嗜酸性粒细胞颗粒蛋白在慢性鼻窦炎中的应用：用于疾病特征描述与结局的生物标志物效用的系统评价

文献信息

中文摘要

背景/目的： 慢性鼻窦炎（CRS）是一种异质性炎症性疾病，通过内型分型对其认识不断深入，其中嗜酸性慢性鼻窦炎（eCRS）代表一种临床上独特且常难治的表型。嗜酸性粒细胞部分通过释放四种高阳离子颗粒蛋白——主要碱性蛋白（MBP）、嗜酸性粒细胞阳离子蛋白（ECP）、嗜酸性粒细胞过氧化物酶（EPX）和嗜酸性粒细胞来源神经毒素（EDN）——发挥其致病作用，每种蛋白具有不同的生物学活性以及可测量的组织和全身表达谱。尽管对CRS管理的精准医学方法兴趣日益增长，这些颗粒蛋白作为生物标志物的临床效用尚未被系统描述。本系统评价评估嗜酸性粒细胞颗粒蛋白作为CRS生物标志物的诊断和预后效用。方法：本系统评价按照PRISMA（系统评价和荟萃分析首选报告项目）2020指南进行，并前瞻性注册于PROSPERO（CRD420261399189）。检索PubMed、Embase、Web of Science和Cochrane Library，纳入在成人CRS患者的组织、血清/血浆、鼻分泌物、灌洗液或鼻拭子中测量MBP、ECP、EPX或EDN并报告预设临床结局（内型/表型区分、疾病严重程度、复发或术后结局）的研究。报告的统计量以p < 0.05视为显著。由于纳入研究间存在显著的方法学异质性和结局报告不完整，未进行荟萃分析。结果：在识别的708篇参考文献中，71项研究符合纳入标准。在纳入研究中，73%为横断面研究，24%为队列研究（前瞻性或回顾性），1%归类为病例对照研究，1%为随机对照试验。ECP是评估最广泛的生物标志物，在符合纳入标准的研究中有65%对其进行了评估。若干研究评估了该蛋白作为区分嗜酸性与非嗜酸性疾病以及区分慢性鼻窦炎伴鼻息肉（CRSwNP）与慢性鼻窦炎不伴鼻息肉（CRSsNP）的工具，结果令人鼓舞。EPX研究较少，但显示出高诊断准确性，包括在微创鼻分泌物和拭子采样中的良好表现。若干研究证明，颗粒蛋白与客观影像学或内镜严重程度的相关性比与患者报告症状评分的相关性更为一致。ECP对术后复发和疾病控制显示出可重复的预后价值。结论：嗜酸性粒细胞颗粒蛋白是用于CRS内型分型和预后判断的有前景的生物标志物。需要进一步工作以直接比较这些蛋白的诊断准确性、标准化标本处理和定量方法，并建立适合临床使用的阈值。最终，需要大规模前瞻性研究来确定这些生物标志物能否可靠地预测临床结局并指导生物制剂治疗候选者的选择。

英文摘要

Background/Objectives: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition increasingly understood through endotyping, with eosinophilic CRS (eCRS) representing a clinically distinct and often refractory phenotype. Eosinophils exert their pathogenic effects in part through the release of four highly cationic granule proteins-major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPX), and eosinophil-derived neurotoxin (EDN)-each with distinct biological activities and measurable tissue and systemic expression profiles. Despite growing interest in precision medicine approaches to CRS management, the clinical utility of these granule proteins as biomarkers has not been systematically characterized. This systematic review evaluates the diagnostic and prognostic utility of eosinophil granule proteins as biomarkers in CRS. Methods: This systematic review was conducted per PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines and prospectively registered in PROSPERO (CRD420261399189). PubMed, Embase, Web of Science, and Cochrane Library were searched for studies measuring MBP, ECP, EPX, or EDN in tissue, serum/plasma, nasal secretions, lavage fluid, or nasal swabs in adults with CRS, reporting a predefined clinical outcome (endotype/phenotype discrimination, disease severity, recurrence, or postoperative outcomes). Reported statistics were deemed significant if p < 0.05. Meta-analysis was not conducted due to substantial methodological heterogeneity and incomplete outcome reporting across the included studies. Results: Of 708 identified references, 71 studies met inclusion criteria. Of the included studies, 73% were cross-sectional studies, and 24% were cohort studies (prospective or retrospective), with 1% classified as case-control and 1% as a randomized controlled trial. ECP was the most extensively evaluated biomarker, evaluated in 65% of the studies meeting inclusion criteria. Several studies evaluated this protein as a tool to discriminate eosinophilic from non-eosinophilic disease and chronic rhinosinusitis with nasal polyps (CRSwNP) from chronic rhinosinusitis without nasal polyps (CRSsNP), with promising results. EPX was less frequently studied but demonstrated a high diagnostic accuracy, including strong performance in minimally invasive nasal secretion and swab sampling. Several studies demonstrated that granule proteins correlated more consistently with objective radiographic or endoscopic severity than with patient-reported symptom scores. ECP showed reproducible prognostic value for postoperative recurrence and disease control. Conclusions: Eosinophil granule proteins are promising biomarkers for endotyping and prognostication in CRS. Further work is needed to compare the diagnostic accuracy of these proteins directly, to standardize specimen handling and quantification methods, and to establish threshold values suitable for clinical use. Ultimately, large-scale prospective studies will be required to determine whether these biomarkers can reliably prognosticate clinical outcomes and inform selection of candidates for biologic therapy.