Despite conventional glucocorticoid and antifungal therapy, acute exacerbation and hospitalization occur frequently in patients with allergic bronchopulmonary aspergillosis (ABPA). Whether omalizumab is an effective and safe treatment for adult patients with ABPA complicating asthma. Patients with ABPA complicating asthma who were treated with omalizumab from October 2019 to May 2023 were collected from five tertiary hospitals and evaluated. The frequencies of acute exacerbation and hospitalization; the number of eosinophils; the total IgE levels; and the average monthly medical dosages after 3, 6, and 12 months of omalizumab treatment were analysed, and the data before and after treatment (up to one year) were compared. The efficacy and safety of omalizumab treatment were assessed. In total, 26 patients were enrolled. The average monthly glucocorticoid dosage significantly decreased (median 0 vs. 24 mg/m) after 6 months of omalizumab treatment compared with 3 months; 73.68% of patients discontinued glucocorticoids after ≤ 12 months of treatment. Similarly, the average monthly dosage of antifungal agents was significantly decreased (median 0 vs. 3.49 g/m) after 12 months of treatment compared with 3 months. The average monthly glucocorticoid dosage (median 213.75 vs. 65.42 mg/m, P = 0.002) and the frequency of acute exacerbation (median 0.94 vs. 0.44 events, P = 0.033) were considerably reduced after omalizumab treatment. Omalizumab is effective in reducing the frequency of acute exacerbation and the necessary dosage of glucocorticoids in adult patients with ABPA complicating asthma. Patient age and BMI may affect the efficacy of treatment.

BACKGROUND: The long-term outcomes of allergic bronchopulmonary aspergillosis (ABPA) are poorly characterised.
METHODS: We retrospectively included treatment-naïve subjects of acute stage ABPA-complicating asthma from three randomised trials. All the subjects received oral prednisolone for 4 months and were monitored every 6 weeks for 6 months and then every 6 months. Our primary objective was to estimate the incidence rate and the frequency of subjects experiencing ABPA exacerbation. The key secondary objectives were to evaluate the factors predicting ABPA exacerbation and the changes in serum total IgE seen during treatment.
RESULTS: We included 182 subjects. Eighty-one (44.5%) patients experienced 120 exacerbations during 512 patient-years of follow-up. The incidence rate of ABPA exacerbations was 234/1000 patient-years. Most (73/81, 90.1%) subjects experienced ABPA exacerbation within three years of stopping therapy. On multivariate logistic regression analysis, peripheral blood eosinophil count ≥1000 cells/μL (adjusted odds ratio [aOR] 2.43; 95% confidence interval (CI), 1.26-4.67), the extent of bronchiectasis (aOR 1.10; 95% CI, 1.03-1.18), age (aOR 0.97; 95% CI, 0.94-0.99), and female sex (aOR 2.16; 95% CI, 1.10-4.24) independently predicted ABPA exacerbation after adjusting for serum total IgE and high-attenuation mucus. The best cut-off for serum total IgE after 6 weeks for identifying treatment response and ABPA exacerbations was a 20% decline and a 50% increase, respectively.
CONCLUSIONS: ABPA exacerbations were common within 3 years of stopping treatment. Age, female sex, peripheral blood eosinophilia and the extent of bronchiectasis predicted ABPA exacerbations. The optimal serum total IgE cut-off for defining ABPA response and exacerbations is a 20% decline and a 50% increase, respectively.

