Pope III et al., 2019 examined the relationship between long-term PM2.5 exposure and all-cause mortality in a cohort of 1,599,329 U.S. adults (aged 18-84 years) who were interviewed in the National Health Interview Surveys (NHIS) between 1986 and 2014 and linked to the National Death Index (NDI) through 2015. The authors also constructed a subcohort of 635,539 adults from the full cohort for whom body mass index (BMI) and smoking status data were available. The authors employed a hybrid modeling technique to estimate annual-average PM2.5 concentrations derived from regulatory monitoring data and constructed in a universal kriging framework using geographic variables including land use, population, and satellite estimates. Pope III et al., 2019 assigned annual-average PM2.5 exposure from 1999-2015 to each individual by census tract and utilized complex (accounting for NHIS's sample design) and simple Cox proportional hazards models for the full cohort and the subcohort. We select the Hazard Ratio calculated using the complex model for the subcohort, which controls for individual-level covariates including age, sex, race-ethnicity, inflation-adjusted income, education level, marital status, rural versus urban, region, survey year, BMI, and smoking status. In a single-pollutant model, the coefficient and standard error for PM2.5 are estimated from the hazard ratio (1.12) and 95% confidence interval (1.08-1.15) associated with a change in annual mean PM2.5 exposure of 10 ug/m[3] (Pope et al. 2019, Table 2, Subcohort).
Medicare
Wu et al., 2020 evaluated the relationship between long-term PM2.5 exposure and all-cause mortality in more than 68.5 million Medicare enrollees (over the age of 64), using Medicare claims data from 2000-2016 representing over 573 million person-years of follow-up and over 27 million deaths. This cohort included over 20% of the U.S. population and was, at the time of publishing, the largest air pollution study cohort to date. The authors modeled PM2.5 exposure at a 1-km[2] grid resolution using a hybrid ensemble-based prediction model that combined three machine learning models and relied on satellite data, land-use information, weather variables, chemical transport model simulation outputs, and monitor data. Wu et al., 2020 fit five different statistical models: a Cox proportional hazards model, a Poisson regression model, and three causal inference approaches (GPS estimation, GPS matching, and GPS weighting). All five statistical approaches provided consistent results; we report the results of the Cox proportional hazards model here. The authors adjusted for numerous individual-level and community-level confounders, and sensitivity analyses suggest that the results are robust to unmeasured confounding bias. In a single-pollutant model, the coefficient and standard error for PM2.5 are estimated from the hazard ratio (1.066) and 95% confidence interval (1.058-1.074) associated with a change in annual mean PM2.5 exposure of 10.0 ug/m[3] (Wu et al., 2020, Table S3, Main analysis, 2000-2016 Cohort, Cox PH).
American Cancer Society

Two independent studies evaluated the same years of data from the large, nationwide ACS CSP-II cohort of those > 29 years old (Pope III et al., 2019, Turner et al., 2016). These studies extended the follow-up period of the ACS CSP-II to 22 years (1982-2004), evaluating 669,046 participants over 12,662,562 person-years of follow up and 237,201 observed deaths. These two studies applied a more advanced exposure estimation approach than had previously been used when analyzing the ACS cohort, combining the geostatistical Bayesian Maximum Entropy framework with national-level land use regression models.
In addition to adjusting for individual-level and ecological covariates, Turner et al., 2016 ADDIN EN.CITE <EndNote><Author>Turner</Author><Year>2016</Year><RecNum>544</RecNum><DisplayText>Turner et al., 2016</DisplayText><record><rec-number>544</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732084">544</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Turner, M. C.</author><author>Jerrett, M.</author><author>Pope, A., III</author><author>Krewski, D.</author><author>Gapstur, S. M.</author><author>Diver, W. R.</author><author>Beckerman, B. S.</author><author>Marshall, J. D.</author><author>Su, J.</author><author>Crouse, D. L.</author><author>Burnett, R. T.</author></authors></contributors><titles><title>Long-term ozone exposure and mortality in a large prospective study</title><secondary-title>American Journal of Respiratory and Critical Care Medicine</secondary-title><alt-title>Am J Respir Crit Care Med</alt-title></titles><periodical><full-title>American Journal of Respiratory and Critical Care Medicine</full-title>Am. J. Respir. Crit. Care Med.Am J Respir Crit Care Med</periodical><alt-periodical><full-title>American Journal of Respiratory and Critical Care Medicine</full-title>Am. J. Respir. Crit. Care Med.Am J Respir Crit Care Med</alt-periodical><pages>1134-1142</pages><volume>193</volume><number>10</number><dates><year>2016</year></dates><isbn>ISSN 1073-449X
EISSN 1535-4970</isbn><accession-num>26680605</accession-num>3060878<urls><related-urls><url>http://dx.doi.org/10.1164/rccm.201508-1633OC</url></related-urls></urls><electronic-resource-num>10.1164/rccm.201508-1633OC</electronic-resource-num><language>English</language></record></EndNote> also controlled for occupational PM2.5 exposure and adjusted for the potential copollutants O3 and nitrogen dioxide. Although the copollutant adjustment did not significantly change the hazard ratio, similar to the risk assessment performed as part of the PM PA (U.S. EPA, 2022a), we identified it as the most suitable hazard ratio when estimating health benefit impacts.  ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2020</Year><RecNum>322</RecNum><DisplayText>U.S. EPA, 2020c</DisplayText><record><rec-number>322</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071274">322</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Policy Assessment for the Review of the National Ambient Air Quality Standards for Particulate Matter</title></titles><edition>January 2020</edition><dates><year>2020</year></dates><pub-location>Research Triangle Park, NC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Air Quality Planning and Standards, Heath and Environmental Impacts Division</publisher><isbn>EPA-452/R-20-002</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-policy-assessments-current-review-0</url></related-urls></urls></record></EndNote> Thus, the total mortality risk estimate is based on the random-effects Cox proportional hazard model that incorporates multiple individual and ecological covariates (relative risk =1.06, 95% confidence intervals 1.04 - 1.08 per 10ug/m[3] increase in PM2.5). The relative risk estimate is identical to a risk estimate drawn from earlier ACS analysis of all-cause long-term exposure PM2.5-attributable mortality (Krewski et al., 2009 ADDIN EN.CITE <EndNote><Author>Krewski</Author><Year>2009</Year><RecNum>554</RecNum><DisplayText>Krewski et al., 2009</DisplayText><record><rec-number>554</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732085">554</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Krewski, Daniel</author><author>Jerrett, Michael</author><author>Burnett, Richard T</author><author>Ma, Renjun</author><author>Hughes, Edward</author><author>Shi, Yuanli</author><author>Turner, Michelle C</author><author>Pope III, C Arden</author><author>Thurston, George</author><author>Calle, Eugenia E</author></authors></contributors><titles><title>Extended follow-up and spatial analysis of the American Cancer Society study linking particulate air pollution and mortality</title></titles><number>140</number><dates><year>2009</year></dates><publisher>Health Effects Institute Boston, MA</publisher><urls></urls></record></EndNote>). Of note, the ACS cohort participants were recruited by approximately 77,000 ACS volunteers and may not precisely represent the overall U.S. population demographics.
 REF _Ref54862054 \h

Figure 11.

 ADDIN EN.CITE <EndNote><Author>Di</Author><Year>2017</Year><RecNum>536</RecNum><DisplayText>Di et al., 2017b</DisplayText><record><rec-number>536</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732083">536</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Di, Q.</author><author>Wang, Y.</author><author>Zanobetti, A.</author><author>Wang, Y.</author><author>Koutrakis, P.</author><author>Choirat, C.</author><author>Dominici, F.</author><author>Schwartz, J. D.</author></authors></contributors><titles><title>Air pollution and mortality in the Medicare population</title><secondary-title>New England Journal of Medicine</secondary-title><alt-title>N Engl J Med</alt-title></titles><periodical><full-title>New England Journal of Medicine</full-title>New Engl. J. Med.New Engl J Med</periodical><alt-periodical><full-title>N Engl J Med</full-title></alt-periodical><pages>2513-2522</pages><volume>376</volume><number>26</number><edition>June 29, 2017</edition><dates><year>2017</year><pub-dates><date>06</date></pub-dates></dates><isbn>ISSN 0028-4793
EISSN 1533-4406</isbn><accession-num>28657878</accession-num>3841341<urls><related-urls><url>http://dx.doi.org/10.1056/NEJMoa1702747</url></related-urls></urls><electronic-resource-num>10.1056/NEJMoa1702747</electronic-resource-num><language>English</language></record></EndNote>
 ADDIN EN.CITE <EndNote><Author>Di</Author><Year>2017</Year><RecNum>536</RecNum><DisplayText>Di et al., 2017b</DisplayText><record><rec-number>536</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732083">536</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Di, Q.</author><author>Wang, Y.</author><author>Zanobetti, A.</author><author>Wang, Y.</author><author>Koutrakis, P.</author><author>Choirat, C.</author><author>Dominici, F.</author><author>Schwartz, J. D.</author></authors></contributors><titles><title>Air pollution and mortality in the Medicare population</title><secondary-title>New England Journal of Medicine</secondary-title><alt-title>N Engl J Med</alt-title></titles><periodical><full-title>New England Journal of Medicine</full-title>New Engl. J. Med.New Engl J Med</periodical><alt-periodical><full-title>N Engl J Med</full-title></alt-periodical><pages>2513-2522</pages><volume>376</volume><number>26</number><edition>June 29, 2017</edition><dates><year>2017</year><pub-dates><date>06</date></pub-dates></dates><isbn>ISSN 0028-4793
EISSN 1533-4406</isbn><accession-num>28657878</accession-num>3841341<urls><related-urls><url>http://dx.doi.org/10.1056/NEJMoa1702747</url></related-urls></urls><electronic-resource-num>10.1056/NEJMoa1702747</electronic-resource-num><language>English</language></record></EndNote>
 REF _Ref54862053 \h

SEQ Figure \* ARABIC
Summary
EPA most recently used two estimates of mortality: one from the American Cancer Society cohort and one from the Medicare cohort (Turner et al., 2016 and Di et al., 2017b, respectively). We use a risk estimate from Pope III et al., 2019 study in place of the risk estimate from the (Turner et al., 2016 analysis, as it: (1) includes a longer follow-up period that includes more recent (and lower) PM2.5 concentrations; (2) the NHIS cohort is more representative of the U.S. population than is the ACS cohort with respect to the distribution of individuals by race, ethnicity, income and education.
We substituted a risk estimate from Wu et al., 2020 in place of a risk estimate from Di et al., 2017b. These two epidemiologic studies share many attributes, including the cohort and model used to characterize population exposure to PM2.5. As compared to Di et al., 2017b, Wu et al., 2020 includes a longer follow-up period and reflects more recent PM2.5 concentrations.
