Targeted Airway Ablation Reduces COPD Exacerbations

Symptoms of persistent chronic obstructive pulmonary disease (COPD) can be significantly reduced when obstructed airways are opened by targeted lung denervation (TLD), claims a new study.

Researchers at University Medical Center Groningen (UMCG; The Netherlands), University Hospital Leuven (UZ Leuven, Belgium), and other institutions conducted a multinational phase 2 clinical study of the Nuvaira lung denervation system and dual cooled radiofrequency ablation (RFA) catheter probe. The trial included 82 patients (50% male, average age 64); half the participants underwent an outpatient TLD procedure, and the other half underwent a sham procedure.

During TLD, performed under general anesthesia, a bronchoscope is used to insert a balloon catheter that contains the RFA probe into the airway. Specific nerves are selectively ablated to target the cholinergic pathway, which regulates the inflammatory response and smooth muscle constriction. The esophagus itself is protected from the electrodes with a tissue-mimicking gel during the 75-minute procedure. In addition, all patients received tiotropium, an anticholinergic bronchodilator. Eighty-one patients completed a six-month follow-up.

The results revealed that TLD improved lung function in COPD patients; while 71% of the patients who received the sham treatment had an adverse respiratory event related to COPD, only 32% of the TLD patients suffered one. None of the patients died, and there were no TLD-related adverse effects. Five patients (12%) in the treatment group experienced gastrointestinal problems such as nausea, abdominal bloating, and digestion discomfort, which disappeared after six months. The study was presented at the European Respiratory Society International Congress, held during September 2018 in Paris (France).

“We have been able to significantly reduce chronic respiratory symptoms such as shortness of breath, exacerbations of the disease, infections and hospitalizations in a group of COPD patients who are already on aggressive medical therapy,” said lead author and study presenter Dirk-Jan Slebos, MD, PhD, of UMCG. “There was also a trend towards improved quality of life and better lung function in the treated patients. It's a new mechanism of treatment that will not replace drugs, but really strengthens them. From my point of view, it's really a step-up approach at the moment.”

The nervous system can suppress inflammation through the cholinergic anti-inflammatory pathway by stimulation of the vagus nerve, which controls parasympathetic tone, heart rate variability, and the release of acetylcholine, which in turn inhibits the inflammatory response by inhibiting release of pro-the inflammatory cytokines interleukin-6 and tumor necrosis factor (TNF). If pro-inflammatory cytokines are released over a prolonged period, they can exacerbate diseases such as rheumatoid arthritis (RA), inflammatory bowel disease, and atherosclerosis.

Related Links:
University Medical Center Groningen
University Hospital Leuven