Eosinophilic COPD Patients Display a Distinctive Serum miRNA Profile From Asthma and Non-eosinophilic COPD

Abstract

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases that may overlap in some individuals. Asthma COPD overlap (ACO) is a heterogeneous conditions that includes smoking-asthma (SA) and COPD with eosinophilia (COPDe). MicroRNAs (miRNA) are regulators of gene expression with a great potential as biomarkers. ObjectivesThe objective of this study was to identify distinctive miRNA signatures in patients from the whole spectrum of chronic obstructive bronchial disease (SA, COPDe, non-smoking asthmatics (NSA), and COPD) that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. MethodsFrom a previously characterized cohort of ACO, COPD and asthma patients, we selected a discovery group of 40 patients for miRNA expression profiling by means of microarray technology. Differential expression of miRNAs were validated by quantitative PCR in the complete cohort (n=274). ResultsThirty differentially expressed miRNAs (eBAYES p<0.05, fold change ≥2) were found among the different groups of patients regarding COPDe: 19 COPD-vs-COPDe, 13 NSA-vs-COPDe, 11 SA-vs-COPDe. A characteristic down-regulated miRNA expression pattern was identified in COPDe patients. Differential expression of miR-619-5p and miR-4486 in COPDe patients were validated in the complete cohort (n=274). ConclusionsWe postulate that COPDe patients show a characteristic expression profile of miRNAs distinctive from asthma and COPD. Also that SA and COPDe patients, which have been typically clustered in the ACO group, display distinct molecular events.