 ADDIN EN.CITE <EndNote><Author>Krewski</Author><Year>2009</Year><RecNum>554</RecNum><DisplayText>Krewski et al., 2009</DisplayText><record><rec-number>554</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732085">554</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Krewski, Daniel</author><author>Jerrett, Michael</author><author>Burnett, Richard T</author><author>Ma, Renjun</author><author>Hughes, Edward</author><author>Shi, Yuanli</author><author>Turner, Michelle C</author><author>Pope III, C Arden</author><author>Thurston, George</author><author>Calle, Eugenia E</author></authors></contributors><titles><title>Extended follow-up and spatial analysis of the American Cancer Society study linking particulate air pollution and mortality</title></titles><number>140</number><dates><year>2009</year></dates><publisher>Health Effects Institute Boston, MA</publisher><urls></urls></record></EndNote>
Infant Mortality
In addition to the adult mortality studies described above, several studies show an association between PM exposure and mortality in children under 5 years of age (U.S. EPA, 2009).  ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2009</Year><RecNum>6</RecNum><DisplayText>U.S. EPA, 2009</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="0">6</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA</author></secondary-authors></contributors><titles><title>Integrated Science Assessment for Particulate Matter (Final Report).</title></titles><edition>December 2009</edition><keywords><keyword>ISA</keyword></keywords><dates><year>2009</year></dates><pub-location>Research Triangle Park, NC</pub-location><publisher>Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA-600/R-08-139F</isbn><urls><related-urls><url>Available at: https://cfpub.epa.gov/ncea/risk/recordisplay.cfm?deid=216546</url></related-urls></urls></record></EndNote> The 2019 PM ISA concluded that evidence exists for a stronger effect at the post neonatal period and for respiratory-related mortality, although this trend is not consistent across all studies. The supplement to the PM ISA did not identify any new studies characterizing PM exposure and mortality among children (U.S. EPA, 2022b).
Although the ISA evidence supports a relationship between PM2.5 exposure and death in children, only studies of infant mortality met the minimum criteria (section 2.1.1). Previously, EPA has included estimates of post neonatal infant mortality from Woodruff et al., 1997 (U.S. EPA, 2012a, U.S. EPA, 2019c). As such, compared to avoided deaths estimated for adult mortality, avoided deaths for infants are significantly smaller due to the size of the population and the smaller risk estimates associated with exposure to PM from epidemiology studies on infant mortality. ADDIN EN.CITE <EndNote><Author>Woodruff</Author><Year>1997</Year><RecNum>1133</RecNum><DisplayText>Woodruff et al., 1997</DisplayText><record><rec-number>1133</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732559">1133</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Woodruff, Tracey J</author><author>Grillo, Jeanne</author><author>Schoendorf, Kenneth C</author></authors></contributors><titles><title>The relationship between selected causes of postneonatal infant mortality and particulate air pollution in the United States</title><secondary-title>Environmental Health Perspectives</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>608-612</pages><volume>105</volume><number>6</number><dates><year>1997</year></dates><isbn>0091-6765</isbn><urls></urls></record></EndNote> ADDIN EN.CITE  ADDIN EN.CITE.DATA
In a more recent study including a larger and more nationally-representative study size by the same group, authors examined the relationship between long-term exposure to fine PM2.5 air pollution and post neonatal infant mortality in 3,583,495 births from 96 counties containing >249,999 residents across the U.S. between 1999-2002 using data from the National Center for Health Statistics (Woodruff et al., 2008 ADDIN EN.CITE <EndNote><Author>Woodruff</Author><Year>2008</Year><RecNum>1154</RecNum><DisplayText>Woodruff et al., 2008</DisplayText><record><rec-number>1154</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732563">1154</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Woodruff, Tracey J</author><author>Darrow, Lyndsey A</author><author>Parker, Jennifer D</author></authors></contributors><titles><title>Air pollution and postneonatal infant mortality in the United States, 1999 - 2002</title><secondary-title>Environmental Health Perspectives</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>110-115</pages><volume>116</volume><number>1</number><dates><year>2008</year></dates><isbn>0091-6765</isbn><urls></urls></record></EndNote>). They linked average PM2.5 monitoring data over the first two months of life with 6,639 post neonatal deaths, using logistic regression that incorporated generalized estimating equations (GEE) to estimate the odds ratios for all-cause and cause-specific post neonatal mortality by exposure to air pollution. The study population experienced a median PM2.5 concentration of 14.8 ug/m[3], with 25% of the population experiencing concentrations below 12 ug/m[3] and above 18.8 ug/m[3]. The study included an evaluation of the appropriateness of a linear form from analysis based on quartiles of exposure and determined the linear form as a reasonable assumption. Study results included a single risk estimate of PM2.5-attributable all-cause mortality, 1.04 (0.98-1.11) per 7 ug/m[3] (interquartile range) increase in PM2.5.
Cardiovascular Hospital Admissions
The ISA found "generally consistent, positive associations observed in numerous epidemiologic studies of emergency department visits and hospital admissions for ischemic heart disease, heart failure, and combined cardiovascular-related endpoints" (U.S. EPA, 2019b, section 6.1.16). ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote> Also, the ISA calls out cardiovascular hospital admissions as a population level health endpoint related to short-term PM2.5 exposure (section <IP_ADDRESS>.1.1).
Available Epidemiologic Literature
Fifteen North American epidemiologic studies of cardiovascular hospital admissions were identified in section 6.1 of the PM ISA (U.S. EPA, 2019b) and in the Supplement to the PM ISA (U.S. EPA, 2019b, U.S. EPA, 2022b). ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote> Relevant information related to the identification criteria, including study location, population attributes, and study period, were extracted from the studies and is available in the associated Study Information Table. The hospital admissions endpoint reports the number of events, as opposed to the number of individuals who experienced the event.
Identifying Suitable Studies for Use in Benefits Assessments
Relevant study information was used to identify the most nationally representative study or studies available. Study details can be found in the associated Study Information Table. The available cardiovascular hospital admissions studies predominantly included locations across the contiguous U.S. and evaluated the Medicare cohort, although two studies evaluated all ages. Few studies included health or air quality data post-2006, used hybrid exposure estimation techniques, or included O3 as a copollutant in the risk estimates. Importantly, while all studies assessed a broad range of cardiovascular effects, the specific ICD codes included varied widely. Of the available studies, Bell et al., 2015 evaluated the most recent study period and included the most nationally representative study locations.
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Bell et al., 2015 investigated the effects of short-term fine particulate matter (PM2.5) exposure on cardiovascular health (ICD-9 410, omitting 410.x2; 410-414; 426-427; 428; 429; 430-438; and 440-448). Authors acquired data for 213 U.S. counties (1999-2010) from the Medicare Claims Inpatient Files for U.S. residents >65 years of age. Authors chose variables including sex, age, county of residence, and cause of hospital admission, as determined by ICD-9 codes. Authors collected PM2.5 exposure data from county population-based ambient monitors from the US EPA Air Quality System and averaged for county and day. Data were present for 56.5% of study days. Bell et al., 2015 utilized Bayesian hierarchal modeling to examine the links between PM2.5 and hospital admissions, running separate models to generate risk models for time lags (0-2 days) and season for any estimated variation in health effects. The percent increase in risk of 0.65% (95% CI: 0.48-0.83) for an increase of 10 ug/m[3] in same-day daily mean PM2.5 concentrations came from a single pollutant model.
Cardiovascular Emergency Department Visits
The ISA found that "generally consistent, positive associations observed in numerous epidemiologic studies of emergency department visits and hospital admissions for ischemic heart disease, heart failure, and combined cardiovascular-related endpoints" (U.S. EPA, 2019b section 6.1.16). ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote> The ISA also calls out cardiovascular emergency department visits as a population level health endpoint related to short-term PM2.5 exposure (section <IP_ADDRESS>.1.1).
Available Epidemiologic Literature
Although there were several studies of both emergency department visits and hospital admissions, there was only one short-term exposure epidemiologic study specific to cardiovascular emergency department visits available in the 2019 PM ISA (3202019c3200xd5s9009txfw1eafstv220i5ds2wvtpwf5d1573071075">320Washington, DCNational U.S. EPA, 2019b).
Study and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Ostro et al., 2016 investigated the association between short-term, source-specific (vehicular emissions, biomass burning, soil, and secondary NO[-]3 and SO4 sources) PM2.5 concentrations and emergency department visits for respiratory and cardiovascular diseases in eight cities in California from 2005 to 2008. Authors obtained medical and demographic data from the Office of Statewide Health Planning and Development in California, and diagnosis was defined with ICD-9 codes: all cardiovascular (390-459), ischemic heart disease (410 - 414), AMI (410), cardiac dysrhythmia (427), and heart failure (428). Ostro et al., 2016 conducted a case cross-over analysis, stratified by year and month, controlling for weather and day of the week covariates. Authors used a county-level logistic regression and random-effects meta-analysis to examine the association between source-specific PM2.5 and emergency department visits for respiratory and cardiovascular diseases. Results indicate a positive association between vehicle PM2.5 emissions and emergency department visits for all cardiovascular diseases. The identified excess risk estimate of 0.7% (95% CI: -0.2-1.7) per 11.4 ug/m[3] (interquartile range) daily mean PM2.5 concentration increase came from a single pollutant model lagged by 2 days.
Cardiac Arrest (Out-of-Hospital)
The 2019 PM ISA stated that "in contrast to the studies from the previous review, recent studies have reported generally positive associations between short-term PM2.5 exposure and out-of-hospital cardiac arrest" (U.S. EPA, 2019b, section 6.1). The ISA also called out conductance abnormalities as a key clinical effect ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote> associated with both short-and long-term PM2.5 exposures (section <IP_ADDRESS>.1.1).
This endpoint, like several others (e.g., lung cancer incidence, section <IP_ADDRESS>) has a very high rate of fatality. As mortality due to any cause is captured separately (section <IP_ADDRESS>), we focus on impacts following cardiac arrest, in the population that survive the initial event when considering this health endpoint.
Available Epidemiologic Literature
The 2019 PM ISA included three epidemiologic studies of out-of-hospital cardiac arrest that met our minimum identification criteria (U.S. EPA, 2019b, section 2.1.1).
 REF _Ref54194714 \r \h
Identifying Suitable Studies for Use in Benefits Assessments
All three studies each evaluated separate locations and were similar with regards to study aspects such as age range (Ensor et al., 2013, Rosenthal et al., 2008, Silverman et al., 2010). Due to differences only in the study period and locations, the three studies are pooled using the random or fixed effects pooling method for benefits assessment purposes.
