Blood Analysis of 2 microRNAs May Help to Predict Risk of Acute Flares in IPF Patients

Differences in the expression of small RNAs, called microRNAs, which may be useful for identifying patients with idiopathic pulmonary fibrosis (IPF) at risk of an acute flare.

The study, “Plasma microRNAs are associated with acute exacerbation in idiopathic pulmonary fibrosis,” was published in the journal Diagnostic Pathology.

An acute IPF exacerbation, defined as a sudden worsening in respiration (dyspnea) and lung function, is extremely serious: 50% of IPF patients die of these flares — a reason doctors are trying to better predict a patient’s risk of an exacerbation.

microRNAs (also called miRNAs) are small RNA molecules increasingly known for their role as regulators of gene expression. microRNAs are present, at quite stable levels, throughout the circulatory system. Several studies have shown that alterations in miRNAs levels in serum samples could be used as noninvasive biomarkers for numerous diseases, including cancers and autoimmune diseases.

Researchers investigated whether differences in certain microRNAs were evident in IPF patients during an acute exacerbation state compared to a stable disease state, and if these differences were reliable biomarkers for predicting acute exacerbation.

They looked at miRNAs plasma levels in two groups of IPF patients, three in a period of acute exacerbation and three with stable IPF, and compared to three healthy controls. They found that six miRNAs showed statistically significant differences in expression between acute exacerbation and stable IPF patients. (Gene expression refers to the process by which information encoded in a gene is used in the synthesis of a functional product, like proteins.)

Additional analyses showed that the expression of a miRNA, called let-7d-5p, was lower in the plasma of stable patients and lower still, a pronounced difference, in acute exacerbation patients. Another microRNA, miRNA-25-3p, was also down-regulated (reduced levels) in stable patients, but significantly up-regulated (increased levels) in those with acute exacerbation. This suggests that, indeed, a different microRNA circulation profile exists between stable and acute exacerbation disease states.

Researchers then tested the effectiveness of the two miRNAs in detecting acute exacerbation patients among all patients. They found that the diagnostic accuracy, when the two miRNAs were combined, rose to 66.7% from 50%.

Overall, these results suggest that the two miRNAs — miRNA-25-3p and let-7d-5p — are differentially expressed in plasma samples of patients having an acute exacerbation and in those with  stable IPF. Analyzing the expression of both these miRNAs may detect people at risk of an acute exacerbation.