Grantee Research Project Results
Particulate Air Pollution and Initiation of Asthma
EPA Grant Number: R826779Title: Particulate Air Pollution and Initiation of Asthma
Investigators: Kobzik, Lester , Gonzalez-Flecha, Beatriz , Shore, Stephanie , Koutrakis, Petros
Institution: Harvard University
EPA Project Officer: Chung, Serena
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: Particulate Matter , Air Quality and Air Toxics , Human Health , Air
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 projectJournal Articles:
Journal Articles have been submitted on this project: View all 4 journal articles for this projectSupplemental Keywords:
human health; infants; sensitive populations., RFA, Health, Air, Scientific Discipline, Susceptibility/Sensitive Population/Genetic Susceptibility, Health Risk Assessment, Risk Assessments, particulate matter, genetic susceptability, Environmental Chemistry, Allergens/Asthma, Children's Health, Toxicology, inhaled, sensitive populations, asthmatic phenotype, infants, childhood respiratory disease, Human Health Risk Assessment, asthma, copollutants, respiratory, sensitive subgroups, co-factors, human exposure, laboratory animals, morbidity, allergic airway, susceptibility, Acute health effects, children, exposure, particulates, acute exposure, chronic health effects, susceptible subpopulations, airborne pollutants, oxidant stress, cytokine production, children's vulnerablity, environmentally caused disease, toxics, ambient air quality, air pollution, metals, assessment of exposure, environmental toxicant, adolescence, human susceptibility, hypersensitive people, human health risk, air toxics, PM 2.5, inhalation, airway diseaseProgress and Final Reports:
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.