January 28, 2008

Protein Patterns Distinguish Asthma Subtypes

Illustration shows a normal lung tubule and an asthmatic tubule, with a central airway narrowed by tight muscles, swelling and mucus NHLBI

People with asthma don't all respond to the same treatments. A new study has shown that different asthma subtypes can be distinguished at a molecular level. If simpler methods can be developed, the finding could lead to more targeted, effective asthma treatments.

Asthma is caused by swelling and inflammation of the airways. When air passages become narrower, less air can get through, causing wheezing, coughing, chest tightness and trouble breathing. Once considered a minor ailment affecting only a small portion of the population, asthma is now the most common chronic disorder of childhood, affecting an estimated 6.2 million children under the age of 18.

Most of the molecular links to asthma discovered in the past have been based on gene expression patterns. Those associations, however, have not been strong. A research team led by Dr. Allan Brasier of the University of Texas Medical Branch at Galveston reasoned that it might be more useful to look at proteins instead, because the levels of the proteins themselves might correlate more strongly with disease than the genes that are encoding them. Their investigations were supported by NIH's National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Environmental Health Sciences (NIEHS) and National Heart, Lung and Blood Institute (NHLBI), among others.

The team decided to look at the mix of cytokines in the lungs of asthma patients. Cytokines are immune system signaling proteins that play an important role in asthma. The researchers squirted a small amount of saline solution through tiny tubes into anesthetized volunteers' lungs and then sucked the saline back out. They took samples from 84 asthmatic volunteers—41 with severe asthma and 43 with mild-moderate asthma—and measured the levels of 25 different cytokines in the samples.

The researchers reported in the January 2008 issue of the Journal of Allergy and Clinical Immunology that they could divide the patients into 4 groups based on the levels of different cytokines they were producing. One of the cytokine patterns they found was associated with severe asthma. Further investigation narrowed down the pattern that could identify people in this severe asthma group to just 10 cytokines.

Another cytokine pattern represented less severe asthma. There were also 2 other groups whose significance the researchers don't yet understand. Glucocorticoid therapy, a common asthma treatment, didn't affect the groupings.

“We know that in asthma some people respond to very specific types of therapies and others don't,” Brasier said. “Being able to discover different asthma subtypes should allow us to tailor our treatments to increase the odds of a positive response.”

This study shows that protein profiles could, in theory, be used to diagnose different types of asthma. More work still needs to be done to develop these profiles, however. Any clinical application will also depend on the development of less invasive techniques for measuring these proteins, such as a blood test or a breath test.

—Harrison Wein, Ph.D.

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