1 San Francisco Veterans Affairs Medical Center, San Francisco, California2 Department of Medicine, University of California at San Francisco, San Francisco, California3 Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California4 Department of Medicine5 Department of Environmental Medicine, and8 Department of Public Health Sciences, University of Rochester Medical Center, Rochester, New York6 Department of Medicine and10 Department of Pediatrics, School of Medicine, and7 Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, North Carolina9 New England Research Institute, Watertown, Massachusetts; and11 Health Effects Institute, Boston, Massachusetts
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Rationale:Acute respiratory effects of low-level ozone exposure are not well defined in older adults.Objectives:MOSES (The Multicenter Ozone Study in Older Subjects), although primarily focused on acute cardiovascular effects, provided an opportunity to assess respiratory responses to low concentrations of ozone in older healthy adults.Methods:We performed a randomized crossover, controlled exposure study of 87 healthy adults (59.9 ± 4.5 yr old; 60% female) to 0, 70, and 120 ppb ozone for 3 hours with intermittent exercise. Outcome measures included spirometry, sputum markers of airway inflammation, and plasma club cell protein-16 (CC16), a marker of airway epithelial injury. The effects of ozone exposure on these outcomes were evaluated with mixed-effect linear models. A P value less than 0.01 was chosen a priori to define statistical significance.Measurements and Main Results:The mean (95% confidence interval) FEV1 and FVC increased from preexposure values by 2.7% (2.0-3.4) and 2.1% (1.3-2.9), respectively, 15 minutes after exposure to filtered air (0 ppb). Exposure to ozone reduced these increases in a concentration-dependent manner. After 120-ppb exposure, FEV1 and FVC decreased by 1.7% (1.1-2.3) and 0.8% (0.3-1.3), respectively. A similar concentration-dependent pattern was still discernible 22 hours after exposure. At 4 hours after exposure, plasma CC16 increased from preexposure levels in an ozone concentration-dependent manner. Sputum neutrophils obtained 22 hours after exposure showed a marginally significant increase in a concentration-dependent manner (P = 0.012), but proinflammatory cytokines (IL-6, IL-8, and tumor necrosis factor-α) were not significantly affected.Conclusions:Exposure to ozone at near ambient levels induced lung function effects, airway injury, and airway inflammation in older healthy adults.Clinical trial registered with www.clinicaltrials.gov (NCT01487005).