2型生物标志物基线水平与哮喘儿童临床缓解预测因素
2025/08/01
摘要
背景：很少有研究探讨2型生物标志物基线水平与儿童哮喘临床特征之间的关系，尤其是在不同哮喘阶段，这可能有助于预测预后和缓解。
目的：探讨基线Th2生物标志物水平与儿童哮喘临床表现之间的关联，识别临床缓解的预测因素。
方法：本研究纳入172名儿童，平均年龄为6.87±3.04岁，包括119名哮喘患者和53名无呼吸道症状对照组。进行了临床评估，包括肺功能测试、FeNO、总IgE、血液嗜酸性粒细胞计数和皮肤试验。通过ELISA检测血清生物标志物（TSLP、IL-4/5/13、TARC、Periostin）和IgE。Th2高哮喘（IgE>100 IU/mL且嗜酸性粒细胞≥140个/μL，n=110）被分为急性发作期（n=48）、持续哮喘期（n=26）和临床缓解期（n=36）。此外，还建立了跨越哮喘阶段的小鼠模型，以测量支气管肺泡灌洗液（BALF）、血清和肺组织中的TSLP水平，验证其作为预测因子的价值。
结果：在急性加重期和持续性哮喘中，血清TSLP显著升高（P<0.01）。多变量回归分析证实其与缓解独立相关（OR=1.009，P=0.023）。ROC分析显示TSLP对缓解的鉴别能力中等（AUC=0.59，敏感性=39.1%，特异性=59.4%）。小鼠模型也显示，在缓解期间TSLP水平恢复正常。
结论：在Th2高儿童哮喘中，血清TSLP与临床缓解独立相关，尽管其单独的预测准确性中等（AUC=0.59）。将其与肺功能和IgE结合可能形成一个用于缓解评估的复合生物标志物组合。这种分层工具可能指导哮喘风险分层和个性化疾病管理。需要纵向研究来验证其预测效用。
Baseline type 2 biomarker levels and clinical remission predictors in children with asthma
Mengmeng Chen, Congcong Li, Qiuyan Yang, Huijie Zhang, Yanli Zhang, Na Wang, Jingcheng Dong
Abstract
Background: Few studies have investigated the relationship between baseline type 2 biomarker levels and clinical features in pediatric asthma, particularly in different asthma stages, which may inform prognosis and remission.
Objective: To explore the association between baseline Th2 biomarker levels and clinical manifestations in pediatric asthma, identifying predictors of clinical remission.
Methods: The study included 172 children with a mean age of 6.87 ± 3.04 years, comprising 119 asthma patients and 53 non-respiratory symptom controls. Clinical evaluations such as lung function tests, FeNO, total IgE, blood eosinophil counts, and skin tests were conducted. Serum biomarkers (TSLP, IL-4/5/13, TARC, Periostin), and IgE were measured by ELISA. Th2-high asthma (IgE >100 IU/mL and eosinophils≥140 cells/μL, n=110) was stratified into acute attack (n=48), persistent asthma (n=26), and clinical remission (n=36). Additionally, mouse models across asthma stages were established to measure TSLP levels in BALF, serum, and lung tissue, to validate its predictor value.
Result: Serum TSLP was significantly elevated in acute exacerbation and persistent asthma(P<0.01). Multivariable regression confirmed its independent association with remission (OR=1.009, P=0.023). ROC analysis indicated moderate discriminative capacity of TSLP for remission (AUC=0.59, sensitivity=39.1%, specificity=59.4%). Murine models also showed TSLP levels normalization during remission.
Conclusion: Serum TSLP is independently associated with clinical remission in Th2-high pediatric asthma, though its standalone predictive accuracy is moderate (AUC=0.59). Integration with lung function and IgE may form a composite biomarker panel for remission evaluation. This stratification tool may guide asthma risk stratification and personalized disease management. Longitudinal studies are warranted to validate its prognostic utility.
