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.     

Allergic bronchopulmonary aspergillosis due to Aspergillus niger without bronchial asthma.

A 65-year-old woman was admitted to our hospital with a dry cough and pulmonary infiltrates. Chest radiograph and CT revealed mucoid impaction and consolidations. Peripheral blood eosinophilia and elevated serum IgE were observed. Aspergillus niger was cultured repeatedly from her sputum, but A. fumigatus was not detected. Immediate skin test and specific IgE (RAST) to Aspergillus antigen were positive. Precipitating antibodies were confirmed against A. niger antigen, but not against A. fumigatus antigen. She had no asthmatic symptoms, and showed no bronchial hyperreactivity to methacholine. Thus, this case was diagnosed as allergic bronchopulmonary aspergillosis (ABPA) without bronchial asthma due to A. niger, an organism rarely found in ABPA. The administration of prednisone improved the symptoms and corrected the abnormal laboratory findings.     

Allergic bronchopulmonary aspergillosis: an Indian perspective

PURPOSE OF REVIEW: Allergic bronchopulmonary aspergillosis is an immunologically mediated lung disease that is caused by hypersensitivity to antigens of the genus Aspergillus. This review summarizes the clinical presentation, radiologic profile, lung functions and immunologic studies on allergic bronchopulmonary aspergillosis from India. Data regarding Aspergillus sensitization in asthmatics are presented. The association of allergic bronchopulmonary aspergillosis with allergic Aspergillus sinusitis and aspergilloma is also highlighted. RECENT FINDINGS: Allergic bronchopulmonary aspergillosis is now an emerging disease in India. Sensitization to Aspergillus antigens is not uncommon in our patients with asthma. Although asthma commenced in these subjects in their early 20s, allergic bronchopulmonary aspergillosis was recognized more than a decade later. Allergic bronchopulmonary aspergillosis can also occur in patients without clinical asthma. Radiology is crucial to the diagnosis of allergic bronchopulmonary aspergillosis. The remarkable radiological similarity to pulmonary tuberculosis has important clinical implications in our country as patients with allergic bronchopulmonary aspergillosis often receive antituberculous therapy for a long time. Although oral corticosteroids still remain the cornerstone for management, itraconazole has emerged as an adjunct therapy in appropriate situations. Concomitant occurrence of allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis is now being increasingly recognized. SUMMARY: All asthmatic subjects with a positive skin prick test to Aspergillus antigens must be evaluated for allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis should be excluded.     

Evidence that Aspergillus fumigatus growing in the airway of man can be a potent stimulus of specific and nonspecific IgE formation.

Serum IgE levels in patients with allergic bronchopulmonary aspergillosis are elevated but the degree of elevation varies markedly. Serum IgE levels in patients with aspergillomas may be strikingly elevated or normal. Absorption of serums with antigens of Aspergillus fumigatus combined with a solid phase radioimmunoassay technic demonstrated that both immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody activity against A. fumigatus were markedly reduced without a parallel reduction in serum total IgE. These results indicate that the very high levels of serum IgE found in allergic bronchopulmonary aspergillosis and aspergilloma are not all specific IgE. These results are similar to those observed in rats infested with Nippostrongylus brasiliensis. An explanation for the elevations of IgE levels in infestations with A. fumigatus may be analogous to the postulate that parasite-produced materials may result in T cell stimulatory factors for IgE-producing cells. Alternatively, A. fumigatus organisms may produce materials that inhibit T suppressor lymphocytes.     

Successful treatment of allergic bronchopulmonary aspergillosis with erythromycin and fluconazole]

A 30-year-old woman was admitted to our hospital because of productive cough, wheezing, and the disclosure of abnormal shadows on chest X-ray films. The patient was given a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) based on eight findings: asthma, eosinophilia, elevated serum IgE concentrations, immediate skin reactivity to Aspergillus antigen, the presence of precipitating antibodies against Aspergillus antigen, lung infiltration, central bronchiectasis, and repeated culture of Aspergillus fumigatus in sputum. Because she refused steroids, we administered erythromycin. The volume of her sputum subsequently decreased, her symptoms were brought under control, and her serum IgE fell, but the lung infiltrates did not clear. Discontinuation of erythromycin resulted in exacerbation of the patient's asthmatic symptoms, with high fever, increased sputum volume and IgE levels, and worsening lung infiltrates. These symptoms responded well to oral prednisolone medication, but sputum culture was still positive for Aspergillus fumigatus. Following discontinuation of prednisolone, the patient was treated with erythromycin, to which oral fluconazole was added for 16 months. Subsequent sputum cultures were negative for Aspergillus fumigatus, and for 7 years thereafter the patient remained in remission. Erythromycin and anti-fungal drugs may be worth trying in cases of allergic bronchopulmonary aspergillosis.     

