变应性支气管肺曲霉病研究新进展

变应性支气管肺曲霉病(allergic bronchopulmonary aspergillosis,ABPA)是由于人体对曲霉发生超敏反应引起的一种变应性肺部疾病,临床常表现为慢性支气管哮喘(简称哮喘)、复发性肺部浸润和支气管扩张等[1].1952年Hinson等[2]最先对该病进行了详细描述.     

Immunology of allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused predominantly by the ubiquitous fungus Aspergillus fumigatus. ABPA is characterized by eosinophilia, fleeting pulmonary infiltrates, central bronchiectasis, elevated serum IgE and Aspergillus specific IgG and IgE. The pathogenetic mechanism implicated in ABPA is not completely understood. The cytokine response detected in ABPA patients is of a CD4+ Th2 type as evidenced by the production of IL-4, IL-5, and very little or no IFN-g on stimulation of T-lymphocytes with Aspergillus antigens. Animal model studies using wild type and gene knockout mice indicate a more precise mechanism of lung injury in antigen exposed animals. IL-4 knockout mice invariably showed a predominant Th1 response. B-cell deficient and IgE knockout mice exposed to A. fumigatus antigens showed airway response similar to wild type mice indicating a lesser role for IgE and other antibodies in the pathogenesis of murine experimental ABPA. RAG negative mice failed to show airway hyperreactivity response, although airway hyperreactivity was induced in naive RAG negative animals when T-cells from wild type Aspergillus immunized mice were transferred. The results of these studies indicate a multi-factorial immunopathogenesis in ABPA, which include T-cells, IgE, eosinophils, mast cells, and various cytokines and chemokines.     

Therapy of allergic bronchopulmonary aspergillosis

The management of ABPA depends on the extent and stage of the disease. Underlying asthma should be controlled with environmental changes, pharmaco- and immunotherapy. Baseline examinations and evaluations of pulmonary function, airway and parenchymal anatomy, and serum total IgE levels are important and should be re-evaluated based on the clinical course of the patient. The mainstay of pharmacotherapy for ABPA remains oral corticosteroids. The dose and duration of treatment in the initial stage of the disease depends on when it was diagnosed as well as the patient's clinical course. Anti-fungal agents should be considered as adjunctive. Clinical data suggests that the early institution of treatment is likely to prevent progression of ABPA to end-stage fibrosis.     

变态反应性支气管肺曲霉菌病误诊23例分析

目的 总结变态反应性支气管肺曲霉菌病(allergic bronchopulmonary aspergillosis,ABPA)的诊治经验及误诊原因.方法 回顾性分析1985至2008年诊断的23例ABPA的临床资料,总结ABPA的诊治经验及误诊原因.结果 本组23例中22例48次被误诊.主要被误诊肺结核、支气管哮喘、肺部感染、嗜酸细胞性肺炎、肺癌等,误诊时程在30个(14,114)月.结论 临床医师对本病的认识不足是误诊的主要原因,提高对本病的认识程度,尽早行过敏原筛查,熟悉其影像学特征是减少误诊的关键.     

Spontaneous pneumothorax in allergic bronchopulmonary aspergillosis

A new roentgenographic finding of spontaneous pneumothorax occurred in a patient with well-advanced (stage V) allergic bronchopulmonary aspergillosis (ABPA). The pneumothorax responded to chest tube evacuation. Patients with well-advanced ABPA and severe chest pain should be carefully examined and treated for pneumothorax, to maintain as much functioning lung as possible.     

变应性支气管肺曲霉病1例

患者男性,22岁,学生,以“反复咳嗽1年半,右侧胸痛10个月余”于2012年1月31日入院。咳嗽呈阵发性,闻刺激性气味加重,伴咳少量黄稠痰、夜间低热。肺功能示：支气管激发试验阳性,CT示：右肺占位性病变。行CT引导性肺穿刺病理示：炎性,予抗感染治疗后症状缓解。患者2011年3月29日查cT（见图1）示：两肺炎症,右肺下叶实变,右侧胸膜局限性增厚、粘连,给予试验性抗结核治疗,2011年9月出现左胸钝痛,吸气时加重,侧卧时可缓解,     

