EPA/600/R-06/063
July 2006
Provisional Assessment of Recent Studies on
Health Effects of Particulate Matter Exposure
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
11
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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.
in
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Table of Contents
Page
List of Tables iii
List of Figures v
Authors vi
Executive Summary E-l
1. INTRODUCTION AND METHODOLOGY 1
2. OVERVIEW OF RECENT HEALTH STUDY RESULTS 2
2.1 Epidemiologic Studies of Long-Term Exposure 2
2.1.1 Mortality 2
2.1.2 Morbidity 11
2.2 Epidemiologic Short-Term Exposure Study Results 13
2.2.1 Mortality 14
2.2.1.1 Associations Between Acute Exposure to Fine
Particles and Mortality 14
2.2.1.2 Associations Between Acute Exposure to
Thoracic Coarse Particles and Mortality 16
2.2.2 Morbidity 17
2.2.2.1 Associations Between Acute Exposure to Fine
Particles and Morbidity 17
2.2.2.2 Associations Between Acute Exposure to
Thoracic Coarse Particles and Morbidity 21
2.2.3 Issues for Interpretation of Epidemiologic Study Results 22
2.3 Intervention Studies 24
2.4 Health Effects Related to Sources or Components of PM 24
2.4.1 Epidemiologic Studies Using Source Apportionment 25
2.4.2 Epidemiologic Studies on Effects of Fine Particle
Components 27
2.4.3 Toxicology Studies—Source Apportionment and Fine
Particle Components 28
2.4.4 Toxicology Studies—Thoracic Coarse Particles 33
2.4.5 Toxicology Studies—Comparison of Ambient PM 34
2.4.6 Studies of Specific Fine Particle Components or
Characteristics 35
3. SUMMARY AND CONCLUSIONS 38
ABBREVIATIONS AND ACRONYMS 41
REFERENCES 47
APPENDIX A A-l
APPENDIX B B-l
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List of Tables
Number Page
1 Mortality and Morbidity Effect Estimates and PM Concentrations from U.S.
and Canadian Studies with Long-Term Exposures to PM2 5 and PMio-2.s 3
2 CAPs Sources and Associated Endpoints: Acute and Subchronic
Exposures 30
3 CAPs Components and Associated Endpoints for Acute Studies 31
4 PM Components, Size Fractions, and Associated In Vitro Toxicity 35
Al Associations Between Long-Term Exposure to PM2.5 and PMio-2.5
and Mortality and Morbidity A-3
A2 Associations of Acute PM2.5 Exposure with Mortality A-13
A3 Associations of Acute PMio-2.5 Exposure with Mortality A-20
A4 Effects of PM2.s on Daily Hospital Admissions A-25
A5 Effects ofPMio-2.5 on Daily Hospital Admissions A-29
A6 Effects of PM2.s on Daily Emergency Department Visits A-32
A7 Effects of PMio-2.5 on Daily Emergency Department Visits A-34
A8 Effects of Acute PM2.5 Exposure on Cardiovascular Outcomes A-3 5
A9 Effects of Acute PMio-2.5 Exposure on Cardiovascular Outcomes A-43
A10 Effects of Acute PM2.5 Exposure on Various Respiratory Outcomes A-44
All Effects of Acute PMio-2.5 Exposure on Various Respiratory Outcomes A-49
A12 Effects of Acute PM2.5 Exposure on Birth Outcomes A-50
A13 Results of Epidemiologic "Intervention" Studies A-54
A14 Associations between Source-related Fine Particles and Health
Outcomes A-59
Al 5 Associations of Acute Exposure to Fine Particle Components with
Health Outcomes A-62
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List of Tables
(cont'd)
Number Page
A16 CAPs Studies with Source Apportionment or Components Analysis A-71
A17 Other Acute CAPs Studies A-76
A18 Subchronic CAPs Studies A-81
A19 Size-fractionated and Collected Ambient PM Studies A-85
A20 Acid Aerosol Studies A-97
IV
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List of Figures
Number Page
1. Relative risk estimates (and 95% confidence intervals) for associations
between long-term exposure to PM (per 10 PM10-2.5) and mortality 7
2 Excess risk estimates for total nonaccidental, cardiovascular, and
respiratory mortality in single-pollutant models for U.S. and Canadian
studies, including aggregate results from multicity studies 15
3 Excess risk estimates for hospital admissions and emergency department
visits for cardiovascular and respiratory diseases in single-pollutant
models for U.S. and Canadian studies, including aggregate results from
a multicity study 18
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Principal Authors
Dr. Jee Young Kim—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Dennis Kotchmar—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Mary Ross—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Lori White—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Lindsay Wichers—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. William Wilson—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Contributors and Reviewers
Mr. John Bachmann—Office of Air Quality Planning and Standards (C404-04),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. James Brown—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Dan Costa—Office of Research and Development (E205-09),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Robert Devlin—National Health and Environmental Effects Research Laboratory
(mail code 58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Janice Dye—National Health and Environmental Effects Research Laboratory
(B143-01), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Kevin Dreher—National Health and Environmental Effects Research Laboratory (B 143-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Ian Gilmour—National Health and Environmental Effects Research Laboratory (B 143-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
VI
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Contributors and Reviewers
(cont'd)
Dr. Barbara Glenn—National Center for Environmental Research (8723F), Ariel Rios Building,
1200 Pennsylvania Ave N.W., U.S. Environmental Protection Agency, Washington, DC 20460
Dr. Lester Grant—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Ms. Beth Hassett-Sipple—Office of Air Quality Planning and Standards (C539-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Bryan Hubbell—Office of Air Quality Planning and Standards (C539-02),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Mary Johnson—National Health and Environmental Effects Research Laboratory
(mail code 58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Srikanth Nadadur—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Lucas Neas—National Health and Environmental Effects Research Laboratory
(mail code 58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. Haluk Ozkaynak—National Exposure Research Laboratory (E205-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Mr. Harvey Richmond—Office of Air Quality Planning and Standards (C539-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. David Svendsgaard—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Dr. John Vandenberg—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
vn
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Executive Summary
In the proposed rule on the National Ambient Air Quality Standards for particulate matter
(PM), EPA committed to conduct a review and assessment of the numerous studies relevant to
assessing the health effects of PM that were published too recently to be included in the 2004
PM Air Quality Criteria Document (AQCD). This report presents the findings of EPA's survey
and provisional assessment of such studies. EPA has screened and surveyed the recent literature
and developed a provisional assessment that places those studies of potentially greatest relevance
in the context of the findings of the 2004 PM AQCD. The focus is on: (a) epidemiologic studies
that used PM2.5 or PMio-2.s and were conducted in the U.S. or Canada, and (b) toxicology or
epidemiologic studies that compared effects of PM from different sources, PM components, or
size fractions. Given the limited time available, the provisional assessment presented here does
not attempt to critically review individual studies or to provide the kind of full integration found
in a typical AQCD.
This survey and assessment finds that that the new studies expand the scientific
information and provide important insights on the relationships between PM exposure and health
effects of PM. Taken in context, however, the new information and findings do not materially
change any of the broad scientific conclusions regarding the health effects of PM exposure made
in the 2004 PM AQCD. In brief, this report finds the following:
• Recent epidemiologic studies, most of which are follow-ups or extensions of earlier
work, continue to find that long-term exposure to fine particles is associated with both
mortality and morbidity, as was stated in the 2004 PM AQCD. Notably, a follow-up to
the Six Cities study shows that an overall reduction in PM2.5 levels results in reduced
long-term mortality risk. Both this study and the analysis of the ACS cohort data in Los
Angeles suggest that previous studies may have underestimated the magnitude of
mortality risks. Some studies provide more mixed results, including the suggestion that
higher traffic density may be an important factor. In addition, the California Children's
Health Study reported that measures of PM2.5 exposure and PM components and gases
were associated with reduction in lung function growth in children, increasing the
evidence for increased susceptibility early in life, as was suggested in the 2004 PM
AQCD. The results of recent epidemiologic and toxicology studies have also reported
new evidence linking long-term exposure to fine particles with a measure of
atherosclerosis development and, in a cohort of individuals with cystic fibrosis,
respiratory exacerbations.
• Recent epidemiologic studies have also continued to report associations between acute
exposure to fine particles and mortality and morbidity health endpoints. These include
three multi-city analyses, the largest of which (in 204 counties) shows a significant
association between acute fine PM exposures and hospitalization for cardiovascular and
respiratory diseases, and suggestions of differential cardiovascular effects in eastern U.S.
as opposed to western U.S. locations. The new studies support previous conclusions that
short-term exposure to fine PM is associated with both mortality and morbidity, including
a substantial number of studies reporting associations with cardiovascular and respiratory
health outcomes such as changes in heart rhythm or increases in exhaled NO.
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• New toxicology and epidemiologic studies have continued to link health outcomes with a
range of fine particle sources and components. Several new epidemiologic analyses and
toxicology studies have included source apportionment techniques, and the results
indicated that fine PM from numerous sources, including traffic-related pollution,
regional sulfate pollution, combustion sources, resuspended soil or road dust, are
associated with various health outcomes. Toxicology studies continue to indicate that
various components, including metals, sulfates, and elemental and organic carbon, are
linked with health outcomes, albeit at generally high concentrations. Recent
epidemiologic studies have also linked different fine PM components with a range of
health outcomes; new studies indicate effects of the organic and elemental carbon
fractions of fine PM that were generally not evaluated in earlier analyses.
• The recent epidemiologic studies greatly expand the more limited literature on health
effects of acute exposure to thoracic coarse particles (PM'10-2.5)- The 2004 PM AQCD
conclusion that PMio-2.s exposure was associated with respiratory morbidity is
substantially strengthened with these new studies; several epidemiologic studies, in fact,
report stronger evidence of associations with PMi0-2.5 than for PM2.s. In two new case-
crossover studies, associations with thoracic coarse particles are robust to the inclusion of
gaseous copollutants. For mortality, many studies do not report statistically significant
associations, though one new analysis reports a significant association with
cardiovascular mortality in Vancouver, Canada.
• Evidence of associations between long-term exposure to thoracic coarse particles and
either mortality or morbidity remains limited.
• New toxicology studies have demonstrated that exposure to thoracic coarse particles, or
PM sources generally representative of this size fraction (e.g., road dust), can result in
inflammation and other health responses. Clinical exposure of healthy and asthmatic
humans to concentrated ambient air particles comprised mostly of PMio-2.5 showed
changes in heart rate and heart rate variability measures. The results are still too limited
to draw conclusions about specific thoracic coarse particle components and health
outcomes, but it appears that endotoxin and metals may play a role in the observed
responses. Two studies comparing toxicity of dust from soils and road surfaces found
variable toxic responses from both urban and rural locations.
• Significant associations between improvements in health and reductions in PM and other
air pollutants have been reported in intervention studies or "found experiments." One
new study reported reduced mortality risk with reduced PM2.5 concentrations. In
addition, several studies, largely outside the U.S., reported reduced respiratory morbidity
with lowered air pollutant concentrations, providing further support for the
epidemiological evidence that links PM exposure to adverse health effects.
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Provisional Assessment of Recent Studies on Health Effects
of Particulate Matter Exposure
1. INTRODUCTION AND METHODOLOGY
EPA is currently in the final stages of the review of the national ambient air quality
standards (NAAQS) for particulate matter (PM). As described in more detail in the Federal
Register Notice of EPA's proposed rule on the PM NAAQS (71 FR 2620), EPA has prepared the
Air Quality Criteria for Particulate Matter (hereafter 2004 PM AQCD) that reviewed,
summarized and integrated the results of studies on PM (EPA, 2004). As noted in the PM
proposal1, EPA is aware that numerous studies potentially relevant to assessing the health effects
of ambient PM have been published recently that were not included in the 2004 PM AQCD. The
proposal notice also indicates the Agency's intent to conduct a review and assessment of these
new studies before a final decision is made on the PM NAAQS. This report presents the findings
of EPA's survey and provisional assessment of potentially relevant recent studies on the health
effects of PM exposure. As outlined below, EPA has 1) screened the recently available literature
to identify potentially relevant studies, 2) surveyed those studies to summarize the key findings,
and 3) developed a preliminary assessment that places those of potentially greatest relevance in
the context of the findings of the 2004 AQCD. Given the limited time available, the provisional
assessment presented here does not attempt to critically review individual studies or to provide
the kind of full integration found in a typical AQCD.
The literature search and submissions from public commenters found that hundreds of
studies have been published in the last few years on the health effects of particulate matter. In an
initial screen of the literature, more than 700 studies were identified as being potentially relevant
to this review. In surveying these studies, EPA emphasized studies more likely to be relevant to
considerations for the PM NAAQS decision. The specific criteria focused on (a) epidemiologic
studies that used PM2.5 or PMio-2.s and were conducted in the U.S. or Canada, and (b) toxicology
or epidemiologic studies that compared effects of PM from different sources, PM components, or
size fractions. These criteria resulted in a list of over 200 studies that are summarized in tables
in this report that provide descriptive and quantitative information. The most significant studies
are discussed in the assessment, and where feasible, quantitative results are compared to those
from the 2004 PM AQCD. Bibliographies have been attached for studies identified as being
potentially relevant through the survey effort but not discussed in detail in this report.
1 As stated in the PM NAAQS proposal notice: "The EPA is aware that a number of new scientific studies
on the health effects of PM have been published since the 2002 cutoff date for inclusion in the Criteria Document.
As in the last PM NAAQS review, EPA intends to conduct a review and assessment of any significant new studies
published since the close of the Criteria Document, including studies submitted during the public comment period
in order to ensure that, before making a final decision, the Administrator is fully aware of the new science that has
developed since 2002. In this assessment, EPA will examine these new studies in light of the literature evaluated in
the Criteria Document. This assessment and a summary of the key conclusions will be placed in the rulemaking
docket." (71FR2625)
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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.s; (2) results from time-series
epidemiologic studies, again focusing on U.S. and Canadian studies with measurements of PM2.5
or PMio-2.5; and (3) results of recent toxicology and epidemiologic studies that have evaluated
health effects with exposure to PM from different sources. This last section includes results of
studies that assessed the effects of a range of sources or components in the same study. Most
studies have focused on components or sources of fine particles, but information related to
sources of thoracic coarse particles was also included to the extent available.
2. OVERVIEW OF RECENT HEALTH STUDY RESULTS
2.1 Epidemiologic Studies of Long-Term Exposure
2.1.1 Mortality
An extensive discussion of prospective cohort studies was included in Section 8.2.3 of
the 2004 PM AQCD. These discussions emphasized the results of four U.S. prospective cohort
studies. The greatest weight was placed on the findings of the American Cancer Society (ACS)
and the Harvard Six Cities studies which had undergone extensive, independent reanalysis and
were based on cohorts that were broadly representative of the U.S. population. These studies
provided strong evidence that long-term exposure to fine particles and sulfates was associated
with mortality. In addition, results from the Seventh-Day Adventist (AHSMOG) cohort
provided some suggestive but less conclusive evidence for associations, and results from the
Veterans Cohort provided inconsistent evidence for associations between long-term exposures to
PM2.5 and mortality. Overall, the 2004 PM AQCD concluded that there was strong
epidemiologic evidence for associations between long-term exposures to PM2.s and mortality
(p. 9-46).
In the 2004 PM AQCD, no association was observed between mortality and long-term
exposure to PMio-2.5 in the ACS study (Pope et al., 2002), and a positive but nonsignificant
association was reported in males in the AHSMOG cohort (McDonnell et al., 2000). Thus, the
2004 PM AQCD concluded that there was insufficient evidence for associations between long-
term exposure to thoracic coarse particles and mortality.
Fine Particles:
Recent studies include results of new analyses for the ACS and Harvard Six Cities
studies; as highlighted below, the new findings strengthen the evidence linking long-term
exposure to PM2.5 and mortality. Recent reports have also included analyses from the AHSMOG
and Veterans study cohorts, as well as a Cystic Fibrosis cohort and a subset of the ACS for
California. These results, along with those from studies available in the 2004 PM AQCD, are
shown in Figure 1. The risk estimates and PM concentrations reported in the studies are
summarized in Table 1, along with results available in the 2004 PM AQCD; further details on
the studies are presented in Appendix A, Table Al.
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Table 1. Mortality and Morbidity Effect Estimates and PM Concentrations from U.S.
and Canadian Studies with Long-Term Exposures to PM2.s and PMio-i.s. Adapted from
Appendix 3B of the 2005 OAQPS Staff Paper. Shaded rows present results from recent
studies that were not available in the 2004 PM Criteria Document.
Study
Increased Total Mortality in Adults
Six CitiesA
Six Cities13
Six Cities ReanalysisD
Six Cities Follow-up^
ACS Study0
ACS Study ReanalysisD
ACS Study Extended
AnalysesE
ACS Los AngelesBB
AHSMOGH
Veterans Cohort0
Veterans Cohort00
Veterans Cohort00
California Cancer
Prevention Study™
Indicator
i Adults
PM25
S042- (15 ug/m3)
PM15_2.5
PM25
PM25
PM25
S042- (15 ug/m3)
PM25
PM15.2.5
PM25 (1979-83)
PM25 (1999-00)
PM25 (average)
PM25
PM25
PM10.2.5
PM25 (1979-81)
PM25 (1999-2001)
PM10.2.5 (1989-96)
PM25 (1979-83)
Relative Risk (95% CI)
1.13(1.04,1.23)
1.54(1.15,2.07)
1.43(0.83,2.48)
1.14(1.05, 1.23)
1.16(1.07,1.26)
1.07(1.04, 1.10)
1.11(1.06, 1.16)
1.07(1.04, 1.10)
1.00 (0.99, 1.02)
1.04(1.01, 1.08)
1.06(1.02, 1.10)
1.06(1.02, 1.11)
1.17(1.05,1.30)
1.09 (0.98, 1.21) (males)
1.05 (0.92, 1.21) (males)
0.90 (0.85, 0.95) (males)
1.12(1.04, 1.20) (males)
1.07(1.01, 1.12) (males)
1.04(1.01, 1.07)
Study
Concentrations
Oig/m3) *
NR(11,30)
NR(5, 13)
NR(11,30)
NR (10.2, 22)
181 (9, 34)
II1 (4, 24)
20 (10, 38)
7.1(9,42)
21 (9, 34)
14 (5, 20)
18 (7.5, 30)
NR (9, 27)
32(17,45)
27 (4, 44)
24 (6, 42)
14.6 (SD 3.1)
16.0 (SD 5.1)
23.4 (10.6-42.0)
U.S. Cystic FibrosisE
PM25
Increased Cardiopulmonary Mortality in Adults
Six CitiesA PM2 5
Six Cities ReanalysisD PM2 5
(deaths 1973-1982)
1.00 (0.98, 1.02)
(deaths 1983-2002)
1.32(0.91,1.93)
1.18(1.06, 1.32)
1.19(1.07, 1.33)
13.7(11.8, 15.9)
NR(11,30)
NR(11,30)
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Table 1. Mortality and Morbidity Effect Estimates and PM Concentrations from U.S.
and Canadian Studies with Long-Term Exposures to PM2.s and PMio-i.s. Adapted from
Appendix 3B of the 2005 OAQPS Staff Paper. Shaded rows present results from recent
studies that were not available in the 2004 PM Criteria Document.
Study
Indicator
ACS Study
ACS Study ReanalysisE
ACS Study Extended
AnalysesE
ACS Cause-specificFF:
All cardiovascular
schemic heart disease
srhythmia, et al.
ypertensive
Other atherosclerosis
erebrovascular disease
iabetes
r cardiovascular
11 Respiratory
OPD
Pneumonia
Other respiratory
ACS Los Angeles:BB
Ischemic heart disease
Cardiopulmonary
AHSMOGH
AHSMOGGG
"atal coronary heart disease
PM25
PM
PM25
PM25
PM10.2.5
PM25
PM
Relative Risk (95% CI)
1.28(1.13-1.44)
(Cardiovascular)
1.08 (0.79-1.49)
(Respiratory)
1.12(1.07, 1.17)
1.12(1.07,1.17)
1.00 (0.98, 1.03)
1.39(1.12, 1.73)
1.12(0.97, 1.30)
1.23 (0.97, 1.55) (males)
1.20 (0.87, 1.64) (males)
1.42 (1.06, 1.90) (females)
1.49 (1.17, 1.89) (postmenopausal)
0.90 (0.76, 1.05) (males)
1.38 (0.97, 1.95) (females)
1.61 (1.12, 2.33) (postmenopausal)
0.92 (0.66, 1.29) (males)
Study
Concentrations
Oig/m3) *
NR (10.2, 22)
181 (9, 34)
20 (10, 38)
7.1(9,42)
PM25 (1979-83)
PM25 (1999-00)
PM25 (average)
PM25 (average)
.06 (1.02,
.08(1.02,
.09(1.03,
.12(1.08,
.18(1.14,
.13(1.05,
.07 (0.90,
.04 (0.89,
.02 (0.95,
0.99 (0.86,
.10)
.14)
.16)
.15)
.23)
.21)
.26)
.21)
.10)
.14)
0.84(0.71,0.99)
0.92 (0.86, 0.98)
0.84 (0.77, 0.93)
1.07 (0.95, 1.20)
0.86 (0.73, 1.02)
21 (9, 34)
14 (5, 20)
18 (7.5, 30)
17.1(7.5,30)
(9, 27)
32(17,45)
27 (4, 44)
29 (SD 9.8)
25.4 (SD 8.5)
Increased Lung Cancer Mortality in Adults
Six Cities
PM25
1.18(0.89, 1.57)
NR(11,30)
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Table 1. Mortality and Morbidity Effect Estimates and PM Concentrations from U.S.
and Canadian Studies with Long-Term Exposures to PM2.s and PMio-i.s. Adapted from
Appendix 3B of the 2005 OAQPS Staff Paper. Shaded rows present results from recent
studies that were not available in the 2004 PM Criteria Document.
Study
Six Cities ReanalysisD
Six Cities Follow-up^
ACS Study0
ACS Study ReanalysisD
ACS Study Extended
AnalysesE
ACS Los AngelesBB
AHSMOGH
Increased Bronchitis in
Six Cities1
24 Cities1
AHSMOGK
12 Southern California
communities1"1
(children with asthma)
12 Southern California
communities1™
(children with asthma)
12 Southern California
communities1™
(children with asthma)
Indicator
PM2.5
PM2.5
PM25
PM25
PM15.2.5
PM2 5 (1979-83)
PM2.5 (1999-00)
PM25 (average)
PM2.5
PM25
M! Q-2.5
Children
PM25
S042- (15 ug/m3)
PM21
SO42" (15 ug/m3)
PM2.5
PM2.5
PM10.2.5
PM25
PM10.2.5
Relative Risk (95% CI)
1.21 (0.92, 1.60)
1.27 (0.96, 1.69)
1.01(0.91, 1.12)
1.01(0.91, 1.11)
0.99 (0.93, 1.05)
1.08(1.01,1.16)
1.13(1.04,1.22)
1.14(1.05,1.24)
1.44(0.98,2.11)
1.39 (0.79, 2.50) (males)
1.26 (0.62, 2.55) (males)
1.3 (0.9, 2.0)
3.02(1.28,7.03)
1.31(0.94, 1.84)
1.39(0.99,1.92)
1.3 (0.9, 1.7)
1.34(1.11,1.63)
1.10(0.82,1.49)
(between communities)
2.37(1.13,4.94)
1.21(0.59,2.54)
(within community change)
Study
Concentrations
Oig/m3) *
NR (11,30)
NR (10.2, 22)
18U(9, 34)
20 (10, 38)
7.1(9,42)
21 (9, 34)
14 (5, 20)
18 (7.5, 30)
NR (9, 27)
32(17,45)
27 (4, 44)
NR(12, 37)
4.7 (0.7, 7.4)
14.5 (5.8, 20.7)
—
15.3(6.7,31.5)
13.8(5.5,28.5)
17.0 (10.2, 35.0)
13.8(5.5,28.5)
17.0 (10.2, 35.0)
Increased Cough in Children
12 Southern California
communities1"1
(children with asthma)
PM25
Increased Pulmonary Exacerbations in Cystic
1.2 (0.8, 1.8)
Fibrosis Patients
15.3(6.7,31.5)
U.S. Cystic Fibrosis1
RE
PM9
1.21(1.07, 1.33)
13.7(11.8, 15.9)
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Table 1. Mortality and Morbidity Effect Estimates and PM Concentrations from U.S.
and Canadian Studies with Long-Term Exposures to PM2.s and PMio-i.s. Adapted from
Appendix 3B of the 2005 OAQPS Staff Paper. Shaded rows present results from recent
studies that were not available in the 2004 PM Criteria Document.
Study
Decreased Lung Function
24 City1
12 Southern California
communities'2
(4th grade cohort)
Indicator
in Children
SO42" (15 ug/m3)
PM21
PM25
PM10_2.5
Relative Risk (95% CI)
-6.56% (-9.64, -3.43) FVC
-2.15% (-3.34, -0.95) FVC
-0.18 (-0.36, 0.0) FVC % growth
-0.4 (-0.75, -0.04) MMEF % growth
-0.22 (-0.47, 0.02) FVC % growth
-0.54 (-1.0, -0.06) MMEF % growth
Study
Concentrations
Oig/m3) *
4.7 (0.7, 7.4)
14.5 (5.8, 20.7)
MR (10, 35)3
NR
12 Southern California
PM7
communities
,Q
(second 4th grade cohort)
-0.06 (-0.30, 0.18) FVC % growth
-0.42 (-0.84, 0.0) MMEF % growth
-0.20 (-0.64, 0.25) PEFR % growth
NR (5, 30)4
12 Southern California
communities11
(first 4th grade cohort, 8-yr
follow-up)
PM25
-26.4 (-72.9, 20.1) FVC growth
-35.0 (-67.1, -2.8) FEVj growth
-74.1 (-151.5, 3.4) MMEF growth
NR (5, 28)
Lung Function Changes in Adults
AHSMOG1 (% predicted
FEVi, males)
S042-(1.6ng/m3)
-1.5% (-2.9, -0.1)FEV!
7.3 (2.0, 10.1)
* Note: Effect estimates presented using standardized increments of 10 ug/m3 PM25 and PM10_25. Concentrations
are presented as mean (min, max), or mean (± SD); NS Changes = No significant changes (no quantitative results
reported); NR = not reported.
1 Median
2 Results only for smoking category subgroups.
3 Estimated from Figure 1, Gauderman et al. (2000)
4 Estimated from figures available in online data supplement to Gauderman et al. (2002)
References:
A Dockery et al. (1993)
B EPA (1996a)
c Pope etal. (1995)
D Krewski et al. (2000)
E Pope et al. (2002)
F Abbey etal. (1999)
G Lipfert et al. (2000b)
H McDonnell et al. (2000)
1 Dockery etal. (1989)
1 Dockery etal. (1996)
K Abbey etal. (1995a,b,c)
L Peters etal. (1999a)
MMcConnelletal. (1999)
NBerglundetal. (1999)
°Raizenne etal. (1996)
p Peters et al. (1999)
Q Gauderman et al. (2000)
R Gauderman et al. (2002)
sAvoletal. (2001)
T
Recent studies:
^ Laden etal. (2006)
BB Jerrett et al. (2005)
cc Lipfert et al. (2006)
DD Enstrom (2005)
EE Goss et al. (2004)
FF Pope et al. (2004)
GG Chen etal. (2005)
^ McConnell et al. (2003)
11 Gauderman et al. (2004)
Abbey etal. (1998)
-------
Relative Risk Estimate
CD
O
3
a.
o
«0
O
Six Cities. Dockery et al . 1993 •
Six Cities, Krewski et al., 2000 •
Six Cities, Laden et al., 2006 -
Sin Cities, Laden et al., 2006' -
ACS, Pope et al.. 1995 -
ACS, Krewski et al.. 2000 -
ACS, Pope et al,, 2002 -
ACS Los Angeles, Jerrett et al., 2005 -
AHSMOG. McDonnell et al.. 2000 (M) -
Veterans cohort, Lipfert et al., 2000 (M) -
Veterans cohort, Lipfert et al., 2006a (M) -
Calif. CPS, Enstrom et al., 2005 (1973-1982) -
Calif. CPS, Enstrom et al., 2005 (1983-2002) -
Cystic Fibrosis cohort, Goss et al., 2004 -
Six Cities Dockery et al.. 1993 -
Six Cities, Krewski et al., 2000 -
Six Cities, Laden et al.. 2006 -
ACS, Pope etal. 1995-
ACS, Krewski et al., 2000 -
ACS, Pope etal.. 2002-
ACS, Pope et al., 2004 (ACV) -
ACS, Pope et al., 2004 (IHD) -
ACS Los Angeles, Jerrett et al., 2005 (ACV) -
ACS Los Angeles, Jerrett et al., 2005 (IHD) -
AHSMOG. McDonnell et al., 2000 (M) -
AHSMOG, Chen et al., 2005 (F. FCD) -
AHSMOG, Chen et al., 2005 (M, FCD) -
Six Cities. Dockery et al.. 1993 -
Six Cities. Krewski et al., 2000 -
Six Cities, Laden et al., 2006 -
ACS, Pope etal.. 1995-
ACS, Krewski et al.. 2000 -
ACS, Pope etal., 2002 -
re
§1
re
O
51
,o t:
, ^ >
6 -ss
1
£
3
a.
.. i-
ACS Los Angeles, Jerrett et al., 2005 —
AHSMOG. McDonnell et al., 2000 (M) —
Six Cities, EPA, 1996 •
ACS, Krewski et al, 2000 .
AHSMOG. McDonnell et al., 2000 (M) •
Veterans Cohort, Lipfert et al., 2006 (M) _
ACS, Krewski et al 2000 •
AHSMOG, Chen etal., 2005 (F, FCD) -
AHSMOG, Chen et al., 2005 (M, FCD) •
»sir
lllL
—irt^1-
a a
81'
ACS, Krewski et al,, 2000 —
AHSMOG. McDonnell et al., 2000 (M) —
0
1
PM2 5 Studies
PM10 2 5 Studies
3
IHD = Ischemic Heart Disease
FCD = Fatal Coronary Disease
ACV = All Cardiovascular
F = Female
M = Male
—•— Studies in 2004 PM AQCD
—*— Post-2002 studies
Figure 1. Relative risk estimates (and 95% confidence intervals) for associations between
long-term exposure to PM (per 10 PMi0-2.s) and mortality. *Note: The second
result presented for Laden et al. (2006) is for the intervention study results.
-------
Harvard Six Cities: A new study has used updated air pollution and mortality data; an
additional 1,368 deaths occurred during the follow-up period (1990-1998) and
1,364 deaths occurred in the original study period (1974-1989). Statistically significant
associations are reported between long-term exposure to PM2 5 and mortality for data for
the two periods (RR =1.16, 95% CI 1.07-1.26 per 10 |ig/m3 PM2.5). Of note, however,
a statistically significant reduction in mortality risk is reported with reduced long-term
fine particle concentrations (RR = 0.73, 95% CI 0.57-0.95 per 10 |ig/m3 PM2.5). This is
equivalent to an RR of 1.27 for reduced mortality risk, suggesting a larger effect than in
the cross-sectional analysis. This reduced mortality risk was observed for deaths due to
cardiovascular and respiratory causes, but not for lung cancer deaths. Mean PM2 5
concentrations from the follow-up period range from 10.2 to 22.0 |ig/m3 in the six cities.
The means across the six cities were 18 |ig/m3 in the first period and 14.8 |ig/m3 in the
follow-up period. The PM2.5 concentrations for recent years were estimated from
visibility data which introduces uncertainty in interpreting the results of this study
(Laden et al., 2006). Coupled with the results of the original analysis (Dockery et al.,
1993), this study strongly suggests that reduction in fine PM pollution has yielded
positive health benefits.
ACS Extended Analyses: One new analysis further evaluated associations between long-
term PM2.5 and sulfate exposures in 50 U.S. cities and mortality, adding new information
about deaths from specific cardiovascular and respiratory causes. Significant
associations were reported with deaths from specific cardiovascular diseases, particularly
ischemic heart disease, and a group of cardiac conditions including dysrhythmia, heart
failure and cardiac arrest (RR for cardiovascular mortality = 1.12, 95% CI 1.08-1.15 per
10 |ig/m3 PM2.5); no associations were reported with respiratory mortality. The mean
PM2.5 concentration (1979-1983 and 1999-2000) was 17.1 |ig/m3 (Pope et al., 2004).
ACS, Los Angeles: Much of the exposure gradient in the national-scale ACS studies was
due to city-to-city differences in regional air pollution. A new analysis using ACS data
focused on neighborhood-to-neighborhood differences in urban air pollutants, on data
from 23 PM2 5 monitoring stations in the Los Angeles area and using interpolation
methods to assign exposure levels to individuals (Jerrett et al., 2005). This resulted in
both improved exposure assessment and an increased focus on local sources of fine
particle pollution. Significant associations between PM2 5 and mortality from all causes
and cardiopulmonary diseases were reported with the magnitude of the relative risks
being greater than those reported in previous assessments (after adjustment for potential
confounders including traffic, RR for cardiovascular diseases =1.17, 95% CI 1.05-1.31,
per 10 |ig/m3 PM2.5; RR for ischemic heart disease = 1.38, 95% CI 1.11-1.72 per
10 |ig/m3 PM2 5). The authors suggest that reducing exposure error can result in stronger
associations between PM2.5 and mortality than generally observed in broader studies
having less exposure detail.
California cancer prevention study: In a cohort of elderly people in 11 California
counties (mean age 73 years in 1983), an association was reported for long-term PM2.5
exposure with all-cause deaths in 1973-1982 (RR = 1.04, 95% CI 1.01-1.07 per 10 |ig/m3
PM2 5). No significant associations were reported with deaths in later time periods
-------
(1983-2002) (RR= 1.00, 95% CI 0.98-1.02 per 10 |ig/m3 PM2.5) when PM2.5 levels had
decreased in the most polluted counties. The PM2 5 data are from the EPA's Inhalation
Particle Network, and represent a subset of data used in the 50-city ACS study (Pope
et al., 1995). The use of average values for California counties as exposure surrogates
likely leads to significant exposure error as many California counties are large and quite
topographically variable. The mean PM2 5 concentration (1979-1983) was 23.4 |ig/m3
(Enstrom, 2005).
AHSMOG: In this analysis for the Seventh-Day Adventist cohort in California, positive,
statistically significant association with coronary heart disease mortality was reported for
92 deaths among females (RR = 1.42, 95% CI 1.06-1.90 per 10 |ig/m3 PM2.5), but not for
53 deaths among males (RR = 0.90, 95% CI 0.76-1.05 per 10 |ig/m3 PM2.5). Associations
were strongest in the subset of postmenopausal women (80 deaths; RR=1.49, 95% CI
1.17, 1.89 per 10 |ig/m3 PM25). The authors speculated that females may be more
sensitive to air pollution-related effects based on differences between males and females
in dosimetry and exposure, along with the generally lower blood cell levels in females.
The mean PM2.5 concentration averaged over 1973-1998 was 29.0 |ig/m3 (Chen et al.,
2005).
Veterans cohort: A recent analysis of the Veterans cohort data focused on exposure to
traffic-related air pollution (traffic density based on traffic flow rate data and road
segment length) reported a stronger relationship between mortality with long-term
exposure to traffic than with PM2 5 mass. A significant association was reported between
total mortality and PM2.5 in single-pollutant models (RR =1.12, 95% CI 1.04-1.20 per
10 |ig/m3 PM2.5); the author observes that this risk estimate is larger than results reported
in a previous study (Lipfert et al., 2000). In multi-pollutant models including traffic
density, the association with PM2 5 was reduced and lost statistical significance. Traffic
emissions contribute to PM2.5 so it would be expected that the two would be highly
correlated, and thus these multi-pollutant model results should viewed with caution. The
mean PM2.5 level was 14.6 |ig/m3 using data from 1997-2001 (Lipfert et al., 2006a).
In a companion study, Lipfert et al. (2006b, in press) used data from EPA's fine particle
speciation network, and reported findings for PM2.5 were similar to those reported in the
Lipfert et al., 2006a. A positive association was also reported for mortality with sulfates
using the more recent data, but was not statistically significant. Using 2002 data from the
fine particle speciation network, significant associations were found between mortality
and nitrates, EC, Ni and V, as well as traffic density and peak ozone concentrations. In
multi-pollutant models, associations with traffic density remained significant, as did
nitrates, Ni and V in some models. The mean PM2 5 level was 13.2 |ig/m3 using data
from 2002 (Lipfert et al., 2006b, in press).
U.S. Cystic Fibrosis cohort: A positive, but not statistically significant, association was
reported in this cohort (RR = 1.32, 95% CI 0.91-1.93 per 10 |ig/m3 PM2.5) in a study that
primarily focused on evidence of exacerbation of respiratory symptoms (as discussed in
the following section). Only 200 deaths had occurred in the cohort of over 11,000 people
-------
(average age in cohort was 18.4 years) thus the power of the study to detect associations
is limited. The mean PM2 5 concentration was 13.7 |ig/m3 (Goss et al., 2004).
Infant mortality: A new study in California has reported statistically significant
associations between mortality from respiratory causes with exposure to PM2.5, using
PM2 5 levels averaged over the time between the infant's birth and death (RR 1.07, 95%
CI 0.93-1.24 per 10 |ig/m3 PM2.5 for overall mortality and 2.13, 95% CI 1.12-4.05 for
respiratory mortality). The mean PM2.5 exposure concentrations ranged from 17.3 to
19.8 |ig/m3 (Woodruff et al., 2006).
Thoracic coarse particles:
In the original analyses of the Six Cities and ACS cohort studies, no associations were
found between long-term exposure to PMi0.2.5 and mortality; the extended and follow-up
analyses that are discussed above for fine particles did not evaluate potential associations with
PMio-2.5. Two recent reports from the AHSMOG and Veterans study cohorts have provided
some limited suggestive evidence for associations between long-term exposure to PMio-2.s and
mortality, as summarized below.
AHSMOG'. As was found with fine particles, a positive association with coronary heart
3
disease mortality was reported for females (RR = 1.38, 95% CI 0.97-1.95 per 10 |ig/m
PM2.5), but not for males (RR = 0.92, 95% CI 0.66-1.29 per 10 |ig/m3 PM2.5);
associations were strongest in the subset of postmenopausal women (80 deaths).
The mean PMi0-2.5 concentration over 1973-1998 was 25.4 |ig/m3 (Chen et al., 2005).
Veterans cohort: A significant association was reported between long-term exposure to
PMio-2.5 and total mortality in a single-pollutant model (RR = 1.07, 95% CI 1.01-1.12 per
10 |ig/m3 PM2 5), but the association became negative and not statistically significant in a
model that included traffic density. As it would be expected that traffic would contribute
to thoracic coarse particle concentrations, it is difficult to interpret the results of these
multi-pollutant analyses. The average PMi0-2.5 concentration over 1989-1996 was
16.0 |ig/m3 (Lipfert et al., 2006).
Conclusions
As shown in Figure 1, the pattern of results from the new studies for both fine and
thoracic coarse particles is generally similar to those available previously. Overall, the recent
evidence supports associations between long-term PM2.5 exposure and mortality, with key new
evidence from the Six Cities cohort study showing a relatively large risk estimate for reduced
mortality risk with decreases in PM2 5 (Laden et al., 2006). The results of new analyses from the
Six Cities cohort and the ACS study in Los Angeles suggest that previous and current studies
may underestimate the magnitude of the association (Jerrett et al., 2005). In addition, exposure
to PM2.5 was associated with increased respiratory mortality in infants in a new study in
California (Woodruff et al., 2006). New evidence from the Veterans cohort study report
associations with PM2.5 in single-pollutant models, though the authors report that traffic density
is a stronger predictor of mortality than PM2.5 (Lipfert et al., 2006a). There is also suggestive
10
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evidence for an association with mortality in the analysis of the Cystic Fibrosis cohort data.
The new study using Cancer Prevention Study cohort data in Los Angeles, however, indicates
no association with PM2.5 except when using the first time period in the study (Enstrom et al.,
2005).
In the 2004 PM AQCD, results from the ACS and Six Cities study analyses indicated that
thoracic coarse particles were not associated with mortality. The new findings from AHSMOG
and Veterans cohort studies provide some suggestive evidence of associations between long-term
exposure to PMi0-2.5 and mortality in areas with mean concentrations from 16 to 25 |ig/m3. The
2004 PM AQCD placed greatest weight on the ACS and Six Cities study findings; further
evidence will need to be evaluated in the next review of the PM NAAQS on whether long-term
exposure to thoracic coarse particles is associated with mortality.
2.1.2 Morbidity
The 2004 PM AQCD (Section 8.3.3.2) included results from two U.S. and Canadian
children's cohort studies that had been available in the 1996 PM AQCD—the Harvard Six Cities
and Harvard 24-cities studies—that reported significant associations between respiratory
symptoms and decreased lung function with long-term exposure to fine particles and acid
aerosols. More recent studies were available, using data from the Children's Health Study in
southern California; these studies also indicated that long-term exposure to fine particles was
associated with decreased lung function growth2 in children. The results from analyses of data
from the AHSMOG showed suggestive, but inconsistent findings between long-term exposure to
PM and respiratory morbidity in adults. Overall, the 2004 PM AQCD concluded that long-term
exposure to PM, especially fine particles, was associated with respiratory morbidity (2004 PM
AQCD, p. 8-343). Limited and inconsistent evidence was available on associations between
long-term exposure to PMio-2.5 and respiratory morbidity.
Among the recently published studies are longer follow-up analyses of respiratory
morbidity using data from the Children's Health Study, as well as a study based on data from the
U.S. Cystic Fibrosis Cohort. The quantitative results of these studies are included in Table 1,
and further details presented in Appendix A, Table Al.
Fine particles:
Children's Health Study: Significant associations are reported between long-term
exposure to fine particles, as well as acid vapor and NO2, and reduced lung function
growth (Gauderman et al., 2004) and increased risk of bronchitic symptoms, prevalence
of chronic cough, or bronchitis (McConnell et al., 2003). These results expand upon the
findings available in the 2004 PM AQCD, including assessment of lung function
measurements in children over an 8-year follow-up period (Gauderman et al., 2004).
In addition, McConnell et al. (2003) measured respiratory symptom prevalence over a
2 In these studies, lung function measurements were repeated several years apart. Increases in lung
function measures over this time period are referred to as lung function growth by the authors, with "decreased
lung function growth" indicating smaller increases in lung function measurements for the children with higher air
pollution exposure.
11
-------
4-year period, and reported larger effect estimates with changes in PM2.5 concentration
over time within the communities than with changes in PM2 5 between communities.
The mean PM2.5 concentration for the 12 California communities in 1994-2000 was
13.8 |ig/m3 (McConnell et al., 2003; mean concentrations range from 5 to 28 |ig/m3 in
Gauderman et al., 2004). One additional analysis, based on monthly prevalence of
respiratory symptoms, reports no significant associations with PM2 5 (Millstein et al.,
2004).
U.S. Cystic Fibrosis cohort: The risk of experiencing pulmonary exacerbations was
significantly increased with long-term exposure to PM2 5 (Goss et al., 2004). The mean
PM2 5 concentration in 2000 was 13.7 |ig/m3.
Cardiovascular clinical studies: One new study has provided insight into the potential
effect of long-term exposure to PM2 5 on the development of cardiovascular disease; no
such studies were available in the 2004 PM AQCD. Using data from two clinical trials
conducted in the Los Angeles area, the authors reported a significant association between
long-term exposure to PM2.5 and carotid intima-media thickness, a measure of
atherosclerosis development. The mean PM2 5 concentration was 20.6 |ig/m3 (Kunzli
et al., 2005).
Thoracic coarse particles:
Two reports from the Children's Health Study included results for thoracic coarse
particles. A significant association was observed between monthly prevalence of wheeze
and PMio-2.s during March-August in one new study, but no association was seen in other
parts of the year (Millstein et al., 2004). No significant associations were reported
between long-term exposure to PMio-2.s and incidence of bronchitic symptoms in another
report in which the mean PMio-2.s concentration was 17.0 |ig/m3 (McConnell et al., 2003).
The recent findings from the southern California Children's Health Study add support to
previous conclusions that long-term fine particle exposure is associated with increased incidence
of respiratory symptoms and decreased lung function growth in children. The new evidence
from the Cystic Fibrosis Cohort provides additional evidence for associations with pulmonary
exacerbations, particularly in a cohort of likely more susceptible individuals. These new studies
also report associations with fine particle concentrations that are somewhat lower than those
from studies available in the 2004 PM AQCD. These recent findings, however, do not show
associations between respiratory morbidity and long-term exposure to PMio-2.s; in contrast, one
earlier analysis from the Children's Health Study in California had suggested such associations.
No studies available in the 2004 PM AQCD had assessed associations between long-term
PM exposure and cardiovascular morbidity. A new analysis shows an association between long-
term PM2.5 exposure and a measure of atherosclerosis development (Kunzli et al., 2005).
12
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2.2 Epidemiologic Short-Term Exposure Study Results
The 2004 PM AQCD included the results of many new epidemiologic studies reporting
associations between short-term exposure to PM and a range of health outcomes. The larger
body of evidence from studies of PMio and other PM indicators provided strong evidence for
associations between short-term PM exposure and both mortality and morbidity (2004 PM
AQCD, p. 8-337).
