Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW)

Slebos DJ et al.

Am J Respir Crit Care Med Volume 200, Issue 12, December 2019, Pages 1477-1486;


What is the key question?

  • What is the impact of bronchoscopic targeted lung denervation (TLD) on respiratory adverse events in symptomatic patients with moderate to severe chronic obstructive pulmonary disease (COPD)?

What is the bottom line?

  • In COPD, acetylcholine released from parasympathetic airway nerve fibers mediates smooth muscle tone, reflex bronchoconstriction, mucus hypersecretion, and airway inflammation, which all contribute to disease symptoms and progression.
  • TLD is a novel bronchoscopic radiofrequency ablation therapy for COPD, which durably disrupts parasympathetic pulmonary nerves to decrease airway resistance and mucus hypersecretion.
  • Authors conducted a multicenter, randomized, sham bronchoscopy–controlled, double-blind trial (AIRFLOW-2) in patients with symptomatic (mMRC >2 or CAT >10) COPD (FEV1, 30–60% predicted). Patients were randomly assigned 1:1 to a sham procedure or TLD and followed for 12.5 months then un-blinded. The primary endpoint was the rate of respiratory adverse events between 3 and 6.5 months after randomization, defined as COPD exacerbation, tachypnea, wheezing, worsening bronchitis, worsening dyspnea, influenza, pneumonia, other respiratory infections, respiratory failure, or airway effects requiring therapeutic intervention).
  • During the predefined 3- to 6.5-month window, patients in the TLD group experienced significantly fewer respiratory adverse events than those in the sham group (32% vs. 71%, P = 0.008; OR 0.19, P = 0.0006). Between 0 and 12.5 months, these findings were not different (83% vs. 90%; P = 0.52). The risk of COPD exacerbation requiring hospitalization in the 0- to 12.5-month window was significantly lower in the TLD group than in the sham group (HR 0.35; P = 0.039). There was no statistical difference in the time-to-first moderate or severe COPD exacerbation, patient-reported symptoms, or other physiologic measures over the 12.5 months of follow-up.
  • Limitations include the relatively small sample size, the short time window during which the primary endpoint was assessed, and the use of investigator-generated definitions for the respiratory adverse events. Furthermore, owing to anatomical limitations (esophageal proximity), not all patients could receive a full circumferential treatment, resulting in potential undertreatment.

Why read on?

  • TLD is a novel and safe bronchoscopic therapeutic option for symptomatic COPD patients. Combined with optimal pharmacotherapy, TLD can result in fewer study-defined respiratory adverse events early after treatment and can potentially decrease hospital admissions for COPD exacerbation at 1 year. Larger clinical trials are needed to substantiate the effect of TLD on exacerbation rates.