An experimental bronchoscopic therapy for chronic obstructive pulmonary disease (COPD), which involves the use of electrical waves to disrupt airway passage nerve transmission, was found to be safe and feasible in a small, early study.
In 15 patients with moderate-to-severe COPD, targeted lung denervation (TLD) was associated with no serious adverse events when given as a single dose through 3 years of follow-up, according to Arschang Valipour, MD, PhD, of Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology in Vienna, and colleagues.
The results confirm those of an earlier pilot studyinvolving 22 patients with COPD treated with TLD in both lungs.
“With long-term safety of targeted lung denervation established between two studies now, focus will be on optimizing the energy dose, further refining the procedure, studying potentially additive effects of targeted lung denervation on top of LAMA [long-acting muscarinic antagonist] treatment, and conducting careful patient phenotyping analysis to identify those patients most likely to benefit from this novel therapy,” the authors wrote in the International Journal of Chronic Obstructive Pulmonary Disease.
James F. Donohue, MD, of the University of North Carolina Chapel Hill, characterized the research as preliminary, but exciting. Donohue, who was not involved in the study, told MedPage Today, “This study, while small, was encouraging and shows the plausibility of this technique. Also the results were enduring at 1 year. But it’s a long way from a small plausible trial to formal FDA approval.”
TLD was performed with the intention of achieving bronchodilation through ablation of parasympathetic pulmonary nerves entering the lung and running along the outside of the two main bronchi, the researchers wrote.
While the earlier pilot study involved treatment of the lungs one at a time, the latest study was performed to examine the treatment given as a single procedure. Patients were also followed for 3 years.
TLD was delivered via a dual cooled radiofrequency generator system. As radiofrequency current is delivered through the airway and surrounding tissues, the tissues are heated and the nerves are ablated, while simultaneous cooling removes heat from the inner surface of the bronchi.
“The net effect is the targeted tissue ablation at depth with minimal heating and damage of the inner surface of the airway. The goal of targeted ablation is to disrupt motor axons within bronchial nerve branches running along the main bronchi, thereby blocking parasympathetic signaling to the lung and decreasing neuronal release of acetylcholine,” the researchers wrote.
The procedure was fully performed in all but one of the participants, with that patient receiving treatment in seven of the eight expected quadrants due to poor balloon contact.
A total of 15 patients (47% male, mean age 63.2) underwent TLD with a total procedure time of 89 minutes. The total fluoroscopy time was 2.5 minutes.
All patients met the primary safety endpoint of freedom from worsening of COPD. There were no procedural complications reported, and results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD.
Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy.
“No significant wall effects (i.e., ulcers and narrowing) were observed during this study at either the 90-day or 365-day follow-up bronchoscopy and CT assessment,” the researchers wrote.
No device-related adverse events were reported and no deaths occurred during the 3-year follow-up period.
The researchers noted that while improvements in lung function were accompanied by benefits in exercise capacity, “they did not translate into consistent benefits of health-related quality of life in this study.”
They hypothesized that this may be due to the small study size or the fact that several patients were not followed beyond 365 days.
The authors conceded that given the lack of a control group undergoing a sham treatment and the lack of direct measurements of therapeutic efficacy of TLD, such as histological proof of denervation in vivo, “improvements in lung function and exercise capacity observed in the current study may have been an intervention effect, rather than a result of the intended mechanism of action.”
“Given the magnitude of response with respect to the FEV1 [forced expiratory volume in 1 second] demonstrated in this study and a strict inhaler washout procedure prior to lung function measurements, however, there is a high likelihood of an independent treatment effect,” they added.
The study was funded by Nuvaira.
Valipour disclosed relevant relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Nuvaira, Olympus, PneumRx, PulmonX, and Uptake Medical. Co-authors disclosed multiple relevant relationships with industry.
Primary Source
International Journal of Chronic Obstructive Pulmonary Disease
