Clinical trial measures ability of focused heat treatment to reduce asthma symptoms.

CHICAGO -- The University of Chicago Hospitals is one of about 30 centers around the world, and the only one in Illinois, participating in the Asthma Interventional Research 2 (AIR2) clinical trial, the first U.S. trial of "Bronchial Thermoplasty," an investigational treatment for patients with moderate to severe asthma.

This study will evaluate the safety and effectiveness of a device -- the Alair(R) System, manufactured by Asthmatx, Inc. This investigational device is designed to prevent the airway constriction that is a hallmark of asthma by reducing 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.

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, M.D., assistant professor of medicine at the University of Chicago and director of the study. "The data from pre-clinical studies were impressive and the early reports from three human trials in Canada, Brazil and Europe have attracted a lot of attention. But this will be the first big human trial."

In Bronchial Thermoplasy, physicians insert a thin flexible tube called a bronchoscope 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 thermal energy, for ten seconds. This reduces smooth muscle cells that line that segment of the airway. Then the catheter is slightly repositioned and re-heated. This routine is repeated multiple 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 will undergo three separate Bronchial Thermoplasy procedures, with at least three weeks between sessions. Each procedure will treat the small- to medium-size airways, those at least 3 mm in diameter, in a different part of the lung.

The first session will treat the airways in the lower lobe of the right lung, the second the left lower lobe, and the third both upper lobes. The right middle lobe, about 15 percent of the total lung volume, will be left untreated.

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 time 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," Noth said, "an acute asthma attack is always characterized by contraction of the smooth muscle in the airway wall. So it makes considerable sense to try to treat asthma by minimizing the ability of this smooth muscle to contract."

Fortunately, smooth muscle is uniquely heat sensitive. It can be reduced without lasting damage to the epithelial cell layers that line the inner surface of the airways. After Bronchial Thermoplasty, epithelial re-growth is quick and complete and the smooth muscle at the treatment site is replaced by loose connective tissue.

"However," he added, "even if this works as we imagine, it is not a cure for asthma. Our fondest hope is that it may reduce the severity and frequency of asthma symptoms, especially for those with severe asthma, and perhaps improve the quality of life for people with moderate to severe asthma."

According to asthma specialist Alan Leff, M.D., professor of medicine at the University of Chicago and a consultant to Asthmatx: "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, especially for patients who wish for a permanent amelioration of their symptoms or have difficulty adhering to medical regimens."

The AIR2 clinical trial is enrolling patients with moderate to severe asthma. Participants must be non-smokers, between 18 and 65 years of age, who are willing to commit to 14 clinic visits over a period of 14 months, with annual follow-up visits for the next four years.

Patients must keep a daily diary of symptoms, medication use and morning and evening expiratory flow rates. They will fill out questionnaires and undergo 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 will be treated with Bronchial Thermoplasty. The other third, selected at random, will undergo three bronchoscopies, but without heat treatment of the airways. The patients and the study's data collectors will not know who received Bronchial Thermoplasty or who receives only the "sham" bronchoscopy.

The benefits of participation include free laboratory tests, considerable medical attention and education about asthma, the possibility of reduced asthma symptoms, and financial compensation for the time and inconvenience involved.

The risks include those associated with bronchoscopy, primarily bronchial irritation causing cough, mucous production and hoarseness for a few days after treatment. Rare but more serious risks include possible lung damage, infection and bleeding.

The risks associated with Bronchial Thermoplasty are not yet fully known but may include scarring of the airways, injury to nearby tissues, and accumulation of thickened mucous after the therapy that could require additional treatment.

For more information on participation in this study please call 773 834 5864 (LUNG). For more information on the AIR2 trial, go to: www.AIR2Trial.com or contact Karen Passafaro at 650-810-1100 x118 or [e-mail].

The study is sponsored by Asthmatx, Inc., of Mountain View, California. Dr. Noth has no financial interest in the company.