Indomethacin Does Not Inhibit the Ozone-induced Increase in Bronchial Responsiveness in Human Subjects

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Abstract

Exposure of human subjects to sufficiently high levels of ozone can result in reversible changes in lung function (restrictive in nature) and increases in nonspecific airway responsiveness. Several studies have implicated products of cyclooxygenase metabolism in the mediation of these changes. The purpose of this study was to determine if indomethacin (a cyclooxygenase inhibitor) would alter the changes in the ozone-induced increase in responsiveness to methacholine or the ozone-induced decrease in lung function. Thirteen male subjects underwent three randomly assigned 2-h exposures to 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (30 L/min/m2, body surface area). For the 4 days before each of the exposures, the subjects received either indomethacin (150 mg/day) or placebo, or no medication. Of the 13 subjects, only seven had both detectable indomethacin serum levels on the Indomethacin Study Day and a significant increase in bronchial responsiveness to methacholine on the No Medication Day. For this group of seven subjects, we found that indomethacin did not alter the ozone-induced increase in bronchial responsiveness to methacholine (decrease in PC100SRaw for the different study days: no medication, −78.4 ± 5.3% [mean ± SEM]; placebo, −48.9 ± 12.2%; indomethacin, −64.5 ± 6.3%; p > 0.2), although indomethacin did attenuate the ozone-induced decrease in lung function. The decrease in the FEV1 for the different study days was as follows: no medication, − 20.7 ± 5.0% (mean ± SEM); placebo, −19.2 ± 6.3%; indomethacin, −4.8 ± 3.7% (p < 0.001). These results suggest that ozone-induced changes in lung function are mediated in part by cyclooxygenase products, but that the ozone-induced increase in bronchial responsiveness occurs by some other mechanism.

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