The 2004 PM AQCD concluded that there was strong epidemiological evidence linking
short-term exposures to PM2 5 with cardiovascular and respiratory mortality and morbidity.
Positive, often statistically significant associations were observed between PM2.5 and these
various health endpoints (2004 PM AQCD, p. 9-46). The epidemiological evidence was found
to support likely causal associations between PM2.5 and both mortality and morbidity from
cardiovascular and respiratory diseases, based on an assessment of strength, robustness, and
consistency in results (2004 PM AQCD, p. 9-48).
Fewer studies were available to assess associations between PMi0-2.5 and health
outcomes. The magnitude of the effect estimates for associations between PMi0-2.5 and mortality
and morbidity effects (especially respiratory morbidity) was found to be similar to that for PM2.5,
but the strength of the evidence for PMi0-2.5 effects was reduced due to lower precision (AQCD,
p. 9-46). Despite the reduced strength, the associations were found to be generally robust to
alternative modeling strategies or consideration of potential confounding by co-pollutants. The
collective evidence was found to be suggestive of associations for morbidity with short-term
changes in PMio.2.5 (2004 PM AQCD, p. 9-48).
Sections 2.2.1 and 2.2.2 highlight results from recent time-series epidemiologic studies.
Tables A2 through A12 (Appendix A) summarize results of recent epidemiologic studies that
evaluated relationships between health effects and short-term exposure to PM2.s and PMi0.2.5.
The discussions below emphasize results of studies conducted in the U.S. and Canada; however,
some results are also presented from additional international studies or studies using indicators,
such as PMio, that assess key issues or questions highlighted in the 2004 PM AQCD.
The 2004 PM AQCD included a particular focus on results of multicity studies due to
their evaluation of a wide range of PM exposures and large numbers of observations, which lead
to generally more precise effects estimates than most smaller scale independent studies of single
cities. The multicity studies also allowed investigation of homogeneity or heterogeneity of PM-
health relationships, evaluation of confounding by co-pollutants across communities with
different air pollution mixtures, and assessment of potential effect modifiers. Numerous
multicity analyses have been published in recent years. Most of the recent multi-city studies
report statistically significant associations between short-term exposure to PMio and mortality or
morbidity and these study results are briefly summarized in Section 2.2.3 as being particularly
relevant to help address key methodological questions. In addition, 3 new multi-city studies
have evaluated associations with PM2.5, one of which included PMio-2.s, and these studies are
highlighted in the following sections.
13
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2.2.1 Mortality
Results from multi- and single-city epidemiologic studies on mortality were presented in
Figure 9-4 of the 2004 PM AQCD. Associations were mostly positive and of similar magnitude
for both PM2.5 and PMio-2.5- A number of the associations between mortality and short-term
PM2.5 exposure were statistically significant, while few associations with PMio-2.5 reached
statistical significance, possibly due to increased measurement error in estimating PMio-2.5
exposure (2004 PM AQCD, p. 9-28). Several recent studies have reported associations between
mortality and short-term exposure to PM2.5 and PMio-2.5- These findings are included with those
available from the 2004 PM AQCD in Figure 2, where it can be seen that the new study results
are generally quite similar to those previously available. Note that Figure 2 presents results from
single-pollutant models for purposes of comparing results across studies that included different
mixes of copollutants, as done in the 2004 PM AQCD.
2.2.1.1 Associations Between Acute Exposure to Fine Particles and Mortality
A number of recent studies have evaluated associations between fine particles and
mortality, including two multicity studies (Appendix A; Table A2). Evidence for associations
between short-term exposure to PM2 5 and all-cause, cardiovascular, and respiratory mortality
comes from the multi-site study by Ostro et al. (2006) conducted in nine California counties that
had mean PM2 5 concentrations ranging from 14 to 29 |ig/m3. Significant associations were
reported in single-pollutant models for all-cause, cardiovascular and respiratory mortality for all
ages, as well as a significant association with all-cause mortality for those aged >65 years. The
authors observed that in multipollutant models, the PM2.5 effect estimate was attenuated when
highly correlated pollutants (NO2 and CO) were added to the model, but was not affected by the
inclusion of 63. However, in those aged >65 yr (who generally experienced stronger
associations with mortality), adjusting for gaseous pollutants did not affect the PM2 5 coefficient.
Burnett et al. (2004) evaluated the relationship between NO2 and mortality in
12 Canadian cities during the period 1981 to 1999. While the focus of this analysis was on
associations with NO2, the analysis included other pollutants as well. PM2 5 data were available
only on 12% of days with mortality data, compared to the other gaseous pollutants that had
>90% data available, and for most of the study time period, PM2.5 was measured every 6th day.
In analyses using these data, the association between PM2.5 and all-cause mortality was
marginally significant (as shown in Figure 2). In two-pollutant models with NO2, the effect
estimate for PM2 5 became negative (not significant), while the estimate for NO2 remained
robust. NO2 concentrations were found to be correlated with PM2.5 concentrations (r = 0.48).
Burnett and colleagues (2004) also report results from a separate analysis using more
recent data with daily PM2 5 measurements (1998-2000). The authors state that a positive
association was found between mortality and PM2.5 in this additional analysis (presumably
significant, but confidence intervals were not provided). In this case, the NO2 association was
reduced considerably after adjustment for PM2 5, whereas the PM2 5 association remained fairly
robust with NO2 adjustment. These findings emphasize the difficulty of working with data
collected every 6th day. The mean PM2 5 concentration for all 12 cities was 12.8 |ig/m3 with
city-specific means ranging from 8.1 |ig/m3 in St. John to 16.7 |ig/m3 in Windsor.
14
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Figure 2. Excess risk estimates for total nonaccidental, cardiovascular, and respiratory mortality in single-pollutant models
for U.S. and Canadian studies, including aggregate results from multicity studies (denoted in bold print below).
PM increment used for standardization was 25 ug/m3 for both PMi.s and PMio-2.s. Results presented in the 2004 PM
AQCD are marked as + in the figure (studies A through T). Results from recent studies are shaded in grey and marked
as x in the figure (studies AA through HH).
A. Burnett and Goldberg (2003), 8 Canadian cities
B. Klemm and Mason (2003), 6 U.S. cities
C. Moolgavkar (2003), Los Angeles
D. Klemm and Mason (2003), St. Louis
E. Klemm and Mason (2003), Boston
F. Klemm and Mason (2003), Kingston-Harriman
G. Klemm and Mason (2003), Portage
H. Ito (2003), Detroit
I. Chock et al. (2003) Pittsburgh (age <75 yr)
J. Chock et al. (2003) Pittsburgh (age 75+ yr)
K. Klemm and Mason (2000), Atlanta
L. Fairley (2003), Santa Clara County
M. Klemm and Mason (2003), Topeka
N. Tsai et al. (2000), Newark
O. Klemm and Mason (2003), Steubenville
P. Tsai et al. (2000), Elizabeth
Q. Tsai et al (2000), Camden
R. Lipfert et al. (2000), Philadelphia
S. Ostro et al. (1995), Southern California
T. Mar et al. (2003), Phoenix
U. Ostro et al. (2003), Coachella Valley
AA. Ostro et al. (2006), 9 counties in CA
BB. Ostro et al. (2006), 9 counties in CA (age >65 yr)
CC. Burnett et al. (2004), 12 Canadian cities
DD. Ito et al. (in press), Washington, DC
EE. Villeneuve et al. (2003), Vancouver, Canada
FF. Slaughter et al. (2005), Spokane
GG. Goldberg et al. (2006), Montreal, Canada (age 65+ yr)
HH. Klemm et al. (2004), Atlanta (age 65+ yr)
II. Klemm et al. (2004), Atlanta (age <65 yr)
-------
Several single-city studies have also been published. Evidence for associations between
fine particles and mortality was seen in studies in Montreal (Goldberg et al., 2006) and Atlanta
(Klemm et al., 2004), as well as in studies that focused on source apportionment in Phoenix (Mar
et al., 2006) and Washington, DC (Ito et al., 2006). No associations were reported in studies in
Vancouver (Villeneuve et al., 2003) and Spokane (Slaughter et al., 2005); these studies reported
low PM2 5 concentrations. Finally, one new analysis reports no evidence for associations
between short-term exposure and death due to sudden infant death syndrome (Dales et al., 2004).
The mean PM2.s concentrations in locations where statistically significant associations were
reported ranged from about 12 to greater than 20 |ig/m3.
In Figure 2, the results of the recent time-series studies are presented alongside the
findings available in the 2004 PM AQCD. In this figure, it can be seen that the results of the
larger multicity studies are quite consistent with those in earlier studies. The studies have been
presented in order of decreasing statistical power (based on number of days and number of health
events per day) from left to right for each group of studies. Some of the recent studies have
fairly low statistical power which is reflected in the large confidence intervals and more variable
effect estimate sizes shown in Figure 2. These results, while imprecise, are also generally
consistent with earlier study results. Collectively, evidence regarding the PM2 5-mortality
association from the most recent literature appears to be consistent with that available from the
2004 PM AQCD.
2.2.1.2 Associations Between Acute Exposure to Thoracic Coarse Particles and Mortality
Several new studies examined the association between PMio-2.5 and mortality in the U.S.
and Canada (Appendix A; Table A3). The multicity study by Burnett et al. (2004), aimed
primarily atNO2, also examined the association between PMio-2.5 and all-cause, nonaccidental
mortality for lag day 1 (i.e., previous day) using data from 12 Canadian cities. The association
with PMio-2.5 was positive but not significant; there was a significant association with PMio that
lost significance with adjustment for NC>2. However, particle data were available only on 12%
of days in this study, as discussed above. The mean PMio-2.5 concentration in this study was
11.4 |ig/m3 (12 city means range from 5.5 to 15.9 |ig/m3).
Figure 2 includes results from the recent single-pollutant studies and those available in
the 2004 PM AQCD. Looking across all studies, it can be seen that associations between
PMio-2.5 and total and cardiovascular mortality are generally positive and a number are
statistically significant, particularly for cardiovascular mortality. As discussed in the 2004 PM
AQCD, some studies indicated stronger associations between acute PMio-2.5 exposure and
cardiovascular mortality than for all-cause mortality. One recent study in Vancouver, Canada,
also observed a statistically significant relationship with cardiovascular mortality on lag day 0
(i.e., same day) but not on lag day 1 or 2 or the 3-day average lag periods (i.e., 24-hour average
concentrations measured 1-, 2- or 3-days prior) (Villeneuve et al., 2003). No associations were
found for all-cause, respiratory, or cancer mortality in this study. The mean PMio-2.5
concentration in this study was 6.1 |ig/m3 (range 0 to 72 |ig/m3).
16
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Other recent studies did not report statistically significant associations between PMio-2.5
and total mortality. Slaughter et al. (2005) did not find a significant relationship for PMio-2.s with
all-cause, nonaccidental mortality in Spokane, WA, which likely had higher PMio-2.5
concentrations than Vancouver, Canada (data not shown). Neither Slaughter et al. (2005) nor
Burnett et al. (2004) investigated the relationship with cardiovascular mortality. A recent PMio
study in El Paso (Staniswalis et al., 2005) supports the hypothesis that wind-blown dust coming
from non-urban areas during high wind speeds (assumed largely coarse-fraction particles) is less
toxic than particles generated within the urban area. Finally, Klemm and colleagues (2004)
reported a positive, but not statistically significant association between PMio-2.5 and mortality in
Atlanta. The mean PMio-2.5 concentration in this study was 9.7 |ig/m3 (range 1.7 to 25.2 |ig/m3).
2.2.2 Morbidity
Results from epidemiologic studies on hospital admissions were presented in Figure 9-5
of the PM AQCD. Associations were all positive and of similar magnitude for both PM2.5 and
PMio-2.5. Many of the associations with short-term PM2.5 exposure were statistically significant,
especially for respiratory diseases. Likely due to increased measurement error, some, but not all,
of the associations with PMio-2.5 reached statistical significance (2004 PM AQCD, p. 9-29).
Several recent studies have reported associations between short-term exposure to PM2.s and
PMio-2.5 and hospitalization or emergency department visits for cardiovascular and respiratory
diseases. These findings are included with those available from the 2004 PM AQCD in Figure 3.
2.2.2.1 Associations Between Acute Exposure to Fine Particles and Morbidity
These new studies substantially expand the evidence for associations between PM2.s and
effects on the cardiovascular system (Appendix A; Tables A4, A6 and A8). These include a
powerful new multi-city study by Dominici et al. (2006) that used data from the Medicare
National Claims History Files for 11.5 million people living in 204 urban counties in the U.S.;
the average PM2.s concentration for 1999-2000 was 13.4 |ig/m3. There was only limited
consideration of other pollutants in this analysis. Hospital admission rates for cause-specific
cardiovascular and respiratory diseases were significantly associated with short-term PM2.s
exposure in individuals aged >65 yr. The largest association was reported with heart failure.
Significant associations were also found between short-term PM2.s exposure and hospital
admissions for cerebrovascular disease, and positive though not statistically significant
associations were seen with peripheral vascular disease, ischemic heart disease, and cardiac
rhythm. When evaluated on a region-specific basis, positive associations with cardiovascular
disease hospitalization were seen in the Midwest, Northeast, and Southern regions; the authors
suggest that differences in the sources and composition of fine particles contributes to the
geographic differences seen in effect estimates.
One recent study reports significant associations between short-term exposure to PM2.s
and emergency department visits for all cardiovascular diseases, congestive heart failure and
peripheral vascular and cerebrovascular disease in Atlanta (Metzger et al., 2004). Another study
reports no evidence of associations with cardiovascular visits in Spokane, where the PM2.s
concentrations were low (authors report that 90% of concentrations ranged between 4.2 and
20.2 |ig/m3) (Slaughter et al., 2005).
17
-------
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diseases in single-pollutant models for U.S. and Canadian studies, including aggregate results from a multicity study
(denoted in bold print below). PM increment used for standardization was 25 ug/m3 for both PM2 5 and PMi0-2.5.
Results presented in the 2004 PM AQCD are marked as *, in the figure (studies A through H). Results from recent
studies are shaded in grey and marked as x in the figure (studies AA through JJ). (CHF = congestive heart failure;
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-------
A. Moolgavkar (2003), Los Angeles
B. Burnett etal. ( 1997), Toronto
C. Ito (2003), Detroit
D. Stieb et al. (2000), St. John
E. Sheppard (2003), Seattle
F. Thurston etal. (1994), Toronto
G. Delfino et al. (1997), Montreal
H. Delfino et al. (1998), Montreal
AA. Dominici et al. (2006), 204 U.S. counties (age >65 yr)
BB. Slaughter et al. (2005), Spokane (age 15+ yr)
CC. Metzger et al. (2004), Atlanta
DD. Slaughter et al. (2005), Atlanta
EE. Chen et al. (2005), Vancouver, Canada (age 65+ yr)
FF. Chen et al. (2004), Vancouver, Canada (age 65+ yr)
GG- Lm et al. (2002), Toronto, Canada (age 6-12 yr, boys)
HH- Lm et al. (2002), Toronto, Canada (age 6-12 yr, girls)
IL Peel et al- (2005)> Atlanta
JJ. Yang et al. (2004), Vancouver, Canada (age >3 yr)
KK. Lin et al. (2005), Toronto, Canada (age <16 yr, boys)
LL. Lin et al. (2005), Toronto, Canada (age <16 yr, boys)
-------
Numerous new studies have reported associations between ambient PM2.5 and subtle
cardiovascular effects such as changes in cardiac rhythm or heart rate variability (Appendix A;
Table A8). In the 2004 PM AQCD, the data base was characterized as having some studies with
conflicting results and a note of caution was raised in regard to drawing conclusions relating
PM2.5 and heart rate variability and other measures of cardiovascular pathophysiological
alterations. Of about 10 new studies evaluating associations between acute PM2 5 exposure and
heart rate variability, most reported statistically significant associations with PM2.5. . Two new
studies showed associations for PM2.5 with ST segment depressions, an indicator of myocardial
ischemia (Gold et al., 2005). One new study examined PM2.5 effects on bronchial artery
reactivity (a marker for cardiovascular disease risk) and reported a significant association
(O'Neill et al., 2005). Noting that many of these studies were conducted over shorter time
periods, nevertheless, it is reported that mean or median PM2.5 concentrations in a number of
studies were in the range of 10-11 |ig/m3, with maximum levels ranging from about 40 to
60 |ig/m3.
For respiratory effects, Dominici et al. (2006) report significant associations between
PM2.5 and hospitalization for chronic obstructive pulmonary disease (COPD) and respiratory
infection in the study of 204 U.S. counties mentioned above (Appendix A; Table A4). Less
regional variation was seen for respiratory hospitalization than for cardiovascular hospital
admissions; in contrast with the results for cardiovascular diseases, effect estimates for both
COPD and respiratory infections admissions were larger for the western U.S. than the eastern
U.S.
There are also several single-city studies that were conducted in Canada that show no
associations between hospitalization and acute exposure to PM2.5 (Lin et al., 2002; Lin et al.,
2005; Yang et al., 2004; Chen et al., 2004; Chen et al., 2005). All were studies of hospitalization
for respiratory diseases, though studies differed in age group and respiratory endpoint, and the
mean PM2.5 concentrations in the studies ranged from 7.7 to 18 |ig/m3. Another recent study
reports positive associations with respiratory emergency department visits, although none are
statistically significant (Peel et al., 2005) (mean concentration of 19.2 |ig/m3). Finally, there was
no evidence of associations with respiratory visits in Spokane, where the PM2 5 concentrations
were low (90th percentile was 20.2 |ig/m3) (Slaughter et al., 2005).
There are numerous new studies that examined various respiratory outcomes in relation
to PM2.s exposure (Appendix A; Table A10), including one new multicity study that reported a
significant association between respiratory symptoms and short-term PM2.5 exposure (Gent et al.,
2003) (mean concentration of 13.1 |ig/m3); however, the effect estimate is reduced and not
statistically significant with adjustment for ozone. Associations have also been reported between
acute PM2.s exposure and a new endpoint not previously reported, F£NO (fractional exhaled nitric
oxide, a marker of airway inflammation), in three studies conducted in Seattle, WA (Jansen
et al., 2005; Koenig et al., 2005; Mar et al., 2005) and one in Steubenville, OH (Adamkiewicz
et al., 2004). In addition, a study in Seattle reports statistically significant associations with
lower respiratory symptoms in children with asthma (Mar et al., 2004). One study in Atlanta
reported no positive associations between PM2.5 and medical visits for various respiratory
conditions—in fact, some associations were negative in direction—but positive associations
were reported for several components of PM2 5 (Sinclair and Tolsma, 2004).
20
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2.2.2.2 Associations Between Acute Exposure to Thoracic Coarse Particles and Morbidity
A number of new epidemiologic studies are available for assessing associations between
short-term PMio-2.5 exposure and various morbidity health outcomes, especially related to
respiratory morbidity (Appendix A; Tables A5, A7, A9, and Al 1). As shown in Figure 3, a
number of recent reports have shown significant associations between respiratory hospitalization
and acute exposure to PMio-2.5. These include associations with hospitalization in Vancouver for
respiratory illness in children <3 years of age (Yang et al., 2004), COPD in the elderly, (Chen
et al., 2004) and respiratory illness in the elderly (Chen et al., 2005). Associations were also
reported with hospitalization for asthma in children (Lin et al., 2002) and respiratory illness in
children (Lin et al., 2005) in Toronto. These associations with hospital admissions for
respiratory disease were observed for PMio-2.5 in both time-series and case-crossover analyses,
and the associations remained significant with adjustment for gaseous co-pollutants in four of the
five studies (except Chen et al., 2005). The effect estimate increased with longer averaging
times up to 4-7 days. Slaughter et al. (2005) did not observe significant associations between
PMio-2.5 and hospitals admissions or emergency room visits in Spokane, WA for all ages taken
together. Overall, these studies provide evidence for associations between acute PMio-2.5
exposure and respiratory morbidity in locations where reported mean concentrations range from
5.6 to 12.2 |ig/m3, and maximum concentrations from 24.6 to 68 |ig/m3.
One new panel study in Spokane indicated that exposure was associated with several
upper respiratory tract symptoms in children with asthma, but no association was reported in
adults (Mar et al., 2004). Peel et al. (2005) reported no significant associations between PMio-2.5
and respiratory emergency department visits in Atlanta; however in another Atlanta study,
significant associations were reported between acute PMio-2.5 exposure and outpatient medical
visits for several respiratory conditions (Sinclair and Tolsma, 2004).
Little evidence was available on associations between cardiovascular morbidity and
PMio-2.5 in the 2004 PM AQCD. In Atlanta, no significant associations were found between
acute exposure and cardiovascular emergency department visits (Metzger et al., 2004).
However, one recent study in Coachella Valley, CA reported significant associations between
decreases in heart rate variability with short-term exposure to PMio-2.5, but not with PM2.s
(Lipsett et al., 2006). In addition, a panel study in Vancouver (Ebelt, et al., 2005) found
significant associations between estimates of personal exposure to ambient particles, and to a
lesser extent, ambient concentrations with decreased FEVi and increases in systolic blood
pressure and supraventricular ectopy. However, associations were not significant with measures
of heart rate variability. No associations were reported with estimates of personal exposure to
nonambient particles. The mean PMio-2.5 concentrations in the Coachella Valley and Vancouver
studies range from about 10 to over 20 |ig/m3 At the low end of reported concentrations is
Vancouver, where PMio-2.5 means were 6-7 |ig/m3 and maxima were about 25 |ig/m3. Of note,
correlations reported between PMio-2.5 and combustion-related gaseous co-pollutants (CO, NO2,
802) are generally higher than those reported between PM2.5 and the gases in Vancouver. At the
high end is Coachella Valley, where PMio concentrations were quite high, with peak levels
exceeding the current PMio standard level.
Taken together, there is a substantial new body of evidence linking acute exposure to
PMio-2.5 with morbidity, including associations with respiratory hospitalization, respiratory
21
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symptoms, and cardiovascular health outcomes. Of note, several recent studies have reported
associations for several indicators of morbidity with PMio-2.s, but not with PM2 5. In addition,
some new studies have used case-crossover methods and reported little evidence for confounding
by co-pollutants. A key research question that has been identified during the current PM
NAAQS review is to better understand the sources and components of PMi0-2.5 that may be
responsible for different health effects, and these findings continue to support that research need.
2.2.3 Issues for Interpretation of Epidemiologic Study Results
More than 20 new multicity studies have been published in recent years. Three of these
studies have included measurements of PM2.5 and one included PMi0-2.5 and these studies are
summarized in more detail above (Burnett et al., 2004; Dominici et al., 2006; Ostro et al., 2006).
The remaining studies used PMio; the results are summarized briefly in an annotated
bibliography (Appendix B). Most of these recent studies continue to report associations between
short-term exposure to PMio and mortality or morbidity.
Methodological Issues: The results of the PMio multicity studies are briefly highlighted
here due to the importance of multicity studies in being able to evaluate issues that are not
readily addressed in single-city analyses. The studies are grouped in Appendix B by the general
issues being evaluated in the analyses. These studies address a range of questions and
uncertainties that remained in the 2004 PM AQCD, including:
• Several recent multicity studies reported that associations between PMio and mortality
are not likely to be confounded by weather or influenza epidemics (Schwartz 2004a;
Welty and Zeger, 2005; Analitis et al., 2006; Touloumi et al., 2005). As observed in the
2004 PM AQCD, assessments of copollutant confounding are complicated when the air
pollutants are closely correlated, such as pollutants generated from common sources.
Results from single-pollutant models may overestimate effects from that pollutant;
however, multi-pollutant model results may be misleading when reporting results for
correlated pollutants. One new multi-city study used case-crossover design and reported
no evidence of confounding between PMio and gaseous co-pollutants in associations with
mortality in 14 U.S. cities (Schwartz et al., 2004b). Using more traditional time-series
methods, Ostro et al. (2006) reported attenuation of associations between PM2.sand
mortality with highly-correlated gaseous pollutants in adults <65 years of age, but not in
analyses for the elderly. In 12 Canadian studies, PM2.5 and PMio-2.s were robust to
adjustment for NO2 in models using only data from the time period when daily PM data
were available, but effect estimates were not statistically significant in models using data
from the full time period (Burnett et al., 2004). Dominici et al. (2006) report little
evidence of effect modification by ozone concentrations in the relationship between
PM2.5 and hospitalization.
• Daniels et al. (2004) reported that there was no evidence for a threshold level in the
PMio-mortality association in analyses of data from the National Morbidity, Mortality
and Air Pollution Study.
22
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• The recent multicity studies continue to report somewhat stronger associations with the
use of a distributed lag model (Analitis et al., 2006; Zanobetti et al., 2003; Zeka et al.,
2005). In addition, one new analysis shows little evidence that the associations are
unlikely to represent advancement of death by only a few days (Dominici et al., 2003).
• The recent studies also report findings that are robust to the use of different analytical
methods (Roberts and Martin, 2006) and assess the influence of measurement error in
underestimation of the PMio-mortality association (Zeka and Schwartz, 2004).
Variation in effects between locations: Numerous new multicity analyses in Europe and
the U.S. have studied the variation of PM-health associations between locations, and assessed
factors that may influence heterogeneity in PM-related health effects (Dominici et al., 2003;
Medina-Ramon et al., 2006; Samoli et al., 2005; Le Tertre et al., 2005; Zeka et al., 2005; Zeka
et al., 2006). Consistent with the findings available in the 2004 PM AQCD, the recent studies
highlight exposure differences (e.g., air conditioning use) and the influence of traffic as
potentially associated with larger effects of PMi0. Some recent studies also suggest that
variability in climate and a number of preexisting health conditions may modify the effects of
PM.
New health outcomes: New multicity analyses have also reported associations between
PMio and new health outcomes, including emergency admissions for myocardial infarction
(Zanobetti and Schwartz, 2005), readmission to the hospital for cardiac causes (Von Klot et al.,
2005) and potential changes in physiological cardiac indicators (Ibald-Mulli et al., 2004;
Timonen et al., 2006)Numerous recent single-city studies also expand of the health endpoints
that are reported to be associated with PM, generally focusing on PM2.5 exposures. These newly
reported health endpoints include: (1) indicators of the development of atherosclerosis with long-
term PM exposure; (2) indicators of changes in cardiac rhythm, including arrhythmia or
ST-segment changes; (3) effects on developing children and infants; (4) markers of inflammation
such as exhaled NO; and (5) effects on organ systems outside the cardiopulmonary systems.
Numerous new epidemiologic studies have reported associations between PM, primarily using
PM2.5, and cardiovascular health outcomes such as cardiac arrhythmia, ST segment depression,
and decreased heart rate variability. New toxicology reports suggest that the brain may be
affected by exposure to PM, including reports of increases in inflammatory biomarkers and
neurodegeneration following exposure to CAPs (Campbell et al., 2005; Veronesi et al., 2005).
Potentially susceptible or vulnerable subpopulations: In the 2004 PM AQCD, people
with preexisting heart or lung disease, children, and older adults were considered likely to be
more susceptible to PM-related effects. Recent studies provide increasing evidence that pre-
existing diseases, particularly diabetes, may increase susceptibility to the cardiovascular effects
of PM. Goldberg et al. (2006) reported significant associations between PM2 5 and diabetes
deaths, as well as total mortality in people with previous diagnoses of diabetes. One new
toxicology study has suggested mechanistic evidence for diabetes-related susceptibility (Proctor
et al., 2006). Additional research utilizing susceptible animal models of vascular conditions
(e.g., the Spontaneously Hypertensive rat and the apolipoprotein deficient mouse) have
demonstrated that exposure to CAPs or surrogate PM can exacerbate symptoms, compromise
function and potentiate disease states.
23
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2.3 Intervention Studies
The 2004 PM AQCD highlighted the results of several new "intervention" studies or
"found experiments" that reported associations between reductions in air pollution and
improvements in public health (2004 PM AQCD, Sections 8.2.3.4 and 9.2.2.6). While few in
number, these studies were found to provide important support to the epidemiologic evidence
linking air pollution exposure with adverse health effects.
One new study reported evidence for reduced mortality risk when ambient pollution
was decreased (Laden et al., 2006). As discussed briefly above, the authors report a statistically
significant reduction in mortality risk with reduced long-term fine particle concentrations
(RR 0.73, 95% CI 0.57-0.95, per 10 |ig/m3 PM2.5).
Several recent intervention studies have evaluated changes in respiratory health outcomes
associated with decreased pollution levels; the results of these studies are summarized in
Table A13 (Appendix A). One U.S. study reported reductions in respiratory medical visits
with decreased traffic volume that resulted from closure of the Peace Bridge in Buffalo, NY,
following September 11, 2001 (Lwebuga-Mukasa et al., 2003). Studies conducted in
Switzerland and East and West Germany have also reported reductions in respiratory symptoms
or improved lung function with decreases in ambient PM concentrations measured as TSP or
PMio (Bayer-Oglesby et al., 2005; Sugiri et al., 2006; Frye et al., 2003; Heinrich et al., 2002).
In addition, Burr et al. (2003) reported associations between reduced respiratory symptoms and
reductions in traffic volume. Overall, this group of studies indicates that declining
concentrations of PM and other pollutants is associated with reduced mortality risk and improved
respiratory health and thus add substantial support to the evidence available in the 2004 PM
AQCD.
2.4 Health Effects Related to Sources or Components of PM
The current PM NAAQS have been established using PM2.5 and PMio mass as the
indicators, as opposed to singling out any particular component or class of particles. This
decision was based on evidence from epidemiologic studies that reported significant associations
between various PM components or characteristics, evidence that PM was associated with health
effects in numerous areas that had differing components or sources of PM, and evidence from
animal toxicology and controlled human exposure studies that had reported health effects
associations with high concentrations of numerous fine particle components (e.g., sulfates,
nitrates, transition metals, organic compounds).
In the 2004 PM AQCD, epidemiologic and toxicology studies provided evidence for
effects associated with various fine particle components or size-differentiated subsets of fine
particles. Toxicology studies reported effects with exposure to different sources or components
of PM (generally at high levels), such as metals, diesel particles, acid aerosols, and bioaerosols
(Chapter 7 of the 2004 PM AQCD). The findings of these studies indicated that, for a given
health response, some fine particle components were more closely linked with that response than
other components. However, the evidence did not suggest that any component could be singled
out as potentially the sole contributor to toxicity, or as having no toxic effects.
24
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Chapter 8 of the 2004 PM AQCD included a discussion of three new epidemiologic
studies that reported associations between various health outcomes and different PM
components. Three new studies that had conducted source-oriented evaluation of PM provided
new insights into the relationship between fine particles from different sources and mortality.
While few in number and somewhat preliminary in nature, these studies suggested that a number
of source types were associated with mortality, including motor vehicle emissions, coal
combustion, oil burning, and vegetative burning; no associations were reported with the crustal
factor from fine particles (2004 PM AQCD, Section 8.2.2.5).Considered together, the 2004 PM
AQCD concluded: "These studies suggest that many different chemical components of fine
particles and a variety of different types of source categories are all associated with, and
probably contribute to, mortality, either independently or in combinations" (p. 9-31).
Conversely, there was no basis to conclude that any individual fine particle component cannot
be associated with adverse health effects.
Many new studies have been published in recent years that provide interesting new
insights into the effects of different sources or types of PM. For the purposes of this provisional
assessment of new literature published since the release of the 2004 PM AQCD, emphasis has
been placed on studies that investigated the health effects related to PM sources or comparisons
of various PM components. To highlight the scientific content of the recent literature while
focusing on key PM study categories, this section focuses on results of studies that evaluated the
effects of a range of sources or components. This includes studies that used source
apportionment, or that compared effects for a range of PM components. Thus, the discussion
includes: (1) recent epidemiologic studies using source apportionment; (2) epidemiologic
evidence on effects with PM components; (3) results of new toxicology studies using source
apportionment with exposures to concentrated ambient particles (CAPs) to provide insight into
potential effects related to PM from different sources, and comparative toxicology studies using
fine particle components; and (4) toxicology study results for different surrogates and size
fractions of PM, including thoracic coarse PM (PMio-2.s). In addition, numerous epidemiologic
and/or toxicology studies have reported effects of several sources, components, or characteristics
as discussed in the 2004 PM AQCD. Specific findings for these PM characteristics are not
discussed in detail; instead, the available new studies are included in reference lists for the
following categories:
• ultrafme PM;
• metals (including residual oil fly ash);
• traffic;
• woodsmoke; and
• endotoxin.
2.4.1 Epidemiologic Studies Using Source Apportionment
Some recent epidemiologic studies have employed statistical approaches of source
contributions from source apportionment analyses in evaluating associations of health effects
with particular source categories of PM. Since source apportionment analysis is based on
finding independent groupings of chemical components, the source categories should not
confound each other.
25
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A workshop was held in May 2003 during which several groups determined source
category contributions (using multiple techniques) using ambient PM chemical concentration
data from Washington, D.C. (U.S. Park Service, IMPROVE) and from Phoenix (U.S. EPA).
An intercomparison of the source apportionment results was also published (Hopke et al., 2006).
The statistical associations of these source category contributions with total (non-accidental) and
cardiovascular mortality were then determined by Ito et al. (2006) for Washington and Mar et al.
(2006) for Phoenix. The results from different groups varied, in part depending on the
participants' experience and expertise with source apportionment and time-series epidemiologic
analyses (Appendix A; Table A14). Although several groups separated the traffic source into
diesel and gasoline, for the reported analyses, all traffic-related source categories were summed
into a "traffic" source category. For Washington, DC, the correlations of daily contributions of
source categories across the various investigators/techniques were fair for crustal, secondary
sulfate, secondary nitrate, primary residual oil combustion, and incinerator, but poor for traffic,
wood burning, and salt (correlation not reported for primary coal combustion). In Phoenix, AZ,
the correlations of daily contributions across the various investigators and analysis techniques
were high for traffic, secondary sulfate, and sea salt, and low for biomass burning, metals, and
primary coal burning.
In Washington, DC, secondary sulfate and primary coal combustion were statistically
significant with total mortality on lag day 3. PM2.s had a statistically significant relationship with
total mortality on lag day 1 and 3 before controlling for temperature, but only on lag day 3 after
controlling for temperature. For cardiovascular mortality, no source categories were statistically
significant across all investigators/techniques. However, for one or more analyses, statistically
significant results were found for soil (lag 2, 3, and 4), traffic (lag 3), secondary sulfate (lag 0
and 3), residual oil (lag 0), wood smoke (lag 3), and primary coal burning (lag 3). The
Washington, DC samples were collected on Saturday and Thursday only; so, each lag has a
different set of mortality days which may introduce some uncertainty into the lag structure.
In Phoenix, only sea salt (lag 5) was statistically significant with total mortality for all
analyses, while 3/5 data sets gave statistically significant results for Cu smelter (lag 0) and 1/8
for sulfate (lag 0). For cardiovascular mortality, most data sets gave statistically significant (or
nearly so) associations for traffic (lag 1, 6/9), secondary sulfate (lag 0, 6/8), sea salt (lag 5, 6/6),
and Cu smelter (lag 0, 3/5). Data sets from both cities show secondary sulfate as the source
category with the highest statistically significant relative risk (5-95th percentile increments),
although the lag days and mortality categories differ by city (lag 0 for cardiovascular mortality in
Phoenix, AZ, and lag 3 for total mortality in Washington, DC, with some Washington, DC, data
sets reporting lags 0 and 3 for cardiovascular mortality). A generalized traffic source is
implicated for cardiovascular mortality at lag 1 in Phoenix, AZ and lag 3 in Washington, DC.
One study used source apportionment techniques to assess relationships between
cardiovascular morbidity and acute fine particle exposure in a panel of healthy young male patrol
officers in Wake County, NC. Riediker et al. (2004) reported the strongest associations between
a "speed change" factor (Cu, S, and aldehydes) and a number of cardiovascular health indicators.
There were suggested associations with a gasoline combustion factor, and there was limited
evidence for associations with fine particles of crustal origin.
26
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Taken together, the results of these new studies are consistent with previously-available
evidence that link health outcomes with fine particles from a range of sources, including motor
vehicles and combustion of oil or coal. The use of source categories in community time-series
epidemiology shows promise but additional work is needed in characterizing the various sources,
understanding the spatial variability of the different source categories, and obtaining daily
composition and concentration data for periods of several years in additional cities.
2.4.2 Epidemiologic Studies on Effects of Fine Particle Components
As summarized in Section 8.2.2.5 of the 2004 PM AQCD, epidemiologic studies have
reported generally positive, often statistically significant associations between various fine
particle components and mortality. Numerous studies have reported associations between short-
term sulfate exposures and mortality and morbidity; the effect estimates reported for mortality
range from about 1 to 9% increases in mortality per 5 |ig/m3 increase in ambient sulfate
concentration (as shown in Figure 8-6 of the 2004 PM AQCD). Associations have also been
reported with other PM components, including carbonaceous components (elemental carbon,
organic carbon, and coefficient of haze), nitrates, and metals.
Associations between mortality and long-term exposure to ambient sulfates was reported
in prospective cohort studies, with effect estimates reported in the range of 11 to 50% increases
in mortality per 15 |ig/m3 increase in sulfates (2004 PM AQCD, Table 8-15). Prospective cohort
studies have also reported associations between long-term exposure to sulfates and respiratory
effects, such as prevalence of chronic bronchitis (2004 PM AQCD, section 8.3.3.2).
Several recent epidemiologic studies have evaluated associations between short-term
exposure to fine particle components and various health outcomes, as shown in Table A15
(Appendix A). Overall, this group of studies reports associations between mortality and
morbidity with several fine particle components. A number of studies report associations with
sulfates that are generally consistent with those in earlier reports. Several recent studies have
also shown associations with the organic carbon and elemental carbon components of fine
particles.
• For mortality, significant associations were reported with sulfates in a new study in
Montreal (Goldberg et al., 2006), and a positive, borderline significant, association with
sulfates was reported in a study of 12 Canadian cities (Burnett et al., 2004). Positive, but
not statistically significant, associations between mortality and fine particle sulfates was
reported in Vancouver (Villeneuve et al., 2003). A study in Atlanta also evaluated
associations with other fine particle components, and reported positive but not significant
associations between mortality and sulfates and EC, OC, and not association with nitrates
(Klemm et al., 2004).
• For emergency department visits, two reports from the ARIES study in Atlanta evaluated
associations between short-term fine particle component exposures and visits for
cardiovascular or respiratory diseases (Metzger et al., 2004; Peel et al., 2005). Both
studies report no significant associations for short-term exposures to either sulfates or
water-soluble metals with visits for cardiovascular or respiratory diseases. Significant
27
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associations were reported between OC and EC and emergency department visits for all
cardiovascular diseases and congestive heart disease (Metzger et al., 2004). No
significant associations were reported between any component and respiratory visits,
except for an association between OC and emergency department visits for pneumonia
(Peel et al., 2005).
• For cardiovascular health outcomes, one study that was conducted in Boston, MA
reported a significant association between short-term sulfate exposure and percent change
in brachial artery diameter, an indicator of vascular reactivity (O'Neill et al., 2005); other
components were not evaluated.
• For respiratory health outcomes, medical visits for asthma in children and lower
respiratory infections (all ages) were associated with the EC and OC components of fine
particles in Atlanta, but no associations were reported with sulfates or acidity (Sinclair
and Tolsma, 2004). Metals were positively associated with medical visits for lower
respiratory infection, but not for other outcomes. For adult asthma and upper respiratory
infections, there were no significant positive associations with any of the fine PM
components; however, sulfates were negatively associated with upper respiratory
infection visits (Sinclair and Tolsma, 2004). In a panel study of Hispanic children, OC
and EC (measured in PMi0) were significantly associated with asthma symptoms; other
PM components were not included in this study (Delfmo et al. 2003).
In addition, one recently published epidemiologic study has also assessed associations
between mortality and long-term exposure to fine particle components (see Table 1). Mortality
was significantly associated with long-term exposure to four fine particle components (EC,
nitrates, nickel, and vanadium), and a positive but not statistically significant association was
reported with sulfates using the Veterans cohort (Lipfert et al., 2006b, in press).
2.4.3 Toxicology Studies—Source Apportionment and Fine Particle Components
There were nine studies in the 2004 PM AQCD that investigated the effects of fine
particle CAPs exposure in humans and laboratory animals (Sections 7.2.2 and 7.3.1). The results
of these studies generally showed associations between the CAPs exposure and cardiovascular
parameters. Effects on the respiratory system were largely absent for pulmonary function, but
were present for markers of inflammation. Source apportionment was largely absent in the
previous CAPs studies, although some evidence linked transition metal components in ambient
PM with lung injury. Additionally, as CAPs composition varies day-to-day, it is difficult to
establish clear relationships between individual components and adverse health effects. The
2004 PM AQCD pointed to a "critical need for the systematic conduct of studies in the potential
respiratory effects of major components of PM from different regions of the U.S., in recognition
that PM of different composition and from different sources can vary markedly in its potency for
producing different respiratory effects" (2004 PM AQCD, p. 7-85).
Toxicological studies employing CAPs offer a relevant surrogate for atmospheric PM.
As ambient PM is just one component of a complex mixture that interacts with gases and other
aerosols, CAPs systems provide a method of exposing subjects to the particle phase. Gases
28
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(such as 63 and 862) are not concentrated and organic PM components in CAPs likely differ
from components in ambient PM, particularly for ultrafme CAPs systems (Su et al., 2006).
Similarly, thoracic coarse PM is not enriched (except for the coarse particle concentrator) and
only certain systems are capable of concentrating ultrafme PM.
There are three main CAPs exposure systems currently in use. The Harvard Air Particle
Concentrator (HAPC) uses virtual impactor technology to concentrate particles from 0.15 to
2.5 |im (Sioutas et al., 1997). The versatile aerosol concentration enrichment system (VACES)
is also based on virtual impactor technology and concentrates ultrafme particles, as well as those
in the fine particle range (Sioutas et al., 1999). It is important to note that both ultrafme systems
(HAPC and VACES) do not uniformly concentrate particles across all size fractions and that the
enrichment factor has been shown to decrease for PM sized <75 nm (Su et al., 2006). The
centrifugal concentrator most efficiently concentrates particles in the 0.5-2.5 jim size range
(Gordon et al., 1998). For the purposes of this provisional assessment, CAPs studies have been
grouped into those that conducted source apportionment analyses or those that linked PM
components to health outcomes. Additional CAPs studies that reported linkages between mass
and toxicity are presented in a subsequent section.
Among the recent toxicology studies are 27 new studies reporting effects of CAPs
exposure. These include several reports from a large study of subchronic exposure to CAPs that
was carried out using three different mice strains. Four of the acute and one subchronic study
(with an additional in vitro study) performed complex source apportionment or factor analyses.
Eight (three human and five animal studies) used regression approaches to estimate the
relationship between health effects and the concentration of individual PM constituents.
Additional exposure details, endpoints, and results for all of the CAPs studies are provided in
Appendix A (Tables A16-A18); the tables present only those findings that were positive in the
"Results" column.
Source Apportionment Studies
Table 2 shows those endpoints which were associated with various source categories
from humans exposed to Chapel Hill, NC, CAPs (Huang et al., 2003b) and mice exposed
subchronically to Tuxedo, NY, CAPs (Lippman et al., 2005b). Increases in blood fibrinogen
levels in healthy humans were correlated with a Cu-Zn-V factor (stated by the authors to be
linked to combustion, including oil combustion) in the acute exposure study (Huang etal.,
2003b). In addition, elevated polymorphonuclear leukocytes in bronchoalveolar lavage fluid
(BALF) were observed with CAPs, and this increase was associated with a Fe-Se-sulfate factor;
the authors considered this factor to represent sulfurous smog and photochemical air pollution.
There were no other identifiable CAPs factors that were linked to any health outcome.
Using mouse models, Lippmann et al. (2005b) reported post-exposure decreases in heart
rate variability (HRV) parameters in subchronic exposures to CAPs for three factors—secondary
sulfate, residual oil, and motor vehicles—but an increase in HRV parameters with a CAPs factor
representing resuspended soil. Similar findings were reported for heart rate, with slight increases
and decreases being observed for different source categories at one interval or another.
29
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Table 2. CAPs Sources and Associated Endpoints: Acute and Subchronic Exposures
Source
Category
Zn-Cu-V
Fe-Se-sulfate
Secondary
sulfate
(S, Si, OC)
Resuspended soil
(Ca, Fe, Al, Si)
Residual oil
(V, Ni, Se)
Motor
vehicle/other
Endpoint Affected
t blood fibrinogen
t BALF PMN
JHR
| SDNN, | RMSSD
JHR
|HR
t SDNN, t RMSSD
| SDNN, | RMSSD
| RMSSD
Time
18 hr post-exposure
18 hr post-exposure
Afternoon post-exposure
Night post-exposure
During exposure
Afternoon post-exposure
Night post-exposure
Afternoon post-exposure
Afternoon post-exposure
Species
Human
Human
ApoE" "mouse
ApoE"7" mouse
ApoE^'mouse
C57 mouse
Reference
Huang, Y-C.T
(2003)
Huang, Y-C.T
(2003)
Lippmann et al.
(2005b)
Lippmann et al.
(2005b)
Lippmann et al.
(2005b)
Lippmann et al.
