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Tuesday, February 3, 2009, 12:00 p.m. EDT
Researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, and Duke University have discovered a cause of airway irritation and wheezing after exposure to ozone, a common urban air pollutant. Using an animal model, the researchers were also able to identify several ways to stop the airways from narrowing. These findings help identify potential new targets for drugs which may eventually help physicians better treat emergency room patients suffering from wheezing, coughing and shortness of breath.
"We found that it is not the ozone itself that causes the body to wheeze, but the way the lungs respond to ozone," said Stavros Garantziotis, M.D., principal investigator in the NIEHS Laboratory of Respiratory Biology and lead author of the paper published online this week in the Journal of Biological Chemistry.
"Animals exposed to ozone produced and released high amounts of a sugar known as hyaluronan," said John Hollingsworth, M.D., a pulmonologist who is an assistant professor in the Department of Medicine at Duke University Medical Center and senior author of the paper. "We found hyaluronan to be directly responsible for causing the airways to narrow and become irritated. We believe this may contribute to asthma symptoms in humans as well."
The researchers found several proteins which can mediate the hyaluronan effect and can be used as treatment targets. They were also able to block the airway responsiveness by binding the native hyaluronan away, as well as by administering a slightly modified form of hyaluronan. "Although more research is needed before these findings can be translated to humans, we are optimistic these treatment options could prove beneficial to patients," said Hollingsworth.
"This finding has real-life therapeutic implications," said Garantziotis. The researchers point out there are approximately 4,500 hospital admissions and 900,000 school absences each year attributed to ozone exposure, especially on high-ozone alert days. "We identified several new approaches to the treatment of ozone-induced airway narrowing."
Ozone has been estimated, in an Environmental Protection Agency analysis, to cost the United States $5 billion a year as a result of premature deaths, hospitalizations and school absences. Inhalation of ozone can lead to irritation of the airways and increased wheezing, particularly in children and adults who have asthma and chronic obstructive lung disease. Ozone is formed in the inner atmosphere in the presence of sunlight from pollutants emitted from vehicles and other sources. Exposure occurs when people inhale air containing ozone.
"This collaborative effort exemplifies the powerful advances we can continue to make to improve human health by teaming the innovativeness of our in-house researchers with our grantees," said Linda S. Birnbaum, Ph.D., NIEHS director. "This is also a good example of how NIEHS is helping to bring a pool of creative, talented young scientists to the field of environmental health sciences."
Dr. Hollingsworth is an NIEHS Outstanding New Environmental Scientists (ONES) grant award recipient. The ONES program identifies outstanding scientists who are in the early, formative stages of their careers and who intend to make a long-term career commitment to research in the mission areas of the NIEHS.
Reference: Garantziotis S, Li Z, Potts EN, Kimata K, Zhuo L, Morgan DL, Savani RC, Noble PW, Foster WM, Schwartz DA, Hollingsworth JW. Hyaluronan Mediates Ozone-Induced Airway Hyperresponsiveness in Mice. The Journal of Biological Chemistry. Advance Access published on January 21, 2009. doi:10.1074/jbc.M802400200.
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