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Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma: A Multicenter, Randomized, Double-Blind, Sham-Controlled Clinical Trial
Castro M, Rubin AS, Laviolette M, et al
Am J Respir Crit Care Med. 2010;181:116-124
StudySummary
Bronchial thermoplasty (BT) is a bronchoscopic procedure in which radiofrequency energy is delivered to several sites in the major airways in order to reduce airway smooth muscle mass and hyperresponsiveness in severe asthmatics. Over a course of 3 procedures, each separated by 2 weeks, several sites along the airway lining are treated with radiofrequency energy, which is essentially controlled heating. The procedure has been in clinical trials for about 5 years, and this large, phase 3, double-blind, randomized, sham-controlled study was concluded last year by Castro and colleagues.
From 30 international sites, 288 adults whose severe asthma was not controlled despite high-dose inhaled corticosteroids and long-acting beta-agonists were randomly selected to receive either BT or sham-BT. The primary outcome was defined as an improvement in the Asthma Quality of Life Questionnaire (AQLQ) averaged over the ensuing year. The AQLQ improved in both groups, and the difference between the 2 treatments was statistically but not clinically greater in the BT group. Secondary outcomes were not significantly different between the study groups. Although not prespecified as outcomes, the BT group experienced fewer severe exacerbations, emergency department visits, and days missed from work or school. Apart from a temporary increase in asthma symptoms following BT, which occasionally resulted in hospitalization, little difference in safety outcomes were observed between the groups.
The Food and Drug Administration (FDA) approved the procedure in April 2010, conditional on a postmarketing long-term safety and efficacy study.
Viewpoint
BT was described as "the first nondrug asthma treatment," a statement that overlooks important measures such as avoidance and education. Nevertheless, it is very helpful that a new invasive procedure has been subjected to a prospective, randomized, sham-controlled study, permitting healthcare practitioners to be relatively confident that the benefits are real.
An accompanying editorial characterizes the net effect of BT as "somewhat disappointing," and I agree. However, a major reason for the unexpectedly limited benefit seems to have been that the control group improved to a much greater extent than was anticipated. In part, this can be attributed to a placebo effect, for which asthma trials are notorious, but the failure to optimize medical treatment in all subjects before the experimental phase began must have been a confounding factor also.
Health utilization and acute exacerbations are important outcomes with respect to asthma, and although this study was not powered for those outcomes, they were improved. Remarkably, despite what seems to be a highly aggressive intervention, the procedure appeared to have been well tolerated, and evidently the FDA felt that the benefits outweighed the risks. The long-term benefit/risk ratio for BT is unknown at present.
Where will the procedure fit into asthma management? First, every effort should be made to optimize medical management according to the latest Global Initiative for Asthma (GINA) guidelines, including emphasis on education and patient compliance. Only at that time -- and not before -- and when asthma remains poorly controlled, the quality of life as assessed by the AQLQ is unacceptable to the patient and/or parent(s), healthcare utilization remains high, and a fatal or near-fatal event appears to be a possibility would I consider referring a patient for BT. Given that BT should be used only after all of the conventional measures have been exhausted, I do not at present expect BT to be warranted in more than a small percentage of asthmatics. With more experience and information about BT's long-term effects, this percentage may well rise.
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