Aspergillosis, Allergic Bronchopulmonary

曲霉病,过敏性支气管肺
  • 文章类型: Letter
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  • 文章类型: Observational Study
    目的:本研究探讨支气管镜检查是否能改善囊性纤维化(CF)的临床放射学和预测因素。该研究还调查了肺不张是否是CF的不良预后因素。
    方法:这个多中心,病例控制,观察,回顾性研究包括两组CF患者:病例组(持续肺不张患者,随访至少2年)和对照组(无肺不张患者,性别和年龄匹配1:1[±3岁]).我们记录了人口统计数据,肺功能检查结果,肺部并发症,合并症,治疗(包括支气管镜检查,手术和移植),和死亡。
    结果:每组包括55名患者(病例组:20名男性,平均年龄25.4±10.4岁;对照组:20名男性,平均年龄26.1±11.4岁)。支气管镜检查未导致临床放射学改善。变应性支气管肺曲霉病(ABPA)在病例组中更为常见。病例组患者更经常使用吸入类固醇,他们的肺不张前肺功能在统计学上较差,他们在随访期间有更多的恶化。
    结论:中重度肺部疾病和ABPA有利于肺不张。肺不张可能是CF的不良预后因素,因为它会增加恶化。尽管我们的结果,我们建议加强治疗,包括支气管镜检查,以防止持续性肺不张。
    OBJECTIVE: This study examined whether bronchoscopy leads to clinicoradiological improvement in cystic fibrosis (CF) and the predictive factors. The study also investigated whether pulmonary atelectasis is a poor prognostic factor in CF.
    METHODS: This multicenter, case-control, observational, retrospective study included two groups of patients with CF: a case group (patients with persistent atelectasis who were followed-up at least for 2 years) and a control group (patients without atelectasis matched 1:1 by sex and age [±3 years]). We recorded demographic data, lung function test results, pulmonary complications, comorbidities, treatments (including bronchoscopies, surgery and transplantation), and deaths.
    RESULTS: Each group included 55 patients (case group: 20 men, mean age 25.4 ± 10.4 years; control group: 20 men, mean age 26.1 ± 11.4 years). Bronchoscopy did not lead to clinicoradiological improvement. Allergic bronchopulmonary aspergillosis (ABPA) was more frequent in the case group. Patients in the case group more frequently used inhaled steroids, their pre-atelectasis lung function was statistically worse, and they had more exacerbations during follow-up.
    CONCLUSIONS: Moderate-to-severe pulmonary disease and ABPA can favor atelectasis. Pulmonary atelectasis can be a poor prognostic factor in CF because it increases exacerbations. Despite our results, we recommend enhancing treatment, including bronchoscopy, to prevent persistent atelectasis.
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  • 文章类型: Journal Article
    背景:过敏性支气管肺曲霉病(ABPA)患者反复加重。然而,T细胞亚群的参与仍不清楚.
    方法:我们招募了ABPA患者,哮喘患者和健康对照。通过流式细胞术分析外周血单个核细胞(PBMC)和ABPA支气管肺泡灌洗液(BALF)的总或分选亚群中的Th1,Th2,Th17,Treg和IL-21CD4T细胞。在恶化的ABPA患者和健康对照中进行CD4+T细胞亚群的RNA测序。测量体外T-B细胞共培养物的抗体。
    结果:ABPA患者Th2细胞增多,Treg细胞相似,循环Th1和Th17细胞减少。IL-5+IL-13+IL-21+CD4+T细胞在健康对照组中很少检测到,但在ABPA患者的血液中显著升高,尤其是加剧的。我们发现IL-5+IL-13+IL-21+CD4+T细胞主要是外周辅助性T(Tph)细胞(PD-1+CXCR5-),也出现在ABPA患者的BALF中。ABPA患者中循环Tph的比例相似,哮喘患者和健康对照,而IL-5+IL-13+IL-21+Tph细胞在ABPA患者中显著增加。转录组数据显示ABPA患者的Tph细胞是Th2偏斜的,并表现出滤泡性T辅助细胞(Tfh)的特征。体外共培养时,ABPA患者的Tph细胞诱导自体B细胞分化为成浆细胞,并显着增强IgE的产生。
    结论:我们确定了在ABPA患者中诱导IgE产生的循环Th2偏斜Tph细胞群明显升高。它可能是ABPA的生物标志物和治疗靶标。
    BACKGROUND: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear.