(2005b)
As shown in Table 2, not all source categories were linked to HR or HRV parameters at
any given time during or after exposure.
One in vivo study employed rats and mice (Steerenberg et al., 2006) which were exposed
to one of five PM types collected from Europe. The traffic, industry/combustion/incinerator, and
wood smoke source clusters were associated with the adjuvant activity for respiratory allergy,
whereas the secondary inorganic/long range cluster correlated with systemic allergy (Steerenberg
et al., 2006). The crustal material and sea spray sources were linked to acute inflammation,
although the endotoxin content also correlated with some of these biomarkers (Steerenberg et al.,
2006).
In the remaining CAPs studies that included source apportionment, Batalha et al. (2002)
reported changes in lumen/wall ratio, an indicator of vasoconstriction, with sulfate and Si
(suggested to be an indicator of road dust) in normal rats and with OC in chronic bronchitic rats.
Wellenius et al. (2003) also linked a cardiovascular response, ST-segment elevation, with Si and
other crustal elements derived from Boston CAPs. In the latter study, there were a number of
tracer elements that were not associated with any electrocardiogram measure, including Ni, S,
and carbon black.
Studies of fine particle components in CAPs
In addition, six CAPs studies have reported associations between observed cardiovascular
or respiratory endpoints and specific PM constituents. Table 3 presents more specific results,
and the overall findings are briefly summarized below:
30
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Table 3. CAPs Components and Associated Endpoints for Acute Studies
Component
Al
Si
Fe
Zn
Mn
Cu
Ti
Sulfate
OC
EC
Pb
Endpoint Affected
lipid peroxidation
oxidative stress (heart)
lipid peroxidation
oxidative stress (heart)
lumen/wall ratio
ST-segment elevation
lipid peroxidation
oxidative stress (lung)
oxidative stress (heart)
oxidative stress (lung)
plasma fibrinogen
oxidative stress (lung)
oxidative stress (lung)
oxidative stress (heart)
FEVi decrements
FVC decrements
lumen/wall ratio
brachial arterial diameter
diastolic blood pressure
lumen/wall ratio
brachial arterial diameter
lumen/wall ratio
lumen/wall ratio
Species
rat
rat
rat
rat
rat
dog
rat
rat
rat
rat
rat
rat
rat
rat
human (+NO2)
human (+NO2)
rat
human
human
rat
human
rat
rat
Reference
Rhoden et al. (2004)
Gurgueira et al. (2002)
Rhoden et al. (2004)
Gurgueira et al. (2002)
Batalha et al. (2002)
Wellenius et al. (2003)
Rhoden et al. (2004)
Gurgueira et al. (2002)
Gurgueira et al. (2002)
Gurgueira et al. (2002)
Kodavanti et al. (2005)
Gurgueira et al. (2002)
Gurgueira et al. (2002)
Gurgueira et al. (2002)
Gong et al. (2005)
Gong et al. (2005)
Batalha et al. (2002)
Urch et al. (2004)
Urch et al. (2005)
Batalha et al. (2002)
Urch et al. (2004)
Batalha et al. (2002)
Batalha et al. (2002)
• Si—oxidative stress and cardiovascular endpoints;
• Fe—oxidative stress;
• OC and EC—cardiovascular effects;
• Zn—oxidative stress and fibrinogen; and
• Sulfate—pulmonary and cardiovascular effects.
Fine Particle CAPs Studies Without Source Apportionment or Identified Components
Effects on the cardiovascular system have been reported in a number of human studies.
Markers of cardiovascular function, such as brachial arterial diameter and blood pressure, have
been shown to decrease with CAPs exposure (Urch et al., 2004, 2005). Increased occurrence of
ectopic and abnormal beats has also been reported in healthy and COPD subjects with exposure
to CAPs (Devlin et al., 2003). Similar to studies cited in the 2004 PM AQCD, elevated blood
fibrinogen levels were observed in volunteers exposed for two hours to Chapel Hill, NC CAPs
31
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(Ohio et al., 2003). Hematological alterations, including increased peripheral basophils (Gong
et al., 2004a) and decreased white blood cell counts (Ohio et al., 2003), have also been reported.
Two recent studies measuring heart rate (HR) and heart rate variability (HRV) have
demonstrated that a single two-hour exposure to CAPs from Los Angeles, CA, or Chapel Hill,
NC, can result in decreased HRV in human volunteers (Devlin et al., 2003; Gong et al., 2004a).
Interestingly, in the Los Angeles studies, healthy subjects were reported to have greater
decreases in HRV compared to compromised individuals with COPD (Gong et al., 2004a).
In addition, a few studies have reported some associations with respiratory health
endpoints. Arterial oxygen saturation decreased in healthy and COPD patients exposed for two
hours to PM2.5 Los Angeles CAPs (Gong et al., 2005). Elevated polymorphonuclear leukocytes
in bronchioalveolar lavage fluid were observed in healthy volunteers at 18-hr post-exposure to
Chapel Hill, NC, CAPs (Ghio et al., 2003). Of the two recent fine CAPs studies that measured
pulmonary function, only one showed decreased maximal mid-expiratory flow, forced expiratory
volume and forced vital capacity and the latter two responses were only observed with co-
exposure to NO2 (Gong et al., 2005); the other study did not report any changes in spirometry or
respiratory symptoms (Gong et al., 2004a).
To date, the CAPs animal studies reported in the scientific literature have been of
relatively short duration (i.e., four weeks or less). There is one large subchronic PM inhalation
study in the recent literature on toxicological effects of repeated exposures to ambient particles in
mice exposed to Tuxedo, NY, CAPs for five or six months during the spring and summer of
2003 (Lippmann et al., 2005a; Sun et al., 2005). Following CAPs exposure, mice models of
aortic and/or coronary atherosclerosis had altered HR and HRV (Chen and Hwang, 2005; Hwang
et al., 2005; Lippmann et al., 2005b), advanced plaque deposits and lesions in the aorta and heart
(Chen and Nadziejko, 2005), and changes in vasomotor tone (Sun et al., 2005). Additional
molecular and biochemical analyses demonstrated altered gene expression post-exposure,
including those genes involved in the regulation of circadian rhythm, heat shock, inflammation,
and signal transduction (Gunnison and Chen, 2005). CAPs exposure also induced
neurodegeneration in the substantia nigra nucleus compacta of ApoE"7" mice (Veronesi et al.,
2005). Interestingly, subchronic CAPs-exposure did not appear to cause pulmonary effects in
any mouse strain.
Finally, three reports do not specifically link PM components to health endpoints, but two
draw inferences that relate the effects seen with a heavy industrial source located near the study
site (Dvonch et al. 2004; Morishita et al., 2004). One additional study of mice exposed to fine
CAPs in Los Angeles, downwind of heavily trafficked highways, demonstrated effects on
biomarkers of inflammation in the brain (Campbell et al., 2005). Additionally, in the one in vitro
study that applied factor analysis to CAPs for cytokine release, the oil-fired power plant emission
source (comprised of V, Ni, and Se) was linked to the response, but not the regional secondary
sulfate or resuspended soil factors (Maciejczyk and Chen, 2005). Considered as a group, these
new studies suggest that many fine particle components can adversely affect health, and that PM-
associated cardiovascular and respiratory effects may be linked to resuspended soil, regionally
transported air pollution, and combustion or industrial sources.
32
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2.4.4 Toxicology Studies—Thoracic Coarse Particles
Few studies examined the effects of thoracic coarse PM on cellular responses prior to the
release of the 2004 PM AQCD. When considered together, the four in vitro studies discussed in
Chapter 7 of the 2004 PM AQCD document provided some evidence that exposure to thoracic
coarse PM may result in proinflammatory effects, as well as cytotoxicity and oxidant generation
(Section 7.4.2). However, as little data was available at that time on thoracic coarse PM toxicity,
a very limited evaluation of the literature was conducted. Recent publications include sixteen
new studies (one human, six in vivo., and nine in vitro) that have specifically focused on the
thoracic coarse fraction of PM, with the majority of these providing direct comparisons with
smaller size fractions (i.e., fine and ultrafine).
In one important new study, healthy and asthmatic humans were exposed to CAPs via a
high concentration efficiency coarse particle concentrator, in which 80% of the PM mass was
comprised of the thoracic coarse fraction (Gong et al., 2004b). Exposure to thoracic coarse
CAPs from Los Angeles also caused lowered HR and HRV. Asthmatics exposed to thoracic
coarse Los Angeles CAPs had no changes in arterial oxygen saturation (Gong et al., 2004b).
Healthy subjects were reported to have greater decreases in HRV compared to compromised
individuals with COPD (Gong et al., 2004b).
Two in vitro studies evaluated cytokine release and cell viability following exposure to
PM2.5 soil dusts from a variety of southwestern U.S. locations (Veranth et al., 2004, 2006). The
responses were quite variable and did not appear to be attributable to sample location category
(e.g., urban/rural, road surface/open land, military/civilian) or endotoxin content. A multivariate
analysis of the findings demonstrated a handful of correlations with soil dust constituents
(Veranth et al., 2006).
The in vivo rodent studies provide evidence that the observed effects from exposure
(via non-inhalation routes) to thoracic coarse or fine PM are related to the endotoxin or allergen
levels, which were often associated with sampling location. These effects included elevated
cytokine release (Nygaard et al., 2005; Schins et al., 2004) and adjuvant activity (Steerenberg
et al., 2005). Schins et al. (2004) reported differences between thoracic coarse PM from rural
and urban areas in The Netherlands, with greater responses for elevated neutrophils and tumor
necrosis factor-a in BALF from rural PM, but greater induction of macrophage inflammatory
protein-2 in vitro from urban PM (both PM types contained relatively high levels of endotoxin).
Otherwise, the thoracic coarse fraction tended to induce similar toxic responses as that observed
with the fine fraction. In the one study that employed coal fly ash, no differences in effects were
reported for the thoracic coarse fraction compared to saline control animals (Gilmour et al.,
2004).
Similar to the in vivo research with surrogate and size-fractionated PM, in vitro studies
have also shown associations between the induction of inflammatory mediators and PM
endotoxin content (Huang et al., 2003a; Pozzi et al., 2003), whereas others have found seasonal
relationships with thoracic coarse PM effects (Becker et al., 2005b; Hetland et al., 2005; Li et al.,
2002). The latter finding could be partially attributable to microbial products or their
interactions with metals (Hetland et al., 2005). Becker et al. (2005b) further examined possible
associations between cellular responses and PM components using principal component analysis
33
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and reported a Cr/Al/Si/Ti/Fe/Cu factor correlating with IL-6 and IL-8 release. Examination of
IL-6 induction in alveolar macrophages and IL-8 release in normal human bronchial epithelial
cells following thoracic coarse PM exposure showed associations with Toll-like receptor
(TLR) 4 and TLR2 gene expression, respectively (Becker et al., 2005a). Generation of hydroxyl
radicals has also been recently observed with thoracic coarse PM (Shi et al., 2003). In contrast,
some studies have also demonstrated greater effects with the fine or ultrafme size fraction
compared to thoracic coarse PM (Li et al., 2002; Li et al., 2003; Gilmour et al., 2004).
2.4.5 Toxicology Studies—Comparison of Ambient PM
There were numerous studies included in the 2004 PM AQCD that employed ambient
particles collected on filters. These included extracts of collected or stored PM and the majority
of studies utilized Ottawa (EHC-93) or Provo, Utah PMio. Generally, animals exposed to these
particles had elevated biomarkers of pulmonary injury and inflammation, as well as systemic and
cardiovascular responses (Chapter 7). The 2004 PM AQCD stated that studies using collected
urban PM "have provided evidence indicating that the chemical composition of ambient particles
can have a major influence on toxicity" (Section 7.10.2.1, pg 7-127). The results of research
published since 2002 have largely supported and expanded the findings of previous studies cited
in the 2004 PM AQCD. Five studies are highlighted which evaluated the toxicity of urban PM
or that collected on filters (one human, two in vivo, and two in vitro). Further details on these
studies are included in Table A19 (Appendix A).
Two recent studies investigated the effects of urban (Hettstedt) and rural (Zerbst)
particles (PM2.s) on lung inflammation and pulmonary function in humans and rodents (Gavett
et al., 2003; Schaumann et al., 2004). In healthy human volunteers, instillation of either PM
induced airway inflammation, whereas Hettstedt PM resulted in greater influxes of BALF
monocytes and increased oxidant radical generation compared Zerbst PM (Schaumann et al.,
2004). In allergic mice, exposure to either PM type induced lung injury and proinflammatory
cytokines (Gavett et al., 2003). However, aspiration of Hettstedt PM caused heightened airway
responsiveness and elevated lung inflammatory cells in sensitized mice exposed before allergen
challenge (Gavett et al., 2003). The endotoxin content was below 0.32 EU/mg in both PM
samples.
Two other in vivo toxicology studies examined the cardiovascular and cytogenetic effects
of urban PM exposure (Rhoden et al., 2005; Scares et al., 2003). Rhoden et al. (2005) compared
autonomic nervous system (ANS) effects between Boston CAPs (via inhalation) and SRM 1649
(via intratracheal instillation). Both particles altered ANS function and these changes preceded
and were required for increased cardiac reactive oxygen species generation (Rhoden et al., 2005).
Scares et al. (2003) measured micronuclei (MN) in peripheral erythrocytes of mice exposed to
urban air of Sao Paulo or Atibaia, Brazil (with the latter being a rural location) and reported that
there were significant increases in MN frequency for mice exposed to the Sao Paulo atmosphere.
The results of recent studies assessing effects of different components from different
particle samples or size classes are summarized in Table 4, along with other studies that
attempted to link in vitro effects with PM components (discussed in the preceding section).
34
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Table 4. PM Components, Size Fractions, and Associated In Vitro Toxicity
Component
Br
Cr
Cu
Si
Fe
Mn
Ni
OC
EC
Endpoint Affected
IL-8
IL-8
IL-8
TNF-a
Hydroxyl radical
8-OHdG formation
IL-6
IL-6
TNF-a
IL-8
Cell viability
IL-6
Lipid peroxidation
IL-6
Hydroxyl radical
Lipid peroxidation
IL-6
Size Fraction
Fine
Fine, ultrafine
Fine
Ultrafine
Coarse
Coarse
Coarse
Coarse, fine
Ultrafine
Fine
Fine
Fine
Fine
Fine
Ultrafine
Fine
Fine
Cell Type
BEAS-2B
NHBE
BEAS-2B
RAW 264.7
A549
A549
Human AM
Human AM
RAW 264.7
BEAS-2B
BEAS-2B
BEAS-2B
BEAS-2B
BEAS-2B
BEAS-2B
BEAS-2B
BEAS-2B
Reference
Veranth et al. (2006)
Becker et al. (2005b)
Huang et al. (2003 a)
Huang et al. (2003 a)
Shi et al. (2003)
Shi et al. (2003)
Becker et al. (2005b)
Becker et al. (2005b)
Huang et al. (2003 a)
Huang et al. (2003 a)
Veranth et al. (2006)
Veranth et al. (2006)
Huang et al. (2003 a)
Veranth et al. (2006)
Li et al. (2003)
Huang et al. (2003 a)
Veranth et al. (2006)
These recent studies continue to show that exposure to different types of surrogate fine
PM is associated with a range of health outcomes, particularly those related to the cardiovascular
system. These findings also expand upon the body of evidence related to the effects of thoracic
coarse particles and PM composition. Exposure to thoracic coarse particles has been linked with
a number of effects, including inflammatory mediator release and reactive oxygen species
generation. The results are still too limited to draw conclusions about specific thoracic coarse
particle components and health outcomes, but it appears that endotoxin and metals potentially
play roles in the observed responses. While these studies provide interesting new insight into
potential links between different types of particles and observed effects, it is much too early to
distinguish any PM components as being primarily responsible for any specific effect or
conversely, as not involved in any toxicological response.
2.4.6 Studies of Specific Fine Particle Components or Characteristics
Toxicological evidence on the effects of different types of particles or particle
components was discussed in Section 7.10.2 of the 2004 PM AQCD. The particle characteristics
or sources discussed included acid aerosols, metals, diesel exhaust particles, organic
components, ultrafine particles and bioaerosols. In addition to the discussions above, EPA
observes that numerous recent individual toxicology studies have investigated the effects of
exposure to these particle components or characteristics. For this provisional assessment,
EPA has not critically reviewed the large number of studies that have assessed effects of
35
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individual components, but will highlight below the general nature of the new findings.
Bibliographies for these groups of particle types or characteristics are included in Attachment B.
The main overarching conclusion from these groups of studies is that the recent studies
generally substantiate and support conclusions drawn from earlier work. For example, numerous
studies had suggested that metals (e.g., transition metals such as V or Ni) contributed to the toxic
effects observed with PM exposures (albeit at generally high exposure levels). Recently-
published studies provide more evidence that metal constituents of particles may play important
roles in PM-related toxicity.
Ultrafme Particles: The 2004 PM AQCD had an extensive discussion of the physical
and chemical properties and behavior of ultrafine particles (diameter <0.1 |im). A growing body
of evidence from toxicology studies indicated that ultrafine particles were linked with a number
of health outcomes; however, there was very limited information on the health effects of
ultrafine particles from epidemiologic studies. The 2004 PM AQCD observed that acute
exposures to ultrafine particles were associated with slight increases in blood viscosity and with
respiratory symptoms or decreased lung function, and one study had reported associations with
mortality. Toxicological studies used various types of ultrafine model particles (e.g., carbon
black), and reported greater inflammatory responses when compared at the same mass of fine
particles of the same chemical composition at similar mass doses (2004 PM AQCD, p. 7-221).
Hence, in the ambient environment where fine particle mass greatly exceeds ultrafine mass, it
remains to be determined whether this relative difference in potency is reflected in real world
exposures.
Since April 2002, about 60 recent studies have evaluated effects of ultrafine particles, and
over 150 have assessed effects associated with diesel exhaust or traffic-related PM (see
Attachment B). Diesel and other forms of traffic are considered to be major sources of
atmospheric ultrafine PM. Recent toxicology studies continue to indicate that ultrafine particles
have effects and many toxicology studies indicate that, on a mass basis, ultrafine particles are
more toxic than fine particles. Ultrafine particles have been observed to translocate from the
olfactory mucosa to the brain and from the lungs to the liver and the systemic circulation.
However, a number of uncertainties remain regarding the extent of ultrafine particle
extrapulmonary translocation, including clearance rates and routes (e.g., lymphatic system or
gastrointestinal tract). Ultrafine particles appear to enter cells and cause mitochondrial damage,
based on evidence from in vitro studies. Most studies using laboratory-generated carbon
particles do not demonstrate lung inflammation, but report cardiac and vascular effects.
Additionally, exposure to ambient ultrafine PM causes lung inflammation that is associated with
organic carbon carried by the ultrafine particles. A few epidemiologic studies have associated
health effects with particle number, particle surface area, or active surface area, all variables that
are thought to be associated more with ultrafine than fine particles. As was true in the 2004 PM
AQCD, the epidemiologic studies generally do not indicate that ultrafine PM is more strongly
associated with health effects than fine PM. In general, studies report associations between both
fine and ultrafine particles, and in a number of cases the associations are reported to be stronger
for fine than for ultrafine PM. Thus, further evaluation is needed on effects of ultrafine particles
in the next review of the PM NAAQS.
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Sulfates and Acid Aerosols: As stated in the 2004 PM AQCD, there is "little new
information on the effects of acid aerosols." There was a much more extensive discussion on the
toxicity of sulfates in Section 11.2 of the previous PM AQCD (U.S. EPA 1996), which
concluded that human and animal toxicology studies indicated that acid aerosols are associated
with small changes in pulmonary function, but generally at concentrations greater than those
measured in ambient air. The results of four recent acid aerosol toxicological studies generally
agree with conclusions in the 2004 PM AQCD. Three of these studies involve controlled human
and animal exposures to acid aerosols with or without gaseous co-pollutants such as ozone (O3).
One study employed in vitro techniques to assess the toxic effects of sulfate on different cell
types, including alveolar macrophages and blood polymorphonuclear leukocytes. As shown in
Table A20 the recent studies reported limited evidence for effects with exposure to sulfuric acid
or sulfate aerosols. One study found that there was some suggestion for interactive effects with
ozone (Kleinman et al., 2003). There were no new toxicological studies published in the last
four years that utilized nitrate aerosols (i.e., ammonium nitrate or nitric acid) to examine health
outcomes.
Diesel exhaust particles: This source of particles has been the subject of numerous
studies; the 2004 PM AQCD highlighted findings from the Diesel Health Assessment Document
along with some additional studies. There are a number of new studies which have investigated
the toxicity of diesel exhaust by eliminating the particle or gas portion of the exposure
atmosphere or by separating the organic constituents from the carbonaceous core. Some studies
have suggested that the gases, organic particle compounds, or particle core are responsible for
the observed effects, and it is likely that all exhaust components contribute to toxicity.
Comparison of these results across laboratories or studies is difficult, as the composition of
diesel exhaust is highly dependent upon the generation method.
Traffic-related particles: A large body of literature is accumulating on a range of health
effects that may be associated with exposure to traffic. These exposures include both paniculate
and gaseous pollutants and the reported findings include cardiovascular responses, inflammatory
changes, allergenic effects, and mutagenicity. Toxicology studies and a partially annotated
bibliography of epidemiologic studies are included in Attachment B.
Organic compounds: Little evidence was available on effects of particulate organic
compounds in the 2004 PM AQCD (Section 7.10.2.5). A number of the recently published
studies have used fine particle speciation data, along with factor analysis methods, to assess
potential effects of the organic component of fine PM. Previous studies indicated that PM
organic compounds (e.g., PAHs) can be mutagenic. However, few studies had provided
information on potential associations with other health endpoints. Recent study results suggest
that organic constituents of ambient PM can be linked to a number of biomarker and
physiological responses, such as lipid peroxidation and oxidative stress generation, cytokine
release, elevated plasma fibrinogen, and decreased diastolic blood pressure and vessel diameter.
Metals: As stated in Section 7.10.2.3 in the 2004 PM AQCD, the effects of metals
leached from ambient filter extracts or residual oil fly ash have been shown to consistently result
in cell injury and inflammation (albeit often at high concentrations). A number of new studies
have reported that exposure to metals results in detectable health effects (see Attachment B).
37
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These recent studies highlight findings for several metals which may be involved in PM
toxicological effects, including Fe, Zn, V, and Ni. Furthermore, the activation of select
pro-inflammatory pathways with metal exposure has been linked to particular cell surface
receptors. Other research suggests a role for metal-containing PM (including those derived from
oil or coal combustion sources) in altering cardiovascular parameters, which is consistent with
the epidemiological findings.
Conclusions
Recent analyses continue to indicate that particles related to traffic, residual oil
combustion, wood smoke, and regional sulfate pollution and primary coal burning are associated
with increased mortality. A number of new studies continue to indicate that traffic-related PM
exposures are associated with mortality and morbidity. Recent epidemiologic observations
continue to support associations between various fine PM components and both mortality and
morbidity effects.
3. SUMMARY AND CONCLUSIONS
The new study results support and expand upon findings in the 2004 PM AQCD and
provide interesting new insights into relationships between ambient particles and health effects.
The essential conclusions of this provisional assessment are that the science supporting
evaluation of the potential health impacts of PM on human health continues to expand and hence
provides a larger knowledge base for better characterizing the relationships between fine and
thoracic coarse particles and health effects. The new studies provide important insights on the
health effects of PM exposure, but the results do not dramatically diverge from previous
findings. We find that: (a) the new studies generally strengthen the evidence that acute and
chronic exposures to fine particles and acute exposure to thoracic coarse particles are associated
with health effects, (b) some of the new epidemiologic studies report effects in areas with lower
concentrations of PM2 5 or PMio-2.s than earlier reports; (c) new toxicology and epidemiologic
studies link various health outcomes with a range of fine particle sources and components, in
particular from traffic-related pollution; and (d) new toxicology studies report effects of thoracic
coarse particles, but do not provide evidence to support distinguishing effects from exposure to
urban and rural particles. This survey and provisional assessment of new studies does not
materially change any of the broad scientific conclusions regarding the health effects of PM
exposure made in the 2004 PM AQCD.
In brief, this provisional assessment found:
• Recent epidemiologic studies, most of which are follow-ups or extensions of earlier
work, continue to find that long-term exposure to fine particles is associated with both
mortality and morbidity, as was stated in the 2004 PM AQCD. Notably, a follow-up to
the Six Cities study shows that an overall reduction in PM2.s levels results in reduced
long-term mortality risk. Both this study and an analysis of the ACS cohort data in Los
Angeles suggest that previous studies may have underestimated the magnitude of
mortality risks. Some studies provide more mixed results, including the suggestion that
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higher traffic density may be an important factor. In addition, the California Children's
Health study reported measures of PM2 5 exposure and PM components and gases were
associated with reduction in lung function growth in children, increasing the evidence for
increased susceptibility early in life, as was suggested in the 2004 AQCD. In addition,
one study reported increased infant mortality from respiratory causes with exposure to
PM2 5. The results of recent epidemiologic and toxicology studies have also reported new
evidence linking long-term exposure to fine particles with a measure of atherosclerosis
development and, in a cohort of individuals with cystic fibrosis, respiratory
exacerbations.
• Recent epidemiologic studies have also continued to report associations between acute
exposure to fine particles and mortality and morbidity health endpoints. These include
three multi-city analyses, the largest of which (in 204 counties) shows a significant
association between acute fine PM exposures and hospitalization for cardiovascular and
respiratory diseases, and suggestions of differential effects in eastern U.S. as opposed to
western U.S. locations. The new studies support previous conclusions that short-term
exposure to fine PM is associated with both mortality and morbidity, including a
substantial number of studies reporting associations with cardiovascular and respiratory
health outcomes such as changes in heart rhythm or increases in exhaled NO. The fine
PM concentrations reported in these studies are in some cases lower than in the
previously-published studies.
• New toxicology and epidemiologic studies have continued to link health outcomes with a
range of fine particle sources and components. Source apportionment epidemiologic
analyses were conducted by teams of analysts for two cities, and the results indicate that
fine PM from several sources, including regional sulfate and several combustion sources,
are associated with mortality. Additionally, a number of new studies indicate that traffic-
related PM exposures are associated with mortality and morbidity. A few new toxicology
studies have used source apportionment techniques to assess effects related to PM from
different emission categories. While limited in number and preliminary in nature, the
findings suggest that several PM sources may contribute to toxicity, including
combustion-related sources and regional sulfate pollution, as suggested in epidemiologic
studies. Several studies have also indicated that particles from resuspended soils, such as
road dust, may be associated with health effects. Toxicology studies indicate that various
components, including metals, sulfates, and elemental carbon and organic carbon, are
linked with health outcomes, albeit at generally high concentrations. Recent
epidemiologic studies also report associations between sulfates and mortality and
morbidity, and provide new evidence that organic or elemental carbon may be linked
with health effects.
• The recent epidemiologic studies greatly expand the evidence on health effects of acute
exposure to thoracic coarse particles. The 2004 PM AQCD conclusion that PMio-2.5
exposure was associated with respiratory morbidity is substantially strengthened with
these new studies; several epidemiologic studies, in fact, report stronger evidence of
associations for hospital admissions with thoracic coarse particles than for fine particles.
Some of the recent morbidity studies were also located in cities with low PMio-2.5
39
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concentrations. For example, significant associations have been reported with respiratory
hospital admissions in several Canadian studies, where the reported mean and maximum
PMio-2.5 concentrations ranged from about 6 to 12 |ig/m3 and 25 to 70 |ig/m3,
respectively. For mortality, many studies do not report statistically significant
associations, though one new analysis reports a significant association with
cardiovascular mortality in Vancouver, Canada.
• New toxicology studies have demonstrated that exposure to thoracic coarse particles, or
PM sources generally representative of this size fraction (e.g., road dust), can result in
inflammation and other health responses. Clinical exposure of healthy and asthmatic
humans to concentrated ambient air particles comprised mostly of PMi0-2.5 showed
changes in heart rate and heart rate variability measures. The results are still too limited
to draw conclusions about specific thoracic coarse particle components and health
outcomes, but it appears that endotoxin and metals may play a role in the observed
responses. Two studies comparing toxicity of dust from soils and road surfaces found
variable toxic responses from both rural and urban locations.
• Evidence of associations between long-term exposure to thoracic coarse particles and
either mortality or morbidity remains limited.
• Significant associations between improvements in health and reductions in PM and other
air pollutants have been reported in intervention studies or "found experiments." One
new study reported reduced mortality risk with reduced PM2.5 concentrations. In
addition, several studies, largely outside the U.S., reported reduced respiratory morbidity
with lowered air pollutant concentrations, providing further support for the
epidemiological evidence that links PM exposure to adverse health effects.
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PM PROVISIONAL ASSESSMENT—ABBREVIATIONS
AND ACRONYMS
A549
AA
ACE
ACS
ADMA
AHSMOG
ARIES
ALP
AM
ApoE"A
AQS
p-gluc
BAD
BALF
BC
BEAS-2B
BN
BP
BrdU
BS
CAPs
CARS
CB
CBC
CC16
CD lib
CI
CL
CO
CO
CoH
CPC
CRP
human alveolar basal epithelial cell line
arachidonic acid
angiotensin converting enzyme
American Cancer Society
asymmetric dimethylarginine
Adventist Health and Smog
Aerosol Research and Inhalation and Epidemiology Study
alkaline phosphatase
alveolar macrophage
apolipoprotein deficient (mouse model of atherosclerosis)
Air Quality System
P-glucuronide
brachial artery diameter
bronchoalveolar lavage fluid
black carbon
human bronchial epithelial cell line
Brown Norway (rat)
blood pressure
bromodeoxyuridine
black smoke
concentrated ambient particles
California Air Resources Board
chronic bronchitis
complete blood count
clara-cell 16 protein
cell surface receptor
confidence interval
chemiluminescence
carbon monoxide
carbon dioxide
Coefficient of Haze
coarse particle concentrator
C-reactive protein
41
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COPD
CVD
DBF
DD
DK
DNA
EC
ECG
eNO
eNOS
ER
ERK
ET
/
F344
FA
FEVi
FVC
GAM
GEE
GGT
GLM
SD
GSH
GSH/GSSG
GSSG
H&E
HAPC
Hb
Hct
5-HETE
HF
12-HHT
HO-1
chronic obstructive pulmonary disease
cardiovascular disease
diastolic blood pressure
desert dust
double knockout mouse strain (for ApoE and LDL)
deoxyribonucleic acid
elemental carbon
el ectrocardi ogram
exhaled nitric oxide
endothelial nitric oxide synthase
emergency room
extracellular signal-regulated kinase
endothelein
breathing frequency
Fischer 344 (rat)
filtered air
fractional exhaled nitric oxide
forced expiratory volume in 1 second
forced vital capacity
general additive model
generalized estimating equations
y-glutamyl transferase
Generalized Linear Model
geometric standard deviation
reduced glutathione
reduced glutathione/glutathione disulfide (ratio)
glutathione disulfide
hematoxylin and eosin
Harvard ambient fine particle concentrator
hemoglobin
hematocrit
5-hydroxy-eicosatetraenoic acid
high frequency of heart rate variability
12-hydroxyheptadecatrienoic acid
heme oxygenase
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HR
HRV
H2SO4
ICAM
ICD
ICP-MS
Ig
fflD
IL
IMPROVE
iNOS
IPN
IQR
IT
JNK
LEW
LDH
LF
LDL/
LPS
LRI
LT
LAV
MAP
MCh
MCT
MCV
MI
MIP
MLRA
MMD
MMEF
MN
mm Hg
MPO
heart rate
heart rate variability
sulfuric acid
intercellular adhesion molecules
Implantable cardioverter defibrillator
inductively coupled plasma mass spectrometry
immunoglobulin (e.g., IgA, IgE, IgG, IgM)
ischemic heart disease
interleukin (e.g., IL-5, IL-6, IL-8, IL-13)
Interagency Monitoring of Protected Visual Environments (network)
inducible nitric oxide synthase
Inhalable Particle Network
interquartile range
Intratracheal instillation
Jun kinase
low birth weight
lactate dehydrogenase
low frequency component of heart rate variability
low-density lipoprotein receptor deficient
lipopolysaccharide
lower respiratory infection
leukotriene (e.g., LTB4)
lumen to wall (ratio)
mean arterial pressure
methacholine
monocrotaline
Mean cell volume
myocardial infarction
macrophage inflammatory protein (e.g., MIP-la, MIP-2)
multiple linear regression analysis
mass median diameter
maximal mid-expiratory flow
micronuclei
millimeters of mercury
myeloperoxidase
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MV
n
NAC
NAG
NHAPS
NHBE
NF-KB
NN
NO
NO2
NO3
NOT
NR
03
OC
OHC
8-OHdG
OR
OVA
P
PAF
PAH
PAU
PE
PEF
PIF
Penh
PG
PLA2
PLN
PM
PM2.5
PM10
PMiQ-2.5
minute ventilation
number of observations
TV-acetyl cysteine
jV-acetyl-p-D-glucosaminidase
National Human Activity Pattern Survey
normal human bronchial epithelial (cells)
nuclear transcription factor-KB
normal-to-normal (R-R) interval of electrocardiogram
nitric oxide
nitrogen dioxide
nitrate
nose-only inhalation
not reported
ozone
organic carbon
oxygenated hydrocarbons
8-hydroxy-2'-deoxyguanosine
odds ratio
ovalbumin
probability value
platelet activating factor
polycyclic aromatic hydrocarbon
pause
post-exposure
peak expiratory flow
peak inspiratory flow
enhanced pause
prostaglandin (e.g., PGE2)
phospholipase-A2
popliteal lymph node
particulate matter
fine particulate matter (mass median aerodynamic diameter <2.5 jim)
combination of coarse and fine particulate matter
Thoracic coarse particulate matter
(mass median aerodynamic diameter between 10 and 2.5 jim)
44
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PMN
PMR
PNC
PNN50
ppb
ppm
QAI
R4
RAW 264.7
Raw
RBC
RMSSD
RO
ROFA
ROI
ROS
RR
RS
RTD
SaO2
SD
SDNN
SES
SH
SIDS
SMPS
S02
SO42
SOD
SRM
Sp02
ss
TEARS
TEOM
polymorphonuclear leukocyte
proportionate mortality ratio
particle number concentration
percentage of NN intervals >50 msec
(measure of heart rate variability)
parts per billion
parts per million
QA-interval
range 40
mouse macrophage cell line
airway resistance
red blood cell
root mean square of successive differences of adjacent normal-to-
normal intervals
residual oil
residual oil fly ash
reactive oxygen intermediates
reactive oxygen species
risk ratio
resuspended oil
road tunnel dust
arterial oxygen saturation
Sprague-Dawley (rat)
standard deviation of normal-to-normal intervals
socioeconomic status
spontaneously hypertensive
sudden infant death syndrome
scanning mobility particle sizer
sulfur dioxide
sulfate
superoxide dismutase
Standard Reference Material
arterial oxygen saturation
secondary sulfate
thiobarbituric acid-reactive species
tapered element oscillating microbalance
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THP-1
TLC
TLR4
TNF
TRPV1
TSP
TWA
TX
UA
UCPC
UF
URI
use
VT
VACES
WB
WBC
WBI
WKY
human monocytic leukemia cell line
total lung capacity
toll-like receptor-4
tumor necrosis factor (e.g., TNF-a)
transient receptor potential vanilloid
total suspended particulates
time-weighted average
tromboxane (e.g., TXB2)
uric acid
ultrafine condensation particle counter
ultrafine
upper respiratory infection
University of Southern California
tidal volume
versatile aerosol concentration enrichment system
whole blood
white blood cell
whole body inhalation
Wi star-Kyoto (rat)
46
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APPENDIX A
Summary Information from Recent Studies on the
Health Effects of Particulate Matter
A-l
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Table Al: Associations Between Long-Term Exposure to PM2.s and PMi0-2.5 and
Mortality and Morbidity
Table A2. Associations of Acute PM2.s Exposure with Mortality
Table A3. Associations of Acute PMio_2.s Exposure with Mortality
Table A4. Effects of PM2.s on Daily Hospital Admissions
Table A5. Effects of PMio_2.s on Daily Hospital Admissions
Table A6. Effects of PM2.s on Daily Emergency Department Visits
Table A7. Effects of PMio_2.s on Daily Emergency Department Visits
Table A8. Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Table A9. Effects of Acute PMio_2.s Exposure on Cardiovascular Outcomes
Table A10. Effects of Acute PM2.s Exposure on Various Respiratory Outcomes
Table All. Effects of Acute PMio_2.s Exposure on Various Respiratory Outcomes
Table A12. Effects of Acute PM2.5 Exposure on Birth Outcomes
Table A13. Results of Epidemiologic "Intervention" Studies
Table A14. Associations between Source-related Fine Particles and Health Outcomes
Table A15. Associations of Acute Exposure to Fine Particle Components with Health
Outcomes
Table A16. CAPs Studies with Source Apportionment or Components Analysis
Table A17. Other Acute CAPs Studies
Table A18. Subchronic CAPs Studies
Table A19. Size-fractionated and Collected Ambient PM Studies
Table A20. Acid Aerosol Studies
A-2
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Table Al: Associations Between Long-Term Exposure to PM2.s and PMi0-2.5 and Mortality and Morbidity
Cohort, Location
Study
PM Data, Concentrations
Cohort
Description
Quantitative Results
Comments and Author
Conclusions
>
Mortality Studies:
Harvard Six Cities
follow-up
Laden et al.
(2006)
Initial Harvard impactor data for
1974-1989 (period I). Period II
data (1990-1998) based on
additional PM2 5 data
(a) estimated from visibility and
PM10 measurements and
(b) measured at AQS monitors
w/in 50 miles; r = 0.93 between
estimated and measured PM2 5.
PM2 5 decreases ranged from
<1 ug/mVdecade in Topeka to
7 ug/m3/decade in Steubenville.
Recent PM2 5 means range from
10.2 to 22 ug/m3
8096 white
participants,
25+ yr, death
records
through 1998.
RR (total mortality) forPM25 (per 10 ug/m3):
entire study period: 1.16 (1.07-1.26)
period I: 1.17(1.08-1.26)
period II: 1.13(1.01-1.27)
RR with PM2 5 in year of death: 1.14 (1.06-1.22)
RR for reduced mortality risk with reduction in
PM25: 0.73 (0.57-0.95).
Similar results presented for cardiovascular and
respiratory deaths. Positive, nonsignificant
associations reported for lung cancer deaths in
different periods, but no significant association for
reduced risk.
Lower risk ratios in second
period suggests that "PM2 5
associated mortality in this
25 year follow-up was at
least in part reversible".
-------
Table Al (cont'd): Associations Between Long-Term Exposure to PM2.s and PMi0-2.s and Mortality and Morbidity
Cohort, Location
Study
PM Data, Concentrations
Cohort
Description
Quantitative Results
Comments and Author
Conclusions
Mortality Studies (cont'd):
AHSMOG
Chen etal, 2005
>
ACS, Los Angeles
Jerrettetal, 2005
1973-1998 CARB data for PM10
and gases; PM2 5 estimated from
visibility; no discussion of PM10.
2.5 determination.
Monthly estimates (1973-1998)
of PM for each individual.
PM2.5 mean = 29.0 ug/m3
PMio-2.5 mean = 25.4 ug/m3
PM2.5 from 23 stations in LA
basin (and 42 ozone monitors)
for year 2000. Krigingand
interpolation methods used to
assign exposure levels. Also
traffic buffers of 500 and 100 m
from freeway based on zip code
centroids
PM2 5 mean = MR, range
9-27 ug/m3
3239 Adventist
adults, fatal
coronary heart
disease (ICD
410-414)
(92 cases)
22,905
subjects in
267 zip code
areas; death
records
1982-2000
Significant associations in females, not males;
stronger and statistically significant associations in
subset of postmenopausal females (80 of 92 cases).
Females: PM25 RR = 1.42 (1.06-1.90) and
remains significant in 2-pollutant models
(increased size with O3 and SO2, no change with
N02)
PM10.2.5 RR = 1.38 (0.97-1.95) and increases,
becomes significant with O3 and NO2 in
2-pollutant models, little change with SO2.
Males: PM25RR = 0.90 (0.76-1.05)
PM10.2.5 RR = 0.92 (0.66-1.29) (both little change
with co-pollutants)
(all per 10 ug/m3)
Significant associations between PM2 5 and deaths
from all causes (RR 1.24, 1.11-1.37 per 10 ug/m3),
IHD, cardiopulmonary diseases, lung cancer,
endocrine disease, digestive disease. No
significant associations with digestive and other
cancers, diabetes, accidents and other causes.
Associations generally decreased with addition of
ecologic covariates. After adjustment for 44
covariates and freeways w/in 500 m, significant
associations with death from all causes (RR 1.17,
1.05-1.31) and IHD (RR 1.38, 1.11-1.72).
Authors note consistency
with results of Kunzli et al.
(2005); "suggests that health
effects of air pollution are
different in males and
females." Also observe
"we cannot rule out the
possibility" that there is
differential measurement
error since males were more
likely to work >5 miles from
home.
Note: susceptible groups
(e.g., CHD, stroke, diabetes)
excluded)
"Generally, our results agree
with recent evidence
suggesting that intraurban
exposure gradients may be
associated with even larger
health effects than reported
in interurban studies."
-------
Table Al (cont'd): Associations Between Long-Term Exposure to PM2.s and PMi0-2.5 and Mortality and Morbidity
Cohort, Location
Study
PM Data, Concentrations
Cohort
Description
Quantitative Results
Comments and Author
Conclusions
Mortality Studies (cont'd):
ACS, cause-
specific deaths
Pope et al. (2004)
Results reported for average
PM2.5 exposure levels, using IPN
data from 1979-1983 (mean
21.1 ug/m3) and AQS data from
1999-2000 (mean 14.0 ug/m3).
3-digit zip codes at residence
used for exposure estimates.
PM25 mean 17.1 ug/m3
(averaged data)
ACS cohort, Significant associations between average PM2 5
16-year and all CV diseases (RR 1.12, 1.08-1.15), IHD
follow-up, (RR 1.18, 1.14-1.23) and dysrhythmias/heart
-300,000 failure/cardiac arrest (RR 1.13, 1.05-1.21).
subjects Positive nonsignificant associations with some
other CV diseases. Negative association with
COPD (RR 0.84, 0.77-0.93) and no associations
with diabetes, pneumonia and other respiratory
diseases.
>
When stratified by smoking
status, significant
associations reported
between PM2 5 and mortality
from all CV diseases and
IHD for all three categories
(never, former and current
smokers). For dysrhythmia
and hypertension, significant
associations in the current
smokers group.
-------
Table Al (cont'd): Associations Between Long-Term Exposure to PM2.s and PMi0-2.5 and Mortality and Morbidity
Cohort, Location
Study
PM Data, Concentrations
Cohort
Description
Quantitative Results
Comments and Author
Conclusions
>
Mortality Studies (cont'd):
Veterans cohort Traffic density estimated
Lipfert et al. [vehicle-km traveled/county
(2006) land area] using data from 1985,
1990 and 1997. PM25data
restricted to 1999-2001,
averaged across period.
PM2 5 mean of 14.6 ug/m3 for
1997-2001;
sulfate mean 10.7 ug/m3 for
1976-1981;
PMi0-2.5 mean 16.0 ug/m3 for
1989-1996.
Veterans For cohort members dying in 1989-1996 who
cohort, deaths originally lived in counties with AQ data:
through 2001, significant associations with:
-25,000
subjects traffic density (PJl 1.176, 1.100-1.258 per 2.6 106
vehicles km2 in 1999 data)
PM2.5 (PJl 1.118, 1.038-1.203 per 8 ug/m3 1999
data)
PM10.2.5 (PJl 1.072, 1.013-1.124 per 12 ug/m3
1999 data)
nonsulfate PM25 (PJl 1.091, 1.025-1.161) but not
sulfates.
In 3-poll models, traffic density is little changed,
PM2 5 effect reduced and nonsignificant (PJl
1.032) and PM10.2.5 effect negative, nonsignificant.
Significant associations between mortality and
traffic density in all time periods (PJTs range from
1.019-1.036). Also significant associations with
peak O3 (95th percentile of daily max values).
"...modest changes in traffic-
related mortality risks over
time, from 1976-2001,
despite the decline in
regulated tailpipe emissions
per vehicle since the mid-
1970s. This suggests that
other environmental effects
may be involved, such as
particles from brake, tire and
road wear, traffic noise,
psychological stress, and
spatial gradients in
socioeconomic status."
-------
Table Al (cont'd): Associations Between Long-Term Exposure to PM2.s and PMi0-2.5 and Mortality and Morbidity
Cohort, Location
Study
PM Data, Concentrations
Cohort
Description
Quantitative Results
Comments and Author
Conclusions
Mortality Studies (cont'd):
Veterans cohort Traffic density and historic air
Lipfert et al. pollution data used as Lipfert
(in press) et al., 2006, also fine particle
speciation data from 2002.
Gravimetric PM2 5 mean of
13.2 ug/m3 for 2002
Veterans In single-pollutant models for 1997-2001 mortality
cohort, deaths and 1999-2001 AQ data and 2002 speciation data,
through 2001 significant associations reported between mortality
and traffic density, EC, nitrate, V and Ni. In two-
or three-pollutant models, traffic density
associations remain significant. Associations with
nitrates, V and Ni also remain significant in some
multi-pollutant models. Peak ozone concentration
also significantly associated with mortality.
