Late Breaking Abstract - Safety and Efficacy of Bronchoscopic cryospray therapy for refractory or Unexplained chronic cough : Preclinical investigations and First-in-human trial

<bold>Background:</bold> Refractory chronic cough (RCC) is a common respiratory disorder with huge disease burden but its effective treatments are still lacking. Recently, cryospray therapy (SCT) can ablate abnormal epithelium and shows potential in improving cough. <bold>Objective:</bold> This study aims to evaluate the efficacy and safety of SCT in animal model and patients with RCC, as well as mechanism exploration. <bold>Methods:</bold> Preclinical feasibility and mechanisam of SCT was explored on the canine model Ten patients with RCC were included in a prospective trial and will be followed up for 3 months after SCT. Primary outcomes were efficacy (severity, quality of life, sensitivity) and safety. Airway remodeling, density of nerves/cough receptors and neurogenic inflammation were also assessed. <bold>Results:</bold> Preclinical results showed that SCT is safe in canine bronchi (n=18), and the cough threshold increased after treatment (p<0.05). All patients successfully underwent the SCT, each lasting 16.5±5.04 min. No adverse events were observed within 3 months after SCT. Clinically meaningful improvements were found in all cough-related outcome(all p<0.01), including severity (VAS score: -33.5±19.2), cough-related quality of life questionnaires (LCQ:3.2±2.5;CET:-5.3±4.6) and sensitivity (capsaicin test, logC5:0.49±0.4). The density of nerves, cough receptors (TRPV1, TRPV4, etc) and goblet cells of airway epithelial were significantly improved. Airway remodeling and neurogenic inflammation were also improved after SCT. <bold>Conclusions:</bold> This is the first translational study to demonstrate that SCT is safe, feasible and associated with clinically meaningful improvements in RCC.