A novel targeted lung denervation multi-polar radiofrequency ablation system for moderate to severe COPD patients: a...

Disruption of parasympathetic pulmonary nerves, which release acetylcholine and trigger airway smooth muscle constriction, has been shown to improve lung function and alleviate symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the current targeted lung denervation (TLD) mono-polar radiofrequency (RF) ablation system has the potential for structural improvement to enhance the generalizability and safety of the TLD procedure.

To develop a novel TLD multi-polar RF ablation for COPD treatment and evaluate its feasibility, safety, and efficacy.

In the preclinical study, we performed TLD in vitro (porcine lung and liver model) to validate its feasibility and in vivo (dogs and sheep) to ensure its safety and preliminary efficacy. Subsequently, we conducted a first-in-man study to evaluate TLD in patients with COPD forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) (FEV₁/FVC < 0.70; FEV₁ 20%-60% predicted) with three energy settings (12 W, 14 W, and 16 W). The primary safety endpoint was the occurrence of any adverse events or serious adverse events deemed related to the TLD device or the procedure. The efficacy endpoints included the instrument and technical success rates of the TLD procedures, as well as changes in lung function, exercise capacity assessments, and health-related quality of life.

In vitro experiments demonstrated that using ice-cold saline irrigation reduced the temperature at the ablation point compared to room-temperature saline (44 °C vs. 63 °C). The ablation range was 6-8 mm when the single electrode power was 12-16 W, coinciding with the distribution of peribronchial nerves. In the in vivo experiments, we confirmed the feasibility of performing TLD in dogs without causing esophageal injury. In sheep, the bronchoscopy and histological examinations showed airway epithelial restitution within a one-year follow-up. Postprocedural pulmonary airway resistance was reduced by approximately 30% with a sustained 30% decrease in axonal staining. In the first-in-man study, the nine patients included reported good tolerance with a success instrument rate of 100% and a technical success rate of 88.9%. FEV₁ increased by 160 ± 120 mL at 6 months post-TLD and 80 ± 150 mL at 12 months post-TLD from baseline. The patients' motor ability and quality of life scores showed improvement but returned to baseline levels by the twelfth month.

This study demonstrated the feasibility of the novel TLD multi-polar RF ablation system in COPD patients. Its safety and clinical efficacy require further validation in larger patient cohorts.

ChiCTR2100047843 ( http://www.chictr.org.cn/ ). Registration date: 27 June, 2021.