Expression Levels of Serum RAGE and CXCL10 in Children with Bronchiolitis and Their Correlation with Disease Severity
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摘要:
目的 探索毛细支气管炎患儿血清晚期糖基化终产物受体（receptor for advanced glycation end product，RAGE）、CXC趋化因子配体10（cxc chemokine ligand 10，CXCL10）水平与病情严重程度的关系。 方法 选取2023年1月至2024年7月张家口市妇幼保健院收治的102例毛细支气管炎患儿为研究对象，按照病情严重程度分为轻度组（n = 39）、中度组（n = 31）、重度组（n = 32）；选取同期张家口市妇幼保健院体检的健康幼儿90例为对照组；收集各组年龄、性别等临床资料；使用t检验、χ2检验或者单因素方差分析各组临床资料和血清RAGE、CXCL10水平，Spearman分析相关性，Logistic回归分析影响因素，ROC曲线分析预测价值。 结果 毛细支气管炎患儿血清RAGE、CXCL10水平显著高于对照组（t = 10.518、9.631，P < 0.05）；轻度组、中度组、重度组毛细支气管炎患儿早产率比较，差异有统计学意义（χ2=11.226，P < 0.05），随着患儿病情加重，中性粒细胞比例、中性粒细胞/淋巴细胞比值、血清RAGE、CXCL10水平逐渐升高（F/χ2=7.883、14.749、30.808、16.483，P < 0.05），淋巴细胞比例逐渐降低（χ2=13.938，P < 0.05）；血清RAGE、CXCL10水平与毛细支气管炎患儿病情严重程度呈正相关（r = 0.699、0.485，P < 0.05）；血清RAGE、CXCL10水平是毛细支气管炎病情严重程度的影响因素（OR = 1.726、1.761，P < 0.05）；血清RAGE、CXCL10高水平患者病情为中/重度的风险分别为低水平患者的1.900倍（95%CI: 1.250～2.887）、1.613倍（95%CI: 1.108～2.347）；血清RAGE、CXCL10二者联合预测毛细支气管炎患儿病情严重程度的AUC是0.951，优于单项检测（ZRAGE-联合=2.084、P = 0.037，ZCXCL10-联合=2.738、P = 0.006）。 结论 毛细支气管炎患儿血清RAGE、CXCL10水平升高，为病情严重的影响因素，二者联合具有更高的临床预测价值。 -
关键词:
- 毛细支气管炎 /
- 病情严重程度 /
- 晚期糖基化终产物受体 /
- CXC趋化因子配体10
Abstract:Objective To explore the relationship between serum levels of receptor for advanced glycation end product （RAGE） and CXC chemokine ligand 10 （CXCL10） and disease severity in children with bronchiolitis. Methods A total of 102 children with bronchiolitis admitted to Zhangjiakou Maternal and Child Health Hospital from January 2023 to July 2024 were enrolled and stratified by disease severity into mild group （n = 39）, moderate group （n = 31）, and severe group （n = 32）. Ninety healthy children from routine physical examinations at the same hospital during the same period served as controls. Clinical data including age and sex were collected for each group. T-test, χ2 test, or one-way ANOVA were used to compare clinical characteristics and serum RAGE and CXCL10 levels among groups. Spearman correlation analysis was conducted to determine correlation, logistic regression analysis was used to identify influencing factors, and ROC curve analysis to assess predictive value. Results Serum RAGE and CXCL10 levels in children with bronchiolitis were significantly higher than those in the control group （t = 10.518, 9.631, P < 0.05）. There was a statistically significant difference in premature birth rate among children with mild, moderate, and severe bronchiolitis （χ2 = 11.226, P < 0.05）. With increasing disease severity, neutrophil percentage, neutrophil/lymphocyte ratio, serum RAGE and CXCL10 levels progressively increased （F/χ2=7.883, 14.749, 30.808, 16.483, P < 0.05）, while lymphocyte percentage progressively decreased （χ2=13.938, P < 0.05）. Serum RAGE and CXCL10 levels were positively correlated with disease severity （r = 0.699, 0.485, P < 0.05）. Elevated serum RAGE and CXCL10 levels were independent risk factors for disease severity（OR = 1.726, 1.761, P < 0.05）. The risk of moderate/severe disease in patients with high serum RAGE and CXCL10 levels was 1.900-fold （95%CI 1.250-2.887） and 1.613-fold （95%CI 1.108-2.347） higher than in those with low levels, respectively. The combined AUC of serum RAGE and CXCL10 for predicting disease severity was 0.951, superior to single biomarker assessment （ZRAGE -combination =2.084, P = 0.037, ZCXCL10 -combination =2.738, P = 0.006）. Conclusion Serum RAGE and CXCL10 levels are elevated in children with bronchiolitis and are risk factors for disease severity. Combined assessment of both biomarkers has superior clinical predictive value. -
图 1 ROC曲线分析血清RAGE、CXCL10水平预测患儿病情程度的价值
