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中华实验和临床感染病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (04) : 268 -274. doi: 10.3877/cma.j.issn.1674-1358.2022.04.008

论著

外周血可溶性Fas蛋白及其配体、髓过氧化物酶水平对重症肺炎患儿预后不良的预测价值
沈杨1, 余海波2,†(), 曾强英3   
  1. 1. 621000　绵阳市，绵阳万江眼科医院儿科
    2. 621000　绵阳市，四川绵阳四〇四医院急诊科
    3. 621000　绵阳市，四川中医药高等专科学校绵阳富临医院儿科
  • 收稿日期:2021-10-29 出版日期:2022-08-15
  • 通信作者: 余海波
  • 基金资助:
    2018年四川省卫生和计划生育委员会科研课题(No. 18PJ037)

Predictive value of peripheral blood levels of soluble Fas protein, soluble Fas protein ligand and myeloperoxidase on poor prognosis in children with severe pneumonia

Yang Shen1, Haibo Yu2,†(), Qiangying Zeng3   

  1. 1. Department of Pediatrics, Mianyang Wanjiang Eye Hospital, Mianyang 621000, China
    2. Emergency Department, Sichuan Mianyang 404 Hospital, Mianyang 621000, China
    3. Department of Pediatrics, Mianyang Fulin Hospital, Sichuan College of Traditional Chinese Medicine, Mianyang 621000, China
  • Received:2021-10-29 Published:2022-08-15
  • Corresponding author: Haibo Yu
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引用本文：

沈杨, 余海波, 曾强英. 外周血可溶性Fas蛋白及其配体、髓过氧化物酶水平对重症肺炎患儿预后不良的预测价值[J]. 中华实验和临床感染病杂志(电子版), 2022, 16(04): 268-274.

Yang Shen, Haibo Yu, Qiangying Zeng. Predictive value of peripheral blood levels of soluble Fas protein, soluble Fas protein ligand and myeloperoxidase on poor prognosis in children with severe pneumonia[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(04): 268-274.

目的

观察重症肺炎患儿外周血可溶性Fas蛋白（sFas）、可溶性Fas蛋白配体（sFasL）和髓过氧化物酶（MPO）水平变化，并探讨三者对重症肺炎预后不良的预测价值。

方法

选取四川中医药高等专科学校绵阳富临医院2016年2月至2020年5月收治的182例重症肺炎、196例轻症肺炎患儿和178例健康儿童，分别为重症组、轻症组和对照组；重症组患儿再根据预后分为预后不良组（29例）和预后良好组（153例）。采用单因素方差分析比较重症组、轻症组治疗前和对照组外周血sFas、sFasL和MPO水平；采用单因素和多因素Logistic回归分析重症组患儿预后不良的影响因素，采用受试者工作特征（ROC）曲线评价外周血sFas、sFasL和MPO水平以及联合指标预测重症组患儿预后不良的价值。