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Ensor et al., 2013 ADDIN EN.CITE <EndNote><Author>Ensor</Author><Year>2013</Year><RecNum>1192</RecNum><DisplayText>Ensor et al., 2013</DisplayText><record><rec-number>1192</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604004380">1192</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ensor, K. B.</author><author>Raun, L. H.</author><author>Persse, D.</author></authors></contributors><auth-address>Rice University, Department of Statistics, PO Box 1892, MS 138, Houston, TX 77251-1892, USA.</auth-address><titles><title>A case-crossover analysis of out-of-hospital cardiac arrest and air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>1192-9</pages><volume>127</volume><number>11</number><edition>2013/02/15</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Aged</keyword><keyword>Air Pollution/*adverse effects</keyword><keyword>Cross-Over Studies</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Out-of-Hospital Cardiac Arrest/*epidemiology</keyword><keyword>Ozone/*adverse effects</keyword><keyword>Particulate Matter/*adverse effects</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Factors</keyword><keyword>Sex Factors</keyword><keyword>Texas</keyword><keyword>Young Adult</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar 19</date></pub-dates></dates><isbn>1524-4539 (Electronic)
0009-7322 (Linking)</isbn><accession-num>23406673</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/23406673</url></related-urls></urls><electronic-resource-num>10.1161/CIRCULATIONAHA.113.000027</electronic-resource-num></record></EndNote> studied the association between short-term ambient air pollution (PM2.5 and O3) exposure and out-of-hospital cardiac arrest. Ensor et al., 2013 ADDIN EN.CITE <EndNote><Author>Ensor</Author><Year>2013</Year><RecNum>1192</RecNum><DisplayText>Ensor et al., 2013</DisplayText><record><rec-number>1192</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604004380">1192</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ensor, K. B.</author><author>Raun, L. H.</author><author>Persse, D.</author></authors></contributors><auth-address>Rice University, Department of Statistics, PO Box 1892, MS 138, Houston, TX 77251-1892, USA.</auth-address><titles><title>A case-crossover analysis of out-of-hospital cardiac arrest and air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>1192-9</pages><volume>127</volume><number>11</number><edition>2013/02/15</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Aged</keyword><keyword>Air Pollution/*adverse effects</keyword><keyword>Cross-Over Studies</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Out-of-Hospital Cardiac Arrest/*epidemiology</keyword><keyword>Ozone/*adverse effects</keyword><keyword>Particulate Matter/*adverse effects</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Factors</keyword><keyword>Sex Factors</keyword><keyword>Texas</keyword><keyword>Young Adult</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar 19</date></pub-dates></dates><isbn>1524-4539 (Electronic)
0009-7322 (Linking)</isbn><accession-num>23406673</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/23406673</url></related-urls></urls><electronic-resource-num>10.1161/CIRCULATIONAHA.113.000027</electronic-resource-num></record></EndNote> gathered medical and demographic data from an Emergency Medical Services database in Houston, Texas between 2004 and 2011. Authors assessed the medical data and defined out-of-hospital cardiac arrest as emergency medical services performing chest compressions. Authors collected ambient air pollution and weather data from Texas Commission of Environmental Quality monitors and calculated hourly and daily averages for PM2.5 and O3. The authors used a time-stratified case crossover analysis and conditional logistic regression to interpret the data and found that with a daily increase of 6 ug/m[3] in PM2.5, averaged from a 0- and 1-day lag, there was an increased risk of out-of-hospital cardiac arrest of 3.9% (95% CI: 0.5-7.4).
Silverman et al., 2010 investigated the link between short-term ambient air pollution exposure (PM2.5, NO2, SO2, O3, and CO) and out-of-hospital cardiac arrest in New York City between 2002 and 2006. Authors obtained medical data from the Emergency Medical Services of the New York City Fire Department for 8,216 subjects aged 0 to 99, average age 65.6 with slightly more men than women. Authors collected air pollution and weather data from the US EPA's Air Quality System monitors within a 20-mile radius of New York City and averaged over 24-hour periods. Authors conducted time series and case crossover analyses with 0- and 1-day lagged air pollution levels and by season. Silverman et al., 2010 found that in a single-pollutant case crossover model, each 10 ug/m[3] increase in ambient PM2.5 resulted in a relative risk of 1.04 (95% CI: 0.99-1.08) in out-of-hospital cardiac arrest incidences 0- and 1-day prior to onset.
Rosenthal et al., 2008 examined the effects of short-term PM2.5 exposure on out-of-hospital cardiac arrest incidence and whether these effects were connected to demographic data or presence of heart rhythm. Additionally, Rosenthal et al., 2008 compared exposure time and measurement method on the effects of short-term PM2.5 exposure and out-of-hospital cardiac arrest incidence. Authors obtained medical data from the Wishard Ambulance Service, a local emergency medical service in Indianapolis, Indiana, from July 2, 2002 to July 7, 2006. The study defined out-of-hospital cardiac arrest using the same criteria as Ensor et al., 2013 ADDIN EN.CITE <EndNote><Author>Ensor</Author><Year>2013</Year><RecNum>1192</RecNum><DisplayText>Ensor et al., 2013</DisplayText><record><rec-number>1192</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604004380">1192</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ensor, K. B.</author><author>Raun, L. H.</author><author>Persse, D.</author></authors></contributors><auth-address>Rice University, Department of Statistics, PO Box 1892, MS 138, Houston, TX 77251-1892, USA.</auth-address><titles><title>A case-crossover analysis of out-of-hospital cardiac arrest and air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>1192-9</pages><volume>127</volume><number>11</number><edition>2013/02/15</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Aged</keyword><keyword>Air Pollution/*adverse effects</keyword><keyword>Cross-Over Studies</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Out-of-Hospital Cardiac Arrest/*epidemiology</keyword><keyword>Ozone/*adverse effects</keyword><keyword>Particulate Matter/*adverse effects</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Factors</keyword><keyword>Sex Factors</keyword><keyword>Texas</keyword><keyword>Young Adult</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar 19</date></pub-dates></dates><isbn>1524-4539 (Electronic)
0009-7322 (Linking)</isbn><accession-num>23406673</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/23406673</url></related-urls></urls><electronic-resource-num>10.1161/CIRCULATIONAHA.113.000027</electronic-resource-num></record></EndNote> and Silverman et al., 2010. Authors collected daily and hourly PM2.5 concentrations from two City of Indianapolis monitoring sites and using two separate methods: the Federal Reference Method (FRM) for 24-hour filter samples, and a Federal Equivalence Method (FEM). The authors used a case crossover analysis with conditional logistic regressions in order to study the effects of short-term PM2.5 exposure on out-of-hospital cardiac arrest incidence. Rosenthal et al., 2008 found a positive but statistically insignificant association between non-dead on arrival (non-DOA) out-of-hospital cardiac arrest cases and ambient PM2.5 concentrations. Although they also noted a statistically significant positive association when restricted to witnessed, non-DOA out-of-hospital cardiac arrest cases, that subgroup is less applicable to the available baseline incidence rate of non-DOA out-of-hospital cardiac arrest cases. The identified risk estimate of 1.02 (95% CI: 0.92-1.12) for each 10 ug/m[3] increase in daily mean PM2.5 concentrations lagged by 0-1 days, came from a single-pollutant model of all non-DOA out-of-hospital cardiac arrest cases.
Acute Myocardial Infarctions (AMI)
 Specifically:
The 2019 PM ISA found that "evidence from the current review strengthens the epidemiologic results reported in the 2009 PM ISA" with respect to AMI (U.S. EPA, 2019b). In addition, the 2022 Supplement to the 2019 PM ISA stated:
Studies examining short-term PM2.5 exposure report consistent positive associations for cardiovascular-related emergency department (ED) visits and hospital admissions, specifically for...myocardial infarction (MI). ... The epidemiologic studies reviewed in the 2019 PM ISA strengthened the evidence characterized in the previous ISA (U.S. EPA, 2009). Most of the evidence for IHD and MI in the 2009 PM ISA was from multicity epidemiologic studies of ED visits and hospital admissions [i.e., the U.S. Medicare Cohort Air Pollution Study (MCAPS) (Dominici et al., 2006), a four-city study in Australia (Barnett et al., 2006), and a study among older adults in several French cities (Host et al., 2008)]. The positive associations reported in these studies were an important line of evidence in the 2009 PM ISA concluding a causal relationship between short-term PM2.5 exposure and cardiovascular effects. Uncertainties noted in the 2009 PM ISA with respect to exposure measurement error for those not living near a PM2.5 monitor were reduced in the 2019 PM ISA with the consideration of studies that applied hybrid exposure assessment techniques that combine land use regression data with satellite aerosol optical depth (AOD) measurements and PM2.5 concentrations measured at fixed-site monitors to estimate PM2.5 concentrations. Further, compared with the 2009 PM ISA, the evidence in the 2019 PM ISA was expanded to include studies examining the association of short-term PM2.5 exposure ST segment depression in addition to ED visits and hospital admissions for MI. ... Overall, recent studies support and extend the findings of the 2019 PM ISA with additional studies reporting positive  ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote>
associations between short ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote>-term PM2.5 exposure and...MI hospital admissions and ED visits (U.S. EPA, 2022b REF _Ref54878707 \r \h ).
Available Epidemiologic Literature
The 2019 PM ISA identified epidemiologic studies associating AMIs with short-term PM2.5 exposures, though the studies passing the initial screening stage were not more suitable than those currently used to estimate benefits (U.S. EPA, 2019b). The Supplement to the ISA identified a single suitable short-term exposure study that passed the screening stage (U.S. EPA, 2022b).
 ADDIN EN.CITE <EndNote><Author>Zhang</Author><Year>2009</Year><RecNum>1415</RecNum><DisplayText>Zhang et al., 2009</DisplayText><record><rec-number>1415</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1611266802">1415</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhang, Z</author><author>Whitsel, Eric A</author><author>Quibrera, P Miguel</author><author>Smith, Richard L</author><author>Liao, Duanping</author><author>Anderson, Garnet L</author><author>Prineas, Ronald J</author></authors></contributors><titles><title>Ambient fine particulate matter exposure and myocardial ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women's Health Initiative (EEAWHI) study</title><secondary-title>Environmental Health Perspectives</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>751-756</pages><volume>117</volume><number>5</number><dates><year>2009</year></dates><isbn>0091-6765</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Delfino</Author><Year>2011</Year><RecNum>1414</RecNum><DisplayText>Delfino et al., 2011</DisplayText><record><rec-number>1414</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1611266683">1414</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Delfino, Ralph J</author><author>Gillen, Daniel L</author><author>Tjoa, Thomas</author><author>Staimer, Norbert</author><author>Polidori, Andrea</author><author>Arhami, Mohammad</author><author>Sioutas, Constantinos</author><author>Longhurst, John</author></authors></contributors><titles><title>Electrocardiographic ST-Segment Depression and Exposure to Traffic‐Related Aerosols in Elderly Subjects with Coronary Artery Disease</title><secondary-title>Environmental Health Perspectives</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>196-202</pages><volume>119</volume><number>2</number><dates><year>2011</year></dates><isbn>0091-6765</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote>
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
The supplement to the PM ISA identified a single new epidemiologic study examining the relationship between short-term PM exposure and AMI (U.S. EPA, 2022b). Wei et al., 2019 evaluated the relationship between short-term PM2.5 exposure and hospital admissions for 214 mutually exclusive disease groups, including acute myocardial infarction, in a time-stratified, case-crossover analysis of over 95 million Medicare inpatient hospital claims from 2000-2012. The authors estimated daily PM2.5 levels at a 1-km[2] grid cell level using a satellite based, neural network model that was calibrated using monitor data and assigned 0-1 day lagged PM2.5 exposure to each participant by zip code of residence. For each disease group, Wei et al., 2019 created a case crossover dataset that controlled for individual level and zip code level variables, day of the week, seasonality, and long-term time trends. The authors used conditional logistic regression models to estimate associations between PM2.5 exposure and risk of hospital admission and found positive associations for numerous rarely studied and numerous well-studied disease groups. In a single-pollutant model, the coefficient and standard error are estimated from a reported relative increase in risk (0.11%) and 95% confidence interval (0.07%-0.16%) associated with a 1 ug/m[3] increase in 0-1 day lagged PM2.5 exposure (Wei et al., 2019, Figure 3, CCS 100 AMI). We thus based our estimates of AMI incidence on this study, assuming that all AMI were associated with a hospital admission.
