PM
ISA. In brief, this report finds the following:
• Recent epidemiologic studies, most of which are extensions of earlier work, continue to
support the conclusions of the 2009 PM ISA for long-term exposure to PM2.5 and
mortality, cardiovascular effects, respiratory effects, and reproductive and
developmental effects. Notably, updated findings from the Harvard Six Cities and
American Cancer Society cohorts continue to observe an association between long-term
PM2 5 exposure and mortality, which supports the findings from previous studies
conducted in these cohorts. Additionally, a new Canadian multicity study observed
associations with mortality at long-term mean PM2.5 concentrations below those reported
in the PM ISA. Recent cause-specific mortality studies also provide more evidence for
cardiovascular mortality associations, especially in women, and additional evidence for
respiratory mortality including lung cancer. Studies of cardiovascular effects provide
evidence of myocardial infarction, hypertension, diabetes, and stroke, especially among
women, which is consistent with the conclusions of the 2009 PM ISA. Recent studies
continue to demonstrate associations with respiratory morbidity including respiratory
symptoms and hospital admissions, as well as incident asthma among children.
Reproductive and developmental effects studies continue to provide evidence for
associations between long-term exposure to PM2.5 and reduced birth weight.
• Recent epidemiologic studies have also continued to report associations between short-
term exposure to PM2.s and mortality and morbidity health endpoints, which further
support the causality determinations presented in the 2009 PM ISA. These include multi-
Vlll
-------
and single-city analyses that demonstrate consistent positive associations across all
respiratory and cardiovascular hospital admissions and emergency department visits as
well as cause-specific outcomes, particularly asthma. Although limited to single-city
studies, recent studies continue to demonstrate associations between short-term fine PM
exposures and nonaccidental and cardiovascular mortality. Additionally, new evidence
for stroke which focuses on assigning exposure from the time of stroke onset, instead of
entry to the hospital, provides new information regarding an uncertainty recognized in
the PM ISA.
• New toxicological and epidemiologic studies have continued to link health outcomes
with a range ofPM2.s sources and components. Several new epidemiologic analyses
continue to demonstrate health effects attributed to multiple sources and PM components
including combustion activities (e.g., motor vehicle emissions, coal combustion, oil
burning, power plants, and wood smoke/vegetative burning), crustal sources, and
secondary sulfate. Toxicological studies examined various source categories and found
that no source consistently showed the strongest association with cardiovascular health
effects. Additionally, an examination of a number of PM2.5 components found
associations with various components and both cardiovascular and respiratory endpoints.
• Only a few recent epidemiologic studies have examined health effects of short- and
long-term exposures to coarse particles (PM'10-2.5)- A short-term exposure and
respiratory emergency department visits (ED) visits study found a positive and
significant association with pediatric asthma ED visits in Atlanta, GA. One long-term
exposure and mortality study did not find any evidence of an association with all-cause
mortality though there was a positive but not statistically significant association with
coronary heart disease (CHD) mortality.
IX
-------
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 (77 FR 38890), EPA has prepared the Integrated
Science Assessment for Particulate Matter (hereafter 2009 PM ISA) which reviewed,
summarized, and integrated the latest scientific knowledge useful in indicating the kind and
extent of all identifiable effects on public health or welfare that may be expected from the
presence of PM in the ambient air in varying quantities, as required by section 108 of the Clean
Air Act (CAA) (U.S. EPA. 2009). As noted in the PM proposal,1 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 2009 PM ISA (U.S. EPA. 2009). 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. The purpose of this report is to present the findings of
EPA's survey and provisional assessment of potentially relevant recent studies on the health
effects of PM exposure. This provisional assessment will inform a decision by the EPA
Administrator to proceed with final rulemaking or to revise the ISA to include the new studies.
This provisional assessment is focused on those studies most important to the major conclusions
presented in the 2009 PM ISA and most relevant to the considerations of the current review of
the PM NAAQS. EPA, therefore, identified potentially relevant studies by applying the
following selection criteria to those studies published through August 2012: (1) epidemiologic
studies that used PM2.5 (i.e., fine PM) or PMio-2.s (i.e., coarse PM) and were conducted in the U.S.
or Canada, and (2) toxicological or epidemiologic studies that compared effects of PM from
different sources, PM components, or size fractions. In addition, we considered studies identified
by public comments submitted to the docket of the proposed rule. Studies that met these criteria
were evaluated by EPA staff and their key findings were summarized. This preliminary
assessment was then developed to place those new studies of potentially greatest relevance in the
context of the findings of the 2009 PM ISA including a judgment as to whether the new studies
materially change the major conclusions of the 2009 PM ISA. 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 ISA.
The literature search and submissions from public commenters found that more than 1,500
studies have been published since the ISA closed on the health effects of particulate matter.
1 As stated in the PM NAAQS proposal: "The EPA is aware that a number of new scientific studies on the health
effects of PM have been published since the mid-2009 cutoff date for inclusion in the Integrated Science
Assessment. As in the last PM NAAQS review, the EPA intends to conduct a provisional review and assessment of
any significant new studies published since the close of the Integrated Science Assessment, including studies that
may be submitted during the public comment period on this proposed rule in order to ensure that, before making a
final decision, the Administrator is fully aware of the new science that has developed since 2009. In this provisional
assessment, the EPA will examine these new studies in light of the literature evaluated in the Integrated Science
Assessment. This provisional assessment and a summary of the key conclusions will be placed in the rulemaking
docket." (77 FR 38899)
-------
Application of the selection criteria resulted in a list of over 100 studies that are summarized in
the main body of this report. Additional details of the air quality distributions observed in these
studies can be found in the annex to this report. The most significant studies are discussed in the
assessment, and where feasible, quantitative results are compared to those from the 2009 PM
ISA. A comprehensive list of studies identified as being potentially relevant through the survey
effort, including those studies not discussed in detail in this report can be found here:
http://hero.epa.gov/pm . Studies not discussed in detail include controlled human exposure
studies, and toxicological studies that examined health effects attributed to specific PM size
fractions, as well as studies that focused on ultrafine particles.
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 PMio-2.5; (2) epidemiologic studies on
effects associated with short-term PM exposure, again focusing on U.S. and Canadian studies
with measurements of PM2.5 or PMio-2.s; and (3) toxicological and epidemiologic studies that
have evaluated health effects with exposure to PM components and PM from different sources.
This last section includes results of studies that assessed the effects of a range of PM sources or
components, including those using source apportionment methods or comparing effects for
numerous PM components, and not on studies of individual components. Most studies have
focused on components or sources of PM2.s, but information related to sources of PMi0-2.5 was
also included to the extent available. Unless otherwise noted, the majority of new studies
included in this assessment did not examine the robustness of single-pollutant results in
copollutants models.
2. OVERVIEW OF RECENT HEALTH STUDIES RESULTS
As stated in the 2009 PM ISA, EPA integrated the scientific evidence from toxicological,
controlled human exposure, and epidemiologic studies in combination with evidence from
atmospheric chemistry and exposure assessment studies and developed causal determinations for
health outcomes categories (e.g., respiratory effects, cardiovascular effects, mortality, etc.) for
different exposure durations (i.e., short- or long-term) and PM size fractions. Causal judgments
drawn for short- and long-term exposure to PM2.5 and short-term exposure to PMio-2.5 are
included in Table 2.1.
-------
Table 2.1. Causal Determinations for Short-and Long-Term Exposure to PM2.5
Long-term Exposure to PM2.s
Size Fraction
PM2.5
Outcome
Cardiovascular Effects
Respiratory Effects
Mortality
Reproductive and Developmental
Cancer, Mutagenicity, and Genotoxicity
Causality Determination
Causal
Likely to be causal
Causal
Suggestive
Suggestive
Short-term Exposure to PM2.s
Size Fraction
Outcome
Causality Determination
Cardiovascular Effects
PM2
Respiratory Effects
Mortality
Causal
Likely to be causal
Causal
Short-term Exposure to
Size Fraction
Outcome
Causality Determination
Cardiovascular Effects
PM-IO-2.5
Respiratory Effects
Mortality
Suggestive
Suggestive
Suggestive
The following sections of this document summarize the scientific evidence published since the
completion of the 2009 PM ISA for each of the health outcome categories presented in Table 2.1.
2.1. Epidemiologic Studies of Long-Term Exposure
The majority of the epidemiologic evidence evaluated in the 2009 PM ISA (U.S. EPA, 2009)
focused on health effects of PM2.5 exposure, with very limited evidence for health effects of
long-term exposure to PMio-2.5. These studies demonstrated consistent positive associations
between long-term PM2.5 exposures and a variety of health effects (Chapter 7, (U.S. EPA, 2009)).
Sections 2.1.1 -2.1.4 highlight results from epidemiologic studies of mortality, cardiovascular
effects, respiratory effects, and reproductive and developmental effects, respectively, published
since the completion of the 2009 PM ISA (U.S. EPA, 2009) because these were the health
outcomes specifically taken into consideration in developing the proposed rule (77 FR 38890).
Tables A.I through A.5 (Appendix A) summarize the recent epidemiologic studies that evaluated
-------
relationships between health effects and long-term exposure to PM2.5 and PMio-2.5- The
discussions below emphasize results of studies conducted in the U.S. and Canada.
2.1.1. Mortality
Long-term exposure to PM2.5
Summary of 2009 PM ISA Conclusions
The 2009 PM ISA synthesized the epidemiologic literature characterizing the association
between long-term exposure to PM2.5 and increased risk of mortality and concluded that "a
causal relationship exists between long-term exposure to PM2.5 and mortality" (See Section 7.6
of the 2009 PM ISA). Long-term mean2 PM2 5 concentrations ranged from 13.2 to 32.0 |ig/m3
during the study periods in the areas in which these studies, comprising the entire body of
evidence reviewed in the 2009 ISA, were conducted. When evaluating cause-specific mortality,
the strongest evidence contributing to this causal determination was observed for associations
between PM2 5 and cardiovascular mortality. Positive associations were also reported between
PM2.s and lung cancer mortality. Both the Harvard Six Cities (Laden et al., 2006; Dockery et al.,
1993) and the American Cancer Society (ACS) (Krewski, 2009: Pope III et al.. 2004: Pope et al..
2002) studies continued to provide strong evidence for the associations between long-term
exposure to PM2 5 and cardiopulmonary disease (CPD) and ischemic heart disease (MD)
mortality. Additional evidence from a study that used the Women's Health Initiative (WHI)
cohort (Miller et al., 2007) found a particularly strong association between long-term exposure to
PM2 5 and cardiovascular disease (CVD) mortality in post-menopausal women.
Recent Mortality Studies
Since the completion of the 2009 PM ISA (U.S. EPA, 2009), a number of studies have been
published that examined the association between long-term exposure to PM2.5 and all-cause
mortality (See Figure 2.1) and cause-specific mortality (See Figures 2.2 and 2.3), including
updated results for both the Harvard Six Cities and ACS cohorts. Lepeule et al. (2012) extended
the analysis of the Harvard Six Cities cohort using 11 additional years of follow-up and PM2.5
monitoring data and explored a variety of issues that might affect the size and timing of the
mortality effect. Generally, the authors observed results similar to those reported by Laden et al.
(2006) for all-cause and cardiovascular mortality, though the central estimate was slightly
diminished and had slightly narrower confidence intervals (all-cause mortality: RR=1.14 [95%
CI: 1.07, 1.22]3 for Lepeule etal. (2012) versus RR= 1.16 [95% CI: 1.07, 1.26] for Laden etal.
(2006): cardiovascular mortality: RR=1.26 [95% CI: 1.14, 1.40] for Lepeule et al. (2012) versus
RR=1.28 [95% CI: 1.13, 1.44] for Laden et al.(2006). The authors applied both spline and linear
2 For long-term exposure studies, the long-term mean PM2 5 concentration refers to the average PM2 5 concentrations
reported across the entire study duration, which could equate to the monthly or annual PM2 5 concentration averaged
over many years.
3 All effect estimates for associations between long-term exposure to PM2 5 and mortality are presented for a 10
ug/m3 increase in PM2 5 concentration.
-------
models to investigate the concentration-response relationship, and observed that for all-cause
mortality, the model fit was better without the spline, indicating a no threshold, linear
relationship with PM2.5 down to the lowest observed concentration (i.e., 8 |ig/m3). Jerrett et al.
(2009a) reanalyzed data from the ACS cohort, including data from 86 metropolitan statistical
areas (MSAs) across the U.S with monitoring data for PM2.5. The authors observed an
association between PM2.5 and all-cause mortality in single pollutant models (RR 1.048 [95% CI:
1.024, 1.071]) that increased in magnitude in a copollutant model adjusting for ozone (Os)
concentration (RR 1.080 [95% CI: 1.048, 1.113]). The associations were stronger when limited
to mortality due to cardiovascular disease (CPD mortality: RR 1.129 [95% CI: 1.094, 1.071];
CVD mortality: RR 1.150 [95% CI: 1.111, 1.191]; IHD mortality: RR 1.211 [95% CI: 1.156,
1.268]); these associations also became stronger in copollutant models adjusting for Os
concentration. No statistically significant association was observed between PM2 5 and
respiratory mortality in this re-analysis of the ACS cohort. In another analysis among the ACS
cohort, McKean-Cowdin et al. (2009) examined the association between long-term exposure to
PM2.5 and brain cancer mortality. The authors observed no associations with brain cancer
mortality.
-------
McDonnell et al (2000)
Enstrom (2005)
Krewskietal. (2009)
Puettetal. (2011)
Ostro et al. (2009)
Laden etal. (2006)
Lepeuleetal. (2012)
Lipsettetal. (2011)
Jerrett et al. (2009)
Lipfertetal. (2006)
Eftim et al. (2008)
Hartetal. (2010)
Krewskietal. (2009)
Goss et al. (2004)
Puettetal. (2009)
Zegeretal. (2008)
Crouse etal. (2012)
^-UlIUI I
AH SMOG
CA Cancer Prevention
ACS-LA
ACSReanalysisII-LA
Health Prof
CA Teachers
Harvard 6-Cities
Harvard 6-Cities
CA Teachers
ACS
Veterans Cohort
Medicare Cohort
US Trucking
ACSReanalysisII
U.S. Cystic Fibrosis
Nurses Health
MCAPS
itrais i
1973 1977
1973-1982
1983-2002
1973-2002
1982-2000
1982-2000
1986-2002
2002-2007
1974-1998
1974-2009
1999-2005
1982-2000
1989-1996
1997-2001
2000-2002
1985-2000
1982-2000
1992-2002
2000-2005
viemi
23.4
___
21
21
17.8
17
16.4
15.9
15.6
14.3
14.3
14.3
13.6
14 1
14.1
14.0
i a -7
1 j . 1
13.9
13.2
ACS ReanalvsisII -NYC1982-2000
CanadianNational 1991-2001
9.4
8.9
8.7
nuics
Males
-i
1 ten A
Women —
Women
ACS Sites
6-Cities sites
Men
Women
65+, Eastern
65-74, Eastern
75-84, Eastern
85+, Eastern
65+, Central
65-74, Central
75-84, Central
85+, Central — 4
65+, Western -•
65-74, Western -•-
75-84, Western H
85+, Western -t
AllCau
»-
•-
A
A
\
-A-
•
-•-
• to
\
— •—
0
-0-
«-
— • —
9
— • —
i —
i—
1 1 cities; rem ote sensing -A-
1 1 cities; monitoring data
Nationwide; remote sensing
— A —
*
0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.
Effect Estimate
Figure 2.1. All-cause mortality risk estimates, long-term exposure to PM2.5 in recent cohort studies. Red text and triangles represent
new studies published since the completion of the 2009 PM ISA.
-------
Study
Popeetal. (2004)
Laden etal. (2006)
Lepeuleetal. (2012)
Lipsettetal. (2011)
Jerrett et al. (2009)
Hart etal. (2010)
Miller et al. (2007)
Crouse etal. (2012)
Chen etal. (2005)
Puett etal. (2011)
Puett etal. (2009)
Gan etal. (2011)
Jerrett etal. (2005)
Krewskietal. (2009)
Popeetal. (2004)
Ostro eta 1(2009)
Lipsettetal. (2011)
Jerrett et al. (2009)
Hart etal. (2010)
Krewskietal. (2009)
Crouse etal. (2012)
McDonnell etal. (2000)
Jerrett etal. (2005)
Krewskietal. (2009)
Ostro eta 1(2009)
Jerrett et al. (2009)
Krewskietal. (2009)
Cohort
ACS
Harvard 6-Cities
Harvard 6-Cities
CA Teachers
ACS
US Trucking
WHI
Canadian National
AHSMOG
Health Prof
Nurses Health
Vancouver,BC
ACS-LA
ACSReanalysisII
ACS
CA Teachers
CA Teachers
ACS
US Trucking
ACSReanalysisII
Canadian National
AHSMOG
ACS-LA
ACSReanalysisII
CA Teachers
ACS
ACSReanalysisII
Years
1982-2000
1974-1998
1974-2009
1999-2005
1982-2000
1985-2000
1994-1998
1991-2001
1973-1998
1986-2002
1992-2002
1999-2002
1982-2000
1982-2000
1982-2000
2002-2007
1995-2005
1982-2000
1985-2000
1982-2000
1991-2001
1973-1977
1982-2000
1982-2000
2002-2007
1982-2000
1982-2000
Mean
17.1
16
15.9
15.6
14.3
14.1
13.5(12.9)*
8.7
29
17.8
13.9
4.08
21
21
17.1
17
15.6
14.3
14.1
14.02
8.7
32
21
21
17
14.3
14.02
Notes
Women —
Men —
Females
Females
j^a JG[. 0
Cause
cv
-•-
A
-A
-A-
-A
CHD
Men A
Women
Women
Women
Nationwide
Women
Nationwide
IHD
• b.
CPD
A,
-A-
-•-
0.5
1 1.5 2
Effect Estimate
2.5
Figure 2.2. Cardiovascular mortality risk estimates, long-term exposure to PM2.5 in recent cohort studies. Red text and triangles
represent new studies published since the completion of the 2009 PM ISA. * As discussed in Federal Register Notice of EPA's
proposed rule on the PM NAAQS (77 FR at 38929 and 38934 n. 82). CV = cardiovascular disease, CHD = coronary heart disease,
IFID = ischemic heart disease, CPD = cardiopulmonary disease.
-------
Study
Laden etal. (2006)
Lipsettetal. (2011)
Jerret et al. (2009)
Hart etal. (2010)
Cohort
Years Mean
Notes
Harvard 6-Cities 1974-1998
CA Teachers 1999-2005
ACS 1982-2000
US Trucking 1985-2010
McDonnell etal. (2000) AHSMOG 1973-1977
Jerrett etal. (2005) ACS-LA 1982-2000
Krewskietal. (2009) ACS ReanalysisII 1982-2000
Laden etal. (2006) Harvard 6-Cities 1974-1998
Lipsettetal. (2011) CA Teachers 1999-2005
Lepeule etal. (2012) Harvard 6-Cities 1974-2009
Hart etal. (2010) US Trucking 1985-2000
Krewskietal. (2009) ACS ReanalysisII 1982-2000 14.02
Krewskietal. (2009) ACS ReanalysisII 1982-2000
0.5
Respiratory
1U
15.6
14.3
14.1
32
21
21
16
15.6
15.9
14.1
4.02
Women
T A
Nationwide
"MVP A
IN 1 ^ W
V
V
A
A-
A
Lung Cancer
A
\
1 1.5
Effect Estimate
2.5
Figure 2.3. Respiratory mortality risk estimates, long-term exposure to PM2.5 in recent cohort studies. Red text and triangles represent
new studies published since the completion of the 2009 PM ISA.
-------
In an update to a study by Janes et al. (2007), Greven et al. (2011) used data from a nationwide
Medicare mortality cohort to develop a statistical approach for estimating the associations
between monthly mean PM2.s concentrations averaged over the preceding 12 months and
monthly mortality rates among subjects living within ZIP codes with a geographic centroid
within a six mile radius of one of 814 monitoring stations from 2000 to 2006. The study authors
decomposed the association between PM2.5 and mortality into two components: (1) the
association between the "national" trend in the monthly PM2.5 concentrations averaged over the
previous 12 months and the national average trend in monthly mortality rates (purely temporal
association); and (2) the association between the "local" trend in the deviation in the
community-specific trend from the national average trend of monthly averages of PM2.5 and the
deviation of the community-specific trends from the national average trend of mortality rates
(residual spatio-temporal association). The authors posit that this second component provides
evidence as to whether locations having steeper declines in PM2.5 also have steeper declines in
mortality relative to the national trend. The authors conclude that differences in effect estimates
at these two spatiotemporal scales raise concerns about confounding bias in these analyses, with
the association for the national trend more likely to be confounded than the association for the
local trend. The authors observed no evidence for a "local" effect, but did observe evidence for a
"national" effect. Similar to the study by Janes et al. (2007), Greven et al. (2011) eliminate all of
the spatial variation in air pollution and mortality in their data set when estimating the "national"
effect, focusing instead on sub-chronic (monthly) temporal differences in the data. As noted by
the authors, this eliminates 90% of the variance in the data set used for these analyses that is
attributable to spatial variability (Janes et al. (2007), Table 1). Only 5% of the variance in the
data set used in these analyses is attributable to the space by time component, which was the
focus of the papers by Janes et al. (2007) and Greven et al. (2011). Thus, while the results of the
papers themselves provide evidence for an association between exposure to PM2.5 and mortality,
it is not possible to directly compare the results of these studies to the results of other cohort
studies investigating the relationship between long-term exposure to PM2.5 and mortality, which
make use of spatial variability in air pollution and mortality data. As noted by Pope and Burnett
(2007) and highlighted in the 2009 PM ISA (Section 7.6.1, (U.S. EPA, 2009)), the conclusions of
Janes et al. (2007) "largely excludes the sources of variability that are exploited in those other
[cohort] studies." These comments are also applicable to the study by Greven et al. (2011).