结果

三组研究对象的性别、年龄和体重，重症组与轻症组患儿病原微生物分布、肺炎分期差异均无统计学意义（P均> 0.05）。重症组患儿治疗前外周血sFas、sFasL和MPO水平分别为（104.63 ± 19.75）ng/L、（1 062.36 ± 179.85）ng/L和（1 020.26 ± 59.71）U/L，轻症组患儿分别为（80.52 ± 13.66）ng/L、（703.57 ± 127.66）ng/L和（796.75 ± 43.02）U/L，对照组儿童分别为（58.78 ± 10.16）ng/L、（577.83 ± 121.22）ng/L和（632.59 ± 38.71）U/L；重症组和轻症组患儿以上3个指标水平均高于对照组（sFas：重症组 vs.对照组：t = 27.605、P < 0.001；轻症组vs.对照组：t = 17.322、P < 0.001；sFasL：重症组 vs.对照组：t = 29.908、P < 0.001，轻症组vs.对照组：t = 9.744、P < 0.001；MPO：重症组 vs.对照组：t = 71.920、P < 0.001；轻症组vs.对照组：t = 38.647、P < 0.001），重症组患儿以上3个指标水平均显著高于轻症组（t = 13.885、22.488、41.973，P均< 0.001）。重症组患儿预后不良发生率为15.93%（29/182）。预后不良组患儿双重/多重感染占比（χ2 = 12.081、P = 0.001）、多肺叶感染占比（χ2 = 32.378、P < 0.001）和外周血白细胞计数（WBC）（t = 6.432、P < 0.001）、中性粒细胞百分比（N%）（t = 3.658、P = 0.001）、C-反应蛋白（CRP）（t = 19.415、P < 0.001）、降钙素原（PCT）（t = 26.101、P < 0.001）、sFas（t = 13.717、P < 0.001）、sFasL（t = 5.357、P < 0.001）和MPO（t = 5.435，P < 0.001）水平均显著高于预后良好组患儿；多因素Logistic回归分析显示以上指标均为重症组患儿预后不良的危险因素，差异均有统计学意义（OR = 5.969、95%CI：4.857~6.304、P = 0.029，OR = 7.485、95%CI：6.785~8.126、P = 0.014，OR = 5.332、95%CI：4.593~5.567、P = 0.010，OR = 4.959、95%CI：4.246~5.337、P = 0.015，OR = 5.143、95%CI：4.879~5.695、P = 0.003，OR = 6.126、95%CI：5.630~6.558、P = 0.008，OR = 8.325、95%CI：6.452~9.902、P = 0.005，OR = 8.469、95%CI：7.879~8.653、P = 0.001，OR = 9.132、95%CI：8.882~9.594，P = 0.003）。外周血sFas、sFasL和MPO水平预测重症组预后不良的Cut-off值分别为125.07 ng/L、1 171.21 ng/L和1 053.04 U/L；sFas、sFasL和MPO以及3个指标联合预测的曲线下面积（AUC）分别为0.875、0.890、0.897和0.955，3个指标联合预测AUC均显著高于sFas、sFasL、MPO水平单独预测，差异均有统计学意义（Z = 5.693、P = 0.005，Z = 5.192、P = 0.007，Z = 4.982、P = 0.009）。

结论

重症肺炎患儿外周血sFas、sFasL和MPO水平均偏高，且在预后不良重症患儿中水平均更高，其联合应用可预测患儿不良预后。

关键词: 重症肺炎, 可溶性Fas蛋白, 可溶性Fas蛋白配体, 髓过氧化物酶
Objective

To investigate the changes of soluble Fas protein (sFas), soluble Fas protein ligand (sFasL) and myeloperoxidase (MPO) in peripheral blood of children with severe pneumonia, and to explore the predictive value on poor prognosis.

Methods

Total of 182 cases of severe pneumonia, 196 cases of mild pneumonia and 178 healthy children in Mianyang Fulin hospital, Sichuan College of traditional Chinese Medicine were enrolled as severe group, mild group and control group, respectively; Children in severe group were then divided into poor prognosis group (29 cases) and good prognosis group (153 cases). The levels of sFas, sFasL and MPO in peripheral blood were compared among cases of severe group and mild group before treatment with those of control group by one way ANOVA. The risk factors for poor prognosis in severe group were determined by univariate and multivariate Logistic regression analysis, and the value of peripheral blood sFasL, sFasL, MPO levels and the combination of the three indexes on predicting poor prognosis in severe group were explored by receiver operating characteristic curve (ROC).

