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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2025, Vol. 18 ›› Issue (05) : 796 -801. doi: 10.3877/cma.j.issn.1674-6902.2025.05.024

论著

血清生物标志物联合检测对支气管哮喘患儿生物靶向治疗效果的预测意义
刘丽辉1, 白玉新1,†(), 张进2, 冯巍1, 黄琰琰1, 邹梦斯1, 刘彩红1   
  1. 1518112　深圳，深圳大学第一附属医院·深圳市第二人民医院儿科
    2518002　深圳，深圳市罗湖区人民医院儿科
  • 收稿日期:2025-05-28 出版日期:2025-10-25
  • 通信作者: 白玉新

Predictive significance of combined detection of serum biomarkers in effect of biological targeted therapy on children with bronchial asthma

Lihui Liu1, Yuxin Bai1,†(), Jin Zhang2, Wei Feng1, Yanyan Huang1, Mengsi Zou1, Caihong Liu1   

  1. 1Department of Pediatrics, the First Affiliated Hospital of Shenzhen University·Shenzhen Second People′s Hospital, Shenzhen 518112
    2Pediatrics Department, Luohu District People′s Hospital, Shenzhen 518002, China
  • Received:2025-05-28 Published:2025-10-25
  • Corresponding author: Yuxin Bai
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引用本文：

刘丽辉, 白玉新, 张进, 冯巍, 黄琰琰, 邹梦斯, 刘彩红. 血清生物标志物联合检测对支气管哮喘患儿生物靶向治疗效果的预测意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(05): 796-801.

Lihui Liu, Yuxin Bai, Jin Zhang, Wei Feng, Yanyan Huang, Mengsi Zou, Caihong Liu. Predictive significance of combined detection of serum biomarkers in effect of biological targeted therapy on children with bronchial asthma[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(05): 796-801.

目的

分析血清生物标志物联合检测对支气管哮喘(bronchial asthma, BA)患儿生物靶向治疗的预测意义。

方法

选取我院2022年3月至2025年4月收治的64例BA患儿，根据奥马珠单抗治疗16周后疗效分组，治疗有效为观察组48例，治疗无效为对照组16例，比较两组患儿临床资料、第1秒呼气容积(forced expiratory volume in one second, FEV1)、第1秒用力呼气量与用力肺活量比值(forced expiratory volume in one second /forced vital capacity, FEV1/FVC)、呼气峰值流速(peak expiratory flow, PEF)、血清生物标志物免疫球蛋白E(Immunoglobulin E, IgE)、白细胞介素(interleukin, IL)-4、IL-6、IL-17A、IL-2R，采用Logistic回归分析BA患儿生物靶向治疗反应性的影响因素，绘制受试者特征曲线(receiver characteristic curve, ROC)判断预测意义。

结果

观察组病情轻度患儿23例(47.92%)、FEV1(94.42±8.54)%高于对照组3例(18.75%)、FEV1(81.53±5.65)%；总IgE(1 102.9±292.5)IU/ml、IL-4(8.86±2.02)pg/ml、IL-6(8.95±2.37)pg/ml、IL-17A(8.62±2.31)pg/ml、IL-2R(164.64±54.16)U/ml低于对照组总IgE(1 677.7±527.9)IU/ml、IL-4(12.78±3.54)pg/ml、IL-6(10.64±3.15)pg/ml、IL-17A(13.39±4.45)pg/ml、IL-2R(248.54±75.39)U/ml(P<0.05)。Logistic回归分析显示，病情严重程度(OR＝0.358，95%CI：0.127~1.006)、FEV1(OR＝1.238，95%CI: 1.102~1.392)、血清总IgE(OR＝0.980，95%CI：1.102~1.392)、IL-2R(OR＝0.974，95%CI: 0.954~0.994)、IL-4(OR＝0.617，95%CI: 0.402~0.947)是BA患儿生物靶向治疗影响因素。ROC曲线分析显示，血清总IgE、IL-4、IL-2R联合预测BA患儿生物靶向治疗曲线下面积(area under the curve, AUC)为0.896(95%CI: 0.906~0.999)，高于血清总IgE、IL-4、IL-2R单独预测AUC 0.683(95%CI: 0.703~0.904)、0.654(95%CI: 0.722~0.917)、0.642(95%CI: 0.676~0.886)。

结论

血清IgE、IL-4、IL-2R水平与BA患儿生物靶向治疗效果呈负相关，血清IgE、IL-4、IL-2R联合预测对BA患儿生物靶向治疗具有临床意义。

关键词: 支气管哮喘, 生物靶向治疗, 血清生物标志物, 疗效预测
Objective

To analyze the predictive significance of combined serum biomarker testing for biological targeted therapy in children with bronchial asthma (BA).

