Key Point

The gene expression signature of acute asthma is clearly different than that of stable asthma in asthmatic children.

CINCINNATI—In children, asthma exacerbations can be readily distinguished from stable asthma by their distinct gene expression profile, a recent study has shown.¹ After analyzing nasal respiratory epithelial samples from 30 children—10 with stable asthma, 10 with acute asthma, and 10 nonatopic asthma-free controls—the authors determined which genes were activated in the asthmatic children and identified clear differences in gene expression between the groups.

“Now that we know what genes are turned on during an asthma attack, we will conduct studies to see how genetic profile can be useful in a clinical setting to personalize care,” explained lead author Gurjit K. Khurana Hershey, MD, PhD, Director of the Center for Translational Research in Asthma and Allergy at the Cincinnati Children’s Hospital Medical Center.

AN AMAZING TECHNOLOGY

Gene expression in the children’s nasal tissue was analyzed with microarray technology that enables vast amounts of genetic data to be stored on a small chip for computer analysis. “The technology is amazing,” said Dr. Hershey, “because each chip contains probes for up to 57,000 genes and you can immediately see which ones are turned on and off relative to the normal group.” In the study, microarray analysis was performed on 34,886 genes.

In the children with asthma exacerbations, 314 genes showed at least a twofold rise or fall in expression relative to the control group, versus only 166 genes in the stable asthma group. Also, the gene expression profile in the acute asthma group was highly consistent among individuals regardless of age, gender, ethnicity, and other variables, whereas the gene expression profile in stable asthma was less conserved.

“Of the genes that were turned on in acute asthma, the majority were related to the immune system,” Dr. Hershey related, “while a number of those that were turned down were related to ciliary function.” The latter finding was a surprise, she said, because one might logically expect genes associated with cilia to be up-regulated in acute asthma as a result of damage to the respiratory epithelium.

In contrast, relatively fewer immune-related genes were up-regulated in the stable asthma group. “A lot of other genes were involved in stable asthma, particularly those specific to lung architecture,” observed Dr. Hershey.

TARGETING ASTHMA THERAPY

Patients with asthma currently receive the same classes of drugs regardless of the status of their disease. “However, since different genes are up-regulated in acute and stable asthma, we may want to look into targeting therapy to the appropriate gene expression profile,” Dr. Hershey suggested.

Extensive research would be required to develop such an approach to asthma treatment. Investigators would have to determine which drugs reduce expression of the genes that are up-regulated in acute and stable asthma and how effectively they do so.

—Tamara Gibb

Reference
1. Guajardo JR, Schleifer KW, Daines MO, et al. Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma. J Allergy Clin Immunol. 2005;115:243-251.PNAS. 2005;102:186-191.

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