Methacholine Responsiveness Is Not Associated With O₃-Induced Decreases in FEV₁

¹ From the Lung Biology Center, Center for Occupational and Environmental Health, and the Medical Services at San Francisco General Hospital, the Veterans Administration Medical Center, University of California, San Francisco, and the Department of Medicine, the University of North Carolina at Chapel Hill

Study objective: Controlled human exposure studies have suggested that the National Ambient Air Quality Standard for ozone (O₃) may not provide a margin of safety to protect the most susceptible members of the population from adverse health effects. Although the subgroups of the population that are most susceptible to O₃ have not been identified, recent work in our laboratory suggested that methacholine responsiveness might be an important determinant of susceptibility to O₃.

Patients and methods: To test the hypothesis that methacholine responsiveness is correlated with FEV₁ response after O₃ exposure, we conducted methacholine challenge tests and O₃ (0.20 ppm) and filtered air exposures for 4 h with moderate exercise on 66 healthy individuals.

Results: Repeated measures analysis of variance demonstrated significant changes in FEV₁ (0.82±0.63 L), FVC (0.69±0.48 L), and specific airway resistance (SRaw) (+1.5±1.1 L x cm H₂O/L/s) across the O₃ exposure that persisted after adjusting for responses to air. Baseline PC100 (the concentration of methacholine that caused a doubling of the baseline SRaw) was weakly associated with O₃-induced increases in SRaw (F_1.54=2.85, p=0.09), but not O₃-induced declines in FEV₁ or FVC. There was a weak association (r=0.29) between O₃-induced responses for SRaw and FEV₁. The FEV₁ responses for O₃ were weakly associated with the symptoms of cough (r=0.37), wheeze (r=0.29), chest pain on deep inspiration (r=0.31), and shortness of breath (r=0.37), but not with chest discomfort or sputum production.

Conclusions: Although we were unable to find support for our hypothesis, we found, somewhat surprisingly, that respiratory symptoms were weakly associated or unassociated with FEV₁ responses after O₃ exposure. This finding implies that individuals may experience adverse effects, ie, respiratory symptoms, without large declines in lung function. Conversely, individuals may suffer large declines in lung function without prominent symptoms and, therefore, may remain in an unhealthy environment despite evidence of toxicity.

Key Words: FEV₁ • methacholine responsiveness • ozone • respiratory symptoms

Submitted on June 2, 1994
Accepted on August 30, 2007

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