2-Drug Strategy May Improve Asthma

New Approach Targets Production of Mucus

Medically Reviewed by Ann Edmundson, MD, PhD on February 02, 2006
From the WebMD Archives

Feb. 2, 2006 -- A treatment that targets mucus production may one day help asthma sufferers and people with other respiratory diseases breathe much easier.

Researchers from the Washington University School of Medicine in St. Louis are reporting that a combination of two novel therapies could hold the key to controlling the potentially dangerous buildup of mucus in people with asthma, chronic bronchitis, and even cystic fibrosis.

Current asthma treatments target inflammation and airway constriction. The two-drug treatment strategy would be the first to target the cellular transformation within the lungs that causes the overproduction of mucus. Mucus plugs block airways, making it difficult for air to go in and out of the lung.

The findings were reported Wednesday in The Journal of Clinical Investigation.

"We haven't had good drugs to treat the problem of mucus that are selective, safe, and effective," researcher Michael J. Holtzman, MD, tells WebMD. "In large part, people with asthma and many other respiratory diseases get in trouble because of these secretions."

Holtzman and Washington University colleagues developed the treatment based on studies in mice and human cell lines. The two-drug combination has not been tested in humans with asthma, but Holtzman says such trials could begin within a year or two.

"Our research should help in the design of these trials," he says.

Combining Therapies

The strategy involves the combination of a new therapy being used to treat late-stage cancers and an experimental therapy being studied for respiratory disease.

Epidermal growth factor receptor (EGFR) is involved in cell growth. An inhibitor of EGFR has been developed to stop cells from growing and spreading elsewhere in the body. This EGFR inhibitor has been used to treat cancer in humans and has been shown to be relatively safe in clinical trials.

In this study, mice with a chronic lung condition were exposed to a virus. An inhibitor of EGFR was able to prevent the buildup of mucus-producing lung cells.

A second inhibitor that targets the interleukin-13 (IL-13) protein is being studied but has not been approved for clinical use. IL-13 is involved in the immune system. The IL-13 inhibitor was shown to block the transformation of cells into mucus-producing lung cells.

The thinking is that the drugs that inhibit the EGFR and IL-13 proteins may act together to prevent cellular changes that lead to dangerous mucus production in respiratory disease.

"We have shown that if you combine the EGFR and IL-13 inhibitors in a rational way, you can restore the normal architecture of the airway lining," Holtzman says.

Important Step

Asthma treatment specialist Clifford W. Bassett, MD, says mucus secretion is an important complication in asthma that has not been well studied in the past.

He calls the Washington University research a potentially important step in the development of a new type of asthma treatment to complement existing treatments.

But he adds that treatments like inhaled steroids, which target inflammation, and bronchodilators, which ease constricted airways, work well to control asthma if they are used properly. Patients most often get into trouble, he says, when they don't use these medications as they should.

Bassett is an allergist at New York's Long Island College Hospital and a spokesman for the American Academy of Allergy, Asthma and Immunology.

"Keeping asthma under control means using medications in a way that prevents complications," he says. "You don't wait until you are in crisis to see a doctor or get treatment."

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SOURCES: Tyner, J.W., The Journal of Clinical Investigation, February 2006; vol 116: online edition. Michael J. Holtzman, MD, director, division of pulmonary and critical care medicine; professor of medicine, cell biology and physiology, Washington University School of Medicine, St. Louis. Clifford W. Bassett, MD, allergist, Long Island College Hospital, Brooklyn, N.Y.; fellow and spokesman, American Academy of Allergy, Asthma and Immunology.
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