Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Centre Giessen and Marburg, Philipps-Universität Marburg, German Centre for Lung Research (DZL), Baldingerstraße, 35043, Marburg, Germany.
GSK, Brentford, Middlesex, UK.
Respir Res. 2021 Oct 28;22(1):279. doi: 10.1186/s12931-021-01859-w.
In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids.
The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.5/25 µg once daily, umeclidinium 62.5 µg once daily, or salmeterol 50 µg twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1 s (FEV) of ≥ 12% and ≥ 200 mL 10-30 min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21-24, and rescue medication use (puffs/day) over Weeks 1-24. Analyses were conducted across the full range of reversibility (-850-896 mL); however, results are presented for the range -100-400 mL because there were few participants with values outside this range.
The mean (standard deviation) reversibility was 130 mL (156) and the median was 113 mL; 625/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV, SAC-TDI, E-RS and rescue medication use with umeclidinium/vilanterol with higher reversibility. Improvements in trough FEV and reductions in rescue medication use were greater with umeclidinium/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium/vilanterol versus monotherapy in the middle of the reversibility range.
FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.
在慢性阻塞性肺疾病（COPD）患者中，短期支气管扩张剂可逆性与长期支气管扩张剂反应之间的关系尚不清楚。在这里，我们研究了在不接受吸入皮质类固醇的低加重风险的 COPD 患者中，长效支气管扩张剂的疗效是否与气流受限的可逆性相关。
这项双盲、双模拟 EMAX 试验将患者随机分配至乌美溴铵/维兰特罗 62.5/25μg 每日 1 次、乌美溴铵 62.5μg 每日 1 次或沙美特罗 50μg 每日 2 次。在筛选时测量沙丁胺醇的支气管扩张剂可逆性，定义为用力呼气量 1 秒（FEV1）增加≥12%和≥200 mL，在沙丁胺醇后 10-30 分钟。事后，使用筛选时的可逆性程度（mL）作为连续变量进行分数多项式（FP）建模，以研究其与从基线到第 24 周时的平均变化之间的关系，第 21-24 周的自我管理计算机化过渡呼吸困难指数（SAC-TDI）和第 1-24 周的急救药物使用（吸数/天）。分析在整个可逆性范围（-850-896 mL）内进行；然而，由于在此范围之外的参与者很少，因此仅报告了-100-400 mL 的结果。
平均（标准差）可逆性为 130 mL（156），中位数为 113 mL；625/2425（26%）患者具有可逆转性。具有较高可逆性的患者，其 FEV1 谷值、SAC-TDI、E-RS 和急救药物使用的改善均有趋势。在整个可逆性范围内，乌美溴铵/维兰特罗与单药治疗相比，FEV1 谷值和急救药物使用减少均更大。在可逆性范围的中间，与单药治疗相比，乌美溴铵/维兰特罗治疗可观察到 SAC-TDI 和 E-RS 总分的更大改善。
FP 分析表明，具有更高可逆性水平的患者对支气管扩张剂的肺功能和症状改善更大。在整个可逆性范围内，乌美溴铵/维兰特罗与单药治疗相比，肺功能和急救药物使用的改善更大，这表明双支气管扩张剂乌美溴铵/维兰特罗可能是治疗有症状的 COPD 患者的合适治疗方法，而与他们的可逆性水平无关。