 ADDIN EN.CITE <EndNote><Author>Peters</Author><Year>2001</Year><RecNum>1137</RecNum><DisplayText>Peters et al., 2001</DisplayText><record><rec-number>1137</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peters, Annette</author><author>Dockery, Douglas W</author><author>Muller, James E</author><author>Mittleman, Murray A</author></authors></contributors><titles><title>Increased particulate air pollution and the triggering of myocardial infarction</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2810-2815</pages><volume>103</volume><number>23</number><dates><year>2001</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Peters</Author><Year>2001</Year><RecNum>1137</RecNum><DisplayText>Peters et al., 2001</DisplayText><record><rec-number>1137</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peters, Annette</author><author>Dockery, Douglas W</author><author>Muller, James E</author><author>Mittleman, Murray A</author></authors></contributors><titles><title>Increased particulate air pollution and the triggering of myocardial infarction</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2810-2815</pages><volume>103</volume><number>23</number><dates><year>2001</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote>
 ADDIN EN.CITE <EndNote><Author>Peters</Author><Year>2001</Year><RecNum>1137</RecNum><DisplayText>Peters et al., 2001</DisplayText><record><rec-number>1137</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peters, Annette</author><author>Dockery, Douglas W</author><author>Muller, James E</author><author>Mittleman, Murray A</author></authors></contributors><titles><title>Increased particulate air pollution and the triggering of myocardial infarction</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2810-2815</pages><volume>103</volume><number>23</number><dates><year>2001</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Sullivan</Author><Year>2005</Year><RecNum>1136</RecNum><DisplayText>Sullivan et al., 2005</DisplayText><record><rec-number>1136</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732559">1136</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sullivan, Jeffrey</author><author>Sheppard, Lianne</author><author>Schreuder, Astrid</author><author>Ishikawa, Naomi</author><author>Siscovick, David</author><author>Kaufman, Joel</author></authors></contributors><titles><title>Relation between short-term fine-particulate matter exposure and onset of myocardial infarction</title><secondary-title>Epidemiology</secondary-title></titles><periodical><full-title>Epidemiology</full-title>EpidemiologyEpidemiology</periodical><pages>41-48</pages><dates><year>2005</year></dates><isbn>1044-3983</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Pope III</Author><Year>2006</Year><RecNum>1138</RecNum><DisplayText>Pope III et al., 2006</DisplayText><record><rec-number>1138</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1138</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pope III, CArden</author><author>Muhlestein, Joseph B</author><author>May, Heidi T</author><author>Renlund, Dale G</author><author>Anderson, Jeffrey L</author><author>Horne, Benjamin D</author></authors></contributors><titles><title>Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2443-2448</pages><volume>114</volume><number>23</number><dates><year>2006</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Zanobetti</Author><Year>2006</Year><RecNum>1139</RecNum><DisplayText>Zanobetti and Schwartz, 2006</DisplayText><record><rec-number>1139</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1139</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zanobetti, Antonella</author><author>Schwartz, Joel</author></authors></contributors><titles><title>Air pollution and emergency admissions in Boston, MA</title><secondary-title>Journal of Epidemiology Community Health</secondary-title></titles><periodical><full-title>Journal of Epidemiology Community Health</full-title></periodical><pages>890-895</pages><volume>60</volume><number>10</number><dates><year>2006</year></dates><isbn>0143-005X</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Zanobetti</Author><Year>2009</Year><RecNum>1140</RecNum><DisplayText>Zanobetti et al., 2009</DisplayText><record><rec-number>1140</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1140</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zanobetti, Antonella</author><author>Franklin, Meredith</author><author>Koutrakis, Petros</author><author>Schwartz, Joel</author></authors></contributors><titles><title>Fine particulate air pollution and its components in association with cause-specific emergency admissions</title><secondary-title>Environmental Health</secondary-title></titles><periodical><full-title>Environmental Health</full-title>Environ. HealthEnviron Health</periodical><pages>58</pages><volume>8</volume><number>1</number><dates><year>2009</year></dates><isbn>1476-069X</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Pope III</Author><Year>2006</Year><RecNum>1138</RecNum><DisplayText>Pope III et al., 2006</DisplayText><record><rec-number>1138</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1138</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pope III, CArden</author><author>Muhlestein, Joseph B</author><author>May, Heidi T</author><author>Renlund, Dale G</author><author>Anderson, Jeffrey L</author><author>Horne, Benjamin D</author></authors></contributors><titles><title>Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2443-2448</pages><volume>114</volume><number>23</number><dates><year>2006</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Pope III</Author><Year>2006</Year><RecNum>1138</RecNum><DisplayText>Pope III et al., 2006</DisplayText><record><rec-number>1138</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1138</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pope III, CArden</author><author>Muhlestein, Joseph B</author><author>May, Heidi T</author><author>Renlund, Dale G</author><author>Anderson, Jeffrey L</author><author>Horne, Benjamin D</author></authors></contributors><titles><title>Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2443-2448</pages><volume>114</volume><number>23</number><dates><year>2006</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Pope III</Author><Year>2006</Year><RecNum>1138</RecNum><DisplayText>Pope III et al., 2006</DisplayText><record><rec-number>1138</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1138</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pope III, CArden</author><author>Muhlestein, Joseph B</author><author>May, Heidi T</author><author>Renlund, Dale G</author><author>Anderson, Jeffrey L</author><author>Horne, Benjamin D</author></authors></contributors><titles><title>Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2443-2448</pages><volume>114</volume><number>23</number><dates><year>2006</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Peters</Author><Year>2001</Year><RecNum>1137</RecNum><DisplayText>Peters et al., 2001</DisplayText><record><rec-number>1137</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peters, Annette</author><author>Dockery, Douglas W</author><author>Muller, James E</author><author>Mittleman, Murray A</author></authors></contributors><titles><title>Increased particulate air pollution and the triggering of myocardial infarction</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2810-2815</pages><volume>103</volume><number>23</number><dates><year>2001</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Pope III</Author><Year>2006</Year><RecNum>1138</RecNum><DisplayText>Pope III et al., 2006</DisplayText><record><rec-number>1138</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1138</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pope III, CArden</author><author>Muhlestein, Joseph B</author><author>May, Heidi T</author><author>Renlund, Dale G</author><author>Anderson, Jeffrey L</author><author>Horne, Benjamin D</author></authors></contributors><titles><title>Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2443-2448</pages><volume>114</volume><number>23</number><dates><year>2006</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote>
 ADDIN EN.CITE <EndNote><Author>Peters</Author><Year>2001</Year><RecNum>1137</RecNum><DisplayText>Peters et al., 2001</DisplayText><record><rec-number>1137</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peters, Annette</author><author>Dockery, Douglas W</author><author>Muller, James E</author><author>Mittleman, Murray A</author></authors></contributors><titles><title>Increased particulate air pollution and the triggering of myocardial infarction</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2810-2815</pages><volume>103</volume><number>23</number><dates><year>2001</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Peters</Author><Year>2001</Year><RecNum>1137</RecNum><DisplayText>Peters et al., 2001</DisplayText><record><rec-number>1137</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peters, Annette</author><author>Dockery, Douglas W</author><author>Muller, James E</author><author>Mittleman, Murray A</author></authors></contributors><titles><title>Increased particulate air pollution and the triggering of myocardial infarction</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2810-2815</pages><volume>103</volume><number>23</number><dates><year>2001</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote> ADDIN EN.CITE  ADDIN EN.CITE.DATA
 ADDIN EN.CITE <EndNote><Author>Peters</Author><Year>2001</Year><RecNum>1137</RecNum><DisplayText>Peters et al., 2001</DisplayText><record><rec-number>1137</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peters, Annette</author><author>Dockery, Douglas W</author><author>Muller, James E</author><author>Mittleman, Murray A</author></authors></contributors><titles><title>Increased particulate air pollution and the triggering of myocardial infarction</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2810-2815</pages><volume>103</volume><number>23</number><dates><year>2001</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote>
 ADDIN EN.CITE <EndNote><Author>Pope III</Author><Year>2006</Year><RecNum>1138</RecNum><DisplayText>Pope III et al., 2006</DisplayText><record><rec-number>1138</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1138</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pope III, CArden</author><author>Muhlestein, Joseph B</author><author>May, Heidi T</author><author>Renlund, Dale G</author><author>Anderson, Jeffrey L</author><author>Horne, Benjamin D</author></authors></contributors><titles><title>Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>2443-2448</pages><volume>114</volume><number>23</number><dates><year>2006</year></dates><isbn>0009-7322</isbn><urls></urls></record></EndNote>
 ADDIN EN.CITE <EndNote><Author>Sullivan</Author><Year>2005</Year><RecNum>1136</RecNum><DisplayText>Sullivan et al., 2005</DisplayText><record><rec-number>1136</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732559">1136</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sullivan, Jeffrey</author><author>Sheppard, Lianne</author><author>Schreuder, Astrid</author><author>Ishikawa, Naomi</author><author>Siscovick, David</author><author>Kaufman, Joel</author></authors></contributors><titles><title>Relation between short-term fine-particulate matter exposure and onset of myocardial infarction</title><secondary-title>Epidemiology</secondary-title></titles><periodical><full-title>Epidemiology</full-title>EpidemiologyEpidemiology</periodical><pages>41-48</pages><dates><year>2005</year></dates><isbn>1044-3983</isbn><urls></urls></record></EndNote>
 ADDIN EN.CITE <EndNote><Author>Zanobetti</Author><Year>2009</Year><RecNum>1140</RecNum><DisplayText>Zanobetti et al., 2009</DisplayText><record><rec-number>1140</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1140</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zanobetti, Antonella</author><author>Franklin, Meredith</author><author>Koutrakis, Petros</author><author>Schwartz, Joel</author></authors></contributors><titles><title>Fine particulate air pollution and its components in association with cause-specific emergency admissions</title><secondary-title>Environmental Health</secondary-title></titles><periodical><full-title>Environmental Health</full-title>Environ. HealthEnviron Health</periodical><pages>58</pages><volume>8</volume><number>1</number><dates><year>2009</year></dates><isbn>1476-069X</isbn><urls></urls></record></EndNote>