Grouse et al. (2012) conducted a nationwide study of the relationship between long-term
exposure and PM2.5 in Canada and provide new evidence for a positive association at relatively
low concentrations of PM2.5. The authors investigated the association between long-term
exposure to ambient PM2.5 and non-accidental mortality. The level of ambient PM2.5 to which the
study population was exposed was estimated from satellite observations and assigned to the
cohort of 2.1 million Canadian adults that completed detailed census data in 1991. The study
included deaths between 1991 and 2001. The authors observed a hazard ratio (HR) of 1.15 (95%
CI: 1.13, 1.16) for non-accidental mortality. Using spatial random-effects models, the HR was
slightly diminished (1.10 [95% CI: 1.05, 1.15]). The strongest association was observed for
-------
deaths due to ischemic heart disease (HR: 1.31 [95% CI: 1.27, 1.35]). Using spatial random-
effects models did not substantially change the association (HR: 1.30 [95% CI: 1.18, 1.43]). The
associations between PM2 5 and deaths due to CVD and circulatory diseases were similar in
magnitude to that observed for non-accidental mortality. There was a weaker association with
mortality due to cerebrovascular disease (CBD) (HR: 1.04 [95%CI; 0.99, 1.10]). Sensitivity
analyses including 11 Canadian cities with ground-based PM2.5 measurements produced similar
associations to those observed in the full cohort that utilized satellite observations to estimate
PM2.5 exposure (See Figure 2.1).
A number of studies have looked at the association between long-term exposure to ambient
PM2.5 and all-cause mortality among different occupational cohorts. Hart et al. (2010) examined
the association between residential exposure to PM2 5 and mortality among men in the U.S.
trucking industry. The authors observed a 10% (95% CI: 2.5, 18) increase in all-cause mortality.
This association was stronger when the cohort was restricted to truck drivers that maintained
local routes, and long haul drivers were excluded (15% increase [95% CI: 5.0, 26.6] for all-cause
mortality; 59.7% increase [95% CI: 18.7, 114.9%] for respiratory mortality). The associations for
other causes of death (i.e., lung cancer, CVD, IHD, chronic obstructive pulmonary disease
[COPD]) were generally positive, but were not statistically significant. Puett et al. (2009)
examined the relationship of long-term PM2.5 exposures with all-cause mortality among women
from the Nurses' Health Study. The authors found an increased risk of all-cause mortality (HR
1.26 [95% CI: 1.02, 1.54]) and coronary heart disease (CHD) mortality (HR 2.02, 95% CI: 1.07,
3.78) associated with long-term exposure to PM2.5. More recently, Puett et al. (2011) used the
same spatiotemporal exposure estimation models to characterize the association between long-
term exposure to PM2.5 and mortality among male subjects in the Health Professionals Follow-up
Study. In this cohort, long-term exposure to PM2.5 was not associated with all-cause or CHD
mortality. Ostro et al. (2010) examined the association between long-term exposures to PM2.5 and
all-cause, CPD, IHD and pulmonary disease mortality among the subjects from the California
Teachers Study. No associations were observed between all-cause mortality and PM2.5. There
was a positive association between long-term exposure to PM2.5 and CPD mortality (HR: 1.19
[95% CI: 1.05, 1.37]) and IHD mortality (HR: 1.56 [95% CI: 1.24, 1.94]). In a follow-up study,
Lipsett et al. (2011) examined the associations between long-term exposure to PM2 5 and all-
cause and cause-specific mortality among the subjects in the California Teachers Study. The
authors did not observe an association between long-term exposure to PM2 5 and all-cause
mortality in this cohort, but observed an association with IHD mortality (HR 1.20 [95% CI: 1.02,
1.41]). They also observed positive associations for respiratory mortality and CBD mortality,
though these associations were not statistically significant.
In a single-city study conducted in Toronto, Ontario, Canada, Jerrett et al (2009b) examined the
association between long-term exposure to PM2.5 and all-cause mortality among subjects from a
respiratory clinic. The authors observed positive, though not statistically significant associations
with all-cause, circulatory or respiratory mortality. A limited number of deaths in the cohort and
low variability in PM2 5 concentrations (limiting the exposure contrast) led the authors to
10
-------
conclude that "no definitive conclusions [could] be drawn about these associations with PM2.5".
In a single-city study conducted in Vancouver, British Columbia, Canada, Gan et al. (2011)
conducted a population-based cohort study to evaluate the association between traffic-related
pollutants and risk of mortality due to CHD. Land-use regression models were used to estimate
exposure over a 5 year period (1994-1998) and the cohort was followed up for 4 years (1999-
2002). Exposure to PM2.5 was weakly associated with CHD mortality.
Recent studies that examined the association between long-term PM2.5 exposure and mortality
further support the conclusions of the 2009 PM ISA. The strongest evidence for mortality was
from the Harvard Six Cities (Laden et al., 2006; Dockery et al., 1993) and American Cancer
Society cohorts (Krewski, 2009; Pope III et al., 2004; Pope et al., 2002), which was supported by
a number of other cohort studies. Updated results from the Harvard Six Cities (Lepeule et al.,
2012) and American Cancer Society (Jerrett et al., 2009a) cohorts support the findings of the
2009 PM ISA, while a new Canadian multicity study (Grouse et al., 2012) observed associations
below those reported in the PM ISA (i.e., < 10 |ig/m3). In the 2009 PM ISA, for cause-specific
mortality, the strongest evidence was for cardiovascular-related mortality, particularly among
post-menopausal women (Miller et al., 2007). Respiratory-related mortality was also observed,
particularly for lung cancer mortality (Naess et al., 2007). Recent studies provide more evidence
for strong associations with cardiovascular-related mortality among women (Lipsett et al., 2011;
Puett et al., 2009) and additional evidence for respiratory mortality including lung cancer
mortality (Lepeule et al., 2012).
Long-term exposure to PM 10-2.5
Summary of 2009 PM ISA Conclusions
The 2009 PM ISA synthesized the epidemiologic literature characterizing the association
between long-term exposure to PMi0-2.5 and increased risk of mortality and concluded that the
evidence was too limited to adequately characterize the associations for PMio-2.5- The findings
from the AHSMOG (Chen et al., 2005) and Veterans (Lipfert et al., 2006) cohort studies
provided limited evidence for associations between long-term exposure to PMio-2.5 and mortality
in areas with mean concentrations in the range of 16 to 25 |ig/m3. Overall, the evidence was
determined to be inadequate to determine if a causal relationship exists between long-term
exposure to PMio-2.5 and mortality (See Section 7.6 of the 2009 PM ISA). Recent studies
published since the completion of the 2009 PM ISA are characterized in Table A.I.
Recent Mortality Studies
Since the completion of the 2009 PM ISA, Puett et al. (2009) examined the relationship of long-
term exposure to PMio-2.5 with all-cause and CHD mortality among women from the Nurses'
Health Study. The authors did not find an association between PMio-2.5 and the risk of all-cause
mortality (HR 1.03 [95% CI: 0.89, 1.18]). The association between PMi0-2.5 and CHD mortality
was positive, but not statistically significant (HR: 1.14 [95% CI: 0.73, 1.77]). More recently,
Puett et al. (2011) used the same spatiotemporal exposure estimation models to characterize the
11
-------
association between PMio-2.5 and mortality among male subjects in the Health Professionals
Follow-up Study. In this cohort, long-term exposure to PMio-2.5 was not associated with all-cause
or CHD mortality.
In summary, two new studies (Puett et al., 2011; Puett et al., 2009) evaluated the association
between long-term exposure to PMio-2.5 and mortality. The long-term mean PMio-2.5
concentrations reported in these studies were lower than those reported in the 2009 PM ISA (7.7
and 10.1|ig/m3, respectively). These studies do not provide any additional evidence for an
association between long-term exposure to PMio-2.5 and mortality that would be sufficient to
materially change conclusions made in the 2009 PM ISA.
2.1.2. Morbidity - Cardiovascular Effects
Summary of 2009 PM ISA Conclusions
The 2009 PM ISA concluded that "the evidence from epidemiologic and toxicological studies is
sufficient to conclude that a causal relationship exists between long-term exposures to PM2.s and
cardiovascular effects." The strongest evidence was provided by large, multicity, U.S.-based
studies of cardiovascular mortality (See Section 7.2.10 of the 2009 PM ISA) with supporting
evidence from a U.S.-based epidemiologic study (Miller et al. (2007)) that reported associations
between PM2.s and incident stroke and myocardial infarction (MI) among post-menopausal
women at mean PM2.5 concentrations of 13.5 |ig/m3.4
Recent Cardiovascular Morbidity Studies
Several new studies of long-term exposure to PM2.5 and cardiovascular disease were conducted
since the completion of the 2009 PM ISA. In a study of male subjects enrolled in the Health
Professionals Follow-Up Study, Puett et al. (2011) used spatiotemporal models to estimate
exposure to PM2.5 by combining data from available air monitoring networks with geographic
information system (GIS) derived variables such as distance to roadway and elevation. The
authors reported no association between long-term PM2.s and total CVD or ischemic stroke;
however, in fully adjusted models (i.e. adjusted for covariates including body mass index (BMI),
hypertension, hypercholesterolemia, diabetes, family history of MI, smoking physical activity,
diet) elevated HRs for non-fatal MI and hemorrhagic stroke were observed (HR: 1.16 [95% CI:
0.81, 1.64] and 1.69 [95%CI: 0.59, 3.71])5. Associations of PM2.5 with all-cause mortality and
fatal CHD were not observed in this all male cohort. A cross-sectional study of male and female
patients attending a pulmonary clinic after reporting respiratory complaints reported no
associations of long-term PM2.s exposure with prevalent IHD, although an association with
nitrogen dioxide (NO2) was reported (Beckerman et al., 2012). Interactions among exposures,
risk factors and potential confounders were tested and no statistically significant effect modifiers
4 Listed as 12.9 ug/m3 for the reasons stated in Federal Register Notice of EPA's proposed rule on the PM NAAQS
(77 FR 38934 n. 82).
5 All effect estimates for associations between long-term exposure to PM2 5 and cardiovascular morbidity are
presented for a 10 ug/m3 increase in PM2 5 concentration.
12
-------
were identified. A study using satellite derived aerosol optical depth (AOD) measurements to
predict PM2.5 concentrations, reported a 3.12% (95% CI: 0.30, 4.29) increase in cardiovascular
hospital admission among older adults for an increase in long-term PM2.5 exposure (Kloog et al.,
2012a). A similar increase in risk was reported for stroke hospital admissions (3.49 [95% CI:
0.09,5.18]).
The stronger evidence linking long-term PM2.5 exposure with cardiovascular disease was
apparent in studies of women as originally demonstrated in the 2009 PM ISA. In a study of
female teachers residing in California, Lipsett et al. (2011) used concentration data from 1999-
2000 and applied inverse distance weighted interpolation techniques to develop monthly PM2.5
concentration surfaces from ambient monitor data. This study reported an increased risk for
incident stroke (HR: 1.15 95% CI 1.00-1.33), which was highest among post-menopausal
women, but no association between PM2.5 and incident MI (HR: 0.99 95% CI 0.84-1.15). This
study supports the findings of Miller et al. (2007) linking incident stroke to long-term PM2 5
exposure among post-menopausal women; however, they also reported an association with
incident MI. Coogan et al. (2012) followed African American women who ranged in age from 21
to 69 years at enrollment in the Black Women's Health Study for 10 years to investigate incident
hypertension and diabetes in association with long-term exposure to PM2 5. PM2 5 concentrations
were spatially interpolated using monitoring data from state and local stations in the Los Angeles
basin for the year 2000. This study reported an increased risk of incident hypertension (IRR: 1.48
95%CI: 0.95-2.31). This risk was attenuated, but remained positive in a copollutant model
containing NO2 (IRR: 1.32 95%CI: 0.84-2.05).
Several studies have been published from the Multi-Ethnic Study of Atherosclerosis (MESA)
that was designed to inform on mechanistic pathways by which PM2 5 exposure may act on the
cardiovascular system. Long-term PM2 5 exposure was associated with increased prevalent QT
prolongation (OR: 1.6 95% CI: 1.2-2.2) and intraventricular conduction delay (OR: 1.7 95% CI
1.0-2.6) (Van Hee et al., 2011). In addition, both long- and short-term PM2.s exposure was
associated with a narrowing of retinal vessel diameter (Adar et al., 2010). Reductions in flow-
mediated dilation have been observed in association with short-term exposures to PM2 5 (See
Section 6.2.4 of the PM ISA); however, O'Neill et al. (2011) found no association of long-term
PM2.s exposure with chronic arterial stiffness.
Generally, the results of recent studies are consistent with the evidence for an association
between long-term exposure to PM2 5 and cardiovascular morbidity characterized in the 2009 PM
ISA. Findings on incident stroke reported by Miller et al (2007) in a cohort of post-menopausal
women are supported by a new study of female teachers (Lipsett et al., 2011), while a recent
study of black women reports an association between PM2 5 and incident hypertension (Coogan
et al., 2012) at long-term mean PM2 5 concentrations ranging from 15.6-21.5 |ig/m3 (Table
A.3).
13
-------
2.1.3. Morbidity - Respiratory Effects
Summary of 2009 PM ISA Conclusions
The epidemiologic evidence reviewed in the 2009 PM ISA demonstrated associations between
long-term exposure to PM2.5 and decrements in lung function growth, increased respiratory
symptoms, and asthma development in study locations with mean PM2.5 concentrations ranging
from 13.8 to 30 |ig/m3 during the study periods (See Sections 7.3.1.1 and 7.3.2.1 of the 2009 PM
ISA). These studies contributed to a body of evidence that was sufficient to conclude that "a
causal relationship is likely to exist between long-term exposures to PM2 5 and respiratory
effects."
Recent Respiratory Morbidity Studies
Since the completion of the 2009 PM ISA, a number of studies have been published that examine
the association between long-term exposure to PM2 5 and respiratory outcomes (Table A.4).
These recent studies are consistent with the associations observed for respiratory outcomes
reported in the 2009 PM ISA and provide additional evidence for associations between long-term
exposure to PM2 5 and respiratory symptoms and asthma development. For example, in a recent
prospective community intervention study in Libby, MT (Noonan et al., 2012) ambient PM2 5
concentrations decreased by 26.7% over four winters following the replacement of over 1,100
wood stoves in the community with new lower emission wood stoves or other heating sources.
This decrease in PM2.5 concentrations was associated with decreases in reported wheeze and
respiratory infections (including colds, bronchitis, influenza and throat infection) among school
children. These results suggest that beneficial health impacts are associated with decreases in
ambient PM2.5 concentrations.
A number of other studies evaluated the association between long-term exposure to PM2 5 and
respiratory symptoms. Several nationwide U.S. studies that used data from the National Health
Interview Survey reported associations between long-term exposure to PM2 5 and respiratory
symptoms among children (including respiratory allergy/hay fever (Parker et al., 2009), and
respiratory allergy and frequent ear infections (Bhattacharyya and Shapiro, 2010) and adults
(including asthma among African-Americans (Nachman and Parker, 2012): sinusitis (Nachman
and Parker. 2012: Bhattacharvva. 2009): and hay fever (Bhattacharvva. 2009). Meng et al.
(2010) examined long-term exposure to PM2.5 in the San Joaquin Valley of California and
weekly asthma symptoms among participants with physician-diagnosed asthma. They observed
associations between annual average concentrations of PM2.5 and frequent asthma symptoms. In
a study conducted in New York City, Patel et al. (2009) examined long-term exposure to PM2.5
and respiratory symptoms in children through 24 months of age. Long-term exposure to PM2.5
was not associated with wheeze or cough in this study, though several PM2 5 constituents were
associated with wheeze and/or cough (see Section 2.4.2 for results on PM2 5 constituents).
A substantial body of evidence exists that has evaluated short-term exposure to PM2.5 and
emergency department visits and hospitalizations for respiratory causes (See Section 2.2.2.1).
14
-------
Several recent studies have evaluated the association between long-term exposure to PM2.5 and
respiratory hospitalizations. Karr et al. (2009a; 2009b) examined exposure to PM2.5 averaged
over an infant's lifetime (0-12 months) and did not observe an association between PM2.5 and
bronchiolitis hospitalizations in the Puget Sound Region of Washington (Karr et al., 2009a) or in
the Georgia Air Basin of British Columbia, Canada (Karr et al.. 2009b). Kloog et al. (2012a)
investigated hospital admissions for all respiratory causes among residents of New England 65
years of age and older. The authors observed a 4.22% (95% CI 1.06, 4.75)6 increase in
respiratory hospital admissions associated with long-term PM2 5 concentrations. Similarly,
Neupane et al. (2010) restricted their analyses of pneumonia hospitalizations to those 65 years of
age and older and found that long-term exposure to PM2 5 was associated with hospitalization for
community-acquired pneumonia (OR 13.64, 95% CI: 1.79, 101.01). Meng et al. (2010)
examined long-term exposure to PM2 5 in the San Joaquin Valley of California and asthma-
related emergency department visits or hospitalizations (analyzed together) among participants
with physician-diagnosed asthma. They observed associations between annual average
concentrations of PM2.5 and emergency department visits and hospitalizations.
The 2009 PM ISA identified a number of prospective cohort studies that provided evidence of an
association between long-term exposure to PM2 5 and the development of asthma. Recent studies
contribute to this weight of evidence, reporting results that are consistent with those summarized
in the 2009 PM ISA. Akinbami et al. (2010) conducted a nationwide U.S. study with data on
children (ages 3-17 years) from the National Health Interview Survey and observed a positive
association between county-wide annual average PM2.5 concentration and current asthma (OR
1.43, 95% CI: 0.98, 2.10 comparing highest quartile of exposure to lowest) and/or a recent
asthma attack (OR 1.30, 95% CI: 0.89, 1.90 comparing highest quartile of exposure to lowest).
Two studies examining the relationship between long-term exposure to PM2.5 and incident
asthma were conducted in British Columbia, Canada. Carlsten et al. (2011) evaluated birth year
exposure to PM2.5 and physician-diagnosed asthma at age 7 and observed an association with an
increased risk of incident asthma. Similarly, Clark et al. (2010) assigned exposure based on
average PM2.5 concentration during the first week of life and the association with incident asthma
between ages 3 and 4. The authors did not observe an association between PM2.5 and incident
asthma. McConnell et al. (2010) characterized the relationship between childhood incident
asthma and long-term exposure to PM2 5 among the Southern California Children's Health Study
participants. In this cohort, asthma-free kindergarten and first-grade children were followed up
for three years and the authors observed a positive association (HR 1.34, 95% CI: 0.95, 1.90),
though this association was diminished when the authors adjusted for traffic related pollution
concentrations measured near the child's home and school.
In summary, the results of recent studies generally continue to demonstrate an association
between long-term exposure to PM2.5 and respiratory morbidity. Recent epidemiologic studies
6 All effect estimates for associations between long-term exposure to PM2 5 and respiratory morbidity are presented
for a 10 ug/m3 increase in PM2 5 concentration.
15
-------
reported associations with respiratory symptoms and respiratory hospitalizations. New findings
on incident asthma among children are consistently positive, though not statistically significant.
These recent studies demonstrate associations at long-term mean PM2 5 concentrations ranging
from 9.7 to 27 |ig/m3 (Table A.4).
2.1.4. Morbidity - Reproductive and Developmental Effects
Summary of 2009 PM ISA Conclusions
The 2009 PM ISA synthesized the epidemiologic literature characterizing the association
between long-term exposure to PM2.5 and increased risk of reproductive and developmental
effects and concluded that the evidence was suggestive of a causal relationship between long-
term exposure to PM2.5 and reproductive and developmental outcomes (See Section 7.4 of the
2009 PM ISA). The strongest evidence was for reduced birth weight and infant mortality,
especially due to respiratory causes during the post-neonatal period. The mean PM2.5
concentrations during the study periods ranged from 5.3 - 27.4 |ig/m3, with effects becoming
more precise and consistently positive in locations with mean PM2.5 concentrations of 15 |ig/m3
and above. The epidemiologic literature did not consistently report associations between long-
term exposure to PM2 5 and preterm birth, growth restriction, birth defects or decreased sperm
quality.
Recent Reproductive and Developmental Outcome Studies
Since the completion of the 2009 PM ISA, a number of studies have been published that examine
the association between long-term exposure to PM2.5 and reproductive and developmental
outcomes (Table A.5). These recent studies are consistent with the associations observed for
reproductive and developmental outcomes reported in the 2009 PM ISA, within similar
concentrations (long-term mean PM2 5 concentrations ranging from 11.0 - 19.8 |ig/m3), and
provide additional evidence for associations between long-term exposure to PM2.5 and reduced
birth weight (Ghosh et al., 2012; Kloog et al., 2012b; Kumar, 2012; Darrow et al., 201 Ib; Bell et
al., 2010; Morello-Frosch et al., 2010; Salihu et al., In Press). Recent evidence remains
inconsistent for the association between exposure to PM2 5 and preterm birth, with some studies
providing evidence for an association (Chang et al., 2012b; Wu et al., 2009), while others did not
(Rudra et al.. 2011; Darrow et al., 2009).
2.2. Epidemiologic Studies of Short-Term Exposure
The 2009 PM ISA included the results of many new epidemiologic studies reporting associations
between short-term exposure to PM and a range of health outcomes. The epidemiologic evidence
evaluated in the ISA contributed to the determination that there is sufficient evidence to conclude
that "a causal relationship exists" between short-term PM2.5 exposure and cardiovascular effects
and mortality, and a "likely to be causal relationship exists" between short-term PM2.5 exposure
and respiratory effects (Chapter 2, 2009 PM ISA). Additionally, the epidemiologic evidence
16
-------
contributed to a "suggestive" causal determination for short-term PMi0-2.5 exposure and
cardiovascular and respiratory effects, and mortality (Chapter 2, 2009 PM ISA).
Sections 2.2.1 and 2.2.2 highlight results from recent epidemiologic studies. Tables A.6 through
A. 11 (Appendix A) summarize results of recent epidemiologic studies that evaluated
relationships between health effects and short-term exposure to PM2.5 and PMio-2.5-
The 2009 PM ISA 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 studies of single cities. The
multicity studies also allowed investigation of homogeneity or heterogeneity of PM health
relationships, evaluation of confounding by co-pollutants across communities with different air
pollution mixtures, and assessment of potential effect modifiers. Since the completion of the
2009 PM ISA, numerous multicity analyses have been published that evaluate morbidity
outcomes.
