PHILADELPHIA — An investigational bronchoscopic procedure marketed as Bronchial Thermoplasty may offer an effective, safe, and permanent treatment for the small proportion of patients with severe asthma who cannot be controlled with conventional medications, Dr. Alan R. Leff said at the annual meeting of the American College of Physicians.
About 10% of all asthma patients have severe disease that is inadequately responsive to available treatments with β-agonists, corticosteroids, or leukotriene modifiers. All of these therapies are directed at the active disease state, rather than modifying the underlying disease process.
Bronchial Thermoplasty, in contrast, aims to permanently “undo” the contractile ability of airway smooth muscle, thereby preventing bronchoconstriction, explained Dr. Leff, professor of medicine, pediatrics, anesthesiology, and critical care at the University of Chicago.
Dr. Leff is a consultant for Asthmatx Inc. (www.asthmatx.com
The treatment involves application of heat via the bronchoscope into all airways with diameters of 3 mm or more, and selectively ablating the airway smooth muscle—which is particularly heat sensitive—while preserving other tissues.
All experimental evidence points to the fact that this is safe because mammalian airway smooth muscle is vestigial and has no function. “In neither human nor animal studies has there been anything to indicate that airway smooth muscle really does anything … the goal of all asthma treatment is to get as little airway smooth muscle tone as possible. Clearly, asthma patients are better off the less tone they have.”
In a preliminary study, 16 patients with mild to moderate asthma underwent Bronchial Thermoplasty. The procedure was well tolerated, with side effects that were transient and typical of effects commonly observed after bronchoscopy.
Reductions in airway hyperresponsiveness occurred in all 16 patients, with a mean increase of 2.37 doublings of the PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) at 12 weeks. At 1 year post procedure, the mean increase in PC20 was 2.77 doublings, and at 2 years, it was 2.64 doublings, Dr. Gerard Cox and his associates reported (Am. J. Respir. Crit. Care Med. 2006;173:965–9).
Data from daily diaries collected for 12 weeks indicated significant improvements over baseline in symptom-free days, morning peak flow, and evening peak flow measurements, while spirometry measurements remained stable throughout the study period, said Dr. Cox and his associates from the institute for respiratory health at McMaster University, Hamilton, Ontario.
Preliminary trials of Bronchial Thermoplasty have been conducted in patients with only mild to moderate disease (forced expiratory volume in 1 second greater than 80% predicted) to ensure that the treatment would not exacerbate human asthma, which cannot be replicated in an animal model.
In follow-up data that have now reached a duration of 3 years, there has been continued improvement, with no worsening seen. “It's looking like the improvement is pretty much a permanent thing,” Dr. Leff noted. Several clinical studies are now underway in patients with moderate to severe asthma, the group for whom the treatment would be indicated.
Dr. Leff said the procedure is typically accomplished in two or three half-hour sessions, roughly the length of an average bronchoscopy.
In an editorial that accompanied the published article, Dr. Elisabeth H. Bel said the study “suggests that Bronchial Thermoplasty has the potential to become a realistic therapeutic option in chronic asthma not satisfactorily controlled with pharmacotherapy.”
However, Dr. Bel, doctor of medicine and philosophy in the pulmonology department at Leiden University Medical Center, the Netherlands, added two cautionary notes. For one, the long-term consequences of the procedure are unknown, and it is possible that problems such as permanent widening of the large airways, chronic infections, or increased airway wall collapsibility might appear over time. “Therefore, long-term observation of subjects undergoing this procedure is mandatory,” she said.
Secondly, it is not yet clear to what degree Bronchial Thermoplasty targets the peripheral airways and it may well be that inadequate treatment of those airways may be the primary reason that patients with refractory asthma do not respond satisfactorily to inhaled therapy. If patients refrain from pharmacotherapy because of symptom improvement following this procedure, the distal airways could become even more inflamed and obstructed than before. Long-term data from the ongoing studies involving patients with moderate to severe asthma will shed further light on the issue.
“Bronchial Thermoplasty should never be applied without proper anti-inflammatory pharmacotherapy in these patients,” said Dr. Bel. He has been a speaker at meetings financed by several pharmaceutical companies and was on the advisory board for Merck, Sharpe & Dohme Ltd. until 2005.