COPD-Associated miR-145-5p is Downregulated in Early Decline FEV1 Trajectories in Childhood Asthma.

Abstract Background Many microRNAs (miRNAs) have been associated with asthma and COPD. Longitudinal lung function growth trajectories of childhood asthmatics – normal growth (NG); reduced growth (RG); early decline (ED); and reduced growth with an early decline (RGED) – have been observed, with RG and RGED associated with adverse outcomes, including COPD. Objective To determine if circulating miRNAs from an early age in asthmatic children would be prognostic of reduced lung function growth patterns over the next 16 years. Methods We performed small RNA sequencing on serum from 492 children aged 5-12 with mild-to-moderate asthma from the CAMP clinical trial, who were subsequently followed for 12-16 years. miRNAs were assessed for differential expression between previously assigned lung function growth patterns. Results We had 448 samples and 259 miRNAs for differential analysis. In the comparison of the normal to the most severe group, NG to RGED, we found one strongly dysregulated miRNA, hsa-miR-145-5p (p Conclusion Our results show that miR-145-5p is associated with the early decline patterns of lung function growth leading to COPD in children with asthma, and additionally increases airway smooth muscle cell proliferation. This represents a significant extension of our understanding of the role of miR-145-5p in COPD and suggests that reduced expression of miR-145-5p is a risk factor for early decline of long-term lung.