    METHODS: We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured.
    RESULTS: ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE.
    CONCLUSIONS: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    背景:ISHAM工作组在近十年前提出了治疗过敏性支气管肺曲霉病(ABPA)的建议。由于诊断和治疗方面的进步,需要更新这些建议。
    方法:召集了一个国际专家组,以制定管理ABPA(由曲霉属引起的。)和过敏性支气管肺真菌病(ABPM,除曲霉属以外的真菌.)在成人和儿童中使用修改后的Delphi方法(两次在线回合和一次面对面会议)。我们将共识定义为≥70%的同意或分歧。当共识≥70%和<70%时,使用术语“推荐”和“建议”。
    结果:我们建议在三级治疗的所有新诊断的成人哮喘患者中使用真菌特异性IgE筛查烟曲霉致敏性,但仅限于难以治疗的哮喘儿童。我们建议在有易感条件或符合临床放射学表现的患者中诊断ABPA,强制性证明了真菌致敏和血清总IgE≥500IU·mL-1以及以下两种:真菌特异性IgG,外周血嗜酸性粒细胞增多,或暗示性成像。在具有ABPA样表现但烟曲霉IgE正常的患者中考虑ABPM。此外,诊断ABPM需要痰中致病真菌的反复生长。我们不建议常规治疗无症状的ABPA患者。我们建议口服泼尼松龙或伊曲康唑单药治疗急性ABPA(新诊断或恶化),仅使用泼尼松龙和伊曲康唑联合治疗复发性ABPA加重。我们设计了一个客观的多维标准来评估治疗反应。
    结论:我们制定了诊断的共识指南,分类,并治疗ABPA(M)用于患者护理和研究。
    BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics.
    METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms \"recommend\" and \"suggest\" are used when the consensus was ≥70% and <70%, respectively.
    RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response.
    CONCLUSIONS: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.
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  • 文章类型: Case Reports
    嗜酸性粒细胞增多的肺浸润是一组异质性疾病,其特征是胸部X光片上的肺浸润和外周血中嗜酸性粒细胞水平升高。在患有这些疾病的患者中,过敏性支气管肺曲霉病(ABPA)或热带肺嗜酸性粒细胞增多(TPE)的报告很常见。然而,ABPA和TPE的同时发生并不经常报道.我们介绍了一个有哮喘病史的年轻人,他被诊断患有ABPA和TPE。最初,患者对ABPA的治疗表现出部分反应,但持续的症状和嗜酸性粒细胞增多导致怀疑并随后诊断为TPE.随着抗丝虫药和类固醇的实施,患者经历了令人满意的临床和血清学改善。该病例强调了在症状重叠的患者中考虑多种诊断的重要性,并强调了对复杂肺部疾病的综合管理策略的需求。
    Pulmonary infiltrates with eosinophilia are a heterogeneous group of disorders that are characterized by pulmonary infiltrates on chest radiograph and elevated levels of eosinophils in the peripheral blood. Among patients with these disorders, reports of either allergic bronchopulmonary aspergillosis (ABPA) or tropical pulmonary eosinophilia (TPE) are common. However, the simultaneous occurrence of ABPA and TPE is not often reported. We present the case of a young man with a history of asthma who was diagnosed with ABPA and TPE. Initially, the patient exhibited a partial response to treatment of ABPA, but persistent symptoms and eosinophilia led to suspicion and subsequent diagnosis of TPE. With implementation of antifilarials and steroids, the patient experienced satisfactory clinical and serological improvements. This case underscores the importance of considering multiple diagnoses in patients with overlapping symptoms and highlights the need for comprehensive management strategies in complex lung diseases.
