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DEFICIENCY OF NOVEL COMPOUND FOUND IN CHILDREN WITH ASTHMA
CHARLOTTESVILLE, Va., April 30 -- Researchers at the University of Virginia Health Sciences Center and Howard Hughes Medical Institute, Duke University Medical Center have found that a deficiency of S-nitrosothiol (SNO), a chemical that dilates the bronchial tubes, is associated with severe asthma in children. The finding, published in the May 2 issue of Lancet, may help doctors develop new asthma therapies aimed at correcting this deficiency.
"This finding was completely unexpected, since severe asthma is classically characterized by an excess of constricting and inflammatory substances in the airways, not by a deficiency of bronchodilating substances," said Dr. Benjamin Gaston, assistant professor of pediatrics at U.Va. and lead author of the study. "From a therapeutic standpoint, increasing the level of the bronchodilator should help ameliorate asthmatic symptoms."
Asthma is a serious breathing problem that is associated with spasm (bronchospasm) of the muscles surrounding the walls of the lung airways (bronchi). Bronchospasm causes narrowing of the airways, which leads to wheezing and shortness of breath.
Importantly, asthma also is associated with airway inflammation, and SNOs inhibit certain inflammatory cells in studies done in the test tube. Therefore, low airway SNO levels may also contribute to the inflammatory component of asthma, Gaston said.
One out of every 20 people in the United States suffers from asthma; half are children between the ages of 2 and 17. Worldwide, several thousand people die from this disease every year.
In this study, tracheal SNO specimens were obtained from eight asthmatic children in respiratory failure and were compared to specimens from 21 children who had no history of respiratory disease. Asthma was defined as a history of three or more episodes of wheezing and shortness of breath responsive to conventional asthma therapy.
Researchers found that the airway SNO concentrations of the asthmatic children were substantially lower than those of normal children. This suggests that previously unrecognized disorders of SNO metabolism might be associated with life-threatening asthma, Gaston said.
"There is clearly room for improvement in current asthma treatment for millions of sufferers, and we hope that learning about this biological pathway will lead to development of a new therapeutic bronchodilator," said Dr. Jonathan Stamler, professor of medicine at Duke University Medical Center and an investigator at the Howard Hughes Medical Institute at Duke.
Additional research efforts are being focused on two areas: replacing the bronchodilator through inhalation, which currently is being tested in clinical trials at U.Va.; and preventing the metabolic breakdown of the compounds, Gaston added.
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April 30, 1998
Dr. Gaston can be reached at 804-963-4420 (pager); Dr. Stamler can be reached at 919-684-6933.
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