short term variation of atropine blockade in the tracheobronchial tree of asthmatic subjects

in asthmatic subjects there is a pronounced diurnal variation in bronchial responsiveness. if this phenomenon is due to variation in factors that control drug delivery, then it should be paralleled by a similar variation in competitive antagonist blockade. in order to study this possibility, we performed the methacholine challenge test and after 45 minutes, administered atropine by inhalation. methacholine rechallenge was performed 25 minutes after premedication with atropine. bronchial responsiveness to methacholine(pb3s) and atropine blockade was then measured. eight normal subjects and 9 asthmatic patients were tested on two separate occasions, one in the morning at 08:00 hours and the other in the evening at 18:00 hours with at least 48 hours gap between them. in normal subjects there was no significant difference between morning and evening concerning airway caliber, bronchial responsiveness to methacholine and atropine blockade. in asthmatic patients there was a significant difference between morning and evening in bronchial responsiveness to methacholine (p<0.001) and atropine blockade (p<0.001), although there was no significant difference in airway caliber. the possible explanation for&apos; enhanced atropine blockade as well as methacholine responsiveness in asthmatic subjects in the morning is increased bronchial and tissue permeability due to worsening bronchial inflammation in the early morning leading to increased drug delivery to active sites in the airways.