[Study on the characteristics of Aspergillus fumigatus-sensitized asthma and allergic bronchopulmonary aspergillosis].

Objective: To investigate the clinical characteristics of Aspergillus fumigatus(A.f)-sensitized asthma and allergic bronchopulmonary aspergillosis (ABPA), which provides a foundation for the diagnosis and differential diagnosis of A.f-sensitized asthma and ABPA, as well as the prevention of ABPA. Methods: This was a single-center retrospective case-control study. Collected the clinical data of patients who visited the Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University from December 2018 to May 2022.A total of 122 patients were included, including 64 males (52.5%) and 58 females (47.5%).The age range was 3 to 89 years.The median age was 44 years.The average age was 41.8 years.The patients were divided into three groups (48 ABPA, 35 A.f-sensitized asthma and 39 HDM-sensitized asthma).Analyzed the differences and correlations among clinical indicators in the three groups, and evaluated the risk factors for the development of ABPA in A.f-sensitized asthma.For statistical analysis, metrological data was tested by t-test or Wilcoxon Mann-Whitney. Classification variables by chi-square test or Fisher's exact test. Pearson correlation analysis for normal distribution data.Spearman correlation analysis for skewed distribution data. Influencing factor analysis was performed using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was made, the area under the ROC curve (AUC) was calculated, and the sensitivity and specificity of the model were evaluated. Results: Compared with patients with A.f-sensitized asthma, the fractional exhaled nitric oxide (FeNO) [75.00(52.00, 87.00)ppb vs. 40.00(32.00, 52.00)ppb], eosinophils% (EO%) [10.60(6.75, 13.05) vs. 4.10(1.20, 7.30)], eosinophils (EO) [1.50(1.07, 2.20)×109/L vs. 0.33(0.10, 0.54)×109/L], A.f-specific Immunoglobulin E (sIgE) [10.24(4.09, 22.88)KU/L vs. 1.13(0.53, 3.72) KU/L], and sIgE to total IgE(tIgE) ratio (sIgE/tIgE) [0.0049(0.0027, 0.0100) vs. 0.0008(0.0004, 0.0017)] were higher in ABPA patients, the differences were statistically significant (P<0.001). In all patients, tIgE was positively correlated with EO% (r=0.206, P<0.05) and EO (r=0.302, P<0.001). sIgE/tIgE was negatively correlated with one-second rate (FEV1/FVC%) (r=-0.256, P<0.01). The percentage of predicted forced vital capacity [FVC(%)] was negatively correlated with FeNO (r=-0.184, P<0.05).In the ABPA group, the percentage of predicted peak expiratory flow [PEF(%)] was negatively correlated with FeNO (r=-0.295, P<0.05). In the HDM-sensitized asthma group, FeNO was positively correlated with EO% (r=0.49, P<0.01) and EO (r=0.548, P<0.001).The results