Ozone is the principal oxidant air pollutant in most American cities. Our program has established that the pathobiologic response of the mammalian respiratory system to inhalation system to inhalation of ambient concentrations of ozone focuses on the epithelium and varies by species, position within the airway tree and duration of exposure. The focus of this renewal will be the cellular, physiologic, and molecular mechanisms by which exposure to oxidant air pollutant sin concern with allergens, contributes to the development of asthma. Our studies will be directed towards the impact of environmental exposures on children, a special population in which the incidence of asthma has been increasing in recent years. The program is organized around the premise that the cellular and acellular components in the walls of tracheobronchial airways form an interactive, trophic unit. The overall hypothesis being tested is that the episodic nature of environmental exposure to oxidant air pollutants: a) promotes the development of asthma and exacerbates the allergen response in asthmatics by altering the homeostasis of the airway epithelial mesenchymal trophic unit in adults; and b) elevates the severity of asthma in the young by fundamentally altering the postnatal development of these trophic interactions. These changes result from continual cycles of acute injury, inflammation and repair superimposed on the immune response to allergen exposure. Project 1 will address the change sin the epithelial and mesenchymal compartments of the trophic unit. Project 2 will address the impact of the immune response and inflammation on the organization of this unit Project 3 will address changes in the nervous components of this unit. All three projects will compare response in the same neonatal and adult rhesus monkeys following episodic exposure to ozone and repeated challenge with a human allergen, house dust mite, during either the injury inflammation phase of ozone exposure or the repair phase.
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