Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes

Christophe Pison,Jorine E Hartman,Anna Mayr,Alexander D Peterson,Romain Kessler,Gaetan Deslee,Wim Janssens,Vincent Ninane,Justin L Garner,Dirk-Jan Slebos,Pallav L Shah,Martin Mayse,Thierry Perez,Arschang Valipour,Bruno Degano

doi:10.1186/s12931-021-01664-5

Abstract

BackgroundTargeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up.MethodsTLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life.ResultsThree-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed.ConclusionTLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

Highlights

Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity
The pathophysiology of Chronic obstructive pulmonary disease (COPD) is characterized by increased autonomic nervous system input to the lung and sensory signaling from the lung mediated by the vagus nerve
Safety Over the 2nd and 3rd years of follow-up, there were no new gastrointestinal serious adverse events related to the procedure or device (SAEs; Table 1)

Summary

Introduction

Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. COPD is characterized by persistent limitation of airflow and respiratory symptoms resulting from abnormalities in the lungs at the level of the alveoli, airways, or both [1, 2]. Anticholinergic agents relax airway smooth muscle, decrease mucus hypersecretion, and improve COPD-related symptoms [1, 8]. Patients continue to exacerbate while on medical therapy, with only about 50% of patients treated with a long acting muscarinic antagonist experiencing a clinically significant benefit [14] and up to 70% of patients experiencing a COPD exacerbation while on optimal medical therapy [11]

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Discussion

Conclusion