Mechanism of action of targeted lung denervation in chronic obstructive pulmonary disease
File(s)
Author(s)
Conway, Francesca
Type
Thesis
Abstract
Background: Chronic Obstructive Pulmonary Disease (COPD) is a common, debilitating disease affecting the lungs, characterised by airflow obstruction and punctuated by exacerbations. Targeted Lung Denervation (TLD) is a novel bronchoscopic treatment being investigated for COPD, which mechanically disrupts the parasympathetic nerve supply to the airways, and appears to reduce exacerbations.
Aim: Assess effects and mechanism of action of TLD in COPD on clinical, physiological, structural and inflammatory outcomes.
Methods: 33 patients with COPD and frequent exacerbations were included and recruited to the AIRFLOW-3 study and where possible AIRFLOW-3 mechanism of action study. Patients undertook assessments before and after randomised, double-blinded TLD or sham bronchoscopy. Clinical evaluations included quality of life, symptom, exercise capacity and exacerbation assessments. Physiological measures comprised spirometry, lung volume, small airways and bronchial provocation testing. Structural evaluations were completed on CT thoraces. Inflammatory analyses were performed on bronchoscopic samples.
Results: Patients post-TLD had stable spirometry and lung volumes, with a significant difference in change to the sham group in post-BD FVC which deteriorated in the sham group. Airways resistance post-TLD significantly improved from baseline. Bronchial hyperreactivity decreased post-TLD (not statistically significant). Structural lung parameters were stable in the TLD group, despite a deterioration in -950HU densitometry post-sham. Patients had a clinically meaningful improvement in mean CAT score post-TLD. Both groups showed significant reductions in exacerbations post-procedure. Sham patients had increased neutrophil microvesicles (associated with disease severity in COPD) over time, whereas TLD neutrophil microvesicles remained stable.
Conclusions: In this small cohort, we demonstrate some novel, positive outcomes regarding the effects and mechanism of action of TLD in COPD. This work adds to the literature suggesting that TLD is a promising new treatment for COPD with some signals as to which patients may respond best. The AIRFLOW-3 trial will discover further information and its results are eagerly anticipated.
Aim: Assess effects and mechanism of action of TLD in COPD on clinical, physiological, structural and inflammatory outcomes.
Methods: 33 patients with COPD and frequent exacerbations were included and recruited to the AIRFLOW-3 study and where possible AIRFLOW-3 mechanism of action study. Patients undertook assessments before and after randomised, double-blinded TLD or sham bronchoscopy. Clinical evaluations included quality of life, symptom, exercise capacity and exacerbation assessments. Physiological measures comprised spirometry, lung volume, small airways and bronchial provocation testing. Structural evaluations were completed on CT thoraces. Inflammatory analyses were performed on bronchoscopic samples.
Results: Patients post-TLD had stable spirometry and lung volumes, with a significant difference in change to the sham group in post-BD FVC which deteriorated in the sham group. Airways resistance post-TLD significantly improved from baseline. Bronchial hyperreactivity decreased post-TLD (not statistically significant). Structural lung parameters were stable in the TLD group, despite a deterioration in -950HU densitometry post-sham. Patients had a clinically meaningful improvement in mean CAT score post-TLD. Both groups showed significant reductions in exacerbations post-procedure. Sham patients had increased neutrophil microvesicles (associated with disease severity in COPD) over time, whereas TLD neutrophil microvesicles remained stable.
Conclusions: In this small cohort, we demonstrate some novel, positive outcomes regarding the effects and mechanism of action of TLD in COPD. This work adds to the literature suggesting that TLD is a promising new treatment for COPD with some signals as to which patients may respond best. The AIRFLOW-3 trial will discover further information and its results are eagerly anticipated.
Version
Open Access
Date Issued
2023-03-31
Date Awarded
2024-03-01
Copyright Statement
Attribution-Non Commercial-No Derivatives 4.0 International Licence (CC BY-NC-ND)
Advisor
Shah, Pallav
Wedzicha, Jadwiga
Sponsor
Medical Research Council (Great Britain)
National Heart and Lung Institute
Nuvaira (Firm)
Grant Number
Medical Research Council Pre-Doctoral Fellowship Grant Ref: MR/V00171X/1
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)