儿童真菌致敏性哮喘的临床和炎症特征分析

Analysis of clinical and inflammatory features of pediatric asthma with fungal sensitization

目的分析儿童真菌致敏性哮喘的临床和炎症特征。方法本研究为横断面研究,采用非随机抽样的方法选取2019年6月至2022年6月于山东第一医科大学附属省立医院小儿呼吸综合科门诊和病房就诊的2902例支气管哮喘(哮喘)患儿为研究对象。根据血清吸入过敏原特异性免疫球蛋白E和血清总免疫球蛋白E(tIgE)检测结果将患儿分为单纯真菌致敏组、真菌多重致敏组、非真菌致敏组和非致敏组。观察真菌致敏哮喘患儿的分布情况和真菌致敏哮喘患儿合并其他吸入过敏原致敏分布情况,比较4组哮喘患儿的一般资料(性别、年龄、就诊季节)、血常规指标[嗜酸性粒细胞(EOS)绝对值、中性粒细胞绝对值、淋巴细胞绝对值、血红蛋白(Hb)、嗜酸性粒细胞/淋巴细胞比值(ELR)和嗜酸性粒细胞/中性粒细胞比值(ENR)]和tIgE,观察4组哮喘患儿不同就诊季节血常规指标和tIgE变化情况。结果本研究中2902例哮喘患儿分为单纯真菌致敏组331例(11.41%)、真菌多重致敏组898例(30.94%)、非真菌致敏组1067例(36.77%)和非致敏组606例(20.88%)。真菌致敏哮喘患儿共1229例(42.35%),其中男851例(69.24%),女378例(30.76%)。不同年龄段真菌致敏哮喘患儿占比总体差异有统计学意义(χ^(2)=63.31,P<0.001),以6~8岁、9~11岁占比较高。不同就诊季节真菌致敏哮喘患儿占比总体差异有统计学意义(χ^(2)=34.51,P<0.001),以夏季占比最高。链格孢致敏哮喘患儿1115例(38.42%),以3级(37.22%)、4级(32.29%)致敏较多;烟曲霉致敏哮喘患儿610例(21.02%),以2级(45.90%)、3级(30.33%)致敏较多。真菌多重致敏组中合并1种其他吸入过敏原者占比为54.23%(487/898),以真菌+尘螨占比最高33.63%(302/898);合并2种其他吸入过敏原者占比为32.18%(289/898),以真菌+尘螨+花草树木占比最高25.84%(232/898);合并3种其他吸入过敏原者占比为13.59%(122/898)。4组哮喘患儿性别、年龄、就诊季节比较总体差异均有统计学意义(均P<0.001)。对于EOS绝对值、ELR和ENR,真菌多重致敏组高于单纯真菌致敏组,其次高于非真菌致敏组,高于非致敏组(均P<0.05)。对于Hb,真菌多重致敏组高于单纯真菌致敏组、非真菌致敏组,真菌多重致敏组和非真菌致敏组高于非致敏组(均P<0.05)。对于tIgE,真菌多重致敏组高于非真菌致敏组,其次高于单纯真菌致敏组,高于非致敏组(均P<0.05)。EOS绝对值、ELR、ENR和tIgE在单纯真菌致敏组、真菌多重致敏组和非真菌致敏组各组内均呈现季节性变化(均P<0.05)。单纯真菌致敏组中EOS绝对值、ELR、ENR和tIgE在夏季升高;真菌多重致敏组中EOS绝对值、ELR、ENR和tIgE在冬季降低;非真菌致敏组中EOS绝对值和tIgE在秋季升高,ELR和ENR在冬季降低,Hb在夏季降低。结论真菌致敏性哮喘是重要的哮喘类型,男童、6~11岁儿童发病居多,发病季节以夏季为主。真菌致敏性哮喘2型炎症突出,EOS绝对值、ELR、ENR和tIgE均升高,并且呈现季节性变化。

