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Gene expression alters corticosteroid response in asthmatic children
Expression of theVNN1 gene allowed for differentiation between good and poor responders to systemic corticosteroid treatment among pediatric patients with asthma, according to study findings.
“Genome-wide analysis allowed us to identify a gene, VNN1, whose expression discriminated between good and poor responders to systemic corticosteroid treatment,” Gurjit Khurana Hershey, MD, PhD, director of Asthma Research at Cincinnati Children’s Hospital Medical Center, said in a press release. “This may serve as clinically useful biomarker to identify a subset of difficult-to-treat asthmatic children, and targeting the VNN1 pathway may be useful as a therapeutic strategy.”
It is estimated that effective treatment is either absent or incomplete in 40% to 70% of asthmatic children — including those who do not respond well to corticosteroid therapy — therefore suggesting the need for new treatment regimens, according to background information in the study.
Hershey and colleagues conducted a genome-wide analysis of nasal epithelial cells pooled from 57 children aged between 5 years and 18 years admitted to the emergency department at Cincinnati Children’s Hospital Medical Center for acute asthma exacerbation. Genetic expression and medical responses were compared between children who responded well to corticosteroid therapy vs. those who did not.
Results indicated that alterations in VNN1 expression were associated with systemic corticosteroid treatment response in children with acute asthma. Eight nominally significant genes (P ≤ .05) with a prediction accuracy of 0.8 or greater were identified in the cohort. In an independent prospective cohort that served to verify results of the first cohort, VNN1 gene expression appeared lower in the poor responder group vs. good responders to corticosteroid therapy (P = .04). This replicated the findings from the discovery cohort (P = .02), according to the researchers.
“Difficult-to-treat patients account for over 50% of health care costs associated with asthma,” Hershey said in the press release. “There are new drugs that may be helpful, as well as those that affect the VNN1 pathway, but they have not been tested in asthma. This study provides the basis for a biomarker to determine which patients might be best to target with new treatments.”
Research is currently ongoing to better identify the role of the VNN1 pathway in contributing to airway inflammation and hyper-responsiveness in asthma as well as to identify therapies that best target theVNN1 pathway and improve treatment in children who do not respond well to current regimens.
Disclosure: The study was funded in part by the National Institutes of Health. The researchers report no relevant financial disclosures.