2.2.1. Mortality
Summary of 2009 PM ISA Conclusions
Overall, in the evaluation of multi- and single-city studies in the 2009 PM ISA and in the 2004
PM Air Quality Criteria Document (AQCD) (U.S. EPA, 2004) consistent positive associations
were observed at mean 24-h average7 PM2.5 concentrations above 12.8 |ig/m3. This collective
evidence contributed to the conclusion that "a causal relationship exists between short-term
PM2.5 exposure and mortality." Building on the evidence presented in the 2004 PM AQCD (U.S.
EPA, 2004), multi- and single-city studies evaluated in the 2009 PM ISA reported consistent
positive associations between short-term PMio-2.5 exposure and mortality (Section 6.5.2.3, 2009
PM ISA).
Recent Mortality Studies
Several recent studies evaluated the effects of short-term exposure to PM2 5 on mortality in single
city analyses. No new multi-city studies have been published. Additionally, no new studies have
been published that examined associations between short-term PMio-2.5 exposure and mortality in
the U.S. or Canada.
New studies have continued to report associations between PM2.5 and mortality that are
consistent with the conclusions of the 2009 PM ISA as shown in Figure 2.4. Two of these studies
were conducted in New York City. Ito et al. (2011 a) examined the relationship between short-
term exposure to PM2.5 and PM components and cardiovascular disease (CVD) mortality for the
population > 40 years old in New York City for the years 2000-2006. PM2 5 was associated with
CVD mortality at lag 1 in the all-year and cold season (October-March) analyses, but the
strongest association with CVD mortality was observed during the warm season (April-
7 For short-term exposure studies the mean 24-h avg PM2 5 concentration refers to the mean of all daily 24-h avg
PM2.5 concentrations over the course of the study duration.
17
-------
September) at lag 0 and 1. Also in New York City, Chang et al. (2012a) used a novel approach to
examine the relationship between short-term exposure to PM2.5 concentrations and
cardiorespiratory mortality. The authors used a spatio-temporal deterministic model that was
bias-corrected with monitoring data to predict daily PM2 5 concentrations. The authors developed
a statistical model to consider personal exposure to PM2.5 from outdoor sources to improve
exposure assessment. Using data from 2001-2005, positive associations were observed for those
greater than 65 years old. The model that accounted for personal exposure found a higher risk of
mortality (2.32% [95% CI: 0.68, 3.94] at lag I)8 compared to a model that used only PM2.5
concentrations (1.13% [95% CI: 0.27, 2.00]) suggesting that risk estimates derived using ambient
concentrations as a proxy for exposure are biased towards the null.
Additional single-city analyses were conducted in Seattle, Detroit, and Atlanta. Zhou et al.
(2011) conducted a study using daily PM2.5 data collected in Seattle and Detroit to examine the
effect of short-term PM2 5 exposure on all-cause, cardiovascular, and respiratory mortality for the
years 2002-2004. In a distributed lag model of 0-2 days, a strong association was observed
between PM2 5 and all-cause and cardiovascular mortality, with some evidence of an association
with respiratory mortality in Detroit during the warm season (April-September) (quantitative
results not presented). There was no evidence of an association with PM2.s and any mortality
outcome in Seattle in the warm season. In the cold season (October-March), the strongest
associations were for all-cause and cardiovascular mortality in Seattle, while there was no
evidence of an association between PM2 5 and any mortality outcome in Detroit. Interestingly the
magnitude of the cardiovascular mortality association in Seattle in the cold season is larger than
that in Detroit in the warm season even though mean PM2.5 concentrations are lower, 11.4 |ig/m3
and 14.9 |ig/m3, respectively. Klemm et al. (2011) conducted an extended analysis of two
previously published studies (Klemm et al., 2004; Klemm and Mason, 2000) that examined the
effect of air pollution on mortality in Atlanta, GA. This analysis included an additional 7.5 years
of data and expanded the study location to include two additional counties. Focusing on deaths in
individuals 65 years of age and older, the authors found a positive association between short-
term PM2.5 exposure and nonaccidental (0.78% [95% CI: -0.43, 2.0]; lag 0-1 for a 10 |ig/m3
increase in 24-h avg PM2.5 concentrations) and cardiovascular mortality (0.83% [95% CI: -1.1,
2.8]), but no evidence of an association with respiratory mortality (-0.86% [95% CI: -4.4, 2.8]).
In summary, multi- and single-city studies evaluated in the 2009 PM ISA provided evidence of
consistent positive associations between short-term PM2.5 exposure and nonaccidental,
cardiovascular, and respiratory mortality. Relatively few mortality studies have been published
in the U.S. and Canada since the completion of the 2009 PM ISA and they are limited to single-
city studies. These studies continue to demonstrate evidence of positive associations between
short-term PM2.5 exposures and mortality in the same range of concentrations as those studies
8 All effect estimates for associations between short-term exposure to PM2 5 and mortality are presented for a 10
ug/m3 increase in PM2 5 concentration.
18
-------
included in the 2009 PM ISA (i.e., mean 24-h avg concentrations of 12.8 |ig/m3 and above in the
multi-city studies).
19
-------
Study
Tsajet al. (2000)
Tsaiet al. (2000)
Tsaiet al. (2000)
Moolgavkar(2003)
Ostro et al. (2006)
Klemm etal. (2004)
Ito (2003)
Klemm et al. (2011)
Franklinetal. (2007)
Franklin etal. (2008)
Klemm andMason (2003)
Fairley (2003)
Burnett and Goldberg (2003)
Zanobettiand Schwartz (2009)
Burnett etal. (2004)
Slaughter etal. (2005)
Villeneuve et al. (2003)
Chock etal. (2000)
Chock etal. (2000)
Dominici et al. (2007a)
Tsaiet al. (2000)
Tsajet al. (2000)
Tsaiet al. (2000)
Dominici etal. (2007)
Chang etal. (2012)
Ostro et al. (1995)
Moolgavkar(2003)
Ostro et al. (2006)
Ostro et al. (2007)
Ito (2003)
Lipfertetal. (2000)
Klemm et al. (2011)
Hollomanetal. (2004)
Franklin etal. (2007)
Franklin etal. (2008)
Klemm andMa son (2003)
Ito etal. (2011)
Zanobettiand Schwartz(2009)
Maretal. (2003)
Fairley (2003)
Wilson etal. (2007)
Villeneuve et al. (2003)
Ostro etal. (1995)
Moolgavkar(2003)
Ostro et al. (2006)
Ito (2003)
Franklin etal. (2007)
Franklin etal. (2008)
Klemm andMa son (2003)
Zanobettiand Schwartz(2009)
Fairley (2003)
Villeneuve et al. (2003)
Location
Newark, NI
Camden,NI
Elrzabeth,NI
Los Angeles, CA
9 California counties
Atlanta, GA
Detroit, MI
Atlanta, GA
27 U.S. cities
25 U.S. cities
6 U.S. Cities
Santa Clara County, CA
8 Canadian Cities
112U.S. cities
12 Canadian cities
Spokane, WA
Vancouver, CAN
Pittsburgh, PA
Pittsburgh, PA
100U.S. cities
Newark, NI
Camden,N!
Elizabeth, NI
100U.S. cities
New York, NY
Southern California
Los Angeles, CA
9 California counties
9 California counties
Detroit, MI
Philadelphia,PA
Atlanta, GA
7 NC counties
27 U.S. cities
25 U.S. cities
6 U.S. Cities
New York, NY
112U.S. cities
Phoenix, AZ
Santa Clara County, CA
Phoenix, AZ
Vancouver, CAN
Southern California
Los Angeles, CA
9 California counties
Detroit, MI
Atknta, GA
27 U.S. cities
25 U.S. cities
6 U.S. Cities
112U.S. cities
Santa Clara County, CA
Vancouver, CAN
Age Lag Mean
98th
All
All
All
All
All
65+
All
65+
All
All
All
All
All
All
All
All
65+
<75
75+
All
All
All
All
All
65+
All
All
All
All
All
All
65+
>16
All
All
All
40+
All
All
All
>25
65+
All
All
All
All
65+
All
All
All
All
All
65+
1
0-1
0-1
3
0-1
0-1
0-1
42.1
39.9
37.1
22.0*
19.9
19.6
18.0
17.0
15.6
14.8
14.7
13.6
13.3
13.2
12.8
10.8
7.9
42.1
39.9
37.1
19.9
18.4
18.0
17.3
17.0
-15.6
15.6
14.8
14.7
144
13.2
13.0
13.0
13.0
7.9
32.5
22.0*
19.9
18.0
17.0
15.6
14.8
14.7
13.2
13.0
7.9
45.8
43.0
59.0
38.9
34.3
38.0
29.6
45.8
43.0
34.3
25-88
31.6
45.8
43.0
34.3
Nonaccidental
Cardio-respiratory
Cardiovascular
H h
Respiratory
-5.0 -3.0 -1.0 1.0 3.0 5.0 7.0 9.0 11.0 13.0 15.(
% Increase
Figure 2.4. Percent increase in non-accidental and cause-specific mortality for a 10 |ig/m3 increase in 24-h average PM2.5
concentrations in single-pollutant models from U.S. and Canadian studies. Red text and triangles represent recent studies published
since the completion of the 2009 PM ISA. Results presented from single-pollutant models for purposes of comparing results across
studies that included different mixes of copollutants.
20
-------
2.2.2. Morbidity
2.2.2.1. Associations between Short-Term Exposures to PM and Respiratory
Morbidity
Summary of 2009 PM ISA Conclusions
The association between short-term PM2.5 exposure and respiratory-related emergency
department (ED) visits, hospital admissions, and physician visits was evaluated in Section 6.3.8
of the 2009 PM ISA (U.S. EPA. 2009). The numerous multi- and single-city studies evaluated
reported consistent positive associations with respiratory ED visits and hospital admissions for
COPD, asthma, and respiratory infection in study areas with mean 24-h average PM2.5
concentrations ranging from 6.1 - 22 |ig/m3. However, associations for asthma were imprecise
and not consistently positive when limiting analyses to children. The evidence from respiratory-
related emergency department (ED) visits, hospital admissions, and physician visits studies
contributed to the conclusion that a "causal relationship is likely to exist between short-term
exposures to PM2.5 and respiratory effects."
Additional epidemiologic studies evaluated in the 2009 PM ISA examined associations between
short-term PMio-2.5 exposure and respiratory hospital admissions and ED visits. This limited
number of studies demonstrated consistent positive associations with respiratory-related hospital
admissions and ED visits with the strongest evidence in children. The evidence from these
studies in combination with the evidence from toxicological and controlled human exposure
studies led to the conclusion that the collective evidence across disciplines "is suggestive of a
causal relationship between short-term exposures to PMi0-2.5 and respiratory effects."
Recent Respiratory Hospital Admission Studies
Within this section, respiratory-related hospital admissions and ED visit studies are discussed
separately. This is because ED visits for respiratory-related outcomes often represent less
serious, but more common health effects. Additionally, only a small percentage of respiratory-
related ED visits result in a hospital admission. Therefore, it is important to discuss the evidence
for each respiratory-related health outcome separately.
Respiratory-related Hospital Admissions
A number of studies published since the completion of the 2009 PM ISA conducted multi city or
multi-location analyses to examine the association between short-term PM2.5 exposures and
respiratory hospital admissions. Figure 2.5 summarizes the evidence from single-pollutant
models from studies evaluated in the 2009 PM ISA as well as recent studies published since its
completion. Bell et al. (2012) represented a consolidated and more detailed account of a number
of previous publications, of which most were discussed in the 2009 PM ISA (Bell et al., 2009a:
Bell et al.. 2009b: Bell et al.. 2008: Bell et al.. 2007). In an all-year analysis of 187 U.S. counties,
short-term exposure to PM2.s was positively associated with respiratory hospital admissions in
individuals 65 years of age and older across lags of 0 to 2 days, with the strongest association at
21
-------
lag 2 (0.41% [95% CI: 0.09, 0.74])9. In seasonal analyses, the association at lag 2 was
consistently positive across seasons, but the strongest association was at lag 0 (1.05% [95% CI:
0.29, 1.82]) in the winter season with the largest magnitude of an effect in the Northeast region.
Of note the Northeast region comprised 53% of all counties included in the analysis. In an
additional analysis using this data (Bell et al., 2009a), there was no evidence of a reduction in the
association between PM2.5 and respiratory hospital admissions when accounting for air
conditioning use. In a multi-city study conducted in the New England region of the U.S., Kloog
et al. (20J_2a) examined associations between short-term PM2.5 exposure and respiratory hospital
admissions in individuals 65 years of age and older. To estimate exposure the authors developed
a novel prediction model that combined land use regression with physical measurements from
satellite aerosol optical depth. The authors observed a 0.70% (95% CI: 0.35, 1.05) increase in
respiratory hospital admissions for lags days 0-1. The results obtained using the novel approach
presented (i.e., 0.70% increase in respiratory hospital admissions) were consistent with the
percent increase in respiratory hospital admissions observed in a traditional time-series analysis
(i.e., 1.51%).
In addition to the multicity studies presented above, a few single city studies were conducted in
the U.S. that examined asthma and acute bronchitis. Silverman and Ito (2010) conducted a study
to evaluate the effect of short-term PM2.5 and Os exposure on asthma hospital admissions, both
general and those that required a stay in the intensive care unit (ICU) in New York City.
Analyses focused on four age groups (i.e., <6, 6-18, 19-49, and 50+) and were limited to the
warm season (April-August). Positive associations were observed for each age group and for all
ages combined when considering general asthma hospital admissions, with the strongest
association for the age group 6-18 (15.5% [95% CI: 9.1, 22.0] at lag 0-1). When limiting the
analysis to ICU asthma admissions, again the strongest association was for the age group 6-18
(21.1% [95% CI: 8.3, 35.5]). The observed associations remained robust in copollutant models
with 63. The authors also examined the shape of the concentration-response (C-R) relationship
using linear, smooth functions, which allowed for a possible nonlinear relationship. This analysis
found evidence that the linear fit is a reasonable approximation of the relationship between short-
term PM2.5 concentrations and asthma hospital admissions. Grineski et al. (2011) primarily
focused on examining the effect of dust and low wind events on asthma and acute bronchitis
hospital admissions in El Paso, TX; however, since daily PM2.5 data were available the authors
also examined associations between short-term PM2.5 exposures and each respiratory health
effect. The authors found that PM2.5 was positively, but weakly associated with asthma
(OR=1.02 [95% CI: 0.96, 1.09]) and acute bronchitis (OR=1.01 [95% CI: 0.92, 1.12]) hospital
admissions.
9 All effect estimates for associations between short-term exposure to PM2 5 and morbidity are presented for a 10
ug/m3 increase in PM2 5 concentration.
22
-------
Recent Respiratory-related ED Visits Studies
Of the recent studies identified that focused on short-term exposures to PM2.5 and respiratory-
related ED visits the majority consisted of single-city studies. However, a couple large, multi-
city studies were conducted in the U.S. and Canada. Zanobetti et al. (2009) examined the
association between short-term PM2.5 exposure and respiratory ED visits in individuals 65 years
of age and older in 26 U.S. communities. In an all-year analysis, PM2.5 was strongly associated
with respiratory ED visits (2.1 [95% CI: 1.2, 3.0] at lag 0-1), while in seasonal analyses positive
associations were observed across seasons with the strongest association in the spring (4.3%
[95% CI: 2.2, 6.5]). Stieb at al. (2009) conducted a study in 7 Canadian cities to examine the
effect of air pollution on ED visits for multiple respiratory-related health outcomes including
asthma, COPD, and respiratory infection. The authors found no evidence of an association
between short-term PM2.5 exposure and COPD ED visits at any of the single-day lags examined.
In all-year analyses, positive associations were observed for asthma with the magnitude of the
association decreasing as lag day increased (i.e., the strongest association was observed at lag 0,
2.1% [95% CI: -3.0, 7.5]). However, in a warm season analysis (April-September), the
magnitude of the association between PM2 5 and asthma was nearly 4 times higher (9.3% [95%
CI: 6.3, 12.5]).
A couple of single city studies were also conducted that examined all respiratory, multiple
respiratory effects, or asthma ED visits. Darrow et al. (2011 a) examined the association between
short-term air pollution exposure and respiratory ED visits in Atlanta using various exposure
metrics (i.e., 1-h max, 24-h avg, Commute (0700-1000, 1600-1900 hours), Day-time (0800-1900
hours), and Night-time (2400-0600 hours). PM2 5 (lag 1) was positively associated with
respiratory ED visits across exposure metrics, with the magnitude ranging from 0.2% to 0.4%.
Kim et al. (2011) examined the associations between short-term PM2 5 exposure and hospital
admissions in Denver, CO. The authors found no evidence of an association with all respiratory
(-0.44% [95% CI: -5.6, 5.4]), COPD or pneumonia hospital admissions (quantitative results only
presented for all respiratory). However, there was evidence of a delayed effect of PM2.s on
asthma hospital admissions with effects not occurring until approximately lag day 4.
A number of studies focused on ED visits and hospital admissions for asthma. Strickland et al.
(2010)conducted an analysis in Atlanta using the same air quality data as Darrow et al. (2011 a)
to examine the association between air pollution and pediatric (ages 5-17) asthma ED visits.
PM2.s was strongly associated with pediatric asthma ED visits in both all-year (2.2% [95% CI:
0.2, 4.2] at lag 0-2) and warm season (4.7% [95% CI: 1.7, 7.6]) analyses. The magnitude of the
association was robust to the inclusion of Os in the model. An examination of the C-R
relationship through a quintile analysis and a loess C-R analysis using lag 0-2 day PM2 5
concentrations found evidence of increased risk of pediatric asthma ED visits down to relatively
low ambient concentrations (i.e., mean 24-h avg concentrations < 14 |ig/m3). In Tacoma, WA,
Mar et al. (2010) also examined the association between short-term PM2.5 exposure and asthma
ED visits. Individual lag days of 0 to 5 days were examined with the strongest association
23
-------
occurring at lag 2 (5.7% [95% CI: 1.4, 10.1]). Li et al. (2011) examined the C-R relationship
between short-term PM2.5 exposures and asthma ED visits in children 2 to 18 years of age in
Detroit. Associations were examined in both a time-series and time-stratified case-crossover
study design assuming: (1) no deviation from linearity and (2) a change in linearity at 12 |ig/m3.
In the analyses assuming linearity, similar effect estimates were observed in both models for a 0-
4 day lag, (time series: RR=1.03 [95% CI: 1.00, 1.07]; case-crossover: OR=1.04 [95% CI: 1.01,
1.07]). In the models assuming a deviation from linearity at 12 |ig/m3, the authors reported
slightly larger effect estimates, compared to the linear model, for asthma ED visits in the time-
series (RR=1.07 [95% CI: 1.03, 1.11]; lag 0-4) and case-crossover analyses (OR=1.06 [95% CI:
1.03, 1.09]; lag 0-4), respectively. Glad et al. (2012) conducted a study in Pittsburgh, PA that
found PM2 5 to be positively associated with asthma ED visits in analyses of all ages and ages 18
to 64 for single lag days and the average of 0-5 days (i.e., all ages: OR=1.04 [95% CI: 0.98, 1.10]
and 18 to 64: OR=1.053 [95% CI: 0.99, 1.12] at lag 0-5). Additionally, when stratifying by race
there was some evidence for larger effects in African Americans compared to Caucasian
Americans.
24
-------
Study
Location
Age Lag Mean 98th
Ostro et al. (2009)
Peeletal. (2005)
Tolbert et al. (2007)
Darrowetal. (2011)*
Zanobettietal. (2009)
Bell etal. (2008)
Slaughteret al. (2005)
Kloog etal. (2012)
Kim etal. (2012)
Fung et al. (2006)
Chen etal. (2005)
Peeletal. (2005)*
Ito etal. (2007)*
Sheppard etal. (2003)
Strickland etal. (2010)*
NYS DOH (2006)*
NYS DOH (2006)*
Li etal. (2011)*
Glad etal. (2012)*
Silver-man and Ito (20 10)
Grineski et al. (2011)
Maretal. (2010)*
Slaughteret al. (2005)*
Stieb et al. (2009)*
Chimonas & Gessner (2006)
Grineski et al. (2011)
Peeletal. (2005)*
Dominici et al. (2006)
Lin etal. (2005)
Stieb et al. (2009)*
Chimonas & Gessner (2006)
6 CA Counties
Atlanta,GA
Atlanta,GA
Atlanta,GA
26 U.S. communities
202 U.S. counties
Spokane
New England
Denver, CO
Vancouver
Vancouver
Atlanta,GA
New York, NY
Seattle, WA
Atlanta,GA
Bronx, NY
Manhattan, NY
Detroit, MI
Pittsburgh, PA
New York, NY
El Paso, TX
Tacoma,WA
Spokane, WA
7 Canadian cities
Anchorage, AK
El Paso, TX
Atlanta,GA
204 U.S. counties
Ontario, CAN
7 Canadian cities
Anchorage, AK
0-19
All
All
All
65+
65+
All
65+
All
65+
65+
All
All
All
5-17
All
All
2-18
All
All
1 +
All
All
All
0-19
1 +
All
65+
<15
All
0-19
3
0-2
0-2
1
0-1
2
1
0-1
0-1 4 DL
0-2
0-2
0-2
0-1
0
0-2
0-4
0-4
0-4
0-5
0-1
0-3
2
1
0
0
0-3
0-3
2
0-3
0
0
19.4
19.2
17.1
16.0
15.3
12.9
10.8
9.6
8.0
7.7
7.7
19.2
—
16.7
16.4
15.0
15.0
15.0
13.3
13.0**
12.8
12.3
10.8
6.7-9.8
6.1
12.8
19.2
13.3
9.6
6.7-9.8
6.1
34.2
29.6
All Respiratory
Asthma
46.6
29.6
Bronchitis
Respiratory Infection
•4—
-15.0
1 1 1 1 1 1 1
-10.0 -5.0 0.0 5.0 10.0 15.0 20.0
% Increase
Figure 2.5. Percent (%) Increase in respiratory-related hospital admissions and ED visits for a 10 |ig/m increase in 24-h average
PM2.5 concentrations in single-pollutant models from U.S. and Canadian studies. Red text and triangles represent recent studies
published since the completion of the 2009 PM ISA. * ED visit studies. ** Median concentration.
