The findings suggest that impaired airway relaxation -- as opposed to active constriction -- may be a more important cause of asthma than previously recognized. The results may also yield a novel approach to therapy, the researchers said.

"In thinking about asthma, scientists have generally focused on processes that actively constrict airways or lead to inflammation, making it difficult to get air in or out," said HHMI investigator Jonathan Stamler, M.D. "We haven't paid much attention to how airways are normally kept open. Our findings suggest the disease may stem from a deficit in the natural bronchodilator that normally relaxes airways."

The Duke team reported in the May 26, 2005, early online version of the journal Science that it had discovered a natural compound, nitrosoglutathione (GSNO), that helps keep airways open. Mice with elevated levels of GSNO were much less susceptible than normal animals to getting asthma, the team found. Moreover, animals deficient for GSNO developed asthma.

People with asthma are also deficient in GSNO, notes first author Loretta Que, M.D., also of Duke. Therefore, drugs that increase GSNO levels could offer a new approach to treating the airway obstruction in asthma.

"The mice closely resemble the human condition, which makes this particularly exciting as a potential new approach toward asthma therapy," Que said.

GSNO is a molecule in the nitric oxide family. Earlier studies suggested that nitric oxide (NO) might regulate the dilation of airways, with the exhaled breath of patients with asthma showing elevated levels of NO, Stamler said. However, studies in which researchers have manipulated
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-1306
Duke University Medical Center
26-May-2005