血清标志物联合检测对儿童呼吸窘迫综合征早期预测的临床价值

doi:10.3969/j.issn.1004-583X.2025.03.008

摘要/Abstract

摘要：

目的探讨血清涎液化糖链抗原-6(Krebs von den Lungen-6,KL-6)、血管性血友病因子(von Willebrand factor,vWF)和白介素8(interleukin-8,IL-8)在儿童急性呼吸窘迫综合征(pediatric acute respiratory distress syndrome, pARDS)早期识别中的临床预测价值。方法纳入2023年11月-2024年11月于郑州大学第三附属医院儿童重症医学科接受机械通气治疗的患儿92例,依据患儿在明确病因损害后的7 d内是否发展为pARDS,将患儿分为pARDS组(n=35)和非pARDS组(n=57)。pARDS组分别于机械通气开始 (T₁)时、确诊pARDS(T₂)时和确诊后第3天(T₃),非pARDS组于T₁时,采用酶联免疫吸附法检测血清标志物水平,收集并分析相关临床数据。结果 T₁时pARDS组KL-6、vWF和IL-8水平高于非pARDS组(P<0.05)。pARDS组KL-6、vWF和IL-8水平在不同时间点的变化差异有统计学意义(P<0.05);KL-6水平在T₂时高于T₁,且在T₃时达到研究期间峰值(P<0.01);IL-8和vWF水平在T₂达到峰值后于T₃有所下降(P<0.05)。受试者工作特征曲线分析显示,KL-6、IL-8和vWF的曲线下面积分别为0.749、0.662和0.631,三者联合检测的曲线下面积为0.776(P<0.05),对应的敏感度分别为74.3%、62.9%、62.9%和85.7%,特异度分别为82.5%、61.4%、68.4%和63.2%。结论血清KL-6、IL-8及vWF水平升高可作为pARDS早期识别的有效生物标志物,三者联合检测可提高诊断效率。

关键词: 呼吸窘迫综合征, 血清涎液化糖链抗原-6, 白介素8, 血管性血友病因子

Abstract:

Objective To investigate the clinical predictive value of serum Krebs von den Lungen-6 (KL-6), von Willebrand factor (vWF), and interleukin-8 (IL-8) in the early identification of pediatric acute respiratory distress syndrome (pARDS). Methods A total of 92 children who received mechanical ventilation in the Department of Pediatric Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University from November 2023 to November 2024 were included. According to the development of pARDS within 7 days after the confirmation of etiological damages, included children were divided into the pARDS group (n=35) and non-pARDS group (n=57). Serum biomarker levels were measured using enzyme-linked immunosorbent assay (ELISA) at the initiation of mechanical ventilation (T₁) in both groups, the time of pARDS diagnosis (T₂), and on the third day post-diagnosis (T₃) in the pARDS group. Relevant clinical data were collected and analyzed. Results At T₁, the levels of KL-6, vWF, and IL-8 were significantly higher in the pARDS group compared to the non-pARDS group (P<0.05). The levels of KL-6, vWF and IL-8 in the pARDS group were significantly different at different time points (P<0.05). The level of KL-6 at T₂ was significantly higher than that at T₁, and reached the peak at T₃ (P<0.01). The levels of IL-8 and vWF reached the peak at T₂ and then decreased at T₃ (P<0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the area under the curve (AUC) of KL-6, IL-8, and vWF in diagnosing pARDS was 0.749, 0.662, and 0.631, respectively, with the sensitivity of 74.3%, 62.9%, and 62.9%, and specificity of 82.5%, 61.4%, and 68.4%. When combined, the AUC reached 0.776(P<0.05), with the corresponding sensitivity of 85.7%, and specificity of 63.2%. Conclusion Elevated serum levels of KL-6, IL-8, and vWF are effective biomarkers for the early identification of pARDS. A combined detection of these biomarkers can improve diagnostic accuracy.

Key words: respiratory distress syndrome, Krebs von den Lungen-6, interleukin-8, von Willebrand factor

中图分类号:

R563.8

冯雨慧, 邹兰兰, 崔晨航, 黄先杰, 乔俊英. 血清标志物联合检测对儿童呼吸窘迫综合征早期预测的临床价值[J]. 临床荟萃, 2025, 40(3): 237-242.

Feng Yuhui, Zou Lanlan, Cui Chenhang, Huang Xianjie, Qiao Junying. Clinical value of combined serum biomarker detection for early prediction of pediatric acute respiratory distress syndrome[J]. Clinical Focus, 2025, 40(3): 237-242.

