Serial distribution of bronchoconstriction in normal subjects. Methacholine versus histamine

We compared the relative sites of airway responses to methacholine and histamine aerosols in normal subjects by simultaneous assessment of respiratory resistance (Rrs) and anatomic dead space (VD). Methacholine (12.5 mg/ml) or histamine (12.5 mg/ml) was continuously inhaled during tidal breathing until a nearly twofold increase in Rrs was observed. Large airway response was determined by VD, and overall airway response was determined by Rrs. Small airways response was inferred from Rrs when the change in VD was slight. Inhalation of methacholine and histamine increased Rrs with decreased VD, but the decrease in VD was significantly greater with methacholine than with histamine for an equivalent change in Rrs (p less than 0.01). Inhalation of atropine (5 mg/ml) decreased Rrs with a simultaneous increase in VD. After inhalation of atropine, time required for a twofold increase in Rrs by histamine inhalation was prolonged, and histamine did little decrease VD. These results suggest that the predominant site of cholinergically mediated constriction is the large airways, and that histamine constricts the large airways in part via a cholinergic reflex mechanism and constricts the small airways via its direct action in normal subjects.