A procedure that had shown early promise in alleviating the symptoms of severe emphysema has failed to replicate its initial success and shows no durable benefit in the first randomised trial of airway bypass, published in a special European Respiratory Society issue of The Lancet.
Currently, there are few treatment options and no cure for the 6 million people worldwide affected by emphysema. The disease is characterised by destruction and hyperinflation of the lungs that leaves patients unable to get air out of their lungs, making it difficult to breathe and to perform even normal daily activities such as eating, bathing, and walking.
Airway bypass was designed to reduce lung inflation and shortness of breath. During the procedure new passages are created into the lungs to release trapped air, supported and reinforced with drug-eluting stents.
A previous feasibility study in 35 patients reported a significant reduction in residual volume (RV; the amount of air remaining in the lungs after full exhalation) and improvement in dyspnoea (shortness of breath) 6 months after airway bypass.
The EASE (Exhale airway stents for emphysema) trial was established to test the safety and efficacy of airway bypass in patients with severe emphysema. Between October, 2006 and April, 2009, 315 patients were enrolled from 38 specialist centres worldwide and randomly assigned to airway bypass (208) or sham procedure (107), and followed for up to 12 months.
Both groups underwent bronchoscopy, but only the treatment group received the airway bypass procedure involving the placement of up to six stents.
Despite a significant reduction in RV and increased forced vital capacity (FVC; the total amount of air breathed in and forced out of the lungs) 1 day after the procedure, these effects were no longer detectable at one month.
At the end of 6 months, no differences were noted in FVC and a breathlessness test (Medical Research Council dyspnoea score) between the treatment groups.
During the first 6 months, 30 (14.4%) patients given airway bypass had at least one respiratory adverse event compared with 12 (11.2%) given sham control. The most common side effects were exacerbation of chronic obstructive pulmonary disease or pulmonary infections that required hospitalisation for more than 7 days.
In attempting to explain the disappointing results, the authors suggest that a combination of factors could be to blame including passages that were created but not stented and stent blockage due to mucus.
However, they point out that the study produced invaluable lessons that will inform future interventions (in particular, that this very unwell population can tolerate general anaesthesia and a complex bronchoscopy procedure), and provides a unique model for the conduct of randomised sham controlled studies on medical devices.
They conclude: "Despite the acute reduction in regional air trapping with an acceptable safety profile, the EASE trial failed to show sustained long-term effects in patients with severe homogenous emphysema. The future use of airway bypass will require improvement of durability to preserve RV reduction."
In a Comment, Walter Weder and Erich Russi from Zurich University Hospital, Zurich, Switzerland say: "Technical development in this area should continue, with the aim of prolonging the patency of airway stents. In future trials, the selection of patients needs to be done carefully so that the chances of producing a persistent therapeutic effect are high. For progress to be made, detailed analysis of the EASE trial will be needed, to identify responding populations and to improve procedural methods."
Dr Pallav Shah, Royal Brompton Hospital, London, UK. T) +44(0)207 351 8021 E) pallav.shah@imperial.ac.uk
Professor Walter Weder Zurich University Hospital, Zurich, Switzerland. T) +41 44 255 88 02 E) walter.weder@usz.ch
Journal
The Lancet