Response to inhaled albuterol during nocturnal asthma

Background During conventional daytime studies of β 2 -agonists, 1 puff of a metered-dose inhaler often produces a near maximum bronchodilator response. Consequently, the US Food and Drug Administration–approved dose of albuterol is only 1 to 2 puffs every 4 to 6 hours. Objective To determine whether a higher dose of albuterol is required to normalize lung function during nocturnal asthma. Methods Fifteen subjects (age, 18-37 years) were treated with albuterol metered-dose inhalers in a randomized crossover manner at the onset of nocturnal symptoms while sleeping in the Clinical Research Center and during the day when they were asymptomatic. The dose was doubled at 15-minute intervals to 16 cumulative puffs. Results The mean ± SD predose FEV 1 was lower at night than during the day (44% ± 12% vs 68% ± 9% predicted; P = .0001). The maximum FEV 1 achieved was also lower at night (84% ± 15% vs 90% ± 12%; P = .02). The nocturnal dose-response curve was shifted to the right. The median (25th, 75th percentiles) dose required to achieve 80% of the subject's personal best FEV 1 was substantially higher at night (5 [1, 19] vs 0.4 [ P = .02), and the median time to achieve this endpoint was longer (47 [21, 90] vs 10 [0.2, 42] minutes; P = .005). No significant systemic effects were observed. Conclusion At night, the response was slower and required a higher dose because more severe airway obstruction was present on awakening. These results suggest that studies establishing the clinical dose of a β 2 -agonist or assessing the equivalence of different formulations should be conducted in subjects with more severe reversible airway obstruction than is present during conventional daytime studies.