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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2024, Vol. 18 ›› Issue (02) : 91 -99. doi: 10.3877/cma.j.issn.1674-1358.2024.02.005

论著

232例手足口病患儿流行特征及预后风险模型的构建与验证
吕巧荣1,†(), 张燕1, 付敏1   
  1. 1. 617067　攀枝花市，四川省攀枝花市中心医院公共卫生科
  • 收稿日期:2023-08-27 出版日期:2024-04-15
  • 通信作者: 吕巧荣
  • 基金资助:
    四川省科委社会类科技发展基金项目(No. SC528-0215B)

Construction and validation of epidemic characteristics and prognostic risk model of hand, foot and mouth disease

Qiaorong Lv1,†(), Yan Zhang1, Min Fu1   

  1. 1. Department of Public Health, Panzhihua Central Hospital, Panzhihua 617067, China
  • Received:2023-08-27 Published:2024-04-15
  • Corresponding author: Qiaorong Lv
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引用本文：

吕巧荣, 张燕, 付敏. 232例手足口病患儿流行特征及预后风险模型的构建与验证[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(02): 91-99.

Qiaorong Lv, Yan Zhang, Min Fu. Construction and validation of epidemic characteristics and prognostic risk model of hand, foot and mouth disease[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2024, 18(02): 91-99.

目的

探讨手足口病（HFMD）流行特征并分析影响其预后的危险因素，行风险模型的构建与验证。

方法

回顾性收集2017年1月至2023年10月四川省攀枝花市中心医院收治的232例HFMD患儿的临床资料，根据预后将入组患儿分为预后良好组178例（男106例，女72例）和预后不良组54例（男30例，女24例）；分析HFMD流行特征，比较两组患儿的临床资料，多因素Logistic回归分析影响HFMD预后的独立因素，并建立风险预测模型进行验证。

结果

入组患儿中< 1岁HFMD发病率显著高于1岁及以上患儿（P < 0.001），女性患儿发病率显著低于男性患儿（χ2 = 2.372、P=0.039），夏季发病率显著高于其他3个季节（χ2 = 9.231、P < 0.001），散居发病率高于托幼和其他居住类型儿童（P < 0.001）。多因素Logistic回归分析显示，年龄≤ 2岁（OR = 3.668、95%CI：1.110～5.332、P = 0.011）、白细胞介素-6（IL-6）> 25 ng/L（OR = 4.968、95%CI：2.382～6.470、P = 0.001）、肿瘤坏死因子α（TNF-α）> 175 ng/L（OR = 5.042、95%CI：3.265～7.044、P < 0.001）、血清淀粉样蛋白A（SAA）> 10 mg/L（OR = 3.970、95%CI：2.053～6.339、P = 0.013）、空腹血糖（FBG）≥6.10 mmol/L（OR = 5.286、95%CI：3.563～6.502、P < 0.001）和白细胞（WBC）计数≥ 10 × 109/L（OR = 4.879、95%CI：2.165～6.361、P = 0.003）均为预后不良的独立危险因素，逐步回归分析显示这6个临床指标与HFMD患儿预后不良关联最紧密；经验证显示预测模型具有良好的准确性和区分度。风险评分显示高危组HFMD患儿预后不良概率显著高于低/中危组（χ2 = 6.032、P = 0.010）；该风险评分系统训练集数据绘制的受试者工作特征曲线（ROC）敏感度和特异度分别为78.11%和77.95%，曲线下面积（AUC）为0.859（95%CI：0.815～0.887），验证集ROC曲线敏感度和特异度分别为77.94%和77.72%，AUC为0.854（95%CI：0.811～0.885）。

结论

不同年龄、性别、居住特点和季节的儿童HFMD分布存在明显差异，对低龄和散居儿童应加强管理，监测HFMD患儿预后不良风险因素并识别高危患儿有利于早期治疗决策和疗效的提升。

关键词: 手足口病, 风险模型, 流行特征, 预后
Objective

To investigate the epidemic characteristics of hand, foot and mouth disease (HFMD) and analyze the risk factors affecting prognosis, as well as the construction and verification of risk model.

Methods

The clinical data of 232 children with HFMD admitted to Panzhihua Central Hospital of Sichuan Province from January 2017 to October 2023 were collected, retrospectively. According to the prognosis, the patients were divided into two groups: good prognosis group (106 males and 72 females) and poor prognosis group (30 males and 24 females). The clinical data and epidemic characteristics of HFMD were collected, and the independent factors affecting prognosis were analyzed by multivariate Logistic regression and a risk prediction model was established.

