Prostaglandins and the control of airways responses to histamine in normal and asthmatic subjects.

Abstract

Inhalation histamine challenges were performed in groups of normal and asthmatic subjects. On each occasion a regression line for the descending part of the long-cumulative dose-response curve was computed. The dose of histamine causing a 20% fall in specific conductance (sGaw) was taken as an index of sensitivity. The slope gave the reactivity. In a double-blind, randomized study the potent inhibitor of prostaglandin synthesis indomethacin (50 mg 4 times/day for 3 days) was associated with a small but significant bronchodilatation in the normal but not the asthmatic subjects. Sensitivity to histamine was considerably decreased in the asthmatic patients (P < 0.005) but unchanged in the normal subjects. In both groups reactivity was significantly increased (P < 0.01). The study was repeated after several weeks of regular salbutamol treatment. In both groups salbutamol caused a decrease in sensitivity (P < 0.001) but no change in reactivity. After indomethacin had been reintroduced while salbutamol was continued, most of the effects of chronic salbutamol treatment were reversed in the normal subjects, with a similar trend in the asthmatic patients. In both groups the dose-response curves after indomethacin treatment were little affected by pretreatment with salbutamol. .beta.-adrenergic stimulation induces changes in the airways that may be dependent on prostaglandin production.