变态反应性支气管肺曲菌病的HRCT表现

目的探讨变态反应性支气管肺曲菌病(ABPA)的HRCT影像学特点。方法分析24例ABPA的发病机制、临床表现、影像学表现。结果 24例患者中,女性15例,男性9例,中位年龄40岁。主要临床表现:咳嗽24例,咳痰19例,喘憋17例,咯血7例,均行胸部HRCT检查,中心性支气管扩张19例,斑片状渗出影或实变影3例,支气管粘液栓6例,其中5例见高密度钙化。结论 ABPA具有相对特征性的临床及HRCT影像学表现。     

Bronchocentric granulomatosis and allergic bronchopulmonary aspergillosis

Considerable clinical and radiologic similarity exists among FB, ABP, MIB, ABPA, and, to a lesser extent, BCG. In the absence of focal obstructive lesions such as tuberculosis or neoplasm, one of the diffuse bronchial hypersecretory diseases, that is, bronchial asthma, acute or chronic bronchitis, asthmatic bronchitis, or cystic fibrosis, is prerequisite to the development of a clinical and radiologic syndrome, resulting from bronchial mucus retention. This hypersecretory bronchial obstruction syndrome characterizes each of the disorders discussed. Thus, the differences existing among these disorders are merely those of size and location of mucus plugs or casts, and there is substantial variation within each individual entity concerning even this aspect. Unfortunately, extensive efforts to elucidate immunopathogenesis exist only for ABPA. Although evidence for the immunologic and morphologic presence of fungi, particularly AF, in ABPA is quite compelling, it is not necessarily conclusive evidence for an etiologic role of AF in the immunopathogenesis of this disorder. In this regard, it is reasonable to speculate that, perhaps, similar immunologic and morphologic information exists for FB, ABP, MIB, and, in some cases, BCG. BCG, because of its unique intrinsic bronchial obstructive and destructive histopathology, is a disorder distinct from the others, though sharing common clinical and radiologic features in some instances. If Aspergillus is involved in the immunopathogenesis of this disease, it cannot be the only etiologic factor, since in many instances no evidence of its presence is found.     

变应性支气管肺曲霉菌病的临床特征

目的：分析我院变应性支气管肺曲霉菌病（ABPA）的临床特征,为临床诊断及治疗提供帮助.方法：回顾性分析诊断为ABPA 8例患者的临床资料.结果：8例ABPA患者临床表现主要为咳嗽、胸闷、喘息.6例有肺部慢性疾病史,肺部CT特征性表现为囊状支气管扩张及黏液栓.结论：对于临床可疑ABPA患者,查血清总IgE及曲霉菌特异性IgE,行曲霉菌变应原皮肤点刺试验和纤维支气管镜检查有助于明确诊断.治疗以激素加抗真菌药物为主.     

The management of allergic bronchopulmonary aspergillosis.

Twenty-five patients with allergic bronchopulmonary aspergillosis (ABPA) were observed for periods of 12 months to 10 years (average duration, 2.6 years) after initial therapy with prednisone, which was then tapered and discontinued unless maintained at minimal doses as required for control of asthma. Thirteen patients have had no recurrence, 4 patients did not comply with the initial regimen and could not be considered to be controlled, and 8 patients had 12 recurrent episodes of ABPA characterized by pulmonary infiltrates with no explanation other than ABPA. The exacerbations were closely correlated with sharp increases in total serum IgE, which subsequently decreased after resumption of prednisone therapy. The increase of IgE preceded the pulmonary infiltrates in 7 or 12 exacerbations. The exacerbations, characterized by increased serum IgE and pulmonary infiltrates, may be associated with minimal symptoms. Acute asthma without pulmonary infiltrates was not associated with increased IgE. Four exacerbations occurred during administration of beclomethasone diproprionate used for control of asthma, and therefore, this agent does not appear to prevent or reverse exacerbations of ABPA. Twelve exacerbations occurred in 8 persons, with 2 patients having 4 and 2 recurrences, respectively. This suggests that exacerbations are more likely to occur in certain patients. Serial measurements of total serum IgE appears to be a useful index of disease activity in ABPA. In the 4 patients who did not comply with the prednisone therapy regimen or regular physician visits, patterns of IgE changes, clinical evaluations, and chest roentgenograms were not of use in evaluation of the clinical state or progress of the patient. A treatment regimen is suggested for initial therapy and recurrences of ABPA on the basis of these observations.     

