Whole blood microRNA markers are associated with acute respiratory distress syndrome

Abstract

Background: MicroRNAs (miRNAs) can play important roles in inflammation and infection, which are common manifestations of acute respiratory distress syndrome (ARDS). We assessed if whole blood miRNAs were potential diagnostic biomarkers for human ARDS. Methods: This nested case-control study (N = 530) examined a cohort of ARDS patients and critically ill at-risk controls. Whole blood miRNA profiles and logistic regression analyses identified miRNAs correlated with ARDS. Stratification analysis also assessed selected miRNA markers for their role in sepsis and pneumonia associated with ARDS. Receiver operating characteristic (ROC) analysis evaluated miRNA diagnostic performance, along with Lung Injury Prediction Score (LIPS). Results: Statistical analyses were performed on 294 miRNAs, selected from 754 miRNAs after quality control screening. Logistic regression identified 22 miRNAs from a 156-patient discovery cohort as potential risk or protective markers of ARDS. Three miRNAs—miR-181a, miR-92a, and miR-424—from the discovery cohort remained significantly associated with ARDS in a 373-patient independent validation cohort (FDR q < 0.05) and meta-analysis (p < 0.001). ROC analyses demonstrated a LIPS baseline area-under-the-curve (AUC) value of ARDS of 0.708 (95% CI 0.651–0.766). Addition of miR-181a, miR-92a, and miR-424 to LIPS increased baseline AUC to 0.723 (95% CI 0.667–0.778), with a relative integrated discrimination improvement of 2.40 (p = 0.005) and a category-free net reclassification index of 27.21% (p = 0.01). Conclusions: miR-181a and miR-92a are risk biomarkers for ARDS, whereas miR-424 is a protective biomarker. Addition of these miRNAs to LIPS can improve the risk estimate for ARDS.