暂无摘要。

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is associated with severe lung damage and requires specific therapeutic management. Repeated imaging is recommended to both diagnose and follow-up response to treatment of ABPA in CF. However, high risk of cumulative radiation exposure requires evaluation of free-radiation techniques in the follow-up of CF patients with ABPA.
OBJECTIVE: To evaluate whether Fourier decomposition (FD) functional lung MRI can detect response to treatment of ABPA in CF patients.
METHODS: Retrospective longitudinal.
METHODS: Twelve patients (7M, median-age:14 years) with CF and ABPA with pre- and post-treatment MRI.
UNASSIGNED: 2D-balanced-steady-state free-precession (bSSFP) sequence with FD at 1.5T.
RESULTS: Ventilation-weighted (V) and perfusion-weighted (Q) maps were obtained after FD processing of 2D-coronal bSSFP time-resolved images acquired before and 3-9 months after treatment. Defects extent was assessed on the functional maps using a qualitative semi-quantitative score (0 = absence/negligible, 1 = <50%, 2 = >50%). Mean and coefficient of variation (CV) of the ventilation signal-intensity (VSI) and the perfusion signal-intensity (QSI) were calculated. Measurements were performed independently by three readers and averaged. Inter-reader reproducibility of the measurements was assessed. Pulmonary function tests (PFTs) were performed within 1 week of both MRI studies as markers of the airflow-limitation severity.
METHODS: Comparisons of medians were performed using the paired Wilcoxon-test. Reproducibility was assessed using intraclass correlation coefficient (ICC). Correlations between MRI and PFT parameters were assessed using the Spearman-test (rho correlation-coefficient). A P-value <0.05 was considered as significant.
RESULTS: Defects extent on both V and Q maps showed a significant reduction after ABPA treatment (4.25 vs. 1.92 for V-defect-score and 5 vs. 2.75 for Q-defect-score). VSI_mean was significantly increased after treatment (280 vs. 167). Qualitative analyses reproducibility showed an ICC > 0.90, while the ICCs of the quantitative measurements was almost perfect (>0.99). Changes in VSI_cv and QSI_cv before and after treatment correlated inversely with changes of FEV1%p (rho = -0.68 for both).
CONCLUSIONS: Non-contrast-enhanced FD lung MRI has potential to reproducibly assess response to treatment of ABPA in CF patients and correlates with PFT obstructive parameters.
METHODS: 4 TECHNICAL EFFICACY: Stage 3.

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。.

暂无摘要。

There are no precise data about the effect of Aspergillus infection on lung function other than allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (pwCF). Here, we aimed to determine clinical phenotypes caused by Aspergillus spp. using laboratory and immunologic parameters and to compare Aspergillus phenotypes in terms of pulmonary function tests (PFT) prospectively.
Twenty-three pwCF who had Aspergillus isolation from respiratory cultures in the last year (case group) and 20 pwCF without Aspergillus isolation in sputum (control group) were included. Aspergillus immunoglobulin (Ig)-G, Aspergillus IgE, Aspergillus polymerase chain reaction (PCR), galactomannan, total IgE from blood samples, and Aspergillus PCR and galactomannan from sputum, and skin prick test reactivity to Aspergillus antigen were used to distinguish different Aspergillus phenotypes. Pulmonary functions and frequency of pulmonary exacerbations were evaluated during a 1-year follow-up.
Of 23 pwCF, 11 (47.8%) had Aspergillus colonization, nine (39.1%) had Aspergillus bronchitis, and three (13%) had ABPA. Aspergillus infection was not associated with worse z-scores of forced expiratory volume in the first second (FEV1) (p = 0.612), forced vital capacity  (p = 0.939), and the median FEV 1% decline (0.0%/year vs. -4.7%/year, p = 0.626). The frequency of pulmonary exacerbations in the Aspergillus infected and noninfected groups was similar.
Although Aspergillus spp. Isolation in pwCF was not associated with decreased lung function, a further decline was seen in the ABPA subgroup, and frequent pulmonary exacerbations during the 1-year follow-up.

