Short-term exposures to US EPA-regulated atmospheric particulate matter (PM) air pollution with diameters <2.5 um (PM2.5) and <10 um (PM10), have been associated with acute increases in cardiovascular hospitalization and mortality. However, the causative chemical components and underlying pathophysiological mechanisms remain to be clarified. Toxicological data suggest pro-oxidant PM chemical species from fossil fuel combustion are causative factors in oxidative stress, inflammation, thrombosis, and vascular dysfunction, which have the potential to precipitate adverse events such as myocardial infarction. Our overall objective is to chemically characterize particle exposures and relate these exposures to interrelated health outcomes in a cohort of potentially susceptible elderly subjects. We will evaluate within-subject exposure-response relations using 12 weekly repeated measures in each of 120 subjects living in the Los Angeles Basin. Outcomes to be measured include systemic biomarkers of oxidative stress and inflammation in the blood, airway inflammation, endothelial dysfunction, blood pressure, and whole blood gene expression (>31,000 genes), focusing on genes in biological pathways relevant to cardiovascular disease. Our overarching hypothesis is that subject health outcomes will be associated with exposure to ultrafine PM (PM<0.1 um), to organic aerosols from fossil fuel combustion, and to the overall oxidative potential of PM exposures. We further hypothesize that these PM characteristics will be linked to vehicular traffic sources, and that we will find weaker associations with PM2.5 and PM10 mass. This hypothesis is based on observations that chemicals with oxidative potential and high toxicity make up a small and highly variable fraction of PM2.5, but comprise a much greater proportion of unregulated ultrafine PM mass in areas near traffic sources. We will test our hypotheses with the following three aims: 1. Assess relations between air pollution exposures and genome-wide gene expression in peripheral blood. 2. Evaluate relations of air pollution exposures to systemic and airway biomarkers of oxidative stress and inflammation. We anticipate that different pollutant components will affect airway vs. systemic inflammation. 3. Examine relations of air pollution exposures to peripheral endothelial function and blood pressure. This will be among the first human transcriptomic studies to evaluate relations between repeated gene expression responses and chemically-characterized ambient air pollution. Our proposed assessment of the estimated effects of PM oxidative potential and toxic chemical components on combined genetic, biomarker, and physiologic outcomes offers a novel approach to air pollution research in populations. The investigation of pathophysiological responses to particle exposures (characterized by size, toxicity and source) challenges and advances existing approaches. Results will inform regulatory decisions aimed at protecting sensitive populations because putative causative constituents of PM are not well-represented by PM2.5 or PM10.

Public Health Relevance

This study would be among the first using repeated measurements to analyze the relation between chemically characterized air pollutants and genome-wide gene expression patterns in peripheral blood cells from a high- risk population of elderly individuals. Gene expression results will be compared with analyses of the relation of air pollutants to vascular function and to biochemical markers of oxidative stress and inflammation in the blood and lungs. This study will contribute to the knowledge and methods needed to establish exposure limits to protect the public's health because the study aims address unresolved questions about which chemical components and sources of air pollution that have the greatest potential for toxicity in the lungs and systemically.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES012243-08
Application #
8415850
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Dilworth, Caroline H
Project Start
2003-04-01
Project End
2016-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
8
Fiscal Year
2013
Total Cost
$593,693
Indirect Cost
$139,828
Name
University of California Irvine
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Hasheminassab, Sina; Pakbin, Payam; Delfino, Ralph J et al. (2014) Diurnal and seasonal trends in the apparent density of ambient fine and coarse particles in Los Angeles. Environ Pollut 187:1-9
Hasheminassab, Sina; Daher, Nancy; Shafer, Martin M et al. (2014) Chemical characterization and source apportionment of indoor and outdoor fine particulate matter (PM(2.5)) in retirement communities of the Los Angeles Basin. Sci Total Environ 490:528-37
Bartell, Scott M; Longhurst, John; Tjoa, Thomas et al. (2013) Particulate air pollution, ambulatory heart rate variability, and cardiac arrhythmia in retirement community residents with coronary artery disease. Environ Health Perspect 121:1135-41
Khan, Alya; Staimer, Norbert; Tjoa, Thomas et al. (2013) Relations between isoprene and nitric oxide in exhaled breath and the potential influence of outdoor ozone: a pilot study. J Breath Res 7:036007
Staimer, Norbert; Nguyen, Tran B; Nizkorodov, Sergey A et al. (2012) Glutathione peroxidase inhibitory assay for electrophilic pollutants in diesel exhaust and tobacco smoke. Anal Bioanal Chem 403:431-41
Delfino, Ralph J; Gillen, Daniel L; Tjoa, Thomas et al. (2011) Electrocardiographic ST-segment depression and exposure to traffic-related aerosols in elderly subjects with coronary artery disease. Environ Health Perspect 119:196-202
Arhami, M; Minguillon, M C; Polidori, A et al. (2010) Organic compound characterization and source apportionment of indoor and outdoor quasi-ultrafine particulate matter in retirement homes of the Los Angeles Basin. Indoor Air 20:17-30
Delfino, Ralph J; Tjoa, Thomas; Gillen, Daniel L et al. (2010) Traffic-related air pollution and blood pressure in elderly subjects with coronary artery disease. Epidemiology 21:396-404
Delfino, Ralph J; Staimer, Norbert; Tjoa, Thomas et al. (2010) Associations of primary and secondary organic aerosols with airway and systemic inflammation in an elderly panel cohort. Epidemiology 21:892-902
Delfino, Ralph J; Staimer, Norbert; Tjoa, Thomas et al. (2010) Association of biomarkers of systemic inflammation with organic components and source tracers in quasi-ultrafine particles. Environ Health Perspect 118:756-62

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