25
-------
The 2009 PM ISA evaluated a number of multi- and single-city studies that found consistent
positive associations with all and cause-specific respiratory hospital admissions and ED visits,
specifically COPD and respiratory infections in study areas with mean 24-h PM2.5 concentrations
ranging from 6.1 - 22.0 |ig/m3. Additionally, there was evidence for asthma hospital admissions
and ED visits, but the effects were not consistent in children. Recent multi- and single-city
studies have continued to demonstrate consistent positive associations for all respiratory-related
hospital admissions and ED visits, and provide additional evidence for increases in asthma
hospital admissions and ED visits. The associations observed in the new studies occur in
locations with mean concentrations similar (i.e., mean 24-h avg concentrations ranging from 6.7
- 16.4 |ig/m3) to those studies included in the 2009 PM ISA.
The 2009 PM ISA also found evidence that associations between short-term PMi0-2.5 exposures
and respiratory-related hospital admissions and ED visits were strongest among children. A
recent study by Strickland et al. (2010) that examined the association between short-term PMio-
2.5 exposure and pediatric asthma ED visits in Atlanta, GA further supports this conclusion.
Positive associations were observed in both all-year (5.8% [95% CI: 1.9, 9.9] at lag 0-2) and
seasonal analyses, with the strongest association in the cold season (7.0% [95% CI: 1.7, 12.7]).
An examination of the C-R relationship in both quintile and smooth estimates of the
concentration-response provided evidence of associations at relatively low ambient
concentrations for all pollutants, including PMio-2.s (i.e., mean 24-h avg concentrations < -12
2.2.2.2. Associations between Short-Term Exposures to PM and
Cardiovascular Morbidity
Summary of 2009 PM ISA Conclusions
The associations between short-term PM2.s exposure and cardiovascular-related hospital
admissions and ED visits was evaluated in Section 6.2.10 of the 2009 PM ISA (U.S. EPA. 2009).
Epidemiologic studies that examined the effect of PM2.s on cardiovascular ED visits and hospital
admissions reported consistent positive associations (predominantly for IHD and congestive
heart failure [CHF]) in study areas with mean 24-h average concentrations ranging from 7.0 - 18
|ig/m3. This evidence contributed to the conclusion that "a causal relationship exists between
short-term PM2.5 exposure and cardiovascular effects."
Epidemiologic studies of the association of short-term PMio-2.s exposure with cardiovascular
hospital admissions and ED visits were also evaluated in the 2009 PM ISA, and the evidence
from these studies contributed to the conclusion that the evidence "is suggestive of a causal
relationship between short-term exposures to PMi0-2.5 and cardiovascular effects.
Recent Cardiovascular-related Hospital Admissions/ED Visits Studies
Recent multi-city and multi-location studies, as well as single-city studies, add to the collective
body of evidence that examined associations between short-term PM2.5 exposure and
cardiovascular-related hospital admissions and ED visits evaluated in the 2009 PM ISA. Figure
26
-------
2.6 summarizes the results from single-pollutant models from studies evaluated in the 2009 PM
ISA as well as recent studies published since its completion. No new studies have been published
that examined the association between short-term PMi0-2.5 exposure and cardiovascular hospital
admissions or ED visits in the U.S. or Canada.
In a recent Health Effects Institute (HEI) report, Bell et al. (2012) compiled findings from
several multicity analyses of Medicare data (older adults, > 65 years of age) for 204 counties
across the U.S. (some analyses included fewer counties). Although additional detail is provided
in the HEI report, these analyses were largely included in the 2009 PM ISA (Bell et al., 2008;
Dominici et al., 2006). In an analysis using the same data, Bell et al. (Bell et al., 2009a) found a
higher prevalence of central air conditioning was associated with a decrease in the risk of PM2.5 -
associated hospitalization for cardiovascular disease.
Recent studies are consistent with the evidence assessed in the 2009 PM ISA. In a time-series
analysis of Medicare records for older adults >65 years of age in 26 US communities for 2000-
2003, Zanobetti et al. (2009) reported increases in hospital admissions for all CVD (1.89%
95%CI: 1.34 to 2.45), MI (2.25% 95%CI: 1.10 to 3.42) and CHF (1.85% 95%CI: 1.19 to 2.51;
lag 0-1). Although the largest excess risks were observed in the spring, statistically significant
excess risks were also observed in the winter. In a time-series analysis of hospital admissions in
seven Canadian cities, a 17% (95%CI: 0 to 37%) increase in hospital admissions for heart failure
was observed at lag 0 (Stieb et al., 2009). Weak, nonsignificant associations were observed
between PM2 5 and dysrhythmia and MI hospitalizations.
In a study of emergency hospitalizations among New York City residents > 40 years of age, Ito
et al. (2011 a) reported an excess risk of 1.0% (95% CI: 0.40, 1.6, lag 0). The excess risk was
stronger in the cold season (1.1% [95% CI 0.2 to 2.0]). These results were not sensitive to the
choice of method used to control temperature. Using a subset of these emergency hospitalization
data, Mathes et al. (2011) defined two cardiovascular syndromes from a database containing text
descriptions of the chief complaint reported by the patient upon admission to the hospital. This
study reported that PM2.5 was associated with both cardiac and more general cardiovascular
syndromes. In case-crossover analysis of cardiovascular disease admissions across New York
state from 2001 to 2005, Haley et al. (2009) found a 3.9% increase in heart failure admissions
per 10 |ig/m3 increase in PM2 5 (lag 0-2). A case-crossover study of atrial fibrillation
hospitalizations between 1993 and 2008 in Utah (Wasatch Front) reported consistently positive,
but non-significant, associations across all lags examined in the study (lag 0 through 21 day
moving average) (quantitative results not provided) (Bunch et al., 2011). Finally, a 1.03% (95%
CI: 0.69, 1.34) increase in cardiovascular admissions was reported in a time-series study of
hospitalizations across New England among older adults (65 years) with predicted PM2.5
concentrations using satellite-derived AOD measurements (Kloog et al., 2012b).
27
-------
Acute Stroke
Wellenius et al. (2012) examined the association of PM2.5 with neurologist-confirmed ischemic
stroke in predominately white female patients admitted to the Beth Israel Deaconess Medical
Center (BIDMC) in Boston from 1999 to 2008. Time of stroke symptom onset (exact or
estimated) was available for most patients included in the study. The OR of stroke onset was
1.30 (95% CI: 1.08 to 1.58) per 10 |ig/m3 increase in PM2.5 in the previous 24 hours. Authors
report a 34% (95% CI: 13 to 58) higher risk of ischemic stroke during the previous 24 hours in
an analysis comparing moderate PM2.5 exposure (>15 |ig/m3) to good (<15 |ig/m3) exposure, as
defined by EPA's Air Quality Index (AQI). These results were confirmed in an additional
analysis conducted by Mostofsky et al. (2012) using a subset of the data (i.e., 2003-2008) used
by Wellenius et al. (2012). Mostofsky et al. (2012) found a 22.7% (95% CI: 3.1, 47.0) increase in
ischemic stroke onset for an increase in PM2.5 over the previous 24 hours.
Out of Hospital Cardiac Arrests
The small number of studies of out-of-hospital cardiac arrest included in the 2009 PM ISA
reported mixed results. A recent time series analysis of cardiac arrests in New York City reported
an increased risk of 1.06 (95%CI 1.02, 1.10, lag 0-1) per 10 ug/m3 increase in PM2.5 (Silverman
et al., 2010). Case cross-over analysis of the same data produced a result that was similar in
magnitude but did not reach statistical significance. The association with cardiac arrest was
stronger in the warm season (1.09 95% CI: 1.03-1.15) compared to the cold season (1.01 95% CI
0.95 to 1.07).
In summary, the 2009 PM ISA found consistent positive associations between short-term PM2.5
exposures and all and cause-specific cardiovascular hospital admissions and ED visits,
specifically IHD and CHF in study areas with mean 24-h PM2.5 concentrations ranging from 7.0
- 18.0 |ig/m3. New multi- and single-city studies further support associations with all
cardiovascular hospital admissions and ED visits at mean 24-h PM2.s concentrations ranging
from 6.7 - 15.3 |ig/m3. Additional support for associations between short-term PM2.s exposures
and cardiovascular effects comes from a new study of stroke onset (Wellenius et al. (2012)).
28
-------
Study
Metzger et al. (2004)
Tolbert et al. (2007)
Zanobettietal. (2009)*
Itoetal. (2011)
Bell et al. (2008)
Slaughter et al. (2005)
Kloogetal. (2012)
Kim etal. (2012)
Burnett etal. (1999)
I to(2003)
Metzger et al. (2004)
Dominici et al. (2006)
Pope et al. (2006)
Zanobettietal. (2009)*
Sullivan etal. (2005)
Peters etal. (2001)
Zanobetti & Schwartz (2005)
Stieb et al. (2009)*
Burnett etal. (1999)
I to(2003)
Metzger etal. (2004)*
Symonsetal. (2006)
Zanobettietal. (2009)*
Dominici et al. (2006)
Haley et al. (2009)
Pope et al. (2008)
Stieb et al. (2009)*
Metzger etal. (2004)*
Dominici et al. (2006)
Kloogetal. (2012)
Szyszkowicz et al. (2012)*
Location
Atlanta, OA
Atlanta, OA
26 U.S. Communities
New York, NY
202U.S. Counties
Spokane, WA
New England
Denver, CO
Age Lag
26 U.S. Communities
King County, WA
Boston, MA
Boston, MA
7 Canadian cities
Atlanta, OA
204U.S. Counties
New England
Edmonton, CAN
AU
AU
65+
40+
65+
0-2
0-2
0-1
0
0
1
0-1
0-2 DL
Mean
17.8
17.1
15.3
14.4
12.9
10.8
9.6
8.0
98th
Toronto, CAN
Detroit, MI
Atlanta, OA
204U.S. Counties
UtahVaney.UT
M
65+
M
65+
M
0-1
1
0-3
0-2 DL
0
18.0
18.0
17.8
13.3
10.1-11.3
15.3
12.8
12.1
11.1**
6.7-9.8
65+
65+
17.8
13.3
9.6
Toronto, CAN
Detroit, MI
Atlanta, OA
Baltimore, MD
:6U.S. Communities
204U.S. Counties
New York State
Utah
7 Canadian cities
M
65+
M
M
65+
65+
M
An
An
0-2
1
0-2
2
0-1
0
0-2
0-1 SDL
0
18.0
18.0
17.8
16.0
15.3
13.3
11.1-15.5
10.8
6.7-9.8
___
___
___
34.8
44.5
___
A11CVD
IHD
MI
CHF
CBVD
Hypertension
-4.0-2.00.0 2.0 4.0 6.0 8.010.012.014.016.018.020.022.024.026.028.030.032.0
% Increase
Figure 2.6. Percent increase in cardiovascular-related hospital admissions and ED visits for a 10 |ig/m increase in 24-h average PM2 5
concentrations in single-pollutant models from U.S. and Canadian studies. Red text and triangles represent recent studies published
since the completion of the 2009 PM ISA. * ED visit studies. ** Median concentration, a = study only presented mean age of
participants.
29
-------
2.3. Health Effects Related to Sources or Components of PM
Summary of 2009 PM ISA Conclusions
The 2009 PM ISA evaluated epidemiologic, lexicological, and controlled human exposure
studies that examined health effects associated with ambient PM components and sources. These
studies used a variety of quantitative methods and examined a broad set of PM components
(Section 6.6), and found evidence of health effects from sources and components associated with
a number of combustion activities (e.g., motor vehicle emissions, coal combustion, oil burning,
power plants, and wood smoke/vegetative burning), crustal sources, and secondary sulfate. As a
result, the ISA concluded that "the evidence is not yet sufficient to allow differentiation of those
components or sources that are more closely related to specific health outcomes." These
conclusions are consistent with those presented in the 2004 PM AQCD where the studies
evaluated found evidence of health effects attributed to a number of source types, including
motor vehicle emissions, coal combustion, oil burning, and vegetative burning.
Recent Studies of Health Effects Related to Sources or Components of PM
Recent studies have continued to examine whether specific PM components or sources are more
closely related to specific health outcomes. For the purposes of this provisional assessment of
new literature published since the release of the 2009 PM ISA, 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. Thus, the discussion includes: (1) recent epidemiologic studies using
source apportionment; (2) epidemiologic evidence on effects with PM components; and (3)
results of new toxicological 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 PM components. In addition, numerous
epidemiologic and/or toxicology studies have reported effects of several ultrafine PM as
discussed in the 2009 PM ISA. Specific findings for ultrafine PM are not discussed in detail;
instead, the available new studies are included in the reference list: http://hero.epa.gov/pm .
2.3.1. Epidemiologic Studies Using Source Apportionment
Lall et al. (2011) examined the association between source-specific daily PM2.5 mass and
component data and hospital admissions in New York City for the years 2001-2002. The use of
daily data allowed for the examination of both single-day lags and a distributed lag. Source
categories identified through positive matrix factorization included long-range transported
sulfates, traffic, residual oil, steel metal works dust, and soil. In single-day lag models, total
respiratory hospital admissions were positively associated with residual oil at lag 2, but the
strongest associations were with steel metal works dust at lag 0 and 3. For cardiovascular
hospital admissions the strongest associations were observed with traffic at lag 0 and residual oil
at lag 3. When examining associations between cause-specific cardiovascular and the traffic
30
-------
source category, the strongest associations were observed at lag 0 for total cardiovascular, heart
failure, and stroke. For associations between cause-specific respiratory hospital admissions and
the steel source category, pneumonia was associated with steel metal works dust at lag 3, while
asthma was observed to have the largest magnitude of an association across all lags. The
distributed lag model demonstrated a stronger association between traffic and cardiovascular
hospital admissions and steel metal works dust and respiratory hospital admissions than the
single-day lag models, indicating that single-day lags may underestimate the magnitude of
associations. Finally, a sensitivity analysis using key tracers of each source (i.e., elemental
carbon for traffic and manganese for steel metal works) found similar patterns of associations as
the source-specific analyses.
2.3.2. Epidemiologic Studies on Effects of Fine PM Components and Sources
In addition to examining the association between short-term PM2.5 exposures and mortality or
hospital admissions and ED visits a number of studies also attempted to identify if an individual
PM component or group of PM components could explain the observed association. The
following section describes the results from these studies some of which have been
aforementioned.
Short-term exposure to PM2.s components and sources and mortality
In addition to examining the association between short-term exposure to PM2.5 and mortality, a
few single-city studies also examined the effect of individual PM2 5 components on mortality. Ito
et al. (2011 a) focused on key PM components (i.e., elemental carbon [EC], organic carbon [OC],
sulfate [864], nickel [Ni], vanadium [V], zinc [Zn], silicon [Si], selenium [Se], sodium [Na], and
bromine [Br]) identified in previous source apportionment studies conducted in NYC. In all-year
analyses, the strongest associations were observed at lag 1 for EC, OC, 864, Si, Se, and Br. In
the warm season, strong associations were observed for secondary aerosols including OC and
864, Se, which is associated with transported coal emissions, EC, and Br. In the cold season, the
components associated with residual oil burning, Ni, V, and Zn, all showed a similar pattern of
associations, with the strongest effects at lag 3. Overall, the components representing regional
transport showed a seasonal pattern of associations similar to those found with PM2.s mass, while
associations were found throughout the year with EC and NO2.
Zhou et al. (2011) examined the association between PM components with all-cause,
cardiovascular, and respiratory mortality in seasonal analyses in Seattle and Detroit. The
components selected for analysis represent the major emissions sources of the two cities: soil
(aluminium [Al] and Si), smelter effluents (iron [Fe] and Zn), residual oil burning (Ni and V),
coal burning (sulfur [S]), traffic (EC), sea salt (Na), and wood burning (potassium [K]). Daily
component data was available in both cities, which allowed for the examination of a 0-2 day
distributed lag. In Detroit, S was associated with all-cause and cardiovascular mortality and S
and Ni were moderately associated with respiratory mortality in the warm season. No
components were positively associated with any mortality outcome in the cold season in Detroit.
31
-------
In Seattle, in the warm season no component was significantly associated with any mortality
outcome, but Fe, K, and EC were positively associated with respiratory mortality. In the cold
season, Al, K, Si, Zn, and EC were strongly associated with all-cause mortality, with the same
components, minus Al, strongly associated with cardiovascular mortality. No components were
associated with respiratory mortality in Seattle in the cold season. Overall, in Detroit the
components associated with mortality are indicative of coal burning while in Seattle the
components associated with mortality represent cold-season traffic and combustion sources, such
as residual oil and wood burning.
In the study conducted by Klemm et al. (2011) in Atlanta, daily concentrations of the PM
components EC, OC, nitrate [NO3], and 864 were also available for the entire study duration.
The authors found that EC, OC, and NO3 were positively associated with nonaccidental mortality
at lag 0-1 in individuals 65 years of age and older, with the strongest association for NO3. In
analyses of cause-specific mortality, a similar pattern of associations was observed for
cardiovascular and respiratory mortality. SO4 was not found to be associated with any of the
mortality outcomes examined.
Respiratory-related Hospital Admissions and ED Visits
Recent multicity studies were identified that examined the effect of PM components on the
relationship between short-term PM exposure and respiratory-related ED visits and hospital
admissions. Zanobetti et al. (2009) conducted a second-stage analysis, using the same
methodology as Franklin et al. (2008) (2009 PM ISA; p. 6-193-195) and examined whether
season and community-specific long-term mean seasonal concentration ratios of PM components
to PM2.s total mass modified the association between short-term PM2 5 concentrations and
respiratory ED visits. Of the components examined only Na+ and Ni were found to modify the
association between PM2 5 and respiratory ED visits. Using a different approach, Levy et al.
(2012) attempted to identify if some PM components are more toxic than others by focusing on
the four components that dominate PM2 5 mass and are highly correlated with PM2 5 (i.e., EC,
OC, SO4, and NO3). In a time-series analysis using Medicare data from 119 U.S. counties the
authors examined the association between each component and respiratory hospital admissions
across the U.S. and regionally (i.e., East and West). Of the components examined, only EC and
OC were positively associated with respiratory hospital admissions.
A few single-city studies were also identified that examined associations between respiratory-
related ED visits and hospital admissions and individual PM components. Strickland et al. (2010)
focused on the PM components SO4, EC, OC, and water-soluble metals. For each component
positive associations were observed with pediatric asthma ED visits in all-year analyses. The
strongest associations were observed in the warm season with the magnitude being similar across
components. In addition, analyses including copollutant adjustment were conducted using warm
season data. Risk estimates for PM2 5, EC, and SO4 were attenuated, but remained positive when
including O3 in the model. In LOESS C-R analyses, there was evidence of a positive C-R
relationship for each component. Kim et al. (2011) examined the lag structure of associations
32
-------
between the PM components EC, OC, SO/t, and NOs and respiratory hospital admissions. The
authors focused on these components because they comprise the majority of PM2.5 mass in
Denver. Consistent with the PM2 5 results, there was no evidence of an association with COPD or
pneumonia and any of the components. For both all respiratory and asthma hospital admissions
there was evidence of greater effects with EC and OC compared to SO/t and NOs, and additional
evidence for delayed effects occurring 2 to 5 days after exposure.
Cardiovascular-related Hospital Admissions and ED Visits
The 2009 PM ISA included multicity analyses of the effect of PM2.5 components on
cardiovascular hospital admissions that reported associations between oil combustion and traffic-
related PM2.5 and CVD hospitalizations.
Two recent studies investigated the association of PM2.5 components with cardiovascular
hospital admissions. Using Medicare data from 26 US communities, Zanobetti et al. (2009)
examined the modification of the associations of PM2.5 with CVD, MI and CHF hospital
admissions by season- and community-specific PM2 5 composition. Authors estimated the
relative contribution of specific components (EC, OC, SO4, NOs, Na, Ni, V, Zn, Si, Se, Br) by
computing concentration ratios (i.e. component species as a proportion of PM2.5 mass). In the
second stage of a hierarchical model, season- and community-specific estimates of the
association between PM2.5 and CVD hospitalizations were regressed on the concentration ratios.
The association of PM2 5 with all CVD hospitalizations was significantly modified when the
proportion of Br, Na+, Ni, V and Al in PM2 5 was high. The association of PM2 5 with all MI
hospitalizations was significantly modified when the proportion of arsenic [As], chromium [Cr],
manganese [Mn], OC, Ni, K and Na+ was high. Additional increases in CVD hospitalizations per
interquartile range (IQR) increase in the proportion of the component ranged from 0.53% to
0.9% (larger, less precise increases were reported for MI). None of the components significantly
modified the association of PM25 with CHF admissions (i.e. p-value > 0.05). Ito et al. (20lib)
conducted a time series analysis of the lag structure and seasonal patterns in the association
between emergency hospitalization for CVD and PM2 5 chemical components. Same day
concentration of most components examined was associated with CVD hospitalizations (EC,
OC, SO4, NO3, Na, Ni, V, Zn, Se, and Br). The association and lag structure of EC with CVD
hospitalization was constant across season; associations of OC, SO/t, Ni, Zn, Si, Se and Br with
CVD hospitalizations were strongest in the cold season.
An additional study (Mostofsky et al., 2012) examined different approaches to modeling the
association between PM components and health outcomes using ischemic stroke onset as an
example. The authors used three different models that included parameters for the following: (1)
component concentration, (2) component concentration adjusted for total PM2 5 mass, which
accounts for total PM2 5 mass, and (3) component residuals, which eliminates confounding by
total PM2.s mass. In model 1, positive associations were observed for a number of components
including Al, calcium [Ca], Br, lead [Pb], Se, titanium [Ti], and Fe with the strongest
associations for V, S, Ni, and black carbon [BC]. Models 2 and 3 resulted in relatively few
33
-------
components with positive associations, but the pattern of associations across pollutants was
consistent between the two models with the strongest associations for V, Ni, and BC.