 ADDIN EN.CITE <EndNote><Author>Zanobetti</Author><Year>2006</Year><RecNum>1139</RecNum><DisplayText>Zanobetti and Schwartz, 2006</DisplayText><record><rec-number>1139</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1139</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zanobetti, Antonella</author><author>Schwartz, Joel</author></authors></contributors><titles><title>Air pollution and emergency admissions in Boston, MA</title><secondary-title>Journal of Epidemiology Community Health</secondary-title></titles><periodical><full-title>Journal of Epidemiology Community Health</full-title></periodical><pages>890-895</pages><volume>60</volume><number>10</number><dates><year>2006</year></dates><isbn>0143-005X</isbn><urls></urls></record></EndNote> ADDIN EN.CITE <EndNote><Author>Zanobetti</Author><Year>2006</Year><RecNum>1139</RecNum><DisplayText>Zanobetti and Schwartz, 2006</DisplayText><record><rec-number>1139</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603732560">1139</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zanobetti, Antonella</author><author>Schwartz, Joel</author></authors></contributors><titles><title>Air pollution and emergency admissions in Boston, MA</title><secondary-title>Journal of Epidemiology Community Health</secondary-title></titles><periodical><full-title>Journal of Epidemiology Community Health</full-title></periodical><pages>890-895</pages><volume>60</volume><number>10</number><dates><year>2006</year></dates><isbn>0143-005X</isbn><urls></urls></record></EndNote>
Stroke
Available Epidemiologic Literature
The 2019 PM ISA included three epidemiologic studies of stroke that met the minimum identification criteria (U.S. EPA, 2019b, section 2.1.1). REF _Ref54194714 \r \h
Identifying Suitable Studies for Use in Benefits Assessments
One of the available epidemiologic studies was more recent, included a larger population, evaluated long-term exposure effects, and was more representative of the U.S. with regards to both geography and population attributes than the other two studies (Kloog et al., 2012 ADDIN EN.CITE <EndNote><Author>Kloog</Author><Year>2012</Year><RecNum>1170</RecNum><DisplayText>Kloog et al., 2012</DisplayText><record><rec-number>1170</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603987570">1170</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kloog, I.</author><author>Coull, B. A.</author><author>Zanobetti, A.</author><author>Koutrakis, P.</author><author>Schwartz, J. D.</author></authors></contributors><titles><title>Acute and chronic effects of particles on hospital admissions in New-England</title><secondary-title>PLoS ONE</secondary-title><alt-title>PLoS ONE</alt-title></titles><periodical><full-title>PLoS One</full-title></periodical><alt-periodical><full-title>PLoS One</full-title></alt-periodical><pages>e34664</pages><volume>7</volume><number>4</number><dates><year>2012</year></dates><isbn>EISSN 1932-6203</isbn><accession-num>22529923</accession-num>1255201<urls><related-urls><url>http://dx.doi.org/10.1371/journal.pone.0034664</url></related-urls></urls><electronic-resource-num>10.1371/journal.pone.0034664</electronic-resource-num><language>English</language></record></EndNote>).
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Kloog et al., 2012 ADDIN EN.CITE <EndNote><Author>Kloog</Author><Year>2012</Year><RecNum>1170</RecNum><DisplayText>Kloog et al., 2012</DisplayText><record><rec-number>1170</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603987570">1170</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kloog, I.</author><author>Coull, B. A.</author><author>Zanobetti, A.</author><author>Koutrakis, P.</author><author>Schwartz, J. D.</author></authors></contributors><titles><title>Acute and chronic effects of particles on hospital admissions in New-England</title><secondary-title>PLoS ONE</secondary-title><alt-title>PLoS ONE</alt-title></titles><periodical><full-title>PLoS One</full-title></periodical><alt-periodical><full-title>PLoS One</full-title></alt-periodical><pages>e34664</pages><volume>7</volume><number>4</number><dates><year>2012</year></dates><isbn>EISSN 1932-6203</isbn><accession-num>22529923</accession-num>1255201<urls><related-urls><url>http://dx.doi.org/10.1371/journal.pone.0034664</url></related-urls></urls><electronic-resource-num>10.1371/journal.pone.0034664</electronic-resource-num><language>English</language></record></EndNote> analyzed the effects of long- and short-term PM2.5 exposure on hospital admissions due to strokes with a new PM2.5 exposure model in New England (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) from 2000 to 2006. We use this endpoint as a surrogate for PM2.5-attributable stroke incidence. Authors collected medical data from 67,678 adults aged 65 to 99 in the U.S. Medicare program database from 2000 to 2006. They defined all respiratory, cardiovascular disease, stroke, and diabetes based on emergency department visits and primary discharge diagnosis records. Authors used a hybrid exposure technique comprised of daily PM2.5 concentration data from aerosol optical depth (AOD) measurements and ambient air monitors from the U.S. EPA and Interagency Monitoring of Protected Visual Improvements (IMPROVE). Authors also obtained land use regressions, meteorological data (National Climatic Data Center), and socioeconomic data (U.S. Census Bureau) matched to zip codes. Utilizing land use Poisson regression single-pollutant models, the authors found an 3.49% (95% CI: 0.09-5.18) increase in stroke incidence for a 10 ug/m[3] increase in the 7-year mean PM2.5 concentrations.
Respiratory Hospital Admissions
After considering the relationships between specific and broad respiratory hospital admissions endpoints, the 2019 PM ISA stated that "recent studies further expand analyses with older adults, with multicity studies conducted in the U.S. providing evidence of consistent, positive associations between short-term PM2.5 exposure and respiratory-related diseases" (U.S. EPA, 2019b ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote>, section 5.1.6).
The ISA noted that "it is often difficult to determine whether the associations observed indicate that PM2.5 may affect the spectrum of respiratory diseases or reflects the evidence supporting associations with specific respiratory diseases, such as asthma." Taking this into consideration, hospital admissions for asthma exacerbation/symptoms, COPD, and respiratory infections were specifically called out in the short-term PM2.5 exposure biological plausibility diagram (section <IP_ADDRESS>.1.2).
Available Epidemiologic Literature
Like the cardiovascular hospital admission/emergency department visit endpoints, several respiratory studies identified by the ISA combined the hospital admissions and emergency department endpoints. There was also a subset of studies that only considered emergency hospital admission, defined as hospital admissions that originated in the emergency department. As using either studies of emergency hospital admissions or combined emergency department and hospital admission studies would result in increased uncertainty around the economic estimate and/or with the baseline incidence data, we limited our pool of available studies to those specifically evaluating unplanned respiratory hospital admissions, of which there were 12 available studies.
Identifying Suitable Studies for Use in Benefits Assessments
Studies for this endpoint tended to focus on specific age groups, with approximately half focusing on older adults (>64) and none specifying ages 19-64. Importantly, studies varied widely by ICD codes, making pooling of two or more studies difficult. Considering the preferred criteria, two studies were identified, one of children and one of older adults, primarily due to the inclusion of diverse and large study locations. The single study of older adults is more informative than pooling it with other studies of the same population as it is more recent and includes exposure to lower PM2.5 concentration levels.
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Bell et al., 2015 investigated the effects of short-term fine particulate matter (PM2.5) exposure on respiratory health (ICD-9 464-466, 480-487, 490-492, 493) in older adults (>64 years). Authors acquired data for 213 U.S. counties (1999-2010) from the Medicare Claims Inpatient Files for U.S. residents >65 years of age. Authors chose variables including sex, age, county of residence, and cause of hospital admission, as determined by ICD-9 codes. Authors collected PM2.5 exposure data from county population-based ambient monitors from the US EPA Air Quality System and averaged for county and day. Data were present for 56.5% of study days due to the sampling schedule of the monitors. Bell et al., 2015 utilized Bayesian hierarchal modeling to examine the links between PM2.5 and hospital admissions. They ran separate models for time lags (0-2 days) and season to determine if there were any estimated variation in health effects. The identified percent increase in risk of 0.25% (95% CI: 0.01-0.48) for an increase of 10 ug/m[3] in same-day daily mean PM2.5 concentrations came from a single-pollutant model.
Ostro et al., 2009 estimated the association between ambient PM2.5, EC, organic carbon (OC), NO3, and SO4 on hospital admissions for respiratory diseases in children ages 5 to 19. The study used the California Office of Statewide Health Planning and Development, Healthcare Quality and Analysis Division hospitalization data from six California counties for the 2000 to 2003 study period. Ostro et al., 2009 classified hospital admissions into: all respiratory disease (ICD-9 codes 460-519), asthma (ICD-9 code 493), acute bronchitis (ICD-9 code 466), and pneumonia (ICD-9 codes 480-486). They aggregated the hospital admission data to the county level to create a daily time series of admissions for each county. Authors took air quality measurements from the California Air Resources Board, which captured speciated 24-hour average pollutant measurements using a filter-based Met One Speciation Air Sampling System. Meteorological measurements for average daily temperature and relative humidity came from the California Air Resources Board or the California Irrigation Management Information System. Authors analyzed data using a Poisson regression with time, day of the week, temperature, relative humidity, and pollutant as explanatory variables. Ostro et al., 2009 controlled for seasonality and time dependent effects by including a natural spline smoother for the daily time trend and meteorology. The identified percent increase in risk of excess risk of 4.1% (95% CI: 1.8-6.4) for a 14.6 ug/m[3] increase in daily mean PM2.5 concentrations, lagged by 3 days, came from a single-pollutant model.
Respiratory Emergency Department Visits
After considering the relationships between specific and broad respiratory emergency department visit endpoints, the 2019 PM ISA stated that "recent studies further expand analyses with older adults, with multicity studies conducted in the U.S. providing evidence of consistent, positive associations between short-term PM2.5 exposure and respiratory-related diseases" (3202019c3200xd5s9009txfw1eafstv220i5ds2wvtpwf5d1573071075">320Washington, DCNational U.S. EPA, 2019b, section 5.1.6).
The ISA noted that "it is often difficult to determine whether the associations observed indicate that PM2.5 may affect the spectrum of respiratory diseases or reflects the evidence supporting associations with specific respiratory diseases, such as asthma." Emergency department visits for asthma exacerbation/symptoms, COPD, and respiratory infections were specifically called out in the short-term PM2.5 exposure biological plausibility diagram (section <IP_ADDRESS>.1.2).