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  • 文章类型: Multicenter Study
    尽管常规的糖皮质激素和抗真菌治疗,过敏性支气管肺曲霉病(ABPA)患者经常急性加重和住院。奥马珠单抗是否是成人ABPA合并哮喘患者的有效和安全的治疗方法。从5家三级医院收集并评估了从2019年10月至2023年5月接受奥马珠单抗治疗的ABPA合并哮喘患者。分析了急性加重和住院的频率;嗜酸性粒细胞数量;总IgE水平;以及奥马珠单抗治疗3、6和12个月后的平均每月药物剂量。并比较治疗前后(长达1年)的数据。评估奥马珠单抗治疗的疗效和安全性。总的来说,26例患者入组。平均每月糖皮质激素剂量显着降低(中位数0vs.24mg/m)在奥马珠单抗治疗6个月后与3个月相比;73.68%的患者在治疗≤12个月后停止糖皮质激素。同样,抗真菌药物的平均每月剂量显着减少(中位数0vs.3.49g/m)治疗12个月后与治疗3个月相比。平均每月糖皮质激素剂量(中位数213.75vs.65.42mg/m,P=0.002)和急性加重的频率(中位数0.94vs.0.44事件,P=0.033)在奥马珠单抗治疗后显著降低。奥马珠单抗可有效降低成人ABPA合并哮喘患者的急性加重频率和糖皮质激素的必要剂量。患者年龄和BMI可能影响治疗效果。
    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.
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  • 文章类型: Case Reports
    过敏性支气管肺曲霉病(ABPA)和慢性肺曲霉病(CPA)是由曲霉感染引起的疾病,在某些情况下,注册会计师可以从ABPA开发。我们在此报告一名CPA与ABPA重叠的患者。在4个时间点评估血清细胞因子水平:ABPA诊断,CPA诊断,伏立康唑(VRCZ)开始后6个月,以及重新施用VRCZ后12个月。白细胞介素(IL)-13水平在糖皮质激素治疗后降低,而IL-25和IL-33水平随着抗真菌药的开始而迅速下降。早期抗真菌治疗对于控制疾病进展和预防CPA重叠可能很重要。
    Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are diseases caused by Aspergillus infection, and CPA can develop from ABPA in some cases. We herein report a patient with CPA overlapping with ABPA. Serum cytokine levels were evaluated at 4 time points: the ABPA diagnosis, CPA diagnosis, 6 months after the start of voriconazole (VRCZ), and 12 months after re-administration of VRCZ. Interleukin (IL)-13 levels decreased upon glucocorticoid treatment, whereas IL-25 and IL-33 levels decreased rapidly with the initiation of antifungals. Early antifungal therapy may be important to control disease progression and prevent CPA overlap.
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  • 文章类型: Journal Article
    背景:奥马珠单抗是治疗过敏性支气管肺曲霉病(ABPA)的一种有价值的替代疗法。这种药物的有效性和安全性尚未得到证实。本研究的主要目的是评估奥马珠单抗治疗ABPA的有效性和安全性。
    方法:本研究包括回顾性图表回顾。使用的主要指标是哮喘控制测试(ACT)评分,肺功能参数,剂量的皮质类固醇,急性加重,住院率,血清总免疫球蛋白E(IgE)水平,和血液嗜酸性粒细胞计数。相关的不良事件也进行了审查,以评估奥马珠单抗的安全性。
    结果:纳入14例ABPA患者,其中10人(71%)同时患有过敏性鼻炎(AR)。强迫肺活量的平均百分比有所改善,1s内用力呼气量的百分比,奥马珠单抗给药后的ACT评分(分别为p<0.05、p<0.01和p<0.01)。奥马珠单抗给药后,皮质类固醇剂量中位数,急性加重率,住院率,与基线值相比,平均血液嗜酸性粒细胞计数降低(分别为p<0.05,p<0.05,p<0.01和p<0.05)。与AR患者相比,无AR的ABPA患者血清总IgE水平降低(p<0.05)。一名患者报告并发皮疹,在没有药物治疗的情况下自发解决。
    结论:对ABPA患者开奥马珠单抗是安全有效的,不管他们是否有AR。奥马珠单抗的剂量调整在疾病控制后是安全的。总血清IgE水平可能是奥马珠单抗在无AR患者中的有效性的预测因子。
    BACKGROUND: Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been confirmed. The main purpose of this study was to evaluate the effectiveness and safety of omalizumab for ABPA.
