The role of the epithelium in chronic obstructive pulmonary disease and the effects of cryoablative intervention
File(s)
Author(s)
Orton, Chris
Type
Thesis
Abstract
Background and rationale
Chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB) are characterised by cough, dyspnoea, and sputum productivity, with therapeutic options limited. Metered cryospray (MCS) is a bronchoscopic treatment that delivers titrated applications of liquid nitrogen to the airways, to enact the controlled ablation and repopulation of the bronchial epithelium with healthier tissues.
Aim
To investigate the effects of bronchial epithelial resurfacing with MCS in patients with COPD and CB, on clinical, histopathological and cellular parameters, to achieve a unified mechanistic translational narrative.
Methods
The open label, FEASIBILITY study (NCT: 02483637) investigated the feasibility and safety of MCS in patients with COPD with CB. The randomised, blinded, sham-controlled MOA study (NCT: 03892694) investigated the mechanistic effects of MCS, in patient with COPD with CB. Clinical characterisation and endobronchial sampling were performed at baseline and post-MCS in each study.
Results
In the FEASIBILITY study, a -6.4 point (SD ± 14.4; paired t test; n=34; p=0.01) change in SGRQ total score was demonstrated at 3-months post-MCS, 34 patients (97 %) completed all three MCS treatments, and a total of 329 adverse events were reported, while no severe procedure or device-related events occurred. In the MOA study, no significant between arms differences in the histological assessment of goblet or basal cell counts were identified in cryobiopsy sections, however, a -9.6 point (unpaired t test; n=31; p=0.02) difference in SGRQ total score, was demonstrated at 6-months post-MCS, relative to baseline.
Discussion
These studies support the efficacy of MCS treatment in patients with COPD, with CB, investigated to 6-months in a blinded capacity, and to 36-months in an open-labelled context, however, the mechanisms through which MCS works remain elusive. These findings support the completion of further studies, and drive a potential translation to the clinical setting.
Chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB) are characterised by cough, dyspnoea, and sputum productivity, with therapeutic options limited. Metered cryospray (MCS) is a bronchoscopic treatment that delivers titrated applications of liquid nitrogen to the airways, to enact the controlled ablation and repopulation of the bronchial epithelium with healthier tissues.
Aim
To investigate the effects of bronchial epithelial resurfacing with MCS in patients with COPD and CB, on clinical, histopathological and cellular parameters, to achieve a unified mechanistic translational narrative.
Methods
The open label, FEASIBILITY study (NCT: 02483637) investigated the feasibility and safety of MCS in patients with COPD with CB. The randomised, blinded, sham-controlled MOA study (NCT: 03892694) investigated the mechanistic effects of MCS, in patient with COPD with CB. Clinical characterisation and endobronchial sampling were performed at baseline and post-MCS in each study.
Results
In the FEASIBILITY study, a -6.4 point (SD ± 14.4; paired t test; n=34; p=0.01) change in SGRQ total score was demonstrated at 3-months post-MCS, 34 patients (97 %) completed all three MCS treatments, and a total of 329 adverse events were reported, while no severe procedure or device-related events occurred. In the MOA study, no significant between arms differences in the histological assessment of goblet or basal cell counts were identified in cryobiopsy sections, however, a -9.6 point (unpaired t test; n=31; p=0.02) difference in SGRQ total score, was demonstrated at 6-months post-MCS, relative to baseline.
Discussion
These studies support the efficacy of MCS treatment in patients with COPD, with CB, investigated to 6-months in a blinded capacity, and to 36-months in an open-labelled context, however, the mechanisms through which MCS works remain elusive. These findings support the completion of further studies, and drive a potential translation to the clinical setting.
Version
Open Access
Date Issued
2022-10-20
Date Awarded
01/07/2023
License URL
Advisor
Shah, Pallav
Bhavsar, Pankaj
Chung, Kian Fan
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)