Indomethacin pretreatment reduces ozone-induced pulmonary function decrements in human subjects

We studied whether O3-induced pulmonary function decrements could be inhibited by the prostaglandin synthetase inhibitor, indomethacin, in healthy human subjects. Fourteen college-age males completed six 1-h exposure protocols consisting of no drug, placebo, and indomethacin (Indocin SR 75 mg every 12 h for 5 days) pretreatments, with filtered air and O3 (0.35 ppm) exposures within each pretreatment. Pretreatments were delivered weekly in random order in a double-blind fashion. Ozone and filtered air exposures, separated by 72 h, were delivered in random order in a single-blind fashion. Exposures consisted of 1-h exercise on a bicycle ergometer with work loads set to elicit a mean minute ventilation of 60 L/min. Statistical analysis revealed significant (p less than 0.05) across pretreatment effects for FVC and FEV1, with no drug versus indomethacin and placebo versus indomethacin comparisons being significant. These findings suggest that cyclooxygenase products of arachidonic acid, which are sensitive to indomethacin inhibition, play a prominent role in the development of pulmonary function decrements consequent to acute O3 exposure.