Associations of Serological Biomarkers of sICAM-1, IL-1β, MIF, and su-PAR with 3-Month Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

Xuran Li,Haoran Chen,Ruyi Zou,Xiaoqin Liu,Ying Zhou,Xiaohua Qiu,Yonglong Xiao,Hourong Cai,Jinghong Dai

doi:10.1155/2020/4534272

Abstract

Objective To investigate prognostic values of serum biomarkers of soluble intercellular adhesion molecule 1 (sICAM-1), macrophage migration inhibitor factor (MIF), interleukin 1β (IL-1β), and soluble urokinase plasminogen activator receptor (su-PAR) in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Methods From August 2017 to November 2019, 122 consecutive IPF patients treated in our center were classified as stable IPF and AE-IPF based on the newly published international guidelines. Serum levels of four biomarkers at admission were measured by the enzyme-linked immunosorbent assay (ELISA). The primary endpoint was 3-month mortality. The log-rank test and logistic regression analysis were used to evaluate the effects of these biomarkers for survival in patients with AE-IPF. Cox proportional hazards analysis was performed to evaluate the prognostic values of serological biomarkers and clinical data. Results Eighty-one patients were diagnosed with stable IPF, and 41 AE-IPF patients were enrolled in the study. Serum levels of sICAM-1 (p < 0.001), IL-1β (p < 0.001), MIF (p < 0.001), and su-PAR (p < 0.001) in patients with IPF were significantly increased compared to those in healthy controls. All the four biomarkers were elevated in patients with AE-IPF compared to those with stable IPF. The 3-month mortality in AE-IPF was 56.1% (23/41). Increased levels of MIF (p = 0.01) and IL-1β (>5 pg/mL, p = 0.033) were independent risk factors for 3-month mortality in patients with AE-IPF. Conclusions We showed the higher serum levels of IL-1β, and MIF had prognostic values for 3-month mortality in AE-IPF. This study provided a clue to promote our understanding in the pathogenesis of the disease.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a progressive, interstitial lung disease with unknown etiologies [1, 2]
The criteria for a diagnosis of IPF were as follows: (a) exclusion of other known causes of interstitial lung disease (ILD), (b) the presence of a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) in patients not subjected to surgical lung biopsy, and (c) specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy
We showed that serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), interleukin 1β (IL-1β), migration inhibitor factor (MIF), and soluble urokinase plasminogen activator receptor (su-PAR) were significantly elevated in patients with IPF compared to healthy controls

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive, interstitial lung disease with unknown etiologies [1, 2]. The clinical course of IPF is highly heterogeneous. Some patients could remain relatively stable with slow decline of pulmonary function, while others may suffer sudden deterioration so called acute exacerbation of idiopathic pulmonary fibrosis (AEIPF). AE-IPF is characterized as an acute worsening of dyspnea and newly emerging ground glass opacities (GGO) on the background of a usual interstitial pneumonia (UIP) pattern in high-resolution computed tomography (HRCT), which has poor prognosis for the median survival of approximately 3-4 months [3,4,5]. The pathogenesis of AE-IPF is still unclear. Increasing evidences indicate that acute inflammation may be responsible for the occurrence of AE-IPF rather than an abrupt fibrosis aggravation. Proinflammatory cytokines intercellular adhesion molecule 1 (sICAM-1) and interleukin 1β (IL-1β) have been reported to be associated with another severe condition, acute respiratory distress syndrome (ARDS), which shares several pathophysiological features with AE-

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Conclusion