支气管哮喘合并过敏性鼻炎患儿舌下特异性免疫治疗前后尘螨sIgE/sIgG4比值变化及对疗效的预测价值

Changes in dust mite sIgE/sIgG4 ratio before and after sublingual specific immunotherapy in children with bronchial asthma complicated with allergic rhinitis and its predictive value for therapeutic efficacy

摘要

目的 分析支气管哮喘合并过敏性鼻炎患儿舌下特异性免疫治疗(SLIT)前后尘螨特异性免疫球蛋白E(sIgE)/特异性免疫球蛋白G4(sIgG4)变化及对疗效的预测价值。方法 将2021年6月至2023年6月于江苏省泰州市人民医院接受治疗的114例支气管哮喘合并过敏性鼻炎患儿作为研究对象,根据治疗1年后症状和药物综合评分(CSMS)分为控制稳定组(80例)和控制不稳定组(34例)。采用两因素方差分析比较两组患儿治疗期间sIgE、sIgG4及sIgE/sIgG4动态变化差异。采用多元线性逐步回归分析不同时间点的炎症因子与sIgE、sIgG4及sIgE/sIgG4的相关性。采用Logistic回归模型分析sIgE/sIgG4与患儿疗效的相关性。通过限制性立方样条模型评估sIgE/sIgG4与患儿疗效的剂量-反应关系。采用单因素log-binomial回归模型分析患儿sIgE/sIgG4与疗效及其亚型间的关联。结果 控制稳定组哮喘视觉模拟评分量表(VAS)评分、鼻炎VAS评分、哮喘控制问卷(ACQ)评分、鼻炎症状评分、鼻炎体征评分、哮喘日间症状评分、哮喘夜间症状评分和嗜酸性粒细胞(Eos)计数均显著低于控制不稳定组(t介于2.015到9.343之间,P<0.05),第一秒用力呼气容积(FEV1)、肺活量(VC)和呼气峰流量(PEF)均显著高于控制不稳定组(t介于3.964到7.572之间,P<0.05)。治疗前后各时间点控制稳定组C-反应蛋白(CRP)、白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)水平均显著低于控制不稳定组(t介于2.005和29.085之间,P<0.05),治疗后两组CRP、IL-17、TNF-α水平均显著降低,差异有统计学意义(t介于2.041和72.629之间,P<0.05)。控制稳定组治疗前后的sIgE和sIgE/sIgG4均低于控制不稳定组,sIgG4均高于控制不稳定组,差异有统计学意义(t介于2.009到11.404之间,P<0.05)。两组患儿sIgE、sIgG4和sIgE/sIgG4动态变化的时间效应、组间效应和交互效应显著(F介于86.013和303.471之间,P<0.05);与治疗前比较,治疗后两组患儿的sIgG4均显著升高,sIgE、sIgE/sIgG4显著降低,差异均有统计学意义(t介于2.259到24.388之间,P<0.05)。多元线性逐步回归分析结果显示,不同时间点的炎症因子与sIgE、sIgG4及sIgE/sIgG4具有一定相关性(β介于-4.836和5.791之间,P<0.05)。Logistic回归模型分析结果显示,sIgE/sIgG4与患儿疗效存在独立相关性(OR=1.68,95%CI:1.57~1.78,P<0.001)。限制性立方样条模型结果显示,sIgE/sIgG4与治疗无效的关联强度呈正向非线性剂量-反应关系(P=0.018),sIgE/sIgG4水平越高,患儿治疗无效风险越高。单因素log-binomial回归模型分析结果显示,sIgE/sIgG4水平与治疗有效呈负相关(RR=0.66)。结论 支气管哮喘合并过敏性鼻炎患儿SLIT治疗后尘螨sIgE/sIgG4显著降低,且sIgE/sIgG4对患儿治疗疗效具有一定预测价值。

