Kevin R. Cromar

Ambient Particulate Matter Air Pollution Exposure and Mortality in the NIH-AARP Diet and Health Cohort

Background: Outdoor fine particulate matter (≤ 2.5 μm; 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: We aimed to test the relationship between long-term exposure PM2.5 and death risk from all nonaccidental 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 United States for a 2000–2009 follow-up period when matching census tract–level PM2.5 exposure data were available. Participants enrolled ranged from 50 to 71 years of age, residing in six U.S. states and two cities. Cox proportional hazard models yielded hazard ratio (HR) estimates per 10 μg/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-μg/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 HRs 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. Citation: Thurston GD, Ahn J, Cromar KR, Shao Y, Reynolds HR, Jerrett M, Lim CC, Shanley R, Park Y, Hayes RB. 2016. Ambient particulate matter air pollution exposure and mortality in the NIH-AARP Diet and Health cohort. Environ Health Perspect 124:484–490; http://dx.doi.org/10.1289/ehp.1509676

A joint ERS/ATS policy statement: What constitutes an adverse health effect of air pollution? An analytical framework

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. Air pollution has many effects on health; this document provides guidance to judge the adversity of such effects http://ow.ly/T2xx304WTZp

Spatial and seasonal distribution of aerosol chemical components in New York City: (2) road dust and other tracers of traffic-generated air pollution.

We describe spatial and temporal patterns of seven chemical elements commonly observed in fine particulate matter (PM) and thought to be linked to roadway emissions that were measured at residential locations in New York City (NYC). These elements, that is, Si, Al, Ti, Fe, Ba, Br, and black carbon (BC), were found to have significant spatial and temporal variability at our 10 residential PM2.5 sampling locations. We also describe pilot study data of near-roadway samples of both PM10−2.5 and PM2.5 chemical elements of roadway emissions. PM2.5 element concentrations collected on the George Washington Bridge (GWB) connecting NYC and New Jersey were higher that similar elemental concentration measured at residential locations. Coarse-particle elements (within PM10−2.5) on the GWB were 10–100 times higher in concentration than their PM2.5 counterparts. Roadway elements were well correlated with one another in both the PM2.5 and PM10−2.5 fractions, suggesting common sources. The same elements in the PM2.5 collected at residential locations were less correlated, suggesting either different sources or different processing mechanisms for each element. Despite the fact that these elements are only a fraction of total PM2.5 or PM10−2.5 mass, the results have important implications for near-roadway exposures where elements with known causal links to health effects are shown to be at elevated concentrations in both the PM2.5 and PM10−2.5 size ranges.

Formation of transient non-protein calcium pores by lysophospholipids in S49 lymphoma cells

Palmitoyl-lysophosphatidylcholine promotes a transient calcium influx in lymphoma cells. Previously, it was observed that this influx was accompanied by a temporary increase in propidium iodide permeability that appeared linked to calcium entry. Those studies demonstrated that cobalt or nickel could block the response to lysophosphatidylcholine and raised the question of whether the calcium conductance involved specific channels. This communication describes a series of experiments to address that issue. The time dependence and structural specificity of the responses to lysophosphatidylcholine reinforced the hypothesis of a specific channel or transporter. Nevertheless, observations using patch clamp or calcium channel blockers suggested that this “channel” does not involve proteins. Alternative protein-mediated mechanisms such as indirect involvement of the sodium-calcium exchanger and the sodium-potassium ATPase were also excluded. Experiments with extracellular and intracellular calcium chelators suggested a common route of entry for calcium and propidium iodide. More directly, the ability of lysophosphatidylcholine to produce cobalt-sensitive permeability to propidium iodide was reproduced in protein-free artificial membranes. Finally, the transient nature of the calcium time course was rationalized quantitatively by the kinetics of lysophosphatidylcholine metabolism. These results suggest that physiological concentrations of lysophosphatidylcholine can directly produce membrane pores that mimic some of the properties of specific protein channels.

Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine

Inhalation of ozone (O₃), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O₃-induced pulmonary injury, pulmonary inflammation, and AHR. To that end, we examined indices of these aforementioned sequelae in mice genetically deficient in OPN and in wild-type, C57BL/6 mice 24 h following the cessation of an acute (3 h) exposure to filtered room air (air) or O₃ (2 parts/million). In wild-type mice, O₃ exposure increased bronchoalveolar lavage fluid (BALF) OPN, whereas immunohistochemical analysis demonstrated that there were no differences in the number of OPN-positive alveolar macrophages between air- and O₃-exposed wild-type mice. O₃ exposure also increased BALF epithelial cells, protein, and neutrophils in wild-type and OPN-deficient mice compared with genotype-matched, air-exposed controls. However, following O₃ exposure, BALF neutrophils were significantly reduced in OPN-deficient compared with wild-type mice. When airway responsiveness to inhaled acetyl-β-methylcholine chloride (methacholine) was assessed using the forced oscillation technique, O₃ exposure caused hyperresponsiveness to methacholine in the airways and lung parenchyma of wild-type mice, but not OPN-deficient mice. These results demonstrate that OPN is increased in the air spaces following acute exposure to O₃ and functionally contributes to the development of O₃-induced pulmonary inflammation and airway and lung parenchymal hyperresponsiveness to methacholine.

Particulate air pollution and clinical cardiovascular disease risk factors

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 <10 &mgr;m in aerodynamic diameter (PM10) at the residences of participants was estimated based on measurements from US 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 increase in PM10 exposure (11.1 &mgr;g/m3) in the study population was associated with 2.42% greater serum triglycerides (95% confidence interval: 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 interquartile range width increase in PM10 was associated with 1.43% greater total cholesterol (95% confidence interval: 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.

Particulate air pollution and carotid artery stenosis

Outdoor fine particulate air pollution (mass concentration of particles <2.5 μm in diameter [PM2.5]) exposure is ubiquitous and is associated with cardiovascular mortality and ischemic heart disease events (1). PM2.5 exposure also increases the risk for ischemic stroke (2). The vascular and hemodynamic effects of PM2.5 may explain some, but not all, of this increased risk (2). However, it is unknown whether PM2.5 is associated with prevalent clinical atherosclerosis, such as carotid artery stenosis (CAS), a lesion critical to the pathophysiology of ischemic stroke (3). To achieve this objective, we examined PM2.5 and prevalent CAS among more than 300,000 residents of New York, New Jersey, and Connecticut.

Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice.

Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpe(fat) mice). Accordingly, Cpe(fat) and lean, wild-type (C57BL/6) mice were sensitized to OVA and then challenged with either aerosolized PBS or OVA. Compared with genotype-matched, OVA-sensitized and PBS-challenged mice, OVA sensitization and challenge elicited airway obstruction and increased BALF eosinophils, macrophages, neutrophils, IL-4, IL-13, IL-18, and chemerin. However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpe(fat) compared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model.

American Thoracic Society and Marron Institute Report. Estimated Excess Morbidity and Mortality Caused by Air Pollution above American Thoracic Society–Recommended Standards, 2011–2013

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.

Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, 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 indexes 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-1α, 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 compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent 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.