Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec; Université Laval, Québec, QC, Canada.
Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, Faculty of Education, McGill University, Montréal, QC, Canada.
Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620939507. doi: 10.1177/1753466620939507.
Exertional dyspnea is a cardinal feature of chronic obstructive pulmonary disease (COPD) and a major cause of activity limitation. Although dual bronchodilation is more effective than bronchodilator monotherapy at improving resting pulmonary function, it is unclear to which extent this translates into superior relief of exertional dyspnea.
We conducted a randomized controlled, double-blind, cross-over trial comparing indacaterol 110 µg/glycopyrronium 50 µg once daily (OD) with tiotropium 50 µg OD in patients with moderate to severe COPD and resting hyperinflation (functional residual capacity >120% of predicted value). The primary outcome was Borg dyspnea score at the end of a 3-min constant speed shuttle test after 3 weeks of treatment. Secondary outcomes included changes in Borg dyspnea score after the first dose of study medication, expiratory flows and lung volumes. Statistical analysis was conducted using a cross-over analysis of variance model with repeated measurements.
A total of 50 patients with COPD and a mean forced expiratory volume in 1 s of 54 ± 11% (mean ± SEM) predicted participated in the cross-over phase of the trial. Compared with baseline, there was a decrease in dyspnea after the first dose of medication with indacaterol/glycopyrronium [mean -1.00, 95% confidence interval (CI) -1.49 to -0.52] but not with tiotropium alone (mean -0.36, 95% CI -0.81 to 0.08). The reduction in dyspnea after the first dose was statistically significant between the two treatments (mean difference of -0.64, 95% CI -1.11 to -0.17). Despite indacaterol/glycopyrronium providing further bronchodilation and lung deflation throughout the trial, the reduction in dyspnea was not sustained at 3 weeks of treatment (mean between-treatment difference at 3 weeks of 0.09, 95% CI -0.44 to 0.61).
In comparison with bronchodilator monotherapy, indacaterol/glycopyrronium provided greater immediate exertional dyspnea relief, although this difference was not sustained after 3 weeks of therapy despite evidence of further bronchodilation and lung deflation.
运动性呼吸困难是慢性阻塞性肺疾病（COPD）的主要特征，也是活动受限的主要原因。尽管双重支气管扩张剂比支气管扩张剂单药治疗更能改善静息肺功能，但尚不清楚这在多大程度上能更好地缓解运动性呼吸困难。
我们进行了一项随机对照、双盲、交叉试验，比较了每天一次吸入 110μg 茚达特罗/50μg 格隆溴铵（OD）与每天一次吸入 50μg 噻托溴铵治疗中重度 COPD 合并静息性过度充气（功能残气量>预测值的 120%）患者的疗效。主要终点是治疗 3 周后 3 分钟恒速踏车试验结束时的 Borg 呼吸困难评分。次要终点包括首次服药后 Borg 呼吸困难评分的变化，呼气流量和肺容积。采用交叉方差分析模型进行重复测量的统计学分析。
共有 50 例 COPD 患者参加了试验的交叉阶段，他们的 1 秒用力呼气量（FEV1）平均为预测值的 54%±11%（均数±SEM）。与基线相比，茚达特罗/格隆溴铵治疗后首次用药时呼吸困难减轻[平均-1.00，95%置信区间（CI）-1.49 至-0.52]，而单用噻托溴铵则无明显变化（平均-0.36，95%CI-0.81 至 0.08）。两种药物治疗之间首次用药时呼吸困难的减轻程度有统计学意义（平均差值-0.64，95%CI-1.11 至-0.17）。尽管茚达特罗/格隆溴铵在整个试验中提供了进一步的支气管扩张和肺萎陷，但在 3 周的治疗中，呼吸困难的减轻并未持续（治疗 3 周时的平均治疗差异为 0.09，95%CI-0.44 至 0.61）。
与支气管扩张剂单药治疗相比，茚达特罗/格隆溴铵能提供更大的即时运动性呼吸困难缓解，但尽管有进一步的支气管扩张和肺萎陷的证据，这种差异在 3 周的治疗后并未持续。
