特发性肺纤维化(IPF)是一种病因不明的慢性、进行性、纤维化性间质性肺疾病(ILD),其特征是肺部结构和功能的不可逆性丧失,导致患者呼吸困难,呼吸衰竭和过早死亡。它是特发性间质肺炎最常见的类型,同时预后也最差。目前,已从IPF患者的血液、肺泡灌洗液、支气管肺组织等生物组织样本中发现多种有价值的生物标志物,尤其是通过血液中获得,因其具有易取样、创伤小、成本低、可连续重复监测等优点,具有较大的临床应用前景。本文从基因组学、血清蛋白质学和血液细胞学三个方面对近年来发现的与IPF预后相关的生物标志物进行综述,旨在为临床工作中IPF患者的管理选择合适的生物标志物提供参考,并在疾病早期更方便、快速地识别IPF预后不良的患者。 Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease (ILD) of unknown cause, characterized by irreversible loss of lung structure and function, resulting in dyspnea, respiratory failure, excessive lung function, and early death. It is the most common and the worst type of idiopathic interstitial pneumonia. At present, a variety of valuable biomarkers have been detected from biological samples such as blood, lavage fluid, and bronchopulmonary tis-sue of IPF patients. Especially from blood, because of its advantages of convenient acquisition, less trauma, low cost, and continuous monitoring, it has great prospects for clinical application. This ar-ticle reviews the biomarkers related to the prognosis of IPF discovered in recent years from three aspects: genomics, serum proteinology, and blood cytology. The purpose of this study is to provide a reference for clinical work to select appropriate biomarkers for the management of IPF patients, and to identify patients with poor prognosis of IPF at an early stage more conveniently and quickly.
特发性肺纤维化(IPF)是一种病因不明的慢性、进行性、纤维化性间质性肺疾病(ILD),其特征是肺部结构和功能的不可逆性丧失,导致患者呼吸困难,呼吸衰竭和过早死亡。它是特发性间质肺炎最常见的类型,同时预后也最差。目前,已从IPF患者的血液、肺泡灌洗液、支气管肺组织等生物组织样本中发现多种有价值的生物标志物,尤其是通过血液中获得,因其具有易取样、创伤小、成本低、可连续重复监测等优点,具有较大的临床应用前景。本文从基因组学、血清蛋白质学和血液细胞学三个方面对近年来发现的与IPF预后相关的生物标志物进行综述,旨在为临床工作中IPF患者的管理选择合适的生物标志物提供参考,并在疾病早期更方便、快速地识别IPF预后不良的患者。
特发性肺纤维化,生物标志物,预后
Jing Ren, Wencheng Yu*
Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao Shandong
Received: Sep. 21st, 2022; accepted: Oct. 14th, 2022; published: Oct. 26th, 2022
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease (ILD) of unknown cause, characterized by irreversible loss of lung structure and function, resulting in dyspnea, respiratory failure, excessive lung function, and early death. It is the most common and the worst type of idiopathic interstitial pneumonia. At present, a variety of valuable biomarkers have been detected from biological samples such as blood, lavage fluid, and bronchopulmonary tissue of IPF patients. Especially from blood, because of its advantages of convenient acquisition, less trauma, low cost, and continuous monitoring, it has great prospects for clinical application. This article reviews the biomarkers related to the prognosis of IPF discovered in recent years from three aspects: genomics, serum proteinology, and blood cytology. The purpose of this study is to provide a reference for clinical work to select appropriate biomarkers for the management of IPF patients, and to identify patients with poor prognosis of IPF at an early stage more conveniently and quickly.
Keywords:Idiopathic Pulmonary Fibrosis, Biomarkers, Prognosis
Copyright © 2022 by author(s) and Hans Publishers Inc.
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MUC5B是一种分泌型蛋白质,主要由支气管远端的粘膜下粘液腺细胞产生和分泌。其主要的功能是黏液屏障保护、气道黏膜纤毛运动清除病原体和气道抗炎防御功能 [
Toll样受体(TLR)是人类早期病原体识别系统和宿主防御系统的组成部分。TLR功能在提供细胞损伤保护和调节组织内稳态方面至关重要 [
端粒是包含数千个核苷酸串联重复序列的核蛋白结构,可以稳定染色体末端,防止DNA降解。随着细胞分裂,这些重复序列逐渐丢失,导致端粒缩短。端粒低于临界阈值会导致染色体不稳定和DNA损伤反应途径的激活,从而导致细胞衰老和凋亡 [
KL-6是在肺泡上皮细胞膜表面表达一种粘蛋白样的高分子糖蛋白。当肺泡上皮细胞增殖、活化或受损时,KL-6会释放到血液之中 [
表面活性蛋白SP-A和SP-D是分布在肺泡气液界面的脂蛋白复合物,由肺泡上皮细胞和细支气管细胞合成和分泌 [
基质金属蛋白酶是锌依赖性内肽酶,可以降解细胞外基质(ECM)所有成分 [
一份源于吡非尼酮和IFNg-1b试验的汇总数据显示,在调整人口统计学,生理功能,合并症特征和长期使用免疫抑制剂后,单核细胞计数为0.60~0.95 × 109/L或> 0.95 × 109/L的IPF患者具有更高的IPF进展风险、全因住院及全因死亡风险,且单核细胞计数与研究结果的关系有别于其他白细胞计数 [
红细胞分布宽度(RDW)可以作为评价肺部疾病、心血管疾病等疾病预后的血清学标志物,并已发现与IPF患者预后相关。RDW与体内炎症介质水平相关,已成为反映炎症反应过程的新型标志物。一项包含319例IPF患者的队列研究显示,RDW值处于正常范围内的IPF患者中位生存期为43.1个月,而RDW > 15%的IPF患者中位生存期仅为16.3个月。RDW变化小于或大于10的患者的中位生存时间分别为43.0个月和23.9个月 [
中性粒细胞淋巴细胞比率(NLR)和血小板–淋巴细胞比率(PLR)是炎症和氧化应激的生物标志物。NLR和PLR的表达与多种疾病的不良预后相关,包括慢性阻塞性肺病、2019冠状病毒病(COVID-2019)、肺栓塞、心血管疾病、类风湿性关节炎和各种实体瘤。一些研究评估了NLR和PLR在IPF患者中的预后价值,表明较高的NLR和PLR可能导致较差的预后。此外,单核细胞数量是IPF进展、全因住院和全因死亡率的独立危险因素。在一项回顾性队列研究中,证实NLR和PLR与PaO2/FiO2显著负相关 [
综上所述,随着近年来IPF研究的逐步深入,与IPF预后相关的生物标志物研究取得了显著进展。除了上述的生物标志物,还有LOXL2、纤维细胞、CCL-8、YKL-40、CXCL13、抗热休克蛋白70等都被作为IPF的生物标志物在研究。但很多研究都来自观察单个队列,病例组的数量相对少,缺乏前瞻性。总之,探索IPF的生物标志物的领域还需要进一步的深入研究,即需要更多的大样本前瞻性研究来证实生物标志物与IPF之间的相关性,从而为临床应用做好充分的准备。
任 静,于文成. 特发性肺纤维化预后生物标志物的研究进展Research Progress of Prognostic Biomarkers in Idiopathic Pulmonary Fibrosis[J]. 临床医学进展, 2022, 12(10): 9569-9575. https://doi.org/10.12677/ACM.2022.12101384