Histamine dose-response relationships in normal and asthmatic subjects. The importance of starting airway caliber

Abstract

We examined the effects of pharmacologic antagonists on the bronchial response to inhaled histamine in 11 normal and 11 asthmatic subjects. We constructed cumulative log dose-response curves and determined the steepest slope and the provocative dose of histamine (PD35) needed to cause a 35% fall in specific airway conductance (SGaw). The slope was positively related to starting SGaw in both groups. Starting SGaw and slope were approximately 2-fold lower in asthmatics. After inhaling salbutamol (200 micrograms) and atropine (4 mg), there was an increase in starting SGaw and slope of the histamine response by approximately 1.5-fold in normal subjects and 2-fold in asthmatics, the relationship between starting SGaw and slope being preserved. Chlorpheniramine (4 mg) had little effect on starting SGaw and slope.l Atropine, salibutamol, and chlorpheniramine increased PD35 by approximately 4-fold in normal subjects and 6-fold in asthmatics. Afte bronchodilatation with atropine or salbutamol, mean starting SGaw, slope, and PD35 of the responses in asthmatics were similar to those of unpremedicated normal subjects. Thus, the slope of the histamine dose-response curve is largely determined by the starting airway caliber, increases in PD35 by drugs reflect in part the effects of bronchodilatation and in part their specific pharmacologic antagonist activity.