外周血EETs水平与咳嗽变异性哮喘患儿Th1和Th2及其细胞因子、小气道功能的相关性分析

Correlation analysis of peripheral blood eosinophil extracellular traps with Th1/Th2, cytokines and small airway function in children with cough variant asthma

摘要

目的 探讨外周血嗜酸性粒细胞胞外诱捕网(EETs)水平与咳嗽变异性哮喘(CVA)患儿的辅助性T淋巴细胞(Th)1和Th2及其细胞因子、小气道功能的相关性。方法 选取2019年10月至2022年10月重庆市开州区人民医院收治的95例CVA患儿为CVA组,选取同期于该院儿科保健门诊体检的67例健康儿童为对照组.检测外周血中形成EETs的嗜酸性粒细胞(EOS)百分比、Th1和Th2细胞占比、Th1/Th2比值、血清Th1和Th2细胞因子[白细胞介素(IL)-2、IL-4、IL-6、干扰素(IFN)-γ]水平及小气道功能[25%、50%、75%肺活量的最大呼气量(FEF25%、FEF50%、FEF75%)和最大中期呼气流速(FEF25%~FEF75%)].分析外周血形成EETs的EOS百分比与Th1和Th2及其细胞因子、小气道功能的相关性,采用受试者工作特征(ROC)曲线分析外周血形成EETs的EOS百分比诊断CVA的价值。结果 CVA组外周血形成EETs的EOS百分比明显高于对照组[(20.35±6.09)% vs.(6.32±1.28)%,t=18.554,P<0.05].CVA组Th2细胞占比、血清IL-4水平、血清IL-6水平均明显高于对照组(t值分别为31.012、13.649、17.644,P<0.05);Th1细胞占比、Th1/Th2比值、血清IL-2水平、血清IFN-γ水平,以及FEF25%、FEF50%、FEF75%、FEF25%~FEF75%均明显低于对照组(t值分别为18.833、43.188、11.652、13.788、16.390、33.090、42.565、39.767,P<0.05).CVA组外周血形成EETs的EOS百分比与Th2细胞占比、血清IL-4水平、血清IL-6水平均呈正相关(r值分别为0.532、0.421、0.395,P<0.05),与Th1细胞占比、Th1/Th2比值、血清IL-2水平、血清IFN-γ水平、FEF25%、FEF50%、FEF75%、FEF25%~FEF75%均呈负相关(r值分别为-0.253、-0.605、-0.321、-0.385、-0.421、-0.377、-0.485、-0.568,P<0.05).ROC曲线分析显示,外周血形成EETs的EOS百分比诊断CVA的曲线下面积(AUC)为0.760(95%CI:0.687~0.824),灵敏度为78.95%,特异度为77.61%。结论 外周血形成EETs的EOS百分比增高与CVA患儿Th1/Th2比值失衡、Th2细胞因子过度释放及小气道损伤有关,其有望作为CVA的潜在标志物.

Abstract

Objective To investigate the correlation between peripheral blood eosinophil extracellular traps (EETs) levels and peripheral blood T helper (Th) lymphocytes 1 and Th2, as well as their cytokines and small airway function in children with cough variant asthma (CVA). Methods 95 children with CVA admitted to Kaizhou District People's Hospital of Chongqing from October 2019 to October 2022 were selected as the CVA group, and 67 healthy children who underwent physical examination at the department of pediatrics during the same period were selected as the control group. Peripheral blood eosinophil (EOS) percentage forming EETs, Th1 and Th2 cell proportions, Th1/Th2 ratio, serum Th1 and Th2 cytokines [interleukin (IL)-2, IL-4, IL-6, interferon-γ (IFN-γ)] and small airway function [25%, 50% and 75% lung maximum expiratory volume (FEF25%, FEF50%, FEF75%) and maximum mid-expiratory flow rate (FEF25%-75%)] were detected. The correlations between peripheral blood EOS percentage forming EETs and Th1 and Th2, Th1 and Th2 cytokines and small airway function were analyzed. Receiver operating characteristic (ROC) curve was used to analyze the value of peripheral blood EOS percentage forming EETs in diagnosing CVA. Results The percentage of EOS forming EETs in peripheral blood of CVA group was significantly higher than that of control group [(20.35±6.09)% vs. (6.32±1.28)%, t=18.554, P<0.05]. The proportion of Th2 cells in peripheral blood, serum IL-4 and IL-6 levels in CVA group were significantly higher than those in control group (t=31.012, 13.649 and 17.644, P<0.05), while the proportion of Th1 cells, Th1/Th2 ratio, serum IL-2 and IFN-γ levels, FEF25%, FEF50%, FEF75% and FEF25%-75% in CVA group were significantly lower than those in control group (t=18.833, 43.188, 11.652, 13.788, 16.390, 33.090, 42.565 and 39.767, respectively, P<0.05). The percentage of EOS forming EETs in peripheral blood of CVA group was positively correlated with the proportion of Th2 cells, serum IL-4 and IL-6 levels (r=0.532, 0.421 and 0.395, respectively, P<0.05), were negatively correlated with the proportion of Th1 cells, Th1/Th2 ratio, serum IL-2 and IFN-γ levels, FEF25%, FEF50%, FEF75% and FEF25%-75% (r=-0.253, -0.605, -0.321, -0.385, -0.421, -0.377, -0.485 and -0.568, respectively, P<0.05). The area under the curve (AUC) of EETs in peripheral blood was 0.760 (95%CI: 0.687-0.824), the sensitivity was 78.95%, and the specificity was 77.61%. Conclusion The increased percentage of EOS forming EETs in peripheral blood is related to Th1/Th2 imbalance, excessive release of Th2 cytokines and small airway injury in children with CVA, and it is expected to serve as a potential marker for CVA.

关键词

咳嗽变异性哮喘 / 嗜酸性粒细胞胞外诱捕网 / 辅助性T淋巴细胞2 / 小气道功能

Key words

cough variant asthma / eosinophil extracellular traps / T helper lymphocytes 2 / small airway function

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