Clinical Significance of Cold-Inducible RNA-Binding Protein in Idiopathic Pulmonary Fibrosis.

BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis with variable clinical course. Early identification of patients at high risk for disease progression and death would lead to early therapeutic intervention and thereby improvement of outcomes. Cold-inducible RNA-binding protein (CIRBP) is produced in response to cellular stresses, which is implicated in multiple biological processes, including cell survival and proliferation. RESEARCH QUESTION:Is CIRBP a useful biomarker for predicting the outcomes of patients with IPF? STUDY DESIGN AND METHODS:This study included 95 and 93 patients with IPF from two independent hospitals (derivation and validation cohorts, respectively). The associations of serum CIRBP level on IPF diagnosis with disease progression within 1 year after diagnosis (ie, ≥10% relative decline in percent predicted FVC or death) and all-cause mortality were retrospectively analyzed. Discrimination performances for predicting these outcomes were evaluated using the c-index. RESULTS:Serum and lung tissue CIRBP levels were higher in patients with IPF than in control subjects. In the derivation cohort, the CIRBPhigh subgroup had significantly higher 1-year disease progression rates and lower cumulative survival rates than the CIRBPlow subgroup, and the results were replicated in the validation cohort. In multivariate analyses, high serum CIRBP level was independently associated with higher 1-year disease progression and all-cause mortality rates in both cohorts. Combining the Gender-Age-Physiology (GAP) and serum CIRBP models improved the c-indexes for predicting 1-year disease progression and all-cause mortality compared with that of each model alone. The c-indexes of serum CIRBP were particularly high in patients with GAP stage I. INTERPRETATION:This study successfully validated that serum CIRBP level was an independent predictor of 1-year disease progression and all-cause mortality in IPF. CIRBP is a promising biomarker that can help identify high-risk patients with IPF, especially in the early stage.