Particulate Air Pollution and Initiation of Asthma

EPA Grant Number: R826779
Title: Particulate Air Pollution and Initiation of Asthma
Investigators: Kobzik, Lester , Gonzalez-Flecha, Beatriz , Koutrakis, Petros , Shore, Stephanie
Institution: Harvard University
EPA Project Officer: Hunt, Sherri
Project Period: October 1, 1998 through September 30, 2001
Project Amount: $557,340
RFA: Health Effects of Particulate Matter and Associated Air Pollutants (1998) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Health Effects , Air , Particulate Matter

Description:

Environmental pollution has often been cited as a potential co-factor in the increasing incidence of asthma in children, but experimental or mechanistic evidence to support this conjecture has been lacking. Epidemiologic data have revealed important health effects of particulate air pollution, including increased morbidity in asthmatics. We propose to study the effects of particulate air pollution on the initiation of the asthmatic phenotype using a novel mouse model. We rely on the following published or preliminary observations to address this problem: 1) the normal response to inhaled allergens is tolerance; 2) exposure of young mice to particulate pollution components can abrogate this tolerance and promote development of an asthma-like phenotype; 3) particulates cause oxidant stress and pro-inflammatory cytokine production in vitro and in vivo. Our central postulate is that air particulate-mediated oxidant stress/injury within developing lungs promotes initiation of hypersensitivity (asthmatic-type) responses to otherwise innocuous inhaled antigens.

Approach:

In specific aim #1, we will characterize development of hypersensitivity to aerosolized antigen in young mice exposed to concentrated air particulates (PM2.5) in the Harvard concentrator. We will measure physiologic (airway hyperresponsiveness), pathologic (airway inflammation), and immunologic (total and allergen specific IgE, IgG levels) features of the asthmatic phenotype. In specific aim #2, the hypothesis to be tested is that oxidant-components of air pollution are critical for initiation of hypersensitivity to inhaled antigens. We will measure oxidant stress in situ in the lungs of young mice exposed to particulates, and measure the effect of removal of redox-active metals by chelation on the potency of air pollutant aerosols to promote asthmatic responses to inhaled antigen. We will also test this hypothesis by use of pharmacologic interventions with in vivo administration of anti-oxidants (e.g., dimethylthiourea, DMTU) to abrogate air pollution effects.

Expected Results:

This research will determine if and at what levels of exposure particulate pollution may contribute to development of asthma in children and will improve our understanding of mechanisms of air particulate health effects in the lungs.

Publications and Presentations:

Publications have been submitted on this project: View all 4 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 4 journal articles for this project

Supplemental Keywords:

human health; infants; sensitive populations., RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Allergens/Asthma, Children's Health, genetic susceptability, asthma, particulates, ambient air quality, sensitive populations, co-factors, cytokine production, copollutants, air toxics, morbidity, PM 2.5, infants, adolescence, airway disease, respiratory problems, exposure, allergic airway, Human Health Risk Assessment, asthmatic phenotype, air pollution, children, laboratory animals, susceptible subpopulations, assessment of exposure, childhood respiratory disease, children's vulnerablity, inhalation, susceptibility, human exposure, chronic health effects, airborne pollutants, environmental toxicant, Acute health effects, inhaled, sensitive subgroups, environmentally caused disease, human susceptibility, acute exposure, respiratory, oxidant stress, metals, hypersensitive people, toxics

Progress and Final Reports:

Final Report