Does Exposure to Influenza A Virus Increase the Risk of Developing Asthma?

[iansmith]

Previous exposure to influenza A virus increases predisposition to asthma | By Cathy Holding



A new study by a team at Stanford questions the controversial hygiene hypothesis, which states that raising children in an overly clean environment leads to the development of asthma. But others in the field say the paper, in the February 16 Nature Immunology, does little to challenge the theory.

Martin Dahl and colleagues at Stanford University School of Medicine report that infection with influenza A increases the likelihood of developing allergic disease, potentially undermining a key tenet of the hypothesis: namely, that being infected with viruses protects against other diseases (Nature Immunology, DOI:10.1038/ni1041, February 16, 2004).

“There has been this very popular idea of the mutually exclusive response for some infections,” David B. Lewis, associate professor of pediatrics at Stanford University School of Medicine and coauthor of the paper, said, referring to T-helper 1 (TH1) and TH2 responses. The TH1 response produces high levels of interferon ã that can decrease the TH2 response, which is classically associated with allergic disease.

“One tends to go down either the TH1 or TH2 pathway in terms of the cytokine profile that the T cells make, and then there's consequences depending on which profiles you have from the infection,” Lewis said.

The hygiene hypothesis discriminates between viruses that enter via the gastrointestinal tract—for example, hepatitis A virus—and those that enter via the respiratory tract. Dahl and colleagues used the respiratory route, infecting mice with influenza A, allowing the infection to clear, and then inducing allergic disease.

“We found somewhat surprisingly that the disease was worse in terms of the allergic response, in terms of asthma,” said Lewis. “Many of the classic features were definitely worse rather than better, so at least it argues that the hygiene hypothesis has probably been very oversimplified and certainly doesn't seem to apply in a general sense to viral infections.”

“We're not trying to attack the hygiene hypothesis, I think we're trying to set straight what we think are some of the issues,” he said.

Dendritic cells, responsible for clearing the bronchioles, were found amongst the lung tissue. “This made us consider whether in fact these cells might have some role in the enhanced allergic disease,” said Lewis. The researchers report that these cells are indeed involved in this response.

But Barton Lambrecht, of the Department of Pulmonary Medicine at Erasmus Medical Center in Rotterdam, told The Scientist, “To me it wasn't very new. It's nice data and they show nice things, but depending on the model and the timing you're looking at, you can still have different outcomes... so to say that it completely breaks down the hygiene hypothesis—it's not true.”

“It was known already that the respiratory viruses carry the higher risk of allergy development compared with the nonrespiratory viruses. If you would do the same with, say, a gastrointestinal virus, like hepatitis A virus, you would probably see a different response,” said Lambrecht, who was not involved in the study.

“In fact, they [Dahl et al.] don't refer to any clinical or epidemiological studies that have actually shown this: that respiratory infections can lead to more asthma development. I mean, I should have expected it… if I had been a reviewer,” Lambrecht added.

Gailen Marshall, professor of medicine and pathology at the University of Texas Medical School at Houston, told The Scientist in an E-mail that he too felt that the hygiene hypothesis had not been challenged by the data.

“The animals were 6 to 8 weeks old—young adults—when initially infected with the flu virus. The hygiene hypothesis generally states that exposures during the first year of life dictate whether an individual will become atopic or asthmatic,” said Marshall, who was also not involved in study. “Further, influenza virus infection may have different effects from respiratory syncytial virus or rhinoviruses much more common in children.”

“[The paper] provides exciting data about the role of dendritic cell stimulation by antigens such as influenza virus on development of allergic sensitization. This really calls the TH1/TH2 paradigm into question more than it does the hygiene hypothesis,” said Marshall.

http://www.biomedcentral.com/news/20040217/01

 

[spuriousmonkey]

I can just remember being at a lecture in which they compared two populations. One in Finland and one just accros the border in Russia. Genetically the populations were similar. The main difference was that the Fins have very hygienic and clean houses and the Russians didn't. The Fins had higher incidence of asthma and such.

I can't really remember the details. It was at least a year ago.