常规比索洛尔对哮喘沙丁胺醇反应的影响：一项双盲随机安慰剂对照交叉试验。

The impact of regular bisoprolol on the response to salbutamol in asthma: A double-blind randomized placebo-controlled crossover trial.

机构信息

Respiratory Research Unit, Department of Respiratory Medicine, Waikato Hospital, Hamilton, New Zealand.

Department of Preventive and Social Medicine, Otago Medical School, University of Otago, Dunedin, New Zealand.

出版信息

Respirology. 2021 Mar;26(3):225-232. doi: 10.1111/resp.13955. Epub 2020 Oct 11.

DOI:10.1111/resp.13955

PMID:33043552

Abstract

BACKGROUND AND OBJECTIVE

Non-selective beta-blockers impair the bronchodilator response to beta -agonists. Cardio-selective beta -blockers are less likely to cause this effect, yet they remain relatively contraindicated in asthma. We investigated whether the response to salbutamol is impaired during cardio-selective beta -blocker treatment in people with asthma.

METHODS

A random-order, double-blind, placebo-controlled, non-inferiority, crossover study was conducted comparing up to 5 mg bisoprolol daily for 2 weeks with matching placebo, with an open-label extension of up to 10 mg bisoprolol daily. After each treatment period, mannitol was inhaled to induce bronchoconstriction with a 15% fall in forced expiratory volume in 1 s (FEV ). Immediately after mannitol challenge, salbutamol (100, 100 and 200 μg) was administered via spacer at 5-min intervals with repeated FEV measures. The FEV recovery with salbutamol was measured as an area under recovery curve (AUC). Based on earlier research, a clinically relevant non-inferiority limit of a 30% reduction in the AUC was set.

RESULTS

A total of 19 adults with mild asthma and positive inhaled mannitol challenge completed the study. Adjusting for the FEV fall induced by mannitol and treatment sequence, the mean AUC response to salbutamol after bisoprolol was 5% lower than after placebo, with a one-sided 95% confidence interval (CI) of 26% lower. Thirteen participants completed the open-label extension up to 10 mg bisoprolol daily with mean AUC 11% higher after bisoprolol with a 95% CI of 5% lower.

CONCLUSION

The bronchodilator response to rescue salbutamol after mannitol-induced bronchoconstriction is non-inferior during regular treatment with the cardio-selective beta -blocker, bisoprolol, compared to placebo.

CLINICAL TRIAL REGISTRATION

ACTRN12618000306213 at https://www.anzctr.org.au.

摘要

背景和目的

非选择性β受体阻滞剂会削弱β受体激动剂对支气管的舒张作用。心脏选择性β受体阻滞剂则不太可能产生这种效果，但在哮喘患者中仍相对禁忌使用。我们研究了在哮喘患者中使用心脏选择性β受体阻滞剂治疗期间，沙丁胺醇的反应是否会受到损害。

方法

进行了一项随机、双盲、安慰剂对照、非劣效性、交叉研究，比较了每天最高 5mg 比索洛尔治疗 2 周与匹配的安慰剂，以及每天最高 10mg 比索洛尔的开放标签扩展期。在每个治疗期间，用吸入甘露醇来诱发支气管收缩，导致用力呼气量在 1 秒内下降 15%（FEV ）。在甘露醇挑战后，立即通过间隔器以 5 分钟的间隔给予沙丁胺醇（100、100 和 200μg），并重复测量 FEV 。沙丁胺醇的 FEV 恢复量作为恢复曲线下面积（AUC）来测量。基于早期的研究，设定了一个具有临床意义的非劣效性限制，即 AUC 减少 30%。

结果

共有 19 名轻度哮喘患者和吸入甘露醇挑战阳性的患者完成了这项研究。调整甘露醇引起的 FEV 下降和治疗顺序后，比索洛尔治疗后的沙丁胺醇 AUC 平均比安慰剂低 5%，单侧 95%置信区间（CI）为低 26%。13 名参与者完成了每天最高 10mg 比索洛尔的开放标签扩展期，比索洛尔治疗后的平均 AUC 比安慰剂高 11%，95%CI 为低 5%。