Value of cytokines in predicting severe hand, foot and mouth disease in children
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摘要:目的 探讨儿童重症手足口病(HFMD)发生情况, 分析相关的危险因素。方法 选择HFMD患儿271例。根据疾病严重程度将患儿分为2组,分析临床特征、实验室检查结果等因素对重症HFMD的影响。结果 2组患儿性别、儿童类型、户籍类型、居住地、是否早产、出生体质量、分娩情况、最高体温、抽搐、面色苍白、流涕、腹泻、手足皮疹、口腔疱疹、臀部皮疹等表现均无显著差异(P>0.05)。2组患儿年龄、母乳喂养情况、发病到就诊时间、易惊、乏力、四肢颤抖、嗜睡、烦躁、心动过速、呼吸困难、呕吐、白细胞计数、血糖、C反应蛋白、肌酸激酶同工酶(CK-MB)、病毒感染类型有显著差异(P < 0.05)。在细胞因子水平方面,重症HFMD组中白介素-4(IL-4)、白介素-6(IL-6)、白介素-8(IL-8)、白介素-10(IL-10)和干扰素-γ(IFN-γ)水平较普通HFMD组显著增高(P < 0.05)。在ROC曲线分析中, IL-6、IL-10和IFN-γ对鉴别普通HFMD和重症HFMD具有重要意义。Logistic回归分析表明, IL-6≥46.0 pg/mL、IL-10≥22.7 pg/mL、IFN-γ≥81.9 pg/mL是重症HFMD的重要预测因子。结论 临床医生和家长要重视年龄小于3岁、四肢颤抖、烦躁、嗜睡、血糖升高、CK-MB升高、EV-71病毒感染的HFMD患儿, IL-6≥46.0 pg/mL、IL-10≥22.7 pg/mL、IFN-γ≥81.9 pg/mL对预测重症HFMD具有重要价值。Abstract:Objective To explore the risk factors and occurrence of severe hand, foot and mouth disease (HFMD) in children.Methods A total of 271 children with HFMD were selected and divided into two groups according to severity of disease. The influence of clinical features and laboratory data on severe HFMD was analyzed.Results There were no significant differences in gender, type of children, type of household registration, residence, preterm delivery, birth weight, delivery status, maximum body temperature, convulsion, pale face, runny nose, diarrhea, hand and foot rash, oral herpes, hip rash between the two groups (P>0.05). There were significant differences in age, breast-feeding condition, time from onset to treatment, vulnerability, fatigue, limb tremor, lethargy, dyspnoea, dyspnea, vomiting, leukocyte count, blood glucose, C reactive protein, creatine kinase isoenzyme (CK-MB) and virus infection type between the two groups (P < 0.05). In term of cytokine level, the levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-6 (IL-8), interleukin-10 (IL-10) and interferon-γ (IFN-γ) in severe HFMD group were significantly higher than those in normal HFMD group (P < 0.05). In ROC curve analysis, IL-6, IL-10 and IFN-γ played important roles in the differentiation of common HFMD and severe HFMD. Logistic regression analysis showed that IL-6 ≥46.0 pg/mL, IL-10 ≥22.7 pg/mL and IFN-γ ≥81.9 pg/mL were important predictors of severe HFMD.Conclusion Clinicians and parents should pay attention to HFMD children with age less than 3 years old, trembling limbs, lethargy, irritability, elevated blood sugar and CK-MB and EV-71 virus infection. IL-6 ≥46.0 pg/mL, IL-10 ≥22.7 pg/mL and IFN-γ ≥81.9 pg/mL could be used as the good predictors of severe HFMD in children.