ObjectiveTo analyze the clinical and inflammatory features of pediatric asthma with fungal sensitization.MethodsThis study was a cross-sectional study.A total of 2,902 children with bronchial asthma who visited the Outpatient Clinic and Pediatric Respiratory Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University from June 2019 to June 2022 were enrolled by non-random sampling method.According to the results of serum inhaled allergen-special immunoglobulin E and serum total immunoglobulin E(tIgE)tests,enrolled children were divided into simple fungal sensitization group,multi-fungal sensitization group,non-fungal sensitization group,and non-sensitization group.The distribution of children with fungal-sensitized asthma and those combined with other inhaled allergens were observed.Baseline characteristics(gender,age,season),blood routine indexes(absolute values of eosinophil[EOS],absolute neutrophil count,absolute lymphocyte count,hemoglobin[Hb],eosinophil-to-lymphocyte ratio[ELR]and eosinophil-to-neutrophil ratio[ENR])and tIgE were compared among four groups.Changes in blood routine indexes and tIgE in different seasons were observed.ResultsA total of 2,902 children with asthma were divided into simple fungal sensitization group(n=331,11.41%),multi-fungal sensitization group(n=898,30.94%),non-fungal sensitization group(n=1,067,36.77%)and non-sensitization group(n=606,20.88%).A total of 1,229(42.35%)children with asthma were diagnosed with fungal sensitization,including 851 boys(69.24%)and 378 girls(30.76%).There was a significant difference in the proportion of children with fungal-sensitized asthma in different age groups(χ^(2)=63.31,P<0.001),which was relatively high in children aged 6-8 years and 9-11 years.There was a significant difference in the proportion of children with fungal-sensitized asthma in different seasons(χ^(2)=34.51,P<0.001),with the highest proportion in summer.A total of 1,115(38.42%)children were sensitized by Alternaria,and most of them were classified into grade three(37.22%)and grade four(32.29%).A total of 610(21.02%)asthmatic children were sensitized by Aspergillus fumigatus,and most of them were grade two(45.90%)and grade three(30.33%).In the multi-fungal sensitization group,54.23%(487/898)children with fungal-sensitized asthma were sensitized with one other inhaled allergen,with the most common mixed allergens of fungus plus dust mite(33.63%,302/898);32.18%(289/898)children with fungal-sensitized asthma were sensitized with two other inhaled allergens,with the most common mixed allergens of fungus plus dust mite and plants/trees(25.84%,232/898);13.59%(122/898)children with fungal-sensitized asthma were sensitized with three other inhaled allergens.There were significant differences in gender,age,and season among the four groups(all P<0.001).Absolute values of EOS,ELR and ENR were significantly higher in the multi-fungal sensitization group than those of the simple fungal sensitization group,followed by the non-fungal sensitization group and non-sensitization group(all P<0.05).Hb was significantly higher in the multi-fungal sensitization group than that of the simple fungal sensitization group and non-fungal sensitization group,and it was significantly higher in the multi-fungal sensitization group and non-fungal sensitization group than that of the non-sensitization group(all P<0.05).tIgE was significantly higher in the multi-fungal sensitization group than that of the non-fungal sensitization group,followed by the simple fungal sensitization group and non-sensitization group(all P<0.05).Absolute values of EOS,ELR,ENR and tIgE showed seasonal changes in the simple fungal sensitization group,multi-fungal sensitization group and non-fungal sensitization group(all P<0.05).In the simple fungal sensitization group,absolute values of EOS,ELR,ENR and tIgE increased in summer.In the multi-fungal sensitization group,absolute values of EOS,ELR,ENR and tIgE decreased in winter.Increased absolute values of EOS and tIgE in autumn,decreased ELR and ENR in winter,and decreased Hb in summer were observed in the non-fungal sensitization group.ConclusionsPediatric asthma with fungal sensitization is an important type of asthma,and it mainly affects boys and children at the age of 6-11 years.The onset season is mainly in summer.Type 2 inflammation is prominent in pediatric asthma with fungal sensitization,presenting increases in the absolute values of EOS,ELR,ENR and tIgE with seasonal changes.