Long-term exposure toPM2.s components and mortality
Ostro et al. (2010) also examined the association between long-term exposures to PM2.5
components (i.e., EC, OC, SO/t, NOs, Fe, K, Si, Zn) and all-cause mortality among the subjects
from the California Teachers Study. No associations were observed between all-cause mortality
and any PM2 5 component. In analyses of cause-specific mortality, Ostro et al. (2010) observed
an association between long-term exposure to several PM2.5 components and mortality from
CPD, IHD and pulmonary disease. The authors observed positive associations of CPD and IHD
mortality with each of the measured components, and between pulmonary mortality and 864 and
NOs. Of the components analyzed, there were positive associations with nitrate, sulfate and
silicon for CPD mortality and all of the components were associated with mortality from IHD
(See Table 2.2).
Table 2.2. Association between mortality outcomes and PM2.5 components using a 30-km buffer
(n=43,220) (adapted from Ostro et al. (2011))
Component (IQR, |jg/m3)
EC (0.65)
OC (0.84)
SO4 (2.2)
N03(3.2)
Fe(0.13)
K(0.07)
Si (0.03)
Zn(0.01)
All-Cause*
1.02(0.93, 1.12)
1.00(0.95, 1.04)
1.06(0.97, 1.16)
1.03(0.98, 1.09)
1.01 (0.93, 1.11)
1.01 (0.94, 1.08)
1.02(0.99, 1.06)
1.03(0.96, 1.11)
CPD*
1.07(0.94, 1.22)
1.04(0.98, 1.11)
1.14(1.01, 1.29)
1.11 (1.03, 1.19)
1.05(0.93, 1.19)
1.06(0.97, 1.17)
1.05(1.00, 1.10)
1.09(0.98, 1.20)
IHD*
1.46(1.17, 1.83)
1.13(1.01, 1.25)
1.48(1.20, 1.82)
1.27(1.12, 1.43)
1.39(1.13, 1.72)
1.27(1.07, 1.49)
1.11 (1.02, 1.20)
1.33(1.12, 1.58)
Pulmonary*
0.88(0.68, 1.15)
0.95(0.84, 1.06)
1.04(0.82, 1.31)
1.04(0.90, 1.20)
0.88(0.69, 1.13)
0.90(0.74, 1.09)
0.98(0.89, 1.08)
0.97(0.79, 1.18)
*Hazard ratio and 95% confidence interval for an increase in PM25 components equal to the interquartile range
(IQR)
Long-term exposure to PM2.s components and sources and morbidity
In a study conducted in New York City, Patel et al. (2009) examined long-term exposure to
PM2 5 components (Ni, V, Zn, EC) and respiratory symptoms in children through 24 months of
age. Positive associations were observed between Ni and wheeze, but not cough. No other
associations were observed between the other metals or EC and either wheeze or cough. PM2.5
mass was not associated with wheeze and/or cough (see Section 2.1.3 for results on PM2.5 mass).
Several recent studies have examined the association between exposure to PM2 5 components and
sources and birth outcomes, including birth weight and preterm birth. Studies examining birth
weight and PM2 5 components and sources found the strongest associations with metals/oil
combustion (Bell etal.. 2012: Darrowet al.. 201 Ib: Bell etal.. 2010) and elemental
34
-------
carbon/motor vehicles (Wilhelm et al., 2012; Darrowetal., 201 Ib; Bell etal., 2010). Similarly,
when evaluating PM2.5 components and preterm birth, the associations with metals, EC, OC and
ammonium nitrate were strongest (Wilhelm et al., 2011; Darrow et al., 2009). Several PM2 5
sources were associated with preterm birth, including biomass burning and diesel traffic
(Wilhelm etal.. 2011).
2.3.3. Toxicology Studies - Source Apportionment and Fine PM Components
The 2009 PM ISA examined health effects associated with exposure to ambient PM components
and sources in animals. In vivo and in vitro studies reported a variety of sources and components
were linked with cardiopulmonary effects; however, there was insufficient evidence overall to
determine which sources or components were most closely related to the observed effects. Since
the completion of the 2009 PM ISA, a small number of animal toxicology studies have continued
to assess the role of PM sources and components on effects observed after exposure to PM2.5.
2.3.3.1. Toxicology Studies Comparing Ambient Fine PM Sources and
Components
Toxicology studies employing CAPs offer a relevant surrogate for atmospheric PM. Table 2.3
shows the endpoints that were associated with various source categories from rodents exposed to
CAPs from four locations. These three studies compare electrocardiogram (ECG) responses
during CAPs inhalation to PM2.5 components associated with source factors (Kamal etal., 2011;
Rohr etal..2011; Chen et al.. 2010).
Chen et al. (2010) compared subchronic CAPs inhalation exposures from two locations in New
York, Sterling Forest (SF; undeveloped woodland park) and Manhattan in male hyperlipidemic
mice. Using Manhattan CAPs (mean CAPs concentration, 122.9 ±81.1 |ig/m3), heart rate (HR)
decreased with increased current day CAPs mass at all lags and several measures of heart rate
variability (HRV) increased with increased CAPs mass (i.e., standard deviation of the normal-to-
normal intervals, SDNN; root mean square of the standard deviation of the normal-to-normal
intervals, rMSSD; and frequency domain indices, high-frequency, HF, low-frequency, LF, and
LF/HF ratio). Using SF CAPs (mean CAPs concentration, 133.3 ± 110.5 |ig/m3), CAPs mass was
positively associated with HR, whereas HRV decreased with increased CAPs. Using Manhattan
CAPs, ECG changes were associated with components related to residual oil combustion > long-
range transport > traffic > iron/steel > incineration > soil. Using SF CAPs, ECG changes were
associated with long-range transport > Ni refinery > soil > residual oil combustion/traffic. Chen
et al. (2010) also performed single-element analysis and note that EC did not account for the
acute ECG changes associated with PM2 5 and that Ni may have an effect in Manhattan but not
SF.
Rohr et al. (2011) reported altered ECG responses in spontaneously hypertensive rats following
CAPs inhalation exposures from Detroit, Michigan over 13 consecutive days in both the summer
and winter. Source factors were identified using positive matrix factorization. In summer (time
weighted average CAPs concentration, 518 |ig/m3), decreased HRV (SDNN) was associated with
35
-------
cement/lime, iron/steel, and gasoline/diesel factors, and less so with sludge incineration. In
winter (time weighted average CAPs concentration, 357 |ig/m3); decreased HR was associated
with sludge incineration, cement/lime, and coal/secondary sulfate factors.
Kamal et al. (2011) also identified source factors (via positive matrix factorization) associated
with ECG alterations in hypertensive rats exposed for 13 days to CAPs (from Steubenville, OH;
mean CAPs concentration 406 ± 266 |ig/m3). Statistically significant associations were found
between acute cardiac responses and PM components linked with incineration, metal processing,
mobile sources, and iron/steel production. The strength of the association with each source was
dependent upon wind direction; however, incineration was consistently found to be associated
with changes in HR and HRV. Several individual CAPs components were also associated with
cardiovascular responses, S, SO2, Pb, and oxides of nitrogen (NOX).
Table 2.3. CAPs Sources and Associated Endpoints
Source Category
Metal processing
Incineration
(including sludge)
Pb
Iron/Steel
manufacturing
Mobile/Traffic
Coal and Secondary
Sulfate
Oil refinery
Cement/lime
processing
Elemental
Loading
V, Cr, Ti,
Mo, La, Ce
Zn, Cd
Zn, Ba, Mn,
Sr, Sb
Zn, Pb, Cu,
Fe
Pb, Cu
Fe, Mn, Cu,
EC, Pb
Mn, Fe
Fe, Mn, Cu
Fe, Sb, As,
K, CO
Fe, Ti, Zn
EC, NO2, Si,
Fe, Cu
S, Se, Al, V,
P
S, Se
La, Ce
Ca, Sr, Mg
Endpoint
Affected
t HR
|SDNN
1HR
|SDNN
1 HR (w)
I SDNN (s)
ECG alterations
1HR
1HR
t rMSSD
ECG alterations
t rMSSD (w)
I SDNN (s)
|SDNN
t rMSSD
| SDNN (s)
t rMSSD (w)
ECG alterations
1HR
t rMSSD
| HR (w)
t rMSSD (w)
t HR (w)
| HR (w)
I SDNN (s)
Location
Steubenville, OH
Steubenville, OH
Detroit, Ml
Manhattan, NY
Detroit, Ml
Steubenville, OH
Manhattan, NY
Detroit, Ml
Steubenville, OH
Detroit, Ml
Manhattan, NY
Steubenville, OH
Detroit, Ml
Detroit, Ml
Detroit, Ml
Exposure
Duration
13 days (s)
13 days (s)
13 days (s &
w)
6 months
13 days (s &
w)
13 days (s)
6 months
13 days (s &
w)
13 days (s)
13 days (s &
w)
6 months
13 days (s)
13 days (s &
w)
13 days (s &
w)
13 days (s &
w)
References
Kamal et al. (2011)
Kamal et al. (2011)
Rohr et al. (2011)
Chen et al. (2010)
Rohr et al. (2011)
Kamal et al. (2011)
Chen et al. (2010)
Rohr et al. (2011)
Kamal et al. (2011)
Rohr et al. (2011)
Chen et al. (2010)
Kamal et al. (2011)
Rohr et al. (2011)
Rohr et al. (2011)
Rohr et al. (2011)
36
-------
Source Category
Residual oil
combustion
Ni-refinery
Soil
Long range
transport
Elemental
Loading
V, Ni, EC,
Fe
Cr, Ni
Al, Si, Ca,
Fe
S, Se, Br
Endpoint
Affected
ECG alterations
ECG alterations
ECG alterations
ECG alterations
Location
Manhattan, NY
Sterling Forest,
NY
Sterling Forest,
NY
Manhattan, NY
Sterling Forest,
NY
Manhattan, NY
Exposure
Duration
6 months
6 months
6 months
6 months
References
Chen et al. (2010)
Chen et al. (2010)
Chen et al. (2010)
Chen et al. (2010)
(w) winter season, (s) summer season, HR: heart rate, SDNN: standard deviation of the normal-to-normal intervals, rMSSD: root
mean square of the standard deviation of the normal-to-normal intervals, Mo: molybdenum, La: lanthanum, Ce: cerium, Cd:
cadmium, Ba: barium, Sr: strontium, Sb: antimony, Cu: copper, CO: carbon monoxide, P: phosphorus
Other studies have used regression and correlation approaches to estimate the relationship
between various PM components and sources with health effects. Happo et al. (201 Ob)
intratracheally instilled mice (10 mg/kg) with size-segregated ambient PM samples collected in
six European cities over various seasons: Duisberg autumn, Prague winter, Amsterdam winter,
Helsinki spring, Barcelona spring, Athens summer. PM exposure (PMio-2.5 and PM2.s-o.2)
increased bronchoalveolar lavage fluid (B ALF) total cell number and B ALF protein
concentration. No formal source apportionment was conducted, but oxidized organic compounds
(e.g., dicarboxylic acids), transition metals (e.g., Fe and Cr), and source tracers for fuel oil
combustion (i.e., Ni and V) were the most strongly correlated components of PM2 5.0.2
contributing to the inflammatory response (i.e., BALF total cell number). These studies
measured response to PMio-2.5 and PM2.5-o.2 PM samples, and generally report stronger
inflammatory responses (e.g., BALF cytokines, cell number, and total protein) after exposure to
coarse PM compared to fine. Source tracers for soil (K+, magnesium [Mg2+], Cu, manganese
[Mn], Fe) and sea spray (Na+, chlorine [Cl~], and N(V) found in PMio-2.5 were the most strongly
correlated with inflammatory response.
A few studies discuss how seasonal variation in PM components may affect PM-induced health
effects. Happo et al. (2010a) intratracheally instilled mice (10 mg/kg) with size-fractionated
ambient PM collected in Helsinki in the winter, spring, summer, and autumn. PM collected in the
spring produced the highest relative inflammatory activity (i.e., total cell number, total protein,
tissue necrosis factor alpha [TNF-a], interleukin-6 [IL-6], and keratinocyte-derived chemokine in
BALF) when dose was adjusted to the PM per cubic meter of urban air, whereas the PM
collected in the autumn produced the highest inflammation per equal mass dose. This difference
was influenced by a greater PM mass concentration in urban air in the springtime. The overall
inflammatory activity of PM decreased with particle size, such that PMio-2.5 and PM2.5-i had a
higher potency than PMi_0.2 and PM0.2. Components of road dust (Ca2+, Fe, Mn, and Al) and
trace metals (presumed to be the result of non-exhaust PM from traffic; Cu, Chromium [Cr],
cobalt [Co]) were consistently correlated with BALF inflammatory response in PM2.s-i.
Resuspension of road dust was also strongly correlated with inflammatory responses to PMio-2.5.
37
-------
Farina et al. (2011) treated mice (100 jig, intratracheal aerosolization) with size-fractionated
ambient PM collected from Milano, Italy in summer and winter. A stronger inflammatory
activity was generally observed after administration of summer PMi0 and PM2.5 than winter PM.
PMio exposure resulted in a higher TNF-a concentration (in BALF) compared to PM2.5, and this
was attributed to the greater endotoxin concentration and bacteria content of PMio.
Additional studies assessed the differential responses of PM collected at different distances from
a highway. Cho et al. (2009) found similar composition in size-fractionated ambient PM
collected near (20 m) and far (275 m) from a road in Raleigh, NC; however, PM collected near-
road was enriched with metals and a greater concentration of endotoxin. Coarse PM samples, but
not fine PM samples, produced pulmonary inflammation (i.e., BALF, macrophage inflammatory
protein 2 [MIP-2], TNF-a, IL-6) in exposed mice (25 and 100 jig) irrespective of distance
collected from the road. Zhang et al. (2011) reported greater increases in protein and lactate
dehydrogenase [LDH] in BALF after instillation (7.5 mg/kg) of PM2.5 collected near traffic
compared to far from traffic in Beijing, China. Chemical analysis of the near-traffic PM revealed
higher concentrations of poly cyclic aromatic hydrocarbons [PAHs] and heavy metal elements
(arsenic [As], Cd, Zn, S), but no statistical correlations were computed between these
components and the health effects observed.
A number of studies have attempted to disentangle the role of PM and gaseous components in
the health effects associated with ambient air pollution exposure by removing PM from the
mixture using a high efficiency particle filter. A few recent studies report cardiovascular,
respiratory, and reproductive effects after exposure to unfiltered (the whole mixture), but not
filtered Sao Paulo urban air (20 m from road) (Pires et al., 2011; Matsumoto et al., 2010;
Akinaga et al., 2009). These studies suggest that PM but not the gaseous components of the
urban air play a role in these responses.
2.3.3.2. Toxicology Studies Comparing Source-Derived PM and Components
A number of studies attempted to characterize effects from ambient PM sources by exposing
animals in the laboratory to PM derived from potential ambient sources (e.g., coal combustion,
diesel).
A series of studies evaluated the health effects resulting from various coal-fired power plant
emissions scenarios (Diaz et al., 2011; Godleski et al., 201 la: Godleski et al., 201 lc: Godleski et
al., 201 lb: Lemos et al., 2011; Wellenius et al., 2011). Stack emissions were collected from three
coal-fired power plants and various atmospheric transformations (e.g., oxidation, reaction with a-
pinene, neutralization) were simulated to investigate the toxicity of primary and photochemically
aged (secondary) particles. Particle mass concentrations varied from 43.8 to 257.1 |ig/m3 (Kang
et al., 2011). Rats were exposed to these simulated emissions scenarios for 6 hours and
demonstrated (1) increased BALF total cells, macrophages, and neutrophils (Godleski et al.,
2011 a): (2) moderately increased heart and lung reactive oxygen species (measured by in vivo
chemiluminescence) (Lemos etal., 2011), 3) increased premature ventricular beat frequency, but
38
-------
no change in heart rate, HRV, or ECG intervals (Wellenius et al., 2011): and 4) breathing pattern
changes (Diazetal., 2011). Overall, specific PM components did not predict respiratory or
cardiovascular effects observed after PM exposure as well as simulated atmospheric
transformation scenarios.
Additionally, a few studies assessed respiratory, cardiovascular, and systemic effects following
exposure to filtered and unfiltered simulated downwind coal combustion emissions (Barrett et
al., 2011; Mauderly et al., 2011). Barrett et al. (2011) reported different respiratory effects after
exposure to filtered and unfiltered emissions. Mauderly et al. (2011) found 17 out of 270 species-
gender-time-outcome comparisons were affected by whole emissions and that PM participated in
only 3 responses (liver weight, serum K+, and MIP-2). The authors concluded that PM
contributed to a few of the effects but that the pollutants responsible for the effects observed
were not able to be identified.
Studies have also evaluated the role of PM in engine emissions on the progression of health
effects. Tzamkiozis et al. (2010) instilled mice with PM collected from a gasoline Euro 3 car, a
diesel Euro 2 car, and a diesel Euro 4 car (with a diesel particle filter). Significant pulmonary
inflammation (i.e., BALF polymorphonuclear leukocytes (PMN) number) and injury (i.e., BALF
protein concentration) occurred 24 hours after treatment. The strongest associations with these
effects were observed for the PM components, P, Mn, Fe, Pb, reactive oxygen species (ROS),
benz(a)anthracene, chrysene, and medium and heavy PAHs. A strong association was also
observed between pulmonary injury and S.
A number of studies evaluated the impact of inhaled diesel exhaust on the cardiovascular system
with and without filtration (Gordon et al.. 2012: Lamb et al.. 2012: Seilkop et al.. 2012: Campen
et al., 2010). Different cardiovascular effects were reported after filtration of diesel exhaust by
Gordon et al. (2012) and Lamb et al. (2012). Campen et al. (2010) found that filtration of PM
from diesel exhaust did not alter the vascular responses observed. Seilkop et al. (2012) ranked
components of diesel or gasoline exhaust, wood smoke, or simulated "downwind" coal emissions
by their ability to induce pro-atherosclerotic responses in the aorta of mice that inhaled these
pollutant mixtures 6 hours/day for 50 days. Filtration of PM did not have a large effect on the
responses measured. Gases (i.e., SO2, ammonia (NH3), NO2, CO)) were found to be most highly
predictive of the response indicators. These studies using filtration of PM from whole mixtures did not
consistently identify whether PM or gases from whole air pollution mixtures led to the cardiovascular,
respiratory, or reproductive effects observed.
Summary
The few epidemiologic studies that have been conducted since the completion of the 2009 PM
ISA continue to report health effects with a number of sources and components. Toxicological
studies have attempted to identify whether particular sources or components are responsible for
the health effects observed by comparing the health effects, primarily cardiopulmonary effects,
observed in response to exposures to ambient fine PM sources and components and source-
derived PM and components. However, the toxicology studies did not find consistent evidence
39
-------
that one source or component is most closely related to a specific health effect. Collectively these
studies continue to report that a variety of sources and components are linked with
cardiopulmonary effects and mortality; however, there is still insufficient evidence to determine
which sources or components are most closely related to the observed effects.
3. SUMMARY AND CONCLUSIONS
The new studies published since the completion of the 2009 PM ISA provide additional evidence
indicating a relationship between exposure to ambient PM and health effects. The new studies
provide important insights on the health effects of PM exposure, with the results continuing to
support a relationship between PM exposure and health effects at ambient concentrations similar
or lower than those observed in previous studies. Overall: (a) the new studies generally
strengthen the evidence that acute and chronic exposures to fine PM; (b) although limited in
number, coarse PM studies provide evidence of an association with short-exposures and pediatric
asthma ED visits, but no association between long-term exposure and mortality; (c) some of the
new epidemiologic studies report effects in areas with long-term mean or mean 24-h avg PM2.5
concentrations lower than that reported in the 2009 PM ISA; and (d) new toxicology and
epidemiologic studies continue to link various health outcomes with a range of fine PM sources
and components. In conclusion, the results of the new studies identified and described in this
provisional assessment does not materially change any of the broad scientific conclusions
regarding the health effects of PM exposure made in the 2009 PM ISA.
In summary, this provisional assessment found:
Long-term PM Exposure
• Mortality: Generally, the results of recent studies are consistent with the evidence for an
association between long-term exposure to PM2.5 and mortality (i.e., all-cause and
cardiovascular) within the range of long-term mean PM2.5 concentrations characterized in the
2009 PM ISA (i.e., 13.2 - 32.0 |ig/m3), with one new Canadian multi-city study showing
associations at concentrations below 10 |ig/m3. New studies provide additional evidence for
respiratory mortality, including lung cancer. Two recent studies that examined associations
between long-term PMio-2.s exposure and mortality do not observe an association in either
men or women.
• Cardiovascular morbidity: Recent studies continue to demonstrate the strongest
cardiovascular effects in women, specifically for stroke, incident MI, and incident
hypertension at long-term mean PM2.5 concentrations ranging from 9.7 - 21.5 |ig/m3.
• Respiratory morbidity: Recent studies provide additional evidence for respiratory
symptoms and incident asthma, as well as respiratory hospitalizations at long-term mean
PM2.5 concentrations ranging from 9.7 - 27.0 |ig/m3' which is consistent with the conclusions
of the 2009PM IS A.
40
-------
• Reproductive and Developmental Outcomes: Recent studies continue to provide evidence
for developmental outcomes, specifically reductions in birth weight, at long-term mean PM2.5
concentrations ranging from 11.0 - 19.8 |ig/m3, which further support the conclusions of the
2009 PM ISA.
Short-Term PM Exposure
• Mortality: The limited number of mortality studies conducted in the U.S. and Canada
further support the conclusions of the 2009 PM ISA and continue to demonstrate associations
between short-term PM2.5 exposure and mortality at mean 24-h average concentrations
greater than 12.8 |ig/m3. Since the completion of the 2009 PM ISA no new studies have been
conducted that examined associations between short-term exposure to PMio-2.s and mortality.
