Genetic Pathway Explains Lack of Response to Asthma Treatment
By monitoring changes in gene expression, clinicians can identify children who will not respond to common asthma medications and may benefit from alternate treatment, according to a study published April 21, in the Journal of Allergy and Clinical Immunology. Nasal expression of the VNN1 gene may be a clinically useful marker to identify a biological […]
By monitoring changes in gene expression, clinicians can identify children who will not respond to common asthma medications and may benefit from alternate treatment, according to a study published April 21, in the Journal of Allergy and Clinical Immunology. Nasal expression of the VNN1 gene may be a clinically useful marker to identify a biological cause for difficult-to-treat asthma. Of the seven million children with asthma, it has been reported that nearly twothirds have had at least one attack in the past year. While systemic corticosteroid treatment is considered the most effective medication for controlling chronic asthma and rescue during acute exacerbation, treatment efficacy varies. In the current study, nasal epithelial cells were collected during presentation to the emergency department for an acute asthma attack and again 18 to 24 hours later. Genome-wide expression profiling was performed before and after treatment in 15 children as part of a discovery cohort. Gene expression ratios were analyzed to identify associations with corticosteroid treatment response phenotypes. These potentially discriminatory genes were then tested in a new cohort of 25 patients. The researchers found that VNN1 mRNA expression was lower in the poor responder group versus the good responder group. After treatment, methylation levels at the CpG4 site significantly differed, with a decrease in methylation among the poor responders and an increase in the good responders. The researchers believe methylation at the CpG4 site might be a “crucial molecular event regulating VNN1 gene expression and modulating the response to corticosteroid treatment.” Relatedly, changes in VNN1 gene expression after treatment were significantly inversely associated with hospital length of stay, with every unit increase in VNN1 expression tied to a decrease in stay by 7.7 hours. “Nasal epithelial cells can be readily sampled safely during an asthma attack and reflect changes observed in the bronchial airways of asthmatic children,” write the authors led by Chang Xiao, M.D., Ph.D., from Cincinnati Children’s Hospital Medical Center in Ohio. “These might be clinically useful biomarkers to identify children with a biologic cause for poor corticosteroid response who would benefit from a different treatment plan.” Takeaway: VNN1 gene expression may be a clinically important marker to improve suboptimal management of childhood asthma in difficult-to-treat patients.