Duration of action of inhaled terbutaline at two different doses and of albuterol in protecting against bronchoconstriction induced by hyperventilation of dry cold air in asthmatic subjects

Although several studies have examined the duration of the bronchodilator effect of several inhaled beta-2-adrenergic agents, the duration of the blocking effect on bronchial hyperresponsiveness, another key feature of asthma, has seldom been studied. We investigated this problem in eight adult asthmatic subjects who underwent hyperventilation tests with dry cold air on 4 different days. On the first day, five hyperventilation tests with assessment of the level of ventilation causing a 20% fall in FEV1 (PD20) were obtained to evaluate the within-day variability of the test. On the three other visits, after a baseline hyperventilation test, albuterol 200 micrograms, terbutaline 500 micrograms, and terbutaline 1,500 micrograms were administered in a double-blind, randomized way. Hyperventilation tests were carried out 1, 2, 4, and 6 h later. The blocking effect on the treatment days, as assessed by the differences in PD20 for each test compared with baseline PD20 for that day, was corrected for the within-day variability of the control day. There was a significant bronchodilator effect 1 h after administering the drug; it was equivalent for albuterol 200 micrograms (25.6 +/- 14.7%) and terbutaline 1,500 micrograms (21.7 +/- 13.5%) and significantly less for terbutaline 500 micrograms (14.1 +/- 10.0%). Complete or partial blockade on bronchial responsiveness was obtained in the majority (six to seven of eight) of the subjects 1 h after inhaling the bronchodilator, with progressive reduction in the effect later on. Four subjects still showed a blocking effect 6 h after terbutaline 1,500 micrograms was administered, one subject after terbutaline 500 micrograms, and no subjects after albuterol (chi square = 6.6, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)