Optimal Aspergillus fumigatus and Asp f 1 serum IgG cut-offs for the diagnosis of allergic bronchopulmonary aspergillosis

BackgroundThe presence of IgG antibodies (Abs) to Aspergillus fumigatus (Af) is a crucial diagnostic criterion for allergic bronchopulmonary aspergillosis (ABPA). Although precipitation is traditionally used to document IgG Abs, anti-Af serum IgG levels can also be measured by enzyme immunoassay (EIA). However, there are insufficient data on the optimal cut-offs to assess diagnostic performance of the EIA method. This study aimed to determine cut-off levels of IgG binding crude Af extracts or recombinant Asp f 1 (by ImmunoCAP®) and to compare their efficacy for ABPA diagnosis with Af-precipitating Abs.MethodsThe age distribution of levels of IgG to crude extracts of Af (Af-IgG) and recombinant Asp f 1 (Asp f 1-IgG) was established using sera from 694 healthy controls (HC). Receiver operating characteristic analysis for Af-IgG and Asp f 1-IgG levels for the purpose of ABPA diagnosis was performed in 306 Af-sensitized asthma patients (including 49 ABPA), and cut-offs were determined.ResultsAn age-dependent decline in the levels of Af-IgG was observed in HC. Thus, cut-offs for Af-IgG levels were determined separately by age as 60 mg/L for patients aged <55 years, and 45 mg/L for those aged ≥55 years. For Asp f 1-IgG, 6.6 mg/L was set as the cut-off regardless of age. Although such IgG testing by EIA allowed a sufficiently good diagnostic performance, Af-precipitating Abs had better diagnostic applicability for ABPA.ConclusionsWe determined cut-offs for Af-IgG and Asp f 1-IgG measured by EIA, which can be useful in clinical settings where precipitating Abs are unavailable.     

烟曲霉致敏的呼吸道疾病患者对其他真菌致敏的sIgE水平及相关性分析

目的 探讨呼吸道疾患者对真菌致敏的免疫球蛋白E (specific ImmunoglobulinE,sIgE)水平及多重致敏现象.方法 筛选广州医科大学附属第一医院烟曲霉sIgE阳性且级别大于等于三级的哮喘或变态反应性支气管肺曲霉菌病(ABPA)成人患者,分为烟曲霉致敏哮喘组及ABPA组.采用ImmunoCAP 1000荧光酶联免疫系统检测患者血清点青霉、分支孢霉、烟曲霉、白假丝酵母霉、链格孢霉与长蠕孢霉sIgE浓度.结果 ABPA患者烟曲霉sIgE显著高于烟曲霉致敏哮喘患者(P＜0.05)[26.7 (13.3,54.3) kU/L vs 12.7 (5.90,33.4) kU/L]、白假丝酵母sIgE[7.90 (1.40,6.00) kU/L vs 1.00 (0.40,6.00) kU/L]、点青霉sIgE[17.6 (6.80,37.6) kU/L vs 4.30 (4.30,4.30) kU/L]、链格孢sIgE[2.60 (1.70,16.0)kU/L vs 0.90 (0.40,2.10) kU/L].所有患者皆有多重霉菌致敏现象,各霉菌sIgE水平存在不同程度相关,最优尺度分析显示烟曲霉与链格孢霉关系最近(Cronbach's Alpha=95.7％).结论烟曲霉菌致敏患者常伴多重霉菌过敏现象,或因霉菌间分泌相同的致敏蛋白引起,多种霉菌sIgE浓度的检测或可作为真菌致敏哮喘辅助检查.     

Treatment of allergic bronchopulmonary aspergillosis (ABPA) in CF with anti‐IgE antibody (omalizumab)

Allergic bronchopulmonary aspergillosis (ABPA) results from IgE induced pulmonary response to aspergillus species. Recognition and management of ABPA is challenging in cystic fibrosis (CF) patients because changes in symptoms, lung function and chest radiograph are similar to that seen in CF related pulmonary infection. Standard therapy for ABPA includes systemic steroids and adjunctive use of antifungal agents. Little has been published regarding the use of monoclonal anti‐IgE antibody in those with ABPA. We report a CF patient with her third exacerbation of ABPA who was treated with monoclonal anti‐IgE (omalizumab) antibody; she had unfavorable side effects with prednisone therapy. This therapy resulted in improvement of pulmonary symptoms and lung function not achieved with antibiotics or prednisone alone. Pediatr. Pulmonol. 2008; 43:1249–1251. © 2008 Wiley‐Liss, Inc.     

