Supplementary Material for: Bronchial Cryo-Denervation for Severe Asthma：A Pilot Study

Introduction
Targeting the parasympathetic nervous system innervating airway with pharmacologic products has been proved to improve the clinical outcomes of severe asthma. Bronchial cryo-denervation (BCD) is a novel non-pharmacologic treatment for severe asthma using an endobronchial cryo-balloon administered via bronchoscopy to denervate parasympathetic pulmonary nerves. Preclinical studies have demonstrated that BCD significantly disrupted vagal innervation to the lung.
Methods
A total of 15 patients with severe asthma were enrolled in this prospective, single-center pilot study. Patients underwent bifurcated BCD treatment at 30-day interval after baseline assessment. Follow-up through 12 months included assessment of adverse event, technical feasibility, and changes in pulmonary function, asthma control questionaire-7 (ACQ-7) and asthma control test (ACT).
Results
BCD was performed in all 15 severe asthma patients, with technical feasibility of 96.7%. There were no device-related and 2 procedure-related serious adverse events through 12 months, which resolved without sequelae. The most frequent nonserious procedure-related adverse event was increased cough in 60% (9 of 15) patients. Pulmonary function remained unchanged and significant improvements from baseline of ACQ-7 (mean, -1.19, p=0.0032) and ACT (mean, 3.18, p=0.0011) scores were observed since the first month's follow-up after a single lung airway treatment, with similar trends till the end of 12-month follow-up.
Conclusion
This study provides the first clinical evidence of the safety, feasibility, and initial efficacy of BCD in patients with severe asthma.

引言
通过药物靶向支配气道的副交感神经系统，已被证实可改善重症哮喘的临床结局。支气管冷冻去神经术（Bronchial Cryo-denervation, BCD）是一种针对重症哮喘的新型非药物治疗手段，其通过支气管镜递送支气管内冷冻球囊，以阻断肺部副交感神经的神经支配。临床前研究已证实，BCD可显著破坏肺部的迷走神经支配。
方法
本前瞻性单中心初步研究共纳入15例重症哮喘患者。患者在基线评估后，以30天为间隔接受分叉式BCD治疗。为期12个月的随访内容包括不良事件评估、技术可行性评估，以及肺功能、哮喘控制问卷-7（Asthma Control Questionnaire-7, ACQ-7）和哮喘控制测试（Asthma Control Test, ACT）的变化情况。
结果
15例重症哮喘患者均顺利完成BCD治疗，技术可行性达96.7%。随访12个月期间，未发生与设备相关的严重不良事件，仅出现2例与操作相关的严重不良事件，上述事件均无后遗症地完全缓解。最常见的非严重操作相关不良事件为咳嗽加重，共累及60%（15例中的9例）的患者。单次肺部气道治疗后首个月的随访结果显示，患者肺功能无明显变化，但哮喘控制问卷-7（ACQ-7）评分（均值为-1.19，p=0.0032）与哮喘控制测试（ACT）评分（均值为3.18，p=0.0011）较基线均出现显著改善，且该改善趋势持续至12个月随访结束。
结论
本研究首次提供了BCD应用于重症哮喘患者的安全性、可行性及初步疗效的临床证据。