{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:55:29Z","timestamp":1788864929608,"version":"build-2803163510"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":2285,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the safety and impact of TLD on respiratory adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a multicenter, randomized, sham bronchoscopy\u2013controlled, double-blind trial in patients with symptomatic (modified Medical Research Council dyspnea scale score, \u22652; or COPD Assessment Test score, \u226510) COPD (FEV1, 30\u201360% 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Eighty-two patients (50% female; mean\u2009\u00b1\u2009SD: age, 63.7\u2009\u00b1\u20096.8 yr; FEV1, 41.6\u2009\u00b1\u20097.3% predicted; modified Medical Research Council dyspnea scale score, 2.2\u2009\u00b1\u20090.7; COPD Assessment Test score, 18.4\u2009\u00b1\u20096.1) 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\u2009=\u20090.008; odds ratio, 0.19; 95% confidence interval, 0.0750\u20130.4923, P\u2009=\u20090.0006). Between 0 and 12.5 months, these findings were not different (83% vs. 90%; P\u2009=\u20090.52). 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\u20130.99; P\u2009=\u20090.039). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with symptomatic COPD treated with TLD combined with optimal pharmacotherapy had fewer study-defined respiratory adverse events, including hospitalizations for COPD exacerbation.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT02058459).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201903-0624oc","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T17:26:49Z","timestamp":1565630809000},"page":"1477-1486","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":65,"title":["Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial"],"prefix":"10.1093","volume":"200","author":[{"given":"Dirk-Jan","family":"Slebos","sequence":"first","affiliation":[{"name":"Department of Pulmonary Diseases and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9052-4638","authenticated-orcid":false,"given":"Pallav L.","family":"Shah","sequence":"additional","affiliation":[{"name":"Royal Brompton & Harefield NHS Trust, Chelsea & Westminster Hospital and Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix J. F.","family":"Herth","sequence":"additional","affiliation":[{"name":"Department of Pneumology and Critical Care Medicine, Thoraxklinik, and"},{"name":"Translational Lung Research Center Heidelberg, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Pison","sequence":"additional","affiliation":[{"name":"CHU Grenoble Alpes, Service Universitaire Pneumologie Physiologie, Universit\u00e9 Grenoble Alpes, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schumann","sequence":"additional","affiliation":[{"name":"Clinic of Pneumology, Thoracic Oncology, Sleep and Respiratory Critical Care, Klinikverbund Kempten-Oberallg\u00e4u, Kempten and Immenstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf-Harto","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Medizinische Klinik m. 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Infektiologie und Pneumologie, Campus Virchow, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter I.","family":"Bonta","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Kessler","sequence":"additional","affiliation":[{"name":"Service de Pneumologie, Nouvel H\u00f4pital Civil, Universit\u00e9 de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Gesierich","sequence":"additional","affiliation":[{"name":"Asklepios-Fachkliniken Munich-Gauting, Comprehensive Pneumology Center Munich, Gauting, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0681-1325","authenticated-orcid":false,"given":"Kaid","family":"Darwiche","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Section of Interventional Pneumology, Ruhrlandklinik\u2013University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Lamprecht","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Kepler Universitatsklinikum GmbH, Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Perez","sequence":"additional","affiliation":[{"name":"CHU de Lille\u2013H\u00f4pital Calmette, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Skowasch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II\u2013Cardiology\/Pneumology, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetan","family":"Deslee","sequence":"additional","affiliation":[{"name":"CHU de Reims, H\u00f4pital Maison Blanche, Service de Pneumologie, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armelle","family":"Marceau","sequence":"additional","affiliation":[{"name":"Service de Pneumologie, H\u00f4pital Universitaire Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank C.","family":"Sciurba","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinoud","family":"Gosens","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; 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