BACKGROUND: The clinical spectrum of Aspergillus fumigatus diseases in cystic fibrosis (CF) patients, including allergic bronchopulmonary aspergillosis (ABPA) and Aspergillus fumigatus chronic colonization, has recently gained attention due to its association with the progression of lung disease. Our aim was to examine whether there is a difference on pathogenic variant frequencies of the CFTR gene between CF patients with ABPA and those with A. fumigatus chronic colonization.
METHODS: Greek CF patients diagnosed with ABPA and/or A. fumigatus chronic colonization were grouped according to their CFTR genotype. Patients with \"minimal\" CFTR function were defined as carrying a combination of class I or II pathogenic variants, while patients with \"residual\" function as carrying at least one class III, IV, V or VI pathogenic variant.
RESULTS: Fifty-four CF patients were included and all except one were defined as having \"minimal\" CFTR function. Among the 108 CFTR alleles, 69 (63.9%) of pathogenic variants belonged to class II, and 32 (29.6%) to class I. Five patients had a history of both ABPA and A. fumigatus chronic colonization. No significant difference was detected among patients diagnosed only with ABPA (n = 29) and those who had only a positive history of A. fumigatus chronic colonization (n = 20). The median age of ABPA diagnosis was significantly lower than the median age of A. fumigatus chronic colonization (P = 0.011), while no significant difference was detected on median FEV1% predicted.
CONCLUSIONS: No significant differences were detected in the type of CFTR pathogenic variants among patients with ABPA and those with A. fumigatus colonization. Similar studies should be performed in larger CF populations of different ethnic origin to further confirm our results.

Whether a combination of glucocorticoid and antifungal triazole is superior to glucocorticoid alone in reducing exacerbations in patients with allergic bronchopulmonary aspergillosis (ABPA) remains unknown. We aimed to compare the efficacy and safety of prednisolone-itraconazole combination versus prednisolone monotherapy in ABPA.
We randomised subjects with treatment-naïve acute-stage ABPA complicating asthma to receive either prednisolone alone (4 months) or a combination of prednisolone and itraconazole (4 and 6 months, respectively). The primary outcomes were exacerbation rates at 12 months and glucocorticoid-dependent ABPA within 24 months of initiating treatment. The key secondary outcomes were response rates, percentage decline in serum total IgE at 6 weeks, time to first ABPA exacerbation and treatment-emergent adverse events (TEAEs).
We randomised 191 subjects to receive either prednisolone (n=94) or prednisolone-itraconazole combination (n=97). The 1-year exacerbation rate was 33% and 20.6% in the prednisolone monotherapy and prednisolone-itraconazole combination arms, respectively (p=0.054). None of the participants progressed to glucocorticoid-dependent ABPA. All of the subjects experienced a composite response at 6 weeks, along with a decline in serum total IgE (mean decline 47.6% versus 45.5%). The mean time to first ABPA exacerbation (417 days) was not different between the groups. None of the participants required modification of therapy due to TEAEs.
There was a trend towards a decline in ABPA exacerbations at 1 year with the prednisolone-itraconazole combination versus prednisolone monotherapy. A three-arm trial comparing itraconazole and prednisolone monotherapies with their combination, preferably in a multicentric design, is required to define the best treatment strategy for acute-stage ABPA.

BACKGROUND: Whether allergic bronchopulmonary aspergillosis (ABPA) affects maternal and perinatal outcomes during pregnancy or vice versa is unknown.
OBJECTIVE: To evaluate the course of ABPA and its consequence on maternal and perinatal outcomes during pregnancy.
METHODS: We retrospectively included pregnant women with ABPA (cases) and compared them with non-pregnant ABPA subjects (controls). We recorded the following details in cases and controls: demographical characteristics, radiological findings, pulmonary function, duration of symptoms and the number of asthma and ABPA exacerbations during follow-up. We also recorded the maternal and perinatal outcomes in the cases.
RESULTS: We included nine cases and 38 controls with a similar age range. All the cases had achieved remission of ABPA before pregnancy and were receiving inhaled medications for asthma control. Serum total IgE levels, the extent of bronchiectasis on CT thorax and pulmonary function were comparable in the two groups. The mean number of asthma (53 vs 7) and ABPA (62 vs 16) exacerbations per 100 person-years was significantly higher in cases compared to the controls. We did not observe any maternal complications. One neonate had low birthweight.
CONCLUSIONS: The risk of asthma and ABPA exacerbations is significantly higher in pregnant subjects with ABPA than non-pregnant women with ABPA. However, maternal and perinatal outcomes are good.