Scientists Discover How Viral Infections Trigger Asthma Attacks

An encounter with the flu will not cause an asthma attack in a healthy person. However, viral infections have long been known to constrict the airways in the lungs of people with asthma, leading to the wheezing and shortness of breath characteristic of an asthma attack. Now a group of scientists at the Johns Hopkins University Schools of Public Health and Medicine have discovered how viral infections trigger asthma attacks in susceptible people, a finding that may lead to strategies for countering such virus-induced health crises. The study appeared in the November issue of The Journal of Experimental Medicine.

In humans with asthma, the eosinophil, a type of white blood cell involved in allergy, is also involved in triggering asthma attacks. However, viral infections, which also trigger asthma, do not normally bring eosinophils into the lungs. "We reasoned that, because many people with asthma are also allergic, it might be the allergies that change the response to a virus," explained author Allison Fryer PhD, associate professor, Environmental Health Sciences, Johns Hopkins University School of Public Health.

In the present study, the scientists created an animal model of an allergic person by injecting ovalbumin -- the protein from chicken egg -- into guinea pigs, causing them to become allergic to this protein. This group of allergic guinea pigs was then infected with parainfluenza virus, one of the viruses known to trigger asthma attacks. A control group of unsensitized animals was also exposed to the virus.

In the allergic animals, before virus infection, eosinophils gathered along the nerves in the lungs. "We had previously shown that eosinophils are clustered along the nerves in the lungs of patients with asthma," said senior author, Dr. David Jacoby, associate professor of Medicine, Johns Hopkins University. The parasympathetic nerves in the lungs secrete a neurotransmitter called acetylcholine (ACh), which binds to receptors on the smooth muscle in the airways causing them to constrict. In earlier studies, the Hopkins investigators determined that M2 muscarinic receptors on the same nerves that secrete ACh are continuously inhibiting release of ACh, thus limiting constriction of the airways. Since an excess of ACh can trigger severe airway constriction these M2 receptors are needed to maintain open airways. If something blocks or disables the M2 receptors, then acetylcholine levels will increase enough that ACh attaches to receptors on the smooth muscles, increasing airway constriction and leading to asthma symptoms. The same group has previously demonstrated that the M2 receptors in virus-infected animals were disabled.

In the present study Drs. Fryer, Jacoby, and colleagues found that viral infection activated these eosinophils, causing the eosinophils to release a protein, called major basic protein (MBP). MBP, the scientists have now discovered, blocks the action of the M2 receptors and keeps them from turning off ACh release. The increased acetylcholine causes increased constriction of the airways.

The authors say their findings suggest that blocking the entire parasympathetic nervous system, or clearing the body of eosinophils or MBP, might head off bronchoconstriction in people with asthma who come down with a viral infection. Moreover, the scientists have identified a group of substances that neutralize MBP, restore M2 receptor, and reverse the increased constriction of the airways in these virus-infected allergic animals.

This study was supported in part by grants from the Maryland Thoracic Society, the Royal College of Physicians of Canada, the National Institutes of Health, the Center for Indoor Air Research, and the American Heart Association.