Attenuated response to repeated daily ozone exposures in asthmatic subjects

The development of attenuated response ("tolerance") to daily ozone (O3) exposures in the laboratory is well established in healthy adult volunteers. However, the capability of asthmatics to develop tolerance during multiday ozone exposures is unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm O3 in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air exposures during the preceding week served as controls. Follow-up O3 exposures were performed 4 and 7 d after the most recent consecutive exposure. All exposures were performed in an environmental chamber at 31 degrees C and 35% relative humidity. The subjects performed moderate exercise (mean ventilation rate of 32 l/min) for 15 min of each half-hour. Responses were measured with spirometry and symptom evaluations before and after each exposure, and a bronchial reactivity test (methacholine challenge) was conducted after each exposure. All response measurements showed clinically and statistically significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s responses were similarly large on the 1st and 2nd O3 exposure days, after which they diminished progressively, approaching filtered air response levels by the 5th consecutive O3 day. This tolerance was partially lost 4 and 7 d later. Bronchial reactivity peaked after the first O3 exposure and remained somewhat elevated after all subsequent O3 exposures, relative to its control level following filtered-air exposures. Individual responses varied widely; more severe initial responses to O3 predicted less rapid attenuation. We concluded that asthmatics can develop tolerance to frequent high-level O3 exposures in much the same manner as normal subjects, although the process may be slower and less fully effective in asthmatics.