Metered cryospray for the treatment of patients with chronic obstructive pulmonary disease with chronic bronchitis - Mechanism of action. A Multicentre Randomised Controlled Clinical Trial

<bold>Introduction:</bold> Metered cryospray (MCS) is a bronchoscopic treatment that uses liquid nitrogen to ablate, and repopulate the bronchial epithelium with a healthier phenotype, in patients with COPD with chronic bronchitis (CB). <bold>Aims:</bold> To investigate the mechanism of action of MCS in patients with COPD with CB. <bold>Methods:</bold> A multicentre, randomised, blinded, sham-controlled trial, in adult patients with COPD with CB, to receive MCS plus standard care, or sham-procedure plus standard care. Serial clinical characterisations and endobronchial samplings were performed. NCT: 03892694 <bold>Results:</bold> 32 patients were randomly assigned to MCS (n=15) or sham-procedure (n=17). There was no significant between groups difference in Goblet cell density (60.7 ± 146.8 cells per mm basement membrane; n=31; p=0.26) at 6-months, relative to baseline. A significant between-group improvement in SGRQ total score (−9.6 points SD ± 11.1; n=31; p=0.02) was observed in the MCS group at 6-months, relative to baseline. A significant reduction in expiratory LAA at -856 HU was demonstrated between groups (−8.6 ± 4.6 %; n=27; p=<0.001), and longitudinally in the MCS group (−4.4 ± 3.8 %; n=13; p=0.001) at 6-months, relative to baseline. Three serious adverse events (SAE) were reported in 2 patients in the sham-procedure group. No SAE were reported in the MCS group. <bold>Conclusions:</bold> MCS was not found to reduce Goblet cell density in patients with COPD with CB, however, the clinical efficacy of the procedure, which could relate to a reduction in air trapping, and of epithelial resurfacing as a treatment modality is demonstrated.