A Model to Study the Development of Persistent Environmental Airway DiseaseEPA Grant Number: R826711C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R826711
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: University of Iowa Children's Environmental Airway Disease Center
Center Director: Hunninghake, Gary W.
Title: A Model to Study the Development of Persistent Environmental Airway Disease
Investigators: Schwartz, David A.
Current Investigators: Schwartz, David A. , Hunninghake, Gary W.
Institution: University of Iowa
EPA Project Officer: Louie, Nica
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 address a fundamental issue in childhood asthma: why only a minority of children who wheeze at an early age develop persistent airway disease that continues throughout their life. Inhalation of grain dust is a common problem in the rural setting that acutely induces airway inflammation and airflow obstruction, and chronically has been shown to cause asthma. Although the acute physiologic changes associated with inhalation of grain dust in the workplace are reversible, these acute changes in airway reactivity are predictive of longitudinal decrements in airflow, suggesting that recurrent episodes of airway inflammation result in structural changes in the airway that lead to the development and progression of chronic airway disease. In our human and murine models of grain dust induced airway disease, we have found: 1) that endotoxin is one of the principal agents in grain dust causing reversible airway inflammation and airflow obstruction; 2) that the acute physiologic response to inhaled grain dust is associated with neutrophils and proinflammatory cytokines; 3) that the acute physiologic and inflammatory response to inhaled grain dust is self-limited; 4) that agents directed at either LPS or proinflammatory cytokines are effective in decreasing the acute inflammatory response to inhaled grain dust; and 5) that chronic inhalation of grain dust results in persistent airway hyperreactivity and airway remodeling. However, little is known about the relationship between the acute and reversible airway inflammatory response and the development of chronic grain dust induced airway disease. The overall hypothesis of this investigation is that many of the biologic features of acute and reversible airway inflammation are fundamental to the development of chronic grain dust induced airway disease. The goal of this project is to determine which specific elements of the acute inflammatory response to inhaled grain dust are essential to the development of chronic grain dust induced airway disease - defined as persistent airway hyperreactivity and airway remodeling.
Publications and Presentations:Publications have been submitted on this subproject: View all 19 publications for this subproject | View all 33 publications for this center
Journal Articles:Journal Articles have been submitted on this subproject: View all 19 journal articles for this subproject | View all 32 journal articles for this center
Supplemental Keywords:children, health, asthma., RFA, Health, Scientific Discipline, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Allergens/Asthma, Children's Health, genetic susceptability, Biology, asthma, model, rural communities, sensitive populations, endotoxin, airway disease, exposure, air pollution, children, airway inflammation, airborne pollutants, human exposure, inhalation, children's vulnerablity, assessment of exposure, childhood respiratory disease, biological markers, grain dust, agricultural community, allergen, disease, toxics
Progress and Final Reports:
Main Center Abstract and Reports:R826711 University of Iowa Children's Environmental Airway Disease Center
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R826711C001 Mechanisms that Initiate, Promote, and Resolve Grain Dust/LPS Induced Inflammation
R826711C002 Multi-component Intervention Study of Asthma in Children from Rural Communities
R826711C003 Role of RSV Infection and Endotoxin in Airway Inflammation
R826711C004 A Model to Study the Development of Persistent Environmental Airway Disease