Methacholine dose-response curves in normal and asthmatic man: effect of starting conductance and pharmacological antagonism

Abstract

The bronchial response of 11 normal and ten stable asthmatic subjects to increasing concentrations of methacholine aerosol was assessed by serial measurements of specific airways conductance (sGaw) in a body plethysmograph. Cumulative log dose-response curves were constructed. The threshold provocative dose of methacholine needed to cause a 35% fall in starting sGaw ( PD35 ) and the steepest slope of the response were measured from each curve. On separate days subjects were premedicated with 0.9% NaCl solution (control) in duplicate, chlorpheniramine, salbutamol and atropine, the last-named at two different doses, one twice the other. Asthmatic subjects had a lower mean PD35 and a lower mean slope than normal subjects. Pretreatment with salbutamol resulted in a greater increase in sGaw than after atropine but caused a smaller increase in PD35 in both groups. There was a dose-dependent increase in PD35 after the two doses of atropine, but no significant difference in bronchodilatation between doses. Mean steepest slope approximately doubled in these three sets of challenges. Chlorpheniramine caused a small degree of bronchodilatation and there was a non-significant increase in mean PD35 and in mean steepest slope in both normal and asthmatic groups. There was a positive linear correlation between starting sGaw and steepest slope in each group of premedicated challenges, such that when sGaw was high, either spontaneously or due to bronchodilatation, the slope was steeper. We conclude that increases in PD35 to methacholine after antagonist drugs are predominantly the result of pharmacological antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)