Two-Year Outcomes for the Double-Blind, Randomized, Sham-Controlled Study of Targeted Lung Denervation in Patients with Moderate to Severe COPD: AIRFLOW-2.
Two-Year Outcomes for the Double-Blind, Randomized, Sham-Controlled Study of Targeted Lung Denervation in Patients with Moderate to Severe COPD: AIRFLOW-2.
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DOI：
10.2147/copd.s267409
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发表时间：
2020
影响因子：
2.8
通讯作者：
AIRFLOW-2 Trial Study Group
中科院分区：
文献类型：
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作者：
Valipour A;Shah PL;Herth FJ;Pison C;Schumann C;Hübner RH;Bonta PI;Kessler R;Gesierich W;Darwiche K;Lamprecht B;Perez T;Skowasch D;Deslee G;Marceau A;Sciurba FC;Gosens R;Hartman JE;Conway F;Duller M;Mayse M;Norman HS;Slebos DJ;AIRFLOW-2 Trial Study Group
尽管使用了最佳药物治疗，COPD急性加重仍与临床结局恶化和医疗费用增加相关。一种新型的支气管镜治疗，靶向肺去神经支配（targeted lung denervation，简称DPN），可破坏肺的副交感神经肺神经支配，已被开发用于减少胆碱能亢进的临床后果及其对COPD急性加重的影响。AIRFLOW-2研究评估了随机化后2年，在中重度症状性COPD受试者中，与假支气管镜检查和单独最佳药物治疗相比，最佳药物治疗中添加抗抑郁药的安全性和有效性的持久性。在1：1随机、假对照、双盲多中心研究（AIRFLOW-2）中，使用新型肺去神经系统（Nuvaira，Inc.，USA）。受试者保持盲态，直至其12.5个月随访访视，此时为对照受试者提供了接受双盲治疗的机会。对COPD中度、重度和重度急性加重进行了至首次事件时间分析。82例受试者（FEV 1 41.6±7.4%预测值，50.0%为男性，年龄63.7±6.8岁，24%在前一年呼吸系统住院）接受随机化。治疗后2年，COPD组至首次重度COPD急性加重的时间显著延长（p=0.04，HR=0.38），中度和重度COPD急性加重的衰减趋势相似（p=0.18，HR=0.71）。两组间随机化后2年未发现肺功能或SGRQ-C的显著变化。在一项随机试验中，研究表明，在2年内，AECOPD的严重风险显著降低，具有持久的效果。此外，肺功能和生活质量保持稳定后，肺切除术。NCT 02058459。
COPD exacerbations are associated with worsening clinical outcomes and increased healthcare costs, despite use of optimal medical therapy. A novel bronchoscopic therapy, targeted lung denervation (TLD), which disrupts parasympathetic pulmonary innervation of the lung, has been developed to reduce clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability of safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization. TLD was performed in COPD patients (FEV1 30–60% predicted, CAT≥10 or mMRC≥2) in a 1:1 randomized, sham-controlled, double-blinded multicenter study (AIRFLOW-2) using a novel lung denervation system (Nuvaira, Inc., USA). Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD. A time-to-first-event analysis on moderate and severe and severe exacerbations of COPD was performed. Eighty-two subjects (FEV1 41.6±7.4% predicted, 50.0% male, age 63.7±6.8 yrs, 24% with prior year respiratory hospitalization) were randomized. Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p=0.04, HR=0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p=0.18, HR=0.71). No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups. In a randomized trial, TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Further, lung function and quality of life remained stable following TLD. NCT02058459.