Grantee Research Project Results

2000 Progress Report: Mechanisms Of Particulate-Induced Allergic Asthma

EPA 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: Center for the Study of Childhood Asthma in the Urban Environment
Center Director: Hansel, Nadia
Title: Mechanisms Of Particulate-Induced Allergic Asthma
Investigators: Wills-Karp, Marsha
Institution: The Johns Hopkins University
EPA Project Officer: Callan, Richard
Project Period: January 1, 1998 through January 1, 2002
Project Period Covered by this Report: January 1, 1999 through January 1, 2000
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 , Human Health

Objective:

The objective of this project is to examine the mechanisms by which ambient particulate matter (PM) may exacerbate allergic airways disease, or play a role in the induction of an asthma-like phenotype in a murine model. Our studies show that a single exposure to ambient PM (0.5mg, < 0. 8µm diameter) collected in inner city Baltimore induces sustained airway hyperresponsiveness (AHR), and pulmonary inflammation (i.e. eosinophilia and neutrophilia) Conversely, these responses are not observed when animals are exposed to a reference source of fly ash. Interestingly, this phenotype is observed in all murine strains studied to date, although to varying degrees suggesting that genetic susceptibility to develop allergic airway responses is not required.

Progress Summary:

Additionally, in an ongoing study, our results indicate that repeated exposure to low doses of PM (5 µg) may have a cumulative effect in the development of AHR accompanied by mild, but persistent eosinophilia. Studies are underway to investigate the role of different cell types such as eosinophils and macrophages in PM-induced airway responses. One of our most interesting findings is that PM-induced AHR appears to be dependent on the complement component (C3). Studies are underway to define the exact mechanisms by which complement activation mediates AHR. Taken together these results indicate that exposure to low levels of ambient PM alone is sufficient to induce an allergic phenotype and may provide an explanation for the increased incidence in asthma in inner city environments.

Future Activities:

The objective of this project is to examine the mechanisms by which ambient particulate matter (PM) may exacerbate allergic airways disease, or play a role in the induction of an asthma-like phenotype in a murine model. Our studies show that a single exposure to ambient PM (0.5mg, < 0. 8µm diameter) collected in inner city Baltimore induces sustained airway hyperresponsiveness (AHR), and puhnonary inflammation (i.e. eosinophilia and neutrophilia) Conversely, these responses are not observed when animals are exposed to a reference source of fly ash. Interestingly, this phenotype is observed in all murine strains studied to date, although to varying degrees suggesting that genetic susceptibility to develop allergic airway responses is not required. Additionally, in an ongoing study, our results indicate that repeated exposure to low doses of PM (5 µg) may have a cumulative effect in the development of AHR accompanied by mild, but persistent eosinophilia. Studies will continue to investigate the role of different cell types such as eosinophils and macrophages in PM-induced airway responses. One of our most interesting findings is that PM-induced AHR appears to be dependent on the complement component (C3). Studies are underway to define the exact mechanisms by which complement activation mediates AHR. Taken together these results indicate that exposure to low levels of ambient PM alone is sufficient to induce an allergic phenotype and may provide an explanation for the increased incidence in asthma in inner city environments.

Supplemental Keywords:

Health, RFA, Scientific Discipline, Allergens/Asthma, Atmospheric Sciences, Biochemistry, Children's Health, Disease & Cumulative Effects, Ecological Risk Assessment, Epidemiology, Health Risk Assessment, Risk Assessments, Human Health Risk Assessment, age-related differences, air pollutants, air pollution, air toxics, airborne pollutants, airborne urban contaminants, airway disease, airway inflammation, ambient particulates, asthma, asthma morbidity, asthmatic children, children, children's environmental health, community based, community-based intervention, disease, environmental health, epidemelogy, epidemeology, health effects, human exposure, human health risk, morbidity, 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, particulates, health effects, sensitive populations, cytokines, community-based intervention, respiratory problems, exposure, airway disease, biological response, children, air pollution, Human Health Risk Assessment, interleukin, community based, airborne pollutants, inhalation, childhood respiratory disease, human exposure, particulate exposure, environmental health hazard, PM, allergen, disease, intervention, air quality, toxics

Relevant Websites:

"A Randomized, Controlled Trial of Home Exposure Control in Asthma"
https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract/1081

"Mechanisms Of Particulate-Induced Allergic Asthma"
https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract/1082

"Genetic Mechanisms of Susceptibility to Inhaled Pollutants"
https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract/1083

Progress and Final Reports:

Original Abstract

1998

1999

Final

Main Center Abstract and Reports:

R826724    Center for the Study of Childhood Asthma in the Urban Environment

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