Methacholine and physostigmine airway reactivity in asthmatic and nonasthmatic subjects

Inhalation challenges using methacholine and physostigmine were performed in 3 human asthmatic and 3 nonallergic normal subjects. Plethysmographic measurements of specific airways conductance ($\text{Gaw}\text{Vtg}$) were used to monitor the response. The dose required to produce a 17% fall in $\text{Gaw}\text{Vtg}$ was significantly lower in asthmatic subjects than in normal subjects for both physostigmine (p < 0.0125) and methacholine (p < 0.05). Moreover, in all subjects the relative airway sensitivity to methacholine correlated with the relative airway sensitivity to physostigmine. Both methacholine and physostigmine are cholinergic agents. Whereas methacholine acts directly at the end organ cholinergic receptor, physostigmine acts by increasing release and decreasing destruction of endogenous acetycholine at the vagal distal innervation. This suggests that the cholinergic airway hyperreactivity characteristic of asthma is a manifestation of end organ hypersensitivity.