Mintz Matthew, Barjaktarevic Igor, Mahler Donald A, Make Barry, Skolnik Neil, Yawn Barbara, Zeyzus-Johns Bree, Hanania Nicola A
George Washington University School of Medicine and Health Sciences, Washington, DC.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Mayo Clin Proc. 2023 Feb;98(2):301-315. doi: 10.1016/j.mayocp.2022.09.007.
In 2020, chronic obstructive pulmonary disease (COPD) was the fifth leading cause of death in the United States excluding COVID-19, and its mortality burden has been rising since the 1980s. Smoking cessation, long-term oxygen therapy, noninvasive ventilation, and lung volume reduction surgery have had a beneficial effect on mortality; however, until recently, the effects of pharmacologic therapies on all-cause mortality have been unclear. Inhaled pharmacologic treatments for patients with COPD include combinations of long-acting muscarinic receptor antagonists (LAMAs), long-acting-βagonists (LABAs), and inhaled corticosteroids (ICS). The recent IMPACT and ETHOS clinical trials reported mortality benefits with ICS/LAMA/LABA triple therapy compared with LAMA/LABA dual therapy. In IMPACT, fluticasone furoate/umeclidinium/vilanterol therapy significantly reduced the risk of on-/off-treatment all-cause mortality vs umeclidinium/vilanterol (hazard ratio, 0.72; 95% CI, 0.53 to 0.99; P=.042). The ETHOS trial found a reduction in the risk of on-/off-treatment all-cause mortality in patients treated with budesonide/glycopyrrolate/formoterol vs glycopyrrolate/formoterol (hazard ratio, 0.51 [0.33 to 0.80]; nominal P=.0035). Both trials included populations of patients with symptomatic COPD at high risk of future exacerbations, and a post hoc analysis of the final retrieved vital status data suggested that the observed mortality benefits are conferred by the ICS component. In conclusion, triple therapy reduces the risk of mortality in patients with symptomatic COPD characterized by moderate or severe airflow obstruction and a recent history of moderate or severe exacerbations. This benefit is likely to be driven by reductions in exacerbations. Future research efforts should focus on improving the long-term prognosis of patients living with COPD.
2020年，慢性阻塞性肺疾病（COPD）是美国除COVID-19外的第五大死因，自20世纪80年代以来其死亡负担一直在上升。戒烟、长期氧疗、无创通气和肺减容手术对死亡率有有益影响；然而，直到最近，药物治疗对全因死亡率的影响仍不明确。COPD患者的吸入性药物治疗包括长效毒蕈碱受体拮抗剂（LAMA）、长效β受体激动剂（LABA）和吸入性糖皮质激素（ICS）联合使用。最近的IMPACT和ETHOS临床试验报告称，与LAMA/LABA双联疗法相比，ICS/LAMA/LABA三联疗法可降低死亡率。在IMPACT试验中，糠酸氟替卡松/乌美溴铵/维兰特罗疗法与乌美溴铵/维兰特罗相比，显著降低了治疗期间/治疗后全因死亡率的风险（风险比，0.72；95%置信区间，0.53至0.99；P = 0.042）。ETHOS试验发现，布地奈德/格隆溴铵/福莫特罗治疗的患者与格隆溴铵/福莫特罗治疗的患者相比，治疗期间/治疗后全因死亡率风险降低（风险比，0.51[0.33至0.80]；名义P = 0.0035）。两项试验均纳入了有症状的COPD患者群体，这些患者未来有较高的急性加重风险，对最终检索到的生命状态数据进行的事后分析表明，观察到的死亡率益处是由ICS成分带来的。总之，三联疗法可降低以中度或重度气流受限以及近期有中度或重度急性加重病史为特征的有症状COPD患者的死亡风险。这种益处可能是由急性加重的减少所驱动的。未来的研究应致力于改善COPD患者的长期预后。
