The increased responsiveness to inhaled methacholine in asthma: combination of causative factors

In asthma the dose-response curve to inhaled methacholine (MCh) is shifted leftwards and shows an increased slope and maximum. Two factors might contribute to the different form and position of this curve: (1) mediator-induced airway muscle hypersensitivity and (2) thickening of the airway wall. We attempted to estimate the effect of a combination of these two factors on the increase in airway resistance of a single isolated human airway to increasing concentrations of MCh. The result suggests that mediator-induced hypersensitivity to cholinergic stimuli may explain a small part of the leftward shift of the asthmatic dose-response curve to MCh, especially at lower levels of bronchoconstriction, and that increased thickness of the airway wall may be more important for the increased slope and maximum of the asthmatic dose-response curve.