Targeted Lung Denervation Found Effective, Safe Over 3 Years of Follow-up

Lung function and quality of life remained stable over three years of follow-up among people with chronic obstructive pulmonary disease (COPD) treated with targeted lung denervation (TLD) — a new therapy developed by Nuvaira — according to the results of a clinical trial.

That trial, called AIRFLOW-1 (NCT02058459) and sponsored by Nuvaira, also showed that the therapy is safe, with no late-onset serious side effects (adverse events).

The findings from the study, “Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW‑1 3‑year outcomes,” was published in the journal Respiratory Research.

COPD is characterized by obstructed airflow in the lungs. Anticholinergic agents, which block the release of the neurotransmitter acetylcholine, often are used to ease COPD-related symptoms.

Treatment with these agents results in decreased mucus hypersecretion — a lessening of mucus overproduction — and also blocks reflexes mediated by the vagus nerve that cause tightening of the airways, or bronchoconstriction.

However, the delivery of these medicines to the lungs is challenging, and patients sometimes have difficulties in adhering to prescribed regimens for inhaled medications. Thus, exacerbations still occur in people with COPD receiving medical treatment.

TLD is a new bronchoscopic therapy that can reduce the impact of acetylcholine in COPD patients. It uses a dual-cooled radiofrequency catheter to disrupt pulmonary nerve input to a patient’s lungs.

AIRFLOW-1 was a randomized, double-blind study, in which 30 people with moderate to severe, symptomatic COPD underwent TLD at two different energy doses. Half of the participants received a dose of 29 Watts (15 patients), while the others (15 patients) were given 32 Watts.

The researchers evaluated COPD exacerbations, pulmonary lung function, and health-related quality of life at one, two, and three years after TLD therapy.

Gastrointestinal events were reported during the randomization phase, in which the participants were assigned doses. After some enhancements to the procedures, an additional 16 patients were included to confirm the safety improvements. These participants received the higher energy dose of 32 Watts.

The final results showed no new gastrointestinal serious adverse events related to the procedure or device over the second and third years of follow-up.

Concerning flare-ups, the annualized rate of moderate-to-severe COPD exacerbations remained stable over the duration of the study.

“The percentage of patients having at least one moderate or severe COPD exacerbation was 70% [31 of 44 patients], 61% [23 of 38], and 46% [16 of 35] at the 1, 2 and 3-year follow up respectively,” the researchers wrote.

Pulmonary function tests revealed that lung function remained stable for the three years in patients who received TLD. The overall quality of life and symptoms measured with the COPD-specific St. George’s Respiratory Questionnaire (SGRQ-C) and COPD Assessment Test (CAT) also were stable during the three years of follow-up.

“These data add to previously published research on the safety and feasibility of the TLD procedure,” the researchers wrote.

“TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up,” they concluded.

The team noted that these observations need to be confirmed in a larger clinical trial comparing the efficacy of TLD in combination with medical therapy against medical therapy alone. In fact, Nuvaira is conducting one such trial, called AIRFLOW-3 (NCT03639051).

AIRFLOW-3 currently is recruiting COPD patients at multiple clinical sites in the U.S. and Europe. More information on enrollment is available here.