Figure 1. ROC curve analysis of the value of serum RAGE and CXCL10 levels in predicting the severity of the disease in children
图 2 DCA曲线分析血清RAGE、CXCL10水平预测患儿病情程度的临床应用价值
注：横坐标为阈值概率，纵坐标为净获益，曲线越高表示临床获益越大。
Figure 2. Analysis of DCA curve to evaluate the clinical application value of serum RAGE and CXCL10 levels in predicting the severity of the disease in children
表 1 两组血清RAGE、CXCL10水平比较（$\bar x \pm s $）
Table 1. Comparison of serum RAGE and CXCL10 levels between two groups （$\bar x \pm s $）
组别 n RAGE（μg/mL） CXCL10（pg/mL） 对照组 90 11.82 ± 2.31 125.83 ± 28.27 毛细支气管炎组 102 16.07 ± 3.16 174.12 ± 39.46 t - 10.517 9.631 P - <0.001* <0.001* *P < 0.05。 
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表 2 不同程度患儿临床资料比较[$\bar x \pm s $，n（%）]
Table 2. Comparison of clinical data in children with different severity levels[$\bar x \pm s $，n（%）]
指标 轻度组（n = 39） 中度组（n = 31） 重度组（n = 32） F/χ2 P 年龄（月） 11.42 ± 3.86 11.37 ± 3.92 11.23 ± 3.67 0.023 0.978 性别（男/女） 18/21 16/15 15/17 0.232 0.891 家族史（有/无） 16/23 17/14 14/18 1.428 0.490 出生体质量（kg） 3.48 ± 0.47 3.51 ± 0.49 3.42 ± 0.43 0.310 0.734 母乳喂养（是/否） 20/19 14/17 14/18 0.465 0.793 体温（℃） 38.34 ± 0.49 38.39 ± 0.46 38.57 ± 0.50 2.115 0.126 病程（d） 3.05 ± 0.31 3.23 ± 0.34α 3.41 ± 0.39α 2.657 0.075 早产（是/否） 3/36 6/25 14/18# 11.226 0.004* 血常规指标 血红蛋白（g/L） 102.25 ± 23.11 101.74 ± 22.83 101.29 ± 2.78 0.022 0.978 白细胞计数（109/L） 8.37 ± 1.14 8.42 ± 1.26 8.21 ± 1.23 0.265 0.767 血小板计数（109/L） 323.43 ± 53.84 319.85 ± 52.43 317.57 ± 52.12 0.111 0.895 中性粒细胞（%） 22.73 ± 3.94 25.02 ± 4.59α 27.13 ± 5.47α# 7.883 0.001* 淋巴细胞（%） 63.82 ± 10.72 56.34 ± 9.24α 51.82 ± 8.78α# 13.938 <0.001* 中性粒细胞/淋巴细胞比值 0.36 ± 0.09 0.45 ± 0.12α 0.52 ± 0.16α# 14.749 <0.001* *P < 0.05；与中度组对比，#P < 0.05；与轻度组对比，αP < 0.05。
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表 3 不同程度患儿血清RAGE、CXCL10水平比较（$\bar x \pm s $）
Table 3. Comparison of Serum RAGE and CXCL10 Levels in Children with Different disease severity（$\bar x \pm s $）
组别 n RAGE（（μg/mL） CXCL10（pg/mL） 轻度组 39 13.23 ± 2.86 147.72 ± 35.62 中度组 31 16.47 ± 3.12α 179.26 ± 40.23α 重度组 32 19.14 ± 3.57α# 201.31 ± 43.39α# F - 30.808 16.483 P - <0.001* <0.001* *P < 0.05；与中度组对比，#P < 0.05;与轻度组对比，αP < 0.05。
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表 4 毛细支气管炎患儿血清RAGE、CXCL10水平与病情程度的相关性
Table 4. Correlation between serum RAGE and CXCL10 levels and disease severity i children with bronchiolitis
指标 病情程度 r P RAGE 0.699 <0.001* CXCL10 0.485 <0.001* *P < 0.05。
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表 5 影响毛细支气管炎患儿病情严重程度的因素
Table 5. Factors affecting the severity of bronchiolitis in children
指标 β SE Wald P OR 95%CI VIP 早产 0.450 0.259 3.025 0.082 1.569 0.944～2.607 2.986 淋巴细胞比例 0.190 0.145 1.699 0.193 1.208 0.909～1.605 3.159 中性粒细胞/淋巴细胞比值 0.263 0.155 2.882 0.090 1.301 0.960～1.763 2.547 RAGE 0.546 0.225 5.885 0.015* 1.726 1.110～2.683 2.689 CXCL10 0.566 0.242 5.468 0.019* 1.761 1.096～2.830 1.967 *P < 0.05。
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表 6 不同血清RAGE、CXCL10水平对毛细支气管炎患儿病情严重程度影响
Table 6. Effects of different serum RAGE and CXCL10 levels on disease severity in children with bronchiolitis
指标 中/重组（n = 63） 轻度组（n = 39） 相对危险度（95%置信区间） χ2 P RAGE 高水平 48 16 1.900（1.250～2.887） 12.743 <0.001* 低水平 15 23 CXCL10 高水平 45 17 1.613（1.108～2.347） 7.832 0.005* 低水平 18 22 *P < 0.05。
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表 7 血清RAGE、CXCL10水平预测病情程度的预测价值
Table 7. Predictive value of serum RAGE and CXCL10 levels in predicting disease severity
指标 AUC 最佳截断值 95%CI P 敏感性（%） 特异性（%） Youden指数 RAGE 0.888 14.78 μg/mL 0.811-0.942 <0.001* 84.13 87.18 0.7131 CXCL10 0.846 148.61 pg/mL 0.761-0.910 <0.001* 95.24 61.54 0.5678 联合 0.951 - 0.890-0.984 <0.001* 85.71 97.44 0.8315 *P < 0.05。
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