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 April 26, 2005
Scientists Take to the 'Airways' to Find New Asthma Treatments
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By Amanda Gardner, HealthDay Reporter

SUNDAY, March 20 (HealthDay News) -- Research focusing on inflammation of the airways in asthma may eventually lead to new therapies for the disease.

Asthma, a chronic and sometimes life-long disease, is characterized by inflammation of the airways, which causes constriction and trouble breathing.

Steroids, the mainstay of asthma therapy, are effective but also have drawbacks. For example, prolonged steroid use can "trick" the body into shutting down its own steroid production. Problems like these have led scientists on a search to find new treatments.

One study presented Sunday at the annual meeting of the American Academy of Allergy, Asthma and Immunology in San Antonio capitalized on a common mechanism linking heart disease and asthma.

In heart disease, a peptide called D-4F binds with lipids, which are fatty acid molecules. The same pro-inflammatory lipids are at play in asthma, a fact that led Dr. Kameswari Konduri, assistant professor of pediatrics and internal medicine at the Medical College of Wisconsin in Milwaukee, and colleagues to test the compound in asthmatic mice.

The study involved three groups of 20 mice each. One group was completely normal while the other two had asthma. The asthmatic mice were divided into two further groups: one that received daily intranasal doses of D-4F and one that was left untreated.

In the treated mice, "very good reversal of inflammation occurred," said Konduri, co-author of the study. "It also decreased airway hyperresponsiveness."

The reversal did not return the mice to normal, healthy levels but the inflammation was less than in the untreated mice.

A separate group of doctors has licensed the compound to Novartis for possible cardiovascular applications (in pill form). The inhalational version is far from clinical trials, but, Konduri said, given that the heart version of the drug is moving forward, "Maybe this will move a little faster than most drugs."

A second study looked at the role of vascular endothelial growth factor (VEGF) in bronchial asthma. Among other things, bronchial asthma is characterized by the formation of new blood vessels (a process called angiogenesis) that eventually leads to thickening of the bronchial wall and constriction of the airways.

After studying 18 asthmatic children and 34 healthy controls, the researchers found a difference in VEGF, a protein that induces angiogenesis.

"VEGF expression during sputum attacks is markedly elevated," said Dr. Elham Hossny, lead author of the study and professor of pediatrics at Ain Shams University in Cairo, Egypt. "Afterwards, it declined but was still higher."

This elevation could be indicative of an ongoing process of chronic inflammation. "Control of inflammation should not be stopped during quiescence of illness because you never know what is going on inside the lungs," Hossny said. Compounds that work on VEGF may one day prove to be therapeutic, she added.

This study is the first to show that this particular process starts in childhood. Previous studies had identified the process only in adults.

Finally, in what seemed to be an oxymoron, scientists in Belgium have apparently found the first biological marker of quality of life in people with asthma.

"Quality of life is assessed by a time-consuming questionnaire, so it's often overlooked," said Dr. Alain Michils, one of the study authors and associate professor in the chest department at Erasme University Hospital in Brussels. "No objective marker has been found so far."

For this study, Michils and his colleagues discovered that levels of exhaled nitric oxide correlated with changes in quality of life. Specifically, as exhaled nitric oxide went up, quality of life correspondingly declined.

A nitric oxide test, which takes one minute to conduct, could be used to fine tune treatment, Michils said.

More Information

For more on asthma and inflammation, visit the National Jewish Medical and Research Center (asthma.nationaljewish.org).

SOURCES: March 20, 2005, news conference with Kameswari S. Konduri, M.D., assistant professor of pediatrics and internal medicine, Medical College of Wisconsin, Milwaukee; Elham M. Hossny, M.D., professor of pediatrics, Ain Shams University, Cairo, Egypt; Alain Michils, M.D., associate professor, chest department, Erasme University Hospital, Brussels, Belgium

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