Relationship between deposition of and responsiveness to inhaled methacholine in normal and asymptomatic subjects

Abstract

The purpose of this study was to determine if the intersubject variability in airway responsiveness to methacholine is a function of the methacholine mass deposited in the airways and if methacholine hyperresponsiveness in asymptomatic subjects with asthma is related to increased methacholine deposition. Ten normal and 10 age-matched asymptomatic subjects with asthma inhaled, with a standardized single breath maneuver, a dry aerosol (mass median aerodynamic diameter, 1.5 μm; geometric SD, 2.1) generated from solutions of methacholine at concentrations ranging from 0.078 mg/ml to 80 mg/ml in buffered saline, mixed with a fixed concentration of the fluorescent tracer quinine. The mass of methacholine deposited was calculated from the fluorescence of the inspired and expired aerosol trapped on an absolute filter before inspiration and during expiration. Specific airway conductance (SG aw) was measured before and after the inhalation of increasing concentration of methacholine, and the provocative deposited mass corresponding to a 35% decrease in SG aw was calculated. Baseline aerosol deposition (quinine-labeled buffered saline) ranged from 63% to 94% and was similar in normal subjects (mean 85%) and asymptomatic subjects with asthma (mean 84%). There was a correlation between the decrease in SG aw and methacholine mass deposited at first dose in the normal subjects ( p < 0.001) but not in asymptomatic subjects with asthma. Mean provocative methacholine mass corresponding to a 35% decrease in SG aw was 86 μg (range 2 to 157 μg) in asymptomatic subjects with asthma and 1361 μg (range 157 to 3434 μg) in normal subjects ( p < 0.01). These results suggest (1) that the magnitude and range of methacholine responsiveness is greater in asymptomatic subjects with asthma than in normal subjects, (2) that the variability in methacholine responsiveness correlates with methacholine deposition in normal subjects but not in asymptomatic subjects with asthma, and (3) that the methacholine hyperresponsiveness in asymptomatic subjects with asthma is not related to enhanced aerosol deposition.