Abstract
RATIONALE: Repeated, short-term exposures to ozone (O3) lead to attenuation of the acute lung function and airway inflammatory responses seen after a single exposure in healthy subjects, but it is unclear whether these acute responses also attenuate in subjects with asthma. OBJECTIVE: To address this question by exposing 14 subjects with asthma to 0.2 ppm O3 for either 4 hours on a single day or 4 hours on 4 consecutive days (multiday [MD]). At least 3 weeks later, subjects underwent the alternate exposure. METHODS: Spirometry was performed immediately pre- and postexposure and bronchoalveolar lavage (BAL) was obtained 18 hours after each exposure. MAIN RESULTS: The decrease in FEV1 was greatest across Day 2 of the MD (MD2) exposure and then gradually declined on successive days of the MD exposure (mean +/- SD decrease in FEV1 of 25.4 +/- 18.0% across MD2 compared with 4.2 +/- 6.5% across MD4). Respiratory symptoms followed a similar pattern to that of FEV1. Although the concentration of neutrophils in BAL after the MD4 exposure was not significantly different from that after the single-day exposure (1.7 +/- 1.3 x 10(4) cells/ml vs. 1.2 +/- 0.8 x 10(4) cells/ml, p = 0.20), the concentration of alveolar macrophages did significantly increase in BAL after the MD exposure (19.9 +/- 9.7 x 10(4) cells/ml after MD4 vs. 12.1 +/- 6.4 x 10(4) cells/ml after the single day). CONCLUSIONS: Alveolar macrophages are recruited to the airways of subjects with asthma with repeated short-term exposures to O3, suggesting a possible role for these cells in the chronic response to oxidant-induced injury.