PM2 5 and sulfates also positively associated with
mortality, but not statistically significant.
>
"Traffic density is also
consistently the most
important environmental
predictor in multiple-
pollutant models ... it is not
possible to discern which
aspects of traffic (pollution,
noise, stress) may be the
most relevant to public health
or whether an area-based
predictor such as traffic
density may have an inherent
advantage over localized
measures of ambient air
quality. It is also possible
that traffic density could be a
marker for unmeasured
pollutants or for geographic
gradients per se"
-------
Table Al (cont'd): Associations Between Long-Term Exposure to PM2.s and PMi0-2.5 and Mortality and Morbidity
Cohort, Location
Study
PM Data, Concentrations
Cohort
Description
Quantitative Results
Comments and Author
Conclusions
Mortality Studies (cont'd):
CA cancer
prevention study
Enstrom et al.
(2005)
>
oo
U.S. cystic
fibrosis cohort
Goss et al. (2004)
1979-1983 IPN data for 11 CA
counties, average over time and
across stations for each county.
overall PM25 mean 23.4 ug/m3
(10.6-42.0 range)
AQS data for 2000, annual
average, subject assigned data
from population-oriented
monitor closest to zip code
centroid. 713 monitors for
PM25
PM10 mean 24.9 (20.3-28.9)
ug/m3
PM25 mean 13.7 (11.8-15.9)
ug/m3
35,789 elderly
people in
11 CA
counties with
PM25data
(28,441 deaths
by 2002)
11,484 adults
and children
>5 yr, enrolled
in Cystic
Fibrosis
Foundation
National
Patient
Registry in
1999-2000.
Many results presented.
RR's presented for each county relative to
Los Angeles (PM2 5 mean 28.2 ug/m3) and none
are significant, many negative.
RR's by decade of death-significant associations
for 1973-1982, not for 1983-92 or 1993-2002.
For 1973-1982 period, RR reduced somewhat but
remains significant with addition of individual
potential confounders (e.g., age, sex); for 1973-
2002 and 1983-2002 more marked reduction in
RR size and loss of significance with addition of
covariates.
Main reported results are respiratory symptoms
(below). Also evaluated associations with
mortality from 22,303 patients in initial cohort
(fewer than 200 deaths in cohort). Positive
nonsignificant association reported for PM2 5
(RR 1.32, 0.91-1.93), no associations withPM10,
O3, NO2, SO2 or CO.
"These epidemiologic results
do not support a current
relationship between fine
paniculate pollution and total
mortality in elderly
Californians, but they do not
rule out a small effect,
particularly before 1983."
Note: use of California
county-level average levels
as an exposure surrogate
likely leads to significant
exposure error.
-------
Table Al (cont'd): Associations Between Long-Term Exposure to PM2.s and PMi0-2.5 and Mortality and Morbidity
Cohort, Location
Study
PM Data, Concentrations
Cohort
Description
Quantitative Results
Comments and Author
Conclusions
>
Mortality Studies (cont'd):
California CARD air monitoring data
Woodruff et al. obtained. Birth record data
(2006) linked to data from monitor w/in
5 miles of mother's residence;
data averaged over time period
between birth and death.
PM2 5 means ranged from 17.3 to
19.8 ug/m3 for different groups
Morbidity studies:
2 atheroschlerosis
clinical trials,
Los Angeles CA,
Kunzli et al.
(2005)
CA Children's
Health Study
Gauderman et al.
(2004)
Using data from 23 monitoring
sites in 2000, modeling used to
assign exposure at zip code
level. Mean PM2 5 exposure
level at 20.6 ug/m3, range
5.2-26.9 ug/m3.
Means of annual averages
(1994-2000) of measurements
from stations in 12 communities,
included PM10 (hourly) and
PM2 5 (2-week integrated filter),
acid vapor, ED and OC.
Mean PM2 5 ranges from 5 to
28 ug/m3 from figure.
Birth records
for infants
born in
California
1999-2000 (n
= 788 infant
deaths)
798 adults in
2 studies in
LA basin.
Recruited
1759 4th grade
children
Median concentrations of PM2 5 were somewhat
higher for infant deaths from all causes or
respiratory causes than concentrations for matched
survivors; not for SIDS or external causes.
OR for all-cause deaths (adjusted for maternal
characteristics) 1.07 (0.93-1.24), and for
respiratory deaths 2.13 (1.12-4.05) per 10 ug/m3
PM25
Outcome measure = CIMT (carotid intima-
media thickness), a measure of atheroschlerosis.
Significant associations of 5.9% (1-11%) increase
in CIMT per 20 ug/m3 PM25 for total study
population. Effects significant in women, not in
men; strongest association for women >60 yr
Significant decreases in FEVi growth with PM2 5,
acid vapor, ED and NO2.
Decreases also for FVC and MMEF growth but
less often statistically significant.
"...current levels of air
pollution have chronic,
adverse effects on lung
development in children
from the age of 10 to 18
years, leading to clinically
significant deficits in attained
FEVi as children reach
adulthood."
-------
Table Al (cont'd): Associations Between Long-Term Exposure to PM2.s and PMi0-2.5 and Mortality and Morbidity
Cohort, Location
Study
PM Data, Concentrations
Cohort
Description
Quantitative Results
Comments and Author
Conclusions
Morbidity studies (cont'd):
CA Children's
Health Study
Millstein et al.
(2004)
CA Children's
Health Study
McConnell et al.
(2003)
U.S. cystic
fibrosis cohort
Goss et al. (2004)
Monthly means of pollutant data
(data presented in figures only).
4-year means of pollutants for
1996-1999 (same sites from
Gauderman et al. (2004);
PMio-2.5 determined by
subtraction of PM2 5 from PM10
(2-wk integrated).
Means across communities of
13.8 ug/m3 PM25, 17.0 ug/m3
PM
AQS data for 2000, annual
average, subject assigned data
from population-oriented
monitor closest to zip code
centroid. 713 monitors for
PM25
PM10 mean 24.9 (20.3-28.9);
PM25 mean 13.7 (11.8-15.9)
2034 4th grade
children,
questionnaire
in 1995.
475 children
with asthma,
questionnaire
1996-1999
11,484 adults
and children
>5 yr, enrolled
in Cystic
Fibrosis
Foundation
National
Patient
Registry in
1999-2000.
Monthly prevalence of asthma medication use
associated with monthly average O3, HNO3, and
acetic acid levels, not with PM2 5, PM10 or
PMi 0-2.5. Prevalence of wheeze associated with
PMio-is during spring and summer months.
Bronchitic symptoms associated with yearly
variability of PM25 (per ug/m3), OR 1.09 (1.01-
1.17), with OC, OR 1.41 (1.12-1.78), NO2 and O3.
No significant associations with PM10.2 5 Larger
OR's with within-community yearly variability
than between-community (per ug/m3 PM2 5 OR =
1.03, 1.01-1.05). OC and NO2 effects strongest in
2-pollutant models
Increased odds of having 2 or more pulmonary
exacerbations per 10 ug/m3 PM25 (21%, 7-33%)
and PM2 5 (8%, 2-15%) as well as ozone.
No associations with NO2, SO2, or CO.
Negative associations with lung function in cross-
sectional analysis. Decreased FEVi with PM2 5
and PM10; no clear associations with gaseous
pollutants.
"In conclusion, exposure to
ambient PM10, PM2 5, and
ozone may increase the risk
for pulmonary exacerbations
and increase the rate of
change in lung function in
the CF population."
-------
Other studies using PMin or other PM indicators:
Mortality:
Evans and Smith (2005) used data from U.S. Health and Retirement Study, a national
panel survey of birth cohorts 1931-1941 with follow-up in 1992-2004. Long-term (1990-2000)
PMio exposure associated with a new heart condition (reported between 1994 and 1996)
(coefficient = 0.004, t = 1.74) and significantly associated with shortness of breath (coefficient =
0.017, t = 2.25) but not with new lung conditions. Recent (1994-6) PMio exposure associated
with new heart condition (coeff = 0.0004, t = 1.74); also association with shortness of breath, but
not with new lung condition. Long-term O3 exposure also associated with new lung condition
and shortness of breath
Filleul et al. (2005) used data from a respiratory disease survey data of 14,000+ adults in
24 areas in 7 cities. For 24 areas no association was reported between particles (BS) and
mortality (RR 0.99, 0.98-1.01). Further analyses excluded data from 6 areas where monitors
were in an area "heavily influenced by the local traffic and, so, non-representative of the mean
exposure of the population of the entire area" based on NO/NO2 ratio. For these 18 areas, RR
with BS of 1.07 (1.03-1.10) for total mortality; nonsignificant RR's of 1.03 and 1.05 for lung
cancer and cardiopulmonary diseases. Significant associations also with TSP for total and
cardiopulmonary diseases. Significant associations also with NO, NC>2, but not SC>2. No
consistent modifying effect of gender or education level. BS means ranged from 21 to 152
|ig/m3; "heavy traffic" BS means of 46, 105, 141, 111, and 91 |ig/m3.
Morbidity:
Tager et al. (2005) used data from UC Berkeley students—255 never-smoking students
from LA and San Francisco areas—and reported consistent inverse associations between Os,
PMio and NC>2 and FEFys, FEF25-75 in both men and women. Os associations were more robust
in co-pollutant models than PMio or NC>2. Mean lifetime PMio exposure was 48 |ig/m3 for men
and 45 |ig/m3 for women.
Salam et al. (2005) used birth certificate information obtained for California-born
children participating in the Children's Health Study (n = 3901) to test for associations between
air pollution exposure and birth weight. Air pollution estimates assigned using zip code of
maternal residence at birth, with spatial interpolation based on data from up to the three nearest
stations within 50 km of zip code. Exposure estimates calculated as monthly average of 24 hr
measurements, computed for trimesters and full pregnancy. A nonsignificant association was
reported between higher PMio exposures during the third trimester and decreased birth weight.
Significant associations were reported with first-trimester CO exposure and third-trimester Os
exposure.
Penard-Morand et al. (2005) uses questionnaire data for 6672 children in six French cities
with air pollution data collected at children's schools from 1998-2000. The PMio mean in high
and low cities was 23.8 and 18.0 |ig/m3, respectively; the overall mean was approximately 21
|ig/m3 (from figure). Significant associations were reported with PMio and asthma, atopic
dermatitis, exercise-induced bronchial reactivity and allergic rhinitis.
A-ll
-------
Pierse et al. (2006) reported an association between PMio and symptoms in children
surveyed in 1998 and 2001 in Leicester UK. The OR for prevalence of cough without cold in
1998 and 2001 was 1.21 (1.07-1.38) and 1.56 (1.32-1.84), respectively, PMio was also associated
with the incidence of wheeze.
Zhang et al. (2002) used questionnaire data for 7621 children in four Chinese cities and
1995-1996 air pollution data. Grand means were PM2.s = 92 |ig/m3 (not a typo) and PMi0-2.5 =
59 |ig/m3. Significant associations were observed between PMio-2.s and incidence of bronchitis
(2.20, 1.14-4.26), persistent cough (1.46, 1.12-1.90) and persistent phlegm (2.83, 1.93-4.16);
positive nonsignificant association with incidence of asthma, wheeze, and ever-hospitalization
for respiratory disease. For all six endpoints positive but nonsignificant associations were
reported with PM2.5. No significant associations (some nonsignificant negative) were observed
with SO2 and NOX.
Bayer-Oglesby et al., (2005) used data from a study of 9591 school-children in nine
Swiss communities with a respiratory questionnaire administered in 1992-2001. A decrease in
PMio (per 10 |ig/m3) was associated with a decrease in prevalence of chronic cough (OR 0.65,
0.54-0.79), bronchitis (OR 0.66, 0.55-0.80), common cold (OR 0.78, 0.6800.89), nocturnal dry
cough (OR 0.70, 0.60-0.83) and conjunctivitis symptoms. No significant associations were
reported with wheeze, asthma, sneezing, or hay fever. PMio decreased 9.8 |ig/m3 between 1993
and 2000; the decreases in PMio concentration were three times greater in urban than rural
communities and ranged from 10-34 |ig/m3 in 2000.
A-12
-------
Table A2. Associations of Acute PMi.s Exposure with Mortality
Reference, Study
Location and Period
PM2.5
Ostro et al. (2006)
9 counties in
California
Jan 1999-Dec 2002
Outcome Measure
All nonaccidental,
cardiovascular, and
respiratory causes, as
well as deaths from
Mean PM Levels
(ug/m3)
24-h avg PM2.5:
Range of means
across counties:
Copollutants
Considered
NO2, CO, O3
Lag Structure
Examined
2-d lag and 0-1 d
avg lag
Method/Design
Time-series study.
Poisson regression
using penalized and
natural spline models.
Effect Estimates/Results
% excess risk per 10 ug/m :
All causes:
All ages:
ischemic heart
disease and diabetes;
all ages and age
>65yr
>
14 (Contra Costa
and Sacramento) to
29 (Riverside)
Range of daily
concentrations
across counties
0-160
Default model used
penalized spine
regression. County-
specific results pooled
based on meta-analysis
using random-effects
model.
At least one monitor
collected daily PM2 5
data in each county. A
substantial number of
days were missing
data, which varied by
county and appeared to
be generally random.
Lag 0-1: 0.6% (0.2, 1.0)
Age >65 yr:
Lag 0-1: 0.7% (0.2, 1.1)
Cardiovascular:
All ages:
Lag 0-1: 0.6% (0.0, 1.1)
Respiratory:
All ages:
Lag 0-1: 2.2% (0.6, 3.9)
In multipollutant models, PM2 5 effect
estimate was attenuated when highly
correlated pollutants (NO2 and CO)
were added to the model,
but was not affected by the inclusion
of O3. However, in those aged
>65 yr, adjusting for gaseous
pollutants did not affect the PM2 5
coefficient.
Analysis of different mortality
categories and subpopulations
indicated somewhat stronger
associations of daily PM25 with
mortality for age >65yr, diabetics,
females, white, and non-high school
graduates.
-------
Table A2 (cont'd). Associations of Acute PM2.s Exposure with Mortality
Reference, Study
Location and Period
Outcome Measure
Mean PM Levels
(ug/m3)
Copollutants
Considered
Lag Structure
Examined
Method/Design
Effect Estimates/Results
PM2.S (cont'd)
Burnett et al. (2004)
12 Canadian cities
Jan 1981-Dec 1999
All nonaccidental,
cardiovascular, and
respiratory causes
24-h avg PM2.5:
All 12 cities:
12.8
SD not provided.
Range of means
across cities:
8.1 (St. John) to
16.7 (Windsor)
PM10.25,PM10,
S042, N02, S02
CO, O3
1-, or2-dlag
Time-series study.
Natural spline
functions used to
model nonlinear
associations.
PM2 5 data collected
every 6th day. PM2 5
data available on 12%
of days with mortality
data. In 11 of 12
cities, daily PM2 5 data
collected from Jan
1998 to Dec 2000.
% excess risk per 12.8 ug/m3:
All causes:
Using all available data:
Single-pollutant model:
Lag 1: 0.77%.(0.04, 1.58)
Two-pollutant model with NO2:
Lag 1: -0.13% (-1.10, 0.85)
Significant associations observed for
NO2 in two-pollutant model. Similar
results observed for PM10.2.5.
Significant associations observed with
PM10, which also became
nonsignificant after adjusting for
N02.
Only using data from period when
daily PM25 levels available (1998-
2000):
Single-pollutant model:
Lag 1: 1.13% (95% CI not presented)
Two-pollutant model with NO2:
Lag 1: 0.98%.(0.16, 2.13)
When restricting analysis to only days
when daily PM2 5 data were available,
the NO2 association was reduced
considerably after adjustment for
PM2 5, whereas PM2 5 effect remained
fairly robust to NO2 adjustment.
-------
Table A2 (cont'd). Associations of Acute PM2.s Exposure with Mortality
>
Reference, Study
Location and Period Outcome Measure
PM2.S (cont'd)
Dales et al. (2004) SIDS; age <1 yr
12 Canadian cities
Jan 1984-Dec 1999
Slaughter et al. (2005) All nonaccidental
Spokane, WA causes
Jan 1 995- Jun 2001
Mean PM Levels Copollutants
(jig/m3) Considered
24-h avg PM2 5: PM10.2 5, PM10,
N02, S02, CO,
All 12 cities: O3
12.27
IQR 8.98
Range of means
across cities:
8.07 (St. John) to
16.67 (Windsor)
24-h avg PM2 5: PMj , PM10.2 5,
10th%-90th% PM10, CO
4.2-20.2
Lag Structure
Examined Method/Design
0-, 1-, 2-, 3-, 4-, Time-series study.
or 5-d lag; Nonlinear random-
multiday lags of effects regression
2 to 6 d model used.
PM2 5 data collected
every 6th day.
0-, 1-, 2-, 3-d lag Time-series study.
Poisson GLM with
natural splines.
Hourly PM2 5 data
available. Daily
averages calculated.
Effect Estimates/Results
No association observed between
incidence of SIDS and PM2 5 (no
effect estimates presented). Similar
results observed for PM10 2 5 and
PM10.
Significant associations observed for
NO2, SO2, and CO.
RRper 10 ug/m3:
Lag 1: 1.01(0.97,1.04)
No associations observed between
nonaccidental mortality and PM2 5.
Similar results observed for PM10.2.5
andPM10.
-------
Table A2 (cont'd). Associations of Acute PM2.s Exposure with Mortality
Reference, Study
Location and Period
PM2.S (cont'd)
Mar et al. (in press)
Phoenix, AZ
Feb 1995-Dec 1997
Mean PM Levels
Outcome Measure (jig/m3)
All nonaccidental and 24-h avg PM2 5:
cardiovascular
causes; age. 65 yr Gravimetric
sampler:
12.0
SD6.6
Range 2-39
TEOM sampler:
13.0
SD7.2
Range 0-42
Copollutants
Considered
Various PM2 5
sources,
including soil,
traffic,
secondary SO42,
biomass/wood
combustion, sea
salt, and copper
smelter
Lag Structure
Examined Method/Design
0-, 1-, 2-, 3-, Time-series study.
4-d, or 5- lag Poisson GLM with
natural splines.
Daily PM2.5 data
collected using both
gravimetric and
TEOM samplers.
Focus of study was to
assess variability of
different methods/
Effect Estimates/Results
% excess risk per 5th% to 95th%
increment (using TEOM sampler):
Cardiovascular:
Lag 1: 15.0% (1.5, 30.3)
Magnitude and lag structure of the
association between PM2 5 and
cardiovascular mortality were similar
to those for the combined traffic
factor.
investigators in
estimating source
apportioned PM2 5
health effects.
-------
Table A2 (cont'd). Associations of Acute PM2.s Exposure with Mortality
>
Reference, Study
Location and Period
PM2.S (cont'd)
Ito et al. (in press)
Washington, DC
Augl988-Dec 1997
Klemm et al. (2004)
Atlanta, GA
Augl998-July2000
Mean PM Levels Copollutants
Outcome Measure (jig/m3) Considered
All nonaccidental, 24-h avg PM2 5: Various PM2 5
cardiovascular, and 17.8 sources,
cardiorespiratory SD 8.7 including soil,
causes 5th%-95th% 28.7 traffic,
secondary SO42,
NO3", residual
oil, wood
smoke, sea salt,
incinerator, and
primary coal
All nonaccidental, 24-h avg PM2.5: PM10.2.5, SO42,
circulatory, 19.62 EC, OC,NO2,
respiratory, cancer, SD 8.32 NO3", SO2, CO,
and other causes; age IQR 1 1 .62 O3, ultrafines,
<65yrand65yr Range 5.29-48.01 hydrocarbons,
acid
Lag Structure
Examined Method/Design
0-, 1-, 2-, 3-, or Time-series study.
4-d lag Poisson GLM with
natural splines.
PM2 5 data collected
every Wednesday and
Saturday.
Focus of study was to
assess variability of
different methods/
investigators in
estimating source
apportioned PM2 5
health effects.
Multiday lag of Time-series study.
0-1 d Poisson GLM using
natural cubic splines
with quarterly,
monthly, or biweekly
knots. Default model
used monthly knots.
Daily PM2 5 data
collected.
Effect Estimates/Results
% excess risk per 28.7 ug/m :
All causes:
Lag 3: 8.3% (3.7, 13.1)
Significant association between all
cause mortality and PM2 5 only
observed at lag 3 d.
% excess risk per 19.62 ug/m3:
All causes:
Age. 65 yr:
Lag 0-1: 11. 3% (3.7, 19.4)
Results differ across model
specifications (i.e., choice of lag and
number of knots). Weaker
associations observed with PM10.2.5.
No significant associations observed
in those aged <65 yr.
-------
Table A2 (cont'd). Associations of Acute PM2.s Exposure with Mortality
>
oo
Reference, Study
Location and Period
PM2.5 (cont'd)
Villeneuve et al.
(2003)
Vancouver, British
Columbia, Canada
Jan 1986-Dec 1998
Mean PM Levels
Outcome Measure (jig/m3)
All nonaccidental, 24-h avg PM2 5:
cardiovascular,
respiratory, and Daily data from
cancer causes; SES 1995-1998:
status 7.9
10th%-90th%
4.0-13.0
Range 2.0-32.0
Every 6th day data
from 1986-1998:
11.6
10th%-90th%
4.7-20.4
Range 1.8-43.0
Copollutants Lag Structure
Considered Examined Method/Design
PM10.2.5, PM10, 0-, 1-, or 2-d lag; Time-series study.
TSP, coefficient multiday lag of Poisson regression
of haze, SO42, 0-2 d using natural spline
SO2, NO2, CO, functions.
03
Daily PM2.5 data
collected from 1995 to
1998 using TEOM;
PM2 5 data collected
every 6th day from
1986 to 1998 using a
dichotomized sampler.
Effect Estimates/Results
% excess risk per 9.0 ug/m3:
Results using daily PM2 5 data:
All causes:
Lag 0:. 0.1% (-4. 1,4.1)
Cardiovascular:
LagO: 4. 3% .(-1.7, 10.7)
Respiratory:
Lag 0: 6.7% .(-3.7, 18.3)
Cancer:
LagO:.4.5%.(-11.2,2.8)
Collectively, results suggest no
association between PM2 5 and
mortality. There is some suggestive
evidence of a modest increase in the
risk of cardiovascular mortality
among individuals of low SES
status. Significant associations with
cardiovascular mortality were
observed for daily PM10.2.5 and
PM10 data.
-------
Table A2 (cont'd). Associations of Acute PM2.s Exposure with Mortality
Reference, Study
Location and Period
Outcome Measure
Mean PM Levels
(ug/m3)
Copollutants
Considered
Lag Structure
Examined
Method/Design
Effect Estimates/Results
PM2.S (cont'd)
Goldberg et al. (2006)
Montreal, Canada
1986-1993
Diabetes, and
nonaccidental
mortality in
subgroups with
diabetes diagnosed at
least 1 year before
death in adults >65
yr. Also considered
subgroups with
cardiovascular
diagnoses.
24-h avg PM2 5:
17.4
SD11.4
24-h avg predicted
PM25:
17.6
SD8.8
PMio, TSP,
coefficient of
haze, SO42,
predicted SO4 ,
S02, N02, CO,
03
0-, 1-, and
average of 0- to
2-day lags ("3-
day mean")
Time-series study.
Poisson regression
using natural spline
functions.
Report results for
predicted PM2 5; used
statistical model to
estimate mass when
measurements were
not available;
measured data
available on 636 days
and predicted data for
3653 days.
% excess risk per 9.5 ug/m3:
(all 3-day mean lag)
mortality from diabetes:
8.37% (L80, 15.37)
nonaccidental mortality in subjects
with diabetes:
3.64% (0.07, 7.33)
Greater effects seen generally in the
warm season.
No significant association for
nonaccidental mortality in subjects
with diabetes, but without cancer,
cardiovascular disease or airways
disease.
Associations reported for
nonaccidental mortality in subjects
with diabetes who also had any
cardiovascular disease, chronic
coronary disease and atheroschlerosis.
-------
Table A3. Associations of Acute PMi0-2.s Exposure with Mortality
to
o
Reference, Study
Location and Period
PM10_2.5
Burnett et al. (2004)
12 Canadian cities
Jan 1981-Dec 1999
Dales et al. (2004)
12 Canadian cities
Jan 1984-Dec 1999
Mean PM Levels
Outcome Measure (jig/m3)
All nonaccidental, 24-h avg PM10.2.5:
cardiovascular, and
respiratory causes All 12 cities:
11.4
SD not provided.
Range of means
across cities:
5.5 (Vancouver) to
15.9 (Winnipeg)
SIDS; age <1 yr 24-h avg PM10-2.5:
All 12 cities:
11.28
IQR 8.76
Range of means
across cities:
5. 46 (St. John) to
15. 88 (Winnipeg)
Copollutants Lag Structure
Considered Examined Method/Design
PM2.5, PM10, 0-, 1-, or2-dlag Time-series study.
SO42, NO2, SO2, Natural spline
CO, O3 functions used to
model nonlinear
associations.
PMio-2.5 data collected
every 6th day. PM! 0-2.5
data available on 12%
of days with mortality
data.
PM2 5, PMio, 0-, 1-, 2-, 3-, 4-, Time-series study.
NO2, SO2, CO, or 5-d lag; Nonlinear random-
O3 multiday lags of effects regression
2 to 6 d model used.
PMio-2.5 data
determined by
difference. PM2 5 and
PM10 data collected
every 6th day.
Effect Estimates/Results
% excess risk per 11.3 ug/m3:
All causes:
Single-pollutant model:
Lag 1: 0.74% (-0.12, 1.61)
Two-pollutant model with NO2:
Lag 1: 0.35%.(-0.55, 1.26)
No significant associations observed
for NO2 in two-pollutant model.
No association observed between
incidence of SIDS and PM10.2.5 (no
effect estimates presented).
Significant associations observed for
NO2, SO2, and CO.
-------
Table A3 (cont'd). Associations of Acute PMi0-2.s Exposure with Mortality
to
Reference, Study
Location and Period
PM10_2.5
Klemm et al. (2004)
Atlanta, GA
Augl998-July2000
Outcome Measure
All nonaccidental,
circulatory,
respiratory, cancer,
and other causes; age
<65 yr and. 65 yr
Mean PM Levels
(ug/m3)
24-havgPM10.25:
9.69
SD 3.94
IQR 5.25
Range 1.71-25. 17
Copollutants Lag Structure
Considered Examined
PM2 5, SO42, EC, Multiday lag of
OC,NO2, 0-1 d
NO3", SO2, CO,
O3 ultrafines
hydrocarbons,
acid
Method/Design
Time-series study.
Poisson GLM using
natural cubic splines
with quarterly,
monthly, or biweekly
knots. Default model
used monthly knots.
Daily PM10.2.5 data
collected.
Effect Estimates/Results
% excess risk per 9.69 ug/m3:
All causes:
Age 65 yr:
Lag 0-1: 6.2% (-0.9, 13.7)
Results differ across model
specifications (i.e., choice of lag and
number of knots).
No significant associations observed
in those aged <65 yr.
-------
Table A3 (cont'd). Associations of Acute PMi0-2.s Exposure with Mortality
to
to
Reference, Study
Location and Period Outcome Measure
PM10_2.5 (cont'd)
Slaughter et al. (2005) All nonaccidental
Spokane, WA causes
Jan 1 995- Jun 2001
Villeneuve et al. All nonaccidental,
(2003) cardiovascular,
Vancouver, British respiratory, and
Columbia, Canada cancer causes; SES
Jan 1986-Dec 1998 status
Mean PM Levels
(ug/m3)
24-h avg PM10.2.5:
Not reported.
24-h avg PM10.2.5:
Daily data from
1995-1998:
6.1
10th%-90th%
2.0-13.0
Range 0.0-72.0
Every 6th day data
from 1986-1998:
8.3
10th%-90th%
3.1-15.0
Range 0.7-35.0
Copollutants Lag Structure
Considered Examined Method/Design
PMi, PM25, 0-, 1-, 2-, 3-d lag Time-series study.
PMj o, CO Poisson GLM with
natural splines.
PMio-2.5 calculated as
difference between
PM10andPM2.5
measurements. Hourly
PM2 5 and PM10 data
available. Daily
average values
calculated.
PM25, PM10, 0-, 1-, or2-dlag; Time-series study.
TSP, coefficient multiday lag of Poisson regression
of haze, SO42, 0-2 d using natural spline
SO2, NO2, CO, functions.
03
Daily PM10.2.5 data
collected from 1995 to
1998 using TEOM;
PM10.2.5 data collected
every 6th day from
1986 to 1998 using a
dichotomized sampler.
Effect Estimates/Results
No associations observed between
nonaccidental mortality and PM10_2 5.
Quantitative results not provided.
% excess risk per 11.0 ug/m3:
Results using daily PM10.2.5 data:
All causes:
LagO: 1.0% .(-1.9, 4.0)
Cardiovascular:
LagO: 5. 9% (1.1, 10.8)
Respiratory:
LagO:. 1.5% (-9.4, 7.1)
Cancer:
LagO: 3.1% (-2. 9, 9.4)
Significant associations with
cardiovascular mortality were
observed for daily PM10.2.5 and PM10
data.
-------
Additional U.S. and Canadian PM-Mortality Studies:
Staniswalis et al. (2005): This study shows that the effects of airborne PM on daily mortality can
be underestimated when using daily averages to summarize hourly profiles, because the daily
average does not capture information about very acute exposures, that is, large exposures
occurring over very short periods of time. A principal component data analysis is shown to be
useful for characterizing hourly measurements of air pollution constituents. In addition, it is
shown that in El Paso, the risk of PM-induced mortality is higher during still-air inversions
(i.e., at low wind speeds) than it is during sandstorms (i.e., at high wind speeds). These results
suggest that coarse and fine PM from resuspended fugitive dust is less toxic than fine PM of
urban type.
De Leon et al. (2003): The effects of PMi0 on circulatory and cancer mortality with and without
contributing respiratory causes were examined in this study conducted in New York City.
Among those aged. 75 yr, effect estimates were greater for circulatory mortality with contributing
respiratory causes (6.6% [95% CI: 2.7, 10.6] per 18.16 |ig/m3 increase in PMio) at a 0- to 1-day
lag compared to that without (2.2% [95% CI: 0.8, 3.5]). Unlike in those aged. 75 yr,
significantly higher risks were not observed with contributing respiratory causes in individuals
aged <75 yr.
Bateson and Schwartz (2004): The association between PMio and all-cause mortality in
individuals aged. 65 yr who were previously admitted to the hospital with a primary or secondary
diagnosis of heart or lung disease was examined in this case-crossover study in Cook County, IL.
A 1.14% (95% CI: 0.44, 1.85) excess risk was observed per 10 |ig/m3 increase in PMio at a lag
of 0 to 1 days. The effect of PMio on the risk of mortality was higher among those with a prior
diagnosis of myocardial infarction (1.98%), diabetes (1.49%), and congestive heart failure
(1.28%).
Sullivan et al. (2003): In this case-crossover study in King County, WA, the association between
PM and out-of-hospital sudden cardiac arrest in individuals with and without preexisting
cardiovascular and respiratory disease was examined. PM2.5 data was estimated using a
nephelometric measure (PMi). No consistent associations were observed between increased
levels of PM2.5 or PMio and risk of primary cardiac arrest.
Holloman et al. (2004): To examine the association between cardiovascular mortality and
estimated exposure to PM2.5 in seven counties in North Carolina, a three-level hierarchical
Bayesian model was used: (1) linking monitor readings to ambient levels over the region;
(2) linking ambient levels to exposure levels (estimated using NHAPS); and (3) linking exposure
levels to mortality. Significant associations were observed between cardiovascular mortality and
PM2.5 at a lag of 2 days. Results obtained by incorporating a simple exposure simulator into the
model indicated that the effect of increased levels of exposure was not equivalent to that of
ambient PM2 5 on cardiovascular mortality.
Vedal et al. (2003): The associations between PMio and all-cause, cardiovascular, and
respiratory mortality were examined in Vancouver, Canada (PMio concentration range 4.1 to
37.2 |ig/m3). During the summer, statistically significant effects on respiratory mortality were
observed for PMio, 0% and SO2, and the effects of NO2 and CO were also nearly significant.
Effects on total and cardiovascular mortality were only seen for 63. During the winter,
significant effects on total mortality were observed for PMio, NO2, and SO2; NO2 and SO2 also
A-23
-------
were associated with cardiovascular mortality. No significant associations with respiratory
mortality were observed in the winter. The authors report that these findings may support the
notion that no threshold pollutant concentrations are present, but they also raise concern that the
observed effects may not be due to the measured pollutants themselves, but rather of some other
factors present in the air pollution-meteorology mix.
Jerrett et al. (2004): Significant associations between CoH and all-cause mortality were
observed in regions of lower SES status at various lags of exposure. Regions of higher SES
status displayed no significant associations except at a multiday lag of 0 to 3 days. These
findings suggest that the effect of PM on mortality may be modified by SES status. Low
educational attainment and high manufacturing employment significantly and positively
modified the effects of PM on acute mortality.
Additional Studies Examining Issues Related to Interpreting the
PM-Mortality Relationship:
Forastiere et al. (2005): Using a case-crossover design, the associations between daily ambient
air pollution levels (particle number concentration [PNC], PMio, CO, NO2, and Os) and the
occurrence of out-of-hospital fatal coronary events in Rome were examined. The association
was statistically significant for PNC, PMio, and CO, with the strongest effect observed on the
same day. An IQR increase in PNC (27,790 particles/cm3) and PMio (29.7 |ig/m3) was
associated with a 7.6% (95% CI: 2.0, 13.6) and 4.8% (95% CI: 0.1, 9.8) excess risk in mortality,
respectively. Stronger effects were observed among people aged. 65 yr, and possibly in those
with hypertension and COPD.
Sunyer et al. (2002): This case-crossover study assessed the acute association between air
pollution and all-cause mortality in a population-based cohort of subjects with asthma recruited
from emergency room admissions for asthma exacerbation in Barcelona, Spain. No significant
associations were observed between PMio or BS and mortality. Slightly larger effect estimates
were observed in subjects admitted more than once compared to those admitted only once to the
emergency department for asthma, but differences were not significant. Stronger associations
were observed for NO2 and Os.
Kan et al. (2005): Using time-series Poisson regression, the relationship between daily SARS
mortality and ambient air pollution in Beijing was examined. An 10 |ig/m3 increase in PMio
(mean 149.1 |ig/m3 [SD 8.1]) over a 5-day moving average corresponded to a RR of 1.06 (95%
CI: 1.00, 1.12). NO2, but not SO2, also was associated with daily SARS mortality (RRs of 1.22
[95% CI: 1.01, 1.48] and 0.74 [95% CI: 0.48, 1.13], respectively).
Goodman et al. (2004): In a Dublin, Ireland study, a constrained (6th order polynomial)
distributed lag model used to examine BS effects through 40 days. Results were compared to
effects estimated for a 0 to 2 day lag of BS exposure. Stronger associations with BS were
consistently observed for all-cause, cardiovascular, and respiratory mortality using the extended
follow-up period. Analyses suggest that studies on acute effects of air pollution have
underestimated the total effects of PM on mortality.
A-24
-------
Table A4. Effects of PM2.s on Daily Hospital Admissions
Reference, Study
Location and Period
Outcomes and Design Mean PM Levels _ ^ . , ,
& Considered
Lag Structure
Examined
Method, Findings,
Interpretation
Quantitative Results
PM2.5
Dominici et al.
(2006)
United States
National
Databasel 999-2002
to
A daily time-series analysis
on hospital admission rates
(from the Medicare
National Claims History
Files) for cardiovascular
and respiratory outcomes
and ambient PM2 5 levels,
temperature for 204 U.S.
urban counties (population
>200,000) with 11.5 million
Medicare enrollees (aged
>65 years) living an
average of 5.9 miles from a
PM2 5 monitor.
PM2 5 county
annual mean:
13.4 ng/m3
IQR
(11.3-15.2 ng
0-2 Nationally, short-term
increase in hospital admission
rates associated with PM2 5 for
all health outcomes except
injuries. The largest
association was for heart
failure. Substantial
homogeneity of fine particle
matter concentration across
geographic area. For
cardiovascular disease, all
estimates in the eastern U.S.
were positive and generally
statistically significant, while
estimates in the western U.S.
were close to 0 except for
heart failure
For respiratory disease, there
was greater consistency
between regions.
The authors noted that they
did not find evidence of the
effect modification by average
concentration of either PM2 5
orO3.
Excess risk per 10 |ig/m3:
Heart failure
1.28% (0.78-1.78%)
Annual reduction in
admissions attributable to a
10 |ig/m3 reduction in daily
PM2 5 level for 204 counties in
2002
Cerebrovascular disease:
1836(680-2992)
Heart failure: 3156(1923-
4389)
Respiratory tract infection:
2085 (929-3241)
-------
Table A4 (cont'd). Effects of PM2.s on Daily Hospital Admissions
to
Reference, Study
Location and Period
PM2.S (cont'd)
Lin et al. (2002)
Toronto
1981-1993
Lin etal. (2005)
Toronto
1998-2001
Outcomes and Design
Both case-crossover and
time-series analyses used to
assess the associations
between various PM
measures and asthma
hospitalization among
children 6-12 years old.
Examined the associations
between pollutants and
hospitalizations for
respiratory infections
among children younger
than 15 years of age.
Bi-directional case-
crossover design used.
»/r T.»/r T i Copollutants
Mean PM Levels _ r . , ,
Considered
PM2 5 mean: PM10.2.5,
17.99 ng/m3 PM10, O3,
Mini. 22 N02,CO,S02
Max 89.59
PM2.5 PMio-2.5,
Mean: SD PM10, CO,
9.59 SO2, NO2, O3
SD 7.06
Lag Structure Method, Findings,
Examined Interpretation
1 -7 Significant effects were not
found for PM2 5, but both
analysis methods did find
relationships with PM10_2 5 for
either sex. Individual PM2 5
results showed some positive
association but not after
consideration of both weather
conditions and gaseous
co-pollutants.
PM2 5 showed no significant
effects when other pollutants
were considered. The effects
for PM10.2.5 were pronounced.
Quantitative Results
PM2.5 (IQR 9.3 |ig/m3)
After controlling for gaseous
pollutants effect estimates
range from -7% to 1% with
95% CI all including 0% for
both bidirectional case-
crossover and time-series
analysis.
PM2.5
(IQR 7.8 ng/m3)
single-pollutant: 10% (2-22)
4 day lag
after adjustment for other
pollutants:
-6% (-19,8)
-------
Reference, Study
Location and Period
Table A4 (cont'd). Effects of PM2.5
Outcomes and Design Mean PM Levels _ ^ . , ,
& Considered
on Daily Hospital Admissions
Lag Structure
Examined
Method, Findings,
Interpretation
Quantitative Results
PM2.S (cont'd)
Yang et al. (2004)
Vancouver, British
Columbia Jun 1,
1995-Mar 31,1999
to
Logistic regression was PM2,5
used to estimate the Mean
associations between PM 7.7 ug/m3
and first hospitalization for SD 3.7
children less than 3 years of Range:
age, a case-control 2.0-32.0
approach. Also, analysis
was conducted using
bidirectional-case crossover
analysis and time-series
analysis.
PM10.25,CO,
03,N02, S02
0-7 The data indicated possible
harmful effects from coarse
PM on first hospitalization for
respiratory disease. No
significant association was
found between PM2 5 and first
hospitalization for respiratory
disease. PM2 5 concentrations
were relatively low.
In this study, only the case-
control and case-crossover
approaches support the notion
of effect of daily average
PM10.2.5 on first
hospitalization for respiratory
disease in early childhood. It
is not clear if these two
approaches overestimated or if
the time-series analysis
underestimated. For PM2 5,
the authors noted that
differences in findings may be
explained, in part, by TEOM
measurements, which may be
lower than those of filter-
based samples.
No quantitative results
reported.
-------
Table A4 (cont'd). Effects of PM2.s on Daily Hospital Admissions
Reference, Study
Location and Period
Outcomes and Design Mean PM Levels
Copollutants
Considered
Lag Structure
Examined
Method, Findings,
Interpretation
Quantitative Results
to
oo
PM2.S (cont'd)
Chen et al. (2004)
Vancouver, British
Columbia
Junl995-Marl999
Chen etal. (2005)
Vancouver, British
Columbia
Junl,1995-Mar31,
1999
A time-series analysis PM2.5
assessing the association Mean
between low levels of size- 7.7 ng/m3
fractionated PM and SD (3.7)
hospitalization for chronic Range:
obstructive pulmonary 2.0-32.0
disease (COPD) in the
elderly. GAMandGLM
models were used.
A time-series analysis was PM2 5
used to evaluate the Mean
associations between 7.7 ng/m3
respiratory admissions and SD(3.7)
PM, looking at first, Range:
second, and overall hospital 2.0-32.0
admission for respiratory
disease among the elderly.
8,989 adults, >65 yr.
PM10-2 5, CO,
O3, NO2, SO2
PM10.25,CO,
03,N02, S02
1-7
1-7
Particle-related measures were For a 3-day average PM2
significantly associated with
COPD hospitalizations in the
Vancouver area, but the
effects are not independent of
other air pollutants.
PM10.2.5 had a larger effect on
respiratory admissions than
PM25. For PM10.2 5, the
second and overall admission
rates were higher than the first
admission rate.
9% (3, 16%)
This association was not
significant when NO2
included in the model.
PM2 5 adjusted for copollutants
First admission
Lagl:
2% (-1,6)
Second admission:
1% (-3, 6)
-------
Table A5. Effects of PMi0-2.s on Daily Hospital Admissions
to
VO
Reference, Study
Location and Period
PM10.2.5
Lin et al. (2002)
Toronto
1981-1993
Lin etal. (2005)
Toronto
1998-2001
Chen et al. (2004)
Vancouver, British
Columbia
Junl995-Marl999
Outcomes and Design
Both case-crossover and
time-series analyses used to
assess the associations
between various PM
measures and asthma
hospitalization among
children 6-12 years old.
Examined the associations
between pollutants and
hospitalizations for
respiratory infections
among children <15 yr.
Bi-directional case-
crossover design used.
A time-series analysis
assessing the association
between low levels of size
fractionated PM and
hospitalization for chronic
obstructive pulmonary
disease (COPD) in the
elderly. GAMandGLM
models were used.
Mean PM Levels
PMio.2.5
Mean 12. 17
Range:
0-68
PMj.jO-2.5
Mean 10.86
(SD 5.37)
Range:
0-45
PM10.2.5
Mean
5.6 |ig/m3
Range:
0.1-24.6
Copollutants
Considered
PM25,PM10,
03,N02,CO,
SO2
PM25,PM10,
CO, S02,
NO2, O3
PM10,PM25,
CO,03,N02,
S02
Lag Structure Method, Findings,
Examined Interpretation
1 -7 Significant associations with
PM10.2.5 for either sex; no
significant associations with
PM2.5.
Significant associations with
PM10.2.5 for either sex; PM2 5
showed no significant effects
when other pollutants were
considered.
1-7 Significant associations for
PM10.2 5 with COPD
hospitalizations in the
Vancouver area. Also
statistically significant
associations with PM10, PM2 5,
and COH, but the effects are
not independent of other air
pollutants.
Quantitative Results
PMio-2.5 (IQR 8.4 ng/m3)
After controlling for gaseous
pollutants:
17% (3-3) 6d avg lag,
bidirectional case-crossover
15% (6-25) 6d avg lag, time-
series analysis.
PMi0.2.5(IQR6.5|ig/m3)
6-day avg lag
after adjustment for gases
boys
15% (2-30)
girls
18% (8-34)
PM10.2.5(IQR4.2ng/m3)
3-day avg lag
8% (2-1 5)
Significance lost with CO,
NO2andSO2butnotO3
-------
Table A5 (cont'd). Effects of PMi0-2.s on Daily Hospital Admissions
Reference, Study
Location and Period
Outcomes and Design Mean PM Levels _ ^ . , ,
& Considered
Lag Structure
Examined
Method, Findings,
Interpretation
Quantitative Results
.s (cont'd)
Yangetal. (2004)
Vancouver, British
Columbia
Junl,1995-Mar31,
1999
Logistic regression was
used to estimate the
associations between PM
and first hospitalization for
children <3 yr, a case-
control approach. Also,
analysis was conducted
using bidirectional-case
crossover analysis and
time-series analysis.
PM10.2.5
Mean
5.6 ug/m3
Range:
0-24.6
PM10, PM25, 0-7 The data indicated possible
CO, O3, NO2, harmful effects from coarse
SO2 PM on first hospitalization for
respiratory disease. No
significant association was
found between PM2 5 and first
hospitalization for respiratory
disease. PM2 5 concentrations
were relatively low.
In this study, only the case-
control and case-crossover
approaches support the notion
of effect of daily average
PM10_2 5 on first
hospitalization for respiratory
disease in early childhood. It
is not clear if these two
approaches overestimated or if
the time-series analysis
underestimated. For PM2 5,
the authors noted that
differences in findings may be
explained, in part, by TEOM
measurements, which may be
lower than those of filter-
based samples.
