Indomethacin does not inhibit the ozone-induced increase in bronchial responsiveness in human subjects

Journal Article · Mon Oct 01 04:00:00 EDT 1990 · American Review of Respiratory Disease (New York); (USA)

DOI:https://doi.org/10.1164/ajrccm/142.4.817· OSTI ID:6066839

Ying, R L; Gross, K B; Terzo, T S; Eschenbacher, W L ^[1]

---

1. Univ. of Michigan Medical Center, Ann Arbor (USA)

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).

• OSTI ID: 6066839
• Journal Information: American Review of Respiratory Disease (New York); (USA), Journal Name: American Review of Respiratory Disease (New York); (USA) Vol. 142:4; ISSN ARDSB; ISSN 0003-0805
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTIPYRETICS
BIOLOGICAL EFFECTS
BODY
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ENZYME INHIBITORS
LUNGS
MAMMALS
MAN
ORGANS
OZONE
PRIMATES
RESPIRATORY SYSTEM
SENSITIVITY
TOXICITY
VERTEBRATES