FeNO和TIgE及外周血EOS计数联合检测对儿童2型气道炎症相关咳嗽变异性哮喘的诊断价值

The diagnostic value of combined detection of FeNO, TIgE and peripheral blood EOS count in children with type 2 airway inflammatory cough variant asthma

摘要

目的 探讨呼出气一氧化氮(FeNO)、总免疫球蛋白E(TIgE)及外周血嗜酸性粒细胞(EOS)计数联合检测对儿童2型气道炎症相关咳嗽变异性哮喘(CVA)的诊断价值。方法 收集2022年12月至2023年8月在陕西中医药大学第二附属医院行FeNO、过敏原及外周血EOS计数检测的163例确诊为慢性咳嗽的4~12岁患儿为观察组,再将其分为CVA组(n=54)、上气道咳嗽综合征(UACS)组(n=52)、感染后咳嗽(PIC)组(n=57);收集同期67例正常体检儿童为对照组.回顾性比较分析四组儿童的FeNO、TIgE、特异性免疫球蛋白E(SIgE)及外周血EOS计数,并采用受试者工作特征(ROC)曲线预测FeNO、TIgE、外周血EOS计数对CVA的诊断价值。结果 CVA组的FeNO、TIgE及外周血EOS计数均明显高于UACS组、PIC组、对照组,经比较差异均有统计学意义(F值分别为17.591、15.654、3.985,P<0.05).两两组间比较显示,UACS组与CVA组、对照组FeNO比较,差异均有统计学意义(t值分别为10.167、14.565,P<0.05),CVA组与PIC组、对照组FeNO比较,差异均有统计学意义(t值分别为18.723、15.541,P<0.05);UACS组与CVA组、PIC组、对照组TIgE比较,差异均有统计学意义(t值分别为-21.400、26.051、20.639,P<0.05),CVA组与PIC组、对照组TIgE比较,差异均有统计学意义(t值分别为44.509、41.546,P<0.05);UACS组与CVA组、对照组外周血EOS计数比较,差异均有统计学意义(t值分别为-2.802、2.434,P<0.05),CVA组与对照组外周血EOS计数比较,差异有统计学意义(t=4.862,P<0.05).慢性咳嗽患儿吸入性过敏原阳性率较高的前三位致敏原分别是交链孢霉(29.62%)、屋尘(25.00%)和粉尘螨(17.30%);食入性过敏原阳性率较高的前三位致敏原分别是鸡蛋(21.15%)、牛奶(21.15%)及虾(7.69%).ROC曲线分析显示,FeNO、TIgE及外周血EOS计数联合诊断CVA的曲线下面积(AUC)为0.890,95%CI:0.837~0.942,灵敏度为85.19%、特异度为93.27%,联合诊断CVA的灵敏度和特异度均高于单一检测指标;FeNO诊断CVA的灵敏度为73.72%、特异度为81.48%,FeNO诊断CVA的最佳阈值是38.65ppb,诊断价值明显高于其他两项单一诊断指标。结论 FeNO、TIgE及外周血EOS计数与儿童2型气道炎症相关CVA的发生联系密切,三者对于典型2型气道炎症相关CVA的鉴别诊断均有价值,联合诊断可以提高对CVA诊断的准确率;诱导2型气道炎症相关CVA发生的主要原因是吸入性过敏原,其中交链孢霉阳性率最高;FeNO为38.65ppb可作为诊断CVA的参考界值,可更好地协助鉴别CVA与其他慢性咳嗽的差别.

Abstract

Objective To explore the diagnostic value of combined detection of fractional exhaled nitric oxide (FeNO), total immunoglobulin E (TIgE) and peripheral blood eosinophils (EOS) in children with type 2 airway inflammatory cough variant asthma. Methods A total of 163 children aged 4 to 12 years diagnosed with chronic cough who underwent FeNO, allergens and peripheral blood EOS count detection in the Second Affiliated Hospital of Shaanxi University of Chinese Medicine from December 2022 to August 2023 were collected as the observation group, and then divided into CVA group (n=54), upper airway cough syndrome (UACS) group (n=52) and post-infection cough (PIC) group (n=57); 67 children with normal physical examinations during the same period were collected as the control group. The FeNO, TIgE, specific immunoglobulin E (SIgE) and peripheral blood EOS counts of the four groups of children were retrospectively compared and analyzed, and the receiver operating characteristic (ROC) curve was used to predict the diagnostic value of FeNO, TIgE and peripheral blood EOS counts for CVA. Results The FeNO, TIgE and peripheral blood EOS counts in the CVA group were significantly higher than those in the UACS group, PIC group and control group, and the differences were statistically significant (F=17.591, 15.654 and 3.985, P<0.05). The comparison between the two groups showed that the FeNO of UACS group was significantly different from that of CVA group and control group (t=10.167 and 14.565, respectively, P<0.05), and the FeNO of CVA group was significantly different from that of PIC group and control group (t=18.723 and 15.541, respectively, P<0.05). The TIgE of UACS group was significantly different from that of CVA group, PIC group and control group (t=-21.400, 26.051 and 20.639, respectively, P<0.05). The TIgE of CVA group was significantly different from that of PIC group and control group (t=44.509 and 41.546, respectively, P<0.05). The EOS count of peripheral blood of UACS group was significantly different from that of CVA group and control group (t=-2.802 and 2.434, respectively, P<0.05). The difference in peripheral blood EOS counts between the CVA group and the control group was statistically significant (t=4.862, P<0.05). The top three allergens with the highest positive rates of inhaled allergens in children with chronic cough were Alternaria (29.62%), house dust (25.00%), and dust mites (17.30%); the top three allergens with the highest positive rates of ingested allergens were eggs (21.15%), milk (21.15%), and shrimp (7.69%). ROC curve analysis showed that the area under the curve (AUC) of FeNO, TIgE and peripheral blood EOS count for the combined diagnosis of CVA was 0.890, 95%CI: 0.837-0.942, sensitivity was 85.19%, and specificity was 93.27%. The sensitivity and specificity of the combined diagnosis of CVA were higher than those of a single detection indicator; the sensitivity of FeNO for diagnosing CVA was 73.72% and the specificity was 81.48%. The optimal threshold of FeNO for diagnosing CVA was 38.65ppb, and its diagnostic value was significantly higher than that of the other two single diagnostic indicators. Conclusion FeNO, TIgE and peripheral blood EOS count are closely related to the occurrence of type 2 airway inflammation-related CVA in children. The three are valuable for the differential diagnosis of typical type 2 airway inflammation-related CVA. Combined diagnosis can improve the accuracy of CVA diagnosis. The main cause of type 2 airway inflammation-related CVA is inhaled allergens, among which Alternaria has the highest positive rate. FeNO of 38.65ppb can be used as a reference value for diagnosing CVA, which can better assist in distinguishing CVA from other chronic coughs.

关键词

儿童 / 一氧化氮 / 免疫球蛋白E / 嗜酸性粒细胞 / 咳嗽变异性哮喘 / 2型气道炎症

Key words

child / nitric oxide / immunoglobulin E / eosinophil / cough variant asthma / type 2 airway inflammation

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基金资助

国家自然科学基金青年科学基金项目(82205188)

咸阳市科技局重点研发计划(2021ZDYFGSFG0043)