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 (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.

Trial registration number: NCT01483534.

Keywords: Bronchoscopy; COPD ÀÜ Mechanisms.

Figure 1

Description of the key components of the targeted lung denervation (TLD) catheter.

Figure 2

(A and B) fluoroscopic view (A) and bronchoscopic view (B) of the electrode during the procedure. The electrode is indicated by the arrow.

Figure 3

Clinical trial profile and patient flowchart.

Figure 4

Bronchoscopic confirmation of airway healing after radiofrequency energy delivery: (A) Left main bronchus pretreatment. (B) During treatment. (C) Immediately post-treatment. (D) 3-month follow-up.

Figure 5

CT and bronchoscopic findings seen before procedural enhancements: (A and B) A 4 mm granuloma indicated by white arrows on both transverse CT and bronchoscopic images. (C and D) Superficial airway effect indicated by white arrow on the bronchoscopic image with normal transverse CT image. (E and F) A 1.5 mm perforation through carina indicated by white arrows on both coronal CT and bronchoscopic images.

Figure 6

Secondary efficacy endpoints. Data represented as mean. Error bars represent SEM. *p <0.05 compared with baseline; FEV₁: forced expiratory volume in 1 s; Cycle Erg. Endurance, Cycle Ergometry Endurance; SGRQ, St. George's Respiratory Questionnaire.

Figure 7

Efficacy measures of targeted lung denervation (TLD) therapy +inhaled ipratropium bromide. Data represented as mean. Error bars represent SEM. *p<0.05 compared with baseline. Follow-up data points were compared with results of TLD alone, and all were statistically significant.