Variability of airway responses to inhaled histamine in normal subjects

Dose-response curves to inhaled histamine were studied in 12 normal subjects. Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured during tidal breathing, and maximum expiratory flow rates, at an absolute lung volume corresponding to 40% of control vital capacity, were obtained during forced expiration from tidal end inspiration (Vmax40p) and from total lung capacity (Vmax40c). Threshold was defined as the histamine dose at which a departure from the range of normal measurements was observed. RL and Vmax40p indicated lowest threshold values, which varied by a factor of 32 and 38, respectively. There was no correlation between reactivity, which reflects the slope of the dose-response curve beyond the threshold dose, and threshold doses, nor between the initial RL (normalized for lung volume) and either threshold or reactivity. In eight subjects, restudied on two occasions after 10 mg propranolol or after saline, injected in a double-blind manner, there was no change in the dose-response curves. These results indicate that different indices of bronchoconstriction may yield different dose-response curves and hence different sensitivities. In addition, a wide variation of airway responses to inhaled histamine exists in the normal population and beta-blockade does not influence this variability.