Results

There was no significant difference in gender, age and weight among cases in the three groups; distribution of pathogenic microorganisms and stages of pneumonia between cases in severe group and mild group were also without significant difference (all P > 0.05). The levels of sFas, sFasL and MPO in peripheral blood of cases in severe group were (104.63 ± 19.75) ng/L, (1 062.36 ± 179.85) ng/L, (1 020.26 ± 59.71) U/L, which were (80.52 ± 13.66) ng/L, (703.57 ± 127.66) ng/L and (796.75 ± 43.02) U/L in cases of mild group, while (58.78 ± 10.16) ng/L, (577.83 ± 121.22) ng/L and (632.59 ± 38.71) U/L in cases of control group, respectively; and the levels of the above indexes of cases in severe group and mild group before treatment were significantly higher than those of the control group (sFas: severe group vs. control group: t = 27.605, P < 0.001; mild group vs. control group: t = 17.322, P < 0.001. sFasL: severe group vs. control group: t = 29.908、P < 0.001; mild group vs. control group: t = 9.744, P < 0.001. MPO: severe group vs. control group: t = 71.920, P < 0.001; mild group vs. control group: t = 38.647, P < 0.001), which were significantly higher in severe group than those of the mild group (t = 13.885, 22.488, 41.973, all P < 0.001). The incidence of poor prognosis in severe group was 15.93% (29/182). The proportions of double/multiple infection (χ2 = 12.081, P = 0.001), multiple lobe infection (χ2 = 32.378, P < 0.001) and white blood cell (WBC) (t = 6.432, P < 0.001), percentage of neutrophils (N%) (t = 3.658, P = 0.001), C-reactive protein (CRP) (t = 19.415, P < 0.001), procalcitonin (PCT) (t = 26.101, P < 0.001), sFas (t = 13.717, P < 0.001), sFasL (t = 5.357, P < 0.001) and MPO (t = 5.435, P < 0.001) levels in peripheral blood of cases with poor prognosis were significantly higher than those with good prognosis; which were all independent risk factors of poor prognosis in severe group by multivariate Logistic regression analysis (OR = 5.969, 95%CI: 4.857-6.304, P = 0.029; OR = 7.485, 95%CI: 6.785-8.126, P = 0.014; OR = 5.332, 95%CI: 4.593-5.567, P = 0.010; OR = 4.959, 95%CI: 4.246-5.337, P = 0.015; OR = 5.143, 95%CI: 4.879-5.695, P = 0.003; OR = 6.126, 95%CI: 5.630-6.558, P = 0.008; OR = 8.325, 95%CI: 6.452-9.902, P = 0.005; OR = 8.469, 95%CI: 7.879-8.653, P = 0.001; OR = 9.132, 95%CI: 8.882-9.594, P = 0.003). The Cut-off values of peripheral blood sFas, sFasL and MPO levels predicting poor prognosis in severe group were 125.07 ng/L, 171.21 ng/L and 1 053.04 U/L, respectively. The area under ROC curve (AUC) predicted by peripheral blood sFas, sFasL and MPO and the three indicators combination were 0.875, 0.890, 0.897 and 0.955, respectively, and the AUC of combination prediction was significantly higher than that of sFas, sFasL and MPO alone (Z = 5.693, P = 0.005; Z = 5.192, Z = 0.007; Z = 4.982, P = 0.009).

Conclusions

The levels of sFas, sFasL and MPO in peripheral blood of children with severe pneumonia are high, especially higher in children with severe pneumonia with poor prognosis, which can be used to predict poor prognosis.

