Faculty Bibliography

The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.

Health risks associated with short-term exposure to ambient air pollution are communicated to the public by the US EPA through the Air Quality Index (AQI), but it remains unclear whether the current regulatory-based, single-pollutant AQI fully represents the actual risks of air pollution-related illness. The objective of this study is to quantify cardiovascular hospital admissions attributable to PM2.5 at each AQI category. Based on National Ambient Air Quality Standards (NAAQS), the highest AQI value among criteria pollutants (driver pollutant) is reported daily. We investigated excess cardiovascular hospital admissions attributable to fine particulate matter (PM2.5) exposure from 2000 to 2010 in Bronx, Erie, Queens, and Suffolk counties of New York. Daily total, unscheduled cardiovascular hospital admissions (principal diagnosis) for individuals aged 20-99 years, concentration-response functions for PM2.5, and estimated quarterly effective daily concentrations were used to calculate excess cardiovascular hospital admissions when PM2.5 was reported as the driver pollutant and when PM2.5 was not reported as the driver pollutant at each AQI category. A higher proportion of excess hospital admissions attributable to PM2.5 occurred when PM2.5 was the driver pollutant (i.e., ~70% in Bronx County). The majority of excess hospital admissions (i.e., >90% in Bronx County) occurred when the AQI was <100 ("good" or "moderate" level of health concern) regardless of whether PM2.5 was the driver pollutant. During the warm season (April-September), greater excess admissions in Suffolk County occurred when PM2.5 was not the AQI driver pollutant. These results indicate that a single-pollutant index may inadequately communicate the adverse health risks associated with air pollution.Journal of Exposure Science and Environmental Epidemiology advance online publication, 15 July 2015; doi:10.1038/jes.2015.43.

Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3 Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O3 To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-beta-methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild-type and PAI-1-deficient mice. With the exception of MIP-2, which was significantly lower in PAI-1-deficient as compared to wild-type mice 24 h following cessation of exposure to O3, no other genotype-related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI-1 neither regulates pulmonary expression of IL-6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3.

Estimates of the health impacts of air pollution are needed to make informed air quality management decisions at both the national and local levels. Using design values of ambient pollution concentrations from 2011-2013 as a baseline, the American Thoracic Society (ATS) and the Marron Institute of Urban Management estimated excess morbidity and mortality in the United States attributable to exposure to ambient ozone (O3) and fine particulate matter (PM2.5) at levels above the American Thoracic Society-recommended standards. Within the subset of counties with valid design values for each pollutant, 14% had PM2.5 concentrations greater than the ATS recommendation, whereas 91% had O3 concentrations greater than the ATS recommendation. Approximately 9,320 excess deaths (69% from O3; 31% from PM2.5), 21,400 excess morbidities (74% from O3; 26% from PM2.5), and 19,300,000 adversely impacted days (88% from O3; 12% from PM2.5) in the United States each year are attributable to pollution exceeding the ATS-recommended standards. California alone is responsible for 37% of the total estimated health impacts, and the next three states (Pennsylvania, Texas, and Ohio) together contributed to 20% of the total estimates. City-specific health estimates are provided in this report and through an accompanying online tool to help inform air quality management decisions made at the local level. Riverside and Los Angeles, California have the most to gain by attaining the ATS recommendations for O3 and PM2.5. This report will be revised and updated regularly to help cities track their progress.

BACKGROUND: Outdoor fine particulate matter (PM2.5) has been identified as a global health threat, but the number of large U.S. prospective cohort studies with individual participant data remains limited, especially at lower recent exposures. OBJECTIVES: To test the relationship between long-term exposure PM2.5 and death risk from all non-accidental causes, cardiovascular (CVD), and respiratory diseases in 517,041 men and women enrolled in the National Institutes of Health-AARP cohort. METHODS: Individual participant data were linked with residence PM2.5 exposure estimates across the continental U.S for a 2000-2009 follow up period when matching census-tract level PM2.5 exposure data were available. Participants enrolled ranged from 50-71 yrs. of age, residing in 6 U.S. States and 2 cities. Cox Proportional Hazard models yielded Hazard Ratio (HR) estimates per 10 microg/m3 of PM2.5 exposure. RESULTS: PM2.5 exposure was significantly associated with total mortality (HR= 1.03, 95% CI =1.00, 1.05) and CVD mortality (HR=1.10, 95% CI=1.05, 1.15), but the association with respiratory mortality was not statistically significant (HR=1.05, 95% CI=0.98,1.13). A significant association was found with respiratory mortality only among never smokers (HR=1.27; 95% CI: 1.03, 1.56). Associations with 10 microg/m3 PM2.5 exposures in yearly participant residential annual mean, or in metropolitan area-wide mean, were consistent with baseline exposure model results. Associations with PM2.5 were similar when adjusted for ozone exposures. Analyses of California residents alone also yielded statistically significant PM2.5 mortality HR's for total and CVD mortality. CONCLUSIONS: Long-term exposure to PM2.5 air pollution was associated with an increased risk of total and CVD mortality, providing an independent test of the PM2.5 - mortality relationship in a new large U.S. prospective cohort experiencing lower post-2000 PM2.5 exposure levels.

BACKGROUND: Long-term exposure to ambient particulate matter (PM) air pollution is associated with increased cardiovascular disease (CVD); however, the impact of PM on clinical risk factors for CVD in healthy subjects is unclear. We examined the relationship of PM with levels of circulating lipids and blood pressure in the Third National Health and Nutrition Examination Survey (NHANES III), a large nationally-representative US survey. METHODS: This study was based on 11,623 adult participants of NHANES III (1988-1994; median age 41.0). Serum lipids and blood pressure were measured during the NHANES III examination. Average exposure for 1988-1994 to particulate matter <10microm in aerodynamic diameter (PM10) at the residences of participants was estimated based on measurements from U.S. Environmental Protection Agency monitors. Multivariate linear regression was used to estimate the associations of PM10 with lipids and blood pressure. RESULTS: An interquartile range width (IQRw) increase in PM10 exposure (11.1 microg/m) in the study population was associated with 2.42 percent greater serum triglycerides (95% confidence interval [CI]: 1.09-3.76); multivariate adjusted means of triglycerides according to increasing quartiles of PM10 were 137.6, 142.5, 142.6, and 148.9 mg/dL, respectively. An IQRw increase in PM10 was associated with 1.43 percent greater total cholesterol (95% CI: 1.21-1.66). These relationships with triglycerides and total cholesterol did not differ by age or region. Associations of PM10 with blood pressure were modest. CONCLUSIONS: Findings from this large diverse study indicate that greater long-term PM10 exposure is associated with elevated serum triglycerides and total cholesterol, potentially mediating air pollution-related effects on CVD.

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines, including interleukin (IL)-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], tumor necrosis factor (TNF) receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1alpha and IL-1beta), promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1alpha, IL-1beta, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin, yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indices of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1alpha, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient as compared to wild-type mice, no genotype-related differences in the other indices existed following O3 exposure. O3 caused AHR to acetyl-beta-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were non-existent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.