Available Epidemiologic Literature
Like the cardiovascular hospital admission/emergency department visit endpoints, several respiratory studies identified by the ISA combined the hospital admissions and emergency department endpoints. As using the combined study endpoint would result in increased uncertainty around the economic estimate, we limited our pool of available studies to those specifically looking at respiratory emergency department visits for the main benefits assessment, of which there were 10 studies.
Identifying Suitable Studies for Use in Benefits Assessments
One study out of the 10 was more recent, provided greater geographic representation, and included all ages.
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Krall et al., 2013 ADDIN EN.CITE <EndNote><Author>Krall</Author><Year>2013</Year><RecNum>1197</RecNum><DisplayText>Krall et al., 2013</DisplayText><record><rec-number>1197</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604066229">1197</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Krall, J. R.</author><author>Anderson, G. B.</author><author>Dominici, F.</author><author>Bell, M. L.</author><author>Peng, R. D.</author></authors></contributors><auth-address>Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.</auth-address><titles><title>Short-term exposure to particulate matter constituents and mortality in a national study of U.S. urban communities</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>1148-53</pages><volume>121</volume><number>10</number><edition>2013/08/06</edition><keywords><keyword>Air Pollutants/*analysis/chemistry</keyword><keyword>*Environmental Monitoring</keyword><keyword>Humans</keyword><keyword>*Mortality</keyword><keyword>Particulate Matter/*analysis/chemistry</keyword><keyword>Regression Analysis</keyword><keyword>Seasons</keyword><keyword>United States</keyword><keyword>Urban Population</keyword></keywords><dates><year>2013</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1552-9924 (Electronic)
0091-6765 (Linking)</isbn><accession-num>23912641</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/23912641</url></related-urls></urls><custom2>PMC3801200</custom2><electronic-resource-num>10.1289/ehp.1206185</electronic-resource-num></record></EndNote> investigated the associations between short-term, source-specific (traffic and coal combustion) ambient PM2.5 exposure and emergency department visits for respiratory diseases in U.S. cities (Atlanta, GA, Birmingham, AL, St. Louis, MO, and Dallas, TX). Authors obtained medical data from hospital electronic billings for emergency department visits due to respiratory disease, identified using ICD-9 codes (460-465, 466, 477, 480-486, 491, 492, 493, 496, 786.07). Authors collected PM2.5 concentrations from one ambient air monitor in each of the four cities and gathered meteorological data from the National Climactic Data Center. Krall et al., 2013 ADDIN EN.CITE <EndNote><Author>Krall</Author><Year>2013</Year><RecNum>1197</RecNum><DisplayText>Krall et al., 2013</DisplayText><record><rec-number>1197</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604066229">1197</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Krall, J. R.</author><author>Anderson, G. B.</author><author>Dominici, F.</author><author>Bell, M. L.</author><author>Peng, R. D.</author></authors></contributors><auth-address>Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.</auth-address><titles><title>Short-term exposure to particulate matter constituents and mortality in a national study of U.S. urban communities</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>1148-53</pages><volume>121</volume><number>10</number><edition>2013/08/06</edition><keywords><keyword>Air Pollutants/*analysis/chemistry</keyword><keyword>*Environmental Monitoring</keyword><keyword>Humans</keyword><keyword>*Mortality</keyword><keyword>Particulate Matter/*analysis/chemistry</keyword><keyword>Regression Analysis</keyword><keyword>Seasons</keyword><keyword>United States</keyword><keyword>Urban Population</keyword></keywords><dates><year>2013</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1552-9924 (Electronic)
0091-6765 (Linking)</isbn><accession-num>23912641</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/23912641</url></related-urls></urls><custom2>PMC3801200</custom2><electronic-resource-num>10.1289/ehp.1206185</electronic-resource-num></record></EndNote> estimated source specific PM2.5 using apportionment models, which separate PM2.5 sources based on chemical composition. This model also included data on gaseous pollutant concentrations from the Community Multiscale Air Quality (CMAQ) with Tracers model. Krall et al., 2013 ADDIN EN.CITE <EndNote><Author>Krall</Author><Year>2013</Year><RecNum>1197</RecNum><DisplayText>Krall et al., 2013</DisplayText><record><rec-number>1197</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604066229">1197</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Krall, J. R.</author><author>Anderson, G. B.</author><author>Dominici, F.</author><author>Bell, M. L.</author><author>Peng, R. D.</author></authors></contributors><auth-address>Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.</auth-address><titles><title>Short-term exposure to particulate matter constituents and mortality in a national study of U.S. urban communities</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>1148-53</pages><volume>121</volume><number>10</number><edition>2013/08/06</edition><keywords><keyword>Air Pollutants/*analysis/chemistry</keyword><keyword>*Environmental Monitoring</keyword><keyword>Humans</keyword><keyword>*Mortality</keyword><keyword>Particulate Matter/*analysis/chemistry</keyword><keyword>Regression Analysis</keyword><keyword>Seasons</keyword><keyword>United States</keyword><keyword>Urban Population</keyword></keywords><dates><year>2013</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1552-9924 (Electronic)
0091-6765 (Linking)</isbn><accession-num>23912641</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/23912641</url></related-urls></urls><custom2>PMC3801200</custom2><electronic-resource-num>10.1289/ehp.1206185</electronic-resource-num></record></EndNote> used Poisson time series regression models to analyze associations between short-term PM2.5 exposure and emergency department visits for respiratory diseases. They then compared source specific PM2.5 exposures across cities to estimate associations with the emergency department visit data. To limit confounders, the authors adjusted models for indicator variables, meteorological variables, and long-term trends in emergency department visits. The identified relative risk estimates of 1.005 (95% CI: 1.000-1.010) for Atlanta, GA; 1.009 (95% CI: 1.003-1.015) for Birmingham, AL; 1.008 (95% CI: 1.002-1.014) for St. Louis, MO; and 1.012 (95% CI: 1.002-1.023) for Dallas, TX were calculated from a single-pollutant model for a 9.16 ug/m[3] increase in daily mean PM2.5 concentrations, lagged by 0 days.
Asthma Onset
The 2019 PM ISA stated that "longitudinal studies provide evidence of associations with asthma incidence in children" and found "evidence for a relationship between PM2.5 exposure and asthma prevalence in children and childhood wheeze" (U.S. EPA, 2019b). ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote> Additionally, asthma onset was called out as a key clinically relevant health endpoint in the biological plausibility pathways included in the ISA (section <IP_ADDRESS>.1.2) (3202019c3200xd5s9009txfw1eafstv220i5ds2wvtpwf5d1573071075">320Washington, DCNational U.S. EPA, 2019b).
Available Epidemiologic Literature
The final 2019 PM ISA found that "recent studies of asthma in children supplement the limited number of studies reviewed in the 2009 PM ISA and provide evidence of an association between long-term PM2.5 exposure and asthma development in children" (U.S. EPA, 2019b). ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote> There was also evidence of PM2.5-attributable asthma onset in adults, but results were inconsistent across studies. As a result, asthma onset in adults is not included in our main benefits assessment.
Five North American epidemiologic studies of asthma onset in children were identified in section 5.2 of the 2019 PM ISA (U.S. EPA, 2019b). ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote> Relevant information related to the identification criteria, including study location, population attributes, and study period, were extracted from the studies and is available in the corresponding Excel file.
Identifying Suitable Studies for Use in Benefits Assessments
Although the available asthma onset studies vary widely in all criteria considered, relevant study information was again used to identify the most nationally representative study or studies (see Excel file). Interestingly, three of the five studies were conducted in Canada. One study conducted in Canada evaluated a recent and extensive time series of air quality and health data; assigned exposures to populations using a combination of monitor and remote sensing data; validated the outcome measure; observed effects with relatively low (~10 ug/m[3]) PM2.5 concentrations and included over 30-fold the number of participants as any other study. Other available literature was also more limited with regards to population demographic and geographic diversity.
Study Identified as Most Suitable for Use in Benefits Assessments
Tetreault et al., 2016 ADDIN EN.CITE <EndNote><Author>Tetreault</Author><Year>2016</Year><RecNum>1183</RecNum><DisplayText>Tetreault et al., 2016</DisplayText><record><rec-number>1183</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603988120">1183</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tetreault, L. F.</author><author>Doucet, M.</author><author>Gamache, P.</author><author>Fournier, M.</author><author>Brand, A.</author><author>Kosatsky, T.</author><author>Smargiassi, A.</author></authors></contributors><auth-address>Department of Environmental and Occupational Health, School of Public Health University of Montreal, Montreal, Quebec, Canada.</auth-address><titles><title>Childhood Exposure to Ambient Air Pollutants and the Onset of Asthma: An Administrative Cohort Study in Quebec</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>1276-82</pages><volume>124</volume><number>8</number><edition>2016/01/06</edition><keywords><keyword>Air Pollutants/analysis</keyword><keyword>Asthma/*epidemiology</keyword><keyword>Environmental Exposure/analysis/*statistics & numerical data</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nitrogen Dioxide/analysis</keyword><keyword>Particulate Matter/analysis</keyword><keyword>Proportional Hazards Models</keyword><keyword>Quebec/epidemiology</keyword></keywords><dates><year>2016</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1552-9924 (Electronic)
0091-6765 (Linking)</isbn><accession-num>26731790</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26731790</url></related-urls></urls><custom2>PMC4977042</custom2><electronic-resource-num>10.1289/ehp.1509838</electronic-resource-num></record></EndNote> investigated the relationship between childhood asthma onset and long-term pollution exposure (PM2.5, NO2, O3) in Quebec, Canada. The authors obtained data from four medical-administrative databases collectively known as Quebec Integrated Chronic Disease Surveillance System (QICDSS) between April 1, 1996 and March 31, 2011. The study defined the onset of asthma as a hospital discharged diagnosis of asthma or two reports of asthma from two separate physicians within a two-year period. The authors used Cox proportional hazard models to estimate the association between asthma onset and pollution exposure, controlling for demographics and socioeconomic status. Time-varying exposure models assessed time-varying exposures to the three pollutants in question. Tetreault et al., 2016 ADDIN EN.CITE <EndNote><Author>Tetreault</Author><Year>2016</Year><RecNum>1183</RecNum><DisplayText>Tetreault et al., 2016</DisplayText><record><rec-number>1183</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603988120">1183</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tetreault, L. F.</author><author>Doucet, M.</author><author>Gamache, P.</author><author>Fournier, M.</author><author>Brand, A.</author><author>Kosatsky, T.</author><author>Smargiassi, A.</author></authors></contributors><auth-address>Department of Environmental and Occupational Health, School of Public Health University of Montreal, Montreal, Quebec, Canada.</auth-address><titles><title>Childhood Exposure to Ambient Air Pollutants and the Onset of Asthma: An Administrative Cohort Study in Quebec</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>1276-82</pages><volume>124</volume><number>8</number><edition>2016/01/06</edition><keywords><keyword>Air Pollutants/analysis</keyword><keyword>Asthma/*epidemiology</keyword><keyword>Environmental Exposure/analysis/*statistics & numerical data</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nitrogen Dioxide/analysis</keyword><keyword>Particulate Matter/analysis</keyword><keyword>Proportional Hazards Models</keyword><keyword>Quebec/epidemiology</keyword></keywords><dates><year>2016</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1552-9924 (Electronic)
0091-6765 (Linking)</isbn><accession-num>26731790</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26731790</url></related-urls></urls><custom2>PMC4977042</custom2><electronic-resource-num>10.1289/ehp.1509838</electronic-resource-num></record></EndNote> showed that childhood asthma onset may be associated with exposure to PM2.5, NO2, and O3.
