The effect of indomethacin on the refractory period occurring after the inhalation of ultrasonically nebulized distilled water.

We examined the involvement of inhibitory prostaglandins in refractoriness induced by repeated ultrasonically nebulized distilled water (UNDW) challenge. Six male subjects with asthma who developed both UNDW-induced bronchoconstriction and refractoriness after UNDW were studied on 3 separate days, 1 week apart. On each study day, subjects had an initial UNDW challenge. UNDW responsiveness was assessed with dose-response curves of UNDW volume output versus the percent fall in FEV1. The output provoking a 20% fall in FEV1 (PO20 UNDW) was calculated. FEV1 was measured again at 5-minute intervals until it returned to within 5% of baseline value. UNDW challenge was then repeated. On day 1, the two successive UNDW challenges were performed in absence of any treatment (control day). Before days 2 and 3, subjects received placebo capsules or indomethacin, 100 mg per day, in a double-blind, randomized fashion for 3 days. On both the control and placebo days, repeated UNDW inhalation provoked a significant increase in PO20 UNDW (p less than 0.01), indicating refractoriness. On the indomethacin day, the mean PO20 UNDW during the second UNDW challenge was not significantly different from that obtained during the initial test on that day (p greater than 0.05), indicating that refractoriness did not occur. We suggest that inhibitory prostaglandins are involved in the development of refractoriness after UNDW inhalation.