PM10.2.5(IQR 4.2 ug/m3)
Respiratory hospital
admissions, 3-day lag:
mean PM10.2.5
12% (-2-25)
*22% (2-48)
max PM10_2 5
13% (0-27)
* 140/0 (-1-32)
*after adjustment for gases
Associations with asthma and
pneumonia hospitalization not
statistically significant.
-------
Table A5 (cont'd). Effects of PMi0-2.s on Daily Hospital Admissions
Reference, Study
Location and Period
Outcomes and Design Mean PM Levels _ ^ . , ,
& Considered
Lag Structure
Examined
Method, Findings,
Interpretation
Quantitative Results
.s (cont'd)
Chen etal. (2005)
Vancouver, British
Columbia
Junl,1995-Mar31,
1999
>
A time-series analysis was
used to evaluate the
associations between
respiratory admissions and
PM, looking at first,
second, and overall hospital
admission for respiratory
disease among the elderly.
8,989 adults, >65 yr.
PM10.2.5
Mean
5.6 |ig/m
Range:
0.1-24.6
PM10,PM25,
CO, O3, NO2,
S02
1 -7 PM10.2.5 had a larger effect on
respiratory admissions than
PM2.5. For PMio-2.5, the
second and overall admission
rates were higher than the first
admission rate.
(1) People with a history of
respiratory admissions are at a
higher risk of respiratory
disease in relation to
particulate air pollution in
urban areas.
(2) Analyses based on overall
rather than repeated hospital
admissions lead to lower
estimates of the risk of
respiratory disease associated
with particulate air pollution.
PM10.2.5(IQR4.2|ig/m3)
3 day avg
first admission
3% (-2-9)
second admission
22% (0-36)
overall
6% (2-11)
No significant associations
with PM2 5
-------
Table A6. Effects of PMi.s on Daily Emergency Department Visits
Reference, Study
Location and Period
Outcomes and
Design
Mean PM
Levels
Copollutants
Considered
Lag Structure
Examined
Method, Findings,
Interpretation
Quantitative Results
PM2.5
Metzger et al. (2004)
Atlanta, GA
Aug 1998-Aug2000
to
Peel et al. (2005)
Atlanta, GA
Aug 1998-Aug2000
Emergency PM25
department visits for ug/m
total and cause-
specific Median:
cardiovascular 17.8
diseases by age
groups >19 yr and Range:
>65 yr. Time-series 8.9 to 32.3
study. 4, 407, 535,
ED V from 31 Atlanta
hospitals.
Emergency PM25
department visits for 19.2±8.9
total and cause-
specific respiratory Range:
diseases by age 8.9 to 32.3
groups 0-1, 2-18,
>19, and>65yr.
Time-series study.
NO2, SO2, CO, 0-2 Poisson GLM regression used
O3, PM10, for analysis. A priori models
PM10.2.5, specified a lag of 0 to 2 days.
ultrafine PM Secondary analyses performed
count, SO42~, to assess alternative pollutant
IT", EC, OC, lag structures, seasonal
metals, influences, and age effects.
oxygenated Cardiovascular visits were
hydrocarbons significantly associated with
several pollutants, including
NO2, CO, and PM2 5, but
not O3.
NO2, SO2, CO, 0-2 Poisson GEE and GLM
O3, PM10, regression used for analysis.
PM10.2.5, A priori models specified a lag
ultrafine PM of 0 to 2 days. Also performed
count, SO42~, secondary analyses estimating
IT", EC, OC, the overall effect of pollution
metals, over the previous 2 wk.
oxygenated Seasonal analyses indicated
hydrocarbons stronger associations with
asthma in the warm months,
especially for O3 and PM2 5
organic carbon. Quantitative
results not presented for
multipollutant, age-specific,
and seasonal analyses.
PM2.5 per 10 ug/m3
All ages:
Total cardiovascular:
3.3% (1,5.6)
Dysrhythmia:
2.1% (-3, 7.0)
Congestive heart failure:
5.5% (0.6, 10.5)
Ischemic heart disease:
2.3% (-2, 6.4)
Peripheral vascular and
cerebrovascular disease:
5(0.8,9.3)
PM25 per 10 ug/m3
All ages:
All available data:
Total respiratory:
1.6% (0,3.5)
Upper respiratory infections:
1.8(0,4.3)
Asthma:
0.5 (-2, 3.3)
Pneumonia:
1.1% (-2, 1.2)
COPD:
1.5 (-3, 6.3)
-------
Table A6 (cont'd). Effects of PM2.s on Daily Emergency Department Visits
Reference, Study
Location and Period
PM2.5 (cont'd)
Slaughter et al. (2005)
Spokane, WA
Jan 1995-Jun 2001
Outcomes and
Design
Study of hospital and
ED visits for
respiratory and
cardiac condition in
relation to PM!,
Mean PM
Levels
PM2.5 90% of
concentration
ranged between
4.2 and 20.2
Hg/m3
Copollutants
Considered
CO
Lag Structure
Examined Method, Findings, Interpretation
1-3 No overall association with
respiratory ED visits and any size
fraction of PM nor with cardiac
hospital admissions.
Quantitative Results
PM2.5 ED visits (10 |ig/m3
increase)
Lagl:
All respiratory:
PM2 5, PM10, and
PMi 0-2.5 using a log-
linear generalized
linear model for lags
0 to 3 and compared
results to a log-linear
generalized additive
model.
Acute asthma:
3% (-2, 9)
Cardiac admissions:
0% (-4, 3)
-------
Table A7. Effects of PMi0-2.s on Daily Emergency Department Visits
Reference, Study
Location and Period
PM10.2.5
Metzger et al. (2004)
Atlanta, GA
Aug 1998-Aug2000
Peel et al. (2005)
Atlanta, GA
Aug 1998-Aug2000
Outcomes and Design
Emergency department
visits for total and cause-
specific cardiovascular
diseases by age groups
>19yrand>65yr.
Time-series study.
4, 407, 535, EDV from
31 Atlanta hospitals.
Emergency department
visits for total and cause-
specific respiratory
diseases by age groups 0-
1,2-18,>19, and>65yr.
Time-series study.
Mean PM
Levels
PM10-2.5
Median:
9.1 ug/m3
Range (10%-
90%):
4.4-16.2
PM10-2.5
Median:
9.7 ug/m3
Range (10%-
90%):
4.4-16.2
Copollutants
Considered
N02, S02, CO,
O3, PMio, PM2.5,
ultrafine PM
count, SO42~,
IT", EC, OC,
metals,
oxygenated
hydrocarbons
N02, S02, CO,
03, PM10, PM2 5,
ultrafine PM
count, SO4 ~,
IT", EC, OC,
metals,
oxygenated
hydrocarbons
Lag
Structure
Examined Method, Findings, Interpretation
0-2 Poisson GLM regression used for
analysis. A priori models specified
a lag of 0 to 2 days. Secondary
analyses performed to assess
alternative pollutant lag structures,
seasonal influences, and age
effects. Cardiovascular visits were
significantly associated with
several pollutants, including NO2,
CO, and PM2 5, but not with
PM10.2.5 or O3.
0-2 Poisson GEE and GLM regression
used for analysis. A priori models
specified a lag of 0 to 2 days. Also
performed secondary analyses
estimating the overall effect of
pollution over the previous 2 wk.
No significant associations with
PMio-2.5- Some significant
associations with gaseous
pollutants and PM10. Quantitative
results not presented for
multipollutant, age-specific,
and seasonal analyses.
Quantitative Results
PM10.2.5 per 5 ug/m3
3 day avg lag
CVD visits:
1.2% (-1-4.0)
PM10.2.5 per 5 ug/m3
3 day avg lag
Respiratory visits:
3% (-2-2.5)
Slaughter et al. (2005)
Spokane, WA
Jan 1995-Jun 2001
Study of hospital and ED
visits for respiratory and
cardiac condition in
relation to PMi,PM2.5,
PMio, and PM10.2.5 using
a log-linear generalized
linear model for lags 0 to
3 and compared results to
a log-linear generalized
additive model.
PM10.2 5 90%
of
concentration
ranged
between 4.2
and 20.2
ug/m3
CO, PM10, PM25 1-3 No overall association with
respiratory ED visits and any size
fraction of PM nor with cardiac
hospital admissions.
PMio-2.5 ED visits (10 ug/m3
increase)
Lagl:
All respiratory:
Acute asthma:
3% (-2, 8)
COPD admissions:
l%(-7, 9)
-------
Table A8. Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
PM,
Pope et al. (2004)
Wasatch Front, UT
Winter 1999-2000 and
summer in Hawthorne
and winter 2000-2001
in Bountiful and
Lindon
Riedker et al. (2004)
North Carolina
Autumn 2001
Study of the effects of pollutants
on autonomic function measured
by changes in HRV and blood
markers of inflammation in a
panel of 88 elderly subjects
using regression analysis.
Nine healthy North Carolina
Highway Patrol troopers were
monitored on 4 successive days
for in-vehicle PM2 5, roadside
PM2 5, and ambient PM2 5
Ambulatory ECGs performed
and various blood indicators
measured.
PM2.5 (TEOM)
Mean (SD)
18.9±13.4
PM2 5 (ambient)
32.3 ug/m3
Range: 9.9-68.9
O3, CO, NO2
While this study observed statistical
associations between PM2 5 and HRV and
C-reactive protein (CRP), most of the
relevant variability in the temporal deviation
of these physiological endpoints was not
explained by PM2 5. These observations
therefore suggest that PM2 5 may be one of
multiple factors that influence HRV and
CRP.
The troopers showed significant and strong
increases of HRV, ectopic beats, blood
inflammation and coagulation markers, and
MCV in association with the in-vehicle
exposure to PM2 5 as indication of increase
of vagal activity.
PM2.5
100 ug/m3 increases
- 35 (SE = 8) in msec decline
SDNN
-0.81 (SE 0.17) mg/dL
increase in CRP
PM2 5 ug/m
In-vehicle 10 ug/m3
decreased lymphocytes
(-11%)
increased neutrophils (6%)
increased C-reactive protein
(32%)
ectopic beats (20%)
-------
Table A8 (cont'd). Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
PM2.5 (cont'd)
Schwartz et al. (2005b)
Boston, MA
12 weeks during the
summer of 1999
Park et al. (2005)
Greater Boston area,
MA
Nov 2000-Oct 2003
A panel study of 28 elderly
subjects (age 61-89 years).
Various HRV parameters were
measured for 30 min once a
week. Analysis using linear
mixed models with log-
transformed HRV
measurements. To examine
heterogeneity of effects,
hierarchical model was used.
Cross-sectional study examining
the effect of pollutants on HRV
in 497 adult males (mean age
72.7 years). Subjects were
monitored during a 4-min rest
period between 8 a.m. and 1 p.m.
Pollutant levels measured at
central site 1 km from study site.
Exposure averaging times of 4,
24, and 48 h investigated.
Modifying effects of
hypertension, IHD, diabetes,
and use of cardiac/anti-
hypertensive medications also
examined. Linear regression
analyses. This subject group is
from the VA Normative Aging
Study.
PM25 during
HRV
measurement:
Median:
10 ug/m3
BC Median:
1.0 ug/m3
BC,O3, CO,
SO2, NO2
PM2.5
Mean (SD):
1 1 .4 (± 8.0)
Range:
6.45-62.9
O3, PNC, BC,
NO2, SO2, CO
HRV parameters examined included:
SDNN, r-MSSD, PNN50, and LF/HF ratio.
Strongest association seen for BC, an
indicator of traffic particles. The random
effects model indicated that the negative
effect of BC on HRV was not restricted to a
few subjects. Subjects with MI experienced
greater BC-related decrements in HRV
parameters.
Of the pollutants examined, only PM2 5 and
O3 showed significant associations with
HRV outcomes. The 4-h averaging period
was most strongly associated with HRV
indices. The PM effect was robust in
models including O3. The associations
between PM and HRV indices were
stronger in subjects with hypertension (n =
335) and IHD (n = 142). In addition,
calcium-channel blockers significantly
influenced the effect of PM on low
frequency power. Limitations of this study
are the use of a short 4-min period to
monitor HRV and the lack of repeated
measurements for each subject.
PM2.5 24 h
Change in HRV parameters:
SDNN:
-2.6(0.8,-6.0)
r-MSSD:
-10.1 (-2.8,-16.9)
BC24h
SDNN
-5.1 (-1.5,-8.6)
r-MSSD:
-10.1 (-2.4,-17.2)
PM2.5 (8 ug/m3) 48 h
Change in low frequency
power:
Subjects with hypertension:
-10.5% (-25.8, 7.9)
Subjects without
hypertension:
-2.9% (-23.5, 23.2)
Subjects with ischemic heart
disease:
0.5% (-26.7, 37.7)
Subjects without ischemic
heart disease:
-7.0% (-21.3, 9.9)
LF/HF ratio increased 18.6%
(95% CI 4.1-35.2%)
-------
Table A8 (cont'd). Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
PM2.5 (cont'd)
Wheeler etal. (2006)
Atlanta, GA
Fall 1999 and spring
2000
Rich et al. (2005)
Boston, MA
Ml 995-Jul 2002
Rich et al., (2006)
Boston, MA
Jun 1995-Dec 1999
Examined pollutant effects on PM2,5 ug/m2 O3, CO, SO2,
HRV in 18 subjects with COPD Mean: 17.8 NO2
and 12 subjects with recent MI.
Data collected 7 days in fall and
spring. Associations examined
using linear-mixed effect model.
Age range 49-76 yrs.
In 203 patients with implantable PM2.5 (ug/m3) O3, BC, CO,
cardioverier defibrillators. Case- 1-h avg NO2, SO2
crossover study design used to Median: 9.2
examine association between air
pollution and ventricular PM2 5 (ug/m3)
arrhythmias. For each case 24-h avg
period, 3-4 control periods were Median: 9.28
selected. Various moving IQR: 7.8
average concentrations of
exposure considered - lags 0-2,
0-6, 0-23, and 0-47 h. Analysis
using conditional logistic
regression models.
In 203 patients with implantable PM2.5 (ug/m3) O3, BC, CO,
cardioverier defibrillators, were 1-h avg NO2, SO2
91 episodes of paroxysmal atrial Median: 9.2
fibrillation (PAF) in 29 subjects. Max: 84.1
Case-crossover design used to
examining association between PM2 5 (ug/m3)
air pollutants and PAF, with 24-h avg
matching control periods on Median: 9.8
weekday and hour within same Max: 53.2
calendar month. Conditional
logistic regression models used.
For COPD patients, PM2 5 exposure related
to an increase in SDNN. The results for MI
subjects were positive, but not significant.
Effects were modified by medication use,
baseline pulmonary function, and health
status. The small numbers studied limit the
study.
Associations were observed for PM2 5 and
O3 with a 24-h moving average, and for
NO2 and SO2 with a 48-h moving average.
In two-pollutant analyses, only PM2 5 and
O3 appeared to act independently.
Positive, but not significant, associations
reported with PM2 5, BC and NO2.
Significant associations reported with O3.
Authors note reduced statistical power for
PM2 5 and BC analyses due to missing data.
Conclude PAF is associated with exposure
to community air pollution.
PM2 5 4-h IQR (11.65 ug/m3)
COPD
8.3% (1.7, 15.3)
MI (IQR: -854 ug/m3)
2.9% (-7.8, 2.3)
Odds ratios:
24 h PM2.5 per 7.8 ug/m3 for
ventricular arrhythmia
1.19(1.02,1.38)
PM2 5 with O3 model:
All events:
1.18(1.01,1.37)
PM2.5 per 9.4 ug/m3 IQR,
0-hour lag:
OR 1.41 (0.82, 2.42)
BC per 0.91 ug/m3 IQR,
1-23 hour lag period:
OR 1.46 (0.67, 3.17)
-------
Table A8 (cont'd). Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
PM2.5 (cont'd)
Dockery et al. (2005)
Boston, MA
Ml 995- Jul 2002
oo
Effect of air pollution on
incidence of ventricular
arrhythmias was examined in
203 patients with implantable
cardioverter defibrillators using
time-series methods. Mean
follow-up period was
3.1 yr/subject. All subjects
located <40 km of air pollution
monitoring site. Two-day mean
air pollution level used in
analysis. Results analyzed by
logistic regression using GEE
with random effects. Modifying
effects of previous arrhythmia
within 3 days also examined.
PM2.5
Median:
10.3 ng/m3
IQR:
6.9 ng/m3
O3, BC, SO42~
particle
number, CO,
N02, S02
No associations were observed between air
pollutants and ventricular arrhythmias when
all events were considered. When only
examining ventricular arrhythmias within 3
days of a prior event, positive associations
were found for most pollutants except for
O3. The associations suggest a link with
motor vehicle pollutants.
PM2.5 (6.9 |ig/m3)
Odds ratios:
All events:
1.08(0.96,1.22)
Prior arrhythmia event
<3 days:
1.60(1.30,1.96)
Prior arrhythmia event
>3 days:
0.98(0.86,1.12)
-------
Table A8 (cont'd). Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
VO
PM2.5 (cont'd)
Rich et al. (2004)
Vancouver, British
Columbia, Canada
Feb-Dec 2000
Gold et al. (2005)
Boston, MA
Summer of 1999
Case-crossover study
design used to investigate
association between air pollution
and cardiac arrhythmia in
patients aged 15-85 yr (n = 34)
with implantable cardioverter
defibrillators. Controls periods
were selected 7 days before and
after each case day. Analysis
using conditional logistic
regression.
Study of associations between
ambient pollutants and
ST-segment levels in repeated
measures involving
269 observations in 24 subjects
61-88 yr; each observed 12 times
between June-September
involving HoIter recording.
PM2.5, BC, and CO were
collected at 5 central sites 0.5 km
from residences of subjects.
PM2.5
Mean:
8.2 ug/m3
IQR: 5.2
PM2.5 12 h
Median:
9.8 ug/m3
BC
Median:
1.14 ug/m3
03, EC, OC,
S042\ CO,
NO2, SO2
No consistent association between any
of the air pollutants and implantable
cardioverter defibrillators discharges.
CO, 03,
NO2, SO2
Elevated BC predicted increased risk of ST-
segment depression with the strongest
association being for the 5-h lagged value.
Odds ratios were less than
1.0 at all lags (0, 1,2, 3) for
PM2.5.
BC 12 h mean estimated
overall ST-segment change:
-0.08mm
p = 0.03
-------
Table A8 (cont'd). Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
PM2.5 (cont'd)
Dubowsky et al. Investigation of ambient PM25
(2006) particles and markers of Mean (SD)
St. Louis, MO systemic inflammation among Hg/m3
Mar-June 2002 repeated measures from 44 16(6.0)
subjects (>60yr). Trips from Range 6.5-28
senior home in diesel bus into
St. Louis. Analyzed using linear
mixed model.
CO, NO2, Modest positive association found between
SO2, O3 fine particles and indicators of systemic
inflammation with larger association
suggested for individuals with diabetes,
obesity, and hypertension. Positive
associations found for longer moving
averages.
PM2.54-hIQR(5.4|ig/m3)
5-day mean PM2 5 (6.1)
14% increased CRP (90%
CI: 5.4 to 37%) for all
individual and 81% (90% CI:
21, 172) for those with
diabetes, obesity,
hypertension
-------
Table A8 (cont'd). Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
PM2.5 (cont'd)
>
O'Neill et al. (2005)
Boston, MA
May 1998-Jan 2000
Baseline period
Time trial
2000-2002
Schwartz et al. (2005a)
Boston
2000
Sullivan et al. (2003)
Western Washington
State
1985-1994
270 patients with diabetes or at
risk for diabetes were studied in
relation to various pollutant
levels and evaluated for
association with vascular
reactivity. Linear regressions
were fit to the percent change in
brachial artery diameter (flow-
mediated and nitroglycerin-
mediated) into particulate
pollutant index and other factors.
Examined the associations
between PM2.5 and HF in 497
subjects in Normative Aging
Study (NAS) using linear
regression controlling for
covariates.
PM25
(1998-2002)
Mean (SD):
11.5 (6.4) ug/m3
Range:
1.1-40.0
PM2.5
Mean:
11.4 ug/m3
(8.0 SD)
A case-crossover study of 1,206 PM
out-of-hospital cardiac arrest (nephelometry,
among persons with (n = 774) km ' bsp)
and without (n = 432) clinically Mean: 0.71
recognized heart disease and Min: 0.05
daily measures of PM2 5. Max: 5.99
SO42 , BC, PM2 5 was associated with nitroglycerin-
ultrafine mediated reactivity; an association was also
reported with ultrafine particles. Effects
were stronger in type II than type I diabetes.
BC and SO4 ~ increases were associated
with decreased flow-mediated reactivity
among those with diabetes. Although the
strongest associations were with the 6-day
moving avg, similar patterns and
quantitatively similar results appear in the
other lags.
— In subjects without the allele (for
glutathione-S-transferase Ml) an increase in
PM2 5 during the 48 h before HF (high-
frequency component of HRV)
measurement was associated with a
decrease in HF. In subjects with the allele,
no effect was noted. The effects of PM2 5
on HR appear to be mediated by ROS,
which may be a lag pathway for effects of
combustion particles.
SO2, CO There was no consistent association
between increased levels of fine particular
matter and risk of primary cardiac arrest.
This differs from results seen in other
airsheds.
PM2 5 6-day moving average
per IQR
Nitroglycerin-mediated
reactivity:
-7.6%;95%CI: 12.8 to
-2.1
PM2 5 ug/m
10 ug/m3 increase
HF
-34% (-9%,-52%)
For cases with preexisting
cardiac disease
OR = 0.97 (0.89-1.07)
-------
Table A8 (cont'd). Effects of Acute PM2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
to
PM2.S (cont'd)
Mar etal. (2005)
Seattle 1999-2001
DeMeo et al. (2004)
Boston
July-August 1999
Lipsett et al. (2006)
Coachella Valley, CA
Feb-May 2000
Ebelt et al. (2005)
Vancouver, Canada
Summer 1998
Study of pollutants in relation to
health parameters in 88 subjects
(>75yrsofage). HR, BP, and
arterial oxygen saturation was
examined using GEE.
Investigated the association
between PM2 5 and oxygen
saturation during a 12-wk
repeated measures study of
28 older Boston residents using
a fixed effects model/GLM.
Weekly ambulatory ECG's
recorded, using Holter monitor,
in 19 nonsmoking adults. Mixed
linear regression models used
with random effects parameters
for inter-individual variation.
Subjects' residences w/in 5 miles
of one of two PM monitoring
sites.
Outcomes: FEVb ectopy, blood
pressure, heart rate and
variability
16 COPD patients, Vancouver,
summer 1998, each subject
measured 7 days
mixed models
PM2 5 outdoor
ug/m3 range
from 9.0 (±4.61)
for healthy to
12.5 (±7.9) for
CVD subjects
PM2 5 ug/m3
IQR(11.45)
PM2.5 ug/m3
mean (range):
Indio:
23.2 (6.3-90.4)
Palm Springs:
14 (4.7-52)
PM2.5
Mean: 11.4
PM,,
PM10, PM10.2.5,
03
PM10_25, and
PM10
Ambient
concentrations
and exposures
Healthy subjects had decreases in HR
associated with PM2 5. SaO2 does not have
a consistent response to PM air pollution.
Sample size was a limitation in this study.
Demonstrated a statistically significant
effect of ambient particle air pollution on
decreased oxygen saturation at rest in a
population of free-living older individuals
with a more-significant interaction in those
taking p-blockers. These small changes
may be related to a pulmonary vascular
and/or inflammatory cascade.
No significant associations reported with
PM2 5; however were significant
associations with PM10.2.5.
PM2 5 significantly associated with
decreased systolic blood pressure and
increased ectopic heart beats
Use of ambient exposure instead of ambient
concentration yields more meaningful
results. Suggest that other Panel studies
which depend on ambient concentrations or
total personal exposure could fail to observe
effects that existed, -day
PM2 5 outdoor change in
heart rate
-0.75 bpm(-1.42,-0.07)
PM2.5
Oxygen saturation
(6-h rest period)
-0.173% (-0.345,-0.001)
Coefficient XI000 (p-value):
SDNN:
24hPM2.5:-1.63 (0.49)
6hPM2.5: -1.21(0.24)
4hPM25: -0.55(0.64)
2hPM2.5:-0.37 (0.72)
No quantitative results
reported. Results presented
in figures only.
-------
Table A9. Effects of Acute PMio_2.s Exposure on Cardiovascular Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
PM,,
>
OJ
Lipsett et al. (2006)
Coachella Valley, CA
Feb-May 2000
Ebelt et al. (2005)
Vancouver, Canada
Summer 1998
Weekly ambulatory ECG's PM10.2.5 ug/m
recorded, using Holter monitor, Mean
in 19 nonsmoking adults. Mixed (difference
linear regression models used between PM10
with random effects parameters and PM2 5):
for inter-individual variation. Indio:
Subjects' residences w/in 5 miles 23.2 (6.3-90.4)
of one of two PM monitoring Palm Springs:
sites. 14 (4.7-52)
Outcomes: FEVb ectopy, blood PM10_2 5
pressure, heart rate and Mean: 5.6
variability
16 COPD patients, Vancouver,
summer 1998, each subject
measured 7 days
mixed models
PM10,PM25,
03
PM25andPM10
Ambient
concentrations
and exposures
Significant associations between PM10.2.5
(2h, 4h and 6h avg) and SDNN, SDANN.
No significant associations reported with
PM2.5.
Associations between PM10_2 5 and
decreased systolic blood pressure and
increased ectopic heart beats similar to
PM2 5 in size, but not statistically significant
Use of ambient exposure instead of ambient
concentration yields more meaningful
results. Suggest that other Panel studies
which depend on ambient concentrations or
total personal exposure could fail to observe
effects that existed.
Coefficient XI000 (p-value):
SDNN:
24hPM10.2.5:0.23 (0.81)
6hPM10.2.5: -1.84(0.006)
4hPM10.2.5: -1.19(0.024)
2hPM10.2.5:-0.72 (0.017)
No quantitative results
reported. Results presented
in figures only.
-------
Table A10. Effects of Acute PM2.s Exposure on Various Respiratory Outcomes
Reference, Study
Location and Period
Outcomes and Design
Mean PM Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
PM2.5
Gent et al. (2003)
Southern New England
Apr-Sept 2001
Rabinovitch et al.
(2006)
Denver, CO
winters 2001-2002 and
2002-2003
Mar et al. (2004)
Spokane, WA
Mar 1997-Jun 1999
Panel study of 271 children (age
<12 years) with active, doctor-
diagnosed asthma followed over
183 days for respiratory symptoms.
For analysis, cohort split into two
groups: 130 who used maintenance
medication during follow-up and
141 who did not, on assumption
that medication users had more
severe asthma. Logistic regression
analyses performed.
A school-based cohort study of
children aged 6-13 years with
physician-diagnosed asthma (n =
92), with data on bronchodilator
use, urinary leukotriene E4, and
reported respiratory infections.
Hourly and 24-h avg PM2 5 data
available from station 2.7 mi from
school, using TEOM and FRM
monitors.
Evaluated the effects of PM2 5 on
respiratory symptoms in both
adults and children with asthma
(16 adults, 9 children) using
logistic regression.
PM2.5
Mean: 13.1 (SD
7.9) ug/m3
PM25(ug/m3)
TEOM:
Daily mean (SD)
year 1:6.5 (3.2)
year 2: 8.2(3.7)
Morning mean (SD)
year 1:7.4 (4.7)
year 2: 9.1(5.0)
Morning max (SD)
year 1:15.5 (9.5)
year 2: 18.4(9.6)
FRM:
Daily mean (SD)
yearl: 11.8(7.2)
year 2: 11.2(5.5)
PM2.5
ug/m3
Mean range over
three years
8.1 to 11.0
03
PM10,PM10.25,
PMj
Correlation between daily PM2 5
and 1-h max O3 was 0.77 during
this warm-season study.
Significant associations between
PM2 5 and symptoms in some
models, but not significant in
two-pollutant models.
Significant associations between
O3 and symptoms only in
medication users, a group
considered to be more sensitive.
Peak PM2 5 associated with
bronchodilator use and urinary
LTE4. Stronger associations
reported with morning mean or
max concentrations than daily
mean; also stronger associations
for severe asthmatics compared
with mild/moderate asthmatics.
In children a strong association
was reported between cough and
PM10, PM25, PM10_2.5, and PMj.
No association for symptoms in
adults.
PM2.5
Shortness of breath
OR for levels >19 ug/m3 on
previous day:
1.26(1.02,1.54)
with O3:
1.20(0.94,1.52)
Morning max PM2 5
per 12 ug/m3:
Increased bronchodilator use
in severe asthmatics:
8.1% (2.9,13.4)
In mild/moderate asthmatics:
1.6% (-2.2, 5.4)
PM25
(10 ug/m3)
Cough
Lagl
1.21(1.00,1.47)
-------
Table A10 (cont'd). Effects of Acute PM2.s Exposure on Various Respiratory Outcomes
Reference, Study
Location and Period
Outcomes and Design
Copollutants
Mean PM Levels Considered
Findings, Interpretation
Quantitative Results
>
(^
PM2.S (cont'd)
Jansen et al. (2005)
Seattle
2002-2003
Koeningetal. (2005)
Seattle, WA
winter 2000 to spring
2001
Mar et al. (2005)
Seattle, WA
1999-2001
Study of 16 older asthma COPD
patients' exposure to pollutants in
relation to various health outcomes
from data collected daily for
12 days analyzed using a linear
mixed effect model.
Examined indoor-generated (Ejg)
and outdoor generated (Eag) PM
pulmonary effects on 19 children
with asthma using exhaled nitric
oxide (eNO), using a linear model
and also by GEE.
Evaluated hourly exposures to
PM2 5 and FENO in 19 children with
asthma using a polynomial
distributed lag model, single and
lag model taking into account
ambient NO levels and use of
inhaled corticosteroids.
PM2.5
Outdoor
IQR (SD)
10.47 (8.87) ug/m3
PM2.5
Outdoor (Eag)
Mean: 11.1 ug/m
Range: 2.8-40.4
PM2.5
1 havg
Ranges from
8.3 ug/m3 at 3-h lag
to 15.2at8-hlas
BC, PM10 FENO (fractional exhaled nitric
oxide) increased in relation to
increasing PM2 5. No association
was found between PM and
changes in spirometry, blood
pressure, pulse rate, or SaO2
(oxygen saturation of blood).
— Based on a recursive model with a
sample size of 8 children. Eag was
marginally associated with
increases in eNO; no association
reported with Ejg. Effects were
only seen in children not using
corticosteroid therapy.
— FENO was associated with hourly
averages of PM25 up to 10-12 h
after exposure. No effects were
seen in subjects on inhaled
corticosteroids. Similar results
were obtained for both analysis
methods.
PM2.5
10 ug/m3 increase
4.2 ppb
(95% 1.3-7.1)
Increase in FENO for asthma
subjects (n = 7)
PM2.5 (10 ug/m3)
increase in eNO
5.6 ppb
(CI: -0.6,11.9)
p = 0.08
PM25 (10 ug/m3)
Single lag
6.9 ppb
(3.4 to 10.6)
-------
Table A10 (cont'd). Effects of Acute PM2.s Exposure on Various Respiratory Outcomes
Reference, Study
Location and Period
Outcomes and Design
Copollutants
Mean PM Levels Considered
Findings, Interpretation
Quantitative Results
PM2.S (cont'd)
Adamkiewicz et al.
(2004)
Steubenville, OH
Sept-Dec 2000
Giradot et al. (2006)
Great Smoky
Mountains NP,
NC-TN
Fall 2002, summer
2003
Delfmo et al. (2004)
Alpine, CA
Aug-Oct 1999,Apr-
Jun 2000
Breath samples collected weekly in PM2 5
panel of 29 elderly subjects, and
analyzed for FEN0. Indoor NO
measured in study room at time of
breath sample collection. Ambient
measurements from a central
monitoring site.
Investigated lung function in 354
adult-hikers over 71 days in
relation to pollutant exposure using
multiple linear regression models
by ordinary least squares
estimation. Hikers averaged 5.Oh
of exercise.
Panel study of 19 asthmatic
children (age 9-17 years) followed
daily for 2 weeks to determine
relationship between air pollutants
and FEVj. Linear mixed model
used for analysis. Personal PM
measurements made with
dataRAM, which approximate
PM2 5 measurements.
Mean (max, IQR):
Ih:
19.5(105.8,17.9)
24h:
19.7(57.8,17.7)
PM2.5
Average daily
13.9±8.2 ng/m
Range
1.6-38.4 ng/m
PM2.5 (24-h)
Outdoor mean (SD)
10.3 (5.6) ng/m3
Outdoor home:
11.0 (5.4) ng/m3
Indoor home:
12.1(5.4)|ig/m3
Personal PM:
37.9 (19.9) ng/m3
NO, NO2, O3, Consistent positive, significant
SO2 associations reported between
FENO and PM2 5, also with
ambient and indoor NO levels.
No associations reported with
NO2, O3, or SO2.
In 2- and 3-pollutant models,
PM2 5 remains significant, while
ambient and indoor NO
associations are reduced and lose
significance.
O3 Findings suggest that low levels
of pollutant exposure over several
hours may not result in significant
declines in lung function in
healthy adults engaged in exercise
or work.
PM10, O3 Significant declines in FEV]
associated with various PM
indices but not ambient O3 levels.
Stronger associations with
multiday moving averages for
both personal and stationary-site
PM.
FENO change per IQR:
lhPM25:
1.36 ppb change (0.58, 2.14)
24hPM25:
1.45 ppb change (0.33, 2.57)
The coefficient for the
percentage change in FEVi as
a function of PM2 5 adjusted
for covariates 0.003%/|ig/m3
p = 0.937
PM2.5
Percent predicted FEV! with
PM from previous 24 h:
per 7.5 |ig/m3 central site:
-0.7% (-1.9, 0.4)
per 7.1 |ig/m3 outdoor home:
-1.1% (-2.5, 0.1)
per 6.7 ng/m3 indoor home:
-1.6% (-2.8, -0.4)
per 30 ng/m3 personal:
-5.9% (-10.8, -1.0)
-------
Table A10 (cont'd). Effects of Acute PM2.s Exposure on Various Respiratory Outcomes
Reference, Study
Location and Period
Outcomes and Design
Copollutants
Mean PM Levels Considered
Findings, Interpretation
Quantitative Results
PM2.S (cont'd)
Newhouse et al. (2004)
Tulsa, OK
Sep-Oct 2000
Sinclair and Tolsma
(2004)
Atlanta, GA
Aug 1998-Aug2000
Panel study of 24 subjects aged 9-
64 years with physician diagnosis
of asthma. Performed PEF twice
daily (morning and afternoon), and
reported daily respiratory
symptoms and medication use.
Forward stepwise regression and
Pearson correlation analysis.
Respiratory medical visit data
collected by Kaiser Permanente,
including ambulatory care visits for
asthma (adult and child), UPJ and
LPJ. ARIES air quality data used.
Poisson GLM regression used for
analysis. A priori models specified
a lag of 0 to 2 days (average). Also
performed analyses using average
lag periods of 3-5 and 6-8 days.
PM2.5
Mean (range):
13.07(0.50-29.90)
PM2.5
mean (SD)
17.62 (9.32)
O3, CO, SO2, Significant associations reported
pollen, fungal between O3 and FEV! and various
spores respiratory symptoms. In multi-
pollutant models, including pollen
and mold spores, maximum PM2 s
negatively associated with cough,
wheeze and shortness of breath;
no discussion of these findings.
NO2, SO2, CO, Adult asthma visits associated
O3, PMio, with ultrafine number count, and
PMio-2.5, negatively associated with PM2 5
ultrafine PM mass. Child asthma associated
count, SO42~, with OHC (0-2 day) and with
Ff, EC, OC, PM10, PM10.2 5, EC and OC (3-5
metals, day). LPJ associated with PM25
oxygenated acidity and SO2 (0-2 day) and
hydrocarbons with PM10, PM10.2.5, EC, OC and
(OHC) PM2 5 water soluble metals. For
URI, significant positive
associations with ultrafine PM (0-
2) and PM10.2.5 (3-5 day) but
negative associations with PM2 5,
SO2 and sulfate.
No quantitative results
PM2.5
Quantitative results only for
significant associations
Adult asthma, per 9.32 |ig/m3
RR= 0.906
LRI visits:
EC, per 1.38 |ig/m3
RR= 1.079
OC, per 2.2 ng/m3
RR= 1.05
PM2 5 acidity, per 0.02 ng/m3
RR= 1.13
PM2 5 water-soluble metals,
per 0.03 |ig/m3
RR= 1.062
-------
Table A10 (cont'd). Effects of Acute PMi.s Exposure on Various Respiratory Outcomes
Reference, Study
Location and Period
Outcomes and Design
Mean PM Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
oo
PM2.S (cont'd)
Lewis et al. (2005)
Detroit
Winter 2001 thru
Spring 2002
Silkoffetal. (2005)
Denver, CO
winters 1999-2000
and 2000-2001
Ebelt et al. (2005)
Vancouver, Canada
Summer 1998
A longitudinal cohort study of
primary-school age children with
asthma, primarily African
American and from low-income
families, examined the relationship
between lung function and PM and
O3 using GEE, considered effects
modification by maintenance
corticosteroid use and URI as
recorded in diaries of 86 children
in six 2-wk seasonal assessments
for various lags.
Two panels of adults with COPD
(n = 16 and 18 for winters 1 and 2,
respectively), with diary of twice-
daily PEF and FEVb symptoms
and bronchodilator use. 4-month
study period included biweekly
visits to collect data.
Outcomes: FEVi, ectopy, blood
pressure, heart rate and variability
16 COPD patients, Vancouver,
summer 1998, each subject
measured 7 days
mixed models
PM25
IQR
12.5 ug/m3
PM2.5 (ug/m3)
Mean (SD):
winter 1: 9.0(5.2)
winter 2: 14.3 (9.6)
PM10,CO,N02
PM2.5
Mean: 11.4
PM10.2 5, and
PM10
Ambient
concentrations
and exposures
Positive associations between
PM2 5 and O3 with diurnal
variability in FEVi, and negative
associations with lowest daily
FEVi; though many not
statistically significant.
Authors conclude that ambient air
pollution exposure associated
with adverse effects on
pulmonary function among at-risk
children with asthma in Detroit.
In winter 1, no evidence of
detrimental effects on lung
function; some significant
associations between PM10, NO2
and CO with increased lung
function.
In winter 2, significant
associations reported between
PMio, NO2 and CO and increased
medication use or symptoms.
No significant associations
reported with PM2 5.
Decrease in AFEV1 associated
with ambient exposure for all PM
components
Use of ambient exposure instead
of ambient concentration yields
more meaningful results. Suggest
that other Panel studies which
depend on ambient concentrations
or total personal exposure could
fail to observe effects that existed.
PM2 5 Lag 1
Children on maintenance CS
FEV] diurnal variability
1.61 (-0.50,3.72)
single pollutant model
No quantitative results
reported. Results presented in
figures only.
No quantitative results
reported. Results presented in
figures only.
-------
Table All. Effects of Acute PMio-2.s Exposure on Various Respiratory Outcomes
Reference, Study
Location and Period
Outcomes and Design
Copollutants
Mean PM Levels Considered
Findings, Interpretation
Quantitative Results
PM10.2.5
Sinclair and Tolsma
(2004)
Atlanta, GA
Aug 1998-Aug2000
Mar et al. (2004)
Spokane, WA
Mar 1997-Jun 1999
Ebelt et al. (2005)
Vancouver, Canada
Summer 1998
Respiratory medical visit data
collected by Kaiser Permanente,
including ambulatory care visits
for asthma (adult and child), URI
and LRI. ARIES air quality data
used. Poisson GLM regression
used for analysis. A priori models
specified a lag of 0 to 2 days
(average). Also performed
analyses using average lag periods
of 3-5 and 6-8 days.
Evaluated the effects of PM2 5 on
respiratory symptoms in both
adults and children with asthma
(16 adults, 9 children) using
logistic regression.
Outcomes: FEV1; ectopy, blood
pressure, heart rate and variability
16 COPD patients, Vancouver,
summer 1998, each subject
measured 7 days
mixed models
PM10-2.5
mean (SD)
9.67 (4.74) ug/m3
PMlQ-2.5
Not reported
PMiQ-2.5
Mean: 5.6
NO2, SO2, CO,
O3, PMio, PM2.5,
ultrafine PM
count, SO42~,
Lf, EC, OC,
metals,
oxygenated
hydrocarbons
(OHC)
PM10,PM25,
PMj
PM2.5 and PMio
Ambient
concentrations
and exposures
Adult asthma visits associated
with ultrafine number count, and
negatively associated with PM2 5
mass. Child asthma associated
with OHC (0-2 day) and with
PMio, PMio-2.5, EC and OC (3-5
day). LRI associated with PM2 5
acidity and SO2 (0-2 day) and
with PM10, PM10_2.5, EC, OC and
PM2 5 water soluble metals. For
URI, significant positive
associations with ultrafine PM (0-
2 day) and PM10.2.5 (3-5 day) but
negative associations with PM2 5,
SO2 and sulfate.
In children a strong association
was reported between cough and
PMio, PM2.5, PMio-2.5, and PMj.
No association for symptoms in
adults.
These findings also suggest that
both larger and smaller particles
can aggravate asthma symptoms
Decrease in AFEV1 associated
with ambient exposure for all PM
components
Use of ambient exposure instead
of ambient concentration yields
more meaningful results. Suggest
that other Panel studies which
depend on ambient concentrations
or total personal exposure could
fail to observe effects that existed.
PM10.2.5
Per 4.74 ug/m3
LRI visits:
RR= 1.07
Child asthma:
RR= 1.053
URI visits:
RR= 1.021
PM
(10 ug/m3)
Cough
Lagl
OR 1.06 (1.02, 1.10)
No quantitative results
reported. Results presented in
figures only.
-------
Table A12. Effects of Acute PM2.s Exposure on Birth Outcomes
Reference, Study
Location and Period
Outcomes and Design
Copollutants
Mean PM Levels Considered
Findings, Interpretation
Quantitative Results
PM2.
Karr et al. (2006)
South Coast Air
Basin, CA
1995-2000
Linked hospital discharge for
bronchiolitis during first year of
life with PM2.s using closest
measurements based on zip code.
Case-crossover design used, with
lag periods of 1-2, 3-5 and 6-8
days.
PM2.5
Means range from
23.3 to 24.1 ng/m3,
for different lag
periods
CO, NO2 No significant associations
reported for any of the pollutants.
PM2.5 (10 |ig/m3)
1-2 day lag:
OR 0.96 (0.94-0.99)
3-5 day lag:
OR 0.98 (0.96, 1.00)
6-8 day lag:
OR 0.96, (0.93, 0.98)
-------
Additional Studies Examining Issues Related to Interpreting the PM-Morbidity
Relationship:
U.S. and Canadian studies:
Liao et al. (2004): A population-based cross-sectional study of 5,431 members of the
Atherosclerosis Risk in Communities cohort study in Minneapolis, MN; Jackson, MS; and
Forsyth County, NC. Significant associations were reported between PMio and decreased heart
rate variability and increased heart rate. The mean PMio concentration was 24.3 |ig/m3.
Delfmo et al. (2002): Panel study of 22 asthmatic children (9-19 years) with diary of symptoms,
medication use and presence of respiratory infection or hay fever for 61 days. Asthma symptoms
were significantly associated with 1-h and 8-h PMio (both lag 0 and 3-day average), but
association with 24-h PMio was not significant. Also significant associations were observed
between asthma symptoms and 1-h ozone (lag 0) and 8-h max NO2 (lag 0). Associations were
stronger in children not using anti-inflammatory medication than in children on medication.
Evidence of significant interaction between 1-h PMio and 8-h max NO2; but in 2-pollutant
models, both lose significance.
Dugandzic et al. (2006): Linked 1998-2000 data from Nova Scotia Atlee Perinatal Database
with air pollution data, using geocoding to link to monitoring site nearest the home. Significant
associations were reported between LEW and exposures during the first trimester for PMio
(RR = 1.33, 1.02-1.74 for >75th percentile) and SO2(RR= 1.36, 1.04-1.78 for >75th percentile).
No associations were reported with pollution exposures during the second and third trimesters.
The mean PMio concentration (trimester average) was 17 |ig/m3.
Letz and Quinn (2005): No correlation observed between Air Quality Index values for PM2 5 or
ozone with emergency department visits (n = 149) for asthma in military trainees.
Sagiv et al. (2005): Using a time-series analysis, this study investigated the effect of ambient
outdoor PMio on risk for preterm delivery counts in three Pennsylvania Counties and the City of
Philadelphia from Jan 1, 1997-Dec 31, 2001. Results suggest an increase in preterm birth risk
with exposure to PMio, with a RR of 1.07 (0.98, 1.18) per 50 |ig/m3 PMio (6 weeks preceding
birth). The mean PMio concentration was 25.3 |ig/m3.
