Indomethacin does not inhibit the ozone-induced increase in bronchial responsiveness in human subjects.
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 exposure 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 modification. 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 greater than 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 less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Ying
R L
RL
Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor.
Gross
K B
KB
Terzo
T S
TS
Eschenbacher
W L
WL
D000293:Adolescent; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride; D010126:Ozone / Q000009:adverse effects*; D011897:Random Allocation; D014797:Vital Capacity / Q000187:drug effects
D016210:Methacholine Chloride; D010126:Ozone; D007213:Indomethacin