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.