Targeted lung denervation for moderate to severe COPD: a pilot study

Abstract

Background Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction. Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms. Aims 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 (FEV 1 )/forced vital capacity (FVC) (FEV 1 / FVC <0.70; FEV 1 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: FEV 1 (+11.6%±32.3 vs +0.02%±15

Anti-inflammatory effects of targeted lung denervation in patients with COPD

“…TLD is a novel potential therapy for COPD, in which parasympathetic airway nerves are ablated by applying radiofrequency energy using a bronchoscopically guided catheter-based lung denervation system (Holaira, Inc., Plymouth, MN, USA) [4]. The lung denervation system includes a cooled electrode that is designed to generate therapeutic lesions at a sufficient depth from the inner surface of the main bronchus to ablate the airway nerves that travel parallel to and outside of the main bronchi and into the lungs.…”

“…An expandable balloon provided protective cooling to minimise airway wall effects in the main bronchi during radiofrequency ablation of the nerves. Clinical evidence in COPD suggests that TLD improves lung function and quality of life [4]. We hypothesised that TLD would inhibit airway inflammation.…”

“…Patients with moderate-to-severe COPD were recruited as part of a safety and technical feasibility study for TLD (clinical trial number NCT01483534) [4]. Subjects recruited at the University Medical Center Groningen (Groningen, the Netherlands) (n=7, two males, age 56±10 years, smoking history 36±14 pack-years, forced expiratory volume in 1 s (FEV1) 27.6±6.7% predicted and 0.70±0.13 L, forced vital capacity (FVC) 2.19±0.27 L; all mean±SD, pre-bronchodilator FEV1 and FVC) were included in the sub-study investigating the effects of TLD on inflammation.…”

Bronchial Thermoplasty by Application of Ultrasound Energy

“…Bronchial nerves are located 2 to 3 times as deep as smooth muscle. If nerve ablation would inhibit bronchial contraction [11] there might be a potential for an easier much faster thermoplasty procedure with ultrasound.…”

Antimuscarinic Bronchodilator Response Retained after Bronchoscopic Vagal Denervation in Chronic Obstructive Pulmonary Disease Patients

“…Current treatment guidelines recommend anticholinergics as first-line therapy for mild to advanced COPD [1]. Targeted lung denervation (TLD) is a novel bronchoscopic therapy that ablates the parasympathetic innervation of the lungs and has a similar proposed mechanism of action to anticholinergic drugs [2]. …”