The identified study presented 24 hazard ratios using various adjustment methods and included multiple sensitivity analyses, evaluating the effects by sex, urbanicity, and those who moved during the study period. More-adjusted risk estimates using a time-varying estimate of PM2.5 exposure and including the full cohort were identified over less-adjusted or stratified estimates using exposure estimates at birth.  The study identified as best characterizing risk across the U.S. was 118311830xd5s9009txfw1eafstv220i5ds2wvtpwf5d1603988120">1183..</>Environ Health Perspect</abbr-2Tetreault et al., 2016, although the two older and demographic-limited U.S. studies were also identified as potentially informative.
The risk estimate identified from Tetreault et al., 2016 for use in the main benefits estimates was a single-pollutant time-varying hazard ratio model of 1.33 (95% CI: 1.31-1.34) for a 6.53 ug/m[3] (interquartile range) increase in annual PM2.5 concentration at the residential address.
 ADDIN EN.CITE <EndNote><Author>Tetreault</Author><Year>2016</Year><RecNum>1183</RecNum><DisplayText>Tetreault et al., 2016</DisplayText><record><rec-number>1183</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603988120">1183</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tetreault, L. F.</author><author>Doucet, M.</author><author>Gamache, P.</author><author>Fournier, M.</author><author>Brand, A.</author><author>Kosatsky, T.</author><author>Smargiassi, A.</author></authors></contributors><auth-address>Department of Environmental and Occupational Health, School of Public Health University of Montreal, Montreal, Quebec, Canada.</auth-address><titles><title>Childhood Exposure to Ambient Air Pollutants and the Onset of Asthma: An Administrative Cohort Study in Quebec</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>1276-82</pages><volume>124</volume><number>8</number><edition>2016/01/06</edition><keywords><keyword>Air Pollutants/analysis</keyword><keyword>Asthma/*epidemiology</keyword><keyword>Environmental Exposure/analysis/*statistics & numerical data</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nitrogen Dioxide/analysis</keyword><keyword>Particulate Matter/analysis</keyword><keyword>Proportional Hazards Models</keyword><keyword>Quebec/epidemiology</keyword></keywords><dates><year>2016</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1552-9924 (Electronic)
0091-6765 (Linking)</isbn><accession-num>26731790</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26731790</url></related-urls></urls><custom2>PMC4977042</custom2><electronic-resource-num>10.1289/ehp.1509838</electronic-resource-num></record></EndNote>
As the physiology and etiology of lung development in children is similar in children 6-17, we apply the 4-12 year age-stratified effect estimate from Tetreault et al., 2016 ADDIN EN.CITE <EndNote><Author>Tetreault</Author><Year>2016</Year><RecNum>1183</RecNum><DisplayText>Tetreault et al., 2016</DisplayText><record><rec-number>1183</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1603988120">1183</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tetreault, L. F.</author><author>Doucet, M.</author><author>Gamache, P.</author><author>Fournier, M.</author><author>Brand, A.</author><author>Kosatsky, T.</author><author>Smargiassi, A.</author></authors></contributors><auth-address>Department of Environmental and Occupational Health, School of Public Health University of Montreal, Montreal, Quebec, Canada.</auth-address><titles><title>Childhood Exposure to Ambient Air Pollutants and the Onset of Asthma: An Administrative Cohort Study in Quebec</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>1276-82</pages><volume>124</volume><number>8</number><edition>2016/01/06</edition><keywords><keyword>Air Pollutants/analysis</keyword><keyword>Asthma/*epidemiology</keyword><keyword>Environmental Exposure/analysis/*statistics & numerical data</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nitrogen Dioxide/analysis</keyword><keyword>Particulate Matter/analysis</keyword><keyword>Proportional Hazards Models</keyword><keyword>Quebec/epidemiology</keyword></keywords><dates><year>2016</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1552-9924 (Electronic)
0091-6765 (Linking)</isbn><accession-num>26731790</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26731790</url></related-urls></urls><custom2>PMC4977042</custom2><electronic-resource-num>10.1289/ehp.1509838</electronic-resource-num></record></EndNote> to children ages 4-17 (Baena-Cagnani et al., 2007, Guerra et al., 2004, Ochs et al., 2004, Sparrow et al., 1991, Trivedi and Denton, 2019).
Asthma Symptoms/Exacerbation
The 2019 PM ISA stated that "evidence for effects on asthma exacerbation are generally more consistent than associations for other respiratory outcomes." The ISA went on to note that "recent studies strengthen the relationship between asthma exacerbation in children and short-term PM2.5 exposure, while, in adults, the relationship continues to be inconsistent" (U.S. EPA, 2019b).
Available Epidemiologic Literature
Based on evidence provided by the 2019 PM ISA, available studies of asthma symptoms were limited to children, of which there were eight.
Identifying Suitable Studies for Use in Benefits Assessments
Due to the specificity required when evaluating this health endpoint, Individual studies of asthma exacerbation/symptoms tended to focus on relatively small cohorts of children of discrete ages in distinct locations, making pooling difficult. One study evaluated a directly monetizable outcome of albuterol inhaler use. Albuterol inhalers are separated from long-term asthma control medications and is considered a "rescue medication" by the Mayo Clinic, making it an informative endpoint when considering asthma symptoms.
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Rabinovitch et al., 2006 analyzed the relationship between short-term PM2.5 exposure and asthma exacerbation in children. The study followed children, ages 6 to 13 attending the Kunsberg School at the National Jewish Medical Research Center with diagnosed asthma for two consecutive winters from 2001-2003. Authors gave an electronic bronchodilator (albuterol) to the children to capture the frequency of use within a 24-hour period. The children also responded to three questions to determine if they may have an upper respiratory infection (URI), and urine samples were taken to measure urinary leukotriene E4 levels on select days. The authors collected hourly ambient PM2.5 levels from the Colorado Department of Health Air Pollution Control Division's Tapered Element Oscillating Microbalance (TEOM) monitor, located 2.7 miles west of the school. Additionally, a Federal Reference Monitor (FRM) located next to the TEOM measured 24-hour PM2.5 levels. The authors obtained meteorological data from the Colorado Department of Health Air Pollution Control Division and the National Climatic Data Center. A Poisson regression modeled albuterol use as a function of the morning (12:00am to 11:00 am) maximum hourly PM2.5 level or the morning mean hourly PM2.5 level. The model used both the TEOM and FRM data, individually, incorporated four lag periods (0 to 2 days and 0- to 2-day average), and included several covariates: temperature, pressure, humidity, time trend, Friday indicator, and URI indicator. Rabinovitch et al., 2006 found that, although the PM2.5 pollution levels were well below the National Ambient Air Quality Standards, there is a consistent association between peak ambient PM2.5 levels and increased albuterol use in asthmatic children. The identified percent of use increase estimate of 1.2% (95% CI: -0.6-2.9) for a 6 ug/m[3] increase in averaged daily mean PM2.5 concentration lagged by 0-, 1-, and 2-days came from a single-pollutant model. As the physiology and etiology of lung development in children is similar in children 6-17, we apply the 6-13-year age-stratified effect estimate to children ages 6 to 17 (Baena-Cagnani et al., 2007, Guerra et al., 2004, Ochs et al., 2004, Sparrow et al., 1991, Trivedi and Denton, 2019).
Allergic Rhinitis (Hay Fever/Respiratory Allergies)
The 2019 PM ISA stated that "recent studies evaluated associations between long-term exposure to PM2.5 and various allergic outcomes in a mix of large representative cohort and cross-sectional survey studies" finding "generally consistent evidence of an association between long-term PM2.5 exposure and allergic sensitization in single pollutant models" (U.S. EPA, 2019b, section 5.2.4). ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2020</Year><RecNum>343</RecNum><DisplayText>U.S. EPA, 2020a</DisplayText><record><rec-number>343</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1581631219">343</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>Office of Research and Development</author></secondary-authors></contributors><titles><title>Integrated Science Assessment for Ozone and Related Photochemical Oxidants</title></titles><dates><year>2020</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency</publisher><isbn>EPA/600/R-20/012</isbn><urls><related-urls><url>Available at: https://www.epa.gov/isa/integrated-science-assessment-isa-ozone-and-related-photochemical-oxidants</url></related-urls></urls></record></EndNote> Additionally, the ISA called out "allergic responses" in the biological plausibility diagram for long-term PM2.5-attributable respiratory effects (U.S. EPA, 2019b ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2020</Year><RecNum>343</RecNum><DisplayText>U.S. EPA, 2020a</DisplayText><record><rec-number>343</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1581631219">343</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>Office of Research and Development</author></secondary-authors></contributors><titles><title>Integrated Science Assessment for Ozone and Related Photochemical Oxidants</title></titles><dates><year>2020</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency</publisher><isbn>EPA/600/R-20/012</isbn><urls><related-urls><url>Available at: https://www.epa.gov/isa/integrated-science-assessment-isa-ozone-and-related-photochemical-oxidants</url></related-urls></urls></record></EndNote>, section <IP_ADDRESS>.1.2). Although cross sectional analyses do not establish a temporal sequence, they can be used to estimate benefits associated with changes in air quality.
Available Epidemiologic Literature

Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
The 2019 PM ISA identified one epidemiologic study of long-term 2019 PM2.5 exposure and allergic rhinitis (U.S. EPA, 2019b).
