Singh Sally, Maltais François, Tombs Lee, Fahy William A, Vahdati-Bolouri Mitra, Locantore Nicholas, Riley John H
Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK.
Centre de Pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, QC, Canada.
Int J Chron Obstruct Pulmon Dis. 2018 Jan 8;13:203-215. doi: 10.2147/COPD.S145285. eCollection 2018.
Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD). However, their relationship remains uncertain. A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD.
Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks. Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured. In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers.
After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [≤0.011]). UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [≤0.001]). Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC. UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (≤0.002) and as a percentage from baseline (≤0.005). There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point.
Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance.
肺过度充气和运动不耐受是慢性阻塞性肺疾病（COPD）的特征。然而，它们之间的关系仍不确定。一项对两项安慰剂对照随机研究的综合分析，分别及联合研究了长效毒蕈碱拮抗剂乌美溴铵（UMEC）和长效β受体激动剂维兰特罗（VI）对COPD患者静态肺过度充气、运动耐力时间（EET）及其关系的影响。
中度至重度稳定期COPD且静息功能残气量>预测值120%的患者被随机分为接受12周的62.5/25μg乌美溴铵/维兰特罗、62.5μg乌美溴铵、25μg维兰特罗或安慰剂治疗。在耐力穿梭步行试验中测量吸气容量（IC）、残气量（RV）、肺总量（TLC）和EET。在这项事后分析中，IC/TLC、RV/TLC和IC被用作肺过度充气标志物。
12周后，与安慰剂相比，当通过IC/TLC自基线的绝对变化测量时（谷值和给药后3小时[≤0.011]），乌美溴铵/维兰特罗、乌美溴铵和维兰特罗在肺过度充气方面均有显著改善。与乌美溴铵和维兰特罗相比，乌美溴铵/维兰特罗在IC/TLC的绝对变化方面有显著改善（谷值和给药后3小时[≤0.001]）。IC的绝对变化以及RV/TLC的百分比变化与安慰剂比较及各治疗组之间比较的统计学显著性与IC/TLC的绝对变化遵循相似模式。在第2天和第12周，与安慰剂相比，乌美溴铵/维兰特罗在EET方面有显著改善，以自基线的秒数变化衡量（≤0.002），以自基线的百分比衡量（≤0.005）。在任何时间点均缺乏证据表明静态肺过度充气的改善与EET之间存在相关性。
尽管双重支气管扩张剂乌美溴铵/维兰特罗在静态肺过度充气标志物方面的改善比乌美溴铵或维兰特罗更大，且在运动耐力方面有显著改善，但未观察到静态肺过度充气与运动耐力之间存在直接关系。