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Keywords:
- hand, foot and mouth disease /
- clinical manifestations /
- cytokines /
- children /
- risk factors /
- predictive value
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表 1 2组患儿一般资料比较(x±s)[n(%)]
组别 n 早产 出生体质量/kg 分娩类型 母乳喂养 发病至就诊时间/d 顺产 剖宫产 普通HFMD组 193 6(3.1) 3.4±0.5 113(58.5) 80(41.5) 178(92.2) 3.8±2.1 重症HFMD组 78 2(2.6) 3.3±0.4 49(62.8) 29(37.2) 65(83.3)* 2.9±1.2* 与普通HFMD组比较, *P < 0.05。 表 2 2组患儿实验室结果比较[n(%)]
组别 WBC>15.0×
109/L血糖>
8.0 mmol/LCRP>
40.0 mg/LCK-MB>
40.0 U/L病原学类型 EV-71 Cox16 其他 普通HFMD组(n=193) 62(32.1) 26(13.5) 41(21.2) 55(28.5) 34(17.6) 130(67.3) 29(15.1) 重症HFMD组(n=78) 40(51.3)* 35(44.9)* 26(33.3)* 58(74.4)* 73(93.6)* 5(6.4)* 0* WBC: 白细胞; CRP: C反应蛋白; CK-MB: 肌酸激酶同工酶。与普通HFMD组比较, *P < 0.05。 表 3 2组患儿血清细胞因子水平pg/mL
细胞因子 普通HFMD组 重症HFMD组 IL-1β 17.0(7.5, 29.8) 18.5(7.9, 31.3) IL-2 82.1(38.8, 129.3) 88.8(47.2, 124.6) IL-4 4.3(2.1, 6.9) 4.8(3.2, 6.2)* IL-6 33.7(15.6, 49.1) 58.5(36.0, 199.7)* IL-8 24.5(11.5, 37.0) 30.5(14.6, 52.1)* IL-10 12.4(7.0, 20.6) 14.0(8.1, 22.7)* TNF-α 18.8(8.9, 30.8) 19.3(9.2, 35.7) IFN-γ 38.2(17.4, 62.3) 82.4(40.3, 112.2)* IL-1β: 白细胞介素-1β; IL-2: 白介素-2; IL-4: 白介素-4;
IL-6: 白介素-6; IL-8: 白介素-8; IL-10: 白介素-10;
IFN-γ: 干扰素-γ; TNF-α: 肿瘤坏死因子-α。
上述指标结果呈非正态分布,采用中位数和四分位数间距(P25, P75)表示。
与普通HFMD组比较, *P < 0.05。表 4 细胞因子预测重症HFMD的ROC曲线分析
参数 AUC 临界值 灵敏度 特异度 P 95%可信区间 IL-1β 0.531 45.440 0.115 0.964 0.426 0.455~0.607 IL-2 0.528 44.960 0.769 0.306 0.474 0.454~0.602 IL-4 0.579 2.610 0.962 0.316 0.043 0.511~0.646 IL-6 0.722 46.010 0.641 0.715 0.001 0.655~0.789 IL-8 0.585 41.680 0.359 0.834 0.028 0.507~0.664 IL-10 0.713 22.700 0.526 0.845 0.001 0.638~0.788 TNF-α 0.533 33.990 0.282 0.813 0.039 0.456~0.611 IFN-γ 0.749 81.920 0.513 0.922 0.001 0.680~0.819 IL-1β: 白细胞介素-1β; IL-2: 白介素-2; IL-4: 白介素-4; IL-6: 白介素-6; IL-8: 白介素-8; IL-10: 白介素-10;
IFN-γ: 干扰素-γ; TNF-α: 肿瘤坏死因子-α。AUC: 曲线下面积。表 5 重症手足口病相关预测因素的多因素Logistic回归分析
变量 B S. E. Wald P OR 95%CI IL-6≥46.0 pg/mL 1.510 0.630 6.270 0.011 2.350 1.690~5.980 IL-10≥22.7 pg/mL 1.790 0.740 7.320 0.004 3.650 2.210~10.050 IFN-γ≥81.9 pg/mL 2.130 0.910 6.210 0.002 4.450 2.080~11.290 IL-6: 白介素-6; IL-10: 白介素-10; IFN-γ: 干扰素-γ。 -
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