Results

The incidence of HFMD of children under one-year old was significantly higher than that of over one-year old (P < 0.001), the incidence of HFMD of female children was significantly lower than that of male children (χ2 = 2.372, P = 0.039), the incidence in summer was significantly higher than that in the other three seasons (χ2 = 9.231, P < 0.001), the incidence of scattered children was higher than that of nursery children and other living types (P < 0.001). Multivariate Logistic regression analysis showed that age ≤ 2 years old (OR = 3.668, 95%CI: 1.110-5.332, P = 0.011), interleukin-6 (IL-6) > 25 ng/L (OR = 4.968, 95%CI: 2.382-6.470, P = 0.001), tumor necrosis factor (TNF-α) > 175 ng/L (OR = 5.042, 95%CI: 3.265-7.044, P < 0.001), serum amyloid A (SAA) > 10 mg/L (OR = 3.970, 95%CI: 2.053-6.339, P = 0.013), fasting blood glucose (FBG) ≥ 6.10 mmol/L (OR = 5.286, 95%CI: 3.563-6.502, P < 0.001) and white blood cell (WBC) ≥ 10 × 109 (OR = 4.879, 95%CI: 2.165-6.361, P = 0.003) were all independent risk factors for poor prognosis. Stepwise regression analysis showed that these six clinical indexes were most closely related to poor prognosis of patients with HFMD. The validation showed that the prediction model had good accuracy and discrimination. The risk score showed that the probability of poor prognosis of HFMD patients in the high risk group was significantly higher than those in the low/medium risk group (χ2 = 6.032, P = 0.010). The area under the ROC curve (AUC) drawn by the training set data of the risk scoring system was 0.859 (95%CI: 0.815-0.887), the sensitivity was 78.11%, the specificity was 77.95%; the AUC of the verification set was 0.854 (95%CI: 0.811-0.885), the sensitivity was 77.94%, and the specificity was 77.72%.

Conclusions

There are significant differences in the distribution of children with HFMD among different ages, genders, living characteristics and seasons. Management and supervision should be strengthened for young and scattered children. Monitoring the poor prognostic risk factors of children with HFMD and identifying high-risk children are conducive to early clinical treatment decision-making and the effect of treatment improvement.