 ADDIN EN.CITE <EndNote><Author>Parker</Author><Year>2009</Year><RecNum>1247</RecNum><DisplayText>Parker et al., 2009</DisplayText><record><rec-number>1247</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1608146211">1247</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parker, J. D.</author><author>Akinbami, L. J.</author><author>Woodruff, T. J.</author></authors></contributors><auth-address>National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland 20782, USA<EMAIL_ADDRESS>pollution and childhood respiratory allergies in the United States</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>140-7</pages><volume>117</volume><number>1</number><edition>2009/01/24</edition><keywords><keyword>Adolescent</keyword><keyword>*Air Pollution</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Humans</keyword><keyword>Hypersensitivity/*epidemiology</keyword><keyword>United States/epidemiology</keyword><keyword>United States Environmental Protection Agency</keyword><keyword>allergy</keyword><keyword>children</keyword><keyword>hay fever</keyword><keyword>ozone</keyword><keyword>particulate matter</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0091-6765 (Print)
0091-6765 (Linking)</isbn><accession-num>19165401</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/19165401</url></related-urls></urls><custom2>PMC2627858</custom2><electronic-resource-num>10.1289/ehp.11497</electronic-resource-num></record></EndNote>Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Parker et al., 2009 investigated the associations between long-term PM2.5 exposure and respiratory allergies in an unrestricted population of children (aged 3-17 years) sampled from the United States National Health Interview Survey. Authors obtained symptom data from participant parents, who reported respiratory allergies on annual surveys. Parker et al., 2009 ADDIN EN.CITE <EndNote><Author>Parker</Author><Year>2009</Year><RecNum>1247</RecNum><DisplayText>Parker et al., 2009</DisplayText><record><rec-number>1247</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1608146211">1247</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parker, J. D.</author><author>Akinbami, L. J.</author><author>Woodruff, T. J.</author></authors></contributors><auth-address>National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland 20782, USA<EMAIL_ADDRESS>pollution and childhood respiratory allergies in the United States</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>140-7</pages><volume>117</volume><number>1</number><edition>2009/01/24</edition><keywords><keyword>Adolescent</keyword><keyword>*Air Pollution</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Humans</keyword><keyword>Hypersensitivity/*epidemiology</keyword><keyword>United States/epidemiology</keyword><keyword>United States Environmental Protection Agency</keyword><keyword>allergy</keyword><keyword>children</keyword><keyword>hay fever</keyword><keyword>ozone</keyword><keyword>particulate matter</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0091-6765 (Print)
0091-6765 (Linking)</isbn><accession-num>19165401</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/19165401</url></related-urls></urls><custom2>PMC2627858</custom2><electronic-resource-num>10.1289/ehp.11497</electronic-resource-num></record></EndNote> placed all study participants reporting symptoms of respiratory allergies or hay fever into a combined rhinitis group. Parker et al., 2009 ADDIN EN.CITE <EndNote><Author>Parker</Author><Year>2009</Year><RecNum>1247</RecNum><DisplayText>Parker et al., 2009</DisplayText><record><rec-number>1247</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1608146211">1247</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parker, J. D.</author><author>Akinbami, L. J.</author><author>Woodruff, T. J.</author></authors></contributors><auth-address>National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland 20782, USA<EMAIL_ADDRESS>pollution and childhood respiratory allergies in the United States</title><secondary-title>Environ Health Perspect</secondary-title></titles><periodical><full-title>Environmental Health Perspectives</full-title>Environ. Health Perspect.Environ Health Perspect</periodical><pages>140-7</pages><volume>117</volume><number>1</number><edition>2009/01/24</edition><keywords><keyword>Adolescent</keyword><keyword>*Air Pollution</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Humans</keyword><keyword>Hypersensitivity/*epidemiology</keyword><keyword>United States/epidemiology</keyword><keyword>United States Environmental Protection Agency</keyword><keyword>allergy</keyword><keyword>children</keyword><keyword>hay fever</keyword><keyword>ozone</keyword><keyword>particulate matter</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0091-6765 (Print)
0091-6765 (Linking)</isbn><accession-num>19165401</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/19165401</url></related-urls></urls><custom2>PMC2627858</custom2><electronic-resource-num>10.1289/ehp.11497</electronic-resource-num></record></EndNote> then linked annual averages of SO2, NO2, PM2.5, and PM2.5-10 and warm season (May to September) O3 averages to participant's addresses through ambient air pollution and meteorological data (O3, SO2, NO2, PM2.5, and PM10-2.5) collected from US EPA Air Quality System monitors. The authors adjusted models for survey year, poverty-level, race/ethnicity, age, family structure, insurance coverage, usual source of care, education of adult, urban-rural status, region, and median county-level income. Through multi-pollutant, logistic regression models, an odds ratio of 1.29 (95% CI: 1.07-1.56) for a 10 ug/m[3] increase in PM2.5 concentrations and respiratory allergies was identified.
Minor Restricted Activity Days
No new epidemiologic studies of minor restricted activity days (MRADs) were identified in the 2019 PM ISA (U.S. EPA, 2019b).
 ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote>
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Ostro and Rothschild, 1989Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
 ADDIN EN.CITE <EndNote><Author>Ostro</Author><Year>1989</Year><RecNum>1372</RecNum><DisplayText>Ostro and Rothschild, 1989</DisplayText><record><rec-number>1372</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1608588120">1372</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ostro, B. D.</author><author>Rothschild, S.</author></authors></contributors><auth-address>California Public Health Foundation, Berkeley 94704.</auth-address><titles><title>Air pollution and acute respiratory morbidity: an observational study of multiple pollutants</title><secondary-title>Environ Res</secondary-title></titles><periodical><full-title>Environmental Research</full-title>Environ. Res.Environ Res</periodical><pages>238-47</pages><volume>50</volume><number>2</number><edition>1989/12/01</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Air Pollutants/adverse effects</keyword><keyword>Air Pollution/*adverse effects/statistics & numerical data</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Information Systems</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Ozone/adverse effects</keyword><keyword>Regression Analysis</keyword><keyword>Respiratory Tract Diseases/epidemiology/*mortality</keyword><keyword>United States</keyword></keywords><dates><year>1989</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0013-9351 (Print)
0013-9351 (Linking)</isbn><accession-num>2583069</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/2583069</url></related-urls></urls><electronic-resource-num>10.1016/s0013-9351(89)80004-0</electronic-resource-num></record></EndNote> estimated the impact of PM2.5 and O3 on the incidence of minor restricted activity days (MRADs) and respiratory-related restricted activity days (RRADs) in a national sample of the adult working population, ages 18 to 65, living in metropolitan areas. The study population is based on the Health Interview Survey (HIS), conducted by the National Center for Health Statistics. In publications from this ongoing survey, non-elderly adult populations are generally reported as ages 18-64. From the study, it is not clear if the age range stops at or includes those aged 65. We apply the risk estimate function to individuals ages 18-64 for consistency with other studies estimating impacts to non-elderly adult populations. The annual national survey results used in this analysis were conducted in the period 1976-1981, controlling for PM2.5, two-week average O3.
Work Loss Days
No new studies of work loss days (WLDs) were identified in the 2019 PM ISA (U.S. EPA, 2019b).
Studies and Risk Estimates Identified as Most Suitable for Use in Benefits Assessments
Ostro, 1987 ADDIN EN.CITE <EndNote><Author>U.S. EPA</Author><Year>2019</Year><RecNum>320</RecNum><DisplayText>U.S. EPA, 2019c</DisplayText><record><rec-number>320</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1573071075">320</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>U.S. EPA,</author></authors><secondary-authors><author>U.S. EPA </author></secondary-authors></contributors><titles><title>Integrated Science Assessment (ISA) for Particulate Matter (Final Report)</title></titles><edition>December 2019</edition><dates><year>2019</year></dates><pub-location>Washington, DC</pub-location><publisher>U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment</publisher><isbn>EPA/600/R-19/188</isbn><urls><related-urls><url>Available at: https://www.epa.gov/naaqs/particulate-matter-pm-standards-integrated-science-assessments-current-review</url></related-urls></urls></record></EndNote>

 ADDIN EN.CITE <EndNote><Author>Ostro</Author><Year>1987</Year><RecNum>1201</RecNum><DisplayText>Ostro, 1987</DisplayText><record><rec-number>1201</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604071574">1201</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ostro, BD</author></authors></contributors><titles><title>Air pollution and morbidity revisited: A specification test</title><secondary-title>Journal of Environmental Economics and Management</secondary-title></titles><periodical><full-title>Journal of Environmental Economics and Management</full-title>J. Environ. Econ. Manage.J Environ Econ Manage</periodical><pages>87-98</pages><volume>14</volume><number>1</number><dates><year>1987</year><pub-dates><date>March 1987</date></pub-dates></dates><urls></urls><electronic-resource-num>10.1016/0095-0696(87)90008-8</electronic-resource-num></record></EndNote> estimated the impact of PM2.5 on the incidence of work-loss days (WLDs), restricted activity days (RADs), and respiratory-related RADs (RRADs) in a national sample of the adult working population, ages 18 to 65, living in metropolitan areas. The study population is based on the Health Interview Survey (HIS), conducted by the National Center for Health Statistics. The annual national survey results used in this analysis were conducted in 1976-1981. Ostro, 1987 ADDIN EN.CITE <EndNote><Author>Ostro</Author><Year>1987</Year><RecNum>1201</RecNum><DisplayText>Ostro, 1987</DisplayText><record><rec-number>1201</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604071574">1201</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ostro, BD</author></authors></contributors><titles><title>Air pollution and morbidity revisited: A specification test</title><secondary-title>Journal of Environmental Economics and Management</secondary-title></titles><periodical><full-title>Journal of Environmental Economics and Management</full-title>J. Environ. Econ. Manage.J Environ Econ Manage</periodical><pages>87-98</pages><volume>14</volume><number>1</number><dates><year>1987</year><pub-dates><date>March 1987</date></pub-dates></dates><urls></urls><electronic-resource-num>10.1016/0095-0696(87)90008-8</electronic-resource-num></record></EndNote> reported that two-week average PM2.5 levels were significantly linked to work-loss days, RADs, and RRADs, however there was some year-to-year variability in the results. Separate coefficients were developed for each year in the analysis (1976-1981); these coefficients were pooled. The coefficient used in the concentration-response function presented here is a weighted average of the coefficients in Ostro, 1987 ADDIN EN.CITE <EndNote><Author>Ostro</Author><Year>1987</Year><RecNum>1201</RecNum><DisplayText>Ostro, 1987</DisplayText><record><rec-number>1201</rec-number><foreign-keys><key app="EN" db-id="0xd5s9009txfw1eafstv220i5ds2wvtpwf5d" timestamp="1604071574">1201</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ostro, BD</author></authors></contributors><titles><title>Air pollution and morbidity revisited: A specification test</title><secondary-title>Journal of Environmental Economics and Management</secondary-title></titles><periodical><full-title>Journal of Environmental Economics and Management</full-title>J. Environ. Econ. Manage.J Environ Econ Manage</periodical><pages>87-98</pages><volume>14</volume><number>1</number><dates><year>1987</year><pub-dates><date>March 1987</date></pub-dates></dates><urls></urls><electronic-resource-num>10.1016/0095-0696(87)90008-8</electronic-resource-num></record></EndNote>, Table III, using the inverse of the variance as the weight.
Lung Cancer