Circulating microRNAs and prediction of asthma exacerbation in childhood asthma

Alvin T. Kho, Michael J. McGeachie, Kip G. Moore, Jody M. Sylvia, Scott T. Weiss, Kelan G. Tantisira

Circulating microRNAs have shown promise as non-invasive biomarkers and predictors of disease activity. Prior asthma studies using clinical, biochemical and genomic data have not shown excellent prediction of exacerbation. We hypothesized that a panel of circulating microRNAs in a pediatric asthma cohort combined with an exacerbation clinical score might predict exacerbation better than the latter alone. Serum samples from 153 children at randomization in the Childhood Asthma Management Program were profiled for 754 microRNAs. Data dichotomized for asthma exacerbation one year after randomization to inhaled corticosteroid treatment were used for binary logistic regression with miRNA expressions and exacerbation clinical score. 12 of 125 well-detected circulating microRNAs had significant odd ratios for exacerbation with miR-206 being most significant. Each doubling of expression of the 12 microRNA corresponded to a 25-67% increase in exacerbation risk. Stepwise logistic regression yielded a 3-microRNA model (miR-146b, miR-206 and miR-720) that, combined with the exacerbation clinical score, had excellent predictive power with a 0.81 AUROC. These 3 microRNAs were involved in NF-kβ and GSK3/AKT pathways. This combined circulating microRNA-clinical score model predicted exacerbation in asthmatic subjects on inhaled corticosteroids better than each constituent feature alone. ClinicalTrials.gov Identifier: NCT00000575 .