A large part of the U.S. population is exposed to ambient ozone (03) levels that are associated with acute respiratory health effects; however, little is known about the effects on human respiratory health of long-term exposure to such ambient concentrations. An ongoing study, R0 1 HL60689 (Effects of Chronic Ozone Exposure on Lung Function) is investigating the effects of long-term exposure to ambient 03 on measures of lung small airway function (forced expiratory flow at 75 percent of expired volume-FEF75). Exposure chamber studies with ozone indicate that some individuals do not respond at all and that among those who do respond, the response patterns tend to be reproducible over time. This diversity of response among individuals and the relative stability of responses within individuals indicate the need to investigate genetic factors as determinants of health consequences of exposure to ambient O3 and other air pollutants. Since human health effects associated with exposure to ambient and experimental concentrations of O3 are related to the fact that O3 is a potent oxidizing agent, it is important to investigate genetic factors as determinants of health consequences of exposure to ambient O3 and other air pollutants. This competing supplement to R0160689 will test the overall hypothesis that polymorphisms among major genes that lead to decreased host antioxidant defense are related to ongoing inflammation and remodeling of the small airways of the human lung as reflected by lower levels of FEF75. The genes to be studied in the cohort of 300 subjects are: Superoxide Dismutase 2,Glutathione-S-Transferases, Glutathione Peroxidase, Catalase, NADPH:Oxidoreductase. The relation between the occurrence and magnitude of inflammation in BAL and bronchial biopsies in subjects with different genetic polymorphisms related to anti-oxidant defenses also will be studied among 40 members of the cohort who are selected to undergo chamber exposure to 03, based on estimated lifetime exposure to ambient 03 and level of FEF75. Markers of cytogenetic (micronuclei) and DNA damage (COMET) assay also will be investigated. Multiple linear regression analyses will be used to evaluate the influence of genetic polymorphism on lung function and markers of airway inflammation in response to controlled exposure to ozone in relation to estimated lifetime exposure to ozone.
