The health of approximately half of the U.S. population continues to be negatively impacted by airpollutants such as ozone (O3), the major oxidant pollutant in photochemical smog. Recent epidemiologicstudies suggest that exposure to ambient O3 induces long-term impairments to the pulmonary function ofchildren. The toxicological mechanisms of O3-related airway injury and how age and exposure historygovern the child's susceptibility to O3-induced airway injury remain poorly understood. Exposure to O3 isalso known to cause injury not only to the lungs, but also to the nose. The overall goal of Project 3 is todetermine the nature and distribution of airway injury, adaptation and repair in the nasal passages of infantmonkeys and rats episodically exposed to O3. Intranasal distribution and severity of the O3-induced lesionswill be determined by image analysis and morphometric techniques. The O3-induced nasal alterations willbe compared to biochemical changes in intracellular and extracellular antioxidants present in the nasalmucosa and extracellular airway lining fluid, respectively. The identified, site-specific alterations in mucosalmorphology and in regional tissue/fluid biochemistry caused by episodic O3 exposures will also becompared to computer-assisted estimates of intranasal, regional dosimetry of O3. The site-specificcomparisons throughout the nasal passages will be used to determine how tissue susceptibility and airflowdrivendosimetry contribute to the pathogenesis of nasal injury and remodeling caused by acute andchronic O3 exposures. The results of these studies will provide a better understanding of how episodic O3exposure affects the growth and development of the nasal airways at the macroscopic, microscopic andmolecular levels. Our underlying premise is that the developing nasal mucosa in infant animals is moresusceptible to the toxic effects of O3 than is the fully developed nasal mucosa of adults. We hypothesizethat this disparity in mucosal responses is due to differences between infants and adults in the regulation ofceNular and extracellular antioxidants in the nasal airways. Project 3 is also designed to test the hypothesisthat O3-induced morphologic, biochemical, and molecular responses in the nose are sentinels for O3-induced alterations in the lung. Furthermore, this project is designed to test the hypothesis that theepisodic nature of the environmental exposure to O3 permanently alters the developing nasal airwaymaking it more vulnerable, later in life, to adverse alterations from subsequent exposures to inhaledtoxicants (e.g., ozone and bacterial endotoxin). Our project will rely heavily on projects 1, 2 and 4 toaccomplish the proposed investigations. Our research will provide important information that is crucial forunderstanding the potential, long-term health effects of air pollution on the developing airways of children.
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