St. Louis, Nov. 7, 2007 — Babies who get severe respiratory viral infections are much more likely to suffer from asthma as they get older. Now researchers at Washington University School of Medicine in St. Louis have pinpointed a key step in the development of asthma in mice after a severe respiratory infection. They suggest that medications designed to interfere with this mechanism could potentially prevent many cases of childhood asthma.
"A severe respiratory infection in infancy greatly increases the risk of developing asthma," says the study's lead author Mitchell Grayson, M.D., assistant professor of medicine in the Division of Allergy and Immunology. "Less than one in 30 people who don't suffer a severe respiratory infection as a baby develop asthma, but of those who do get these infections, one in five goes on to have asthma."
Grayson and colleagues published their research in the Oct. 29, 2007, issue of the Journal of Experimental Medicine. They found that mice that developed asthma-like symptoms after a severe respiratory viral infection had an unusual immune reaction. During the infection, the mice produced antibodies and immune signals similar to those produced during an allergic response, instead of those typically made in response to infection. That started a chain reaction that led to asthma. The researchers propose that a similar reaction occurs in some people who suffer severe respiratory viral infections.
"We think genetically predisposed individuals will tend to have this kind of immune reaction to a severe respiratory viral infection," Grayson says. "In those people an allergic-type response could be part of their antiviral immune response. That sets them up to make antibodies against a lot of environmental substances, like pet dander or pollen, and they can go on to develop allergies or asthma."
Reports by the Centers for Disease Control and Prevention indicate that the number of people with asthma in the United States rose from approximately 7 million in 1980 to about 20 million in 2003. The reasons for this trend are unclear, Grayson indicates. But he suggests that a growing population density and the resulting increase in transmission of respiratory viral infections might be a cause.
Respiratory syncytial virus (RSV) is a common source of respiratory infections. In the United States nearly all children have been infected with RSV by two or three years of age. Severe RSV infections, typified by persistent coughing, wheezing and gasping for breath, send many thousands of children to the hospital each year.
To investigate the connection between severe respiratory viral infections and subsequent asthma, the researchers used mice genetically selected to have an asthma susceptibility and infected them with a virus similar to RSV. They found that severe respiratory infections in the mice induced an allergic-type immune response and ultimately caused long-term changes in the airways of the lungs that are hallmarks of chronic asthma.
The researchers discovered that certain immune cells in the mouse lungs reacted to severe viral infections by releasing compounds that instigated an inflammatory response. That in turn induced many lung airway cells to transform into mucus-producing cells, which can cause the obstruction of lung passages and shortness of breath characteristic of asthma.
The researchers found that interfering with this process by altering the immune cells or removing the inflammatory compounds they secreted prevented overgrowth of mucus-producing cells.
The findings promise a new approach to asthma prevention, according to Grayson. "This offers a different way of thinking about what happens in the development of asthma," Grayson says. "It may be possible to prevent many cases of asthma and other chronic inflammatory airway diseases by stopping allergic-type antibody production after a severe viral infection in infants."
Grayson MH, Cheung D, Rohlfing MM, Kitchens R, Spiegel DE, Tucker J, Battaile JT, Alevy Y, Yan L, Agapov E, Kim EY, Holtzman MJ. Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia. Journal of Experimental Medicine 2007 Oct 29;204(11):2759-69.
Funding from the National Institute of Allergy and Infectious Disease, the National Heart, Lung and Blood Institute, Genentech Inc., Novartis International AG, the Martin Schaeffer Fund and the Alan A. and Edith L. Wolff Charitable Trust supported this research.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
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