Allergic bronchopulmonary aspergillosis: a US perspective

PURPOSE OF REVIEW: The present article is an update of allergic bronchopulmonary aspergillosis. Although a rare condition, allergic bronchopulmonary aspergillosis does affect a number of patients with asthma and cystic fibrosis. Prompt recognition and treatment of the disease is critical to improving patient outcomes. RECENT FINDINGS: There is currently much active research being performed in the area of allergic bronchopulmonary aspergillosis. Fascinating insights are being made into the pathophysiology and genetics of the disease. Additionally, research is ongoing on the use of recombinant Aspergillus allergens as an aid to the diagnosis of allergic bronchopulmonary aspergillosis. SUMMARY: These new insights into the genetics and pathophysiology of allergic bronchopulmonary aspergillosis and the development of these new diagnostic techniques could ultimately lead to improved patient treatment. These areas form an important basis for further research.     

Correlations between clinical and laboratory findings in patients investigated for aspergillosis

We investigated 120 patients suspected clinically to have pulmonary aspergillosis with different clinical manifestations "aspergilloma (Subgroup A), allergic bronchopulmonary aspergillosis (Subgroup B) and invasive pulmonary aspergillosis (Subgroup C)" and correlated between their clinical and laboratory findings and endogenous specific aflatoxin production. They were subjected to isolation of Aspergillus strains, measurement of serum total IgE and specific Aspergillus IgG by ELISA and identification of aflatoxin producing Aspergillus strains using fluorescence analysis of spectroline. Aspergillus was isolated from 45 patients (37.5%). Subgroup A had a negative statistically non-significant correlation between clinical and laboratory findings as regard total IgE and for Aspergillus IgG (only haemoptysis &weight loss had significant correlation with aspergillus IgG). Subgroup B & Subgroup C had positive, statistically significant correlation &negative statistically non significant correlation respectively as regard all clinical findings and both total IgE & serum IgG. This study also showed that 6 Aspergillus strains out of 45(13.3%) produced endogenous aflatoxin. It is concluded that a significant correlation that exists between clinical and serological findings in allergic pulmonary aspergillosis. Aflatoxins may be produced in vivo by strains of Aspergillus and may result in manifestations similar to those caused by ingestion of aflatoxin in food.     

Asthma and allergic aspergillosis in monozygotic twins

Monozygotic twins are reported; both had bronchial asthma with type I hypersensitivity to Aspergillus fumigatus but only one had type III hypersensitivity, together with pulmonary infiltrations compatible with the diagnosis of allergic bronchopulmonary aspergillosis. It is suggested that non-inherited factors other than the intensity of exposure to antigen may be important in determining the development of allergic bronchopulmonary aspergillosis.     

Allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis is an uncommon but serious respiratory condition characterized by chronic airway inflammation and airway damage resulting from persistent colonization by and sensitization to the fungus Aspergillus fumigatus. The immunopathogenesis of allergic bronchopulmonary aspergillosis involves several pathways. Aspergillus allergens stimulate an interleukin 5-mediated Th2 pathway responsible for the eosinophilic infiltrate, whereas aspergillus proteases promote epithelial activation and a potent chemokine response that induces neutrophilic airway inflammation. The resulting airway inflammation is intense, involves tissue damage and remodeling, and is linked with the severity of bronchiectasis. Treatment involves corticosteroids and antifungal therapy with oral azoles. Additional management seeks to monitor and control the other disease components of severe asthma, bronchiectasis, and disease exacerbations.     

Stage V (fibrotic) allergic bronchopulmonary aspergillosis. A review of 17 cases followed from diagnosis

A review of the records of 17 patients with stage V (fibrotic stage) allergic bronchopulmonary aspergillosis observed since initial diagnosis (mean observation period, 4.9 years) demonstrated that, of the 11 surviving patients, four have very severe respiratory impairment. The other seven patients have mild or moderate functional impairment, but most of these have not shown clinical deterioration during the observation period. The occurrence of new roentgenographic infiltrates after the time of diagnosis was observed in only one patient in this series. Serum IgE and IgG levels against Aspergillus fumigatus, when compared with those of a control pool of serum samples from asthmatic patients with immediate cutaneous reactivity to Aspergillus, were the most useful immunologic studies diagnostically. Lung biopsy specimens obtained in five patients were of relatively little diagnostic value. All patients have required long-term prednisone therapy for control of asthma. Those patients whose forced expiratory volume in 1 s (FEV1) remained less than or equal to 0.8 L after initial corticosteroid treatment demonstrated a poor prognosis. When only moderate lung damage has occurred at the time of diagnosis, a stable subsequent course may be expected even in patients with stage V disease.     

