Tomos Ioannis, Roussis Ioannis, Matthaiou Andreas M, Dimakou Katerina
5th Department of Respiratory Medicine, 'SOTIRIA' Chest Diseases Hospital of Athens, 11527 Athens, Greece.
Laboratory of Molecular and Cellular Pneumonology, Medical School, University of Crete, 714 09 Heraklion, Greece.
Biomedicines. 2023 Oct 16;11(10):2796. doi: 10.3390/biomedicines11102796.
Idiopathic pulmonary fibrosis (IPF) represents a chronic progressive fibrotic interstitial lung disease of unknown cause with an ominous prognosis. It remains an unprecedent clinical challenge due to its delayed diagnosis and unpredictable clinical course. The need for accurate diagnostic, prognostic and predisposition biomarkers in everyday clinical practice becomes more necessary than ever to ensure prompt diagnoses and early treatment. The identification of such blood biomarkers may also unravel novel drug targets against IPF development and progression. So far, the role of diverse blood biomarkers, implicated in various pathogenetic pathways, such as in fibrogenesis (S100A4), extracellular matrix remodelling (YKL-40, MMP-7, ICAM-1, LOXL2, periostin), chemotaxis (CCL-18, IL-8), epithelial cell injury (KL-6, SP-A, SP-D), autophagy and unfolded protein response has been investigated in IPF with various results. Moreover, the recent progress in genetics in IPF allows for a better understanding of the underlying disease mechanisms. So far, the causative mutations in pulmonary fibrosis include mutations in telomere-related genes and in surfactant-related genes, markers that could act as predisposition biomarkers in IPF. The aim of this review is to provide a comprehensive overview from the bench to bedside of current knowledge and recent insights on biomarkers in IPF, and to suggest future directions for research. Large-scale studies are still needed to confirm the exact role of these biomarkers.
特发性肺纤维化（IPF）是一种病因不明的慢性进行性纤维化间质性肺疾病，预后不良。由于其诊断延迟和临床病程不可预测，它仍然是一个前所未有的临床挑战。在日常临床实践中，对准确的诊断、预后和易感性生物标志物的需求比以往任何时候都更加必要，以确保及时诊断和早期治疗。识别此类血液生物标志物也可能揭示针对IPF发生和发展的新药物靶点。到目前为止，已经在IPF中研究了多种血液生物标志物的作用，这些生物标志物涉及各种致病途径，如纤维生成（S100A4）、细胞外基质重塑（YKL-40、MMP-7、ICAM-1、LOXL2、骨膜蛋白）、趋化作用（CCL-18、IL-8）、上皮细胞损伤（KL-6、SP-A、SP-D）、自噬和未折叠蛋白反应，结果各异。此外，IPF遗传学的最新进展有助于更好地理解潜在的疾病机制。到目前为止，肺纤维化的致病突变包括端粒相关基因和表面活性剂相关基因的突变，这些标志物可作为IPF的易感性生物标志物。本综述的目的是全面概述从实验室到临床床边关于IPF生物标志物的当前知识和最新见解，并提出未来的研究方向。仍需要大规模研究来确认这些生物标志物的确切作用。
