Department of Pulmonary Diseases and.
Royal Brompton & Harefield NHS Trust, Chelsea & Westminster Hospital and Imperial College London, London, United Kingdom.
Am J Respir Crit Care Med. 2019 Dec 15;200(12):1477-1486. doi: 10.1164/rccm.201903-0624OC.
Targeted lung denervation (TLD) is a bronchoscopic radiofrequency ablation therapy for chronic obstructive pulmonary disease (COPD), which durably disrupts parasympathetic pulmonary nerves to decrease airway resistance and mucus hypersecretion. To determine the safety and impact of TLD on respiratory adverse events. We conducted a multicenter, randomized, sham bronchoscopy-controlled, double-blind trial in patients with symptomatic (modified Medical Research Council dyspnea scale score, ≥2; or COPD Assessment Test score, ≥10) COPD (FEV, 30-60% predicted). The primary endpoint was the rate of respiratory adverse events between 3 and 6.5 months after randomization (defined as COPD exacerbation, tachypnea, wheezing, worsening bronchitis, worsening dyspnea, influenza, pneumonia, other respiratory infections, respiratory failure, or airway effects requiring therapeutic intervention). Blinding was maintained through 12.5 months. Eighty-two patients (50% female; mean ± SD: age, 63.7 ± 6.8 yr; FEV, 41.6 ± 7.3% predicted; modified Medical Research Council dyspnea scale score, 2.2 ± 0.7; COPD Assessment Test score, 18.4 ± 6.1) were randomized 1:1. During the predefined 3- to 6.5-month window, patients in the TLD group experienced significantly fewer respiratory adverse events than those in the sham group (32% vs. 71%, = 0.008; odds ratio, 0.19; 95% confidence interval, 0.0750-0.4923, = 0.0006). Between 0 and 12.5 months, these findings were not different (83% vs. 90%; = 0.52). The risk of COPD exacerbation requiring hospitalization in the 0- to 12.5-month window was significantly lower in the TLD group than in the sham group (hazard ratio, 0.35; 95% confidence interval, 0.13-0.99; = 0.039). There was no statistical difference in the time to first moderate or severe COPD exacerbation, patient-reported symptoms, or other physiologic measures over the 12.5 months of follow-up. Patients with symptomatic COPD treated with TLD combined with optimal pharmacotherapy had fewer study-defined respiratory adverse events, including hospitalizations for COPD exacerbation.Clinical trial registered with www.clinicaltrials.gov (NCT02058459).
靶向肺去神经支配（TLD）是一种用于慢性阻塞性肺疾病（COPD）的支气管镜下射频消融治疗方法，它可持久破坏副交感神经肺神经，从而降低气道阻力和粘液过度分泌。为了确定 TLD 对呼吸不良事件的安全性和影响。我们在有症状的患者中进行了一项多中心、随机、假支气管镜对照、双盲试验（改良医学研究理事会呼吸困难量表评分≥2；或 COPD 评估测试评分≥10）COPD（FEV，30-60%预测值）。主要终点是随机分组后 3 至 6.5 个月的呼吸不良事件发生率（定义为 COPD 加重、呼吸急促、喘息、支气管炎恶化、呼吸困难恶化、流感、肺炎、其他呼吸道感染、呼吸衰竭或需要治疗干预的气道效应）。通过 12.5 个月保持盲法。82 名患者（50%女性；平均±标准差：年龄 63.7±6.8 岁；FEV，41.6±7.3%预测值；改良医学研究理事会呼吸困难量表评分 2.2±0.7；COPD 评估测试评分 18.4±6.1）按 1:1 随机分组。在预先确定的 3 至 6.5 个月的窗口期内，TLD 组患者经历的呼吸不良事件明显少于 sham 组（32%对 71%， = 0.008；优势比 0.19；95%置信区间 0.0750-0.4923， = 0.0006）。在 0 至 12.5 个月之间，这些发现没有差异（83%对 90%； = 0.52）。在 0 至 12.5 个月的窗口期内，TLD 组患者因 COPD 加重而需要住院的风险明显低于 sham 组（风险比 0.35；95%置信区间 0.13-0.99； = 0.039）。在 12.5 个月的随访期间，TLD 组患者的首次中度或重度 COPD 加重、患者报告的症状或其他生理测量的时间没有统计学差异。接受 TLD 联合最佳药物治疗的有症状 COPD 患者发生研究定义的呼吸不良事件较少，包括因 COPD 加重而住院。临床试验在 www.clinicaltrials.gov 上注册（NCT02058459）。