Noninvasive Aspergillus pulmonary disease

Noninvasive Aspergillus pulmonary disease may be the result of a host response to Aspergillus antigens or colonization of the lung with Aspergillus species. The prototype example of each of these phenomena are allergic bronchopulmonary aspergillosis and aspergilloma. Allergic bronchopulmonary aspergillosis is a form of asthma associated with a Type I, III, and IV allergic response to Aspergillus antigens. It presents clinically as asthma but is also associated with bronchiectasis, airway destruction, and permanent lung injury if inadequately treated. Treatment consists of anti-inflammatory agents such as corticosteroids. Antifungal agents may also be useful to lower the fungal antigen load. Aspergillomas grow in areas of devitalized lung. They may manifest as asymptomatic radiographic abnormalities. The concern is that they may lead to hemoptysis that can be life threatening. Definitive treatment is surgical resection, but this is often prohibited because these patients often have inadequate lung function to tolerate thoracic surgery. Other treatment options include azoles and percutaneous instillation of antifungals.     

Correlation of IgE antibody titer to Aspergillus fumigatus with decreased lung function in cystic fibrosis

Obstructive pulmonary disease is a typical feature of cystic fibrosis (CF) and is often associated with bronchial hyperreactivity. Positive skin-test reactions to Aspergillus fumigatus antigens are frequently seen even in nonatopic patients with CF. Full-fledged allergic bronchopulmonary aspergillosis (ABPA) has been estimated to occur in 10% of patients with CF. The relationship between lung function and presence of IgE antibodies to Aspergillus antigens in patients without ABPA is not clear. In 148 outpatients with CF (aged 6-34 years) specific immunoglobulin E (IgE) to Aspergillus fumigatus antigens, basic lung-function parameters, and bronchial response to salbutamol were measured. Multiple regression was performed for age, weight as percentile for actual height (indicating general condition), and Aspergillus RAST. Aspergillus IgE was present in 46% of patients; 19% had RAST class 3 or 4. Independent negative correlations of Aspergillus RAST with FEV1, FEF50%, FEF25%, RV, Chrispin Norman score, and sRaw (P less than 0.05) were found. Bronchodilator sensitivity did not correlate significantly with age and weight percentile. However, Aspergillus RAST did correlate significantly with bronchodilator response measured by sRaw (P less than 0.05). High titers of Aspergillus RAST might serve as a selective criterion for patients to be included in future studies evaluating broncholytic or antiphlogistic therapies.     

呼出气一氧化氮检测在变应性支气管肺曲霉菌病诊疗中的应用

目的探讨呼出气一氧化氮(FeNO)检测在变应性支气管肺曲霉菌病(ABPA)诊疗中的应用,为ABPA的诊疗及管理提供新思路。方法收集2016年12月至2020年1月于河南省人民医院呼吸内科确诊的30例ABPA患者作为观察组;同期收集就诊于河南省人民医院呼吸内科非ABPA哮喘患者74例作为对照组,其中完善烟曲霉特异性血清免疫球蛋白E(IgE)及血清总IgE者41例。回顾性分析2组患者临床资料。结果2组患者年龄、性别及病程相比较,差异无统计学意义。观察组患者烟曲霉特异性IgE、血清总IgE、血嗜酸粒细胞计数、FeNO均高于对照组(t值分别为4.049、8.077、2.051、2.894,P值均<0.05)。spearman相关系数分析结果显示FeNO与ABPA具有一定相关性(r=-0346,P<005)。结论FeNO与ABPA的诊断具有一定的相关性,可为ABPA患者诊疗提供帮助。     

变态反应性支气管肺曲霉菌病合并血清癌胚抗原升高5例报道并文献复习

目的 分析变态反应性支气管肺曲霉菌病(ABPA)患者血清癌胚抗原(CEA)的变化规律及其与血嗜酸粒细胞计数、血清总IgE水平、影像学表现及临床表现的相关性.方法 回顾我院5例血清CEA增高的ABPA患者,对其治疗前后血清CEA水平、血嗜酸粒细胞计数、血清总IgE水平、影像学表现及临床症状进行对比分析.结果 治疗前,5例患者有明显的咳嗽、气促或活动后气促等症状,血清CEA水平、嗜酸粒细胞计数和血清总IgE均明显增高,影像学表现为典型的指套征;治疗后症状明显减轻或消失,血清CEA、嗜酸粒细胞计数恢复正常,血清总IgE明显下降,影像学指套征消失,支气管扩张程度减轻.结论 ABPA患者血清CEA可以升高,其水平血嗜酸粒细胞计数、血清总IgE、影像学表现及临床表现相平行.针对ABPA的治疗可使其恢复正常水平.     

