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