Acute Cardiopulmonary Responses to Fine Particulate Pollution and Copollutant Oxidant Gases in Los AngelesEPA Grant Number: R827999
Title: Acute Cardiopulmonary Responses to Fine Particulate Pollution and Copollutant Oxidant Gases in Los Angeles
Investigators: Gong, Henry , Sioutas, Constantinos
Institution: University of Southern California , Rancho Los Amigos Medical Center
EPA Project Officer: Chung, Serena
Project Period: March 15, 2000 through March 14, 2003 (Extended to January 14, 2004)
Project Amount: $613,894
RFA: Airborne Particulate Matter Health Effects (1999) RFA Text | Recipients Lists
Research Category: Air , Health Effects , Particulate Matter
The goal of this project is to document acute effects of inhaled fine particulate matter (PM2.5) on cardiopulmonary symptoms, lung function (spirometry), airways inflammation (induced sputum cells and interleukin-6), hemostasis (D-dimer), and cardiac electrophysiology (ambulatory digital Holter electrocardiograms, including heart rate variability) in human volunteers exposed to "worst-case" Southern California air pollution. More specifically, we intend to differentiate effects of fine particulate matter (PM2.5 at approximately 200 ug/m3) and a ubiquitous oxidant gas (NO2 at 0.4 ppm), and determine whether they act additively or synergistically when combined. An overall goal of the human toxicologic research program is to design realistic xposures to concentrated particulate matter (PM) and to measure appropriate outcomes so that we can relate their findings to health outcomes in epidemiology and better understand the cause-and-effects of PM exposure and the identification of causative PM agents. Reductions in knowledge gaps and uncertainties are necessary to adequately conduct PM health risk assessments. One major need is more information about the health effects of combined PM and gaseous copollutants since PM normally exists in ambient air as a variable mixture which includes the criterion and hazardous air pollutants. We hypothesize that combined exposure to PM and nitrogen dioxide (NO2) elicits acute cardiopulmonary effects which are significantly worse than observed with the individual pollutants.
Approximately 24 medically-screened men and women , age 50-75 years, with and without stable chronic obstructive pulmonary disease (COPD) will be exposed in a quasi-double-blind, randomized order to NO2, PM2.5, both pollutants together, and filtered air as a control, for 2-hour periods with intermittent exercise. An ambient fine particle concentrator will be used to concentrate particulates from outside Los Angeles air and then expose each volunteer inside a specially constructed whole-body chamber. Chamber air will be monitored for pollutant gases and particulates, which will be analyzed for mass, size, and chemical composition. Statistical analysis (analysis of covariance with repeated measures) will test the hypothesis about the effects of PM2.5 and NO2 and their interactive effects on the outcome variables.
Expected Results:The hypothesis will be tested by separating the effects of PM from the effects of other pollutants and the effects of PM exposure in the presence of an oxidant copollutant (NO2). If significant pulmonary inflammatory effects and/or electrocardiographic changes are found in PM2.5 or PM2.5 + NO2 exposures, this will provide powerful support for previous epidemiologic findings of morbidity and mortality generally associated with combustion-related pollutants, relevant to essentially all urban dwellers. In addition, more mechanistic studies can be considered and added on, such as systemic markers of inflammation or abnormal coagulation, e.g., plasma fibrinogen, intercellular adhesion molecule-1, or interleukin-6. If a broad range of individual responses to PM2.5 is found, the detailed information on PM2.5 components and potentially relevant covariates will suggest what factors contribute most to unfavorable response, and these can be investigated in future studies. If relatively little response is found, the study can be extended to other "high-risk" populations such as individuals with cardiovascular disease and/or to different pollutants, e.g., combined PM2.5 and ozone. This research project combines expertise in human health effects research (RLA) and aerosol engineering and exposure assessment (USC) to develop and improve methods for studying the health effects of ambient PM2.5 and allowing a focus on atmospheres that are significantly different from those under study elsewhere in the United States. The effective synthesis of established investigators, a fine particle concentrator located in Southern California, and evaluation of susceptible subjects may lead to a better understanding of the causative role of ambient particulates in the aggravation of cardiopulmonary diseases.
Improvement in Risk Assessment or Management: The results of the health outcomes and identification of mechanisms with combined air