Effects of Airborne Particles on Allergic Airway DiseaseEPA Grant Number: R829216
Title: Effects of Airborne Particles on Allergic Airway Disease
Investigators: Harkema, Jack , Sioutas, Constantinos
Institution: Michigan State University , University of Southern California
EPA Project Officer: Chung, Serena
Project Period: October 31, 2001 through October 30, 2004 (Extended to October 30, 2006)
Project Amount: $854,702
RFA: Health Effects of Particulate Matter (2001) RFA Text | Recipients Lists
Research Category: Health Effects , Particulate Matter , Air
People with pre-existing respiratory disease may be at increased risk from the toxic effects of airborne particulate matter (PM). Childhood asthma is currently a major public health problem, especially among urban and minority populations that are exposed to high levels of air pollutants (e.g., Los Angeles, Detroit). Though recent epidemiologic studies suggest that children with asthma are one of the major susceptible populations to the toxic effects of PM, little is known about the physicochemical character of PM to which asthmatic children are exposed or the underlying toxicologic mechanisms responsible for the PM-induced adverse effects. The overall objective of this project is to conduct atmospheric and toxicologic research designed to understand the adverse effects of airborne particulate matter (PM) of various size fractions (coarse, fine, and ultrafine particles) on pulmonary airways with pre-existing allergic airway disease. We will test the following hypotheses: 1) that PM exposure exacerbates the airway injury associated with allergic airway disease; 2) that the magnitude of PM-induced airway toxicity is dependent on particle size; 3) that PM in transported ("aged") air pollution is more toxic to airways than that in locally generated air pollution; and 4) that PM-induced airway toxicity is most severe during periods of intense photochemical activity.
An integrated investigative team of environmental and biomedical scientists from Michigan State University (MSU) and the Southern California Particle Center and Supersite (SCPCS) will conduct atmospheric and toxicologic research at three sites in the Los Angeles Basin (LAB), each of which have distinct air-pollution profiles. One designated site in the LAB contains locally generated PM and gaseous co-pollutants (source emission site). Another site contains transported PM and gaseous co-pollutants (receptor site). The third site is geographically located between the source and the receptor sites. The team will use a recently built, state-of-the-art mobile air research laboratory (AirCARE 1), parked at the LAB sites, to conduct inhalation toxicology studies exposing laboratory rodents with and without pre-existing allergic airway disease (animal model of human asthma) to concentrated PM (CAPs) from the local environment.
Brown Norway (BN) rats with and without allergic airway disease will be concurrently exposed to either concentrated ambient coarse (2.5 - 10 mm), fine ( 0.15 - 2.5 mm) or ultrafine (0.01 - 0.15 mm) particles taken from the ambient air in three different locations in the LAB over a period of three years. In each location, one series of exposures will be conducted during a period of intense photochemical activity, in early October, and another series will be conducted in January, during which photochemical reactions are less intense.
Post-exposure evaluation of airway morphology, immunology, and cellular/molecular biology will be conducted to assess the possible toxic effects of CAPs on normal and diseased airways of the exposed rodents. Specifically, biomedical investigators will identify the pulmonary pathology caused by the inhalation of coarse, fine, and ultrafine particles by measuring the number and types of airway epithelial and inflammatory cells, and the amount of secretory mucus and inflammatory cytokines at various sites throughout the respiratory tract. In addition, the investigators will use state-of-the art techniques to identify how inhaled particles alter the expression of genes that regulate airway inflammation and mucus hypersecretion.
Our proposed project will provide scientific information that is crucial for understanding the biological mechanisms involved in the airway toxicity of PM and for estimating the human health risk from inhaled PM of various sizes and composition and in locations with different gaseous co-pollutants. This data will be particularly important for understanding the cellular and molecular mechanisms behind pollution-associated exacerbation and perpetuation of chronic airway diseases and for determining emission standards that are necessary to protect the health of a growing susceptible population (i.e., children with asthma).