Key words: Severe pneumonia, Soluble Fas protein, Soluble Fas protein ligand, Myeloperoxidase
表1 三组患儿一般资料
一般资料 重症组（182例） 轻症组（196例） 对照组（178例） 统计量 P值
性别[例（%）]       χ2 = 0.146a 0.897
  男 103（56.59） 109（55.61） 98（55.06）    
  女 79（43.41） 87（44.39） 80（44.94）
年龄（± s，岁） 5.10 ± 1.05 5.20 ± 1.02 5.15 ± 1.00 F = 0.451 0.638
体重（± s，kg） 18.45 ± 3.22 18.25 ± 3.20 18.40 ± 3.25 F = 0.199 0.820
病原微生物分布[例（%）]       χ2 = 0.356 0.548b
  肺炎支原体 29（15.93） 34（17.35）      
  呼吸道合胞病毒 26（14.29） 23（11.73）      
  肺炎链球菌 24（13.19） 27（13.78）      
  其他 103（56.59） 113（57.65）      
肺炎分期[例（%）]       χ2 = 1.126 0.248a
  充血期 71（39.01） 75（38.27）      
  实变期 111（60.99） 121（61.73）  
表2 重症组、轻症组患儿治疗前和对照组儿童外周血sFas、sFasL和MPO水平（± s）
组别 例数 sFas（ng/L） sFasL（ng/L） MPO（U/L）
重症组 182 104.63 ± 19.75 1 062.36 ± 179.85 1 020.26 ± 59.71
轻症组 196 80.52 ± 13.66 703.57 ± 127.66 796.75 ± 43.02
对照组 178 58.78 ± 10.16 577.83 ± 121.22 632.59 ± 38.71
F值   192.543 260.578 1 215.604
P值   < 0.001 < 0.001 < 0.001
表3 重症组预后不良与预后良好患儿的影响因素
影响因素 预后不良（29例） 预后良好（153例） 统计量 P值
双重/多重感染     χ2 = 12.081 0.001a
  是 15（51.72） 32（20.92）    
  否 14（48.28） 121（79.08）    
多肺叶感染     χ2 = 32.378 < 0.001b
  是 13（44.83） 10（6.54）    
  否 16（55.17） 143（93.46）
WBC（± s，× 109/L） 18.38 ± 3.63 15.25 ± 2.10 t = 6.432 < 0.001
N%（± s，%） 83.49 ± 8.15 78.15 ± 7.02 t = 3.658 0.001
CRP（± s，mg/L） 22.29 ± 4.57 12.09 ± 2.03 t = 19.415 < 0.001
PCT（± s，μg/L） 5.46 ± 1.20 1.87 ± 0.53 t = 26.101 < 0.001
sFas水平（± s，ng/L） 145.86 ± 22.78 99.68 ± 15.22 t = 13.717 < 0.001
sFasL水平（± s，ng/L） 1 236.54 ± 192.86 1 053.59 ± 163.75 t = 5.357 < 0.001
MPO水平（± s，U/L） 1 185.95 ± 176.30 1 012.11 ± 154.29 t = 5.435 < 0.001
机械通气     χ2 = 2.030 0.154b
  是 22（75.86） 132（86.27）    
  否 7（24.14） 21（13.73）
规范抗感染治疗     χ2 = 1.124 0.289b
  是 26（89.66） 145（94.77）    
  否 3（10.34） 8（5.23）
表4 重症组患儿预后不良的危险因素Logistic多元回归分析
影响因素 β值 SE值 Wald χ2值 P值 OR值 95%CI
双重/多重感染 1.689 0.867 3.795 0.029 5.969 4.857~6.304
多肺叶感染 1.753 0.842 4.335 0.014 7.485 6.785~8.126
WBC 1.996 0.883 5.110 0.010 5.332 4.593~5.567
N% 1.432 0.695 4.245 0.015 4.959 4.246~5.337
CRP 1.674 0.647 6.694 0.003 5.143 4.879~5.695
PCT 1.858 0.756 6.040 0.008 6.126 5.630~6.558
sFas 2.034 0.810 6.306 0.005 8.325 6.452~9.902
sFasL 2.169 0.825 6.912 0.001 8.469 7.879~8.653
MPO 2.155 0.837 6.629 0.003 9.132 8.882~9.594
图1 外周血sFas、sFasL、MPO水平以及联合指标预测重症患儿预后不良的ROC曲线
表5 外周血sFas、sFasL、MPO水平以及联合指标对重症患儿预后不良的预测价值
指标 Cut-off值 灵敏度（%） 特异度（%） AUC 95%CI
sFas 125.07 ng/L 82.76 96.08 0.875 0.818~0.920
sFasL 1 171.21 ng/L 79.31 97.39 0.890 0.836~0.932
MPO 1 053.04 U/L 75.86 98.04 0.897 0.843~0.937
联合 — 100.00 95.42 0.955 0.914~0.980
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