de Jong J W, van der Mark T W, Koëter G H, Postma D S
Department of Pulmonology, University Hospital Groningen, The Netherlands.
Am J Respir Crit Care Med. 1996 Jan;153(1):70-5. doi: 10.1164/ajrccm.153.1.8542165.
Regular monotherapy with inhaled beta 2-agonists may lead to a temporary increase of airway obstruction and increase of airway responsiveness after cessation of treatment. We investigated whether anti-inflammatory therapy may affect these rebound phenomena. In a double-blind, placebo-controlled study, we assessed lung function (FEV1) and airway responsiveness (PC20 methacholine [PC20]) during and after cessation of 2 wk of regular treatment with placebo and low-dose (250 micrograms) and high-dose (1,000 micrograms) inhaled terbutaline three times daily. Patients with mild allergic asthma (means [+/- SD] age of 28.2 +/- 6.6 yr, mean FEV1% of 91.9 +/- 14.6%, and geometric mean PC20 of 0.25 mg/ml) were studied. One group (n = 16) was randomized to budesonide treatment, 400 micrograms three times daily; the other group (n = 14) to placebo. PC20 and FEV1 were measured 10, 14, 34, and 82 h after the last terbutaline or placebo inhalation. A different method of statistical analysis was used, in that measurements performed at 10, 14, and 34 h were expressed relative to 82 h values in each period as an area-under-the-curve (AUC) value. FEV1 did not significantly change during placebo and budesonide treatment. Mean PC20 and morning and evening peak expiratory flow were significantly higher during budesonide treatment (p < 0.01). PC20 did not significantly change after cessation of terbutaline treatment in both placebo and budesonide treatment groups. AUC-FEV1 values after cessation of treatment with both doses of terbutaline were significantly different from the 82 h values (p < 0.05). The decrease in FEV1 was significantly greater after the last terbutaline and placebo inhalation in the placebo group compared with the budesonide treatment group (p = 0.02). We conclude that cessation of regular treatment after 2 wk with both low-dose and high-dose inhaled terbutaline does not result in a significant rebound airway responsiveness in patients with mild asthma. However, the results suggest a small rebound bronchoconstriction that does not occur when asthmatic patients are also treated with budesonide.
吸入性β2受体激动剂常规单一疗法可能导致气道阻塞暂时加重，并在治疗停止后气道反应性增加。我们研究了抗炎治疗是否会影响这些反跳现象。在一项双盲、安慰剂对照研究中，我们评估了在每日三次使用安慰剂、低剂量（250微克）和高剂量（1000微克）吸入特布他林进行2周常规治疗期间及治疗停止后患者的肺功能（FEV1）和气道反应性（乙酰甲胆碱激发试验PC20 [PC20]）。研究对象为轻度过敏性哮喘患者（平均年龄[±标准差]28.2±6.6岁，平均FEV1%为91.9±14.6%，几何平均PC20为0.25毫克/毫升）。一组（n = 16）随机接受布地奈德治疗，每日三次，每次400微克；另一组（n = 14）接受安慰剂治疗。在最后一次吸入特布他林或安慰剂后10、14、34和82小时测量PC20和FEV1。采用了一种不同的统计分析方法，即把在10、14和34小时进行的测量值相对于每个时间段82小时的值表示为曲线下面积（AUC）值。在安慰剂和布地奈德治疗期间，FEV1无显著变化。在布地奈德治疗期间，平均PC20以及早晚呼气峰值流量显著更高（p < 0.01）。在安慰剂和布地奈德治疗组中，特布他林治疗停止后PC20均无显著变化。两种剂量特布他林治疗停止后的AUC-FEV1值与82小时的值显著不同（p < 0.05）。与布地奈德治疗组相比，安慰剂组在最后一次吸入特布他林和安慰剂后FEV1的下降显著更大（p = 0.02）。我们得出结论，轻度哮喘患者在使用低剂量和高剂量吸入特布他林进行2周常规治疗后停止治疗，不会导致气道反应性出现显著反跳。然而，结果提示存在轻微的反跳性支气管收缩，而哮喘患者同时接受布地奈德治疗时则不会出现这种情况。