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.     

Surfactant protein D in serum from patients with allergic bronchopulmonary aspergillosis.

Surfactant protein D (SP-D) interacts with Aspergillus fumigatus and is strongly increased in the lavage from animals with acute allergic reactions to the fungus, suggesting a central role for SP-D. As the course of cystic fibrosis (CF) is often complicated by an allergic bronchopulmonary aspergillosis (ABPA), the authors hypothesised that SP-D may also be increased in serum during an ABPA, potentially assisting in its diagnosis and follow-up. In 22 patients with CF (11 with ABPA, 11 matched without ABPA) and 19 control patients without a pulmonary disease, SP-D concentrations in serum were assessed by an enzyme immunoassay. Serum SP-D in CF patients (130 +/- 16 ng x mL(-1) (mean +/- SEM)) was significantly higher than in the controls without lung disease (66 +/- 8 ng x mL(-1)). During the whole ABPA-episode, SP-D level did not change significantly, despite large changes of total serum immunoglobulin E. There was a clear negative correlation between SP-D concentration and overall lung function, i.e. forced expiratory volume in one second and forced vital capacity. Serum level of surfactant protein D may be of value to follow pulmonary function and lung injury in cystic fibrosis patients. Surfactant protein D serum levels are not helpful for the diagnosis and follow-up of an allergic bronchopulmonary aspergillosis episode, contrary to what was expected from animal experiments.     

Allergic bronchopulmonary aspergillosis and aspergilloma. Long-term follow-up without enlargement of a large multiloculated cavity

A 47-year-old man with a history of mild asthma presented with hemoptysis attributed to a large multiloculated cavitary mycetoma. Peripheral blood eosinophilia of 43 percent led to the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). Treatment of ABPA with prednisone led to resolution of an upper lobe infiltrate and a dramatic reduction in the total serum IgE level. Evaluation over a two-year period did not demonstrate enlargement of the cavity or disseminated aspergillosis.     

Serum IgE and IgG antibody activity against Aspergillus fumigatus as a diagnostic aid in allergic bronchopulmonary aspergillosis.

Serum IgE and IgG antibody activity against Aspergillus fumigatus was measured in 3 groups of subjects by 2 different immunologic methods. Group A consisted of 23 patients with allergic bronchopulmonary aspergillosis (ABPA). Group B was composed of 19 patients with extrinsic asthma who had marked immediate type skin reactivity to A. fumigatus (prick skin test, 3 or 4+) but no other manifestation of ABPA. Group C, the control group, was composed of 12 healthy subjects. Two immunological methods, including a solid-phase polystyrene tube radioimmunoassay and an iodine-125-labeled, A. fumigatus antigen radioimmunoassay, were used to study each patient's serum sample, so as to demonstrate IgE antibody activity against A. fumigatus (IgE-Af) and IgG antibody activity against A. fumigatus (IgG-Af). Both IgE-Af and IgG-Af were significantly greater among patients in Group A than among those in Group B and Group C, as measured by both methods (P is less than 0.001). The results of this study suggest that either method can be used as a diagnostic aid for ABPA. These methods may provide a laboratory test permitting diagnosis of ABPA in its early stages before bronchial or pulmonary destruction occurs.     

呼吸系统曲霉菌病重叠综合症的新进展

肺部曲霉菌病是少见病,但近年逐年增多,包括变应性支气管肺曲菌病(allergic bronchopulmonary aspergillosis,ABPA)、曲菌球(aspergilloma)、慢性坏死性肺曲菌病(chronic necrotizing aspergillosis,CNA)、侵袭性肺曲菌病(invasive pulmonary aspergillosis,IPA)及全身播散性曲菌病等5型.其中ABPA、曲菌球甚至IPA可合并变应性曲霉菌性鼻窦炎(allergic Aspergillus sinusitis,AAS),可能与基础病及其治疗等因素有关.本文就近期文献报告的呼吸系统曲霉菌病重叠综合症作一综述.     

Prolonged therapeutic response to voriconazole in a case of allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis is a lung disease characterized by an immune response to several antigens of Aspergillus species. Corticosteroids are the treatment of choice in the acute phase, although some studies have shown the efficacy of itraconazole. We describe the case of a favorable, prolonged therapeutic response to voriconazole in a patient with allergic bronchopulmonary aspergillosis who did not tolerate itraconazole.