Targeted lung denervation for moderate to severe COPD: a pilot study.
BACKGROUND
Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction. Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms.


OBJECTIVE
To evaluate 'targeted lung denervation' (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD.


METHODS
This 1-year, prospective, multicentre study evaluated TLD in patients with COPD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (FEV1/FVC <0.70; FEV1 30%-60% predicted). Patients underwent staged TLD at 20 watts (W) or 15 W following baseline assessment off bronchodilators. Assessments were repeated on tiotropium before treatment and off bronchodilators at 30, 90, 180, 270 and 365 days after TLD. The primary endpoint was freedom from documented and sustained worsening of COPD directly attributable to TLD to 1 year. Secondary endpoints included technical feasibility, change in pulmonary function, exercise capacity, and quality of life.


RESULTS
Twenty-two patients were included (n=12 at 20 W, n=10 at 15 W). The procedures were technically feasible 93% of the time. Primary safety endpoint was achieved in 95%. Asymptomatic bronchial wall effects were observed in 3 patients at 20 W. The clinical safety profiles were similar between the two energy doses. At 1 year, changes from baseline in the 20 W dose compared to the 15 W dose were: FEV1 (+11.6%±32.3 vs +0.02%±15.1, p=0.324), submaximal cycle endurance (+6.8 min±12.8 vs 2.6 min±8.7, p=0.277), and St George's Respiratory Questionnaire (-11.1 points ±9.1 vs -0.9 points ±8.6, p=0.044).


CONCLUSIONS
Bronchoscopic TLD, based on the concept of ablating parasympathetic pulmonary nerves, was feasible, safe, and well tolerated. Further investigation of this novel therapy is warranted.


BACKGROUND
NCT01483534.
Department of Pulmonary diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Dirk-Jan
DJ
Slebos
Department of Pulmonary diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Karin
K
Klooster
Faculty of Medicine and Health Sciences, Division of Pulmonology, Department of Medicine, Stellenbosch University, Cape Town, South Africa.
Coenraad F N
CF
Koegelenberg
Medi Clinic Panorama, Cape Town, South Africa.
Johan
J
Theron
Faculty of Medicine and Health Sciences, Division of Pulmonology, Department of Medicine, Stellenbosch University, Cape Town, South Africa.
Dorothy
D
Styen
Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology, Otto-Wagner-Spital, Vienna, Austria.
Arschang
A
Valipour
Holaira, Inc., Minneapolis, Minnesota, USA.
Martin
M
Mayse
Faculty of Medicine and Health Sciences, Division of Pulmonology, Department of Medicine, Stellenbosch University, Cape Town, South Africa Medi Clinic Panorama, Cape Town, South Africa.
Chris T
CT
Bolliger
D000368:Aged; D001999:Bronchoscopy; D017115:Catheter Ablation / Q000295:instrumentation*; D015331:Cohort Studies; D017079:Exercise Tolerance; D005240:Feasibility Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D017764:Parasympathectomy / Q000295:instrumentation*; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000601:surgery*; D011788:Quality of Life; D014109:Total Lung Capacity; D016896:Treatment Outcome
Bronchoscopy; COPD ÀÜ Mechanisms