Background: Inhaled corticosteroids (ICS) are the most effective and most prescribed asthma controller medications. However, the response of asthma patients to ICS is inconsistent and difficult to measure. We have previously defined a Cross-sectional Asthma STEroid Response (CASTER) measure of ICS response, based on a combination of asthma control indicators and spirometry measures. MicroRNAs (miRNAs) can be effective tools as a biomarker that predict the response to ICS treatment.
Objective: The purpose of this study was to identify key associations between circulating miRNAs and ICS response in childhood asthma.
Methods: Small RNA sequencing in peripheral blood serum from 580 children with asthma on ICS treatment from The Genetics of Asthma in Costa Rica Study was used. miRNAs were assessed for differential expression between good and poor CASTER/ICS response using DESeq2. Experimentally validated gene targets of these miRNAs were identified using the MultimiR R package and enriched biological pathway clusters using DAVID.
Results: 580 samples and 317 miRNAs were used for differential analysis. We identified 35 dysregulated miRNAs between good and poor ICS response groups at 5% FDR. Biological pathway enrichment analysis of target genes highlighted Rap1, Toll-like receptor, ErbB, T cell receptor, TGF-beta, p53, Ras, Jak-STAT, Wnt, Chemokine and B cell receptor signaling pathways at FDR <0.01.
Conclusion: This study highlighted significant association between circulating miRNAs and ICS response. These miRNAs regulate the expression of target genes involved in well-known asthma-associated pathways, which point to possible mechanisms of action for these miRNAs, including airway hyperreactivity, airway remodeling, and inflammatory response.