肺炎继发脓毒症患者血清sFasL和s-Met水平及预后评估价值

doi:10.11958/20230029

摘要/Abstract

摘要：

目的探讨肺炎继发脓毒症患者的血清可溶性Fas配体（sFasL）和可溶性间质表皮转化因子（s-Met）的临床预后价值。方法纳入150例肺炎继发脓毒症患者并根据其入院28 d生存情况分为存活组（96例）和死亡组（54例），另纳入70例肺炎患者为肺炎组，60例体检健康者为对照组。酶联免疫吸附试验检测血清sFasL和s-Met水平。Spearman秩相关分析肺炎继发脓毒症患者sFasL、s-Met水平与序贯器官衰竭评分（SOFA）、快速序贯器官衰竭评分（q-SOFA）的相关性。多因素Logistic回归分析影响肺炎继发脓毒症患者死亡的危险因素。受试者工作特征曲线分析各指标对肺炎继发脓毒症患者死亡的诊断价值。结果对照组、肺炎组入院即刻及肺炎继发脓毒症组入院时sFasL和s-Met水平依次升高（P<0.05）。与存活组相比，死亡组0、24、48、72及120 h血清sFasL和s-Met水平均较高（均P<0.05）。肺炎继发脓毒症患者血清sFasL、s-Met及PCT与SOFA、q-SOFA呈正相关性（均P<0.01）。较高水平血清PCT、sFasL、s-Met和q-SOFA是影响肺炎继发脓毒症患者死亡的独立危险因素。血清PCT、sFasL、s-Met和q-SOFA联合检测对肺炎继发脓毒症患者死亡预测的曲线下面积（AUC）为0.872（95%CI：0.838~0.909），高于血清PCT、sFasL、s-Met和q-SOFA单项指标检测0.778（95%CI：0.739~0.817）、0.795（95%CI：0.761~0.829）、0.712（95%CI：0.672~0.753）、0.815（95%CI：0.774~0.857），Z分别为6.450、4.305、5.117、2.384（均P<0.05）。结论肺炎继发脓毒症患者血清sFasL和s-Met是评估肺炎继发脓毒症预后的血清标志物。

关键词: 脓毒症, 肺炎, 预后, 可溶性Fas配体, 可溶性间质表皮转化因子, 序贯器官衰竭评分

Abstract:

Objective To investigate the prognostic value of serum soluble Fas ligand (sFasL) and soluble interstitial epidermal transforming factor (s-Met) in patients with pneumonia and sepsis. Methods A total of 150 patients with pneumonia secondary sepsis were were divided into the survival group (96 cases) and the death group (54 cases) according to the prognosis of 28 days after admission. Seventy patients with pneumonia were selected as the pneumonia group, and 60 healthy people were selected as the control group. Serum sFasL and s-Met levels were detected by ELISA in all subjects. Spearman rank correlation analysis was used for correlation analysis of sFasL, s-Met levels and SOFA, q-SOFA scores in patients with pneumonia secondary sepsis. Multivariate Logistic regression analysis was used to analyze factors influencing the death of patients with pneumonia secondary sepsis. The diagnostic value of each index in death of patients with pneumonia secondary sepsis was analyzed by receiver characteristic operating curve. Results Levels of sFasL and s-Met increased sequentially immediately after admission in the control group, the pneumonia group and the pneumonia combined with sepsis group (P<0.05). Compared with the survival group, serum sFasL and s-Met levels were higher at 0, 24, 48, 72 and 120 h in the death group (P<0.05). Serum PCT, sFasL, s-Met and q-SOFA score were independent risk factors for death of patients with pneumonia secondary sepsis. The area under the curve of the combined detection of serum PCT, sFasL, s-Met, and q-SOFA scores for predicting mortality in patients with pneumonia secondary sepsis was 0.872 (0.838-0.909), which was higher than the single indicator detection of serum PCT, sFasL, s-Met, and q-SOFA scores of 0.778 (0.739-0.817), 0.795 (0.761-0.829), 0.712 (0.672-0.753) and 0.815 (0.774-0.857) (Z=6.450, 4.305, 5.117, 2.384, all P<0.05). Conclusion The serum sFasL and s-Met levels in patients with pneumonia secondary sepsis are serum biomarkers for evaluating the prognosis of pneumonia secondary sepsis patients.

