1 Institute for Diagnostic and Interventional Radiology.
2 German Center for Lung Research (BREATH), Hannover, Germany.
Am J Respir Crit Care Med. 2019 May 1;199(9):1086-1096. doi: 10.1164/rccm.201805-0995OC.
In the CLAIM study, dual bronchodilation with indacaterol/glycopyrronium (IND/GLY) significantly reduced hyperinflation, which translated into improved cardiac function, measured by left ventricular end-diastolic volume and cardiac output. Pulmonary microvascular blood flow (PMBF) is reduced in chronic obstructive pulmonary disease (COPD); however, the effect of reduced lung hyperinflation on PMBF remains unknown. To determine the effect of lung deflation with IND/GLY on PMBF and regional pulmonary ventilation using magnetic resonance imaging (MRI) in hyperinflated patients with COPD. In this double-blind, randomized, two-period crossover study, gadolinium-enhanced MRI and phase-resolved functional lung MRI were used to measure PMBF and regional ventilation, respectively, in patients with COPD receiving IND/GLY versus placebo. Sixty-two patients were randomized to receive once-daily IND/GLY (110/50 μg) for 14 days, followed by 14 days of placebo, or vice versa. Treatment periods were separated by a 14-day washout. Sixty patients were included in the per-protocol analysis. MRI measurements showed significant improvements in total PMBF ( = 0.006) and regional PMBF ( values for individual lobes were between 0.004 and 0.022) in response to IND/GLY versus placebo. Regional ventilation was also significantly improved with IND/GLY, as evidenced by a 12.4% increase versus placebo ( = 0.011), a 14.3% relative decrease in ventilation defect percentage of nonventilated/hypoventilated lung tissue (cutoff was defined as 0.075 regional ventilation; = 0.0002), and a 15.7% reduction in the coefficient of variation of regional ventilation compared with placebo ( < 0.0001). Pharmacologic intervention with IND/GLY improves pulmonary microvascular blood flow and regional ventilation in patients with COPD with hyperinflation. Clinical trial registered with www.clinicaltrials.gov (NCT02442206).
在 CLAIM 研究中，茚达特罗/格隆溴铵（IND/GLY）的双重支气管扩张作用显著减少了肺气肿，这转化为左心室舒张末期容积和心输出量等心脏功能的改善。在慢性阻塞性肺疾病（COPD）中，肺微血管血流（PMBF）减少；然而，减少的肺过度充气对 PMBF 的影响尚不清楚。为了确定使用磁共振成像（MRI）在 COPD 中过度充气的患者中使用 IND/GLY 进行肺排气对 PMBF 和区域性肺通气的影响。在这项双盲、随机、两周期交叉研究中，使用钆增强 MRI 和相位分辨功能肺 MRI 分别测量 COPD 患者接受 IND/GLY 与安慰剂时的 PMBF 和区域性通气。62 名患者被随机分为每天一次接受 IND/GLY（110/50μg）治疗 14 天，然后接受安慰剂治疗 14 天，或者反之亦然。治疗期之间间隔 14 天洗脱期。60 名患者被纳入方案分析。MRI 测量显示，与安慰剂相比，总 PMBF（ = 0.006）和区域性 PMBF（各个叶的 值在 0.004 至 0.022 之间）显著改善。IND/GLY 还显著改善了区域性通气，表现为与安慰剂相比增加了 12.4%（ = 0.011），非通气/低通气肺组织的通气缺陷百分比相对减少了 14.3%（定义为 0.075 区域性通气； = 0.0002），与安慰剂相比，区域性通气的变异系数降低了 15.7%（ < 0.0001）。IND/GLY 的药物干预改善了 COPD 伴肺气肿患者的肺微血管血流和区域性通气。在 www.clinicaltrials.gov 上注册的临床试验（NCT02442206）。
