Mechanisms Of Particulate-Induced Allergic AsthmaEPA Grant Number: R826724C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R826724
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - Johns Hopkins University Hospital
Center Director: Eggleston, Peyton A.
Title: Mechanisms Of Particulate-Induced Allergic Asthma
Investigators: Wills-Karp, Marsha , Eggleston, Peyton A.
Current Investigators: Wills-Karp, Marsha
Institution: The Johns Hopkins University
EPA Project Officer: Callan, Richard
Project Period: January 1, 1998 through January 1, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998) RFA Text | Recipients Lists
Research Category: Children's Health , Health Effects , Health
Objective:This project will examine the mechanisms by which particulate matter (PM) may exacerbate an allergen-driven inflammatory response in the airways. In as much as 70-80% of children with asthma have evidence of IgE mediated hypersensitivity, and epidemiologic evidence indicates that environmental particulate matter (PM) increases morbidity in asthma this work will provide insight into the interaction of particulate pollutants with IgE mediated inflammation in asthma. PM exposure has been shown to consistently increase the production of the pro-inflammatory cytokine, interleukin 6 (EL-6), known to be critical in the development of allergen-driven pathogenic Th-2 immune responses. To test the hypothesis that PM exposure exacerbates allergic asthma by inducing airway epithelial cell release of IL-6, we have created a model utilizing susceptible A/J mice that develop antigen-dependent airway hyperresponsiveness, eosinophilic inflammation and elevated IgE levels, concomitant with increases in lung levels of Th-2 cytokines while resistant C3H/HeJ mice fail to develop these responses. First we will establish the exposure response relationship between PM and allergic airway responses in genetically susceptible AIJ mice. Secondly we will determine the biological effects of PM exposure in nonallergic strains of mice. Third, we will determine the role of IL-6 in mediating PM induced inflammation and exacerbations or allergic asthmatic symptoms by neutralizing its activity in vivo and examining PM induced effects on allergic air way responses. We anticipate that Dr. Wills-Karp's studies will provide important pathopysiologic correlates of epidemiologic associations made in the community-based studies. In addition her studies will allow us to examine dose-response of the interaction of PM and allergens and to determine if there is a threshold dose for interaction, both important considerations for future community-based interventions.
Supplemental Keywords:children, health, asthma, exposure, allergic, PM, particulate matter., RFA, Health, Scientific Discipline, Air, Water, Toxicology, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Allergens/Asthma, Children's Health, genetic susceptability, Biology, Mercury, asthma, health effects, particulates, sensitive populations, community-based intervention, cytokines, airway disease, exposure, respiratory problems, biological response, air pollution, children, Human Health Risk Assessment, community based, interleukin, airborne pollutants, human exposure, inhalation, particulate exposure, childhood respiratory disease, PM, environmental health hazard, air quality, allergen, disease, human health risk, toxics
Progress and Final Reports:2000 Progress Report
2002 Progress Report
Main Center Abstract and Reports:R826724 CECEHDPR - Johns Hopkins University Hospital
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R826724C001 A Randomized, Controlled Trial of Home Exposure Control in Asthma
R826724C002 Mechanisms Of Particulate-Induced Allergic Asthma
R826724C003 Genetic Mechanisms of Susceptibility to Inhaled Pollutants
R826724C004 The Relationship Of Airborne Pollutants And Allergens To Asthma Morbidity