Medical Centre Leeuwarden, Department of Respiratory Medicine, Leeuwarden, the Netherlands; University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.
Respir Med. 2020 Sep;171:106064. doi: 10.1016/j.rmed.2020.106064. Epub 2020 Jul 3.
Most guidelines recommend long-acting bronchodilators over short-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD). The available evidence for the guidelines was based on dry powder or pressurized metered dose inhalers, but not nebulizations. Nevertheless, there is considerable, poorly evidenced based, use of short acting nebulized bronchodilators.
This was an investigator initiated, randomized, active controlled, cross-over, double-blind and double-dummy single centre study in patients with stable COPD. The active comparators were indacaterol/glycopyrronium 110/50 μg as Ultibro® via Breezhaler® (IND/GLY) and salbutamol/ipratropium 2,5/0,5 mg via air driven nebulization (SAL/IPR), both given as a single dose on separate days. The primary end point was the area under the FEV curve from baseline till 6 h. Secondary end points included change in Borg dyspnoea score, adverse events and change in hyperinflation measured by the inspiratory capacity.
A total of 33 COPD patients completed the trial and were evaluable, most of them were ex-smokers. The difference between the tested regimens for the primary endpoint, FEV AUC 0-6 h, 2965 ± 1544 mL (mean ± SD) for IND/GLY versus 3513 ± 1762 mL for SAL/IPR, was not significant (P = 0.08). The peak in FEV1 was higher and was reached faster with SAL/IPR compared to IND/GLY. No other significant differences were detected for the secondary endpoints including the Borg score, or adverse events.
Among patients with stable COPD, dry powder long-acting single inhalation of a LABA and a LAMA (IND/GLY) was not superior compared to nebulized short-acting salbutamol plus ipratropium (SAL/IPR) in its bronchodilating effects over 6 h.The effects of the nebulization kicked in faster and peaked higher. The observed differences may be caused by the difference in dosing between the two regimens. The improvement in Borg dyspnoea score did not favour the nebulization. Long-term outcomes were not assessed in this study.
大多数指南建议慢性阻塞性肺疾病（COPD）患者使用长效支气管扩张剂而非短效支气管扩张剂。制定这些指南所依据的现有证据是基于干粉或压力定量吸入器，但不包括雾化吸入。然而，临床中大量使用的却是短效雾化支气管扩张剂，其使用依据并不充分。
这是一项由研究者发起的、随机的、活性对照的交叉、双盲和双模拟的单中心研究，纳入了稳定期 COPD 患者。活性对照药物为乌美溴铵/格隆溴铵 110/50μg 干粉（Ultibro®经 Breezhaler®给药）和沙丁胺醇/异丙托铵 2.5/0.5mg 雾化吸入（SAL/IPR），两种药物均为单剂量，在不同天给药。主要终点是从基线到 6 小时的 FEV 曲线下面积。次要终点包括 Borg 呼吸困难评分的变化、不良事件以及吸气量测量的过度充气变化。
共有 33 例 COPD 患者完成了试验并可评估，其中大多数为戒烟者。两种治疗方案的主要终点，即 FEV AUC 0-6 h，IND/GLY 组为 2965±1544 mL（平均值±标准差），SAL/IPR 组为 3513±1762 mL，差异无统计学意义（P=0.08）。与 IND/GLY 相比，SAL/IPR 组的 FEV1 峰值更高，且更快达到峰值。其他次要终点，包括 Borg 评分或不良事件，均无显著差异。
在稳定期 COPD 患者中，与雾化吸入短效沙丁胺醇加异丙托铵（SAL/IPR）相比，干粉长效单吸入 LABA 和 LAMA（乌美溴铵/格隆溴铵）在 6 小时内的支气管扩张作用并无优势。雾化吸入起效更快，峰值更高。观察到的差异可能是由于两种方案之间的剂量差异造成的。Borg 呼吸困难评分的改善并不支持雾化吸入。本研究未评估长期结局。
