B24-15 Targeted Lung Denervation in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis of Randomized Trials

Rationale Cholinergic hyperactivity contributes to airflow limitation and exacerbation risk in COPD. Targeted lung denervation (TLD)—a bronchoscopic radiofrequency ablation of parasympathetic pulmonary nerves—has emerged as a novel adjunctive therapy. Individual randomized trials (AIRFLOW program) have reported promising reductions in exacerbations, but pooled efficacy and safety data are lacking. Methods A systematic review and meta-analysis were conducted of all randomized controlled trials evaluating TLD in moderate-to-severe COPD. Searches of PubMed, Embase, and CENTRAL identified 5 studies, of which 2 (AIRFLOW-2 RCT and its 2-year follow-up) met inclusion criteria for pooled analysis while all 5 were considered for synthetic analysis. Random-effects models (DerSimonian-Laird) were applied for continuous (mean difference, MD) and binary outcomes (risk ratio, RR) with 95% confidence intervals (CIs). Primary outcome: severe COPD exacerbations. Secondary outcomes: moderate/severe exacerbations, respiratory adverse events, FEV1, and SGRQ change. Results Across 164 patients, TLD significantly reduced the risk of severe COPD exacerbations (pooled HR = 0.37; 95% CI 0.20-0.69; p = 0.002; I² = 0%), corresponding to a 63% relative risk reduction. Moderate/severe exacerbations trended lower (HR = 0.69; 95% CI 0.44-1.09). Early respiratory adverse events (≤ 90 days) were significantly less frequent with TLD (RR = 0.45; 95% CI 0.28-0.72; p = 0.001). No difference was observed in FEV1 change (MD = +25 mL; p = 0.64) or SGRQ score (MD = -0.8; p = 0.71). No procedure-related deaths occurred. Long-term follow-up confirmed durable safety and stable lung function. Conclusions TLD is a safe, minimally invasive bronchoscopic therapy that significantly reduces severe COPD exacerbations without impairing lung function or quality of life. These findings support cholinergic pathway modulation as a viable adjunct to maximal inhaled therapy. Ongoing AIRFLOW-3 results will be pivotal in defining clinical integration of TLD into COPD management algorithms.