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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: This combined circulating microRNA-clinical score model predicted exacerbation in asthmatic subjects on inhaled corticosteroids better than each constituent feature alone.

Trial registration: ClinicalTrials.gov Identifier: NCT00000575 .

Keywords: Asthma exacerbation; Biomarker; Circulating microRNA.

Conflict of interest statement

Ethics approval and consent to participate

The CAMP Genetics Ancillary Study was approved by the Brigham and Women’s Hospital Internal Review Board, protocol # 2015P001622/BWH. Informed consent and assent was obtained from parents and participants respectively.

Competing interests

The authors declare that they have no conflicting interests for this study.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Univariate logistic regression models for miR-206 expression (Panel a) and asthma exacerbation clinical score (Panel b) relative to exacerbation. The horizontal axis represents the miRNA cycle threshold and asthma exacerbation clinical score for panels a and b, respectively. The right vertical axis represents number of patients. In each panel, the top (inverted) histogram represents subjects who had an exacerbation and the bottom histogram represents subjects who did not have an exacerbation. The red line represents the unadjusted logistic regression function with probability of exacerbation on the left vertical axis. For instance in panel a, as the miR-206 cycle threshold increases (abundance in blood decreases), the risk of asthma exacerbation decreases. Whereas in panel b, as the asthma exacerbation clinical score increases, the risk of asthma exacerbation increases
Fig. 2
Fig. 2
Comparison of Receiver Operator Characteristic curves between 3 models. Asthma exacerbation clinical score (blue), miRNA (red) and combined (miRNA and clinical score, green) models in the testing set data. AUROCs were 0.671, 0.714, and 0.807, respectively. A linear LOESS smoothing function was applied with 95% confidence interval shown

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