脓毒症早期诊断生物标志物的研究进展

Advances in biomarkers for early diagnosis of sepsis

脓毒症是一种因宿主对感染反应失调而导致危及生命的器官功能障碍疾病。在重症监护病房(ICU)中,脓毒症的发病率和病死率极高。脓毒症的病理生理机制主要涉及炎症反应平衡失调、免疫功能紊乱、凝血功能障碍以及线粒体损伤等多个方面,多重机制共同作用使脓毒症的发生发展难以预测,临床上对于脓毒症的早期诊断和规范治疗仍处于探索阶段。目前最新的《脓毒症与感染性休克定义的国际共识(Sepsis-3)》推荐使用序贯器官衰竭评分(SOFA)协助临床诊断脓毒症,若患者SOFA评分>2分且合并感染即可诊断为脓毒症。SOFA评分通过结合各项检验数据对全身多个组织器官的功能损伤程度进行综合评估,但其缺乏对脓毒症的特异性识别能力,因此SOFA评分对早期诊断脓毒症及指导治疗仍存在局限性。临床上除了运用SOFA评分,还会结合降钙素原(PCT)、C-反应蛋白(CRP)、白细胞介素家族等感染标志物协助诊断脓毒症,随着组学研究的深入,越来越多的早期诊断标志物被发现,这些标志物对于脓毒症的早期诊断、治疗以及预后监测同样具有重要价值。早期诊断标志物的理想特征应具备较好的敏感性、特异性和病情适用性。现对近年来报告的针对脓毒症早期诊断具有较高效能的生物标志物进行了综述,并对它们进行了分类介绍和特点比较,以期为临床诊疗提供参考。

Sepsis is a disease in which organ function is severely jeopardized by a dysregulated host response to infection.The morbidity and mortality rates of sepsis are extremely high in the intensive care unit(ICU).The pathophysiological mechanism of sepsis is very complex,mainly involving dysregulation of the balance of inflammatory response,immune dysfunction,coagulation dysfunction and mitochondrial damage,etc.Multiple mechanisms work together to make the development of sepsis unpredictable,and the early diagnosis and standardized treatment of sepsis are still in the exploratory stage in clinical practice.The latest International Consensus on the Definition of Sepsis and Infectious Shock(Sepsis-3)recommends the use of the sequential organ failure assessment(SOFA)score to assist in the clinical diagnosis of sepsis,and if the patient's SOFA score is greater than 2 and combined with infections,the patient can be diagnosed sepsis.The SOFA score can be used to comprehensively assess the degree of functional damage to multiple tissues and organs throughout the body by combining the data from various tests,but it lacks the specificity.Therefore,the SOFA score still has limitations in early diagnosis of sepsis and guiding the treatment.In addition to the SOFA score,infection markers such as procalcitonin(PCT),C-reactive protein(CRP),and interleukin family are also used to assist in the diagnosis of sepsis.With the deepening of omics research,more and more early diagnostic markers have been discovered,and these markers are also of great value in early diagnosis,treatment,and prognostic monitoring of sepsis.The ideal characteristics of early diagnostic markers should have good sensitivity,specificity and applicability to the condition.In this paper,we reviewed the biomarkers reported to be highly effective in the early diagnosis of sepsis in recent years,and introducedtheir classification and comparison of their characteristics,to provide reference for clinical diagnosis and treatment.