Key words: sepsis, pneumonia, prognosis, soluble Fas ligand, soluble mesenchymal epidermal transforming factor, sequential organ failure assessment

中图分类号:

R563.1

图/表 6

参考文献 21

[1]	王海波, 时详, 王宇, 等. IL-8和GRO-α与U-HBP评估ICU脓毒症患者预后的临床价值[J]. 中华医院感染学杂志, 2023, 33(2):161-165.
	WANG H B, SHI X, WANG Y, et al. The clinical value of evaluating the prognosis of ICU sepsis patients with U-HBP,IL-8 and GRO-α[J]. Chin J Nosocomiol, 2023, 33(2):161-165. doi:10.11816/cn.ni.2023-213102.
[2]	周燕南, 周思颖, 慕婉晴, 等. 血清炎性标志物连续监测联合序贯器官衰竭评分对肺部感染所致脓毒症患者预后的评估价值[J]. 中国临床医学, 2021, 28(3):364-369.
	ZHOU Y N, ZHOU S Y, MU W Q, et al. The value of continuous monitoring of serum inflammatory markers combined with sequential organ failure score in evaluating the prognosis of patients with sepsis caused by pulmonary infection[J]. Chin J Clin Med, 2021, 28(3):364-369. doi:10.12025/j.issn.1008-6358.2021.20202056.
[3]	PIERRAKOS C, VELISSARIS D, BISDORFF M, et al. Biomarkers of sepsis:time for a reappraisal[J]. Crit Care, 2020, 24(1):287-295. doi:10.1186/s13054-020-02993-5.
[4]	SALEKI K, BANAZADEH M, MIRI N S, et al. Triangle of cytokine storm,central nervous system involvement,and viral infection in COVID-19:the role of sFasL and neuropilin-1[J]. Rev Neurosci, 2022, 33(2):147-160. doi:10.1515/revneuro-2021-0047.
[5]	LORENTE L, MARTIN M M, ORTIZ-LOPEZ R, et al. Serum sFasL concentrations and mortality prediction in patients with sepsis[J]. Infect Dis(Lond), 2021, 53(8):643-646. doi:10.1080/23744235.2021.1901982.
[6]	王利公, 白凯, 陶慧, 等. 血清HGF、MMP-9及s-Met水平对脓毒症患者预后的评估价值[J]. 中国急救复苏与灾害医学杂志, 2022, 17(6):759-762,771.
	WANG L G, BAI K, TAO H, et al. The prognostic value of serum HGF,MMP-9,and s-Met levels in sepsis patients[J]. Chin J Emerg Resus Disaster Med, 2022, 17(6):759-762,771. doi:10.3969/j.issn.1673-6966.2022.06.016.
[7]	WANG Z, HE Y, ZHANG X, et al. Prognostic accuracy of SOFA and qSOFA for mortality among children with infection:a Meta-analysis[J]. Pediatr Res, 2022, 4(5):114-120. doi:10.1038/s41390-022-02213-6.
[8]	KALIL A C, METERSKY M L, KLOMPAS M, et al. Executive Summary:Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia:2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society[J]. Clin Infect Dis, 2016, 63(5):575-582. doi:10.1093/cid/ciw504.
[9]	SINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The third international consensus definitions for sepsis and septic shock(Sepsis-3)[J]. JAMA, 2016, 315(8):801-810. doi:10.1001/jama.2016.0287.
[10]	RUDD K E, JOHNSON S C, AGESA K M, et al. Global,regional,and national sepsis incidence and mortality,1990-2017:analysis for the Global Burden of Disease Study[J]. Lancet, 2020, 395(10219):200-211. doi:10.1016/S0140-6736(19)32989-7.