International studies:
Romieu et al. (2005): A randomized double-blind trial, evaluating effect of supplementation with
omega-3 fatty acids on reduction of PM2.s-related HRV reduction. In 50 subjects living in
nursing home with 6-month follow-up, HRV high-frequency change associated with 8 |ig/m3
PM2.5 was -0.54% (95% CI -72, -24) with supplementation, and -7% (95% CI -20, +7) without
supplementation. The mean PM2 5 concentration was 19.6 |ig/m3
Sorensen et al. (2003): In Copenhagen, personal exposure to PM2.5 was associated with
cardiovascular biomarkers (RBC count, hemoglobin) in women, but not men. No significant
associations were observed with ambient PM2 5 concentrations; however, personal exposure to
carbon black was associated with plasma protein oxidation.
Boezen et al. (2005): In a panel of 327 elderly patients, symptom diaries and twice-daily PEF
were collected for 3 months. Statically significant associations were reported for PMio, BS and
A-51
-------
NO2 with respiratory symptoms in subjects with airway hyperresponsiveness and high IgE levels
(AHR+/IgE+). There were no significant associations with the pollutants in the AHRVIgE"
subjects.
Chan et al. (2004): In Taipei, Taiwan, continuous measurements of ECG and personal exposure
measurements of ultrafme particles (NCo.o2-i) (time period not indicated) were collected for a
panel of nine young adults (19-29 years) and ten elderly patients (42-79 years). Decreases in
HRV measures (SDNN, r-MSSD, LF, HF) were reported with personal exposure to NCo.o2-i for
both age groups.
Chuang et al. (2005): In Taipei, Taiwan, ECG and PM were measured continuously in a panel of
26 subjects (ten with coronary heart disease, 16 with hypertension) from November 2002
through March 2003; HRV measurements were used only for times when the subjects were
awake. For all PM indicators, there were associations with decreases in several HRV
measurements—SDNN, r-MSSD, LF, and HF—and positive associations with LF/HF.
Associations were only significant for PM0.3_i.o; the authors concluded that HRV was associated
with PMo.3-i.o, but not PMi.o-2.5 or PM2.s_io.
Lanki et al. (2006): In Helsinki, levels of PM2 5 were related to ST-segment depression in 45
elderly (mean age 68.2 yrs [6.5]) nonsmoking subjects with stable coronary heart disease.
Depression of ST-segment indicates a number of conditions including myocardial ischemia.
The mass of fine particles was apportioned between five sources. ST-segment depression was
associated with PM2 5 originating from local traffic (RR = 1.53 [1.19-1.97] per 1 |ig/m3, at a
2-day lag) and long-range transport (RR =1.11 [1.02, 1.20] per 1 |ig/m3). In multipollutant
models where indicator elements were used for sources, only the absorbance (elemental carbon)
indicator for local traffic and other combustion was associated with ST-segment depression.
The mean PM2 5 concentration was 12.8 |ig/m3
Penttinen et al. (2006): In a panel study of 57 adult asthmatics in Helsinki, subjects were
followed for 181 days, and principal component analysis was used to evaluate source
apportionment based on PM2 5 mass. Decreases in morning PEF was linked to PM2 5 from long-
range transport and local combustion sources (1- and 2-day lags). There were no associations
with PM2.5 derived from oil combustion, soil, or sea salt.
Ruckerl et al. (2006): Blood parameters were measured in 57 male patients with coronary heart
disease living in Erfurt, Germany, and positive associations were reported between elevated
C-reactive protein and all measured pollutants - PMio, PM2.5, accumulation mode particles
(PMo.i-i), ultrafme particles, ED, OC, NO2 and CO. The authors reported the strongest
association with accumulation mode particles (3-day lag); significant associations were also
observed with PMio, ultrafme particles, NO2 and CO (2-day lag strongest). Positive associations
were also reported between ICAM-1 (indicator of endothelial dysfunction) and PMio, PM2.5,
accumulation mode particles, EC and OC. No consistent associations were observed with
various clotting factors.
Pekkanen et al. (2002): In three panels of elderly subjects in Amsterdam, Erfurt, and Helsinki
(ULTRA study), biweekly submaximal exercise tests were done for six months. ST-segment
depression was significantly associated with both PM2.5 mass (OR 2.84, 1.42-5.66, 2-day lag)
and ultrafme particles (OR 3.14, 1.56-6.32), and also with NO2 and CO. No consistent
associations were reported with thoracic coarse particles.
A-52
-------
de Hartog et al. (2003): Three panels of elderly (aged 50+ years) subjects in Amsterdam, Erfurt,
and Helsinki (ULTRA study) were followed for six months, with daily diaries and biweekly
clinic visits. Prevalence of shortness of breath and phlegm were associated with PM2.5, but not
with ultrafine particles, CO or NO2. The authors concluded that PM2.5 was more closely
correlated with cardiorespiratory symptoms than ultrafine particles.
Timonen et al. (2005): Repeated ECG measurements in panels of elderly subjects in
Amsterdam, Erfurt, and Helsinki (ULTRA study) over six months. There were no consistent
associations between HRV measurements and PM2 5, but a pattern of generally positive
associations between ultrafine particles and HF were reported, along with negative associations
between ultrafine particles and LF/HF ratio.
Henneberger et al. (2005): Repeated ECG measurements in a panel of 56 patients with ischemic
heart disease in Erfurt, Germany. PM2.5 (6h average) was significantly associated with decreased
T-wave amplitude, increased T-wave complexity and nearly significant with increased variability
of the T-wave complex. Associations with 6h PM2 5 were stronger than those with 24h PM2 5
averages. Similar associations were seen with 6h ultrafine particles, accumulation mode
particles, OC and EC, although most were not statistically significant. Significant associations
were reported between OC and QT duration.
A-53
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Table A13. Results of Epidemiologic "Intervention" Studies
Reference, Study
Location and Period
U.S. studies
Lwebuga-Mukasa et al,
2003
Buffalo, NY
European studies
Bayer-Oglesby et al.,
2005
9 Swiss communities
1991-2001
Outcome Measure
Hospital admissions
and emergency
department visits
for respiratory
illnesses
Respiratory
symptoms via
questionnaires,
collected in 1 992-
1993 and 1998-
2001
Change in
pollution/emissions
50% drop in total
traffic at Peace
Bridge following
9/11/2001
General air pollution
abatement measures
in Switzerland
resulting in reduced
PM10 concentrations
Reported PM Levels
(ug/m3)
PM10 concentration declined
an average of 9.8 ug/m3 over
all communities, ranged from
4.0 to 12.7 ug/m3 declines.
Mean PM10 concentrations in
1997-2000 ranged from 10 to
38 ug/m3.
Method/Design
Multivariate logistic
regression models used,
including adjustment for
covariates including
indicators for SES, health
status, indoor exposure
factors, and avoidance
behavior.
Effect Estimates/Results
Statistically significant decreases in
number of patients admitted to hospital
or seen in emergency departments for
respiratory illnesses.
OR per 10 ug/m decline in PM10:
chronic cough
0.65 (0.54, 0.79)
bronchitis
0.66(0.55,0.80)
common cold
0.78 (0.68, 0.89)
nocturnal dry cough
0.70 (0.60, 0.83)
conjunctivitis symptoms
0.81 (0.70., 0.95)
No significant changes in prevalence of
asthma, hay fever, wheeze or sneezing.
-------
Table A13 (cont'd.). Results of Epidemiologic "Intervention" Studies
Reference, Study
Location and Period
Outcome
Measure
Change in
pollution/emissions
Reported PM Levels
(ug/m3)
Method/Design
Effect Estimates/Results
European studies (cont'd)
Frye et al, 2003
3 communities in East
Germany
1992-1999
Pulmonary
function
measurements for
2,493 children 11-
14 years of age, in
1992-1993, 1995-
1996, and 1998-
1999.
Reduction in air
pollution
concentrations
following German
reunification in
1990.
Mean TSP concentrations
fell from 79 to 23 ng/m3,
while mean SO2
concentration declined from
113 to 6 |ig/m .
Linear regression using
MIXED procedure in SAS,
with log-transformed lung
function measures and
covariates including sex,
height, season, lung function
equipment, parental
education, parental atopy,
ETS exposure.
Percent change in lung function
parameter per 50 |ig/m3decrease in
TSP:
FVC: 4.7% (0.2, 9.5)
FEVi:2.9%(-1.4,7.3)
Associations larger in magnitude and
more often statistically significant for
girls than for boys. Similar results
reported with decreases in SO2
concentration.
Heinrichetal.,2002
3 communities in East
Germany
1992-1999
Respiratory
symptom
questionnaires for
4,949 children 11-
14 years of age, in
1992-1993, 1995-
1996, and 1998-
1999.
Reduction in air
pollution
concentrations
following German
reunification in
1990.
In 1991, mean TSP
concentrations range from
45 to 79 |ig/m in the three
communities; in 1998, range
from 25 to 33 |ig/m . Fine
particle concentrations
(NCo.oi-2.5) reported for 1993
(11.7-12.6 ng/m3) and 1999
(10.6-16.7 ng/m3)
Two-stage analyses, using
repeated-measures in
generalized estimating
equations. GEE logistic
regression model used to
compute symptom
prevalences, adjusting for
age, gender, parental
education, parental atopy,
and four indoor exposure
factors (dampness/mold, gas
cooking, ETS, cats); in
second stage, logits of
prevalence regressed against
air pollution variables.
OR per 50 ng/m3 TSP:
Bronchitis:
3.02(1.72,5.29)
Sinusitis:
2.58(1.00,6.65)
Frequent colds:
1.90(1.17,3.09)
Otitis media:
1.45(0.89,2.37)
Febrile infections:
1.79(0.92,3.48)
Cough in morning:
1.23 (0.82, 1.84)
Shortness of breath:
1.33(0.83,2.12)
-------
Table A13 (cont'd.). Results of Epidemiologic "Intervention" Studies
Reference, Study
Location and Period
Change in
Outcome Measure pollution/emissions
Reported PM Levels
(ug/m3)
Method/Design
Effect Estimates/Results
European studies (cont'd)
Neuberger et al. (2002)
Linz, Austria
1985-1990
Sugiri et al. (2006)
East and West Germany
1991-2000
Lung function
measured 2-8 times
in 3,451 children in
elementary and high
schools, repeated
measures over study
time period.
Lung function
measurements in
2,574 children aged
5-7 years
Uniform decreases
across districts of
Linz for SO2 and
TSP; some areas
report little changes
and some dramatic
decreases in NO2
concentrations
Dramatic decline in
pollution in East
Germany; smaller
decline in West
Germany
NR
NR
Annual average for TSP in
year preceding measurement
declined from 74 to 51 ug/m3
in East Germany, from 54 to
44 in West Germany, average
on the day of investigation
decreased from 133 to 30
ug/m3.
Linear regression with
covariates as for Frye et al.
(2003); included test for
homogeneity of effects based
on proximity to busy streets.
Focus on lung function improvements
with reduction in NO2 concentrations;
report that TSP and SO2 do not act as
confounders.
Lung function improved with reduction
in air pollution; differences between
East and West Germany vanished
during study time period.
Stronger associations reported for
reactive airway measure with short-term
TSP exposure measure, and with TLC
with chronic TSP exposure measure.
Per 40 ug/m3 daily mean TSP:
Raw: 0.969 (0.936, 1.004)
per 40 ug/m3 annual mean TSP:
TLC: 0.938 (0.884, 0.996)
Exposure to traffic also associated with
reduced lung function.
-------
Table A13 (cont'd.). Results of Epidemiologic "Intervention" Studies
Reference, Study
Location and Period
Change in
Outcome Measure pollution/emissions
Reported PM Levels
(ug/m3)
Method/Design
Effect Estimates/Results
European studies (cont'd)
Burr et al., 2003
North Wales, UK
1996-1999
Repeated
questionnaires for
respiratory
symptom
prevalence and PEF
measures in 448
adults in congested
and uncongested
neighborhoods,
before (1996-7) and
after (1998-9)
bypass opened and
reduced traffic flow
Heavy goods vehicle
counts and air
pollution decreases
with bypass opening
PM2 5 mean before and after
bypass in congested
neighborhood:
21.2 ng/m3 and 16.2 |ig/m3
(23.5% reduction) and in
uncongested neighborhood:
6.7 ng/m3 and 4.9 ng/m3
(26.6% reduction)
For PM10 in congested
neighborhood:
35.2 ng/m3 and 27.2 ng/m3
(22.7% reduction) and in
uncongested neighborhood:
11.6 ng/m3and8.2 |ig/m3
(28.9% reduction)
46.9% reduction in heavy
goods vehicles per hour
Percent subjects reporting
improvement calculated for
congested and uncongested
streets and difference
expressed as percent
improvement.
% reduction in symptoms::
any wheeze-6.5 (-14.9, 2.0)
# attacks-8.5 (-18.2,1.2)
No association with cough, phlegm,
consulted doctor, rhinitis. Positive
association with "affects activities"
10.3(3.1,17.3)
-------
Toxicology studies:
Carvalho-Oliveira et al. (2004): Mutagenesis testing of particles collected during and after a bus
strike in Sao Paulo, Brazil. Significant reduction in damage to DNA was observed, without
significant changes in overt toxicity to cells, with exposure to PM collected during the strike.
PM2.5 mass concentrations were high (-40 |ig/m3) during strike; authors note "intense traffic
jam" during this period. Concentrations of sulfur and BETX were lower on strike than non-
strike days.
Somers et al. (2004): Study of heritable mutation rates in laboratory mice housed an urban-
industrial area (near a major highway and two integrated steel mills) in Ontario, and mice housed
in rural area. In both areas, one group of mice exposed to ambient air for 10 weeks and one
group housed in a chamber with HEPA filtration system to remove 99.97+% of particles.
HEPA filtration reduced heritable mutations in urban-industrial area, with larger effect on
paternal mutation rates; no effect in rural area.
A-58
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Table A14. Associations Between Source-related Fine Particles and Health Outcomes
Reference, Study
Location and Period
Mar et al. (2006)
Phoenix, AZ
Feb 1995-Dec 1997
Mean PM Levels Copollutants Lag Structure
Outcome Measure (u,g/m3) Considered Examined Method/Design
Mortality: All PM25: Estimated mean None
nonaccidental and range across 9
cardiovascular independent analyses
causes; age. 65 yr (24-h avg):
SO42: 1.3 to 3.6
Traffic: 4.0 to 7.7
Cu: 0.2 to 0.8
Sea salt: 0.1 to 0.2
Wood: 0.9 to 2.8
Soil: 0.8 to 2. 6
Estimated 5^-95*%
range across 9
0-, 1-, 2-, 3-, Time-series study.
4-day, or 5- lag Poisson GLM with
natural splines. Eight
independent analyses
performed.
Daily PM2.5 data
collected using both
gravimetric and TEOM
samplers. Several teams
of investigators used
different source
apportionment methods
with PM2 5 data.
Effect Estimates/Results
Results from all investigators
combined:
Median % excess risk per 5^-95^/0
increment:
(95% CPs not presented)
Cardiovascular:
Sulfate, lag 0: 16.0%
Traffic, lag 1: 13%
Cu smelter, lag 0: 12%
Sea salt, lag 5: 10%
Biomass/wood burning, lag 3: 9%
No association reported with soil
independent analyses
(24-h avg):
SO42: 2.5 to 6.9
Traffic: 10.3 to 16.1
Cu: 0.5 to 3.5
Sea salt: 0.2 to 0.6
Wood: 2.3 to 6.2
Soil: 2.0 to 7.9
Traffic and secondary
sulfate contributions, as
estimated by different
analyses, were well
correlated.
factor.
Among all sources, the largest effect
size for cardiovascular mortality
observed for secondary SO42, followed
by traffic. Associations weaker for all-
cause mortality.
Variations in results across
investigators/methods were small
compared to the variations across
source categories.
-------
Table A14 (cont'd). Associations between Source-related Fine Particles and Mortality
Reference, Study
Location and Period
Outcome Measure
Mean PM Levels
(ug/m3)
Copollutants
Considered
Lag Structure
Examined
Method/Design
Effect Estimates/Results
Ito et al. (2006)
Washington, DC
Aug 1988-Dec 1997
Mortality: All
nonaccidental,
cardiovascular, and
cardiorespiratory
causes
PM2.5: Estimated mean
range across 9
independent analyses
(24-havg):
S042: 5.1 to 10.7
Traffic: 1.6 to 4.7
NO3": 1.6 to 6.7
Residual oil: 0.3 to 0.6
Wood smoke: 0.2 to 1.9
Incinerator: 0.3 to 1.0
Primary coal: 1.2 to 2.1
Sea salt: 0.2 to 0.9
Soil: 0.3 to 3.7
Estimated 5th% to
95th% range across 9
independent analyses
(24-h avg):
SO42: 10.4 to 22.0
Traffic: 3.2 to 9.7
NO3": 5.0 to 17.9
Residual oil: 0.9 to 3.3
Wood smoke: 0.6 to 5.7
Incinerator: 0.7 to 1.6
Primary coal: 3.2 to 3.8
Sea salt: 0.7 to 4.3
Soil: 0.9 to 4.8
None
0-, 1-, 2-, 3-, or
4-d lag
Time-series study.
Poisson GLM with
natural splines. Nine
independent analyses
performed.
PM2 5 gravimetric data
collected on Thursday
and Saturday only
(U.S. Park Service,
IMPROVE). Traffic
contributions, as
estimated by different
analyses, were not well
correlated; however,
secondary sulfate
contributions were
fairly well correlated.
Results from all investigators
combined:
Median % excess risk per 5th-95th%
increment:
(95% CPs not presented)
All causes:
Sulfate, lag 3: 6.7% (1.7, 11.7)
Traffic: 2.6% (-1.6, 6.9)
Residual oil, lag 2: 2.7% (-1.1, 6.5)
Primary coal, lag 3: 5.0% (1.0, 9.1)
Soil: 2.!%(-!.8,4.9)
No significant associations were
reported with the following factors:
NO3", wood burning, incinerator and
sea salt.
Among all sources, largest and most
significant association with all-cause
mortality observed for secondary SO42
at lag 3 d. Cardiovascular and
cardiorespiratory mortality
associations were generally similar to
all-cause mortality.
Variations in results across
investigators/methods were small
compared to the variations across
source categories.
-------
Table A14 (cont'd). Associations Between Source-related Fine Particles and Health Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean PM
Levels
Copollutants
Considered
Findings, Interpretation
Quantitative Results
Riediker et al. (2004)
Wake County, NC
Fall 2001
>
Cardiovascular outcomes: Nine
healthy young non-smoking male
troopers studied on 4 consecutive
days, working 3PM to midnight
shift. HRV measured with
ambulatory ECG during shift and
subsequent sleep phase. Blood
parameters from blood sample
drawn 15 min after work shift.
Mixed effects regression models
used.
In-vehicle PM2 5
(ug/m3)
mean (SD):
23.0 (8.0)
Source apportionment of PM2 5 mass
identified 4 components: crustal material
(Al, Si, Ca, Ti, Fe), wear of steel automotive
components (Ti, Cr, Fe), gasoline
combustion (benzene, CO), and speed-
changing traffic (Cu, S, aldehydes).
The "speed change" factor was significantly
associated with increased heart cycle length,
increased FfRV, decreased % lymphocytes,
decreased protein C and increases in von
Willebrand factor, % neutrophils, mean red
cell volume, and blood urea nitrogen.
The "crustal" factor was significantly
associated with increased uric acid.
Nearly significant associations were seen
between the "gasoline" factor and mean
heart cycle length, decreased protein C and
increased von Willebrand factor.
No quantitative results
reported. Results presented
in figures only.
-------
Table A15. Associations of Acute Exposure to Fine Particle Components with Health Outcomes
Reference, Study
Location and Period
Burnett et al. (2004)
12 Canadian cities
Jan 1981-Dec 1999
Outcome Measure
Mortality: All
nonaccidental,
cardiovascular, and
respiratory causes
Mean Component Copollutants Lag Structure
Levels (jig/m3) Considered Examined Method/Design
24-h avg S042:
All 12 cities:
2.84
SD not provided.
PM25, PM10_25, 0-, 1-, or2-dlag Time-series study.
PM10, NO2, SO2, Natural spline functions
CO, O3 used to model nonlinear
associations.
SO42 data determined
from75%ofPM2.5
filters. SO42data
Effect Estimates/Results
% excess risk per 2.84 ug/m3:
All causes:
Single-pollutant model:
Lag 1: 0.67% (0.00, 1.35)
Two-pollutant model with NO2:
available on 9% of days Lag 1: 0.46% .(0.25, 1.18)
with mortality data.
NO2 effect also nonsignificant in two-
pollutant model.
to
-------
Table A15 (cont'd). Associations of Acute Exposure to Fine Particle Components with Health Outcomes
Reference, Study
Location and Period
Goldberg et al. (2006)
Montreal, Canada
1986-1993
Outcome Measure
Mortality: Diabetes,
and nonaccidental
mortality in subgroups
with diabetes
diagnosed at least 1 yr
before death in adults
>65. Also considered
subgroups with
cardiovascular
diagnoses.
Mean Component
Levels (jig/m3)
24-h avg measured
SO42:
mean (SD)
3.3(3.6)
24-h avg predicted
SO42 (from PM2.5):
mean (SD)
4.1 (3.6)
Copollutants
Considered
PM10, TSP,
coefficient of
haze, PM2 5,
predicted PM25,
SO2, NO2, CO,
03
Lag Structure
Examined
0-, 1-, and avg
of 0- to 2-day
lags ("3-day
mean")
Method/Design
Time-series study.
Poisson regression using
natural spline functions.
Report results for SO42
predicted from PM2 5;
used statistical model to
estimate mass when
measurements were not
available; measured data
available on 2680 days
and predicted data for
3653 days.
Effect Estimates/Results
Measured SO42:
% excess risk per 2. 5 ug/m3:
mortality from diabetes:
5.1% (0.638, 9.71)
nonaccidental mortality in subjects
with diabetes:
2. 31% (0.11, 4. 56)
Predicted SO42:
% excess risk per 2. 9 ug/m3:
mortality from diabetes:
5.42% (0.44, 10.64)
nonaccidental mortality in subjects
with diabetes:
2.77% (0.23, 5.38)
(all 3-day mean lag)
Greater effects seen generally in the
warm season.
No significant association for
nonaccidental mortality in subjects
with diabetes, but without cancer,
cardiovascular disease or airways
disease.
Associations reported for
nonaccidental mortality in subjects
with diabetes who also had any
cardiovascular disease, chronic
coronary disease, or atherosclerosis.
-------
Table A15 (cont'd). Associations of Acute Exposure to Fine Particle Components with Health Outcomes
Reference, Study
Location and Period
Klemm et al. (2004)
Atlanta, GA
Augl998-July2000
Outcome Measure
Mortality: All
nonaccidental,
circulatory,
respiratory, cancer,
and other causes; age
<65 yr and. 65 yr
Mean Component
Levels (jig/m3)
24-h avg
mean (SD; range):
S042: 5.46(0.79-
19.34)
EC: 2.03(0.45.-
9.76)
OC: 4.54(1.41-
14.61)
nitrates: 1.17(0.15-
5.40)
Copollutants
Considered
PM25,PM10.25,
EC, OC, NO2,
NO3', SO2, CO,
O3, ultrafines,
hydrocarbons,
acid
Lag Structure
Examined Method/Design
Multiday lag of Time-series study.
0-1 d Poisson GLM using
natural cubic splines
with quarterly, monthly,
or biweekly knots.
Default model used
monthly knots.
Analyses done by
individual components,
as well as three major
PM2 5 fractions: sulfate,
carbon (OC and EC
combined) and "balance"
(remaining components
combined).
Effect Estimates/Results
% excess risk
per 5. 46 ug/m3 SO42:
All causes, age >65:
Coefficient (t-statistic) for monthly
knot models (lag 0-1):
SO42: 0.00843 (1.54)
EC: 0.01343(1.54))
OC: 0.00529 (0.79)
N03': -0.00103 (-0.06)
For age >65, significant associations
with PM2 5 mass (quarterly and
monthly knots; not significant for
biweekly) but not with any individual
PM2 5 component.
Results differ across model
specifications (i.e., choice of lag and
number of knots).
Villeneuve et al. (2003) Mortality: All
Vancouver, British
Columbia, Canada
Jan 1986-Dec 1998
24-h avg S042: PM2.5, PM10.2.5,
nonaccidental, 2.7 PM10, TSP,
cardiovascular, 10th-90*% coefficient of
respiratory, and cancer 1.1-4.4 haze, SO2, NO2,
causes; SES status Range 0.4-9.0 CO, O3
No significant associations observed in
those aged <65 yr.
0-, 1-, or 2-d Time-series study. % excess risk (95% CI) per 3.3 ug/m3
lag; multiday Poisson regression using SO/'.
lag of 0-2 d natural spline functions.
All causes:
SO42 data collected every Lag 0: 2.9% (-4.4, 10.8)
6th day.
Cardiovascular:
Lag 0:. 3.2%.(-14.1, 9.1)
Respiratory:
Lag 0: 8.3%.(-12.3, 33.8)
Cancer:
LagO: 8.0%.(-4.5,22.1)
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Table A15 (cont'd). Associations of Acute Exposure to Fine Particle Components with Health Outcomes
Reference, Study
Location and Period
Metzger et al. (2004)
Atlanta, GA
Aug 1998-Aug2000
Outcomes and
Design
Emergency
department visits for
total and cause-
specific cardiovascular
diseases by age groups
>19yrand>65 yr.
Time-series study. 4,
407, 535, EDV from
31 Atlanta hospitals.
Components included
acidity (IT"), EC, OC,
water-soluble (WS)
metals, sulfates
Mean Component
Levels
Median (ug/m3)
(10-90% Range)
S042: 4.5(1.9-10.7)
WS metals: 0.021
(0.006-0.061)
OC: 4.1 (2.2-7.1)
EC: 1.6(0.8-3.7)
Copollutants
Considered
N02, S02, CO,
03,PM10,
PMio-2.5, PM2.5,
ultrafme PM
count,
oxygenated
hydrocarbons
Lag Structure Method, Findings,
Examined Interpretation
0-2 Poisson GLM regression
used for analysis. A
priori models specified a
lag of 0 to 2 days.
Secondary analyses
performed to assess
alternative pollutant lag
structures, seasonal
influences, and age
effects. Cardiovascular
visits were significantly
associated with several
pollutants, including
NO2, CO, and PM2.5, but
not O3 or sulfates
Effects
(Relative Risk and 95% CI)
Relative Risks for:
SO42 per 5 ug/m3
WS metals per 0.03 ug/m
OC per 2 ug/m3
EC per 1 ug/m
All ages:
Total cardiovascular:
SO42 1.003 (0.968, 1.005)
WS metals 1.027 0.998, 1.056)
OC 1.026 (1.006, 1.046)
EC 1.020 (1.005, 1.036)
Congestive heart failure:
S042 1.009 (0.938, 1.162)
WS metals 1.040 (0.981,1.051)
OC 1.048 (1.007, 1.091)
EC 1.035 (1.003, 1.068)
Ischemic heart disease:
SO42 0.997 (0.936, 1.090)
WS metals 1.000 (0.951,1.051)
OC 1.028 (0.994, 1.064)
EC 1.019 (0.992, 1.046)
Peripheral vascular and
cerebrovascular disease:
SO42 1.025(0.964, 1.090)
WS metals 1.043 (0.991,1.036
OC 1.026 (0.990, 1.062)
EC 1.021 (0.994, 1.049)
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Table A15 (cont'd). Associations of Acute Exposure to Fine Particle Components with Health Outcomes
Oi
Reference, Study
Location and Period
Peel et al. (2005)
Atlanta, GA
Aug 1998-Aug2000
Outcomes and
Design
Emergency
department visits for
total and cause-
specific respiratory
diseases by age groups
0-1, 2-18, >19, and
>65 yr. Time- series
study. Components
included acidity Qf),
EC, OC, water-soluble
(WS) metals, sulfates
Mean Component
Levels
Median (|ig/m3)
(10-90% Range)
S042: 5. 5 (1.9-10.7)
WS metals: 0.028
(0.006-0.061)
OC: 4. 5 (2.2-7.1)
EC: 2.0 (0.8-3.7)
Copollutants
Considered
N02, S02, CO,
03,PM10,PM10.
2.5, PM2.5,
ultrafme PM
count,
oxygenated
hydrocarbons
oxygenated
hydrocarbons
Lag Structure Method, Findings,
Examined Interpretation
0-2 Poisson GEE and GLM
regression used for
analysis. A priori
models specified a lag of
0 to 2 days. Also
performed secondary
analyses estimating the
overall effect of
pollution over the
previous 2 weeks.
Seasonal analyses
indicated stronger
associations with asthma
in the warm months,
especially for O3 and
PM2 5 organic carbon.
Quantitative results not
presented for
multipollutant, age-
specific, and seasonal
analyses.
Effects
(Relative Risk and 95% CI)
All ages relative risks for:
SO42 per 5 ng/m3
WS metals per 0.03 |ig/m
OC per 2 ng/m3
EC per 1 |ig/m
All available data:
Total respiratory:
SO42 0.998 (0.968, 1.028)
WS metals 1.005 (0.981, 1.031
OC 1.011 (0.997, 1.025)
EC 0.999 (0.987, 1.011)
Upper respiratory infections:
S042 1.001 (0.965, 1.039)
WS metals 1.010 (0.980, 1.040)
OC 1.011 (0.995, 1.028)
EC 0.999 (0.985, 1.013)
Asthma:
SO42 0.991 (0.949, 1.035)
WS metals 1.007 (0.973,1.043)
OC 1.000 (0.978, 1.023)
EC 0.993 (0.976, 1.011)
Pneumonia:
SO42 1.013 (0.959, 1.069)
WS metals 0.997 (0.958,1.039)
OC 1.028 (1.004, 1.053)
EC 1.006 (0.987, 1.026)
COPD:
80/1.004(0.929,1.085)
WS metals 0.971 (0.913,1.032
OC 0.996 (0.959, 1.035)
EC 0.981 (0.952, 1.012)
-------
Table A15 (cont'd). Associations of Acute Exposure to Fine Particle Components with Health Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean Component
Levels
Copollutants
Considered
Findings, Interpretation
Effects
O'Neill et al. (2005)
Boston, MA
May 1998-Jan 2000
Baseline period
Time trial
2000-2002
Cardiovascular Outcomes: 270
patients with diabetes or at risk
for diabetes were studied in
relation to various pollutant
levels and evaluated for
association with vascular
reactivity. Linear regressions
were fit to the percent change in
BAD (flow-mediated and
nitroglycerin-mediated) into
particulate pollutant index and
other factors.
SO4 PM2 5, BC, PM2 5 was associated with nitroglycerin-
mean: ultrafine mediated reactivity; an association was
3.3 |ig/m3 also reported with ultrafine particles.
Effects were stronger in type II than type I
Range: diabetes. Black carbon and SO42 increases
0.3 to 12.9 were associated with decreased flow-
mediated reactivity among those with
diabetes. Although the strongest
associations were with the 6-day morning
average, similar patterns and
quantitatively similar results appear in the
other lags.
Effect estimate per IQR SO42
6-day morning average
Nitroglycerin-mediated
. 6.2%; 95% CI11.5 to. 0.6
-------
Table A15 (cont'd). Associations of Acute Exposure to Fine Particle Components with Health Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean Component
Levels
Copollutants
Considered
Findings, Interpretation
Effects
Sinclair and Tolsma
(2004)
Atlanta, GA
Augl998-Aug2000
Respiratory medical visit data
collected by Kaiser Permanente,
including ambulatory care visits
for asthma (adult and child), URI
and LRI. ARIES air quality data
used. Poisson GLM regression
used for analysis. A priori
models specified a lag of 0 to
2 days (avg). Also performed
analyses using avg lag periods of
3-5 and 6-8 days. Fine particle
components included SO42, Ff",
EC, OC, water-soluble (WS)
metals.
mean (SD) in NO2, SO2, CO, Adult asthma visits associated with
|ig/m3: O3, PMio, ultrafine number count, and negatively
PM2 5, associated with PM2 5 mass. Child asthma
SO42: 5.52 (3.5) PM10.2 5, associated with OHC (0-2 day) and with
FT: 0.02 (0.02) ultrafine PM PM10, PM10.2 5, EC and OC (3-5 day). LRI
EC: 2 (1.38) count, associated with PM2 5 acidity and SO2 (0-2
OC: 4.49 (2.2) oxygenated day) and with PM10, PM10.2.5, EC, OC and
WS metals: 0.03 hydrocarbons PM25 WS metals. For URI, significant
(0.03) (OHC) positive associations with ultrafine PM (0-2
day) and PM10.2.5 (3-5 day) but negative
associations with PM2 5, SO2 and sulfate.
Risk Ratios per SD:
Adult asthma visits:
SO42 NS
FTNS
ECNS
OCNS
WS metals NS
Child asthma:
SO42 NS
FfNS
ECRR= 1.046
OCRR= 1.046
WS metals NS
OO
LRI visits:
SO42 NS
FTNS
EC RR= 1.079
OCRR= 1.05
WS metals RR= 1.062
URI visits:
S042RR= 0.976
FfNS
ECNS
OCNS
WS metals NS
Quantitative results provided
only for statistically
significant findings.
-------
Table A15 (cont'd). Associations of Acute Exposure to Fine Particle Components with Health Outcomes
Reference, Study
Location and Period
Outcomes and Methods
Mean Component Copollutants
Levels Considered
Findings, Interpretation
Effects
Delfino et al. (2003)
Los Angeles, CA
Nov 1999-Jan 2000
Respiratory outcomes: Panel
study of 22 Hispanic children
(10-15 yr) with asthma, living in
the Huntington Park region of
LA. Daily diary with
symptoms, inhaler use, and PEF
measurements made three times
daily. GEE regression methods
used.
Mean (range) in NO2, SO2, Significant associations reported between
|ig/m3: CO, O3, increased asthma symptoms and PM10,
PMio, EC, OC, NO2 and SO2, acetaldehyde,
EC: numerous air benzene, ethylbenzene and
5.09(1.79-9.42) toxics tetrachloroethylene. Associations with
IQR = 2.91 PMIO, EC, and OC generally decreased in
OC: size and lose significance in 2-pollutant
9.47 (4.29-17.05) models with air toxics.
IQR = 4.64
Authors conclude that their findings
(Measured in support the view that air toxics in the
PM10) pollutant mix from traffic and industrial
sources may have adverse effects on
asthma in children.
Odds Ratio for asthma
symptom per IQR:
EC:
lagO: 1.85(1.11-3.08)
lag 1: 1.01(0.66,1.53)
OC:
lagO: 1.88(1.12,3.17)
lag 1: 1.08(0.80,1.46)
vo
-------
Additional U.S. and Canadian Studies:
Bennett et al. (2006): Assessed relationship between Asian dust event in April 1998 and hospital
admissions. No statistically significant difference in hospital admissions rates for either
respiratory or cardiovascular diseases between 4-day period in 1998 and corresponding 4-day
period in 1997; methods include graphical display and chi-square test for difference.
Clairborn et al. (2002): This report includes discussion of ongoing research in Spokane, WA, that
will examine relationships between health outcomes and particle sizes and fine and thoracic
coarse particle metal concentrations. In addition, results of previous publications from this
research group are discussed, and it is suggested that fine particulate metals, particularly Zn, are
significantly associated with asthma hospital admissions.
Henneberger et al. (2005): Repeated ECG measurements in a panel of 56 patients with ischemic
heart disease in Erfurt, Germany. PM2.5 (6 h avg) was significantly associated with decreased
T-wave amplitude, increased T-wave complexity and nearly significant with increased variability
of T-wave complex. Associations with 6 h PM2.5 were stronger than those with 24 h PM2.5.
Similar associations were observed with 6 h ultrafme particles, accumulation mode particles,
OC and EC, although most were not statistically significant. A significant association was
reported between OC and QT duration.
Moshammer and Neuberger (2003): In a panel of 78 children, biweekly lung function tests and
daily symptom diaries were collected for 4 weeks. Ambient monitoring was conducted to
determine "active surface" of particles by unipolar diffusion charging. The results of this study
demonstrated that active surface correlates with PAH levels of particles. Significant associations
reported between active surface of particles and evening cough, shortness of breath and wheeze.
A-70
-------
Table A16: CAPs Studies with Source Apportionment or Components Analysis
Reference
Species
CAPs
Exposure
CAPs Characterization
Endpoints
Results
Factor or Principal Component Analysis
Huang,
Y-C.T et al.
(2003)
Human, M
(n = 35), F (n = 2)
26.2±0.7 yr
>
Batalha Rat, M, SD,
et al. (2002) 200-250 g; CB
induced with SO2
2 h with
15 min
alternating rest
and exercise
-50 L/min;
assessed 18 h
PE
5 h/day for
3 consecutive
days in 6
experimental
sets; assessed
24hPE
Chapel Hill, NC air; HAPC; 72.2
|ig/m3 (range 0-311 |ig/m3)
Median soluble
components (|ig/m3):
sulfate 17.6; V 2.1; Fe 42.6;
Zn 66.4; Cu 13.1; As 2.2; Ni 1.2;
Se6.0;Pb3.4
Boston, MA; HAPC; mean mass
cone. 262.21 ±213 |ig/m (range
73.5-733)
Elemental composition (ng/m );
sulfate 66.9; EC 11.45; OC 57.73;
Al 1.22; Si 4.62; S 25.61; Cl 0.68;
K 1.68; Ca 1.82; Ti 0.20; V 0.05; Cr
0.01; Mn 0.09; Fe 3.47; Ni 0.05; Cu
0.10; Zn 0.26; As 0.01; Se 0.02; Br
0.07; Cd 0.02; Ba 0.73; Pb 0.12
BALF:
Cell counts
Cell differential
protein Cytokines
PGE2
Protein
Fibrinogen
NO
Fibronectin
Venous blood:
CBC
Ferritin
Fibrinogen
Histopathology
Morphometry for
LAV ratios (muscular
hypertrophy and
constriction of
vessels)
Factor 1 (sulfate/Fe/Se) correlated with increases in
BALF PMN.
Factor 2 (Cu/Zn/V) correlated with elevated blood
fibrinogen levels.
BALF fibronectin correlated positively with BALF
PMN.
Factor 1 correlated highly with PM mass.
CAPs caused vasoconstriction of small pulmonary
arteries.
Exposure to CAPs in normal and CB rats resulted in
decreased LAV ratio that was associated with CAPs
mass, Si, Pb, sulfate, EC and OC.
In normal rats exposed to CAPs, decreased LAV ratio
was associated with sulfate and Si.
In CB rats, decreases in LAV ratio were associated
with Si and OC.
No significant associations were observed between the
LAV ratio and Day 1 of exposure (reported effects due
only to Days 2 and 3).
-------
Table A16 (cont'd): CAPs Studies with Source Apportionment or Components Analysis
Reference Species
CAPs
Exposure
CAPs Characterization
Endpoints
Results
Factor or Principal Component Analysis (cont'd)
Goldsmith
et al. (2002)
to
Wellenius
et al. (2003)
Mice, Balb/c;
sensitized to OVA
on days 7 and 14,
pretreated with
OVA via
inhalation on days
21, 22, and 23
Dog, F, retired
mongrel;
implanted balloon
occluder on left
anterior
descending
coronary artery
5 h/day for 3
days (21, 22,
and 23);
exposure to
CAPs only, O3
only (0.3 ppm),
or CAPs+O3;
assessed 24 or
48hPE
6 h/day;
immediately
PE a 5 min
preconditionin
g occlusion
followed 20
min later by a 5
min study
occlusion
Boston, MA; HAPC; mean mass
cone. 302±58 ug/m ; range 63.3-
1569 ug/m3
Elemental composition (ug/m ): Al
nd-17.2, Si 0.9-35.1,8 3.5-187, Cl
nd-7.9, K 0.4-5.7, Ca 0.6-12.5, Ti
nd-1.9, V nd-0.26, Cr nd-0.05, Mn
0.01-0.43, Fe 1.4-21.9. Nind-0.16,
Cu 0.02-0.43, Zn 0.06-1.1, Br
0.01-0.24, Ba 0.04-0.83, Pb 0.001-
0.34, As nd-0.31, Se nd-0.06, Cd
nd
Boston CAPs; HAPC; mean mass
cone. 345±194 (range 161-957)
Elemental composition (ug/m3):
sulfate 77.90; BC 9.78; EC 21.48;
OC 66.71; Al 2.13; As 0.028; Br
0.09; Ca 4.31; Cr 0.03; Cu 0.19; Fe
8.26; K 2.15; Mn 0.18; Ni 0.16; Pb
0.15; S 27.41; Se 0.02; Si 8.17; Ti
0.41; V 0.16; Zn 0.58
Pulmonary function
BALF:
Cell viability
Cell counts
Cell differentials
ECG:
Peak and integrated
ST-segment elevation
PeakHR
Incidence of
arrhythmias
CAPs alone caused increases in penh (a measure of
airway responsiveness) immediately following
exposure, although the magnitude of response was
small (approximately 0.9% for a 100 ug/m3 increase
in CAPs).
CAPs+O3 exposure resulted in elevated penh when
sensitized animals were challenged with
methacholine.
An Al/Si component for daily and 3-day cumulative
concentrations was associated with increased penh for
OVA animals exposed to CAPs+O3.
A S component was associated with elevated penh for
non-OVA mice exposed to CAPs only.
CAPs enhanced occlusion-induced peak ST-segment
elevation.
HR was not affected by CAPs.
ST-segment elevation was associated with Si and
other crustal elements.
CAPs mass or particle number was not associated
with any endpoint.
-------
Table A16 (cont'd): CAPs Studies with Source Apportionment or Components Analysis
Reference Species
CAPs
Exposure
CAPs Characterization
Endpoints
Results
Components (Elements, sulfate, nitrate, organic/elemental carbon)
Gong et al.
(2005)
Human, healthy
(4F,2M,68±11
yr) and COPD
(9F,9M, 72±7 yr);
exposures were on
separate days
followed by at
least 2 wks
2 h with Los Angeles, CA; HAPC
15 min Exposures to:
alternating rest (a) FA
and exercise; (b) 0.4 ppm NO2
assessed (c) CAPs - predominantly PM2 5 at
during, at Oh -200 ug/m3 collected with HAPC
PE, 4 h PE, and (d) CAPs + NO2
day 2 (~22h <0.l um contributed ~6 ug/m3 in all
PE) exp; >2.5 um contributed ~6 ug/m3
in FA or NO2 exp and 12 ug/m3 in
CAPs and CAPs +NO2 exp; CAPs
and CAPs+NO2 (1-2.5 urn)
-170 ug/m3
Elemental composition (ug/m3):
Si 4.0; Fe 2.9; EC 10.1; Al 1.6; Ca
2.3;Na2.0;Kl.l;C12.5;N0242
ppb
ECG
SaO2
Puhnonary function
BP
HR
Sputum:
Cell counts
Cell differentials
For all exposure groups, there were no changes in
symptoms, spirometry, or differential cell counts.
In subjects exposed to CAPs and CAPs+NO2,
decrements in MMEF and SaO2 (greater in healthy
than COPD) were observed. Decreased percentages
of columnar epithelial cells in sputum were also
reported.
For subjects exposed to CAPs+NO2, FEVj and FVC
decreases were associated with sulfate levels; total
mass did not correlate with sulfate.
HR increased for both CAPs groups post-exposure;
for COPD subjects, the tendency of increased HR was
lower with increasing mass.
There was a decrease in self-reported symptoms
during CAPs+NO2 that were associated with elevated
Fe concentration.
Urch et al.
(2004)
Human, healthy
(14M, 10F; 35±10
yr)
2 h CAP + O3 Toronto CAPs; HAPC; mean mass
(crossover cone. 148 ug/m3 (range 102-257)
design); Major constituents (ug/m3): C 22.7
O3 cone. (OC 19.7, EC 2.5), sulfate 14.2,
120 ppb nitrate 14.0, ammonium 5.4,
CaO.78
BAD
A decrease in OC or EC concentration was associated
with changes in BAD.
When multiple linear regression analysis (MLRA)
was conducted on the dose metric (a product of mean
ventilation, exposure duration, and mass
concentration), elevated OC+sulfate was associated
with change in BAD (although p-value = 0.06 for
sulfate in the MLRA).
Sulfate was not associated with changes in BAD
alone.
-------
Table A16 (cont'd): CAPs Studies with Source Apportionment or Components Analysis
Reference
Species
CAPs Exposure CAPs Characterization
1 ml points
Results
Components (Elements, sulfate, nitrate, organic/elemental carbon) (cont'd)
Urch et al.
(2005)
Dvonch et al.
(2004)
Human, healthy
(13M, 10F;35±10
yr)
Rat, BN, M;
7 rats/group
Gurgueira
et al. (2002)
Rat, SD, 250-300g
Kodavanti
et al. (2005)
Rat, WKY and SH,
10-12 wk old
1 h CAP + O3
(crossover
design); O3 cone.
121 ppb
8 h/day for
3 consecutive
days (22-24 July
2004); assessed
24hPE
1, 3, or 5 h
SH one 4 h exp,
assessed 1-3 h
PE; SH and
WKY 4h/day or
2 days, assessed
1 day PE
Toronto CAPs; HAPC; mean mass
conc.!47±27 ug/m3 (range 102-214);
C 28.4 ug/m3
Urban Detroit CAPs; HAPC; mean mass
cone. 354 ug/m3
Elemental composition ranges (ng/m3):
sulfur 1393-26839, Mg 173^187; Ca
1137-2125; V 2-15; Fe 1035-2377; Ni
4.3-11.5; Cu 101-152; Cd 0.44-1.75;
La 0.3-9.7; Ce 0.6-18.5; Sm 0.03-0.21;
Pb 48.6-57.5
Boston, MA; HAPC; cone, mass range
100-956 |ig/m3; mean mass cone.
