Gromelsky Ljungcrantz Emily, Askman Sanna, Sjövall Fredrik, Paulsson Magnus
Infection Medicine, Department of Clinical Sciences Lund, Medical Faculty, Lund University, Lund, Sweden.
Mitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
Eur Respir Rev. 2025 Apr 30;34(176). doi: 10.1183/16000617.0229-2024. Print 2025 Apr.
Ventilator-associated pneumonia (VAP) is the most common intensive care unit-acquired infection, yet its diagnosis is complicated by the lack of reliable diagnostic criteria and validated biomarkers. Due to the compartmentalisation of the immune response, host proteins in respiratory tract samples are more likely than serum proteins to accurately identify VAP. However, a reliable biomarker is still missing and it is generally agreed that >90% sensitivity and specificity are required for the introduction of a VAP biomarker into clinical routine.
A structured database search was performed to identify publications aimed at deriving or verifying human respiratory tract VAP biomarkers. The results were screened by two independent reviewers and summarised using statistical and narrative synthesis.
40 articles were identified, focusing on 29 unique biomarkers with clinical and microbiological diagnoses of VAP as the reference standard. The most frequently studied biomarker was soluble triggering receptor expressed on myeloid cell 1 (sTREM-1) (n=16), followed by various interleukins (n=7), neutrophil-related proteins (n=8) and amylase as a surrogate for microaspiration (n=4). The target accuracy of >90% specificity and sensitivity for VAP was reported in four publications on sTREM-1, one on pentraxin-3 (PTX3) and one on heparin-binding protein (HBP). Meta-analysis of sTREM-1 resulted in a sensitivity of 78% (95% CI 61-89%) and specificity of 76% (95% CI 49-91%).
This systematic review found that no biomarker can currently be recommended for clinical use due to performance below 90% specificity or sensitivity, or insufficient data (PTX3 and HBP). Accurate clinical phenotyping into VAP subcategories may enable the discovery of VAP biomarkers with higher accuracy.
呼吸机相关性肺炎（VAP）是重症监护病房获得性感染中最常见的一种，但由于缺乏可靠的诊断标准和经过验证的生物标志物，其诊断较为复杂。由于免疫反应的区室化，呼吸道样本中的宿主蛋白比血清蛋白更有可能准确识别VAP。然而，仍缺少可靠的生物标志物，并且普遍认为将VAP生物标志物引入临床常规需要>90%的敏感性和特异性。
进行结构化数据库搜索，以识别旨在推导或验证人类呼吸道VAP生物标志物的出版物。结果由两名独立评审员筛选，并使用统计和叙述性综合进行总结。
共识别出40篇文章，重点关注29种独特的生物标志物，以VAP的临床和微生物学诊断作为参考标准。研究最频繁的生物标志物是髓样细胞表达的可溶性触发受体1（sTREM-1）（n=16），其次是各种白细胞介素（n=7）、中性粒细胞相关蛋白（n=8）以及作为微量误吸替代指标的淀粉酶（n=4）。有4篇关于sTREM-1的出版物、1篇关于五聚体蛋白3（PTX3）的出版物和1篇关于肝素结合蛋白（HBP）的出版物报道了VAP特异性和敏感性>90%的目标准确性。对sTREM-1的荟萃分析得出敏感性为78%（95%CI 61-89%），特异性为76%（95%CI 49-91%）。
本系统评价发现，由于性能低于90%的特异性或敏感性，或数据不足（PTX3和HBP），目前没有生物标志物可推荐用于临床。对VAP亚类进行准确的临床表型分析可能有助于发现准确性更高的VAP生物标志物。