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链接本文: https://lchc.magtechjournal.com/CN/10.3969/j.issn.1004-583X.2025.03.008

https://lchc.magtechjournal.com/CN/Y2025/V40/I3/237

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参考文献 22

[1]	Goodman D, Crocker ME, Pervaiz F, et al. Challenges in the diagnosis of paediatric pneumonia in intervention field trials: Recommendations from a pneumonia field trial working group[J]. Lancet Respir Med, 2019, 7(12): 1068-1083. doi: 10.1016/S2213-2600(19)30249-8 pmid: 31591066
[2]	原静, 李书芳, 郎元法. 急性呼吸窘迫综合征儿童的临床特征研究[J]. 中国急救复苏与灾害医学杂志, 2024, 19(3): 374-378.
[3]	Emeriaud G, López-Fernández YM, Iyer NP, et al. Executive summary of the second international guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PALICC-2)[J]. Pediatr Crit Care Med, 2023, 24(2): 143-168.
[4]	Guérin C, Thompson T, Brower R. The ten diseases that look like ARDS[J]. Intensive Care Med, 2015, 41(6): 1099-1102. doi: 10.1007/s00134-014-3608-x pmid: 25527375
[5]	Kalbhenn J, Glonnegger H, Wilke M, et al. Hypercoagulopathy, acquired coagulation disorders and anticoagulation before, during and after extracorporeal membrane oxygenation in COVID-19: A case series[J]. Perfusion, 2021, 36(6): 592-602.
[6]	Williams JG, Jones RL, Yunger TL, et al. Comparison of 16 pediatric acute respiratory distress syndrome-associated plasma biomarkers with changing lung injury severity[J]. Pediatr Crit Care Med, 2024, 25(1): e31-e40.
[7]	Carlton EF, Flori HR. Biomarkers in pediatric acute respiratory distress syndrome[J]. Ann Transl Med, 2019, 7(19): 505. doi: 10.21037/atm.2019.09.29 pmid: 31728358
[8]	Matthay MA, Zemans RL, Zimmerman GA, et al. Acute respiratory distress syndrome[J]. Nat Rev Dis Primers, 2019, 5(1): 18. doi: 10.1038/s41572-019-0069-0 pmid: 30872586
[9]	曾宪飞, 卢东雪, 张西京, 等. 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[J]. 西安交通大学学报(医学版), 2019, 40(4): 588-592,618.
[10]	Jiang LN, Shao CL, Jiang WJ, et al. Advanced research of KL-6 in respiratory diseases[J]. Int J Respir, 2019, 39(21): 1665-1669.
[11]	Aisiku IP, Yamal JM, Doshi P, et al. Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury[J]. Crit Care, 2016, 20: 288.
[12]	Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: The Berlin Definition[J]. JAMA, 2012, 307(23): 2526-2533. doi: 10.1001/jama.2012.5669 pmid: 22797452
[13]	张涛, 刘春峰. 2023版国际儿童急性呼吸窘迫综合征诊疗指南解读[J]. 中国小儿急救医学, 2023, 30(11): 801-808.
[14]	高杨, 李军. 生物标志物联合应用在急性呼吸窘迫综合征患者诊断及预后评估中的意义[J]. 中华危重病急救医学, 2021, 33(1): 69-73.
[15]	Han L, Wang S, Ma J, et al. Expression and significance of serum KL-6 in patients with acute respiratory distress syndrome[J]. J Thorac Dis, 2023, 15(12): 6988-6995. doi: 10.21037/jtd-23-1787 pmid: 38249915
[16]	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.
[17]	Whitney JE, Feng R, Koterba N, et al. Endothelial biomarkers are associated with indirect lung injury in sepsis-associated pediatric acute respiratory distress syndrome[J]. Crit Care Explor, 2020, 2(12): e0295. doi: 10.1097/CCE.0000000000000295 pmid: 33299985
[18]	何琛璐, 王雪君, 刘润武, 等. 血清vWF:Ag、Claudin-5及sTM联合检测在ARDS患儿早期诊断及预后评估中的应用[J]. 国际检验医学杂志, 2021, 42(21): 2614-2618.
[19]	孙夏烨, 朱晓东. 小儿急性肺损伤及其生物标记物研究进展[J]. 中国小儿急救医学, 2015, 22 (2): 140-142.
[20]	van der Zee P, Rietdijk W, Somhorst P, et al. A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality[J]. Crit Care, 2020, 24(1): 243.
[21]	李双凤, 高延秋, 李晓燕, 等. EVLWI、sICAM-1和KL-6联合检测在重症肺炎ARDS患者预后评估中的价值[J]. 中华急诊医学杂志, 2021, 30(6): 730-736.
[22]	王丽阳, 王艺璁, 刘欢, 等. 血清RAGE、PBEF水平对重症肺炎患儿继发急性呼吸窘迫综合征的预测价值[J]. 疑难病杂志, 2024, 23(9):1085-1089+1099.

