5种血清学标志物对急性呼吸窘迫综合征的诊断和预后预测价值
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摘要
目的探讨血管生成素2(Ang-2)、Ⅱ型肺泡细胞表面抗原(KL-6)、肺表面活性蛋白D(SP-D)、血管性血友病因子(vWF)、白介素8(IL-8)在急性呼吸窘迫综合征(ARDS)患者外周血水平变化和对ARDS诊断、预后预测的临床价值。方法选择两个医学中心重症医学科49例ARDS患者,同期50例非ARDS患者(对照组)作为研究对象,检测入科时(T_1)、诊断为ARDS时(T_2)血清标志物水平,记录临床基本资料。结果 ARDS组5种标志物水平较对照组增高(P<0.05),且T_2时间点高于T_1(P<0.05);除vWF(P>0.05)外,ARDS死亡组(n=17)标志物水平均高于存活组(n=32)。受试者工作特征曲线分析表明,单一标志物(T_1)诊断ARDS的最大曲线下面积(AUC)为0.816(95%CI:0.730, 0.902)(KL-6),联合诊断最大AUC为0.869(95%CI:0.795, 0.942)(KL-6+Ang-2);单一标志物(T_2)预测死亡的最大AUC 0.764(95%CI:0.627, 0.901)(IL-8),联合预测最大AUC 0.829(95%CI:0.715, 0.943)(IL-8+KL-6)。结论 5种血清标志物与重症患者ARDS的发生及预后密切相关。血清KL-6和Ang-2水平变化有助于诊断,血清IL-8与KL-6水平升高预示预后不良。
Objective To explore the changes in serum angiopoietin 2(Ang-2), Krebs von den lungen 6(KL-6), surfactant protein D(SP-D), von Willebrand factor(vWF) and lnterleukin-8(IL-8) in peripheral blood of patients with acute respiratory distress syndrome(ARDS) and evaluate their clinical value in diagnosis and mortality predication of ARDS. Methods In this prospective study, 49 ARDS patients and 50 non-ARDS were enrolled in two intensive care units(ICUs). Blood samples collected from the participants at admission to ICU(T_1) and the time-point when diagnosed for ARDS(T_2) were tested for the five serum biomarkers by enzyme-linked immunosorbent assay. Receiver operating characteristic curve(ROC) was used to evaluate the performance of the biomarkers in ARDS diagnosis and mortality prediction. Results The levels of all the five serum biomarkers were elevated in ARDS patients compared with non-ARDS ones(P<0.05). At T_2 time-point the serum concentrations of the five biomarkers in ARDS patients were significantly higher than those at T_1 time-point(P<0.05). The dead patients(n=17) in ARDS group had higher levels of Ang-2, KL-6, SP-D and IL-8 than the survivors(n=32)(P<0.05). With regard to the diagnosis of ARDS, at T_1 time-point the largest areas under the receiver operating characteristic curve(AUCs) for single biomarker and combination were 0.816 [95% confidence interval(CI): 0.730, 0.902](KL-6) and 0.869(95% CI: 0.795, 0.942)(KL-6+Ang-2), respectively. The best predictive AUCsof 28-day mortality for single biomarker and combination at T2 time-point were 0.764(95% CI:0.627,0.901)(IL-8)and 0.829(95% CI:0.715,0.943)(IL-8+KL-6),respectively.Conclusion The five serum biomarkers are associated with the occurrence,development,and poor prognosis of ARDS in ICU.It is possible that serum KL-6 and Ang-2 should be as diagnostic indicators for ARDS and IL-8 and KL-6 as predictive markers for poor prognosis of ARDS.
Objective To explore the changes in serum angiopoietin 2(Ang-2), Krebs von den lungen 6(KL-6), surfactant protein D(SP-D), von Willebrand factor(vWF) and lnterleukin-8(IL-8) in peripheral blood of patients with acute respiratory distress syndrome(ARDS) and evaluate their clinical value in diagnosis and mortality predication of ARDS. Methods In this prospective study, 49 ARDS patients and 50 non-ARDS were enrolled in two intensive care units(ICUs). Blood samples collected from the participants at admission to ICU(T_1) and the time-point when diagnosed for ARDS(T_2) were tested for the five serum biomarkers by enzyme-linked immunosorbent assay. Receiver operating characteristic curve(ROC) was used to evaluate the performance of the biomarkers in ARDS diagnosis and mortality prediction. Results The levels of all the five serum biomarkers were elevated in ARDS patients compared with non-ARDS ones(P<0.05). At T_2 time-point the serum concentrations of the five biomarkers in ARDS patients were significantly higher than those at T_1 time-point(P<0.05). The dead patients(n=17) in ARDS group had higher levels of Ang-2, KL-6, SP-D and IL-8 than the survivors(n=32)(P<0.05). With regard to the diagnosis of ARDS, at T_1 time-point the largest areas under the receiver operating characteristic curve(AUCs) for single biomarker and combination were 0.816 [95% confidence interval(CI): 0.730, 0.902](KL-6) and 0.869(95% CI: 0.795, 0.942)(KL-6+Ang-2), respectively. The best predictive AUCsof 28-day mortality for single biomarker and combination at T2 time-point were 0.764(95% CI:0.627,0.901)(IL-8)and 0.829(95% CI:0.715,0.943)(IL-8+KL-6),respectively.Conclusion The five serum biomarkers are associated with the occurrence,development,and poor prognosis of ARDS in ICU.It is possible that serum KL-6 and Ang-2 should be as diagnostic indicators for ARDS and IL-8 and KL-6 as predictive markers for poor prognosis of ARDS.
