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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."

Note for Human respiratory syncytial virus

Human respiratory syncytial virus (RSV) is a negative-sense, single-stranded RNA virus of the family Paramyxoviridae, which includes common respiratory viruses such as those causing measles and mumps. RSV is a member of the paramyxovirus subfamily Pneumovirinae.

RSV causes respiratory tract infections in patients of all ages. It is the major cause of lower respiratory tract infection during infancy and childhood. In temperate climates there is an annual epidemic during the winter months. In tropical climates, infection is most common during the rainy season. In the United States, 60% of infants are infected during their first RSV season, and nearly all children will have been infected with the virus by 2-3 years of age. Natural infection with RSV does not induce protective immunity, and thus people can be infected multiple times. Sometimes an infant can become symptomatically infected more than once even within a single RSV season. More recently, severe RSV infections have increasingly been found among elderly patients as well.

Note for Asthma

Asthma is a chronic illness involving the respiratory system in which the airway occasionally constricts, becomes inflamed, and is lined with excessive amounts of mucus, often in response to one or more triggers. These episodes may be triggered by such things as exposure to an environmental stimulant (or allergen), cold air, warm air, moist air, exercise or exertion, or emotional stress. In children, the most common triggers are viral illnesses such as those that cause the common cold. This airway narrowing causes symptoms such as wheezing, shortness of breath, chest tightness, and coughing. The airway constriction responds to bronchodilators. Between episodes, most patients feel well but can have mild symptoms and they may remain short of breath after exercise for longer periods of time than the unaffected individual. The symptoms of asthma, which can range from mild to life threatening, can usually be controlled with a combination of drugs and environmental changes.

About Researcher:

Mitchell H. Grayson, M.D. 
Current Position 
Assistant Professor, Internal Medicine
Division of Allergy and Immunology

Specialty Areas 
Allergy/Immunology 
Allergy 
Asthma 
Sinus Disease 

Mailing Address
Washington University School of Medicine
Division of Allergy & Immunology
660 South Euclid Avenue, Campus Box 8122
St. Louis, MO 63110
Areas of Clinical Interest
Allergies, stinging insect allergies, asthma, immunodeficiencies, rhinitis and angioedema

Board Certification 
Allergy & Immunology--Certified 
Internal Medicine--Certified 

Medical Education
B.A.: Knox College, Galesburg, Illinois, 1989
Medical Degree: University of Chicago, Pritzker School of Medicine, Chicago, Illinois, 1993
Residency: Internal Medicine, Hospitals of the University of Pennsylvania, Philadelphia, Pennsylvania, 1995
Fellowship: Allergy & Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 1998