指标	pARDS组(n=35)	非pARDS组(n=57)	统计值	P值
年龄(月)	9.80(2.77, 12.50)	10.37(2.02, 18.00)	Z=0.076	0.939
体重(kg)	8.20(5.00, 10.50)	8.50(4.00, 10.00)	Z=1.127	0.260
男性[例(%)]	24(68.6)	34(59.6)	χ²=0.741	0.389
白细胞(×10⁹/L)	10.84(6.74, 14.77)	9.61(6.55, 15.73)	Z=0.197	0.844
血小板(×10⁹/L)	350(257, 523)	314(236, 441)	Z=0.993	0.321
肌酐( μmol/L)	20.30(16.70, 26.00)	18.80(16.00, 23.44)	Z=0.768	0.442
D-二聚体(mg/L)	0.35(0.27, 0.60)	0.47(0.28, 1.09)	Z=1.693	0.090
总蛋白(g/L)	57.38±8.26	55.30±10.41	t=1.005	0.318
白蛋白(g/L)	35.57±6.12	34.83±6.98	t=0.519	0.605
PCIS评分(分)	80.17±4.93	82.60±4.39	t=2.453	0.016
机械通气时长(h)	199(150, 277)	104 (29, 131)	Z=5.825	0.000
住院天数(d)	23.00(17.00, 27.00)	18.00(13.00, 27.50)	Z=1.787	0.074
原发疾病[例(%)]			χ²=3.661	0.300
肺炎	20(57.1)	29(50.9)
脓毒症	9(25.7)	9(15.8)
大手术术后	4(11.4)	15(26.3)
其他	2(5.7)	4(7.0)

指标	pARDS组(n=35)	非pARDS组(n=57)	统计值	P值
年龄(月)	9.80(2.77, 12.50)	10.37(2.02, 18.00)	Z=0.076	0.939
体重(kg)	8.20(5.00, 10.50)	8.50(4.00, 10.00)	Z=1.127	0.260
男性[例(%)]	24(68.6)	34(59.6)	χ²=0.741	0.389
白细胞(×10⁹/L)	10.84(6.74, 14.77)	9.61(6.55, 15.73)	Z=0.197	0.844
血小板(×10⁹/L)	350(257, 523)	314(236, 441)	Z=0.993	0.321
肌酐( μmol/L)	20.30(16.70, 26.00)	18.80(16.00, 23.44)	Z=0.768	0.442
D-二聚体(mg/L)	0.35(0.27, 0.60)	0.47(0.28, 1.09)	Z=1.693	0.090
总蛋白(g/L)	57.38±8.26	55.30±10.41	t=1.005	0.318
白蛋白(g/L)	35.57±6.12	34.83±6.98	t=0.519	0.605
PCIS评分(分)	80.17±4.93	82.60±4.39	t=2.453	0.016
机械通气时长(h)	199(150, 277)	104 (29, 131)	Z=5.825	0.000
住院天数(d)	23.00(17.00, 27.00)	18.00(13.00, 27.50)	Z=1.787	0.074
原发疾病[例(%)]			χ²=3.661	0.300
肺炎	20(57.1)	29(50.9)
脓毒症	9(25.7)	9(15.8)
大手术术后	4(11.4)	15(26.3)
其他	2(5.7)	4(7.0)

指标	例数	KL-6 (ng/ml)	IL-8 (pg/ml)	vWF (μg/ml)
pARDS组	35	3.33(2.44, 4.05)	45.39(33.94, 65.30)	5.81±1.53
非pARDS组	57	2.13(1.50, 2.68)	36.74(19.21, 48.95)	4.86±2.12
统计值		Z=3.993	Z=2.598	t=2.489
P值		0	0.009	0.015

指标	例数	KL-6 (ng/ml)	IL-8 (pg/ml)	vWF (μg/ml)
pARDS组	35	3.33(2.44, 4.05)	45.39(33.94, 65.30)	5.81±1.53
非pARDS组	57	2.13(1.50, 2.68)	36.74(19.21, 48.95)	4.86±2.12
统计值		Z=3.993	Z=2.598	t=2.489
P值		0	0.009	0.015

	KL-6 (ng/ml)	IL-8 (pg/ml)	vWF (μg/ml)
T₁	3.33(2.44, 4.05)	45.39(33.94, 65.30)	5.81±1.53
T₂	5.19(3.02, 6.72)^*	76.24(45.71, 109.75)^*	6.72±1.94^*
T₃	6.47(5.11, 8.47)^#	53.78(36.19, 76.87)^#	5.66±1.71^#
统计值	H=36.289	H=10.006	F=3.824
P值	0	0.007	0.025