[11]	CECCONI M, EVANS L, LEVY M, et al. Sepsis and septic shock[J]. Lancet, 2018, 392(10141):75-87. doi:10.1016/S0140-6736(18)30696-2.
[12]	QI Z, WANG R, LIAO R, et al. Neferine ameliorates sepsis-induced myocardial dysfunction through anti-apoptotic and antioxidative effects by regulating the PI3K/AKT/mTOR signaling pathway[J]. Front Pharmacol, 2021, 12(8):7062-7071. doi:10.3389/fphar.2021.706251.
[13]	DUPLESSIS C, GREGORY M, FREY K, et al. Evaluating the discriminating capacity of cell death(apoptotic) biomarkers in sepsis[J]. J Intensive Care, 2018, 6(5):72-80. doi:10.1186/s40560-018-0341-5.
[14]	李英, 邓超, 计超. 微小RNA-98与脓毒症患者可溶性自杀相关因子/配体系统、疾病严重程度及短期预后关系研究[J]. 创伤与急危重病医学, 2022, 10(2):105-109,114.
	LI Y, DENG C, JI C. A study on the relationship between small RNA-98 and soluble suicide related factors/ligand systems,disease severity,and short-term prognosis in sepsis patients[J]. Trau and Crit Care Med, 2022, 10(2):105-109,114. doi:10.16048/j.issn.2095-5561.2022.02.07.
[15]	JIN B, LIANG Y, LIU Y, et al. Notch signaling pathway regulates T cell dysfunction in septic patients[J]. Int Immunopharmacol, 2019, 76(5):1059-1067. doi:10.1016/j.intimp.2019.105907.
[16]	MESSER M P, KELLERMANN P, WEBER S J, et al. Silencing of fas,fas-associated via death domain,or caspase 3 differentially affects lung inflammation,apoptosis,and development of trauma-induced septic acute lung injury[J]. Shock, 2013, 39(1):19-27. doi:10.1097/SHK.0b013e318277d856.
[17]	OU Q, TAN L, SHAO Y, et al. Electrostatic charge-mediated apoptotic vesicle biodistribution attenuates sepsis by switching neutrophil NETosis to apoptosis[J]. Small, 2022, 18(20):2200-2206. doi:10.1002/smll.202200306.
[18]	TSUJIMOTO H, HORIGUCHI H, MATSUMOTO Y, et al. A potential mechanism of tumor progression during systemic infections via the hepatocyte growth factor(HGF)/c-Met signaling pathway[J]. J Clin Med, 2020, 9(7):1258-1264. doi:10.3390/jcm9072074.
[19]	GIEBELER A, BRANDENBURG L O, KALDENBACH M, et al. Lack of hepatic c-Met and gp130 expression is associated with an impaired antibacterial response and higher lethality after bile duct ligation[J]. Lab Invest, 2012, 92(12):1726-37. doi:10.1038/labinvest.2012.122.
[20]	FIESTAS V E, DE R C, DE E L. The role of growth factors in the pathogenesis of dengue:a scoping review[J]. Pathogens, 2022, 11(10):478-485. doi:10.3390/pathogens11101179.
[21]	陈静波. C-反应蛋白、降钙素原对脓毒症患者早期诊断及病情评估的应用价值[J]. 国际检验医学杂志, 2020, 41(2):242-244.
	CHEN J B. The value of C-reactive protein and pro Calcitonin in the early diagnosis and assessment of sepsis[J]. Inter J Lab Med, 2020, 41(2):242-244. doi:10.3969/j.issn.1673-4130.2020.02.029.