引文
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[11] PARK J,PABON M,CHOI AMK,et al.Plasma surfactant protein-D as a diagnostic biomarker for acute respiratory distress syndrome:Validation in US and Korean cohorts[J].BMC Pulm Med,2017,17(1):204-210.
[12] AGRAWAL A,MATTHAY MA,KANGELARIS KN,et al.Plasma angiopoietin-2 predicts the onset of acute lung injury in critically ill patients[J].Am J Respir Crit Care Med,2013,187(7):736-742.
[13] 王冉,张巧,马千里,等.血清学生物标志物对急性呼吸窘迫综合征进展及预后的预测研究[J].第三军医大学学报,2017,39(19):1926-1932.
[14] WARE LB,KOYAMA T,BILLHEIMER DD,et al.Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury[J].Chest 2010,137(2):288-296.
[15] CARTIN-CEBA R,HUBMAYR RD,QIN R,et al.Predictive value of plasma biomarkers for mortality and organ failure development in patients with acute respiratory distress syndrome[J].J Crit Care,2015,30(1):219 e211-217.
[16] CALFEE CS,JANZ DR,BERNARD GR,et al.Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies[J].Chest,2015,147(6):1539-1548.
[2] GARCIA-LAORDEN MI,LORENTE JA,FLORES C,et al.Biomarkers for the acute respiratory distress syndrome:How to make the diagnosis more precise [J].Ann Transl Med,2017,5(14):283-293.
[3] RANIERI VM,RUBENFELD GD,THOMPSON BT,et al.Acute respiratory distress syndrome:The Berlin Definition[J].JAMA,2012,307(23):2526-2533.
[4] THILLE AW,ESTEBAN A,FERNANDEZ-SEGOVIANO P,et al.Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy[J].Am J Respir Crit Care Med,2013,187(7):761-767.
[5] GUERIN C,THOMPSON T,BROWER R.The ten diseases that look like ARDS[J].Intensive Care Med,2015,41(6):1099-1102.
[6] 袁超,金娜.APACHEⅡ评分和血管性血友病因子对急性呼吸窘迫综合征肺损伤程度及预后的评估价值[J].中国呼吸与危重监护杂志,2016,15(2):142-146.
[7] 钟明媚,张琳,王璠,等.急性呼吸窘迫综合征患者血浆血管生成素2水平及其对预后的诊断价值[J].中华危重病急救医学,2014,26(11):804-809.
[8] 宗晓龙,李真玉,魏殿军,等.肺泡表面活性蛋白D、血管性血友病因子及白介素8对脓毒症诱发急性呼吸窘迫综合征的预测和预后意义[J].临床检验杂志,2017,35(2):118-121.
[9] TERPSTRA ML,AMAN J,VAN NIEUW AMERONGEN GP,et al.Plasma biomarkers for acute respiratory distress syndrome:A systematic review and meta-analysis[J].Crit Care Med,2014,42(3):691-700.
[10] ZHENG Y,LIU SQ,SUN Q,et al.Plasma microRNAs levels are different between pulmonary and extrapulmonary ARDS patients:A clinical observational study[J].Ann Intensive Care,2018,8(1):23-35.
[11] PARK J,PABON M,CHOI AMK,et al.Plasma surfactant protein-D as a diagnostic biomarker for acute respiratory distress syndrome:Validation in US and Korean cohorts[J].BMC Pulm Med,2017,17(1):204-210.
[12] AGRAWAL A,MATTHAY MA,KANGELARIS KN,et al.Plasma angiopoietin-2 predicts the onset of acute lung injury in critically ill patients[J].Am J Respir Crit Care Med,2013,187(7):736-742.
[13] 王冉,张巧,马千里,等.血清学生物标志物对急性呼吸窘迫综合征进展及预后的预测研究[J].第三军医大学学报,2017,39(19):1926-1932.
[14] WARE LB,KOYAMA T,BILLHEIMER DD,et al.Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury[J].Chest 2010,137(2):288-296.
[15] CARTIN-CEBA R,HUBMAYR RD,QIN R,et al.Predictive value of plasma biomarkers for mortality and organ failure development in patients with acute respiratory distress syndrome[J].J Crit Care,2015,30(1):219 e211-217.
[16] CALFEE CS,JANZ DR,BERNARD GR,et al.Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies[J].Chest,2015,147(6):1539-1548.