Modification of induced airway constriction in healthy subjects.

Unlike asthmatics, healthy persons are relatively unresponsive to airway constrictors. By using partial expiratory flow-volume (PEFV) curves the authors have demontrated, in healthy subjects, dose-related decreases in flow rates following challenge with histamine and methacholine aerosols. With the use of semilogarithmic dose-response curves they have shown that 80 mg oral propranolol augmented, whereas oral pretreatment with 400 mg W10294A (an experimental bronchodilator) decreased, histamine and methacholine-induced airway constriction. However, 300 mg of orally administered aminophylline failed to modify the airway constrictor effects of histamine and methacholine. Moreover, variation was noted in induced airway constriction in healthy subjects with decreases in flow rates being greater in the morning than in the afternoon. The authors conclude that (1) propranolol augments whereas theophylline fails to prevent nonspecific induced airway constriction in healthy subjects. This suggests that the bronchodilator action of theophylline may be unrelated to its phosphodiesterase inhibitory activity, (2) control of volume history, by use of partial expiratory flow-volume curves, is useful in quantifying pharmacologic protection and augmentation of nonspecific induced airway constriction in healthy subjects and (3) conclusions resulting from observations of induced airway constriction in healthy subjects may be dependent upon the effects of diurnal variation.