Your Family Physician

One-year results from the pivotal AIR2 Trial, which evaluated the safety and effectiveness of bronchial thermoplasty delivered by the Alair System, an investigational novel therapeutic nondrug procedure, found that it can significantly improve quality of life and reduce asthma exacerbations and respiratory-related emergency-department visits in adults with severe asthma, according to clinical-trial results released here at ATS 2009: the American Thoracic Society International Conference.

Bronchial thermoplasty is a minimally invasive treatment performed through the working channel of a standard flexible bronchoscope that is introduced through the patient's nose or mouth, down into their lungs, under mild sedation. The tip of the small-diameter catheter is expanded to come into contact with the walls of targeted airways; thermal energy is delivered to the airway walls, reducing the amount of airway smooth muscle that narrows the airways in asthma patients who are experiencing an attack.

Dr. Mario Castro

"There has been an unmet need in severe asthma," Mario Castro, MD, principal investigator in the AIR2 Trial and professor of medicine and pediatrics at the Washington University School of Medicine in St. Louis, Missouri, said during his presentation. "Right now, we have 20% of the severe asthma patients accounting for 80% of the costs; with bronchial thermoplasty, severe exacerbations per year are reduced and there is a 66% reduction in the number of days lost at work or school."

Researchers at 30 sites in 6 countries enrolled 297 patients with severe asthma who, despite high doses of asthma medications, continued to experience symptoms. They were split into 2 groups — thermoplasty (n =190) and sham therapy (n = 98). The sham group underwent the procedure on 3 occasions so that they had the same experience as those in the thermoplasty group, including the same noises and lights, except the catheter was introduced without heat.

The study's stated primary effectiveness end point was the change from baseline in the Asthma Quality of Life Questionnaire (AQLQ) score. Safety was assessed by comparing the short- and long-term safety profiles for both the thermoplasty and the sham groups.

As presented, key statistically significant clinical findings of the AIR2 Trial were as follows:

• Improvement in the average AQLQ score at 6, 9, and 12 months in the thermoplasty group, compared with the sham group.
• Four of 5 of the thermoplasty patients responded with a clinically significant improvement in AQLQ, compared with 64% of the sham controls.
• There was a 32% reduction in asthma attacks in the thermoplasty group.
• There was an 84% reduction in emergency-department visits for respiratory symptoms in the thermoplasty group.
• There was a 36% reduction in patients reporting episodes of asthma (multiple symptoms) adverse events in the thermoplasty group.
• There was a 66% reduction in days lost from work/school or other activities because of respiratory symptoms in the thermoplasty group.

Both the thermoplasty and the sham groups had improvements in the AQLQ score, with the thermoplasty group achieving a greater and statistically significant improvement; 81% of thermoplasty subjects achieved a statistically significant and clinically meaningful AQLQ change of ≥0.5, compared with 63% of the sham group. The groups were followed for a posttreatment period of 46 weeks, during which the rates of severe exacerbations were lower in the thermoplasty group than in the sham group (0.48 vs 0.70 exacerbations).

Dr. Castro mentioned that in the period immediately following the treatment, there was a worsening of respiratory-related symptoms. "These events occur within a day or so of the procedure but are resolved on average within about a week with standard care."

Sham Response Called "Staggering"

The treatment did not reach statistical significance on secondary end points, a phenomenon that Dr. Castro explained was due to the "big surprise" of the study — the sham group improved in the areas of change in symptom-free days and use of their rescue medication. Changes from baseline in forced expiratory volume in 1 second (FEV₁) were not different between the 2 groups. During the Q&A session, one pulmonary physician in the audience called the sham response "staggering."

"We never predicted the sham would have such a dramatic effect," responded Dr. Castro, who pointed out that the thermoplasty patients, after their first bronchial thermoplasty procedure, were better at guessing what treatment they had received than those in the sham group. "They were most likely starting to respond already to the treatment."

John Heffner, MD, past president of the American Thoracic Society and professor of medicine at Oregon Health & Science University in Portland, said he would need more data to "truly characterize the effect of this intervention."

"It was pretty impressive that there was such a large response; however, one wonders if this population of patients' asthma wasn't quite as bad as billed. Typically, when patients are managed in routine practice, when they're put into aggressive protocols, their asthma improves," Dr. Heffner pointed out. "So typically, one would like to have a long run-in period where patients are managed by the investigative group until they achieve their maximal benefit, [and] they characterize themselves as having severe asthma after the run-in period — then you've achieved a baseline status to better characterize the effect of the intervention."

Dr. Heffner theorized that patients who respond to the bronchial thermoplasty have a combination of hypertrophy of the muscles and an increased reactivity of the muscles. "Theoretically, the heat in the airways will affect the muscles in a manner that they're less inclined to reduce the same degree of bronchial spasms."

When asked if he would consider using this new device on his patients, Dr. Heffner said: "I think at this point, I would be inclined [to use it] with a patient I was aggressively managing with severe depression of quality of life, despite aggressive therapy with high-dose combination drug regimens. Then I would refer them to a center that was either studying the intervention through a protocol or that was doing the procedure after it was approved — after they have demonstrated they have uncontrolled asthma despite maximal therapy. It would be a consideration. I'm aware of previous studies, and this study has demonstrated that it is safe with some potential benefit."

Source : http://www.medscape.com/viewarticle/703303?sssdmh=dm1.477186&src=nldne