Studies show path to tailored asthma prescribing

Young asthmatic children who have not had the disease long could respond best to leukotriene receptor antagonists, but those with an allergic component and low pulmonary function might need inhaled corticosteroids. African-Americans may require higher doses to control their asthma. And the genetic expression profiles of nasal cells are different in those whose disease is stable versus those who are experiencing or at high risk of an asthma attack.

These are the conclusions of two studies published in the February Journal of Allergy and Clinical Immunology and another study in the journal Chest that experts say will lead to more effective prescribing from the get-go.

"We're hopefully getting closer to being able to identify why certain people respond to one type of treatment and some to another," said William E. Berger, MD, past president of the American College of Allergy, Asthma and Immunology.

Authors acknowledged, though, that none of these data is quite ready to play a role in determining initial prescribing, and the American Medical Association encourages physicians to make use of treatment guidelines from the National Heart, Lung and Blood Institute and the American Academy of Allergy, Asthma and Immunology.

"These things all have to be tested, validated and applied," said Stanley Szefler, MD, lead author on one of the JACI papers and head of pediatric clinical pharmacology at the National Jewish Medical and Research Center in Denver. "But it's an exciting era."

While these papers might not yet be ready to determine first-line treatment, physicians who treat asthma say they provide much needed explanations for why various treatment modalities may or may not work and could guide second-line choices.

"All three of them provide us some evidence for what clinically had been noticed for quite a while, and that's very important to have," said Barbara Yawn, MD, a family physician in Rochester, Minn., and director of research at Olmsted Medical Center. "But none change the initial treatment. What they do is remind us that if it's not working, there may be a reason. Maybe you need to add another kind of medication earlier instead of later or try something else entirely."

Nearing prime time

Experts agreed, however, that one paper was particularly close to guiding treatment choices.

Findings by Dr. Szefler showed that various biomarkers of inflammation could indicate whether inhaled corticosteroids or leukotriene receptor agonists or both would be most effective. Demographic factors such as duration of illness and the age of the patient also played a role.

"Right now, physicians base their decisions on things like ease of administration, safety of the medications, convenience and cost," Dr. Szefler said. "This paper says that maybe you ought to look at some of the patient features and add that into the equation."

Though this paper is a likely candidate for incorporation into clinical practice, physicians complained that many of the tests used to make these decisions were not readily accessible.

"Measures of inflammation like exhaled nitric oxide, eosinophil cationic protein and urinary leukotrienes -- we don't order those," said Kathleen Sheerin, MD, staff physician with Atlanta Allergy and Asthma Associates. "You can't get them."

Another paper, however, did suggest an easy-to-determine factor that could affect treatment. The paper in Chest, also based on studies conducted at Denver's National Jewish Medical and Research Center, found that t-lymphocytes taken from African-Americans were less responsive to corticosteroids in vitro than that of Caucasians. This finding was true whether the subjects had asthma or not. The authors suggest that this difference indicates that there are more than socioeconomic factors contributing to the additional burden of asthma-related morbidity and mortality among African-Americans.

"There may be an inherent difference ... that may predispose [African Americans] to poorer response to steroids," said Ronina A. Covar, MD, one of the study authors and a pediatric allergist. "In those patients who are not responding to recommended doses and, especially among blacks, there might be a reason to consider higher dosing or alternative or complementary treatment."

The third study, conducted at the Cincinnati Children's Hospital and also published in JACI, suggested that genetic profiles also might some day play a role in treatment courses. Researchers identified the gene expression signatures that indicated whether a child's asthma was stable or experiencing an exacerbation.

These findings are furthest from application in clinical practice, but authors suggest that it eventually could lead to new drug targets or might indicate children at risk for a worsening in their condition.

"Now that we know what genes are turned on during an asthma attack, we will conduct studies to see if this genetic profile can be used to customize care," said Gurjit K. Khurana Hershey, MD, PhD, senior author and director of the Center for Translational Research in Asthma and Allergy at Cincinnati Children's Hospital.