Sears M R, Taylor D R, Print C G, Lake D C, Li Q Q, Flannery E M, Yates D M, Lucas M K, Herbison G P
Department of Medicine, University of Otago Medical School, Dunedin, New Zealand.
Lancet. 1990 Dec 8;336(8728):1391-6. doi: 10.1016/0140-6736(90)93098-a.
89 subjects with stable asthma took part in a double-blind, placebo-controlled, randomized, crossover study of the effects of regular versus on-demand inhaled bronchodilator therapy. The subjects inhaled fenoterol or placebo by a dry powder delivery system for 24 weeks. Control of asthma was judged by daily morning and evening peak expiratory flow rates, symptom diaries, use of additional inhaled bronchodilator, and requirement for short courses of prednisone. Of 64 subjects who completed the trial, 57 showed a clear difference in degree of control of asthma between the fenoterol and placebo periods: in 17 (30% [95% confidence interval 18.4-43.4%]) asthma was better controlled during regular inhaled bronchodilator treatment, whereas in 40 (70% [56.6-81.6%]) control was better during placebo treatment with bronchodilator for symptom relief only. Mean airway responsiveness to methacholine increased slightly during the fenoterol period. The adverse effect of regular bronchodilator inhalation occurred not only among subjects who used a bronchodilator as sole treatment (2 were better and 10 were worse during regular bronchodilator treatment) but also among those who took inhaled corticosteroids (14 were better and 29 were worse). Thus, regular inhalation of a beta-sympathomimetic agent was associated with deterioration of asthma control in the majority of subjects. The trends to use of regular, higher doses or longer-acting inhaled beta-sympathomimetic treatment may be an important causal factor in the worldwide increase in morbidity from asthma.
89名患有稳定型哮喘的受试者参与了一项双盲、安慰剂对照、随机交叉研究，以探讨规律吸入支气管扩张剂治疗与按需吸入支气管扩张剂治疗的效果。受试者通过干粉给药系统吸入非诺特罗或安慰剂，为期24周。通过每日早晚的呼气峰值流速、症状日记、额外吸入支气管扩张剂的使用情况以及泼尼松短期疗程的需求来判断哮喘的控制情况。在完成试验的64名受试者中，57名在非诺特罗治疗期和安慰剂治疗期之间的哮喘控制程度有明显差异：17名（30%[95%置信区间18.4 - 43.4%]）在规律吸入支气管扩张剂治疗期间哮喘控制更好，而40名（70%[56.6 - 81.6%]）在仅用于缓解症状的安慰剂支气管扩张剂治疗期间控制更好。在非诺特罗治疗期，气道对乙酰甲胆碱的反应性略有增加。规律吸入支气管扩张剂的不良反应不仅发生在将支气管扩张剂作为唯一治疗方法的受试者中（2名在规律支气管扩张剂治疗期间病情好转，10名病情恶化），也发生在吸入皮质类固醇的受试者中（14名病情好转，29名病情恶化）。因此，在大多数受试者中，规律吸入β-拟交感神经药物与哮喘控制的恶化有关。规律使用更高剂量或长效吸入β-拟交感神经药物治疗的趋势可能是全球哮喘发病率上升的一个重要因果因素。
