On April 27, 2010, the U.S. Food and Drug Administration approved the first medical device that uses heat, produced by radiofrequency energy, to treat severe asthma. The Alair Bronchial Thermoplasty System is intended for patients 18 and older whose severe and persistent asthma is not well-controlled with inhaled corticosteroids and long-acting beta-agonist medications.
The FDA based its approval on data from a clinical trial of 297 patients. The trial showed a reduction of severe asthma attacks after treatment. The University of Chicago Medical Center was one of about 30 centers around the world, and the only one in Illinois, that participated in the Asthma Interventional Research 2 (AIR2) clinical trial.
“The approval of the Alair system provides adult patients suffering from severe and persistent asthma with an additional treatment option for a disease that is often difficult to manage,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health.
The FDA is requiring a five-year post-approval study of the device to study its long-term safety and effectiveness. The device manufacturer, Asthmatx, will follow many of the patients who participated in the initial trial and enroll 300 new patients at several medical centers across the United States.
The study found that this treatment, known as “bronchial thermoplasty,” improved asthma-specific quality of life when assessed at 6, 9 and 12 months after therapy. Although six percent more treated patients than controls were hospitalized for complications soon after treatment, the treated group over the first year had 32 percent fewer severe asthma exacerbations, an 84 percent decrease in emergency room visits, and 66 percent fewer days missed from work.
Although the Alair system is designed to reduce severe asthma attacks on a long-term basis, there is a risk of asthma attacks during the course of the treatment. Possible side effects during this period may also include wheezing, chest tightness or pain, partially collapsed lung, coughing up blood, anxiety, headaches and nausea.
The short-term risks, however, were “outweighed by the benefits that persist for at least a year,” said pulmonologist Kyle Hogarth, MD, assistant professor of medicine at the University of Chicago and a member of the AIR2 study group.
Bronchial thermoplasty is designed to prevent the airway constriction that is a hallmark of asthma by eliminating some of the smooth muscle that surrounds the breathing passages. When irritated or inflamed, this airway smooth muscle contracts, narrowing the breathing passages. This causes wheezing and reduced breathing capacity that can be severe and even life threatening.
Prior to the AIR2 trial, fewer than 100 patients have ever been treated with bronchial thermoplasty and none in the United States. In a Canadian trial involving 16 asthma patients, the procedure improved average air-flow rates in and out of the lungs, even when tested two years after treatment. About 75 percent of those treated reported that they were “less limited” in their daily activities one to three years after therapy.
“This is an entirely novel and quite exciting approach to treating asthma, unlike anything else available,” said pulmonologist Imre Noth, MD, associate professor of medicine and co-director of the study at the University of Chicago.
In bronchial thermoplasty, physicians insert a thin flexible tube through the nose or mouth, down the throat and into the major airways of the lungs. Then they pass a narrow catheter, with a small expandable heat source at the tip, through that tube.
Once the catheter is in position it is expanded to hold it snugly in place and heated, using radiofrequency energy, to about 150 degrees Fahrenheit — a little cooler than a cup of hot coffee — for ten seconds. This kills about half of the smooth muscle cells that line that segment of the airway. Then the catheter is slightly repositioned and re-heated.
This routine is repeated about 30 times, until all the accessible airways from one lobe of the lung have been treated, a process that takes about 30 to 45 minutes.
Patients in this study were given three separate thermoplasty procedures, with at least three weeks between sessions. Each procedure treated the small- to medium-size airways, those at least 3 mm in diameter, in a different part of the lung.
The smooth muscle that lines the human airway “is a lot like the appendix, it serves no known purpose,” Noth said, “other than to cause serious medical problems.” There is no disease or deficit caused by the loss of airway smooth muscle.
In people with asthma, however, this vestigial tissue can become hypersensitive, responding vigorously to all sorts of stimuli, gaining size and strength over time and contracting when irritated. It is these contractions that narrow the airway and restrict breathing for patients with asthma.
Although there are many different triggers, an acute asthma attack is always characterized by contraction of the smooth muscle in the airway wall. Fortunately, smooth muscle is uniquely heat sensitive. It can be eliminated without lasting damage to the epithelial cell layers that line the inner surface of the airways. After thermoplasty, epithelial re-growth is quick and complete. The smooth muscle at the treatment site is replaced by loose connective tissue.
According to asthma specialist Alan Leff, MD, professor of medicine at the University of Chicago, who worked as a paid consultant to Asthmatx on development of this instrument over an eight-year period: “The compelling use of this procedure is for patients who are inadequately controlled on current drug therapy. But if this therapy lives up to its early promise, bronchial thermoplasty may eventually have a very broad application.”
The AIR2 clinical trial enrolled nearly 300 patients with persistent asthma. Participants were non-smokers, between 18 and 65 years of age, who were willing to commit to 14 clinic visits over a period of 14 months, with annual follow-up visits for the next four years.
Patients kept a daily diary of symptoms, medication use and morning and evening expiratory flow rates. They filled out questionnaires and went through a series of medical tests, including lung function tests, x-rays, CT scan, heart tests and three separate bronchoscopic procedures.
Only two out of three participants were treated with bronchial thermoplasty. The other third, selected at random, received “sham” treatments — bronchoscopies, but without heat treatment of the airways. The patients and the study’s data collectors did not know who received thermoplasty or who receives only the sham treatment.
The long-term risks associated with thermoplasty are not yet fully known. Patients in the AIR2 trial will be followed for five years.
The Alair system is not for use in asthma patients with a pacemaker, internal defibrillator, or other implantable electronic device. Patients with known sensitivities to lidocaine, atropine, or benzodiazepines should not use the device. Alair has not been studied for success in retreatment of the same area of the lung. Currently, patients should not be retreated with the Alair system in the same area of the lung.
Asthma patients considering the Alair system should not be treated while the following conditions are present: an active respiratory infection, coagulopathy (bleeding disorder), asthma exacerbations, or if they have had changes to their corticosteroid regimen 14 days before the proposed treatment.
The study was sponsored by Asthmatx, Inc., of Sunnyvale, California, which makes the treatment device.
For more information about bronchial thermoplasty and asthma care, please call (773) 834-5864 (834-LUNG).
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