Outcomes of Targeted Lung Denervation in COPD in AIRFLOW-2 compared to AIRFLOW-3 open-label cohort.

<bold>Rationale:</bold> Targeted Lung Denervation (TLD) is intended to improve clinical stability and reduce the frequency and severity of exacerbations in patients with moderate to very severe COPD. TLD procedural modifications to esophageal management and electrode placement were made after AIRFLOW-2 to improve safety. <bold>Methods:</bold> AIRFLOW-3 is a randomized double-blind sham-controlled trial with an open-label cohort (the first 2 to 3 patients treated at each study site). AIRFLOW-2 also randomized subjects to TLD or sham bronchoscopy in a similar population of symptomatic COPD patients, however, AIRFLOW-3 patients had documented prior year exacerbation history (GOLD E) and greater range of airflow obstruction (25% ≤ FEV1 ≤ 80, FEV1/FVC<0.70) than AIRFLOW-2 patients. Peri-procedural safety and 1-year impact on severe COPD exacerbations were compared between the three cohorts. <bold>Results/Discussion:</bold> 76 AIRFLOW-3 open-label patients underwent TLD, and 82 AIRFLOW-2 patients were randomized (41 TLD, 41 Sham). AIRFLOW-3 patients were like AIRFLOW-2 patients in age 67.0 ± 7.5 vs 63.7 ± 6.8 years, smoking history 53.1 ± 27.3 vs 46.1 ± 26.8 pack-years, FEV1% pred. 39.3 ± 8.2 vs 41.6 ± 7.3, and SGRQ-C scores (57 ± 16.1 vs 53 ± 16.5). AIRFLOW-3 patients had lower rates of GI SAE compared to AIRFLOW-2 TLD patients (AIRFLOW-3 TLD = 1% vs AIRFLOW-2 TLD = 12%), reflecting procedural improvements. TLD patients had lower rates of recurrent hospitalization for COPD exacerbation compared to AIRFLOW-2 sham patients (AIRFLOW-2 TLD = 20%, AIRFLOW-3 TLD = 29% vs AIRFLOW-2 Sham = 70%). TLD procedural modifications implemented in AIRFLOW-3 appear to have improved patient safety with sustained benefit on patient outcomes.