Grover Vimal, Pantelidis Panagiotis, Soni Neil, Takata Masao, Shah Pallav L, Wells Athol U, Henderson Don C, Kelleher Peter, Singh Suveer
Magill Department of Anaesthesia, Critical Care and Pain, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, United Kingdom; Immunology Section, Department of Medicine, Imperial College, London, United Kingdom; Department of Surgery and Cancer, Imperial College, London, United Kingdom.
Immunology Section, Department of Medicine, Imperial College, London, United Kingdom; Department of Immunology, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
PLoS One. 2014 Oct 7;9(10):e109686. doi: 10.1371/journal.pone.0109686. eCollection 2014.
Ventilator-associated pneumonia (VAP) increases mortality in critical illness. However, clinical diagnostic uncertainty persists. We hypothesised that measuring cell-surface and soluble inflammatory markers, incorporating Triggering Receptor Expressed by Myeloid cells (TREM)-1, would improve diagnostic accuracy.
A single centre prospective observational study, set in a University Hospital medical-surgical intensive Care unit, recruited 91 patients into 3 groups: 27 patients with VAP, 33 ventilated controls without evidence of pulmonary sepsis (non-VAP), and 31 non-ventilated controls (NVC), without clinical infection, attending for bronchoscopy. Paired samples of Bronchiolo-alveolar lavage fluid (BALF) and blood from each subject were analysed for putative biomarkers of infection: Cellular (TREM-1, CD11b and CD62L) and soluble (IL-1β, IL-6, IL-8, sTREM-1, Procalcitonin). Expression of cellular markers on monocytes and neutrophils were measured by flow cytometry. Soluble inflammatory markers were determined by ELISA. A biomarker panel ('Bioscore'), was constructed, tested and validated, using Fisher's discriminant function analysis, to assess its value in distinguishing VAP from non VAP.
The expression of TREM-1 on monocytes (mTREM-1) and neutrophils (nTREM-1) and concentrations of IL-1β, IL-8, and sTREM-1 in BALF were significantly higher in VAP compared with non-VAP and NVC (p<0.001). The BALF/blood mTREM-1 was significantly higher in VAP patients compared to non-VAP and NVC (0.8 v 0.4 v 0.3 p<0.001). A seven marker Bioscore (BALF/blood ratio mTREM-1 and mCD11b, BALF sTREM-1, IL-8 and IL-1β, and serum CRP and IL-6) correctly identified 88.9% of VAP cases and 100% of non-VAP cases.
A 7-marker bioscore, incorporating cellular and soluble TREM-1, accurately discriminates VAP from non-pulmonary infection.
呼吸机相关性肺炎（VAP）会增加危重症患者的死亡率。然而，临床诊断仍存在不确定性。我们假设，检测细胞表面和可溶性炎症标志物，包括髓系细胞表达的触发受体（TREM）-1，将提高诊断准确性。
在一家大学医院的内科-外科重症监护病房进行了一项单中心前瞻性观察研究，将91例患者分为3组：27例VAP患者、33例无肺部感染证据的机械通气对照患者（非VAP）和31例无临床感染的非机械通气对照患者（NVC），这些患者均接受支气管镜检查。对每个受试者的支气管肺泡灌洗液（BALF）和血液配对样本进行感染相关生物标志物分析：细胞标志物（TREM-1、CD11b和CD62L）和可溶性标志物（IL-1β、IL-6、IL-8、可溶性TREM-1、降钙素原）。通过流式细胞术检测单核细胞和中性粒细胞上细胞标志物的表达。通过酶联免疫吸附测定法测定可溶性炎症标志物。使用Fisher判别函数分析构建、测试并验证了一个生物标志物组合（“生物评分”），以评估其在区分VAP和非VAP方面的价值。
与非VAP和NVC相比，VAP患者BALF中单核细胞（mTREM-1）和中性粒细胞（nTREM-1）上TREM-1的表达以及IL-1β、IL-8和可溶性TREM-1的浓度显著更高（p<0.001）。与非VAP和NVC相比，VAP患者的BALF/血液mTREM-1显著更高（0.8对0.4对0.3，p<0.001）。一个包含七个标志物的生物评分（BALF/血液mTREM-1和mCD11b比值、BALF可溶性TREM-图1可溶性TREM-1、IL-8和IL-1β、血清CRP和IL-6）正确识别了88.9%的VAP病例和100%的非VAP病例。
一个包含细胞和可溶性TREM-1的七标志物生物评分能够准确区分VAP与非肺部感染。
