Lehmann Sverre, Ringbæk Thomas, Løkke Anders, Grote Ludger, Hedner Jan, Lindberg Eva
Department of Thoracic Medicine, Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway,
Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway,
Int J Chron Obstruct Pulmon Dis. 2019 Jan 9;14:199-210. doi: 10.2147/COPD.S184127. eCollection 2019.
This study investigated the effect of dual bronchodilation with the long-acting β-receptor agonist/long-acting muscarinic antagonist combination, indacaterol/glycopyrronium (IND/GLY), on nighttime oxygenation, lung function, sleep quality, and symptoms in patients with moderate-to-severe COPD.
This was a 4-week, double-blind, multicenter, placebo-controlled, two-period crossover study. Patients were randomized in a 1:1 ratio to receive IND/GLY 110/50 µg once daily or matching placebo. The primary objective was to evaluate the effect of treatment with IND/GLY on mean nighttime oxygenation, compared with placebo. The secondary objective was to determine the time spent <90% in blood oxygen saturation (SpO) compared with placebo. Exploratory objectives were to assess the effect of IND/GLY, compared with placebo, on sleep quality measured by the Medical Outcomes Study (MOS) Sleep Scale and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaires and on symptoms assessed by COPD Assessment Test (CAT) questionnaire.
In total, 38 patients were randomized (n=22, IND/GLY; n=16, placebo). The change in nighttime oxygenation (SpO) was similar, and there was a comparable difference in time spent <90% SpO between IND/GLY and placebo. Increases from baseline for the difference between IND/GLY and placebo for trough FEV, FVC, and inspiratory capacity (<0.05) were seen, with a corresponding reduction in residual volume and functional residual capacity (<0.05). IND/GLY treatment showed an improvement in scores for CAT (=0.0208), CASIS, and the MOS Sleep Scale measures, Sleep Problems Index I, Sleep Problems Index II (=0.0315), Sleep Adequacy, Sleep Disturbance Scale, Somnolence Scale, and Short of Breath Scale (=0.0031).
In this study, IND/GLY 110/50 µg once daily improved symptoms, sleep quality, and lung function, but showed no effect on nighttime oxygenation in patients with moderate-to-severe COPD.
本研究调查长效β受体激动剂/长效毒蕈碱拮抗剂组合药物茚达特罗/格隆溴铵（IND/GLY）双重支气管扩张作用对中重度慢性阻塞性肺疾病（COPD）患者夜间氧合、肺功能、睡眠质量及症状的影响。
这是一项为期4周的双盲、多中心、安慰剂对照、两阶段交叉研究。患者按1:1比例随机分组，分别接受每日一次的IND/GLY 110/50μg或匹配的安慰剂。主要目的是评估IND/GLY治疗与安慰剂相比对平均夜间氧合的影响。次要目的是确定与安慰剂相比血氧饱和度（SpO）<90%的时长。探索性目的是评估IND/GLY与安慰剂相比对通过医学结局研究（MOS）睡眠量表和慢性阻塞性肺疾病与哮喘睡眠影响量表（CASIS）问卷测量的睡眠质量以及通过慢性阻塞性肺疾病评估测试（CAT）问卷评估的症状的影响。
总共38例患者被随机分组（n = 22，IND/GLY组；n = 16，安慰剂组）。夜间氧合（SpO）的变化相似，IND/GLY组与安慰剂组之间SpO<90%的时长差异相当。IND/GLY组与安慰剂组相比，用力呼气容积（FEV）、用力肺活量（FVC）和吸气量的谷值从基线开始增加（<0.05），残气量和功能残气量相应减少（<0.05）。IND/GLY治疗使CAT（=0.0208）、CASIS及MOS睡眠量表测量指标、睡眠问题指数I、睡眠问题指数II（=0.0315）、睡眠充足度、睡眠障碍量表、嗜睡量表和气短量表得分得到改善（=0.0031）。
在本研究中，每日一次的IND/GLY 110/50μg改善了中重度COPD患者的症状、睡眠质量和肺功能，但对夜间氧合无影响。