300±60 ug/m3
Research Triangle Park, NC; HAPC
1-day exp: 1138-1765 ug/m3, size range
1.07-1.19, mean 1.12 urn
2-day exposure 144-2758 ug/m3,
size range 1.27-1.48, mean 1.39 urn
BP
HR
Plasma ADMA
Organ CL (for ROS
concentration); organ
water content; LDH;
SOD; catalase
Pulmonary function
BALF:
Cell count
Cell differentials
Total protein, albumin,
LDH, NAG, GOT,
glutathione, ascorbic
acid, cytokines
Blood:
CBC
Plasma fibrinogen
ACE activity
CRP
DBF increased an average of 6 mm Hg over the 2 h of
exposure. A nonlinear relationship was reported between
DBF change and estimated exposure concentration of OC;
a similar correlation was observed between MAP and OC.
Elevated levels of ADMA were observed in CAPs-exposed
rats.
CAPs mass concentration was the highest on the first day of
exposure (4-5 times greater than Days 2 or 3).
Increased PM mass was associated with elevated levels of S,
V, La, Ce, and Sm.
An industrial complex (coal combustion, oil refineries, coke
ovens, iron/steel mills, sewage sludge incineration) was
located SW of the study location.
Exposure to CAPs for 5 h resulted in increased oxidative
stress in the lung, that was associated with the PM content of
Fe, Mn, Cu, and Zn. Oxidative stress observed in the heart
following exposure was associated with Fe, Al, Si, and Ti in
CAPs.
Organ water content and LDH activity also increased.
Elevated levels of the antioxidants SOD and catalase were
also reported following exposure.
In the 1-day exposure, no biologic effects were observed.
In the 2-day exposure, WKY rats exposed to CAPs had
decreased total cells and AM and increased PMN.
Fibrinogen levels were also elevated in these animals.
In the 2-day exposure, SH rats exposed to CAPs had
increased total protein, GGT activity, ascorbate, UA, and
PMN. Decreases in albumin were observed in these rats.
For SH rats exposed to CAPs, plasma fibrinogen correlated
with Zn and OC when expressed as mg/CAP.
-------
Table A16 (cont'd): CAPs Studies with Source Apportionment or Components Analysis
Reference
Species
CAPs Exposure CAPs Characterization
1 ml points
Results
Components (Elements, sulfate, nitrate, organic/elemental carbon) (cont'd)
Morishita
et al. (2004)
Rhoden et al.
(2004)
Rat, BN, M; some
sensitized to OVA
(days 1-3) and
challenged (days
14-16), n = 6/group
Rat, SD, M,
250-300 g; control
and NAC-pretreated
4 days after
challenge;
10 h/day for
either 4 days
(July) or 5 days
(Sept); assessed
24hPE
5 h, assessed
24hPE
Urban Detroit; HAPC; mean mass cone.
676 ug/m3 (July), 313 ug/m3 (Sept)
Elemental composition (TWA in ng/m3
in July): La 1.2; S 77716; V 17; Mn 206
Elemental composition (TWA in ng/m3
in Sept): La 1.5; S 19272; V 46; Mn 309
Boston, MA; HAPC; 1060300 ug/m3
(range 150-2520 ug/m3)
Elemental composition (ug/m3):
Na 2.54; Mg 1.93; Al 5.21; Si 14.03; S
141.9; Cl 0.18; K 4.32; Ca 4.59; Ti
0.67; V 0.08; Cr 0.02; Mn 0.69; Fe
10.91; Ni 0.05; Cu 0.18; Zn 1.58; Br
0.20; Cd 0.01; Ba 0.83; Pb 0.10
BALE (left lung):
Cell counts
Cell differentials
Leukocytes
Total protein
Right lung: trace
elements by ICP-MS
TEARS
Carbonyl
BALE:
Cell counts
Cell differentials
Edema
CAPs caused increases in BALE eosinophils and protein in
allergenic rats. Increased levels of La, V, Mn, and S in
normal rats and greater increases in allergenic rats that were
colocalized with eosinophilic infiltrates.
For the September allergic CAPs-exposed rats, elevated
eosinophils and protein were reported.
Increased levels of La were reported in the lungs of rats in
both CAPs groups in September.
Increased levels of V and S were observed in the lungs of
rats in the OVA/CAPs group in September.
Heavy industrial source complex located 2 miles downwind
of exposure site in September.
CAPs caused increases in TEARS, oxidized proteins, PMN,
and edema. No change in BALE protein, total cells or LDH.
NAC pretreatment attenuated increases in TEARS, edema,
and PMNs.
Component analysis:
Al, Si, and Fe correlated with TEARS
Cr and NA trended with carbonyl
Cr, Zn, and Na trended with PMN
-------
Table All: Other Acute CAPs Studies
Reference
Humans
Devlin et al.
(2003)
Ohio et al.
(2003)
Gong et al.
(2004a)
Species
Human, M&F
(66.9±1.0yr);
healthy elderly
subjects (n = 10)
Human, M (n = 14),
F (n = 6),
25.3±0.8yr;
5 to FA, 15 to CAPs
Human, M and F;
healthy (68±llyr,
n = 6) and COPD
(73±8 yr, n = 13)
CAPs Exposure
2 h, alternating
15 min exercise
and rest; HRV
assessed pre-and
post-exposure
and 24 h PE;
cross-over design
2 h alternating
15 min rest and
exercise
~50L/min;
assessed 0 or
24hPE
2 h, alternating
15 min exercise
and rest; assessed
just PE, at 4h,
and at day 2.
ECG before,
during and after
exposure
CAPs Characterization
Chapel Hill, NC; HP AC; mean mass
cone. 40.5 ± 8.6 ug/m3 (range 21.2-
80.3 ug/m3)
Chapel Hill, NC; HAPC; mean mass
121±14.0 ug/m3, range 15.0 to 358
ug/m3
Los Angeles, CA; HAPC; mean mass
cone. 194±26 ug/m3; range 135-229
ug/m3
>2.5 urn: 20±7 ug/m3; range 7-31
ug/m3
0.1-2.5 urn: 167±27 ug/m3; range 104-
201 ug/m3
<0. 1 um: 8±5 ug/m3; range 3-23 ug/m3
Mass percentages:
25% nitrate; 10% sulfate; 6% elemental
carbon.
Element composition (ug/m3):
silicon 4.1; iron 3.1; chlorine 2.7;
sodium 2.4; calcium 2.3; aluminum 1.7;
potassium 1.2
1 ml points
HRV
Venous blood:
CBC
Biochemical indices
(total protein, albumin,
UA, LDH, CRP)
Cytokines
ET-1
Fibrinogen and other
clotting factors
Pulmonary function
SaO2
BP
Exhaled NO
HRV
Ectopic beat incidence
Venous blood:
WBC, platelet, and
clotting factors
Sputum:
Cell counts
Results
CAPs caused significant decreases in time and frequency
domain HRV parameters (PNN50 and HF) at 0 and 24 h PE.
Individual subjects (n = 5) experienced abnormal beats
(premature atrial contractions and/or bradycardia).
Source apportionment not done.
CAPs caused decreases in WBC counts at 24 h PE, but no
other changes CRC values.
CAPs caused decreases in LDH at 24 h PE, but no other
changes in blood chemistries.
CAPs caused increases in fibrinogen, but other coagulation
factors and inflammatory mediators were unchanged.
Source apportionment not done.
CAPS had no effect on symptoms, spirometry, or induced
sputum. Decreased SaO2 and increased peripheral basophils
in healthy subjects. Modest increase in ectopic beats in
COPD subjects. HRV was lower in healthy subjects than
COPD subjects.
Source apportionment not done.
-------
Table A17 (cont'd): Other Acute CAPs Studies
Reference
Animals
Gong et al.
(2004b)
Campbell et
al. (2005)
Cassee et al.
(2005)
Species
Human, M&F
(19-5 lyr); healthy
(4) and mild
asthmatics (12)
Mice, M, Balb/c (6
wk); 9 mice/group;
pretreated daily with
OVA (50 ug) via
intranasal instillation
prior to CAPs
exposure; OVA
challenge 1 and 2 wk
PE, assessed 1 day
after challenge
Rat, M, SH (8-12
wk) or WKY (7 wk);
a subset were
preexposed to ozone
for 8 h 1 day before
CAPs
CAPs Exposure
2 h, alternating
15 min exercise
and rest; assessed
immediately PE,
at 4h, and at day
2. ECG before,
during and after
exposure
4 hr/day, 5
day/wk for 2 wk
in whole body
chambers
6 h, assessed 2 h
PE
CAPs Characterization
Los Angeles, CA; CPC; 80% coarse
(2.5-10 urn), 20% fine (<2.5 urn);
157 ug/m3 (range 56-218 ug/m3 )
Elemental composition (%):
silicon 19; sodium 18; iron 15;
chlorine 11; sulfur 9; aluminum 7;
potassium 4; magnesium 2;
titanium 1; 16 others
-------
Table A17 (cont'd): Other Acute CAPs Studies
oo
Reference
Animals (cont
Chang et al.
(2004)
Chang et al.
(2005)
Cheng et al.
(2003)
Kleinman
et al. (2005)
Species
'd)
Rat, M, SH, -200 g,
implanted with
radiotelemetry
transmitters
Rat, M, SH, -200 g,
implanted with
radiotelemetry
transmitters
Rat, M,. SD,
MCT-treated;
implanted with
telemetry
transmitters
Mice, Balb/c, M;
pretreated with OVA
via nasal instillation
and challenge one
and two weeks after
exposure
CAPs Exposure
5 h/day in
nose-only
exposure
chambers in
spring (4 days
total) and
summer (6 days
total)
5 h/day in
nose-only
exposure
chambers in
spring (4 days
total)
6 h/day in
nose-only
exposure
chambers for
3 consecutive
days, then rested
4 days; exposed
to CAPs on wk
2,3, and 4 and to
FA wk 1 and 5
WBI; 4 h/day for
5 day/wk for 2
wk; assessed 24
h after second
OVA challenge;
4 experiments
(July and
October 2001,
June and August
2002)
CAPs Characterization
Taipei suburb; VACES; mean mass
cone. 202±68.8 ug/m3 (spring) and
141±54.9 ug/m3 (summer); particle
number 2.30 x 105 particles/cm3 (spring)
and 2.78 x 105 particles/cm3 (summer)
Taipei suburb; VACES; mean mass
cone. 202±68.8 ug/m3; particle number
2.30 x 105 particles/cm3
Taipei suburb; VACES; mean mass
cone. 240±77 ug/m3; range 108 to 338
ug/m3
Elemental composition (ug/m3): Al 26.5;
Mg 6.8; S 2.8; Si 2.7; Fe 1.4; Ga 0.7; P
0.5; Zn 0.2; Ni 0.07; Mn 0.03; Cu 0.02;
Co 0.01; V 0.01
Los Angeles, CA; 50 or 150 m
downwind of heavily trafficked
roadway; VACES UF (< 150 nm) or F
(<2.5 jim)
UF ranges: mass 283^142 ug/m3; count
2.9-5. 9xl05 particles/cm3; elemental
composition (ug/m3): EC 16-18, OC
135-189, total metals 45-51, nitrate
24.7-53.7, sulfate 25.0-35.5
F ranges: mass 313-498 ug/m3; count
1.6-2.85xl05 particles/cm3; elemental
composition (ug/m3): EC 8.5-13, OC
86.0-253.8, total metals 10-109, nitrate
75.0-107, sulfate 25.3-76.9
Endpoints
HR
BP
QAI
HRV
HR
BP
core temperature
BALF:
Cell counts
Cell differentials
Cytokines
Plasma:
Cytokines
IgE
IgGl
Results
HR and BP significantly increased during spring CAPs
exposure (maximum |52 bpm and |9 mm Hg, respectively).
QAI decreased throughout the CAPs exposure in spring to a
maximum of 1.6 msec.
Statistically significant decreases in SDNN (60-85% of
baseline period) were observed during PM exposure.
The effects of CAPs on RMSSD were not significant,
although there was a trend toward decreased HRV.
An early decrease in HR (J.14.9 bpm) was observed,
followed by a gradual increase in HR (|8.6 bpm) to a
maximum observed 1 1 h after the start of the exposure.
BP initially decreased (J.3.3 mm Hg) during the first h of
exposure, then returned to normal.
No changes in core temperature were observed.
Mice exposed to fine CAPs in 2001 at the 50 m location had
elevated eosinophils and cytokines in BALF and elevated
IgGl in blood plasma compared to air controls.
Mice exposed to UF CAPs in 2002 at the 50 m location had
elevated IL-5 in BALF and increased IgGl in blood plasma.
Significant interactions were observed between treatment and
location for IL-5, eosinophils, and IgGl (i.e., mice exposed
to CAPs at 50-m had higher levels of allergic response
biomarkers than mice exposed to CAPs at 1 50-m downwind
of the freeway).
-------
Table A17 (cont'd): Other Acute CAPs Studies
Reference
Animals (cont
Lei et al.
(2004a)
Lei et al.
(2004b)
Nadziejko
et al. (2004)
Smith et al.
(2003)
Species
'd)
Rat, SD, M, 60 days
old;318.7±8.3g;
pretreated with
single 60 mg/kg ip
injection of MCT
Rat, SD, M, 300-
350 g; pretreated
with single 60 mg/kg
ip injection of MCT;
4 rat/group
Rat, M, F344,
18 mo; 6 rats/group,
crossover design
Rat, M, SD,
9-10 wk;
6 rats/group
CAPs Exposure
6 h/day for
3 days;
pulmonary
function assessed
5 h PE; blood,
lung and BALF 2
days PE
Low - 6h;
high - 4.5 h;
assessed 36 h PE
4 h/day for 1 day;
NOI; repeated
twice for CAPs
and ultrafine
C (500 and 1280
ug/m3) and 4
times for SO2
(1.2 ppm)
4 h/day for
3 consecutive
days in
6 experimental
sets (3 weeks in
fall, 3 weeks in
winter); assessed
immediately after
exposure on
day 3
CAPs Characterization
Taipei, Taiwan; VACES; mean mass
cone. 371.7 ug/m3
Elemental composition (ug/m3):
K 33.7;S 25.5; Al 6.1; Fe 4.7; P 2.7; Ca
2.3; Si 2.1; Zn 1.7; Mo 0.5; Ti 0.4; Cu
0.3; Mn 0.2; Pt 0.07; V 0.06; Co 0.04
Taiwan, Asian dust event particles;
ACES
Low: mean mass cone 315.6 ug/m3;
elemental composition (ug/m3): Si 53.3;
Al 14.0; S 6.25; Ca 6.1; K 3.1; Mg 2.7;
Fe 2.1; As 2.1; Ni 0.09; W 0.9; V 0.2
High: mean mass cone 684.5 ug/m3;
elemental composition: Si 41.6; Al 10.7;
K 3.6; As 2.9; Mg 1.2; Ca 1.7; W 1.4; V
0.1
Tuxedo, NY; centrifugal concentrator;
161 and 200 ug/m3
Fresno, CA; VACES; fall mean mass
cone. 260-847 ug/m3 (number 1.1-
1.2xl05 particles/cm3), winter mean
mass cone. 190-815 ug/m3 (number 0.9-
1.2xl05 particles/cm3); largest
contributors to PM mass were
ammonium nitrate and OC (60-80%)
Elemental composition ranges (ug/m3);
sulfate 13-51; nitrate 58-527; OC 61-
141;
EC 4-59; metals 8-38 (mostly Al, Si, S,
Ca, and Fe); unexplained 30-174
1 ml points
Pulmonary function
BALF:
Cell counts
Cell differentials
Total protein
LDH
Cytokines
BALF:
Cell counts
Cell differentials
Total protein
LDH
IL-6
Blood:
CBC
HR
Body temperature
Activity
Arrhythmia
BALF:
Cell counts
Cell differential
Cell viability
Results
CAPs caused decreased/and increased VT.
CAPs caused increased BALF total cells, PMN percentage,
protein, IL-6, and LDH.
MCh challenge following exposure caused increased penh.
A dose-dependent increase in WBC was observed following
exposure; no other blood parameters were altered.
Dose-dependent increases in total cells, percent PMN, total
protein, LDH and IL-6 were observed; no increase for AMs
or lymphocytes.
Increases were observed in the number of delayed beats
following CAPs exposure. No changes in arrhythmia
frequency were observed following ultrafine C or SO2
exposure.
Elevated PMN were observed following exposure during the
first week of fall and the first week of winter. The highest
levels of PM mass, nitrate, and OC were observed during
these two weeks.
The most consistent particle characteristics for all weeks
were particle number, OC, Cl, Ti, Fe, Zn, Mn, and Pb.
The particle characteristics that varied considerably across
the exposure periods were mass, nitrate, sulfate, and trace
elements (EC, Al, Si, S, K, Ca, Ba, Ni, Cu, Se, Cd).
-------
Table A17 (cont'd): Other Acute CAPs Studies
Reference Species CAPs Exposure CAPs Characterization Endpoints Results
Animals (cont'd)
Zelikoff Rat, F-344, M, 5 h/day for 1 day; NYC; centrifugal concentrator; 65- Lungs (affected rats): Rats exposed to NYC CAPs had increased bacterial burdens
etal. (2002) 7-9 mo, infected NOI; assessed 90 ug/m3 Absolute levels of at 9 h (10% above control), 18 h (300% greater than control),
with Streptococcus 4.5, 9, 18, 24, bacteria 24 h (70% above control), and 5 days (30% above control).
pneunoniae (15- and!20hPE Bacteria per g lung
20 x 106) via IT; 4
rats/group
oo
o
-------
Table A18: Subchronic CAPs Studies
Reference
Factor Analysis
Lippman et al.
(2005c)
Species
Mice, M, C57,
ApoE"'"
CAPs Exposure
6 h/day, 5 day/wk
for 5 mo.
CAPs Characterization
Tuxedo, NY CAPs; VACES; mean
mass cone. 113 ug/m
Endpoints
HR
HRV (SDNN, RMSSD); data
Results
SS was the largest contributor to PM mass (56%), then RS
(12%); MV/other were 30.9% and RO was 1.4%.
Source categories:
1. Secondary sulfate (SS)—high S, Si,
andOC
2. Resuspended soil (RS)—high Ca,
Fe, Al, and Si
3. Residual oil (RO)—V, Ni, and Se
4. Motor vehicle (MV) emissions
and other
analyzed from 1600-1800
(afternoon) and 130-430
(night)
RS (and PM mass) were associated with decreased HR during
CAPs exposure in ApoE"" mice.
SS (but not PM mass) was associated with short-term decreases
in HR in the afternoons following exposure in ApoE mice; RS
was associated with short-term increases in HR during the same
period.
MV traffic/other source category was associated with short-term
decreases in RMSSD in the afternoons following CAPs
exposures in C57.
>
oo
RO was associated with short-term decreases in SDNN and
RMSSD in the afternoons following CAPs exposure in ApoE"'
mice.
SS was associated with short-term decreases in SDNN and
RMSSD (also PM mass) in nighttime following CAPs exposure
in ApoE"" mice.
Maciejczyk et al.
(2005)
BEAS-2B; 0,
100, 300,
500 ug/mL for
24 h
9 104 cells/well
Ambient
(12.6±9.3 ug/m3)
and CAPs (108.6±
177.5 ug/m3) filter
samples collected
3/4-9/5/2003 M-F
(900-1500)
Tuxedo, NY; VACES
Source categories:
1. Secondary sulfate (SS)—S, Si, P,
EC, and OC
2. Resuspended soil (RS)—K, Ca, Mn,
Zn, Fe, Al, and Si
3. Residual oil (RO)—V and Ni
4. Motor vehicle (MV) emissions and
other—Zn, Se, Br, Pb, nitrate
NF-KB
RS was associated with short-term increases in SDNN and
RMSSD at night following CAPs exposure in ApoE mice.
The NF-KB response was correlated with the RO source
category.
SS contributed on average 65% to overall PM mass, RS
contributed 20%, and RO contributed 2%; 13% of the CAPs
mass was unaccounted for and included high loadings of Pb, Br,
Zn, Se, and nitrate.
S and OC correlated well with each other.
-------
Table A18 (cont'd): Subchronic CAPs Studies
Reference
Species
CAPs Exposure CAPs Characterization
1 ml points
Results
Other
Chen and
Hwang (2005)
Mice, C57
and ApoE"'";
3-10 rats/group
6 h/day,
5 day/wk for 5 mo
(4/1 1-9/5/2003)
>
oo
to
Chen and
Nadziejko
(2005)
Mice, C57,
ApoE"'", M&F
ApoE"'" + LDL"'"
(DK);
4-12 rats/group
6 h/day, 5 day/wk
for up to 6 mo
(3/10-9/5/2003);
C57 6 mo,
ApoE"'" 5 mo,
DK4mo
Tuxedo, NY; VACES; mean mass
cone. 110 |ig/m3
Tuxedo, NY; VACES ; mean mass
cone. 110±79, 120±90, and
131±99ng/m3
HR
HRV (SDNN, RMSSD);
data analyzed from 1600-
1800 and 130-430
Heart: histopathology
Aorta roots: total
atherosclerotic lesion area,
lipid contents, cellularity
For ApoE"" mice, SDNN gradually increased the first 6 wk
of CAPs exposure, then slightly decreased for next 12 wk,
and progressively increased at the end of study (1600-1800
and 130-430).
No changes in evening HR or HRV were observed in C57
mice. Slight increases in SDNN were observed at nighttime
after 6 wk of CAPs exposure.
No lag effects were observed.
There was no clear pattern between CAPs concentration and
estimated acute effects (48 h).
20 DK mice died (lesions were indicative of myocardial
infarction) during air or CAPs exposure. CAPs-exposed DK
mice seemed to die earlier than air-exposed DK mice and
females were more susceptible.
No abnormal lipid deposition in coronary artery in C57 or
ApoE"'" mice.
More mice in the CAPs group had coronary artery disease
(7/10) compared to the air (3/13) group. Similarly, more
mice in the CAPs group had complex atherosclerotic lesions
in the coronary artery (3/10) compared to the air group
(0/13).
All DK mice developed extensive lesions in the aortic sinus
regions; plaque lesion cellularity was elevated in
CAPs-exposed mice (28%).
ApoE"'" and DK mice had severe atherosclerosis covering
>40% of lumenal surface of aortic tree, which was
significantly greater for CAPs-exposed ApoE"" mice (66%).
-------
oo
Lippmann et al.
(200b)
Table A18 (cont'd): Subchronic CAPs Studies
Reference
Other (cont'd)
Gunnison and
Chen (2005)
Hwang et al.
(2005a)
Species
Mice, M&F
ApoEv- + LDL"
'-(DK);
3 rats/group
Mice, C57
and ApoE" ";
3-10 rats/group
CAPs Exposure
6 h/day, 5 day/wk
for 4 mo
(5/12-9/5/
2003); sacrifice
3 or 4 days PE
6 h/day, 5 day/wk
for 5 mo
(4/11-9/5/2003)
CAPs Characterization
Tuxedo, NY; VACES; median size
of 4 exposure days 389±2 nm; mean
mass cone. 131±99 ug/m3 (range
13-441 ug/m3)
Tuxedo, NY; VACES; median size
of 4 exposure days 389±2 nm;
mean mass cone. 133 ug/m3 (range
1 ml points
Heart gene expression
Lung gene expression
HR
Core temperature
Activity
Results
Many genes were up- or down-regulated following exposure
to CAPs. The largest functional categories with alterations
were heat shock proteins and other stress-response genes.
Other genes related to DNA binding and regulation of
transcription, defense responses, proteolysis, inflammatory
response, and signal transduction and signaling pathways
were changed.
The Dbp gene associated with circadian rhythm was
upregulated.
Chronic CAPs exposure was associated with nighttime
decreased HR (—34 bpm), body temperature (~1.0°C), and
activity (2.4 count/min) in ApoE" " mice starting 30 days after
5-627 ug/m3)
data analyzed from 130-430
(night) and 1100-1300
(morning)
exposure began.
There were few changes observed in HR, body temperature,
or activity at night in C57 mice with CAPs.
ApoE"" mice had increased body temperature and activity
during exposure (1100-1300) that was not associated with
CAPs (chamber effect). Decreased HR (12.4 bpm) was
associated with mean CAPs concentration during exposure.
Fluctuation of HR in ApoE"'" mice within longer time
intervals (4-7 h) increased 1.35-fold by the end of exposure;
fluctuation within short term intervals (15 min) decreased
0.7 fold.
Mice, C57,
ApoE"'", M&F
ApoE"'" +
LDL"'-(DK)
Whole-body
inhalation, 6 h/day,
5 day/wk up to
6 mo.; sacrifice
3 days after last
exposure day
Tuxedo, NY; VACES
Same as Lippmann et al. (I) Summary of results.
No inflammation was observed in the lungs as measured
by BALF.
-------
Sun et al.
(2005)
Table A18 (cont'd): Subchronic CAPs Studies
Reference
Other (cont'd)
Veronesi et al.
(2005)
Species
Mice, C57
and ApoE"'";
5-9 rats/group
CAPs Exposure CAPs Characterization
6 h/day, 5 day/wk Tuxedo, NY; VACES
for 4 mo; sacrifice
3 or 4 days PE
1 ml points
Dopamine-containing
neurons
Astrocytes
Results
In ApoE"'" mice exposed to CAPs, decreased tyrosine
hydro xylase-stained neurons (29%) in the substantia nigra
region of the brain were observed.
oo
Mice, M, ApoE"
'" fed normal and
high fat chow
6 h/day, 5 day/wk Tuxedo, NY; VACES; mean mass cone.
for 6 mo 85 ug/m3
Composite
atherosclerotic plaque in
thoracic and abdominal
aorta, vasomotor tone
changes
Increased glial fibrillary acidic protein-stained astrocytes
(8%) in nucleus compacta were observed in CAPs-exposed
ApoE"'" mice.
There were no effects of CAPs on neurons or astrocytes in
C57 mice exposed to CAPs.
The peak constriction due to serotonin or phenylephrine was
enhanced in high fat chow mice exposed to CAPs and the
half-maximal dose for dilation to acetylcholine was increased
in the same group.
The mean percentage positive areas of 3-nitrotyrosine and
iNOS in aortic sections was observed in normal and high fat
chow mice exposed to CAPs compared to the respective air
controls; there were no differences in eNOS staining.
Mice fed high fat chow and exposed to CAPs had elevated
lipid content in the aortic arch.
There was increased hydrogen peroxide generation in the
aorta of mice exposed to CAPs.
-------
Table A19: Size-fractionated and Collected Ambient PM Studies
Reference
Species (in vivo)!
Cell Type (in vitro)
Exposure
PM Characterization
Endpoints
Results
Humans
Schaumann
et al. (2004)
Humans, 12 healthy
subjects (8 F, 4 M); avg
27 yr
In Vivo
Gavett et al.
(2003)
Mice, Balb/c, F, 1-21 g;
OVA sensitized, 2-
12 mice/group
oo
Instillation into lingula,
100 ng/10 mL; HALF
collected 24 h PE
OA, 100 ng total in 50
|iL saline (1 or 2 doses);
assessed 18 h, 2 and 7
days after challenge
2 exposure protocols:
1) 10 ng OVA on Days
0 and 2 for sensitization
2 h prior to PM
exposure on both days
and 20 jig OVA on Day
14 for challenge
2) 20 jig OVA on Day 0
and PM exposure on
Day 14 with OVA
challenge 2 h later
Ambient PM from Zerbst,
Germany (agricultural
sources) or Hettstedt,
Germany (industrial and
domestic sources); collected
in 1999; PM2.5
Ambient PM from Zerbst,
Germany (agricultural
sources) or Hettstedt,
Germany (industrial and
domestic sources); collected
in 1999; PM2.5
HALF:
Cell counts
Cell differentials
AM surface markers
Cytokines
Total protein
Albumin
CL
Pulmonary function after
MCh challenge
Serum OVA-specific IgE
HALF:
Cell counts
Total protein
Albumin
LDH
NAG
Cytokines
Exposure to Hettstedt PM resulted in more
numerous responses compared to Zerbst
PM.
Endotoxin levels were very low in both
samples.
Allergic mice exposed to either PM had
elevated penh at challenge and a number of
BALF markers were increased 2 days post-
challenge.
Mice exposed to Hettstedt PM also had
elevated penh, PMN, eosinophils, and IgE
2 days post-challenge and those exposed to
Zerbst PM had increased IL-13.
Hettstedt had much greater levels of Zn, Pb,
Cu, Cd, Sn, and As.
Neither Hettstedt nor Zerbst administered
before sensitization enhanced allergic
responses (except IgE in Hettstedt-exposed
mice).
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
Species (in vivo)!
Cell Type (in vitro)
Exposure
PM Characterization
Endpoints
Results
In Vivo (cont'd)
Corey et al.
(2006)
Gerlofs-Nijland
et al. (2005)
Mice, ApoE", 11-12 mo,
2-3 mice/group
Rats, SH, M,
250-350 g,
4-6 rats/group
Nasal instillation, 1.5
mg/kg; assessed through
4 day PE
IT, 0.3, 1,3, and
10 mg/kg; assessed 4,
24, or 48 h PE
oo
Gilmour et al.
(2004)
Mice, F, CD1, 20-25 g,
5 mice/group
IT, 25 and
100 jig/mouse (approx.
1.25 and 5 mg/kg);
assessed at 18 h PE
Seattle, WA PM2.5 collected in
close proximity to a freeway
and industrial area
Road tunnel dust (RTD)
collected outside a traffic
tunnel in Netherlands; coarse
and fine fractions were
combined together prior to
exposure
Coal fly ash derived from
Montana (low-sulfur
subbituminous; 0.83% sulfur,
11.72% ash content) or
Western Kentucky (high-
sulfur bituminous;
3.11% sulfur, 8.07% ash
content); thoracic coarse, fine,
and UF fractions
HR
HRV (SDNN, RMSSD,
HF, LF)
Activity
BrdU
HALF (right lung);
Cell counts
Cell differentials
MPO activity
LDH
NAG
ALP
UA
Albumin
Total protein
CC16
GSH, GSSG
Cytokines
Fibrinogen
Hematology
ET-1
Histopathology
(left lung)
HALF:
Cell counts
Cell differentials
Cell viability
Cytokines
Increased HR immediately following
exposure; decreased HR on days 2 and 3.
Decreased SDNN on days 2, 3, and 4 and
decreased RMSSD on days 2 and 3.
Lowered LF/HF ratio on days 3 and 4.
Increased PMN and AM were observed in
rats exposed to RTD at 24 h, regardless of
dose.
Increases in fibrinogen were observed in
rats exposed to 10 mg/kg of RTD at 24 and
48 h.
A number of HALF biomarkers were
increased with exposure to RTD at all time
points.
There was a dose-dependent increase in the
number of inflammatory foci at 24 and 48 h
in rats exposed to 3 or 10 mg/kg RTD.
There were no differences in effects for
either coarse particle types compared to
saline.
The UF fraction of combusted Montana coal
induced greater neutrophilic inflammation
and cytokine production than thoracic
coarse or fine PM.
The fine fraction of the western Kentucky
fine PM caused increases in PMN, albumin,
and protein.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
Species (in vivo)!
Cell Type (in vitro)
Exposure
PM Characterization
Endpoints
Results
In Vivo (cont'd)
Nygaard et al.
(2005)
Mice, BALB/cA, F,
5-9 mice/group
Subcutaneous injection Ambient PM from Oslo,
of particles (100 jig)
with or without OVA
(50 \ig) into hind
footpads; 20 )iL
solution; assessed 5
days PE
Rome, Lodz, Amsterdam;
spring, summer, and winter
2001/2002; thoracic coarse
and fine fractions
Popliteal lymph node
(PLN):
Cell count
Cell surface molecules
Cell cytokines
Histology
There was no observed difference between
most of the coarse and fine fractions in the
induction of IL-4 and IL-10. However, the
Lodz coarse PM (+OVA) caused effects that
were statistically significant compared to
the Lodz fine PM (+OVA).
Allergic mice exposed to PM had
exacerbated effects compared to allergen
alone or PM alone.
oo
Exposure to Rome or Oslo PM resulted in
increased cytokine production.
Exposure to Oslo PM caused alterations in
PLN cell counts.
Rhoden et al.
(2005)
Rat, SD, M, 300 g;
pretreated with 1) atenolol
or glycopyrrolate or 2)
NAC
CAPs: WEI, Boston CAPs
700 ng/m , 5 h; assessed
immediately PE Urban air particles; SRM
1649
SRM 1649: IT, 750 ng;
assessed 30 min PE
Heart CL
SDNN
HR
TEARS (heart)
Wet/dry heart ratios
Exposure to OVA+PM resulted in increased
expression of surface molecules on B
lymphocytes.
CAPs caused increases in TEARS, CL, and
wet/dry heart ratio.
SRM 1649 exposure resulted in elevated
TEARS, CL, and SDNN during recovery.
Pretreatment with NAC prevented changes
in heart rate, SDNN, heart wet/dry ratio, and
CL in SRM 1649- and CAPs-exposed rats.
Administration of atenolol or glycopyrrolate
prior to SRM 1649 or CAPs exposure
prevented changes in CL and TEARS.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
In Vivo (cont'd)
Schins et al.
(2004)
Species (in vivo)!
Cell Type (in vitro)
Rat, Wistar, F,
350—550 g; 5 rats/group
Exposure
IT, 0.35 mg/rat
(0.6—1 mg/kg); assessed
18hPE
PM Characterization
Ambient PM from Duisburg
(D) and Borken (B) Germany
collected in weekly intervals
Feb-May 2000; thoracic
coarse and fine fractions
D: heavily-industrialized
area; endotoxin 0.3 EU/mg
for fine, 5 EU/mg for coarse
Endpoints
BALF:
Cell differentials
GSH, GSSG
LDH
Total protein
Cytokines
In vitro whole blood
(WB) assay: Cytokines
Results
Rats exposed to coarse PM (regardless of
location) had increased percent PMN in
BALF and TNF-a and IL-8 in the whole-
blood assay.
Only rats exposed to coarse Borken PM had
depleted GSH levels and elevated TNF-a in
BALF.
oo
oo
Scares et al. Mice, Balb/c, 8—10 weeks;
(2003) 20 mice/group
WBI,
(monthly average) for
120 days; for Sao Paulo
SO2 ranged from 12-20
jig/m3, CO (8 h) ranged
from 2.4-3.2 ppm, and
NO2 ranged from
97-108jig/m3
B: Rural area; endotoxin
0.6 EU/mg for fine,
6.6 EU/mg for coarse
Urban air of Sao Paulo, Brazil
(including gases)
Urban air of Atibaia (AT) in
rural Brazil, 65 km from Sao
Paulo
Blood from tail vein:
Micronuclei (MN) in
peripheral erythrocytes
Rats exposed to coarse Duisburg PM had
increased MIP-2 in BALF.
The greatest MN increase was observed at
90 days.
Significant increases in MN frequency were
observed for Sao Paulo mice compared to
AT mice, with no significant time
interaction.
A positive association between all air
pollution measures (PMio, NO2, and CO)
and MN frequency difference was observed
for the previous 8-14 days of exposure.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
In Vivo (cont'd)
Steerenberg
et al. (2005)
Species (in vivo)!
Cell Type (in vitro)
Mice, Balb/cByJ.ico, M;
6-8 weeks; OVA
sensitization (0.4 mg/ml) at
days 0 and 14,
challenge +/- PM on days
35, 38, and 41
Exposure
IN, 0, 3, or 9 mg/mL
PM with OVA
(1 50-450 (igPM
/mouse); assessed on
day 42
PM Characterization
Ambient PM collected during
spring, winter, and summer
from: (1) Oslo (near road),
(2) Lodz (near heavy traffic),
(3) Rome (rail station),
(4) Amsterdam (near busy
roadway), or (5) De Zilk (low
traffic and natural allergens);
thoracic coarse and fine
fractions
Endpoints
Serum from abdominal
aorta:
IgE
IgGl
IgG2a
HALF:
Total cells
Cell differentials
LDH
Cytokines
Lung histopathology
Results
Spring and winter PM samples were more
potent than summer PM samples.
The order of mild response for IgE, IgGl,
IgG2a, and eosinophil influx was (Lotz>
Rome> Oslo>Amsterdam).
The coarse fraction induced greater adjuvant
activity for De Zilk PM compared to the fine
fraction.
oo
VO
The coarse and fine fractions from Lodz or
Rome with OVA exposure induced a number
of effects including increased eosinophils,
PMN, and monocytes.
The adjuvant activity with immunoglobulins
was greater with the fine than the coarse
fraction.
In general, the insoluble portion of the coarse
PM was responsible for the observed
adjuvant activity.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
Species (in vivo)!
Cell Type (in vitro)
Exposure
PM Characterization
Endpoints
Results
In Vivo (cont'd)
Steerenberg
et al. (2006)
Rat, Wistar, M,
8 rats/group (also mice, but
data reported in other
studies—Nygaard et al.
2005 and Steerenberg et al.
2005)
IT, 1 or2.5mgPM/rat;
assessed 24-h PE
Ambient PM collected during
spring, winter, and summer
from: 1) Oslo (near road), 2)
Lodz (near heavy traffic), 3)
Rome (rail station), 4)
Amsterdam (near busy
roadway); thoracic coarse and
fine fractions combined in the
analysis
HALF:
Albumin
CC16
Cytokines
Correlations between the traffic and
industry/combustion/ incinerator source
cluster and pathology lesion occurrence and
increased IgE were observed in the
respiratory allergen model.
The combustion of black and brown
coal/wood smoke source cluster correlated
with albumin in rats and IgE and pathology
score in the respiratory allergen model.
Crustal material source cluster correlated
with CC16 in rats and IL-6, TNF-a, and
MIP-2 in macrophage and type 2 cells
(in vitro).
Secondary inorganic/long-range aerosol
source cluster correlated with IgE in the
systemic allergen model.
Sea spray source cluster correlated with
CC16 in rats and IL-6 in macrophages
(in vitro); the CC16 response also correlated
with endotoxin.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
In Vitro (cont'd)
Becker et al.
(2003)
Species (in vivo)!
Cell Type (in vitro)
Human AM
(3 x 105 cell/mL)
Exposure
50 ng/mL; 18-20 h
PM Characterization
PM downwind of Utrecht
(background site; collected
Endpoints
Cytokines
Phagocytosis
Results
Increased IL-6, MlP-la, and phagocytosis
and decreased CL and GDI Ib receptor
>
105 cells/cm2) and
Becker et al. Human AM
(2005) (2-3
normal bronchial epithelial
(NHBE) cells (1 x 105
cells/cm2)
AM: 50 ng/mL; NHBE:
11 ng/mL;
18-24 h
March 1999) and west of
Utrecht, Netherlands
(influenced by light industrial
activities and freeway traffic,
esp. diesel; collected June
1999); thoracic coarse, fine,
and UF fractions
Chapel Hill, NC PM;
collected Oct 2001, Jan 2002,
Apr 2002, Jul 2002; thoracic
coarse, fine, and UF fractions
CL
Cell surface receptor
expression
Cytokines
ROS
CL
expression were greater for the thoracic
coarse fraction than those observed with the
other size fractions.
Endotoxin was detected in water extracts of
thoracic coarse particles.
Thoracic coarse PM was more potent in
inducing IL-6 and IL-8. For IL-6, Oct
thoracic coarse PM caused the greatest
response.
The July thoracic coarse PM exerted the
greatest production of ROS as measured in
AM.
Thoracic coarse Fe and Si were positively
associated with IL-6 release in AM.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Species (in vivo)/
Reference Cell Type (in vitro) Exposure PM Characterization Endpoints Results
In Vitro (cont'd)
Becker etal. Human AM (2-3x105 AM: 50 |xg/mL; Chapel Hill, NC PM; Cytokines Thoracic coarse PM was more potent in
(2005b) cells/cm2) and normal NHBE: 25, 50, 100, 250 collected for 72 h; thoracic Gene expression inducing IL-8 release in NHBE cells. This
bronchial epithelial \ig/mL; coarse, fine, and UF fractions response was blocked with an antibody for
(NHBE) cells (IxlO5 18-24 h TLR2 was added.
cells/cm2)
IL-6 release in AM was inhibited by
addition of TLR4 agonist or an endotoxin-
binding protein for all size fractions.
Expression of TLR4 was increased in
NHBE cells exposed to thoracic coarse PM
only.
Expression of TLR2 was increased in AM
exposed to all three size fractions, although
the largest increase was observed for the
thoracic coarse fraction. A decrease in
TLR4 expression was observed in AM
exposed to thoracic coarse PM.
Thoracic coarse PM was the most effective
inducer of Hsp70 in NHBE cells. Fine PM
also stimulated an increase in Hsp70
expression.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
In Vitro (cont'd)
Hetland et al.
(2005)
Species (in vivo)/
Cell Type (in vitro)
WKYratAM; 1.5x106
cells/mL
Exposure
10, 20, 50, or 100
Hg/mL; 20 h
PM Characterization Endpoints
Ambient PM collected during Cytokines
spring, winter, and summer
Results
Thoracic coarse PM collected during spring
and summer from Lodz was the most potent
2001/2002 from: 1) Oslo
(near road), 2) Lodz (near
heavy traffic), 3) Rome (rail
station), 4) Amsterdam (near
busy roadway); thoracic
coarse and fine fractions
for IL-6 release, followed by Rome and
Oslo.
Thoracic coarse PM collected from
Amsterdam had the greatest IL-6 induction
for the winter compared to thoracic coarse
PM from other locations.
The spring thoracic coarse PM from Rome
and Lodz induced TNF-a release.
The fine fractions did not induce a marked
increase in TNF-a release in any city for
any season.
The thoracic coarse fractions had higher Fe,
Cu, and Al content than fine PM.
Endotoxin levels were also greater in the
thoracic coarse fractions, but IL-6 release
was similar when cells were treated with an
endotoxin-binding protein (polymyxin).
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
Species (in vivo)!
Cell Type (in vitro)
Exposure
PM Characterization
Endpoints
Results
In Vitro (cont'd)
Huang et al.
(2003)
Human BEAS-2B and
mouse RAW 264.7;
5 x 105 cells/mL
100 jig/mL; 8-16 h
PM from 4 different sites
in Taiwan-background
(B), urban (U), traffic (T),
or industrial (I); thoracic
coarse, fine, and UF
fractions
BEAS-2B:
IL-8
Lipid peroxidation
RAW 264.7:
TNF-a
Cell viability
Increases in TNF-a due to PMi 0
exposure correlated with Fe and Cr,
although 77% of the response was
attributable to the endotoxin content.
For thoracic coarse PM, there was
significant correlation between IL-8
and lipid peroxidation findings; Mn
and Fe were more abundant in the
thoracic coarse fraction compared to
the other sizes.
For the fine PM fraction, increases in
IL-8 correlated with Mn and Cr and
increases in lipid peroxidation were
associated with EC and OC content.
Li et al. (2002)
RAW 264.7 and THP-1
cells
10-200 jig/mL; 8 h
CAPs from Downey, CA HO-1
in Los Angeles basin
using VACES from
Mar 15-Dec 7 2000;
thoracic coarse and fine
fractions
MnSOD
INK
B-actin
GSH/GSSG
Apoptosis
Cu and Zn were most abundant in
PMl.O-2.5.
There were no differences in Ni, V,
and Cr among size fractions.
The fine fraction induced a greater
effect than thoracic coarse PM on all
endpoints.
Coarse PM collected in Sept and Dec
resulted in increased HO-1
expression and cell cytotoxicity. The
highest levels of OC were observed
in December.
Thoracic coarse PM collected from
Jan-Feb 2001 induced HO-1
expression and had higher PAH
content than the December thoracic
coarse samples.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
In Vitro (cont'd)
Li et al. (2003)
Species (in vivo)/
Cell Type (in vitro)
Human BEAS-2B and
mouse RAW 264.7
Exposure
8-100 ng/mL (12.3 or 21.1 for
coarse, 17.3 or 20. 9 for fine,
and 1.9 or 3.9 ug/m3 for
PM Characterization
CAPs from Los Angeles
basin (USC as a typical
urban site with vehicular
Endpoints
HOI
GSH/GSSG
ROS
Results
UF PM was the most potent in
inducing oxidative stress which was
associated with OC and PAH content.
ultrafme); 16 h
Pozzi et al. (2003) Mouse RAW 264.7
30 or 120jWmL(13.6or
54.5 ng/cm*); 5 or 24 h
traffic and Claremont as a
receptor site) using
VACES from Nov 2001-
March 2002; thoracic
coarse, fine, and UF
fractions
Ambient PM from Rome,
Italy (mainly traffic-
derived) collected for 15
days in Sept 1999;
thoracic coarse and fine
fractions
Endotoxin:
Thoracic coarse = 7.68
EU/mg
Fine= 1.92 EU/mg
LDH
AA
Cytokines
Thoracic coarse PM showed little
toxic effects.