变态反应性支气管肺曲霉病的诊断与治疗

变态反应性支气管肺曲霉病是哮喘和囊性纤维化患者常见的并发症,由机体对曲霉的变态反应引起,表现为喘息、肺部浸润、支气管扩张和肺纤维化;病理改变包括黏液嵌塞、中心性支气管肉芽肿、嗜酸细胞肺炎和慢性或渗出性毛细支气管炎;诊断依靠临床表现、实验室以及影像学改变等标准,并分为囊性纤维化和非囊性纤维化两组;治疗主要是口服激素联合依曲康唑。     

Allergic bronchopulmonary aspergillosis and related allergic syndromes

While allergic bronchopulmonary aspergillosis (ABPA) is well recognized as a fungal complication of asthma, severe asthma with fungal sensitization (SAFS) is not. In ABPA the total immunoglobulin E (IgE) is usually >1,000 IU/mL, whereas in SAFS it is <1,000 IU/mL, and either skin prick tests or fungus-specific IgE tests are positive. ABPA may present with any severity of asthma, and occasionally with no asthma or cystic fibrosis, the other common underlying disease. SAFS is a problem in patients with poorly controlled asthma and occasionally presents in the intensive care unit (ICU). Production of mucous plugs and coughing paroxysms is more common in ABPA. Certain underlying genetic defects seem to underpin these remarkable phenotypic differences. From a management perspective both ABPA and SAFS respond to both high doses of corticosteroids and oral antifungal agents, with ～60% response rate in both ABPA and SAFS with itraconazole. In 50% of patients itraconazole boosts inhaled corticosteroid exposure, sometimes leading to cushingoid features. Second-line therapy data are scant, but we have shown that 70 to 80% of patients who tolerate either voriconazole or posaconazole also respond. Other useful therapies include nebulized hypertonic saline to aid expectoration of thick sputum and long-term azithromycin for its anti-inflammatory effect on the airways. Omaluzimab is useful in some patients with SAFS and occasionally in ABPA. Complications of ABPA include bronchiectasis, typically central in distribution, and chronic pulmonary aspergillosis. Most patients with ABPA and SAFS can be stabilized for long periods with inhaled corticosteroids and itraconazole or another antifungal agent. Novel immunotherapies are on the horizon.     

Eosinophilic pleural effusion complicating allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is primarily a disease of patients with cystic fibrosis or asthma, who typically present with bronchial obstruction, fever, malaise, and expectoration of mucus plugs. We report a case of a young man with a history of asthma who presented with cough, left-sided pleuritic chest pain and was found to have lobar atelectasis and an eosinophilic, empyematous pleural effusion. Bronchoscopy and sputum cultures grew Aspergillus fumigatus, and testing confirmed strong allergic response to this mold, all consistent with a diagnosis of ABPA. This novel and unique presentation of ABPA expands on the differential diagnosis of eosinophilic pleural effusions.     

变态反应性支气管肺曲霉病研究进展

变态反应性支气管肺曲霉病(allergic bronchopulmonary aspergillosis,ABPA)与烟曲霉引起的变态反应相关,常发生在哮喘和肺囊性纤维化患者中.ABPA可引起血清总IgE水平升高,外周血嗜酸粒细胞增多,肺浸润和中心性支气管扩张,严重者可导致肺纤维化等肺组织的不可逆破坏.故ABPA的早期明确诊断和及时治疗十分重要.本文将对近年来ABPA的发病机制、临床分期、诊断标准、辅助检查及治疗研究新进展进行介绍.     

A familial occurrence of allergic bronchopulmonary aspergillosis.

A family was recently studied in which two brothers with identical HLA serotypes had allergic bronchopulmonary aspergillosis. One of the two had a normal bronchogram. A field investigation of the family residence showed that a barn was the probable source of the organism causing disease in these patients. Immunologic characterization of the family members showed a broad spectrum of response to the environmental exposure.