• Respiratory hospital admissions/ED visits: New multi-city and single-city studies
demonstrate consistent positive associations for all respiratory-related hospital
admissions/ED visits, and provide additional evidence for increases in asthma hospital
admissions/ED visits in areas with mean 24-h average PM2.5 concentrations ranging from 6.7
- 22.0 |ig/m3, which further supports the conclusions of the 2009 PM ISA. One new study
was identified that examined the association between short-term PMi0-2.5 exposure and
respiratory-related ED visits, and provided evidence of increases in pediatric asthma ED
visits.
• Cardiovascular hospital admissions/ED visits: New studies focusing primarily on all
cardiovascular hospital admissions/ED visits continue to demonstrate consistent positive
associations in areas with mean 24-h average PM2.s concentrations ranging from 6.7 - 15.3
|ig/m3. Additionally, there is new evidence for potential associations with hypertension ED
visits, and a new study demonstrating an association with stroke onset.
Health Effects Related to Sources or Components ofPM
• Consistent with those studies evaluated in the 2009 PM ISA, new studies continue to
demonstrate cardiovascular and mortality effects with sources and components related to a
number of combustion activities (e.g., motor vehicle emissions, coal combustion, oil burning,
power plants, and wood smoke/vegetative burning), crustal sources, and secondary sulfate.
Additional new studies also add to the limited number of studies that have examined
associations between sources and components and respiratory and birth outcome effects, as
well as, long-term exposure and mortality. Overall, new studies support the conclusions of
the 2009 PM ISA that many PM components can be linked with differing health effects and
the evidence is not yet sufficient to allow differentiation of those components or sources that
are more closely related to specific health outcomes.
41
-------
APPENDIX A. Studies Included in the PM Provisional Science Assessment
Table A.I. Characterization of Studies of Long-term Exposure to PM2.5 and Mortality
Author
Grouse
etal.
(2012)
Can et
al.
(2011)
Greven
etal.
(2011)
Hartet
al.
(2010)
Jerrett
etal.
(2009b)
Jerrett
etal.
(2009a)
Lepeule
etal.
(2012)
Lipsett
etal.
(2011)
Years
of
Study
1991-
2001
AQ:
1994-
1998;
Death
s:
1999-
2002
2000-
2006
AQ:
2000
Death
s:
1985-
2000
1992-
2002
AQ:
1999-
2000
Death
s:
1982-
2000
1974-
2009
AQ:
1999-
2005;
Death
s:
1995-
2005
Location
Canada
(nationwide
)
Vancouver,
BC
Canada
U.S.
(nationwide
)
U.S.
(nation-
wide)
Toronto,
Canada
U.S.
(nation-
wide; 86
MSAs)
U.S(6
cities in
East and
Midwest)
California
Outcome
All-Cause,
CVD, IHD
Mortality
CHD Mortality
All-Cause
All-Cause,
Lung Cancer,
CVD Disease,
IHD,
Respiratory
Disease,
COPD Mortality
All-Cause,
Circulatory
Mortality
All-Cause,
Cardiopulmona
ry, CVD, IHD,
Respiratory
All Cause, CVD
and Lung
Cancer
Mortality
All-Cause,
CVD,
Respiratory,
Lung Cancer,
IHD, CBD
Population
Nonimmigrant
Canadian
adults
Adults (45-85)
without known
CHD at
baseline
Medicare
recipients
(65+ yrs)
Adult males
from 4 U.S.
trucking
companies
Adults from
respiratory
clinic
Adults
Adults
Adults
(Female
teachers)
Size
Fraction
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
Long-term
Mean
Concen-
tration
(ug/m3)
8.7
4.08
13.0
14.1
8.71
14.3
15. 9 (six
cities
combined);
means for
individual
cities ranged
from 1 1 .4-
23.6
15.64
Upper
Percentile
Concen-
trations
(ug/m3)
Max: 19.2
Max: 10.24
75th: 14.7
NR
75th: 8.83
NR
NR
Max: 28.35
42
-------
Author
McKean
Cowden
etal.
(2009)
Ostro et
al.
(2010)
Puett et
al.
(2009)
Puett et
al.
(2011)
Years
of
Study
AQ:
1979-
1983;
1999-
2000;
Death
s:
1982-
2000
AQ:
2002-
2007
1992-
2002
1986-
2002
Location
U.S.
(nation-
wide)
California
U.S. (East
and
Midwest)
U.S. (East
and
Midwest)
Outcome
Brain Cancer
Mortality
All-Cause,
CPD, IHD
Mortality
All Cause and
CHD Mortality
All Cause and
CHD Mortality
Population
Adults
Adults
(Female
teachers)
Adults
(Female
Nurses)
Adults (Male
Health
Professionals)
Size
Fraction
PM2.5
PM2.s and
componen
ts (EC,
OC, SO4,
NO3, Fe,
K, Si, Zn)
PM2.5
PM2.5
Long-term
Mean
Concen-
tration
(ug/m3)
1979-1983:
21.1
1999-2000:
14.0
Avg: 17.7
17.0
13.9
17.8 (at
baseline)
Upper
Percentile
Concen-
trations
(ug/m3)
Max:
1979-1983:
30.0
1999-2000:
22.2
Avg: 23.6
Max: 34.7
75th:15.6
Max: 27.6
NR
CVD: Cardiovascular Disease, CHD: Coronary Heart Disease; IHD: Ischemic Heart Disease; COPD: Chronic Obstructive Pulmonary
Disease; CBD: Cerebrovascular Disease; NR: Not reported
Table A.2. Characterization of Studies of Long-term Exposure to PMio-2.5 and Mortality
Author
Puett et
al.
(2009)
Puett et
al.
(2011)
Years
of
Study
1992-
2002
1986-
2002
Location
U.S. (East
and
Midwest)
U.S. (East
and
Midwest)
Outcome
All-Cause
and CHD
Mortality
All-Cause
and CHD
Mortality
Population
Adults
(Female
Nurses)
Adults (Male
Health
Professionals)
Size
Fraction
PM10-2.5
PM-IO-Z5
Long-term Mean
Concentration
(ug/m3)
7.7
10.1 (at baseline)
Upper Percentile
Concentrations
(ug/m3)
75th: 9.2
Max: 26.9
NR
CHD: Coronary Heart Disease; NR: Not reported
43
-------
Table A.3. Characterization of Studies of Long-term Exposure to PM2.5 and Cardiovascular
Effects
Author
Puett et al.
(2011)
Lipsett et
al. (2011)
Coogan et
al. (2012)
Beckerman
etal.
(2012)
Adar et al.
(2010)
Study
Years
1989-
2003
1995-
2000
1995-
2005
1992-
1999
2002-
2003
Location
North-
east and
Midwest,
U.S.*
California
Los
Angeles,
CA
Toronto,
Ontario
6 US
Cities**
Outcome
All-cause
Mortality,
Nonfatal Ml,
fatal CHD,
and
Hemorrhagic
and Ischemic
Stroke
All Cause
Mortality,
CVD
mortality, IHD
mortality,
cerebro-
vascular
disease
mortality, Ml
incidence,
stroke
incidence
Hypertension
and Diabetes
Mellitus
(incidence)
IHD
(prevalence)
Retinal
Microvasculat
ure
Population
Health
Professionals
Fo I low-Up
Study
men, 40-75
yrs of age
California
Teachers
Study
N=124,614
women, 20-
>80 yrs
Black
Women's
Health Study
N=4204
(hypertension)
N-3236
(diabetes)
disease free
at baseline
N=2360
pulmonary
clinic patients
MESA,
N=4,607
46-87 years ,
no clinical
cardiovascular
disease at
baseline
Size
Fraction
PM2.5,
PM-lO-2.5
PM2.5
PM2.5
PM2.5
Long-term
Mean
Concen-
tration
(ug/m3)
Predicted
PM2s = 17.8
+ 34
_1 \J .^
Predicted
PM-IO-Z5 =
101 "*" 3 3
15.64
20.7
50th
percentile:
8.71
16 (±3)
Upper
Percentile
Concen-
trations
(ug/m3)
Interquartile
range (IQR):
PM2.5: 4.3
PM10-2.5: 4.3
Max: 28.35
75th: 21 .6
75th: 8.83
75th: 17.2
personal PM
prediction;
17.2; nearest
monitor PM-
17.3
Max: personal
PM prediction-
26.3; nearest
monitor PM-
25.4
44
-------
Author
O'Neill et
al. (2011)
Van Hee et
al. (2011)
Kloog et al.
Study
Years
2000-
2002
Jul
2000-
Aug
2002
2000-
2006
Location
6 US
Cites**
6 US
Cites**
New
England
Outcome
Arterial
Stiffness
Ventricular
Conduction
and
Repolarization
Abnormalities
Hospital
Admissions
Population
MESA
N-3,996
men and
women, 44-84
yrs
MESA
N-4,783
45 to 84 yrs
>65 years
Size
Fraction
PM2.5
PM2.5
PM2.5
(predicted)
Long-term
Mean
Concen-
tration
(ug/m3)
Imputed 20 yr
avg: 21.47±
5.00
16.80 ±3.90
(2005)
9.65
Upper
Percentile
Concen-
trations
(ug/m3)
17.79
Table A.4. Characterization of Studies of Long-term Exposure to PM2.5 and Respiratory Effects
Author
Noonan et al.
(2012)
Bhattacharyya
(2009)
Bhattacharyya
and Shapiro
(2010)
Patel et al.
(2009)
Years
of
Study
2003-
2009
1997-
2006
1997-
2006
1998-
2006
Location
Libby, MT
US
(Nation-
wide)
US
(Nation-
wide)
NYC, NY
Outcome
Respiratory
infections
(including
bronchitis)
Hay Fever and
Sinusitis
Ear Infections
Wheeze and
Cough
Population
National
Health
Interview
Survey
respondents
National
Health
Interview
Survey
respondents
Participants in
Columbia
Center for
Children's
Environmental
Health birth
cohort
Size
Fraction
PM2.5
PM2.5
PM2.5
PM2.5
Long-term
Mean
Concen-
tration
(ug/m3)
19.0-27.0
13.4-11.6
13.4-11.6
13.0
Upper
Percentile
Concen-
trations
(ug/m3)
NR
NR
NR
Max: 38.4
45
-------
Author
Parker et al.
(2009)
Nachman and
Parker (2012)
Karr et al.
(2009a)
Karr et al.
(2009b)
Kloog et al.
Neupane et al.
(2010)
Meng et al.
(2010)
Akinbami et al.
(2010)
Carlsten et al.
(2011)
Years
of
Study
1999-
2005
2002-
2005
1997-
2003
1999-
2003
2000-
2006
2003-
2005
2000-
2001
2001-
2004
1995-
2003
Location
US
(Nation-
wide)
US
(Nation-
wide)
Puget
Sound
Region,
WA
Georgia Air
Basin of
BC,
Canada
New
England
Hamilton,
ON,
Canada
San
Joaquin
Valley, CA
US
(Nation-
wide)
Vancouver,
BC,
Canada
Outcome
Respiratory
Allergies
Asthma,
sinusitis,
chronic
bronchitis
Bronchiolitis
hospital
admission
Inpatient or
outpatient
bronciolitis
Respiratory
hospital
admission
Pneumonia
hospital
admissions
Asthma
Symptons;
Asthma ED
visits or
hospitalizations
Asthma
prevalence
Incident
Asthma
Population
Children
(ages 3-17) in
National
Health
Interview
Survey
National
Health
Interview
Survey
respondents
Washington
State Birth
Events
Registry
Database
Infants born
between
1999-2002
Residents >65
years
Residents >65
years
San Joaquin
Valley
residents
participating
in 2001
California
Health
Interview
Survey)
Children
(ages 3-17) in
National
Health
Interview
Survey
Birth cohort
born in 1995
Size
Fraction
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
Long-term
Mean
Concen-
tration
(ug/m3)
13.1
12.1
12.0
5.8
9.7
10.7
21.4
13.3
5.6
Upper
Percent! le
Concen-
trations
(ug/m3)
75th: 15.2
75th: 14.4
Max: 27.5
75th: 14.0
Max: 36.9
Max: 12.0
75th: 10.1
Max: 17.8
75th: 113
95th: 12.4
Max: 13.0
75th: 23.5
75th: 15.7
NR
46
-------
Author
Clark et al.
(2010)
McConnell et
al. (2010)
Years
of
Study
1999-
2004
2002-
2006
Location
South-
western
BC,
Canada
Southern
California
Outcome
Incident
Asthma
Incident
Asthma
Population
Children born
in 1999 and
2000 and
followed up to
3-4 yrs
Kindergarten
and First
grade children
in Southern
California
Children's
Health Study
Size
Fraction
PM2.5
PM2.5
Long-term
Mean
Concen-
tration
(ug/m3)
5.6
13.9
Upper
Percentile
Concen-
trations
(ug/m3)
75th: 6.1
Max: 17.4
Table A.5. Characterization of Studies of Long-term Exposure to PM2.5 and Reproductive and
Developmental Effects
Author
Lee et al.
(2011)
Legro et
al.
(2010)
Vinikoor-
Imler et
al.
(2012)
Rich et
al.
(2009)
Chang et
al.
(2012b)
Darrow
etal.
(2009)
Rudra et
al.
(2011)
Wilhelm
etal.
(2011)
Years
of
Study
1997-
2001
2000-
2007
2000-
2003
1999-
2003
2001-
2005
1994-
2004
1996-
2006
2004-
2006
Location
PA
Northeastern
US
NC
NJ
NC
Atlanta, GA
Western WA
Los Angeles,
CA
Outcome
C-reactive
protein
In Vitro
Fertilization
(IVF)
success
Gestational
Hypertension
Fetal Growth
P re-term
birth (PTB)
PTB
PTB
PTB
Population
Healthy
women
Women
undergoing
IVF
All births in
NC
All births in
NJ
All births in
NC
All births in
Atlanta (5
counties)
Healthy
Women
All births in
LA county
Size
Fraction
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
Long-term
Mean
Concentration
(ug/m3)
16.4
14.0-14.5
14.5
13.8
13.0-15.3
16.5
10.0
18.0
Upper
Percentile
Concentrations
(ug/m3)
75th: 18.7
95th: 26.2
100th: 40.8
NR
75th: 15.7
NR
NR
Max: 34.1
75th: 12.7
100th: 17.2
NR
47
-------
Author
Marshall
etal.
(2010)
Bell et al.
(2012)
Bell et al.
(2010)
D arrow
etal.
(2011 b)
Ghosh et
al.
(2012)
Kloog et
al.
(2012b)
Kumar
(2012)
Morello-
Frosch et
al.
(2010)
Salihu et
al. (]n
Press)
Wilhelm
etal.
(2012)
Faiz et
al.
(2012)
Years
of
Study
1998-
2003
2000-
2004
2000-
2004
1994-
2004
1995-
2006
2000-
2008
2000-
2004
1996-
2006
2000-
2007
2004-
2006
1998-
2004
Location
NJ
CT and MA
CT and MA
Atlanta, GA
Los Angeles,
CA
MA
Chicago, IL
CA
Tampa, FL
Los Angeles,
CA
NJ
Outcome
Birth Defects
(Oral Clefts)
birth weight
(BW)
BW
BW
BW
BW, PTB
BW
BW
BW, PTB
BW
Stillbirth
Population
All births in
NJ
All births
from 5
counties
All births
from 5
counties
All births in
Atlanta (5
counties)
All births in
LA county
All births in
MA
All births
from
Chicago
MSA
All births in
CA
Women
participating
in Health
Start
Project
All births in
LA county
All births in
NJ
Size
Fraction
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
PM2.5
Long-term
Mean
Concentration
(ug/m3)
13.4
14.0
14.0
16.5
19.8
9.6
18.0
16.7
11.0
17.9
14.0
Upper
Percentile
Concentrations
(ug/m3)
NR
75th: 16.0
NR
NR
NR
75th: 11.6
NR
75th: 21.0
Max: 23.2
NR
NR
48
-------
Table A.6. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5 and
Mortality
Author
Ito et al.
(2011 a)
Zhou et
al.
(2011)
Chang
etal.
(2012a)
Klemm
etal.
(2011)
Years
2000-
2006
2000-
2004
2001-
2005
1998-
2007
Location
New
York, NY
Detroit,
Ml
Seattle,
WA
New
York, NY
Atlanta,
GA(4
counties)
Mortality
Cardiovascular
Non-accidental,
Cardiovascular,
Respiratory
Cardiovascular,
Respiratory
Non-accidental,
Cardiovascular,
Respiratory
Population
>40
All
>65
>65
Size
Fraction
PM2.5, PM
components
(EC, OC,
SO4, Ni, V,
Zn, Si, Se,
Na, Br, NO3)
PM2.5, PM
components
(Al, Fe, K,
Na, Ni, S, Si,
V, Zn, EC)
PM2.5
PM2.5, PM
components
(EC, OC,
N03, S04)
Mean 24-h avg
Concentration
(ug/m3)
PM2.5
All-Year: 14.4
Warm (April-
September):
14.8
Cold (October-
March): 14.1
Detroit
All-Year
(Median): 13.2
Warm (April-
September)
(Mean):15.3
Cold (October-
March) (Mean):
14.9
Seattle
All-Year
(Median): 7.9
Warm (April-
September)
(Mean): 8.0
Cold (October-
March) (Mean):
11.4
Spring (March-
May): 14.3
Summer (June-
August): 17.5
Fall
(September-
November):
13.3
Winter
(December-
February): 15.4
17.0
Upper
Percentile
Concentrations
(ug/m3)
NR
Detroit
Max: 65.8
Seattle
Max: 41. 3
NR
75th: 21. 6
Max: 72.9
49
-------
Table A.7. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5 and
Respiratory Hospital Admissions and Emergency Department Visits
Author
Bell et al.
(2012)
Zanobetti
etal.
(2009)
Stieb et
al. (2009)
Levy et
al. (2012)
Years
2000-
2005
2000-
2003
1992-
2003
2000-
2008
Location
187 U.S.
counties
26 U.S.
communities
7 Canadian
cities
119 U.S.
counties
Hospital
Admission/
ED Visit
Hospital
admissions:
All
respiratory
ED Visits:
All
respiratory
ED Visits:
Asthma
COPD
Respiratory
Infection
Hospital
Admissions:
All
respiratory
Popul-
ation
>65
>65
All
>65
Size
Fraction
PM2.5, PM
components
PM2.5, PM
components
(As, Al, Br,
Cr, Fe, Pb,
Mn, Ni, K,
Si, V, Zn,
NO3, SO4,
NH4, Na+,
EC, OC)
PM2.5
PM
components
(EC, OC,
SO4, NO3)
Mean 24-h
avg Concen-
tration
(ug/m3)
All-Year: 14.0
Summer: 16.2
Winter: 13.9
15.3
Montreal
(1/97-12/02):
8.6
Ottawa (4/92-
12/00): 6.7
Edmonton
(4/92-3/02):
8.5
Halifax (1/99-
12/02): 9.8
Toronto (4/99-
6/03): 9.1
Vancouver
(1/99-2/03):
6.8
Upper
Percentile
Concen-
trations
(ug/m3)
Max:
All Year: 26.0
Summer: 28.5
Winter: 32.8
PM2.5Max
Spring: 24
(Riverside, CA)
PM25Max
Winter: 29.9
(Fresno, CA)
75th:
Montreal: 10.9
Ottawa: 8.7
Edmonton: 10.9
Halifax: 11.3
Toronto: 11.9
Vancouver: 8.5
50
-------
Darrow et
al.
(2011 a)
Strickland
etal.
(2010)
Kim et al.
(2011)
Mar et al.
(2010)
Kloog et
al.
(2012a)
Li et al.
(2011)
Glad et
al. (2012)
1993-
2004
(PM2.5
collecte
d from
8/1/98-
12/31/0
4)
1993-
2004
(PM2.5
collecte
d from
8/1/98-
12/31/0
4)
2003-
2007
1998-
2002
2000-
2006
2004-
2006
2002-
2005
Atlanta, GA
Atlanta, GA
Denver, CO
Tacoma, WA
New England
Detroit, Ml
Pittsburgh,
PA
ED Visits:
All
respiratory
ED Visits:
Asthma
Hospital
Admissions:
All
respiratory
COPD
Asthma
Pneumonia
ED Visits:
Asthma
Hospital
Admissions:
All
respiratory
ED Visits:
Asthma
ED Visits:
Asthma
All
5-17
All
All
>65
2-18
All
PM2.5
PM2.5, PM
components
(SO4, EC,
OC, water-
soluble
metals)
PM2.5, PM
components
(EC, OC,
S04, N03)
PM2.5
PM2.5
PM2.5
PM2.5
1-h max: 29
24-h avg: 16
Commute: 17
Day-time: 15
Night-time: 17
PM2.5
All-Year: 16.4
Warm (May-
October): 18.4
Cold
(November-
April): 14.3
PMlO-2.5
All-Year: 9.0
Warm: 9.7
Cold: 8.3
8.0
12.3
9.6
15.0
13.3
1-h max:
75th: 36
Max: 188
24-h avg:
75th: 21
Max: 72
Commute:
75th: 21
Max: 76
Day-time:
75th: 19
Max: 71
Night-time:
75th: 14
Max: 88
NR
59.4
NR
Max: 72.6
75th: 18.5
Max: 69.0
Max: 55.0
51
-------
Grineski
etal.
(2011)
2000-
2003
El Paso, TX
Hospital
Admissions:
Asthma
Acute
bronchitis
>1
PM2.5
12.8
75th: 15.6
95th: 26.6
Max: 119.1
52
-------
Table A.8. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PMi0-2.5 and Respiratory Hospital Admissions
and Emergency Department Visits
Author
Strickland et al.