组别	n	sFasL/（ng/L）	s-Met/（mg/L）
对照组	60	10.26±2.41	0.41±0.08
肺炎组	70	16.73±3.19^a	0.89±0.12^a
肺炎继发脓毒症组	150	39.13±8.14^ab	1.79±0.39^ab
F		586.531^＊＊	547.702^＊＊

组别	n	sFasL/（ng/L）	s-Met/（mg/L）
对照组	60	10.26±2.41	0.41±0.08
肺炎组	70	16.73±3.19^a	0.89±0.12^a
肺炎继发脓毒症组	150	39.13±8.14^ab	1.79±0.39^ab
F		586.531^＊＊	547.702^＊＊

组别		n	年龄/岁		性别（男/女）		吸烟史			高血压史			糖尿病史		慢性阻塞性肺疾病病史
死亡组		54	64.25±11.09		30/24		25（46.30）			22（40.74）			16（29.63）		15（27.78）
存活组		96	63.18±10.13		56/40		50（52.08）			34（35.42）			22（22.92）		17（17.71）
t或χ²			0.600		0.109		0.463			0.419			0.823		2.088
组别	冠状动脉粥样硬化性心脏病病史					ICU住院天数/d			抗生素种类
组别	冠状动脉粥样硬化性心脏病病史					ICU住院天数/d			β-内酰胺类			碳青霉烯类				利奈唑胺		氟喹诺酮类
死亡组	13（24.07）					11（7，16）			11（20.37）			13（24.07）				15（27.78）		15（27.78）
存活组	16（16.67）					14（10，22）			23（23.96）			25（26.04）				20（20.83）		28（29.17）
t或χ²	1.216					2.147			0.987
组别	抗生素使用时间/d			WBC/（×10⁹/L）				PCT/（μg/L）			CRP/（mg/L）			SOFA/分			q-SOFA/分
死亡组	12.09±2.74			13.84（7.84，18.29）				0.97±0.31			122.05±28.29			9.59±2.28			2.31±0.47
存活组	11.45±2.15			11.64（7.18，16.79）				0.81±0.20			116.48±21.25			4.30±1.67			1.18±0.36
t或χ²	1.582			0.647				3.837^＊＊			1.364			16.274^＊＊			16.490^＊＊

组别		n	年龄/岁		性别（男/女）		吸烟史			高血压史			糖尿病史		慢性阻塞性肺疾病病史
死亡组		54	64.25±11.09		30/24		25（46.30）			22（40.74）			16（29.63）		15（27.78）
存活组		96	63.18±10.13		56/40		50（52.08）			34（35.42）			22（22.92）		17（17.71）
t或χ²			0.600		0.109		0.463			0.419			0.823		2.088
组别	冠状动脉粥样硬化性心脏病病史					ICU住院天数/d			抗生素种类
组别	冠状动脉粥样硬化性心脏病病史					ICU住院天数/d			β-内酰胺类			碳青霉烯类				利奈唑胺		氟喹诺酮类
死亡组	13（24.07）					11（7，16）			11（20.37）			13（24.07）				15（27.78）		15（27.78）
存活组	16（16.67）					14（10，22）			23（23.96）			25（26.04）				20（20.83）		28（29.17）
t或χ²	1.216					2.147			0.987
组别	抗生素使用时间/d			WBC/（×10⁹/L）				PCT/（μg/L）			CRP/（mg/L）			SOFA/分			q-SOFA/分
死亡组	12.09±2.74			13.84（7.84，18.29）				0.97±0.31			122.05±28.29			9.59±2.28			2.31±0.47
存活组	11.45±2.15			11.64（7.18，16.79）				0.81±0.20			116.48±21.25			4.30±1.67			1.18±0.36
t或χ²	1.582			0.647				3.837^＊＊			1.364			16.274^＊＊			16.490^＊＊

组别	n		sFasL/（ng/L）										F
组别	n		0 h		24 h		48 h		72 h		120 h		F
存活组	96		32.15±6.55		32.46±6.70		33.11±6.14		33.25±6.55		32.69±6.30		0.480
死亡组	54		51.54±10.46		53.17±11.25		54.64±11.70		57.94±10.46		63.18±13.45		8.654^＊＊
t			13.955^＊＊		14.140^＊＊		14.379^＊＊		17.770^＊＊		18.857^＊＊
组别		s-Met/（mg/L）										F
组别		0 h		24 h		48 h		72 h		120 h		F
存活组		1.71±0.38		1.72±0.39		1.74±0.38		1.78±0.35		1.77±0.36		0.644
死亡组		1.93±0.41		1.98±0.42		2.13±0.45		2.26±0.48		2.63±0.51		20.411^＊＊
t		3.308^＊＊		3.812^＊＊		5.641^＊＊		7.030^＊＊		12.040^＊＊