Abstract

Background:
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by declining lung function and severe, irreversible scarring. The early diagnosis of IPF is particularly challenging due to the presence of nonspecific symptoms and a shortage of accurate, noninvasive biomarkers. Recently, interest in microRNAs (miRNAs) as IPF diagnostic biomarkers has emerged due to their stability and involvement in inflammation and fibrosis regulation.

Aim:
This study aimed to measure the level of circulating miRNA-374 in patients with IPF, assess the level of diagnostic accuracy of miRNA-374, and determine the relationship between miRNA-374 and lung function and various inflammatory indices in the blood.

Methods:
A case-control design was applied where 30 patients with IPF and 30 age-, sex-, and BMI-matched healthy controls were included. Lung function was assessed using FVC% and FEV1/FVC%. Hematological indices were measured with a focus on WBC, neutrophils, lymphocytes, and neutrophil percentage. The expression level of miRNA-374 was quantitated using stem-loop RT-qPCR and GAPDH as the internal control. Data were reported as means with the comparison of the means was achieved using t-tests, and correlation was done using Pearson’s coefficient, with receiver operating characteristic curve analysis used to determine diagnostic accuracy.

Results:
FVC% in IPF patients was much lower than in controls showing clear restrictive physiology (41.81 ± 6.11 vs 97.00 ± 4.36; p < 0.001). Furthermore, patients with IPF had significantly higher levels of FEV1/FVC (91.64 ± 10.1 vs 80.45 ± 1.41; p = 0.017). Furthermore, the WBC, neutrophils, neutrophil% levels, and lymphocytes showed statistically significant changes (all p < 0.05). Patients with IPF had significantly elevated levels of miRNA-374 expression (2.51 ± 0.58) compared with controls (0.41±0.10; p < 0.001). In the ROC analysis, the diagnostic accuracy was perfect (AUC = 1.000; sensitivity = specificity = 100%). miRNA-374 was positively correlated with neutrophil% (r = 0.500, p = 0.001), further supporting the association between miRNA-374 and IPF inflammation.

Conclusion:
IPF is associated with elevated levels of circulating miRNA-374, which is likely to be of diagnostic significance as it relates to neutrophilic inflammation. Therefore, circulating miRNA-374 may serve as an important non-invasive biomarker and provide an opportunity as a target for therapeutic intervention.

Key words: Biomarker; Idiopathic pulmonary fibrosis; Inflammation; miRNA-374.