(2010)
Years
1993-2004
(PM2s collected from
8/1/98-12/31/04)
Location
Atlanta,
GA
Hospital
Admissions/
ED Visit
ED Visits:
Asthma
Population
5-17
Size
Fraction
PM-IO-2.5
Mean 24-h avg
Concentration
(ug/m3)
PM-IO-2.5
All-Year: 9.0
Warm: 9.7
Cold: 8.3
Upper Percentile
Concentrations (ug/m3)
NR
Table A.9. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5 and Cardiovascular Hospital Admissions
and Emergency Department Visits
Author
Zanobetti et al.
(2009)
Stieb et al.
(2009)
Study
Years
2000-2003
1990's-early
2000 's
(depending
on city)
Location
USA (26
communities)
Candada (7
Cities)
Outcome
ED Visits:
MI, CHF
ED
Visits : Angina/Ml,
Heart Failure,
Dysrhythmia
Population
Older
adults > 65
yrs
Size Fraction
PM25
PM25
components:
As, Al, Br, Cr,
Fe, Pb, Mn, Ni,
K, Si, V, Zn,
NO3, SO4,
NH4, Na+, EC,
OC
PM25
Mean 24-h avg
Concentration
ftig/m3)
15.3
City-specific means (range):
6.7-9.8
Upper Percentile
Concentrations (jig/m3)
PM25Max Spring: 24
(Riverside, CA)
PM25Max Winter: 29.9
(Fresno, CA)
City Specific 75th
Percentiles:
8.5-11.9
53
-------
Author
Ito et al.
QQlla)
Mathes et al.
(2011)
Szyszkowicz
et al. (20121
Haley et al.
(2009)
Bunch et al.
(2011)
Kloog et al.
(2Q12a)
Study
Years
2000-2006
2000-2002
Apr 1992-
Mar 2002
2001-2005
1993-1998
Location
New York,
NY
New York,
NY
Canada
(Edmonton)
New York
State
Wasatch
Front, Utah
New England
Outcome
ED Visits: CVD
ED Visits: CVD
ED Visits:
Hypertension
ED Visits
Hospital
Admissions
Hospital
Admissions
Population
>40 yrs
>40 yrs
N=5,365
Discharges
from all
NYS
hospitals
All
>65
Size Fraction
PM25
PM25
components:
EC, OC, SO4,
NO3, Na+, Ni,
V, Zn, Si, Se,
Br
PM25
PM25
PM25
PM25
PM25
(predicted)
Mean 24-h avg
Concentration
ftig/m3)
All yearAVarm/Cold:
14.44/14.79/ 14.09
1.13/1.03/1.24
4.3/4.51/4.08
4.14/4.81/3.42
2.12/1.52/2.78
0.14/0.14/0.15
0.0171/0.0111/0.0236
0.0066/ 0.0054/0.0080
0.0300/0.0216/0.0389
0.0769/ 0.0886/ 0.0643
0.0013/0.0011/0.0015
0.0036/0.0031/0.0040
—
8.5
NR
City specific means (range):
9.3-11.1
9.6
Upper Percentile
Concentrations (jig/m3)
Not presented
(Note: SD provided so
we could compute)
—
75thpercentile: 10.9
Max: 1.3.1
NR
City specific max:
9.3-11.1
72.59
54
-------
Author
Kim et al.
(2011)
Study
Years
2003-2007
Location
Denver
Outcome
Hospital
Admissions
Population
All
Size Fraction
PM25
EC
OC
Sulfate
Nitrate
Mean 24-h avg
Concentration
ftig/m3)
7.98
0.47
3.09
1.08
1.03
Upper Percentile
Concentrations (jig/m3)
59.41
3.02
10.28
14.32
19.72
55
-------
Table A.10. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.s
and Out of Hospital Cardiac Arrests
Author
Silverman
etal.
(2010)
Study
Years
2002-
2006
Location
USA
(New
York
City)
Outcome
Out-of-
hospital
cardiac
arrests
Population
N=8,216
<40 to > 70
yrs
Size
Fraction
rlvl2.5
Mean 24-h
avg
Concentration
(ug/m3)
Median:
All year = 12
Apr-Sept = 12
Oct-Mar= 12
Upper Percentile
Concentrations
(ug/m3)
Upper (95%):
All year = 30
Apr-Sept = 31
Oct-Mar = 28
Table A.11. Characterization of U.S. and Canadian Studies of Short-Term Exposure to PM2.5
and Time of Stroke Symptom Onset
Author
Wellenius
etal.
(2012)
Study
Years
1999-
2008
Location
Boston,
MA
Outcome
Time of
Symptom
Onset
(Ischemic
Stroke)
Population
Patients
admitted to
BIDMC
Size
Fraction
PM2.5
Mean 24-h
avg
Concentration
(ug/m3)
NR
Upper Percentile
Concentrations
(ug/m3)
NR
BIDMC= Beth Israel Deaconess Medical Center
56
-------
REFERENCES
Adar. SD: Klein. R: Klein. BEK: Szpiro. AA: Cotch. MF: Wong. TY: O'Neill. MS: Shrager. S: Barr. RG:
Siscovick. PS: Daviglus. ML: Sampson. PD: Kaufman. JD. (2010). Air Pollution and the
Microvasculature: A Cross-Sectional Assessment of In Vivo Retinal Images in the Population-Based Multi-
Ethnic Study of Atherosclerosis (MESA). PLoS Med 7: e!000372.
Akinaga. LM: Lichtenfels. AJ: Carvalho-Oliveira. R: Caldini. EG: Dolhnikoff. M: Silva. LF: Bueno. HM:
Pereira. LA: Saldiva. PH: Garcia. ML. (2009). Effects of chronic exposure to air pollution from Sao Paulo
city on coronary of Swiss mice, from birth to adulthood. Toxicol Pathol 37: 306-314.
http://dx.doi.org/10.1177/0192623309332994
Akinbamj LJ: Lynch. CD: Parker. JD: Woodruff. TJ. (2010). The association between childhood asthma
prevalence and monitored air pollutants in metropolitan areas, United States, 2001-2004. Environ Res 110:
294-301. http://dx.doi.0rg/10.1016/i.envres.2010.01.001
Barrett. EG: Day. KG: Gigliotti. AP: Reed. MD: Mcdonald. JD: Mauderly. JL: Seilkop. SK. (2011). Effects of
simulated downwind coal combustion emissions on pre-existing allergic airway responses in mice. Inhal
Toxicol 23: 792-804. http://dx.doi.org/10.3109/08958378.2011.609917
Beckerman. BS: Jerrett M: Finkelstein. M: Kanaroglou. P: Brook. JR: Arain. MA: Sears. MR: Stieb. D:
Balmes. J: Chapman. K. (2012). The association between chronic exposure to traffic-related air pollution
and ischemic heart disease. J Toxicol Environ Health A 75: 402-411.
http://dx.doi.org/10.1080/15287394.2012.670899
Bell ML: Belanger. K: Ebisu. K: Gent. JF: Leaderer. BP. (2012). Relationship between birth weight and
exposure to airborne fine paniculate potassium and titanium during gestation. Environ Res 117: 83-89.
http://dx.doi.0rg/10.1016/i.envres.2012.05.004
Bell ML: Belanger. K: Ebisu. K: Gent. JF: Lee. HJ: Koutrakis. P: Leaderer. BP. (2010). Prenatal exposure to
fine paniculate matter and birth weight: Variations by paniculate constituents and sources. Epidemiology
21: 884-891. http://dx.doi.org/10.1097/EDE.Ob013e3181f2f405
Bell ML: Committee. HHR. (2012). Assessment of the health impacts of paniculate matter characteristics. Res
Rep Health EffInst5-38.
Bell ML: Dominici F: Ebisu. K: Zeger. SL: Samet JM. (2007). Spatial and Temporal Variation in PM2. 5
Chemical Composition in the United States for Health Effects Studies. Environ Health Perspect 115: 989-
995. http://dx.doi.org/10.1289/ehp.9621
Bell ML: Ebisu. K: Peng. RD: Dominici F. (2009a). Adverse health effects of paniculate air pollution:
modification by air conditioning. Epidemiology 20: 682-686.
http://dx.doi.org/10.1097/EDE.Ob013e3181aba749
Bell. ML: Ebisu. K: Peng. RD: Samet JM: Dominici. F. (2009b). Hospital admissions and chemical
composition of fine particle air pollution. Am J Respir Crit Care Med 179: 1115-1120.
http://dx.doi.org/10.1164/rccm.200808-1240OC
Bell ML: Ebisu. K: Peng. RD: Walker. J: Samet. JM: Zeger. SL: Dominic. F. (2008). Seasonal and regional
short-term effects of fine particles on hospital admissions in 202 U.S. counties, 1999-2005. Am J
Epidemiol 168: 1301-1310. http://dx.doi.org/10.1093/aje/kwn252
Bhattacharwa. N. (2009). Air quality influences the prevalence of hay fever and sinusitis. Laryngoscope 119:
429-433. http://dx.doi.org/10.1002/lary.20097
Bhattacharwa. N: Shapiro. NL. (2010). Air quality improvement and the prevalence of frequent ear infections
in children. Otolaryngol Head Neck Surg 142: 242-246. http://dx.doi.0rg/10.1016/i.otohns.2009.10.052
57
-------
Bunch. TJ: Home. BD: Asirvatham. SJ: Day. JD: Crandall BG: Weiss. JP: Osborn. JS: Anderson. JL:
Muhlestein. JB: Lappe. PL: Pope. CA. (2011). Atrial fibrillation hospitalization is not increased with short-
term elevations in exposure to fine paniculate air pollution. Pacing Clin Electrophysiol 34: 1475-1479.
http://dx.doi.0rg/10.llll/i.1540-8159.2011.03200.x
Burgess. JA: Matheson. MC: Gurrin. LC: Byrnes. GB: Adams. KS: Wharton. CL: Giles. GG: Jenkins. MA:
Hopper. JL: Abramson. MJ: Walters. EH: Dharmage. SC. (2011). Factors influencing asthma remission: a
longitudinal study from childhood to middle age. Thorax 66: 508-513.
http://dx.doi.org/10.1136/thx.2010.146845
Campen. MJ: Lund. AK: Knuckles. TL: Conklin. DJ: Bishop. B: Young. D: Seilkop. S: Seagrave. J: Reed.
MD: Mcdonald. JD. (2010). Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE(-/-)
mice. Toxicol Appl Pharmacol 242: 310-317. http://dx.doi.0rg/10.1016/i.taap.2009.10.021
Carlsten. C: Dybuncio. A: Becker. A: Chan-Yeung. M: Brauer. M. (2011). Traffic-related air pollution and
incident asthma in a high-risk birth cohort. Occup Environ Med 68: 291-295.
http://dx.doi.org/10.1136/oem.2010.055152
Chang. HH: Fuentes. M: Frev. HC. (2012a). Time series analysis of personal exposure to ambient air pollution
and mortality using an exposure simulator. J Expo Sci Environ Epidemiol 22: 483-488.
http://dx.doi.org/10.1038/ies.2012.53
Chang. HH: Reich. BJ: Miranda. ML. (2012b). Time-to-event analysis of fine particle air pollution and preterm
birth: Results from North Carolina, 2001-2005. Am J Epidemiol 175: 91-98.
http://dx.doi.org/10.1093/aje/kwr403
Chen. LC: Hwang. JS: Lall R: Thurston. G: Lippmann. M. (2010). Alteration of cardiac function in ApoE-/-
mice by subchronic urban and regional inhalation exposure to concentrated ambient PM2.5. Inhal Toxicol
22: 580-592. http://dx.doi.org/10.3109/08958371003596579
Chen. LH: Knutsen. SF: Shavlik. D: Beeson. WL: Petersen. F: Ghamsary. M: Abbey. D. (2005). The
association between fatal coronary heart disease and ambient paniculate air pollution: Are females at
greater risk? Environ Health Perspect 113: 1723-1729.
Cho. SH: Tong. H: Mcgee. J: Baldauf. R: Krantz. Q: Gilmour. M. (2009). Comparative Toxicity of Size-
Fractionated Airborne Paniculate Matter Collected at Different Distances from an Urban Highway. Environ
Health Perspect 117: 1682-1689. http://dx.doi.org/10.1289/ehp.0900730
Clark. NA: Demers. PA: Karr. CJ: Koehoorn. M: Lencar. C: Tamburic. L: Brauer. M. (2010). Effect of early
life exposure to air pollution on development of childhood asthma. Environ Health Perspect 118: 284-290.
http://dx.doi.org/10.1289/ehp.0900916
Coogan. PF: White. LF: Jerrett M: Brook. RD: Su. JG: Seto. E: Burnett. R: Palmer. JR: Rosenberg. L. (2012).
Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles.
Circulation 125: 767-772. http://dx.doi.org/10.1161/CIRCULATIONAHA.lll.052753
Grouse. PL: Peters. PA: van Donkelaar. A: Goldberg. MS: Villeneuve. PJ: Brion. O: Khan. S: Atari. DO:
Jerrett M: Pope. CA: Brauer. M: Brook. JR: Martin. RV: Stieb. D: Burnett RT. (2012). Risk of
nonaccidental and cardiovascular mortality in relation to long-term exposure to low concentrations of fine
paniculate matter: a Canadian national-level cohort study. Environ Health Perspect 120: 708-714.
http://dx.doi.org/10.1289/ehp. 1104049
Darrow. LA: Klein. M: Flanders. WD: Waller. LA: Correa. A: Marcus. M: Mulholland. JA: Russell AG:
Tolbert PE. (2009). Ambient air pollution and preterm birth: A time-series analysis. Epidemiology 20:
689-698. http://dx.doi.org/10.1097/EDE.Ob013e3181a7128f
Darrow. LA: Klein. M: Sarnat JA: Mulholland. JA: Strickland. MJ: Sarnat SE: Russell AG: Tolbert. PE.
(201 la). The use of alternative pollutant metrics in time-series studies of ambient air pollution and
respiratory emergency department visits. JExpo Sci Environ Epidemiol 21: 10-19.
http://dx.doi.org/10.1038/ies.2009.49
58
-------
Darrow. LA: Klein. M: Strickland. MJ: Mulholland. JA: Tolbert. PE. (201 Ib). Ambient air pollution and birth
weight in full-term infants in Atlanta, 1994-2004. Environ Health Perspect 119: 731-737.
http://dx.doi.org/10.1289/ehp. 1002785
Diaz. EA: Lemos. M: Coull B: Long. MS: Rohr. AC: Ruiz. P: Gupta. T: Kang. CM: Godleski. JJ. (2011).
Toxicological evaluation of realistic emission source aerosols (TERESA)--power plant studies: assessment
of breathing pattern. Inhal Toxicol 23 Suppl 2: 42-59. http://dx.doi.org/10.3109/08958378.2010.578169
Dockerv. DW: Pope. CA. Ill: Xu. X: Spengler. JD: Ware. JH: Fay. ME: Ferris. BG. Jr: Speizer. FE. (1993). An
association between air pollution and mortality in six US cities. N Engl J Med 329: 1753-1759.
http://dx.doi.org/10.1056/NEJM199312093292401
Dominici F: Peng. RD: Bell. ML: Pham. L: Mcdermott A: Zeger. SL: Samet. JL. (2006). Fine particulate air
pollution and hospital admission for cardiovascular and respiratory diseases. 295: 1127-1134.
http://dx.doi.org/10.100 l/iama.295.10.1127
Faiz. AS: Rhoads. GG: Demissie. K: Kruse. L: Lin. Y: Rich. DQ. (2012). Ambient air pollution and the risk of
stillbirth. Am J Epidemiol 176: 308-316. http://dx.doi.org/10.1093/aje/kws029
Farina. F: Sancini. G: Mantecca. P: Gallinotti. D: Camatini. M: Palestini. P. (2011). The acute toxic effects of
particulate matter in mouse lung are related to size and season of collection. Toxicol Lett 202: 209-217.
http://dx.doi.0rg/10.1016/i.toxlet.2011.01.031
Franklin. M: Koutrakis. P: J. S. (2008). The role of particle composition on the association between PM2.5 and
mortality. 19: 680-689. http://dx.doi.org/10.1097/EDE.Ob013e3181812bb7
Gan. W: Koehoorn. M: Davies. H: Demers. P: Tamburic. L: Brauer. M. (2011). Long-term exposure to traffic-
related air pollution and the risk of coronary heart disease hospitalization and mortality. Environ Health
Perspect 119: 501-507. http://dx.doi.org/10.1289/ehp. 1002511
Ghosh. JK: Wilhelm. M: Su. J: Goldberg. D: Cockburn. M: Jerrett M: Ritz. B. (2012). Assessing the Influence
of Traffic-related Air Pollution on Risk of Term Low Birth Weight on the Basis of Land-Use-based
Regression Models and Measures of Air Toxics. Am J Epidemiol 175: 1262-1274.
http://dx.doi.org/10.1093/aje/kwr469
Glad. JA: Brink. LL: Talbott EO: Lee. PC: Xu. X: Saul M: Rager. J. (2012). The relationship of ambient
ozone and PM(2.5) levels and asthma emergency department visits: possible influence of gender and
ethnicity. Arch Environ Occup Health 67: 103-108. http://dx.doi.org/10.1080/19338244.2011.598888
Godleski. JJ: Diaz. EA: Lemos. M: Long. M: Ruiz. P: Gupta. T: Kang. CM: Coull B. (201 la). Toxicological
evaluation of realistic emission source aerosols (TERESA)-power plant studies: assessment of cellular
responses. Inhal Toxicol 23 Suppl 2: 60-74. http://dx.doi.org/10.3109/08958378.2010.563804
Godleski. JJ: Rohr. AC: Coull. BA: Kang. CM: Diaz. EA: Koutrakis. P. (20lib). Toxicological evaluation of
realistic emission source aerosols (TERESA): summary and conclusions. Inhal Toxicol 23 Suppl 2: 95-103.
http://dx.doi.org/10.3109/08958378.2011.604687
Godleski. JJ: Rohr. AC: Kang. CM: Diaz. EA: Ruiz. PA: Koutrakis. P. (201 Ic). Toxicological evaluation of
realistic emission source aerosols (TERESA): Introduction and overview. Inhal Toxicol 23: 1-10.
http://dx.doi.org/10.3109/08958378.2010.568019
Gordon. CJ: Schladweiler. MC: Krantz. T: King. C: Kodavanti. UP. (2012). Cardiovascular and
thermoregulatory responses of unrestrained rats exposed to filtered or unfiltered diesel exhaust. 24: 296-
309. http://dx.doi.org/10.3109/08958378.2012.670811
Greven. S: Dominici. F: Zeger. S. (2011). An Approach to the Estimation of Chronic Air Pollution Effects
Using Spatio-Temporal Information. J Am Stat Assoc 106: 396-406.
http://dx.doi.org/10.1198/iasa.2011.apQ9392
Grineski. SE: Staniswalis. JG: Bulathsinhala. P: Peng. Y: Gill. TE. (2011). Hospital admissions for asthma and
acute bronchitis in El Paso, Texas: do age, sex, and insurance status modify the effects of dust and low
wind events. Environ Res 111: 1148-1155. http://dx.doi.org/10.1016/i.envres.2011.06.007
59
-------
Haley. VB: Talbot TO: Felton. HP. (2009). Surveillance of the short-term impact of fine particle air pollution
on cardiovascular disease hospitalizations in New York State. Environ Health Global Access Sci Source 8:
42. http://dx.doi.org/10.1186/1476-069X-8-42
Happo. MS: Hirvonen. MR: Halinen. AI: Jalava. PI: Pennanen. AS: Sillanpaa. M: Hillamo. R: Salonen. RO.
(2010a). Seasonal variation in chemical composition of size-segregated urban air particles and the
inflammatory activity in the mouse lung. Inhal Toxicol 22: 17-32.
http://dx.doi.org/10.3109/08958370902862426
Happo. MS: Salonen. RO: Halinen. AI: Jalava. PI: Pennanen. AS: Dormans. JA: Gerlofs-Nijland. ME: Cassee.
FR: Kosma. VM: Sillanpaa. M: Hillamo. R: Hirvonen. MR. (2010b). Inflammation and tissue damage in
mouse lung by single and repeated dosing of urban air coarse and fine particles collected from six European
cities. Inhal Toxicol 22: 402-416. http://dx.doi.org/10.3109/08958370903527908
Hart. JE: Garshick. E: Dockery. DW: Smith. TJ: Ryan. L: Laden. F. (2010). Long-term ambient multi-pollutant
exposures and mortality. Am J Respir Crit Care Med InPress: In Press.
http://dx.doi.org/10.1164/rccm.200912-1903OC
Ito. K: Mathes. R: Ross. Z: Nadas. A: Thurston. G: Matte. T. (201 la). Fine paniculate matter constituents
associated with cardiovascular hospitalizations and mortality in New York City. Environ Health Perspect
119: 467-473. http://dx.doi.org/10.1289.ehp. 1002667
Ito. K: Mathes. R: Ross. Z: Nadas. A: Thurston. G: Matte. T. (201 Ib). Fine paniculate matter constituents
associated with cardiovascular hospitalizations and mortality in New York City. 119: 467-473.
http://dx.doi.org/10.1289/ehp. 1002667
Janes. H: Dominici. F: Zeger. SL. (2007). Trends in air pollution and mortality: an approach to the assessment
of unmeasured confounding. Epidemiology 18: 416-423.
Jerrett M: Burnett. RT: Pope. CA. Ill: Ito. K: Thurston. G: Krewski. D: Shi. Y: Calle. E: Thun. M. (2009a).
Long-term ozone exposure and mortality. N Engl J Med 360: 1085-1095.
http://dx.doi.org/10.1056/NEJMoa0803894
Jerrett M: Finkelstein. MM: Brook. JR: Arain. MA: Kanaroglou. P: Stieb. DM: Gilbert. NL: Verma. D:
Finkelstein. N: Chapman. KR: Sears. MR. (2009b). A cohort study of traffic-related air pollution and
mortality in Toronto, Ontario, Canada. Environ Health Perspect 117: 772-777.
http://dx.doi.org/10.1289/ehp.11533
Kamal AS: Rohr. AC: Mukherjee. B: Morishita. M: Keeler. GJ: Harkema. JR: Wagner. JG. (2011). PM2.5-
induced changes in cardiac function of hypertensive rats depend on wind direction and specific sources in
Steubenville, Ohio. Inhal Toxicol 23: 417-430. http://dx.doi.org/10.3109/08958378.2011.580387
Kang. CM: Gupta. T: Ruiz. PA: Wolfson. JM: Ferguson. ST: Lawrence. JE: Rohr. AC: Godleski. J: Koutrakis.
