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 log-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, randomised study the potent inhibitor of prostaglandin synthesis indomethacin (50 mg four times per day for three 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 less than 0.005) but unchanged in the normal subjects. In both groups reactivity was significantly increased (p less than 0.01). The study was repeated after several weeks of regular salbutamol treatment. In both groups salbutamol caused a decrease in sensitivity (p less than 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.