Thoracic coarse PM collected in
large cytoplasmic vacuoles in RAW
264.7 cells and UF particles lodged
inside mitochondria.
At 120 |xg/mL, thoracic coarse PM
induced significant release of LDH
and fine PM did not result in any
change in LDH release.
Thoracic coarse PM fraction was
slightly more effective in releasing
AA and IL-6 compared to the fine
fraction at 5 h.
Thoracic coarse PM fraction at
30 |xg/mL induced greater amounts of
TNF-a production at 5 and 24 h.
-------
Table A19 (cont'd): Size-fractionated and Collected Ambient PM Studies
Reference
Species (in vivo)/
Cell Type (in vitro)
Exposure
PM Characterization
Endpoints
Results
In Vitro (cont'd)
Shi et al. (2003)
Human A549; 1.2xl05
cells/ chamber
50 jxg/mL; 2 h
Ambient PM from
Dusseldorf, Germany
from Jul-Dec 1999;
coarse and fine fractions
Hydroxyl radical
formation (using electron
spin resonance)
8-Hydroxyde-
oxyguanosine (8-OHdG)
in A549 DNA or calf
thymus DNA
Coarse PM had greater ability to
generate hydroxyl radicals and 8-
OHdG compared to fine PM at equal
mass. Cu correlated with hydroxyl
radical and 8-OHdG formation in
coarse PM.
For coarse PM, the autumn/winter
samples induced nearly double the
hydroxyl radicals generated by the
summer samples.
Both coarse and fine fractions
induced 8-OHdG in A549 cells.
Vernanth et al. BEAS-2B; 2.0x 104
(2004) cells/cm2
Veranth et al. BEAS-2B; 3.5 x 104
(2006) cells/cm2
10, 20, 40, 80, 160 jig/cm2; Dust PM2.5 (0.3-3 urn): Cell viability
(=25^100 ng/mL), 24 h Cytokines
DD: desert dust (unpaved TRPV1 receptor
road) ROS
WM: west mesa (wind-
generated dust area)
R4: range 40 (unpaved
road)
UN: Uinta (wind and
recreation activity)
10, 20, 40 or 80 jig/cm2 Urban and rural surface Cell viability
(=25-200 ng/mL); 24 h soils (32) from the Cytokines
Southwestern U.S.; PM2.5
The cytotoxicity ranking was as
follows: UN>WM>R4>DD.
The IL-6 response was as follows at
the highest dose: DD>R4>UN>WM.
Heating the particles attenuated the
IL-6 response.
LPS induction of IL-6 and IL-8
release was significantly less than
that from DD.
Rank order of potency was different
at low and high PM concentrations.
Coal fly ash samples did not affect
IL-6 compared to soil-derived dusts.
Strongest correlations for IL-6 and
IL-8 were with low volatility EC and
OC.
-------
Table A20. Acid Aerosol Studies
Reference
Species
Exposure
Exposure Characterization
Endpoints
Sulfate Effects
Controlled human study
Tunnicliffe et al.
(2003)
Humans, healthy
(7F, 5M; avg 34.5
yr) and mild
asthmatics (5F, 7M;
avg 35.7 yr; all using
short-acting p
agonists); double
blind, random order
design; prior to
exposure subjects
brushed teeth and
gargled with
mouthwash to reduce
oral ammonia levels
Animal toxicology studies
Kleinman et al.
(2003)
Rat, F344, 22-
24 mo; 10-
12 rats/group
1 h; head-only
exposure system;
measured during,
pre- and/or post-
exposure, or 5.5-6 h
later
4h/day,
3 consecutive
day/wk, 4 wk; NOI;
12hPE
Six exposures:
1)FA
2) SO2 (200 ppb)
3) sulfuric acid (200 ug/m3;
low)
4) sulfuric acid (2000 ug/m3;
high)
5) NH4HSO4 (200 ug/m3; low)
6)NH4HS04(2000ug/m3;
high)
Particle exposures target MMD
0.3 um, count mode =30 nm.
Four exposures:
(1)FA
(2) 03 (0.2 ppm)
(3) Low cone, particle mixture
(50 ug/m3 EC + 70 ug/m3
NH4HSO4) +O3 (0.2 ppm)-0.3
umMMAD,2.5GSD
(4) High cone, particle mixture
(100 ug/m3 EC+140
ug/m3 NH4HSO4) + O3 (0.2
ppm)-0.3 urn MMAD, 2.3 GSD
Self-reported symptoms
Ventilation (breaths/min,
VT)
Lung function
Exhaled NO
Nasal lavage (AA and
UA)
Lung histology
Cell replication in lung
epithelial and interstitial
cells
BALF:
Albumin
mucus glycoprotein
total protein
AM Fc receptor binding
AM function
Asthmatics exposed to SO2 had
increased respiratory rates.
Asthmatics exposed to low or high
concentrations of NH4HSO4 had
increased exhaled NO levels.
Healthy subjects exposed to low or high
concentrations of sulfuric acid or
NH4HSO4 had elevated UA levels in
nasal lavage.
Exposure to either concentration of the
particle mixture resulted in elevated cell
replication (290-340%) and decreased
AM Fc receptor binding and respiratory
burst activity.
Greater cell replication was observed in
the interstitial lung compared to the
epithelial region.
At the end of exposure, AM were
activated but by 12 h, function was
depressed.
Increases in total protein were observed
in the low concentration particle
mixture group only.
-------
Table A20 (cont'd). Acid Aerosol Studies
Reference
Species
Exposure
Exposure Characterization
Endpoints
Sulfate Effects
In Vitro
Kleinman et al.
(2006)
00
Beck-Speier
etal. (2003)
Rat, SD, M, 200 j
5-15 rats/group
4 h; NOI; assayed 42
h post-exposure
Dog, AM
(1 x 106/mL)and
blood PMN
Sulfite and sulfate at
pH6orpH7;30
Nine exposures:
(1) FA
(2) O3-0.3ppm
(3) O3-0.6ppm
(4) H2SO4-0.5 mg/m3
(5) H2SO4-1.0mg/m3
(6) O3 + H2SO4-0.3ppm + 0.5
mg/m3
(7) O3 + H2SO4-0.3 ppm + 1.0
mg/m
(8) O3 + H2SO4-0.6ppm + 0.5
mg/m
(9) O3 + H2SO4-0.6 ppm + 1.0
mg/m
Aerosol MMD 0.23-0.28 urn
(GSD2.1-2.3).
l.OmM
Lung histology
DNA synthesis in nose,
trachea, and lung
AM Fc receptor binding
AM function
PAF
LTB4
5-HETE
12-HHT
TXB2
PGE2
PLA2
Exposure to O3 resulted in Type 2
lesions in the lung parenchyma at
0.6 ppm; co-exposure with H2SO4
attenuated this effect (significant
interaction).
O3 and H2SO4 do not act synergistically
in this study.
Sulfite at pH 7 activates PLA2 enzymes
for release of arachidonic acid and
synthesis of PAF.
Sulfite activates cPLA2 and sPLA2
through signaling of the ERK1,2
pathway.
-------
APPENDIX B
Bibliographies and Annotated Bibliographies for Recent Studies
on the Health Effects of Particulate Matter Exposure
Recent Multicity Epidemiologic Studies
Epidemiologic Studies on Health Effects Associated with Exposure to Traffic
Toxicology Studies of Traffic, Diesel, or Vehicle Exhaust
Toxicology and Epidemiology Studies of Ultrafme Particles
Toxicology and Epidemiology Studies of Metals or Metal-Containing Particles
Toxicology Studies of Traffic, Diesel, or Vehicle Exhaust
Epidemiologic Studies on Health Effects Associated with Exposure to Traffic
Toxicology Studies of Endotoxin/LPS or Endotoxin/LPS-Containing Particles
Toxicology and Epidemiology Studies of Wood Smoke
B-l
-------
Recent Multicity Epidemiologic Studies
The following three studies are described in detail in Tables 1 and 2. The remaining
studies are grouped by the general issues being evaluated.
Ostro B, Broadwin R, Green S, Feng W-Y, Lipsett M. 2006. Fine particulate air
pollution and mortality in nine California counties: results from CALFINE. Environ
Health Perspect 114: 29-33.
Burnett RT, Stieb D, Brook JR, Cakmak S, Dales R, Raizenne M, Vincent R, Dann T.
2004. Associations between short-term changes in nitrogen dioxide and mortality in
Canadian cities. Arch Environ Health 59:2280236.
Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, Samet JM. 2006.
Fine particulate air pollution and hospital admission for cardiovascular and respiratory
diseases. JAMA 295:1127-1134.
Confounding by co-pollutants, weather, influenza epidemics:
Schwartz J. (2004a): Potential confounding of associations between PMio and mortality by
weather and season was assessed in 14 U.S. cities. A 0.36% (95% CI: 0.22, 0.50) excess risk in
mortality per 10 |ig/m3 increase in PMio was estimated using symmetrical sampling of control
days. Results were little changed when control days were matched on temperature, the time
stratified method was applied, or more lags of winter time temperatures were used. These results
indicated that associations between PMio and mortality risk are unlikely to be confounded by
weather and season, and are robust to the analytical method.
Schwartz J. (2004b): Uses case-crossover design to assess potential confounding of associations
between PMIO and mortality by gaseous co-pollutants in 14 U.S. cities. Significant associations
reported with case-crossover matching for each of the 4 gaseous co-pollutants; effect estimate
sizes range from 0.45% to 0.81% increases per 10 |ig/m3 PMio.
Welty LJ, and Zeger SL. (2005): Used two flexible versions of distributed lag models to control
for weather and season in 100 cities (1987-2000), with a 0-, 1- or 2-day lag for PMio. Results
were consistent with previous analyses, with effect estimates of approximately 0.2% increase in
mortality per 10 |ig/m3 PM.
Touloumi G et al. (2005): Used data from 7 APHEA-2 cities and found that adjustment for
influenza epidemics increased effect estimate for PMio-mortality associations in most cases.
Concentration-response function and threshold evaluation:
Daniels MK et al. (2004): Applied flexible modeling strategies to daily time-series data for
20 U.S. cities (1987-1994). Spline model showed a linear relation without indicating a threshold
for relative risks of death from all causes and for cardiovascular-respiratory cases with short-
term PMio exposure.
B-2
-------
Evaluation of factors influencing heterogeneity:
Dominici F et al. (2003): City-specific and regional effect estimates provided for the 88-city
analysis (1987-1994). The authors report "some modest variation in the relative risks across the
nation ... we were unable to explain the heterogeneity using descriptors of the population, air
pollution characteristics, and reliability of the PMio measurement data."
Martins et al. (2004): Significant associations were observed between PMio and respiratory
mortality in the elderly (^60 yr) in the combined analysis for six regions in Sao Paulo, Brazil,
with an effect estimate of 5.4% (2.3, 8.6) excess risk per 10 |ig/m3 increase in PMio at a multiday
lag of 0 to 2 days. The greatest effect (14.2% [95% CI: 0.4, 28.0]) was found in the region with
the highest % of slums, and the lowest % with college education and high monthly income. The
effect of PMio on respiratory mortality was strongly and negatively correlated with two SES
indicators: % with college education and family income, and positively correlated with greater
% living in slums.
Le Tertre A, et al. (2005): Used data from 21 cities (includes one non-APHEA city), reporting
heterogeneity in associations between PMio and mortality and calculates Bayesian estimates.
A meta-regression method was then used to adjust for the identified sources of the heterogeneity.
The authors state that the heterogeneity present in the data could be better taken into account
by deriving an estimated underlying distribution that represents the dispersion observed
between cities.
Medina-Ramon M, et al. (2006): Uses case-crossover design to evaluate effects of ozone and
PMio on respiratory hospital admissions and evaluate city characteristics that may explain
heterogeneity in data from 36 U.S. cities. Significant associations found for both pollutants with
pneumonia and COPD hospital admissions (effect estimates per 10 |ig/m3 PMio of 1.47% and
0.84%, respectively). Effect estimates for PMio reduced with greater air conditioning use in
cities; little difference based on percentage of PMio from traffic.
Samoli E, et al. (2005): Using data from 22 cities, found that association between PMio or BS
and mortality could be adequately estimated using a linear model. Tested thresholds at 10 and
20 |ig/m3 PMio and found that linear models had better fit. The authors also report heterogeneity
in associations between cities that is partly explained by several factors, with increased effect
estimates associated with hotter climates, mean NC>2 concentration as an indicator of traffic
emissions, and lower standard mortality rates (more elderly people in population).
Zeka A, etal. (2005): Using case-crossover design, significant associations were reported
between PMio and both cardiovascular and respiratory mortality in 20 U.S. cities that were
stronger using 3-day cumulative distributed lag model. Associations were increased in size with
increasing percent PMio from traffic and with increasing summer temperature variability.
Zeka A, etal. (2006): Using data from 20 U.S. cities with case-crossover design, reported
significant associations between PMio and mortality from all causes, respiratory, and heart
disease, and positive but not significant associations with MI and stroke deaths. Substantial
effect modification was found for some sociodemographic factors (larger with >75 years, little
difference for gender or race), location of death (larger for out-of-hospital), season (larger in
B-3
-------
spring and fall) and coexisting medical conditions (e.g., secondary diagnoses of pneumonia,
diabetes, heart failure).
Lag Structure:
Analitis A, et al. (2006): Used 2-stage hierarchical model with data from 29 APHEA-2 cities,
and report significant associations with cardiovascular mortality (0.76% per 10 |ig/m3 PMio) and
respiratory deaths (0.58% per 10 |ig/m3 PMio) using 0-1 day average lag. With distributed lag
model effect sizes increase, particularly for respiratory mortality. The associations are
independent of ozone, but reduced in size with adjustment for 862 and NC>2.
Roberts, S. (2005): This investigation finds that distributed lag models return particulate air
pollution mortality effect estimates that are more robust and less prone to negative bias than
single- and multi-day moving average exposure measures. The author concludes that distributed
lag models should be preferred in future air pollution mortality time series studies and helps
quantify the negative bias that can result from using single or multi-day moving average
exposure measures.
Zanobetti A, et al. (2003): Using distributed lag models in 10 cities from the APHEA-2 project,
effect estimate size for association with PMio doubles for cardiovascular deaths and is five times
higher for respiratory disease deaths compared with 1-day lag models.
Zeka A, et al. (2005): Using case-crossover design, significant associations were reported
between PMio and both cardiovascular and respiratory mortality in 20 U.S. cities that were
stronger using 3-day cumulative distributed lag model. Associations were increased in size with
increasing percent PMio from traffic and with increasing summer temperature variability.
Mortality displacement:
Dominici F, et al. (2003): Used decomposed time series of PMio data for 4 U.S. cities for which
daily data were available (1987-1994), and reported larger relative rates of mortality associated
with PMio using longer timescale (14 days to 2 months) than shorter timescale (1 to 4 days),
indicating that association does not represent advancement of death by just a few days for frail
individuals.
Seasonal variation:
Peng RD, et al. (2005): Bayesian semiparametric hierarchical models for estimating time-
varying effects of pollution on mortality in multisite time series studies. Effect estimates for
winter, spring, summer, and fall were, respectively, 0.15%, 0.14%, 0.36% and 0.14% increases
per 10 |ig/m3 PMio (1-d lag), with an all-year estimate of 0.19% per 10 |ig/m3 PMio. Effects were
stronger in the summer for the Northeast and Industrial Midwest, but little difference across
seasons in the southern regions and northwest.
New health outcomes:
Ballester et al. (2006): Significant associations reported between PMio (lag 0-1 day) and
emergency admissions for cardiovascular diseases and heart diseases. Significant associations
B-4
-------
were also reported with ozone and CO, while associations with 862 and NO2 were more
sensitive in two-pollutant models.
Ibald-Mulli A, et al. (2004): Study of 131 adults in Helsinki, Erfurt and Amsterdam with
biweekly clinic visits for 6 months. Results suggest decreased blood pressure (diastolic and
systolic) and in heart rate.
Timonen KL, et al. (2006): Same cohort as above with analysis of heart rate variability (5-min
measurement). Ultrafine particles associated with decreased LF/HF in pooled analysis; PM2.5
associated with decreased HF and reduced LF/HF in Helsinki but opposite association in Erfurt,
and no clear association in Amsterdam. Suggest that effects may be modified by location and
characteristics of individual.
von Klot S, et al. (2005): In cohort of 22,000+ first MI survivors in Augsburg, Barcelona,
Helsinki, Rome and Stockholm, significant associations were reported for cardiac hospital
readmissions with PMio, ultrafine particle number count, CO, NO2 and 63.
Wellenius et al. (2006a): Using case-crossover analysis, a significant association was reported
between PMio and hospital admissions for congestive heart failure in the elderly in 7 U.S. cities
(7% increase [95% CI 0.35 to 1.10%] per 10 |ig/m3 PMio [0-day lag]). Effect seemed to be
smaller in those with secondary diagnosis of hypertension. No consistent effect modification
observed for age, gender, race or other secondary diagnoses.
Wellenius et al. (2006b): Using case-crossover analysis, a significant association was reported
between PMio (3-day distributed lag) and hospital admissions for ischemic stroke (1.03%
increase [95% CI 0.04 to 2.04%] per 10 |ig/m3 PMio). No association was found for
hemorrhagic stroke admissions.
Zanobetti A, and Schwartz J. (2005): Case-crossover analysis showed significant association
between PMio and emergency hospitalization for myocardial infarction in elderly people (0.65%
[0.3-1.0] per 10 |ig/m3 PMio) in 21 U.S. cities. Effect size doubled for subjects with previous
admission for COPD or secondary diagnosis of pneumonia (difference in size not statistically
significant).
Analytical methods:
Biggeri et al. (2005): A meta-analysis was conducted to examine the associations between PMio
and all-cause, cardiovascular, and respiratory mortality in six Italian cities. Daily PMio data
were collected in 2 cities; in the other cities, daily TSP collected. Conversion factors, estimated
through validation studies, were applied to convert TSP to PMio. Significant associations with
PMio were observed for all-cause (0.90% [95% CI: 0.21, 1.66] excess risk per 10 |ig/m3 increase
in PMio at a 0- to 1-day lag) and cardiovascular (1.11% [95% CI: 0.22, 2.19]) mortality. All
other pollutants examined (NC>2, SC>2, CO, Os) also were significantly associated with all-cause
mortality. The effect of PMio on mortality was greater during the warm season and for those
aged. 65 yr.
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Daniels MJ, et al. (2004): Investigated impact of variance underestimation in both a simulation
study and using NMMAPS data; report that underestimation as large as 40% had little effect on
the national average relative risk of mortality.
Roberts S. (2005): Introduces model that uses information available in daily mortality time
series to infer otherwise lost information about the effect of PM on mortality, considering that
PM measurements may only be available every sixth day while the effect of PM on mortality
may be spread over multiple days. Analyses use data from NMMAPS, a simulated data set, and
daily PM measurements from Cook County, IL and Allegheny County, PA. New model
produces more precise effect estimates compared with standard model.
Roberts S, and Martin, MA. (2006): New model tested use of moving total mortality time series
that "allows inference on the information about the effect of PM on mortality that is lost when
daily PM data is unavailable." Using the 100-city database (1987-2000), report results that are
"consistent with those found in the NMMAPS analysis" with effect estimates of 0.12% increase
in total mortality and 0.17% increase in cardiovascular and respiratory mortality per 10 |ig/m3
PMio.
Simpson et al. (2005): Using three statistical methods—GLM, R, and a two-stage Poisson
GAM with stringent convergence criteria—PM-related excess risks of total nonaccidental,
cardiovascular, and respiratory mortality in Brisbane, Sydney, Melbourne, and Perth were
estimated. Daily PM2.5 data were collected using nephelometers in all four cities. Daily PM2.5
data were available in all four cities, but Brisbane was excluded from the analysis as more than
40% of data was missing. Daily PMio data were only available in Brisbane, Sydney, and
Melbourne. Melbourne, which was included in all analyses, was missing -30% of PM2 5 and
PMio data. Significant associations were observed for all cause and cardiovascular mortality
using the nephelometric data, but no associations were found with PM2 5 or PMi0. Results using
different statistical methods were similar. Mean PM2 5 levels ranged from 9.00 |ig/m3 (Sydney
and Perth) to 9.30 |ig/m3 (Melbourne) across the 3 cities.
Measurement error:
Zeka A and Schwartz J. (2004): Used 90-city database (1987-1994) and approach developed by
Schwartz and Coull (2003) to test associations between pollutants and mortality, correcting for
measurement error in the other pollutants. Effect estimates from models adjusting for the
gaseous pollutants ranged from 0.14 to 0.35% increases in mortality per 10 |ig/m3 PMio, with an
overall effect of 0.24% per 10 |ig/m3 PMio.
Review article:
Sandstrom T et al. (2005): Review article, concludes "The PM investigated generally induced
significant biological responses, with both coarse (2.5-10 jim) and fine (0.1-2.5 jim) PM being
able to induce toxic effects." Three studies briefly described: HEPMEAP (health effects of
particles from motor engine exhaust and ambient air pollution) RAIAP (respiratory allergy and
inflammation due to ambient particles) PAMCHAR (chemical and biological characterization of
ambient air coarse, fine and ultrafine particles for human health risk assessment in Europe).
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Epidemiologic Studies on Health Effects Associated
with Exposure to Traffic
Mortality
Finkelstein MM, Jerrett M, Sears MR. (2004) Traffic air pollution and mortality rate
advancement periods. Am JEpidemiol 160:173-177.
Firestone Institute pulmonary function cohort (5228 adults), using residence w/in 50 m or
major urban road or w/in 100 m of a highway as traffic index. CVD mortality
significantly associated with pollution index [RR 1.06 (1.00-1.13)]; stronger association
with deprivation index (RR 1.15) and traffic indicator (RR 1.40). In 2- and 3-variable
models, pollution index reduced (RR 1.04 and nonsignificant) with little change in traffic
indicator and some reduction for deprivation index. Deprivation and pollution indices
were highly collinear, so created a combined (sum) index; both traffic and
deprivation/pollution index were significantly association with CVD mortality
(RR1.05, 1.01-1.10)
Finkelstein MM, Jerrett M, DeLuca P, Finkelstein N, Verma DK, Chapman K, Sears MR. (2003)
Relationship between income, air pollution and mortality: a cohort study. Can Med Assoc J
169(5):397-402.
Firestone Institute pulmonary function cohort (5228 adults), using residence w/in 50 m or
major urban road or w/in 100 m of a highway as traffic index. Significant association
between mortality and residence w/in a road/highway buffer: RR 1.18 (1.02-1.38) for all
subjects. By interpolation from Ontario life tables, estimated "rate advancement period"
associated with traffic pollution of 2.5 years (0.2-4.8).
Finkelstein MM, Jerrett M, Sears MR (2005) Environmental inequality and circulatory disease
mortality gradients. J Epidemiol Community Health 59:481-486.
Hart JE, Laden F, Schenker MB, Garshick E. (2006) Chronic obstructive pulmonary disease
mortality in diesel exposed railroad workers. Environ Health Perspect 114:(in press)
Hoek G, Brunekreef B, Goldbohm S, Fischer P, van den Brandt PA. (2002) Association between
mortality and indicators of traffic-related air pollution in the Netherlands: a cohort study.
Lancet 360(9341): 1203-1209.
Jerrett M, Burnett RT, Ma R, Pope CA III, Krewski D, Newbold KB, Thurston G, Shi Y,
Finkelstein M, Calle EE, Thun MJ. (2005) Spatial analysis of air pollution and mortality in
Los Angeles. Epidemiology 16:727-736.
American Cancer Society cohort, using traffic buffers of 500 and 100 m from freeway based on
zip code centroids (22,905 subjects in 267 zip code areas). Significant association between
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PM2 5 and deaths from all causes; after adjustment for 44 covariates and freeways w/in
500 m, significant associations were reported with death from all causes (RR 1.17,
1.05-1.31) and IHD (RR 1.38, 1.11-1.72).
Lipfert FW, Wyzga RE, Baty JF, Miller JP. (2006) Traffic density as a surrogate measure of
environmental exposures in studies of air pollution health effects: long-term mortality in a
cohort of U.S. veterans. Atmos Environ 40:154-169.
Veterans cohort; traffic volume estimated from [vehicle-km traveled/county land area]
using data from 1985, 1990 and 1997. Significant association with traffic (RR 1.176,
1.100-1.258 per 2.6 in 1999 data). In 3-pollutant models, traffic effect was little changed,
with the PM25 effect estimate reduced and not significant (RR 1.032) and PMi0-2.5 effect
negative and nonsignificant.
Lipfert FW, Baty JD, Wyzga RE, Miller JP. (2006) PM2.5 constituents and related air quality
variables as predictors of survival in a cohort of U.S. military veterans. Inhal Toxicol (in press).
Veterans cohort; traffic volume estimated from [vehicle-km traveled/county land area],
also PM2.5 speciation data. Significant associations between mortality and traffic density,
EC, nitrates, V and Ni, with the strongest effects for traffic density and EC. Positive,
nonsignificant associations with PM2 5 mass and sulfates. Negative nonsignificant
associations with elements association with crustal particles (Al, Ca, Si).
Maheswaran R, Elliott P. (2003) Stroke mortality associated with living near main roads in
England and Wales: a geographical study. Stroke 34(12):2776-2780.
Zeka A, Zanobetti A, Schwartz J. (2005) Short term effects of particulate matter on cause
specific mortality: effects of lags and modification by city characteristics. Occup Environ Med
62:718-725.
Multicity study, associations for PMi0 with cause-specific mortality in 20 U.S. cities.
Heterogeneity in effect estimates partially explained by differences in city characteristics,
including increased % PMi0 from traffic.
Respiratory morbidity:
Brauer M, Hoek G, Van Vliet P, Meliefste K, Fishcer PH, Wijga A, Koopman LP, Neijens HJ,
Gerritsen J, Kerkhof M, Heinrich J, Bellander T, Brunekreef B. (2002) Air pollution from traffic
and the development of respiratory infections and asthmatic and allergic symptoms in children.
Am J Respir Crit Care Med 166(8): 1092-8.
The Netherlands: respiratory symptoms for 4,135 in birth cohort, 3,730 reassessed at
2 yr; numerous cities. Associations with NO2, PM2 5, soot; long-term average based on
2-wk samples. Positive, borderline significantly associations between all three pollutants
and prevalence of wheeze, E, N, T infections, and flu/serious colds
Brunekreef B, Janssen NAH, de Hartog J, Harssema H, Knape M, van Vliet P. (1997) Air
pollution from truck traffic and lung function in children living near motorways. Epidemiol
8(3): 298-303.
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Buckeridge D, Gozdyra P, Ferguson K, Schrenk M, Skinner J, Tarn T, Amrhein C. (1998)
A study of the relationship between vehicle emissions and respiratory health in an urban area.
Geogr Environ Modeling 2:17-36.
Buckeridge DL, Glazier R, Harvey BJ, Escobar M, Amrhein C, Frank J. (2002) Effect of motor
vehicle emissions on respiratory health in an urban area. Environ Health Perspect
110(3):293-300.
Three year hospitalization rates determined in SE Toronto; PM2 5 emissions estimated
from traffic data; modeled exposures. Hospitalization rate for subset of respiration
diseases (asthma, bronchitis, COPD, pneumonia, URI) significantly increased with PM2 5
emission density (RR 1.24, 1.05-1.45)
Burr ML, Karani G, Davies B, Holmes BA, Williams KL. (2004) Effects on respiratory health of
a reduction in air pollution from vehicle exhaust emissions. Occupational and Environmental
Medicine 61:212-218.
PM10, PM2 5 via dichot, daily for 3-wk and 2-wk periods, before and after bypass;
respiratory symptoms in 448 adults living in congested and uncongested neighborhoods.
PM2 5 means decreased between before/after bypass by 23.5% in congested and 26.6%
in uncongested neighborhoods. Reduction in symptoms with decreased traffic for any
wheeze -6.5% (-14.9, 2.0) and number of attacks -8.5% (-18.2, 1.2). No association with
cough, phlegm, consulted doctor, rhinitis. Positive association with "affects activities"
10.3(3.1, 17.3).
De Marco R, Poli A, Ferrari M, Accordini S, Giammanco G, Bugiani M, Villani S, Ponzio M,
Bono R, Carrozzi L, Cavallini R, Cazzoletti L, Dallari R, Ginesu F, Lauriola P, Mandrioli P,
Perfetti L, Pignato S, Pirina P, Struzzo P; ISAYA study group. (2002) Italian Study on Asthma
in Young Adults. The impact of climate and traffic-related NO2 on the prevalence of asthma
and allergic rhinitis in Italy. Clin Exp Allergy 32(10): 1405-1412.
Delfino RJ, Gong H, Linn WS, Pellizzari ED, Hu Y. (2003) Asthma symptoms in Hispanic
children and daily ambient exposures to toxic and criteria air pollutants. Environ Health
Perspect 111(4):647-656.
Los Angeles, CA, community with high traffic density. Positive associations with both
criteria pollutants and VOCs; two-pollutant models showed stronger association with EC
or OC fractions of PMi0 than PMi0 mass. Suggest air toxics from traffic and industrial
sources may have adverse effects on asthma in children.
Delfino RJ, Gong H, Linn WS, Hu Y, Pellizzari E. (2003) Respiratory symptoms and peak
expiratory flow in children with asthma in relation to volatile organic compounds in exhaled
breath and ambient air. J Expos Analysis Environ Epidemiol 13:348-363.
Los Angeles, CA, community with high traffic density. Ambient VOCs, NO2 and SO2
associated with decreased peak flow in Hispanic children.
Fritz GJ, Herbarth O. (2004) Asthmatic disease among urban preschoolers: an observational
study. Int J Hyg Environ Health 207:23-30.
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Garshick E, Laden F, Hart JE, Caron A. (2003) Residence near a major road and respiratory
symptoms in U.S. Veterans. Epidemiol 14(6):728-736.
U.S. male veterans in SE Massachusetts: persistent wheeze increased in men living w/in
50 m of major roadway, compared with those living >400 m away.
Gauderman WJ, Avol E, Lurmann, F, Kuenzli N, Gilliland F, Peters J, McConnell R. (2005)
Childhood asthma and exposure to traffic and nitrogen dioxide. Epidemiology 16(6):737-743.
Children's Health Study in southern California; NO2 (from 2000) as indicator of freeway-
related pollutants and 3 traffic metrics: proximity to freeway, number of vehicles/day,
modeling of traffic-related air pollution. Significant association between asthma history
and distance to freeway (OR 1.89, 1.19-3.02) and model-based freeway pollution (OR
2.22, 1.36-3.63); positive nonsignificant association with traffic volume and model-based
pollution from other roads.
Gehring U, Cyrys J, Sedlmeir G, Brunedreef B, Belander T, Fischer T, Bauer CP, Reinhardt D,
Wichmann HE, Heinrich J. (2002) Traffic-related air pollution and respiratory health during the
first 2 yrs of life. Eur Respir J 19(4): 690-698.
Gordian ME, Hanuese S, Wakefield J. (2006) An investigation of the association between traffic
exposure and the diagnosis of asthma in children. J Expo Sci Environ Epidemiol 16(l):49-55.
Anchorage, AK, survey of parents of children in kindergarten and 1st grade, traffic index
based on GIS mapping of traffic density w/in 100 m of home. Increased risk of asthma
diagnosis with medium and high exposure; significant for high-exposure group (OR
2.84, 1.23-6.51).
Heinrich J, Topp R, Gehring U, Thefeld W. (2005) Traffic at residential address, respiratory
health, and atopy in adults: the National German Health Survey 1998. Environmental Research
98:240-249.
Heinrich, J.; Wichmann, H-E. (2004) Traffic related pollutant in Europe and their effect on
allergic disease. Current Opin Clinical Epidemiol 4: 341-348.
Hirsch T, Weiland SK, von Mutius E, Safeca AF, Grafe H, Csaplovics E, Duhme H, Keil U,
Leupold W. (1999) Inner city air pollution and respiratory health and atopy in children. Eur
Respir J 14(3):669677.
Hirsch T, Neumeister V, Weiland SK, von Mutius E, Hirsch D, Grafe H, Duhme H, Leupold W.
(2000) Traffic exposure and allergic sensitization against latex in children. J Allergy Clin
Immunol. 106(3):573-8.
Ising H, Lange-Asschenfieldt H, Lieber GF, Weinhold H, Eilts M. (2003) Respiratory and
dermatological diseases in children with long-term exposure to road traffic emissions. Noise
Health 5:41-50.
Janssen NAH, Brunekreef B, van Vliet P, Aarts F, Meliefste K, Harssema H, Fishcer P. (2003)
The relationship between air pollution from heavy traffic and allergic sensitization, bronchial
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hyper responsiveness and respiratory symptoms in Dutch school children. Environ Health
Perspectlll(12):1512-1518.
Kim JJ, Smorodinsky S, Ostro B, Lipsett M, Singer BC, Hogdson AT. (2002) Traffic-related air
pollution and respiratory health: the East Bay Children's Respiratory Health Study. Epidemiol
13(4):S100.
Kim JJ, Smorodinsky S, Lipsett M, Singer BC, Hogdson AT, Ostro B. (2004) Traffic-related air
pollution near busy roads: the East Bay Children's Respiratory Health Study. American Journal
of Respiratory Critical Care Medicine. Am J Respir Crit Care Med 170:520-526.
Respiratory symptoms for 1109 children in 10 schools, grades 3-5. Authors state
positive, generally larger effect estimates for BC, NOX and NO suggest effects of primary
emissions more than regional pollutants for these outcomes.
Lee YL, Shaw CK, Su HJ, Lai JS, Ko YC, Huang SL, Sung FC, Guo YL. (2003) Climate,
traffic-related air pollutants and allergic rhinitis prevalence in middle-school children in Taiwan.
Eur Respir J 21(6):964-70.
Lewis SA. Antoniak M. Venn AJ. Davies L. Goodwin A. Salfield N. Britton J. Fogarty AW.
2005. Secondhand smoke, dietary fruit intake, road traffic exposures, and the prevalence of
asthma: a cross-sectional study in young children. American Journal of Epidemiology.
161(5):406-11.
UK study, 11,562 children 4-6 years of age, questionnaire at school on respiratory
symptoms. Traffic index of living w/in 30, 60, 90, 120 or 150 m of main road; asthma
prevalence not associated with proximity of home to main road.
Lin S, Munsie JP, Hwang SA, Fitzgerald E, Cayo MR. (2002) Childhood asthma hospitalization
and residential exposure to state route traffic. Environ Res 88(2):73-81.
Livingstone AE, Shaddick G, Grundy C, Elliott P. (1996) Do people living near inner city main
roads have more asthma needing treatment? Case-control study. BMJ 312:676-677.
Lwebuga-Mukasa JS, Ayirookuzhi SJ, Hyland A. (2003) Traffic volumes and respiratory health
are utilization among residents in close proximity to the Peace Bridge before and after September
11, 2001. J Asthma 40(8):855-864.
Buffalo, NY: Decrease in traffic on Peace Bridge (50%) after Sept 11, 2001 was
associated with decreased hospital admissions or emergency department visits for
respiratory illnesses.
Lwebuga-Mukasa JS, Oyana T, Thenappan A, Ayirookuzhi SJ. (2004) Association between
traffic volume and health care use for asthma among residents at a U.S.-Canadian border
crossing point. J Asthma 41(3):289-304.
Buffalo, NY: Data on commercial traffic volume across Peace Bridge, and hospital
discharges and outpatient visits for asthma. Highest asthma prevalence rates and health
care use rates were in the two zip codes that surround the Peace Bridge.
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Lwebuga-Mukasa JS, Oyana TJ, Johnson C. (2005) Local ecological factors, ultrafine
particulate concentrations, and asthma prevalence rates in Buffalo, New York. J Asthma
42:337-348.
Buffalo, NY: Cross-sectional survey of 2000 households, OR of 2.57 (1.85-3.57) for
having at least one person with asthma in households on west side compared to east side.
Ultrafine particle levels also higher in communities downwind of Peace Bridge.
McConnell R, Birhane K, Yao L, Jerrett M, Lurmann F, Gilliland F, Kunzli N, Gauderman J,
Avol E, Thomas D, Peters J. (2006) Traffic, susceptibility, and childhood asthma. Environ
Health Perspect 114:766-772.
13 Southern California communities: Cohort study of kindergarten and first grade
children in 13 communities. Risk of asthma and wheeze was increased with residence
within 75 m of a major road, also with exposure to nonfreeway traffic pollution
(modeled) but not to freeway or total traffic pollution.
Montnemery P, Popovic M, Andersson M, Greiff L, Nybert P, Lofdahl CG, Svensson C, Persson
CG. (2003) Influence of heavy traffic, city dwelling and socio-economic status on nasal
symptoms assessed in a postal population survey. Respir Med 97(8):970-977.
Nicolai T, Carr K, Weiland SK, Duhme H, von Ehrenstein O. (2003) Urban traffic and pollutant
exposure related to respiratory outcomes and atopy in a large sample of children. Eur Respir J.
21(6):956-63.
Oftedal B, Nafstad P, Magnus P, Bjorkly S, Skrondal A. (2003) Traffic related air pollution and
acute hospital admission for respiratory diseases in Drammen, Norway 1995-2000. Eur J
Epidemiol. 18(7):671-675.
Oyana TJ, Lwebuga-Mukasa JS. (2004) Spatial relationships among asthma prevalence, health
care utilization, and pollution sources in neighborhoods of Buffalo, New York. J Environ Health
67:25-37.
Buffalo, NY: Statistically significant association between proximity to source and
diagnosed asthma. Asthma clusters located along major roadways, in communities near
Peace Bridge, and in the west side of city.
Penttinen P, Vallius M, Tiittanen P, Ruuskanen J, Pekkanen J. (2006). Source-specific
fine particles in urban air and respiratory function among adult asthmatics. Inhal Toxicol
18:191-198.
EPIC, European multi-city study, deviation of peak expiratory flow in 78 adult
asthmatics, during winter and spring seasons, 1996-1997. Used PM2 5 data with source
apportionment (long-range transport, local combustion, soil, heavy fuel oil, sea salt).
Most consistent association with PM2 5 from local combustion sources; significant
association between decreased morning APEF and PM2 5 from long range transport;
positive nonsignificant association with PM2 5 from soil.
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Ryan, P.H.; LeMasters, G.; Biagnini, J.; Bernstein, D.; Grinshpun, S.A.; Shukla, R.; Wilson,
M.S.; Villareal, M.; Burkle, J.; Lockey, J. (2005) Is it traffic type, volume, or distance?
Wheezing in infants living near truck and bus traffic. J Allergy Clin Immunol 116: 279-284.
Cincinnati allergy and air pollution study cohort: GIS and traffic classification used to
categorize traffic exposures based on type (bus, truck), traffic volume and distance from
road. Significant increase in prevalence of wheeze in infants living very near (<100 m)
stop-and-go bus and truck traffic; no increase in infants living <400 m from high volume
moving traffic; also greater risk for nonwhite infants compared with white infants.
Salam MT, Yi Y-F, Langholz B, Gilliand FD. (2004) Early life environmental risk factors for
asthma: findings from the Children's Health Study. Environ Health Perspect 112(6): 760-725.
Sekine K, Shima M, Nitta Y, Adachi M. (2004) Long term effects of exposure to automobile
exhaust on the pulmonary function of female adults in Tokyo, Japan. Occup Environ Med.
61:350-357.
Shima M, Nitta Y, Adachi M. (2003) Traffic-related air pollution and respiratory symptoms in
children living along trunk roads in Chiba Prefecture, Japan. JEpidemiol 13(2): 108-19.
Sugiri D, Ranft U, Schikowski T, Kramer U. (2006) The influence of large-scale airborne
particle decline and traffic-related exposure on children's lung function. Environ Health
Perspect 114:282-288.
Lung function measures in 2574 children, 5-7 years of age, living at least 2 years at their
residence, with measurements of TSP and SO2 in 1991, 1994, 1997 and 2000; also < or
> 50 m from busy street. Lung function improved with decreasing TSP; traffic-related
exposure was linked with decreased lung function; for children living close to busy roads,
the beneficial changes in lung function associated with reduced TSP were smaller
Tamura K, Jinsart W, Yano E, Karita K, Boudoung D. (2003) Particulate air pollution and
chronic respiratory symptoms among traffic policemen in Bangkok. Arch Environ Health
58:201-207.
Venn A., Yemaneberhan H., Lewis S., Parry E., Britton J. 2005. Proximity of the home to roads
and the risk of wheeze in an Ethiopian population. Occupational and Environmental Medicine.
62:376-380.
Volpino P, Tomei F, La Valle C, Tomao E, Rosati MV, Ciarrocca M, De Sio S, Cangemi B,
Vigliarolo R, Fedele F. (2004) Respiratory and cardiovascular function at rest and during
exercise testing in a healthy working population: effects of outdoor traffic air pollution.
Occup Med (Lond.) 54:475-482.
Yang CY, Yu ST, Chang CC. (2002) Respiratory symptoms in primary schoolchildren living
near a freeway in Taiwan. J Toxicol Environ Health A 65(10):747-55.
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Zmirou D, Gauvin S, Pin I, Momas I, Sahraoui F, Just J, Le Moullec Y, Bremont F, Cassadou S,
Reungoat P, Albertini M, Lauvergne N, Chiron M, Labbe A. (2004) Traffic related air pollution
and incidence of childhood asthma: results of the Vesta case-control study. J Epidemiol
Community Health 58(1): 18-23.
Cancer:
Cordier S, Monfort C, Filippini G, Preston-Martin S, Lubin F, Mueller BA, Holly EA, Peris-
Bonet R, McCredie M, Choi W, Little J, Arslan A. (2004) Parental exposure to polycyclic
aromatic hydrocarbons and the risk of childhood brain tumors. Am J Epidemiol. 159:1109-1116.
Crosignani P, Tittarelli A, Borgini A, Codazzi T, Rovelli A, Porro E, Contiero P, Bianchi N,
Tagliablue G, Fissi R, Rossitto F, Berrino F. (2004) Childhood leukemia and road traffic:
A population-based case-control study. Int J Cancer 108(4):596-599.
Feychting M, Svensson D, Ahlbom A. (1998) Exposure to motor vehicle exhaust and childhood
cancer. Scand. J. Work Environ. Health 24: 8-11.
Ippen M, Fehr R, Krasemann EO. (1989) Cancer in residents of heavy traffic areas.
Versicherungsmedizin 41(2):39-42.
Knox EG. (2005) Childhood cancers and atmospheric carcinogens. J Epidemiol Community
Heath 59:101-105.
Knox EG. (2005) Oil combustion and childhood cancers. J Epidemiol Community Health
59:755-560.
Langholz B, Ebi KL, Thomas DC, et al. (2002) Traffic density and the risk of childhood
leukemia in a Los Angeles case-control study. Ann Epidemiol 12(7):482-7.
Mannes T, Jalaludin B, Morgan G, Lincoln D, Sheppeard V, Corbett S (2005) Impact of ambient
air pollution on birth weight in Sydney, Australia. Occup Environ Med 62:524-530.
Nafstad P, Haheim LL, et al. (2003) Lung cancer and air pollution: a 27 year follow up of
16,209 Norwegian men. Thorax 58(12): 1071-1076.
Perera FP, Tang D, Tu Y-H, Cruz LA, Borjas M, Bernert T, Whyatt RM. (2004) Biomarkers in
maternal and newborn blood indicate heightened fetal susceptibility to procarcinogenic DNA
damage. Environ Health Perspect. 112(10):1133-1136.
Reynolds P, von Behren J, Gunier RB, Goldberg DE, Hertz A, Smith D. (2002) Traffic patterns
and childhood cancer incidence rates in California, United States. Cancer Causes and Control
13:665-673.
Reynolds P, von Behren J, Gunier RB, Goldberg DE, Hertz A. (2004) Residential exposure to
traffic in California and childhood cancer. Epidemiol 15(1):6-12.
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Steffen C, Auclere MF, Auvrignon A, Baruchel A, Kebaili K, Lambilliotte A, Leverger G,
Sommelet D, Vilmer E, Hemon D, Clavel J. (2004) Acute childhood leukaemia and
environmental exposure to potential sources of benzene and other hydrocarbons; a case-control
study. Occup Environ Med 61(9):773-778.
Vincents PS, Moller P, Sorensen M, Knudsen LE, Herte LQ, Jensen FP, Schibye B, Loft S.
(2005) Personal exposure to ultrafme particles and oxidative DNA damage. Environ Health
Perspect 113:1485-1490.
Other morbidity:
Brauer M. Gehring U, Brunekreef B, de Jongste J, Gerritsen J, Rovers M, Wichmann H-E,
Wijga A, Heinrich J. (2006) Traffic-related air pollution and otitis media. Environ Health
Perspec 114: (in press)
De Rosa M, Zarrilli S, Paesano L, Carbone U, Boggia B, Petretta M, Maisto A, Cimmino F,
Puca G, Coalo A, Lombardi G. (2003) Traffic pollutants affect fertility in men. Human Reprod
18(5):1055-1061.
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Toxicology and Epidemiology Studies of Metals or Metal-Containing Particles3
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abstract.
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Toxicology Studies of Endotoxin/LPS or Endotoxin/LPS-Containing Particles
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Toxicology and Epidemiology Studies of Wood Smoke
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