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Researchers find common childhood asthma unconnected to allergens or inflammation
Date:5/23/2013

Asthma is a significant health problem affecting about 7 million children in the United States. Nearly 10 percent of American children 017 years of age have asthma, making it the most common serious respiratory childhood disease. Its prevalence is even higher among inner-city children, says Dr. Worgall. Besides causing suffering, disability and alarm, the economic toll is significant, he says: In 2009, asthma caused 640,000 emergency room visits and 157,000 hospitalizations, plus 10.5 million missed school days.

"Yet while it has become increasingly evident that asthma takes several forms, treatment of the disorder is uniform," he says. "Most therapies are designed to reduce inflammation, but they do not help all sufferers."

The notion that asthma has different forms gained ground after several genome-wide association studies (GWAS) found variation in a gene, later identified as ORMDL3, in to up to 30 percent of asthma cases. In 2007, over-production of the gene's protein was connected to childhood asthma, and this gene has been the most consistent genetic factor identified so far for asthma.

In 2010, a study in yeast found that ORMDL3 protein inhibits sphingolipid de-novo synthesis.

This finding prompted the researchers to investigate whether sphingolipid production is connected to asthma. Their study shows that this is indeed true in mouse models of the disease. Using mouse models, the researchers found that inhibition of an enzyme, serine palmitoyl-CoA transferase (SPT), which is critical to sphingolipid synthesis, produced asthma in mice and in human airways, as it did in mice that had a genetic defect in SPT.

The airway hyperactivity seen in the mice was not linked to increased inflammation, and the scientists saw a decreased response of the lung and airways to magnesium -- which is often used in emergency rooms to relieve chest tightness of patients with asthma attacks.

"In our mouse model
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Contact: John Rodgers
jdr2001@med.cornell.edu
646-317-7401
Weill Cornell Medical College
Source:Eurekalert

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