of logistic regression analysis showed that FeNO and EO were the influencing factors for the development of ABPA in A.f-sensitized asthma. ROC curve analysis results showed that A.f-sIgE (cut-off, 4.108; AUC=0.749;95%CI, 0.632-0.867), sIgE/tIgE(cut-off, 0.0026;AUC=0.749;95%CI, 0.631-0.868), FeNO(cut-off, 55.5;AUC=0.794; 95%CI, 0.687-0.900), EO% (cut-off, 8.70;AUC=0.806;95%CI, 0.709-0.903) and EO (cut-off, 0.815;AUC=0.865;95%CI, 0.779-0.950) had differential diagnostic value in A.f-sensitized asthma and ABPA.The combination of FeNO, EO and EO% had good diagnostic efficiency in differentiating A.f-sensitized asthma from ABPA, with a sensitivity of 91.4% and a specificity of 84.4%. Conclusion: Compared with patients with A.f-sensitized asthma, patients with ABPA have more severe eosinophil inflammation. The higher the FeNO and EO, the more likely A.f-sensitized asthma will develop into ABPA.sIgE/tIgE may have differential diagnostic value in A.f-sensitized asthma and ABPA.The combination of FeNO, EO and EO% has good diagnostic efficacy in differentiating A.f-sensitized asthma from ABPA.目的： 探讨烟曲霉致敏性哮喘和变应性支气管肺曲霉病（ABPA）的临床特征，为烟曲霉致敏性哮喘和ABPA的诊断与鉴别诊断以及ABPA的预防提供依据。 方法： 本研究为单中心回顾性病例对照研究，收集2018年12月至2022年5月就诊于武汉大学中南医院呼吸与危重症医学科的患者的临床资料。共纳入122例患者，男性64例（52.5%），女性58例（47.5%）；年龄范围3~89岁、中位数年龄44岁、平均41.8岁。将患者分为三组，其中ABPA组48例，烟曲霉致敏性哮喘组35例，尘螨致敏性哮喘组39例。分析三组中临床指标间的差异性与相关性以及影响烟曲霉致敏性哮喘发展为ABPA的危险因素。计量资料用t检验或Wilcoxon Mann-Whitney检验；分类变量用卡方检验或Fisher确切概率法进行统计分析。正态分布资料用Pearson相关分析；偏态分布资料用Spearman相关分析。影响因素分析用多因素logistic回归分析。制作受试者工作特征（ROC）曲线，计算ROC曲线下面积，评估模型的敏感度和特异度。 结果： 与烟曲霉致敏性哮喘患者相比，ABPA患者的呼出气一氧化氮（FeNO）［75.00（52.00，87.00）ppb vs. 40.00（32.00，52.00）ppb］、血液嗜酸性粒细胞百分比（EO%）［10.60（6.75，13.05）vs. 4.10（1.20，7.30）］、嗜酸性粒细胞计数（EO）［1.50（1.07，2.20）×109/L vs. 0.33（0.10，0.54）×109/L］、烟曲霉特异性免疫球蛋白E（sIgE）［10.24（4.09，22.88）KU/L vs. 1.13（0.53，3.72）KU/L］以及sIgE与总IgE（tIgE）的比值（sIgE/tIgE）［0.004 9（0.002 7，0.010 0）vs. 0.000 8（0.000 4，0.001 7）］更高，差异有统计学意义（P<0.001）。在所有患者中，tIgE与EO%（r=0.206，P<0.05）、EO（r=0.302，P<0.001）呈正相关。sIgE/tIgE与一秒率（FEV1/FVC%）呈负相关（r=-0.256，P<0.01）。用力肺活量占预计值百分比［FVC（%）］与FeNO呈负相关（r=-0.184，P<0.05）。在ABPA组中，呼气峰值流量占预计值百分比［PEF（%）］与FeNO呈负相关（r=-0.295，P<0.05）。在尘螨致敏性哮喘组中，FeNO与EO%（r=0.49，P<0.01）、EO（r=0.548，P<0.001）呈正相关。logistic回归分析结果显示，FeNO与EO是烟曲霉致敏性哮喘发展为ABPA的影响因素。ROC曲线分析结果显示，烟曲霉sIgE（截断值，4.108；曲线下面积，0.749；95%置信区间，0.632~0.867）、sIgE/tIgE（截断值，0.0026；曲线下面积，0.749；95%置信区间，0.631~0.868）、FeNO（截断值，55.5；曲线下面积，0.794；95%置信区间，0.687~0.900）、EO%（截断值，8.70；曲线下面积，0.806；95%置信区间，0.709~0.903）和EO（截断值，0.815；曲线下面积，0.865；95%置信区间，0.779~0.950）在烟曲霉致敏性哮喘和ABPA中具有鉴别诊断价值。FeNO、EO和EO%组合在鉴别烟曲霉致敏性哮喘和ABPA方面具有良好的诊断效率，敏感度为91.4%，特异度为84.4%。 结论： 与烟曲霉致敏性哮喘患者相比，ABPA患者嗜酸性粒细胞炎症更严重。FeNO与EO值越高，烟曲霉致敏性哮喘发展为ABPA的可能性越大。sIgE/tIgE在烟曲霉致敏性哮喘和ABPA中可能具有鉴别诊断价值。FeNO、EO和EO%组合在鉴别烟曲霉致敏性哮喘和ABPA方面具有良好的诊断效能。.