    METHODS: This study involved a retrospective chart review. The main indicators used were asthma control test (ACT) scores, lung function parameters, doses of corticosteroids, acute exacerbation, hospitalization rates, total serum immunoglobulin E (IgE) levels, and blood eosinophil counts. Related adverse events were also reviewed to evaluate the safety of omalizumab.
    RESULTS: Fourteen patients with ABPA were included, of whom 10 (71%) concurrently had allergic rhinitis (AR). There were improvements in the mean percentages of the forced vital capacity, percentages of the forced expiratory volume in 1 s, and ACT score after omalizumab administration (p < 0.05, p < 0.01, and p < 0.01, respectively). After the initiation of omalizumab administration, the median corticosteroid dose, acute exacerbation rate, hospitalization rate, and mean blood eosinophil count decreased when compared with the baseline values (p < 0.05, p < 0.05, p < 0.01, and p < 0.05, respectively). A reduction in the total serum IgE level was observed in patients with ABPA without AR compared with that in patients with AR (p < 0.05). One patient reported a concurrent skin rash, which spontaneously resolved without medication.
    CONCLUSIONS: It is safe and effective to prescribe omalizumab to patients with ABPA, irrespective of whether they have AR. Dose adjustment of omalizumab is safe after disease control. The total serum IgE level might be a predictor of the effectiveness of omalizumab in patients without AR.
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  • 文章类型: Case Reports
    过敏性支气管肺曲霉病(ABPA)是对烟曲霉的超敏反应,发生在哮喘或囊性纤维化患者中。这里,我们报告了一例年轻女性支气管哮喘患者,她因劳累而出现呼吸困难。她被诊断为患有ABPA,并开始口服伊曲康唑,同时继续吸入长效β-2肾上腺素能激动剂和中等剂量吸入皮质类固醇(ICS)治疗哮喘。治疗开始三个月后,患者的呼吸困难有了显著改善.然而,她体重增加了,面部浮肿,增加面部毛发和大腿内侧条纹的发育,小腿和小腹。发现她的血清皮质醇水平受到抑制,因此诊断为医源性库欣综合征。我们的案例描述了ICS和口服伊曲康唑之间潜在的严重相互作用,ABPA患者中非常常见的治疗方法。
    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus that occurs in patients with asthma or cystic fibrosis. Here, we report a case of a young female with bronchial asthma who presented to our hospital with worsening breathlessness on exertion. She was diagnosed to have ABPA and was initiated on oral itraconazole while continuing inhaled long acting beta-2 adrenergic agonist and medium dose inhaled corticosteroid (ICS) for her asthma. Three months after initiation of therapy, the patient had significant improvement in breathlessness. However, she had weight gain, facial puffiness, increased facial hair and development of striae on her inner thighs, calf and lower abdomen. Her serum cortisol levels were found to be suppressed and hence a diagnosis of iatrogenic Cushing\'s syndrome was made. Our case describes the potentially serious interaction between ICS and oral itraconazole, a treatment very commonly prescribed in patients with ABPA.
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