Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial
Authors: Dirk-Jan Slebos, Pallav L. Shah, Felix J. F. Herth, Christophe Pison, Christian Schumann, Ralf-Harto Hübner, Peter I. Bonta, Romain Kessler, Wolfgang Gesierich, Kaid Darwiche, Bernd Lamprecht, Thierry Perez, Dirk Skowasch, Gaetan Deslee, Armelle Marceau, Frank C. Sciurba, Reinoud Gosens, Jorine E. Hartman, Karthi Srikanthan, Marina Duller, Arschang Valipour, Arschang Valipour, Christine Abele, Irene Firlinger, Kiran Kothakuzhakal, Marina Duller, Bernd Lamprecht, Roland Kropfmueller, Kornelia Holzmann, Sandra Rathmeier, Ralf Hubner, Leonore Erdmann, Bettina Temmesfeld-Wollbrück, Christoph Ruwwe Glösenkamp, Wolfgang Gesierich, Frank Reichenberger, Christa Niehaus, Felix Herth, Ralf Eberhardt, Daniela Gompelmann, Brigitte Rump, Kaid Darwiche, Stephan Eisenmann, Ulrike Kaiser, Birte Schwarz, Ulrike Sampel, Christian Schumann, Robert Kaiser, Kathryn Schumann-Stoiber, Dirk Skowasch, Sabine Ring, Christophe Pison, Amandine Briault, Francois Arbib, Marie Jondot, Thierry Perez, Clement Fournier, Regis Matran, Michele Catto, Nathalie Bautin, Virginie De Broucker, Marie Willemin, Anne Prevotat, Ludivine Wemeau, Alice Gicquello, Morgane Foulon, Hasna Camara, Gaetan Deslee, Herve Vallerand, Sandra Dury, Delphine Gras, Margaux Bonnaire-Verdier, Romain Kessler, Sandrine Hirschi, Michele Porzio, Tristan Degot, Mathieu Canuet, Armelle Schuller, Julien Stauder, Sahra Ali Azouaou, Armelle Marceau, Hervé Mal, Yolande Costa, Pallav L. Shah, Justin Garner, Karthi Srikanthan, Cielito Caneja, John Thornton, Dirk-Jan Slebos, Nick Ten Hacken, Jorine Hartman, Karin Klooster, Sonja Augustijn, Peter Bonta, Jouke Annema, Marianne van de Pol, Annika Goorsenberg
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Targeted lung denervation (TLD) is a bronchoscopic radiofrequency ablation therapy for chronic obstructive pulmonary disease (COPD), which durably disrupts parasympathetic pulmonary nerves to decrease airway resistance and mucus hypersecretion.Objectives: To determine the safety and impact of TLD on respiratory adverse events.Methods: We conducted a multicenter, randomized, sham bronchoscopy-controlled, double-blind trial in patients with symptomatic (modified Medical Research Council dyspnea scale score, ≥2; or COPD Assessment Test score, ≥10) COPD (FEV1, 30-60% predicted). The primary endpoint was the rate of respiratory adverse events between 3 and 6.5 months after randomization (defined as COPD exacerbation, tachypnea, wheezing, worsening bronchitis, worsening dyspnea, influenza, pneumonia, other respiratory infections, respiratory failure, or airway effects requiring therapeutic intervention). Blinding was maintained through 12.5 months.Measurements and Main Results: Eighty-two patients (50% female; mean ± SD: age, 63.7 ± 6.8 yr; FEV1, 41.6 ± 7.3% predicted; modified Medical Research Council dyspnea scale score, 2.2 ± 0.7; COPD Assessment Test score, 18.4 ± 6.1) were randomized 1:1. During the predefined 3- to 6.5-month window, patients in the TLD group experienced significantly fewer respiratory adverse events than those in the sham group (32% vs. 71%, P = 0.008; odds ratio, 0.19; 95% confidence interval, 0.0750-0.4923, P = 0.0006). Between 0 and 12.5 months, these findings were not different (83% vs. 90%; P = 0.52). The risk of COPD exacerbation requiring hospitalization in the 0- to 12.5-month window was significantly lower in the TLD group than in the sham group (hazard ratio, 0.35; 95% confidence interval, 0.13-0.99; P = 0.039). There was no statistical difference in the time to first moderate or severe COPD exacerbation, patient-reported symptoms, or other physiologic measures over the 12.5 months of follow-up.Conclusions: Patients with symptomatic COPD treated with TLD combined with optimal pharmacotherapy had fewer study-defined respiratory adverse events, including hospitalizations for COPD exacerbation.Clinical trial registered with www.clinicaltrials.gov (NCT02058459).