背景：很少有研究探讨2型生物标志物基线水平与儿童哮喘临床特征之间的关系，尤其是在不同哮喘阶段，这可能有助于预测预后和缓解。
目的：探讨基线Th2生物标志物水平与儿童哮喘临床表现之间的关联，识别临床缓解的预测因素。
方法：本研究纳入172名儿童，平均年龄为6.87±3.04岁，包括119名哮喘患者和53名无呼吸道症状对照组。进行了临床评估，包括肺功能测试、FeNO、总IgE、血液嗜酸性粒细胞计数和皮肤试验。通过ELISA检测血清生物标志物（TSLP、IL-4/5/13、TARC、Periostin）和IgE。Th2高哮喘（IgE>100 IU/mL且嗜酸性粒细胞≥140个/μL，n=110）被分为急性发作期（n=48）、持续哮喘期（n=26）和临床缓解期（n=36）。此外，还建立了跨越哮喘阶段的小鼠模型，以测量支气管肺泡灌洗液（BALF）、血清和肺组织中的TSLP水平，验证其作为预测因子的价值。
结果：在急性加重期和持续性哮喘中，血清TSLP显著升高（P<0.01）。多变量回归分析证实其与缓解独立相关（OR=1.009，P=0.023）。ROC分析显示TSLP对缓解的鉴别能力中等（AUC=0.59，敏感性=39.1%，特异性=59.4%）。小鼠模型也显示，在缓解期间TSLP水平恢复正常。
结论：在Th2高儿童哮喘中，血清TSLP与临床缓解独立相关，尽管其单独的预测准确性中等（AUC=0.59）。将其与肺功能和IgE结合可能形成一个用于缓解评估的复合生物标志物组合。这种分层工具可能指导哮喘风险分层和个性化疾病管理。需要纵向研究来验证其预测效用。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Front Immunol. 2025 May 28:16:1492644. doi: 10.3389/fimmu.2025.1492644.）
Baseline type 2 biomarker levels and clinical remission predictors in children with asthma
Mengmeng Chen, Congcong Li, Qiuyan Yang, Huijie Zhang, Yanli Zhang, Na Wang, Jingcheng Dong
Abstract
Background: Few studies have investigated the relationship between baseline type 2 biomarker levels and clinical features in pediatric asthma, particularly in different asthma stages, which may inform prognosis and remission.
Objective: To explore the association between baseline Th2 biomarker levels and clinical manifestations in pediatric asthma, identifying predictors of clinical remission.
Methods: The study included 172 children with a mean age of 6.87 ± 3.04 years, comprising 119 asthma patients and 53 non-respiratory symptom controls. Clinical evaluations such as lung function tests, FeNO, total IgE, blood eosinophil counts, and skin tests were conducted. Serum biomarkers (TSLP, IL-4/5/13, TARC, Periostin), and IgE were measured by ELISA. Th2-high asthma (IgE >100 IU/mL and eosinophils≥140 cells/μL, n=110) was stratified into acute attack (n=48), persistent asthma (n=26), and clinical remission (n=36). Additionally, mouse models across asthma stages were established to measure TSLP levels in BALF, serum, and lung tissue, to validate its predictor value.
Result: Serum TSLP was significantly elevated in acute exacerbation and persistent asthma(P<0.01). Multivariable regression confirmed its independent association with remission (OR=1.009, P=0.023). ROC analysis indicated moderate discriminative capacity of TSLP for remission (AUC=0.59, sensitivity=39.1%, specificity=59.4%). Murine models also showed TSLP levels normalization during remission.
Conclusion: Serum TSLP is independently associated with clinical remission in Th2-high pediatric asthma, though its standalone predictive accuracy is moderate (AUC=0.59). Integration with lung function and IgE may form a composite biomarker panel for remission evaluation. This stratification tool may guide asthma risk stratification and personalized disease management. Longitudinal studies are warranted to validate its prognostic utility.
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哮喘患者过度使用短效β₂受体激动剂的不良结局：一项系统评价与荟萃分析
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代谢表型与未控制的儿童哮喘、肠道菌群及全身性炎症相关
