A double-blind, randomized, sham-controlled study of Targeted Lung Denervation in patients with moderate to severe COPD : AIRFLOW-2 One Year Outcomes

Background: Targeted Lung Denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung to reduce clinical consequences of cholinergic hyperactivity. Aim: To evaluate one-year safety and efficacy of TLD + maximal drug therapy compared to sham bronchoscopy + maximal drug therapy in patients with moderate-to-severe, symptomatic COPD. Methods: TLD was performed in COPD patients (FEV1 30-60% pred, CAT≥10 or mMRC≥2) in a double-blind, 1:1 randomized, sham-controlled, multicenter study (NCT02058459) using a novel lung denervation system (Nuvaira, Inc., USA). Patients remained blinded until after their 12 month follow-up visit. The impact of TLD on respiratory hospitalization and severe COPD exacerbations (AECOPD) was analyzed. Results: 82 patients (FEV1 41.6±7.4 %pred., 50.0% male, age 63.7±6.8 yrs, 24% with prior year respiratory hospitalization) were randomized; 74 completed 12-month follow-up. The percentage of patients with at least 1 severe AECOPD was significantly lower in the TLD arm (12%) in comparison to the sham arm 32% (p=0.039). The percentage of patients experiencing any respiratory-related serious adverse event, including pneumonia, was significantly less in the TLD arm (15%) vs. the sham arm (37%) (p=0.042). Of patients with prior year respiratory hospitalization, 20% in the TLD arm compared to 70% in the sham arm were re-hospitalized for AECOPD (p=0.069). Conclusion: In a randomized sham-controlled double-blinded trial, TLD demonstrated a significantly lower rate of severe AECOPD, and respiratory serious adverse events. Furthermore, TLD may lower the rate of re-hospitalization.