Oxidative Stress Responses to PM Exposure in Elderly Individuals With Coronary Heart Disease

EPA Grant Number: R832413C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R832413
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Southern California Particle Center
Center Director: Froines, John R.
Title: Oxidative Stress Responses to PM Exposure in Elderly Individuals With Coronary Heart Disease
Investigators: Delfino, Ralph , Gastanaga, Victor , Neuhausen, Susan , Staimer, Norbert , Vaziri, Nosratola D
Current Investigators: Delfino, Ralph , Gastanaga, Victor , Gillen, Dan , Neuhausen, Susan , Staimer, Norbert , Vaziri, Nosratola D
Institution: University of California - Irvine
EPA Project Officer: Hunt, Sherri
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2012)
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

The overall goal of this study is to advance knowledge on the importance of particle size and composition to the induction of oxidative stress responses in a high-risk population of elderly people with coronary heart disease (CHD). We hypothesize that biomarkers of oxidative stress responses will be associated with indoor and outdoor home PM mass and total particle number concentration, which will support the view that PM leads to systemic inflammatory responses. We further hypothesize that biomarkers will be more strongly associated with predicted indoor exposure to PM of outdoor origin (from source tracer analyses). We will also evaluate effects of exposure to specific metals, elemental and organic carbon, and specific organic components used as source tracers. We further hypothesize that biomarker associations with ultrafine and fine PM will be better explained by chemical assays that measure reactive oxygen species (ROS) and electrophilic activity.

Approach:

We will conduct a study of repeated measures to evaluate the relationship between circulating biomarkers of oxidative stress responses and exposure to PM in elderly subjects with CHD. Biomarkers will include: oxidized glutathione (GSSG), reduced glutathione (GSH), an F2-isoprostane biomarker of lipid peroxidation (8-iso-PGF2α), extracellular superoxide dismutase (SOD) activity, and erythrocyte SOD and glutathione peroxidase 1 activities. The balance of capacity and stress will be represented by the ratio GSH/GSSG, which is expected to decrease with higher PM exposures, while 8-iso-PGF2α , and SOD and GPx-1 activities will increase. Changes in these biomarkers are expected to be associated with cardiovascular outcomes and inflammatory biomarkers measured in the parent study funded by NIEHS. Subjects will include 72 nonsmokers age 65 and older living in retirement homes in areas of the Los Angeles air basin with high concentrations of both freshly emitted and aged PM. Each subject will be followed with blood draws for biomarkers at the end of each of 12 weeks (864 person-days of observation). This intensive follow-up will be spread across 240 monitored days over two years, and include in each year a period of high photochemical activity and a period of high air stagnation to enhance contrasts in PM composition, number and size distribution. Intensive exposure assessments will be made at indoor and outdoor home sites, including methods described under Projects 1 and 3. Data will be analyzed with the general linear mixed model controlling for temporal trends, study site, weather variables, as-needed or inconsistent medication use, respiratory infections and key clinical and subject characteristics. We will also evaluate whether individual characteristics that may increase susceptibility predict associations between oxidative stress biomarkers and PM exposure.

Expected Results:

We expect to clarify findings in the epidemiologic literature of associations between ambient PM and cardiovascular mortality and hospital admissions. Results of this study will advance knowledge on the acute effects of ultrafine and fine particles on biomarkers of oxidative stress responses that are relevant to acute and chronic cardiovascular outcomes. Results are expected to inform policy makers on the sources, particle components, size fractions and concentrations that affect key intermediate endpoints in the progression of atherosclerosis and in acute changes in cardiovascular function and thrombosis. We will advance understanding of the adverse effects of particulate air pollutants on the cardiovascular health of high-risk individuals living in ethnically diverse neighborhoods with high exposures to airborne pollutants.

Publications and Presentations:

Publications have been submitted on this subproject: View all 35 publications for this subprojectView all 236 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 15 journal articles for this subprojectView all 152 journal articles for this center

Supplemental Keywords:

Health effects, human health, sensitive populations, dose-response, enzymes, genetic polymorphisms. particulates, epidemiology, environmental chemistry, modeling,, RFA, Health, Scientific Discipline, Air, particulate matter, Health Risk Assessment, Risk Assessments, Biochemistry, Ecology and Ecosystems, elderly adults, particulates, atmospheric particulate matter, human health effects, PM 2.5, airway disease, cardiovascular vulnerability, airborne particulate matter, air pollution, human exposure, vascular dysfunction, cardiovascular disease, human health risk

Progress and Final Reports:

2006 Progress Report
2007 Progress Report
2008 Progress Report
2009 Progress Report
2010 Progress Report
Final Report


Main Center Abstract and Reports:

R832413    Southern California Particle Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832413C001 Contribution of Primary and Secondary PM Sources to Exposure & Evaluation of Their Relative Toxicity
R832413C002 Project 2: The Role of Oxidative Stress in PM-induced Adverse Health Effects
R832413C003 The Chemical Properties of PM and their Toxicological Implications
R832413C004 Oxidative Stress Responses to PM Exposure in Elderly Individuals With Coronary Heart Disease
R832413C005 Ultrafine Particles on and Near Freeways