R (2011). Aged particles derived from emissions of coal-fired power plants: The TERESA field results.
Inhal Toxicol 23: 11-30. http://dx.doi.org/10.3109/08958371003728040
Karr. C: Rudra. C: Miller. K: Gould. T: Larson. T: Sathyanaravana. S: Koenig. J. (2009a). Infant exposure to
fine paniculate matter and traffic and risk of hospitalization for RSV bronchiolitis in a region with lower
ambient air pollution. Environ Res 109: 321-327. http://dx.doi.0rg/10.1016/i.envres.2008.ll.006
Karr. CJ: Demers. PA: Koehoorn. MW: Lencar. CC: Tamburic. L: Brauer. M. (2009b). Influence of Ambient
Air Pollutant Sources on Clinical Encounters for Infant Bronchiolitis. Am J Respir Crit Care Med 180: 995-
1001. http://dx.doi.org/10.1164/rccm.200901-0117OC
Kim. SY: Vedal S: Peel JL: Hannigan. MP: Dutton. SJ: Sheppard. L. (2011). Lag structure of the associations
between PM2.5 components and hospitalization in Denver [Abstract]. Epidemiology 22: S199.
http://dx.doi.org/10.1097/01.ede.0000392292.03735.ee
Klemm. PJ: Lipfert. FW: Wyzga. RE: Gust C. (2004). Daily mortality and air pollution in Atlanta: two years
of data from ARIES. 16 Suppl 1: 131-141. http://dx.doi.org/10.1080/08958370490443213
Klemm. RJ: Mason. RM. Jr. (2000). Aerosol Research and Inhalation Epidemiological Study (ARIES): air
quality and daily mortality statistical modeling-interim results. 50: 1433-1439.
60
-------
Klemm. RJ: Thomas. EL: Wyzga. RE. (2011). The impact of frequency and duration of air quality monitoring:
Atlanta, GA, data modeling of air pollution and mortality. J Air Waste Manag Assoc 61: 1281-1291.
Kloog. I: Coull BA: Zanobetti. A: Koutrakis. P: Schwartz. JD. (2012a). Acute and chronic effects of particles
on hospital admissions in New-England. PLoS ONE 7: e34664.
http://dx.doi.org/10.1371/iournal.pone.0034664
Kloog. I: Melly. SJ: Ridgwav. WL: Coull BA: Schwartz. J. (2012b). Using new satellite based exposure
methods to study the association between pregnancy pm 2.5 exposure, premature birth and birth weight in
Massachusetts. Environ Health Global Access Sci Source 11: 40. http://dx.doi.org/10.1186/1476-069X-ll-
40
Krewskj D. (2009). Evaluating the effects of ambient air pollution on life expectancy. 360: 413-415.
Kumar. N. (2012). Uncertainty in the relationship between criteria pollutants and low birth weight in Chicago.
Atmos Environ 49: 171-179.
Laden. F: Schwartz. J: Speizer. FE: Dockery. DW. (2006). Reduction in fine paniculate air pollution and
mortality: extended follow-up of the Harvard Six Cities study. Am J Respir Crit Care Med 173: 667-672.
Lall R: Ito. K: Thurston. G. (2011). Distributed lag analyses of daily hospital admissions and source-
apportioned fine particle air pollution. Environ Health Perspect 119: 455-460.
http://dx.doi.org/10.1289/ehp.1002638
Lamb. CM: Hazari. MS: Haykal-Coates. N: Carll AP: Krantz. QT: King. C: Winsett. DW: Cascio. WE: Costa.
PL: Farrai. AK. (2012). Divergent electrocardiographic responses to whole and particle-free diesel exhaust
inhalation in spontaneously hypertensive rats. Toxicol Sci 125: 558-568.
http://dx.doi.org/10.1093/toxsci/kfr296
Lee. PC: Talbott EO: Roberts. JM: Catov. JM: Sharma. RK: Ritz. B. (2011). Paniculate air pollution exposure
and c-reactive protein during early pregnancy. Epidemiology 22: 524-531.
http://dx.doi.org/10.1097/EDE.Ob013e31821c6c58
Legro. RS: Sauer. MV: Mottla. GL: Richter. KS: Li. X: Dodson. WC: Liao. D. (2010). Effect of air quality on
assisted human reproduction. Hum Reprod 25: 1317-1324. http://dx.doi.org/10.1093/humrep/deq021
Lemos. M: Diaz. EA: Gupta. T: Kang. CM: Ruiz. P: Coull BA: Godleski. JJ: Gonzalez-Flecha. B. (2011).
Cardiac and pulmonary oxidative stress in rats exposed to realistic emissions of source aerosols. Inhal
Toxicol 23: 75-83. http://dx.doi.org/10.3109/08958378.2011.601433
Lepeule. J: Laden. F: Dockery. D: Schwartz. J. (2012). Chronic Exposure to Fine Particles and Mortality: An
Extended Follow-up of the Harvard Six Cities Study from 1974 to 2009. Environ Health Perspect 120: 965-
970. http://dx.doi.org/10.1289/ehp. 1104660
Lew. JI: Diez. D: Dou. Y: Barr. CD: Dominici F. (2012). A meta-analysis and multisite time-series analysis
of the differential toxicity of major fine paniculate matter constituents [Review]. Am J Epidemiol 175:
1091-1099. http://dx.doi.org/10.1093/aie/kwr457
Li. S: Batterman. S: Wasilevich. E: Wahl. R: Wirth. J: Su. FC: Mukherjee. B. (2011). Association of daily
asthma emergency department visits and hospital admissions with ambient air pollutants among the
pediatric Medicaid population in Detroit: Time-series and time-stratified case-crossover analyses with
threshold effects. Environ Res 111: 1137-1147. http://dx.doi.0rg/10.1016/i.envres.2011.06.002
Lipfert. FW: Wyzga. RE: Batv. JD: 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 US veterans. Atmos
Environ 40: 154-169.
Lipsett MJ: Ostro. BD: Reynolds. P: Goldberg. D: Hertz. A: Jerrett M: Smith. DF: Garcia. C: Chang. ET:
Bernstein. L. (2011). Long-term exposure to air pollution and cardiorespiratory disease in the California
teachers study cohort. Am J Respir Crit Care Med 184: 828-835. http://dx.doi.org/10.1164/rccm.201012-
2082OC
61
-------
Mar. TF: Koenig. JQ: Primomo. J. (2010). Associations between asthma emergency visits and paniculate
matter sources, including diesel emissions from stationary generators in Tacoma, Washington. Inhal
Toxicol 22: 445-448. http://dx.doi.org/10.3109/08958370903575774
Marshall E: Harris. G: Wartenberg. D. (2010). Oral cleft defects and maternal exposure to ambient air
pollutants in New Jersey. Birth Defects Res A Clin Mol Teratol 88: 205-215.
http://dx.doi.org/10.1002/bdra.20650
Mathes. RW: Ito. K: Matte. T. (2011). Assessing syndromic surveillance of cardiovascular outcomes from
emergency department chief complaint data in New York City. PLoS ONE 6: e!4677.
http://dx.doi.org/10.1371/iournal.pone.0014677
Matsumoto. G: Kondo Nakagawa. N: de Paula Vieira. R: Mauad. T: da Silva. LF: de Andre. CD: Carvalho-
Oliveira. R: Saldiva. PH: Garcia. ML. (2010). The time course of vasoconstriction and endothelin receptor
A expression in pulmonary arterioles of mice continuously exposed to ambient urban levels of air pollution.
EnvironRes 110: 237-243. http://dx.doi.0rg/10.1016/i.envres.2010.01.003
Mauderly. JL: Barrett EG: Gigliotti AP: Mcdonald. JD: Reed. MD: Seagrave. J: Mitchell LA: Seilkop. SK.
(2011). Health effects of subchronic inhalation exposure to simulated downwind coal combustion
emissions. Inhal Toxicol 23: 349-362. http://dx.doi.org/10.3109/08958378.2011.572932
McConnell R: Islam. T: Shankardass. K: Jerrett. M: Lurmann. F: Gilliland. F: Gauderman. J: Avol E:
Kuenzli. N: Yao. L: Peters. J: Berhane. K. (2010). Childhood incident asthma and traffic-related air
pollution at home and school. Environ Health Perspect 118: 1021-1026.
http://dx.doi.org/10.1289/ehp.0901232
Mckean-Cowdin. R: Calle. EE: Peters. JM: Henley. J: Hannan. L: Thurston. GD: Thun. MJ: Preston-Martin. S.
(2009). Ambient air pollution and brain cancer mortality. Cancer Causes Control 20: 1645-1651.
http://dx.doi.org/10.1007/sl0552-009-9412-l
Meng. YY: Rull RP: Wilhelm. M: Lombardi C: Balmes. J: Ritz. B. (2010). Outdoor air pollution and
uncontrolled asthma in the San Joaquin Valley, California. J Epidemiol Community Health 64: 142-147.
http://dx.doi.org/10.1136/iech.2008.083576
Miller. KA: Siscovick. PS: Sheppard. L: Shepherd. K: Sullivan. JH: Anderson. GL: Kaufman. JD. (2007).
Long-term exposure to air pollution and incidence of cardiovascular events in women. N Engl J Med 356:
447-458.
Morello-Frosch. R: Jesdale. BM: Sadd. JL: Pastor. M. (2010). Ambient air pollution exposure and full-term
birth weight in California. Environ Health 9: 44. http://dx.doi.org/10.1186/1476-069X-9-44
Mostofsky. E: Schwartz. J: Coull BA: Koutrakis. P: Wellenius. GA: Suh. HH: Gold. PR: Mittleman. MA.
(2012). Modeling the association between particle constituents of air pollution and health outcomes. Am J
Epidemiol 176: 317-326. http://dx.doi.org/10.1093/aie/kws018
Nachman. KE: Parker. JD. (2012). Exposures to fine paniculate air pollution and respiratory outcomes in
adults using two national datasets: a cross-sectional study. Environ Health Global Access Sci Source 11:
25. http://dx.doi.org/10.1186/1476-069X-ll-25
Naess. O: Nafstad. P: Aamodt G: Claussen. B: Rosland. P. (2007). Relation between concentration of air
pollution and cause-specific mortality: four-year exposures to nitrogen dioxide and paniculate matter
pollutants in 470 neighborhoods in Oslo, Norway. 165: 435-443.
Neupane. B: Jerrett. M: Burnett RT: Marrie. T: Arain. A: Loeb. M. (2010). Long-term exposure to ambient air
pollution and risk of hospitalization with community-acquired pneumonia in older adults. Am J Respir Crit
Care Med 181: 47-53. http://dx.doi.org/10.1164/rccm.200901-0160OC
Noonan. CW: Ward. TJ: Navidi W: Sheppard. L. (2012). A rural community intervention targeting biomass
combustion sources: effects on air quality and reporting of children's respiratory outcomes. Occup Environ
Med 69: 354-360. http://dx.doi.org/10.1136/oemed-2011-100394
62
-------
O'Neill MS: Diez-Roux. AV: Auchincloss. AH: Shen. M: Lima. JA: Polak. JF: Barr. RG: Kaufman. J: Jacobs.
DR. Jr. (2011). Long-term exposure to airborne particles and arterial stiffness: The Multi-Ethnic Study of
Atherosclerosis (MESA). Environ Health Perspect 119: 844-851. http://dx.doi.org/10.1289/ehp.0901524
Ostro. B: Lipsett M: Reynolds. P: Goldberg. D: Hertz. A: Garcia. C: Henderson. KD: Bernstein. L. (2010).
Long-term exposure to constituents of fine paniculate air pollution and mortality: Results from the
California teachers study. Environ Health Perspect 118: 363-369. http://dx.doi.org/10.1289/ehp.Q901181
Ostro. B: Reynolds. P: Goldberg. D: Hertz. A: Burnett RT: Shin. H: Hughes. E: Garcia. C. (2011). Assessing
long-term exposure in the California teachers study [Erratum]. Environ Health Perspect 119: A242-A243.
Parker. JD: Akinbamj LJ: Woodruff. TJ. (2009). Air pollution and childhood respiratory allergies in the
United States. Environ Health Perspect 117: 140-147. http://dx.doi.org/10.1289/ehp. 11497
Patel MM: Hoepner. L: Garfinkel R: Chillrud. S: Reyes. A: Quinn. JW: Perera. F: Miller. RL. (2009).
Ambient metals, elemental carbon, and wheeze and cough in New York City children through 24 months of
age. Am J Respir Crit Care Med 180: 1107-1113. http://dx.doi.org/10.1164/rccm.200901-0122OC
Pires. A: Neves de Melo. E: Mauad. T: Hilario Nascimento Saldiva. P: de Siqueira Bueno. HM. (2011). Pre-
and postnatal exposure to ambient levels of urban paniculate matter (PM2.5) affects mice spermatogenesis.
Inhal Toxicol 23: 237-245. http://dx.doi.org/10.3109/08958378.2011.563508
Pope. CA. Ill: Burnett RT. (2007). Confounding in air pollution epidemiology: the broader context.
Epidemiology 18: 424-426. http://dx.doi.org/10.1097/EDE.Ob013e318065c008
Pope. CA. Ill: Burnett RT: Thun. MJ: Calle. EE: Krewski. D: Ito. K: Thurston. GD. (2002). Lung cancer,
cardiopulmonary mortality, and long-term exposure to fine paniculate air pollution. JAMA 287: 1132-
1141.
Pope III. CA: Burnett. RT: Thurston. GD: Thun. MJ: Calle. EE: Krewski. D: Godleskj JJ. (2004).
Cardiovascular mortality and long-term exposure to paniculate air pollution: epidemiological evidence of
general pathophysiological pathways of disease. Circulation 109: 71-77.
http://dx.doi.org/10.1161/01.cir.0000108927.80044.7f
Puett RC: Hart. JE: Suh. H: Mittleman. M: Laden. F. (2011). Paniculate matter exposures, mortality and
cardiovascular disease in the health professionals follow-up study. Environ Health Perspect 119: 1130-
1135. http://dx.doi.org/10.1289/ehp.1002921
Puett. RC: Hart. JE: Yanosky. JD: Paciorek. C: Schwartz. J: Suh. H: Speizer. FE: Laden. F. (2009). Chronic
fine and coarse paniculate exposure, mortality, and coronary heart disease in the Nurses' Health Study.
Environ Health Perspect 117: 1697-1701. http://dx.doi.org/10.1289/ehp.0900572
Rich. DQ: Demissie. K: Lu. SE: Kamat L: Wartenberg. D: Rhoads. GG. (2009). Ambient air pollutant
concentrations during pregnancy and the risk of fetal growth restriction. J Epidemiol Community Health
63: 488-496. http://dx.doi.org/10.1136/jech.2008.082792
Rohr. A: Kamal A: Morishita. M: Mukherjee. B: Keeler. G: Harkema. J: Wagner. J. (2011). Altered heart rate
variability in spontaneously hypertensive rats is associated with specific paniculate matter components in
Detroit, Michigan. Environ Health Perspect 119: 474-480. http://dx.doi.org/10.1289/ehp. 1002831
Rudra. CB: Williams. MA: Sheppard. L: Koenig. JQ: Schiff. MA. (2011). Ambient carbon monoxide and fine
paniculate matter in relation to preeclampsia and preterm delivery in western Washington state. Environ
Health Perspect 119: 886-892. http://dx.doi.org/10.1289/ehp. 1002947
Salihu. HM: August. EM: Mbah. AK: Alio. AP: de Cuba. R: Jaward. FM: Berry. EL. (In Press) Effectiveness
of a federal healthy start program in reducing the impact of paniculate air pollutants on feto-infant
morbidity outcomes. Matern Child Health J. http://dx.doi.org/10.1007/sl0995-011-0854-l
Seilkop. SK: Campen. MJ: Lund. AK: Mcdonald. JD: Mauderly. JL. (2012). Identification of chemical
components of combustion emissions that affect pro-atherosclerotic vascular responses in mice. Inhal
Toxicol 24: 270-287. http://dx.doi.org/10.3109/08958378.2012.667455
Silverman. RA: Ito. K. (2010). Age-related association of fine particles and ozone with severe acute asthma in
New York City. J Allergy Clin Immunol 125: 367-373. http://dx.doi.0rg/10.1016/i.jaci.2009.10.061
63
-------
Silverman. RA: Ito. K: Freese. J: Kaufman. BJ: De Claro. D: Braun. J: Prezant DJ. (2010). Association of
ambient fine particles with out-of-hospital cardiac arrests in New York City. Am J Epidemiol 172: 917-
923. http://dx.doi.org/10.1093/aje/kwq217
Stieb. DM: Szyszkowicz. M: Rowe. BH: Leech. JA. (2009). Air pollution and emergency department visits for
cardiac and respiratory conditions: A multi-city time-series analysis. Environ Health Global Access Sci
Source 8: 25. http://dx.doi.org/10.1186/1476-069X-8-25
Strickland. MJ: Darrow. LA: Klein. M: Flanders. WD: Sarnat JA: Waller. LA: Sarnat. SE: Mulholland. JA:
Tolbert PE. (2010). Short-term associations between ambient air pollutants and pediatric asthma
emergency department visits. Am J Respir Crit Care Med 182: 307-316.
http://dx.doi.org/10.1164/rccm.200908-1201OC
Szyszkowicz. M: Rowe. BH: Brook. RD. (2012). Even low levels of ambient air pollutants are associated with
increased emergency department visits for hypertension. Can J Cardiol 28: 360-366.
http://dx.doi.0rg/10.1016/i.cica.2011.06.011
Tzamkiozis. T: Stoeger. T: Cheung. K: Ntziachristos. L: Sioutas. C: Samaras. Z. (2010). Monitoring the
inflammatory potential of exhaust particles from passenger cars in mice. Inhal Toxicol 22 Suppl 2: 59-69.
http://dx.doi.org/10.3109/08958378.2010.519408
U.S. EPA (U.S. Environmental Protection Agency). (2004). Air quality criteria for paniculate matter [EPA
Report]. (EPA/600/P-99/002aF-bF). Research Triangle Park, NC.
http ://cfpub. epa. gov/ncea/cfm/recordisplav. cfm?deid=87903
U.S. EPA (U.S. Environmental Protection Agency). (2009). Integrated science assessment for paniculate
matter [EPA Report]. (EPA/600/R-08/139F). Research Triangle Park, NC.
http://cfpub.epa.gov/ncea/cfm/recordisplav.cfm?deid=216546
VanHee. VC: Szpiro. AA: Prineas. R: Never. J: Watson. K: Siscovick. D: Park. SK: Kaufman. JD. (2011).
Association of long-term air pollution with ventricular conduction and repolarization abnormalities.
Epidemiology 22: 773-780. http://dx.doi.org/10.1097/EDE.Ob013e31823061a9
Vinikoor-Imler. LC: Gray. SC: Edwards. SE: Miranda. ML. (2012). The effects of exposure to paniculate
matter and neighbourhood deprivation on gestational hypertension. Paediatric and Perinatal Epidemiology
(Online) 26: 91-100. http://dx.doi.0rg/10.llll/i.1365-3016.2011.01245.x
Wellenius. G: Diaz. E: Gupta. T: Ruiz. P: Long. M: Kang. C: Coull. B: Godleski. J. (2011).
Electrocardiographic and respiratory responses to coal-fired power plant emissions in a rat model of acute
myocardial infarction: results from the Toxicological Evaluation of Realistic Emissions of Source Aerosols
Study. Inhal Toxicol 23: 84-94. http://dx.doi.org/10.3109/08958378.2010.554461
Wellenius. GA: Burger. MR: Coull BA: Schwartz. J: Suh. HH: Koutrakis. P: Schlaug. G: Gold. PR:
Mittleman. MA. (2012). Ambient air pollution and the risk of acute ischemic stroke. Arch Intern Med 172:
229-234. http://dx.doi.org/10.1001/archinternmed.2011.732
Wilhelm. M: Ghosh. JK: Su. J: Cockburn. M: Jerrett M: Ritz. B. (2011). Traffic-related air toxics and preterm
birth: a population-based case-control study in Los Angeles county, California. Environ Health Global
Access Sci Source 10: 89. http://dx.doi.org/10.1186/1476-069X-10-89
Wilhelm. M: Ghosh. JK: Su. J: Cockburn. M: Jerrett M: Ritz. B. (2012). Traffic-related air toxics and term
low birth weight in Los Angeles County, California. Environ Health Perspect 120: 132-138.
http://dx.doi.org/10.1289/ehp. 1103408
Wu. J: Ren. C: Delfino. RJ: Chung. J: Wilhelm. M: Ritz. B. (2009). Association between Local Traffic-
Generated Air Pollution and Preeclampsia and Preterm Delivery in the South Coast Air Basin of California.
Environ Health Perspect x: 49. http://dx.doi.org/10.1289/ehp.0800334
Zanobetti. A: Franklin. M: Koutrakis. P: Schwartz. J. (2009). Fine paniculate air pollution and its components
in association with cause-specific emergency admissions. Environ Health Global Access Sci Source 8: 58.
http://dx.doi.org/10.1186/1476-069X-8-58
64
-------
Zhang. W: Lei. TA: Lin. ZQ: Zhang. HS: Yang. DF: Xi. ZG: Chen. JH: Wang. W. (2011). Pulmonary toxicity
study in rats with PM10 and PM2.5: Differential responses related to scale and composition. Atmos
Environ 45: 1034-1041.
Zhou. J: Ito. K: Lall R: Lippmann. M: Thurston. G. (2011). Time-series analysis of mortality effects of fine
paniculate matter components in Detroit and Seattle. Environ Health Perspect 119: 461-466.
http://dx.doi.org/10.1289/ehp.1002613
65
------- |