The initial observation that bronchoconstriction occurs more readily in asthmatics than nonasthmatics after exposure to a constrictor agonist was made by Alexander and Paddock (3) in 1921, who demonstrated "asthmatic breathing" in asthmatic, but not normal subjects after subcutaneous administration of the cholinergic agonist pilocarpine. This observation was conflnned subsequently by Weiss et al. (4), who reported in 1932 that asthmatic subjects, but not nonnal subjects, exhibited bronchoconstriction, as measured by changes in the vital capacity, after administration of intravenous histamine. Curry (5) noted that this increased bronchoconstrictor response to histamine in asthmatics occurred with
40 Mild asthmatic
FEV1 30 (X Change)
.25 .5 1 2 4 8 16 32 64 128 256
CONCENTRATION (mg/ml) Figure 1 Dose-response curves to inhaled constrictor agonists in a nonnal subject and asthmatic subjects with mildly and severely increased airway hyperresponsiveness. The responses are measured as the fall in FEV 1 from baseline values, and in these examples, the responses are expressed as the provocative concentrations of the agonist causing a 20% fall in FEVt. Both mild asthmatic and normal subjects demonstrate a plateau response, which is lost in more severe asthmatic subjects. FEV ,, forced expiratory volume in 1 sec.