Methods

A total of 64 children with BA admitted to our hospital from March 2022 to April 2025 were selected. Based on the efficacy after 16 weeks of omalizumab treatment, they were divided into two groups: 48 effective cases as the observation group and 16 ineffective cases as the control group. Clinical data, forced expiratory volume in one second (FEV1), forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC), peak expiratory flow (PEF), and serum biomarkers including immunoglobulin E (IgE), interleukin (IL)-4, IL-6, IL-17A, and IL-2R were compared between the two groups. Logistic regression analysis was used to identify factors influencing the responsiveness of BA children to biological targeted therapy, and receiver operating characteristic (ROC) curves were plotted to evaluate predictive value.

Results

In the observation group, 23 cases (47.92%) had mild disease, and FEV1 (94.42±8.54)% was higher than that in the control group [3 cases (18.75%), FEV1 (81.53±5.65)%]. Total IgE (1 102.9±292.5)IU/ml, IL-4 (8.86±2.02)pg/ml, IL-6(8.95±2.37)pg/ml, IL-17A(8.62±2.31)pg/ml, and IL-2R(164.64±54.16)U/ml in the observation group were lower than those in the control group total IgE (1 677.7±527.9)IU/ml, IL-4 (12.78±3.54)pg/ml, IL-6 (10.64±3.15)pg/ml, IL-17A (13.39 ± 4.45)pg/ml, IL-2R (248.54±75.39)U/ml (P<0.05). Logistic regression analysis showed that disease severity (OR=0.358, 95%CI=0.127~1.006), FEV1(OR=1.238, 95%CI=1.102~1.392), serum total IgE (OR=0.980, 95%CI: 1.102~1.392), IL-2R(OR=0.974, 95%CI: 0.954~0.994), and IL-4(OR=0.617, 95%CI: 0.402~0.947) were influencing factors for biological targeted therapy in children with BA. ROC curve analysis revealed that the area under the curve (AUC) for the combined prediction of serum total IgE, IL-4, and IL-2R for biological targeted therapy in children with BA was 0.896 (95%CI=0.906~0.999), which was higher than the AUCs for individual predictions of serum total IgE (0.683, 95%CI=0.703~0.904), IL-4 (0.654, 95%CI: 0.722~0.917), and IL-2R (0.642, 95%CI: 0.676~0.886).

Conclusion

Serum levels of IgE, IL-4, and IL-2R are negatively correlated with the efficacy of biological targeted therapy in children with BA. The combined prediction of serum IgE, IL-4, and IL-2R holds clinical significance for biological targeted therapy in children with BA.

Key words: Bronchial asthma, Biological targeted therapy, Serum biomarkers, Therapeutic effect prediction
表1 两组BA患儿临床资料结果比较(±s)
临床资料 观察组(n＝48) 对照组(n＝16) t/χ2值 P值
FEV1(%) 94.42±8.54 81.53±5.65 6.876 0.000
FEV1/FVC 84.23±9.15 78.89±10.58 1.806 0.085
PEF(%) 80.42±11.63 75.56±10.23 1.589 0.123
总IgE(IU/ml) 1 102.9±292.5 1 677.7±527.9 4.147 0.001
IL-4(pg/ml) 8.86±2.02 12.78±3.54 4.207 0.001
IL-6(pg/ml) 8.95±2.37 10.64±3.15 1.968 0.063
IFN-γ(pg/ml) 12.54±1.62 13.81±2.65 1.808 0.087
IL-17A(pg/ml) 8.62±2.31 13.39±4.45 4.107 0.001
IL-1β(pg/ml) 4.61±1.03 5.34±1.59 1.720 0.102
IL-2(pg/ml) 7.87±1.53 8.25±1.68 0.801 0.431
IL-2R(U/ml ) 164.64±54.16 248.54±75.39 4.112 0.001
IL-8(pg/ml ) 19.54±4.12 21.91±4.96 1.723 0.099
TNF-α(pg/ml ) 10.43±1.56 12.87±5.29 1.819 0.089
表2 BA患儿生物靶向治疗反应Logistic回归分析
自变量 β 标准误 Wald P值 OR 95%CI
下限 上限
病情严重程度 －1.027 0.527 3.797 0.041 0.358 0.127 0.506
FEV1 0.214 0.060 12.829 0.000 1.238 1.102 1.392
总IgE －0.020 0.013 2.443 0.018 0.980 0.856 0.995
IL-2R －0.027 0.011 6.294 0.012 0.974 0.954 0.994
IL-4 －0.483 0.219 4.889 0.027 0.617 0.402 0.947
IL-17A －0.190 0.270 0.491 0.483 0.827 0.487 1.406
常量 21.402 6.909 9.595 0.002      
表3 生物标志物预测BA患儿生物靶向治疗反应ROC曲线分析
自变量 AUC 95%CI P值 敏感性 特异性 约登指数
总IgE 0.819 0.703~0.904 0.000 87.50 70.83 0.683
IL-4 0.836 0.722~0.917 0.000 81.25 65.42 0.654
IL-2R 0.796 0.676~0.886 0.000 62.50 61.70 0.642
联合 0.978 0.906~0.999 0.000 89.58 90.00 0.896
图1 患儿典型胸部X线摄片。图A为10岁男孩重度哮喘首诊胸片；图B为8岁男孩重度哮喘首诊胸片
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