A large part of the U.S. population is exposed to ambient ozone (O3) concentrations 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. Chronic exposure of non-human primates to high concentrations of O3 are associated with pathologic changes in the centriacinar region of the lung that are similar to changes observed in young cigarette smokers. Based on pilot studies completed by the investigators, the current study tests the hypothesis that, humans, there is an exposure-response relationship between the amount of chronic exposure to ambient O3 and measures of lung function that reflect changes in the centriacinar region of the human lung (FEF25-75); and this relationship is not seen with measures of more proximal airway function (FEV1). First-year UC Berkeley students, ages 18-21 yrs, who are lifelong residents of the Los Angles Basin (n=200, high O3) and the San Francisco Bay Area (n=100, low O3) will be studied. Lifetime exposure to ambient O3 will be estimated with methods developed by the investigators that combine questionnaire and ambient O3 data. Lung function will be assessed with maximum expiratory flow-volume curves. Students will be studied after 4-6 months of low ambient O3 exposure and immediately after 2-3 months of exposure to summertime O3. Forty students (20 from each area) who are at the upper and lower tails of the FEF25-75 distribution will undergo 2 controlled O3 exposures (seasonal as above) followed by BAL/biopsy to evaluate relationships between measures of inflammation, injury/repair and oxidant induce damage/repair and FEF25-75. Regression will be used to evaluate relationships between lifetime O3 exposure and lung function, adjusted for past and family respiratory history, allergy history, home characteristics, exposure to environmental tobacco smoke and particle air pollution and NO2. This is the first detailed epidemiologic study of the effects of chronic exposure to an air pollutant based on individual estimates of lifetime exposure and controlled exposure data. The study tests a specific toxicologic model in humans that has relevance for chronic respiratory disease and explores mechanisms of effects.