Abstract

Objective To analyze the changes in dust mite specific immunoglobulin E/specific immunoglobulin G4 (sIgE/sIgG4) before and after sublingual specific immunotherapy (SLIT) in children with bronchial asthma complicated with allergic rhinitis, and its predictive value for efficacy. Methods A total of 114 children with bronchial asthma complicated with allergic rhinitis who were treated in Taizhou People's Hospital of Jiangsu Province from June 2021 to June 2023 were selected as the research objects. According to the combined symptom and medication score (CSMS) after one year of treatment, they were divided into stable control group (80 cases) and unstable control group (34 cases). Two factor analysis of variance was used to compare the dynamic changes in sIgE, sIgG4 and sIgE/sIgG4 between two groups of patients during treatment. Using multiple linear stepwise regression analysis to investigate the correlation between inflammatory factors and sIgE, sIgG4, and sIgE/sIgG4 at different time points. Logistic regression model was used to analyze the correlation between sIgE/sIgG4 and the efficacy of children. The dose-response relationship between sIgE/sIgG4 and the efficacy of children was evaluated by restricted cubic spline model. Using a single factor log genomic regression model to analyze the association between sIgE/sIgG4 and therapeutic efficacy and its subtypes in pediatric patients. Results The asthma visual analogue scale (VAS) score, rhinitis VAS score, asthma control questionnaire (ACQ) score, rhinitis symptom score, rhinitis sign score, asthma daytime symptom score, asthma nighttime symptom score and eosinophill (Eos) count in the stable control group were significantly lower than those in the unstable control group (t ranged from 2.015 to 9.343, P<0.05). The forced expiratory volume in one second (FEV1), vital capacity (VC), and peak expiratory flow (PEF) were significantly higher in the unstable control group (t ranged from 3.964 to 7.572, P<0.05). The levels of C-reactive protein (CRP), interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) in the stable control group were significantly lower than those in the unstable control group at each time point before and after treatment (t ranged from 2.005 to 29.085, P<0.05). After treatment, the levels of CRP, IL-17 and TNF-α in the two groups were significantly lower than those in the unstable control group (t ranged from 2.041 to 72.629, P<0.05). The sIgE and sIgE/sIgG4 in the stable control group before and after treatment were lower than those in the unstable control group, and the sIgG4 was higher than that in the unstable control group, the difference was statistically significant (t ranged from 2.009 to 11.404, P<0.05). The time effect, intergroup effect, and interaction effect of sIgE, sIgG4, and sIgE/sIgG4 dynamic changes in two groups of children were significant (F ranged from 86.013 to 303.471, P<0.05). Compared with before treatment, the levels of sIgG4 in the two groups were significantly increased after treatment, and the levels of sIgE and sIgE/sIgG4 were significantly decreased, the differences were statistically significant (t ranged from 2.259 to 24.388, P<0.05). The results of multiple linear stepwise regression analysis showed that inflammatory factors at different time points were correlated with sIgE, sIgG4 and sIgE/sIgG4 (β ranged from -4.836 to 5.791, P<0.05). Logistic regression model analysis showed that sIgE/sIgG4 was independently correlated with the efficacy of children (OR=1.68, 95%CI: 1.57-1.78, P<0.001). The results of the restricted cubic spline model showed that there was a positive nonlinear dose-response relationship between sIgE/sIgG4 and treatment failure (P=0.018). The higher the level of sIgE/sIgG4, the higher the risk of treatment failure in children. The analysis results of the single factor log genomic regression model showed that the levels of sIgE/sIgG4 were negatively correlated with treatment effectiveness (RR=0.66). Conclusion The sIgE/sIgG4 of dust mites in children with bronchial asthma complicated with allergic rhinitis decreased significantly after SLIT treatment, and sIgE/sIgG4 had a certain predictive value for the therapeutic effect of children.

关键词

儿童 / 支气管哮喘 / 过敏性鼻炎 / 舌下特异性免疫治疗 / sIgE/sIgG4 / 治疗效果

Key words

child / bronchial asthma / allergic rhinitis / sublingual specific immunotherapy / sIgE/sIgG4 / therapeutic effect

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基金资助

泰州市人民医院院级科研项目(ZD202210)