Key words: Hand, Foot and mouth disease, Risk model, Epidemic characteristics, Prognosis
表1 232例HFMD患儿的人口学特征
人口学特征 例数 构成比（%） χ2值 P值
年龄     － < 0.001b
< 1岁 103 44.40    
1～2岁 59 25.43c    
3～4岁 27 11.64cd    
5～6岁 23 9.91cd    
7～10岁 20 8.62cd    
性别     2.372 0.039a
男 136 58.62    
女 96 41.38    
居住特点     － < 0.001b
托幼 42 18.10    
散居 173 74.57    
其他 17 7.33    
图1 HFMD患儿发病的季节特征
图2 HFMD患儿发病率箱线图注：A：2017至2023年月均发病率箱线图；B：2017至2023年季度发病率箱线图
表2 预后良好组和预后不良组HFMD患儿一般资料
指标 预后良好组（178例） 预后不良组（54例） 统计量 P值
年龄[例（%）]     χ2 = 4.537 0.033a
> 2岁 60（33.71） 10（18.52）    
≤ 2岁 118（66.29） 44（81.48）    
性别[例（%）]     χ2 = 0.273 0.602a
男 106（59.55） 30（55.56）    
女 72（40.45） 24（44.44）    
病原[例（%）]     χ2 = 0.376 0.945a
CA16 40（22.47） 12（22.22）    
EV71 56（31.46） 18（33.33）    
其他肠道病毒 46（25.84） 15（27.78）    
阴性及不详 36（20.22） 9（16.67）    
发热[例（%）]     χ2 = 7.061 0.008a
有 40（22.47） 22（40.74）    
无 138（77.53） 32（59.26）    
惊厥[例（%）]     χ2 = 0.254 0.614a
有 34（19.10） 12（22.22）    
无 144（80.90） 42（77.78）    
心率[例（%）]     χ2 = 0.000 0.984a
< 160次/min 125（70.22） 38（70.37）    
≥ 160次/min 53（29.78） 16（29.63）    
住院时间[例（%）]     χ2 = 0.032 0.858a
< 14 d 113（63.48） 35（64.81）    
≥ 14 d 65（36.52） 19（35.19）    
就诊时间[例（%）]     χ2 = 2.979 0.084a
< 3 d 83（46.63） 18（33.33）    
≥ 3 d 95（53.37） 36（66.67）    
不典型皮疹[例（%）]     χ2 = 5.872 0.015a
有 69（38.76） 31（57.41）    
无 109（61.24） 23（42.59）    
CRP（ ± s，mg/L） 13.32 ± 4.06 13.96 ± 3.42 t = 1.050 0.295
PCT（ ± s，ng/mL） 57.21 ± 7.02 57.03 ± 7.11 t = 0.165 0.869
SAA（ ± s，mg/L） 2.12 ± 0.41 69.85 ± 7.26 t = 124.432 < 0.001
LTB4（ ± s，ng/L） 26.03 ± 6.28 44.15 ± 13.26 t = 13.855 < 0.001
COX-2（ ± s，µg/L） 23.78 ± 5.82 45.01 ± 12.84 t = 17.074 < 0.001
IL-6（ ± s，ng/L） 18.93 ± 3.46 48.17 ± 13.46 t = 26.365 < 0.001
TNF-α（ ± s，ng/L） 58.57 ± 6.83 269.54 ± 41.26 t = 65.624 < 0.001
hs-cTnT（ ± s，µg/L） 0.08 ± 0.03 3.19 ± 1.08 t = 38.563 < 0.001
NSE（ ± s，µg/L） 6.64 ± 1.68 20.25 ± 3.76 t = 37.595 < 0.001
FBG [例（%）]     χ2 = 8.886 0.003a
< 6.10 mmol/L 125（70.22） 26（48.15）    
≥ 6.10 mmol/L 53（29.78） 28（51.85）    
WBC计数[例（%）]     χ2 = 5.563 0.018a
< 10 × 109/L 132（74.16） 31（57.41）    
≥ 10 × 109/L 46（25.84） 23（42.59）    
表3 HFMD患儿预后不良的多因素Logistic回归分析
指标 β值 S.E.值 Wald χ2值 OR值 95%CI P值
年龄 1.300 0.610 4.539 3.668 1.110～5.332 0.011
发热 1.198 0.695 2.969 3.312 0.924～5.679 0.087
不典型皮疹 0.862 0.662 1.697 2.369 0.872～4.665 0.072
SAA 1.379 0.579 5.671 3.970 2.053～6.339 0.013
LTB4 0.960 0.631 2.313 2.611 0.791～3.592 0.064
COX-2 1.189 0.644 3.411 3.285 0.921～5.411 0.070
IL-6 1.603 0.560 8.194 4.968 2.382～6.470 0.001
TNF-α 1.618 0.482 11.266 5.042 3.265～7.044 < 0.001
hs-cTnT 1.116 0.693 2.594 3.053 0.888～5.421 0.075
NSE 1.201 0.734 2.678 3.324 0.987～5.708 0.111
FBG 1.665 0.519 10.293 5.286 3.563～6.502 < 0.001
WBC 1.585 0.526 9.079 4.879 2.165～6.361 0.003
图4 基于逐步回归的HFMD患儿预后不良风险因素筛选注：A：AIC分布图；B：训练集和验证集在不同临床因素的构建预后模型一致性指数：1：年龄；2：IL-6；3：SAA；4：TNF-α；5：FBG；6：WBC；7：WBC/FBG/TNF-α；8：WBC/FBG/TNF-α/SAA；9：WBC/FBG/TNF-α/SAA/IL-6；10：WBC/FBG/TNF-α/SAA/IL-6/年龄
表4 HFMD患儿预后不良危险因素在训练集和验证集的C指数
危险因素 训练集 验证集
P值 C指数 95%CI P值 C指数 95%CI
年龄 < 0.001 0.432 0.413～0.662 < 0.001 0.430 0.326～0.522
IL-6 < 0.001 0.511 0.542～0.578 < 0.001 0.509 0.487～0.593
SAA < 0.001 0.529 0.517～0.574 < 0.001 0.526 0.509～0.591
TNF-α < 0.001 0.572 0.539～0.621 < 0.001 0.566 0.524～0.618
FBG < 0.001 0.617 0.589～0.631 < 0.001 0.621 0.584～0.703
WBC < 0.001 0.646 0.628～0.683 < 0.001 0.652 0.620～0.662
图5 预测模型的准确度评价注：A：训练集；B：验证集
图6 各危险分层患儿预后分布
图7 评分系统及预测模型判断患儿预后的ROC曲线注：A：训练集；B：验证集
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