Randomized Sham-controlled Trial of Targeted Lung Denervation in Patients with Chronic Obstructive Pulmonary Disease (AIRFLOW-3).

Objective: To evaluate the impact of TLD on COPD exacerbations compared with optimal medical treatment.

目标：评估 TLD 对比最佳药物治疗对 COPD 急性加重的影响。

Methods: AIRFLOW-3 patients were symptomatic (COPD Assessment Test score ⩾10) with moderate to very severe airflow obstruction (FEV1 ≥25% but ⩽80% predicted) and Global Initiative for Chronic Obstructive Lung Disease E status (at least two moderate or one severe exacerbation during the previous 12 mo).

方法：AIRFLOW-3患者有症状（COPD评估测试得分⩾10），伴有中度至非常严重的气流阻塞（FEV1⩾25%但⩽80%预测值），以及全球慢性阻塞性肺疾病倡议（GOLD）E状态（过去12个月内至少有两次中度或一次重度加重）。

The primary endpoint was a comparison of time to the first moderate or severe COPD exacerbation through 12 months between the treatment (TLD plus optimal medical treatment) and sham control groups (sham procedure plus optimal medical treatment).

主要终点是比较治疗组（TLD加最佳药物治疗）与安慰剂对照组（安慰剂程序加最佳药物治疗）在12个月内首次出现中度或重度COPD加重的时间。

Secondary endpoints included the rate of severe COPD exacerbations, change in quality of life (St. George's Respiratory Questionnaire for COPD and Short Form-36 questionnaire), change in lung function (FVC, FEV1, residual volume), and change in COPD Assessment Test score.

次要终点包括严重COPD加重的比率、生活质量的变化（圣乔治呼吸问卷COPD版和简短形式-36问卷）、肺功能的变化（FVC、FEV1、残气量）以及COPD评估测试评分的变化。

Measurements and Main Results: 388 patients were randomized at a 1:1 ratio at 32 sites.

测量和主要结果：在32个地点，388名患者以1:1的比例进行了随机分组。

There was no difference between treatment and the sham procedure in terms of the probability of participants having a moderate or severe COPD exacerbation (hazard ratio, 1.268; 95% confidence interval, 0.988-1.628).

在接受治疗的患者与接受假手术的患者中，发生中度或重度慢阻肺急性加重的概率没有差异（风险比，1.268；95%置信区间，0.988-1.628）。

At 1 year, the TLD group had less dyspnea (>1-point improvement in Transitional Dyspnea Index, 35.4 vs. 24.1%; P = 0.021) compared with the sham group.

在1年时，TLD组与假手术组相比，呼吸困难有所减轻（过渡性呼吸困难指数改善超过1分，35.4%对比24.1%；P = 0.021）。

Post hoc analyses suggests that failure to reach the primary endpoint was driven by an insufficient number of patients exhibiting an airway-predominant phenotype (lung hyperinflation without significant emphysema).

事后分析表明，未能达到主要终点是由于表现出气道主导表型（肺过度膨胀而无显著肺气肿）的患者数量不足。

Conclusions: AIRFLOW-3 failed to meet its primary endpoint.

结论：AIRFLOW-3未能达到其主要终点。

However, post hoc analyses identified a responder profile; a prospective multicenter randomized controlled trialis being designed to confirm these findings.

然而，事后分析确定了一种反应者特征；目前正在设计一项前瞻性多中心随机对照试验以确认这些发现。

Clinical trial registered with www.clinicaltrials.gov (NCT03639051).

临床试验已在www.clinicaltrials.gov注册（NCT03639051）。