Sensitization to Aspergillus antigens and occurrence of allergic bronchopulmonary aspergillosis in patients with asthma

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA), which is predominantly a disease of asthmatic subjects, is caused by hypersensitivity to Aspergillus antigens. Screening for Aspergillus sensitization in asthmatic subjects could identify those who are at risk for ABPA. Few studies have shown that fungal sensitization could be an important risk factor for asthma severity. We sought to determine the frequency of sensitization to Aspergillus antigens in asthmatic subjects and its effect on disease severity. We also determined the occurrence of ABPA in these subjects. DESIGN: Prospective study of consecutive patients with asthma. SETTING: Tertiary university referral hospital, outpatient department. PATIENTS AND METHODS: One hundred five asthmatic subjects and 26 volunteers underwent skin testing with aeroallergens, including Aspergillus, serum precipitins against Aspergillus antigens, and specific IgG against Aspergillus fumigatus, total serum IgE levels, and routine blood and radiologic investigations. ABPA was diagnosed when all eight major criteria were fulfilled. RESULTS: Thirty patients (28.5%) had a positive skin reactivity to Aspergillus antigens. Eleven patients (10.4%) had positive specific reactions to IgG, and 8 patients (7.6%) demonstrated positive reactions to serum precipitins. Eight of these 30 patients (26.6%) received diagnoses of ABPA, which was 7.6% of the total. None of the control subjects were sensitized to Aspergillus antigens. The patients were classified into the following four groups: negative skin test results; positive reactions to aeroallergens other than Aspergillus; positive reactions to aeroallergens including Aspergillus antigens; and patients with ABPA. Based on clinical and serologic parameters, patients with Aspergillus-sensitive asthma and ABPA had a significantly more severe form of the disease. CONCLUSIONS: Sensitization to the mold Aspergillus increases the severity of asthma. ABPA should be excluded in all patients with Aspergillus-sensitive asthma.     

Mucoid impaction: a localized form of allergic bronchopulmonary aspergillosis.

Mucoid impaction is defined as the obstruction of proximal bronchi by mucous plugs and exudates. There are striking similarities between patients with mucoid impaction and those with allergic bronchopulmonary aspergillosis (ABPA), often referred to as "mucoid microimpaction." We evaluated three patients with mucoid impaction for diagnostic criteria of ABPA and human leukocyte antigen type. We found that certain human leukocyte antigen types were common among mucoid impaction patients and those with ABPA. It is possible that patients with mucoid impaction could represent a localized form of ABPA.     

Acute and chronic pulmonary function changes in allergic bronchopulmonary aspergillosis.

Pulmonary functions of patients with allergic bronchopulmonary aspergillosis were studied during an acute episode (n = 6); during a mean follow-up period of 44 months (range four months--14.8 years) (n = 16); and for any correlation between duration of ABPA and asthma with the total lung capacity (helium dilution), 1 second forced expiratory volume (FEV1), vital capacity, 1 second forced expiratory volume-forced vital capacity ratio (FEV1:FVC per cent) and diffusing capacity of carbon monoxide (DL:CO) (single breath) for the entire group (n = 22). All patients were treated with corticosteroids (intermittent or continuous) and bronchodilators. For the 16 patients, slopes using linear regression analysis were determined from the function as per cent predicted versus time in months from diagnosis and then analyzed for significance. Significant functional loss was shown in three of 16 patients for FEV1, two of 16 patients for vital capacity, one of 16 patients for FEV1:FVC per cent, none of 10 patients for DL:CO and one of 10 patients for total lung cital capacity, FEV1:FVC per cent and the duration of asthma or allergic bronchopulmonary aspergillosis was found by multiple regression analysis correcting for age and smoking (mean 4.24 years; range 0.3 to 14.8 years). Roentgenographic criteria and blood eosinophilia were used to define a "flare" of allergic bronchopulmonary aspergillosis. The six patients during a flare showed a significant reduction in total lung capacity (P less than 0.001), vital capacity (P less than 0.05), FEV1 (P less than 0.01) and DL:CO (P less than 0.001) which uniformly returned to baseline values during steroid therapy. The FEV1:FVC per cent remained unaltered. These findings, contrary to suggestions in the literature, indicate that in the majority of our patients there was no significant progressive functional deterioration after diagnosis. However, during acute episodes of allergic bronchopulmonary aspergillosis, transient reduction of volumes and DL:CO were uniformly present.     

Using rare diseases as models for biobehavioral research: allergic bronchopulmonary aspergillosis.

Biobehavioral science explores links between biological, psychosocial, and behavioral factors and health. Maintaining positive health outcomes over time and across a variety of populations and settings requires understanding interactions among biological, behavioral, and social risk factors as well as other variables that influence behavior. Some barriers to biobehavioral research are related to performing biobehavioral research along the natural history of an illness, limitations in existing methodologies to assess the biological impact of behavior, the unknowns relating to impact of behavior on biology, and lack of valid and reliable biobehavioral methods to assess outcomes. A rare disease, such as allergic bronchopulmonary aspergillosis (ABPA) can be used as a model of biobehavioral research. ABPA complicates asthma and cystic fibrosis. It is a hypersensitivity reaction to Aspergillus fumigatus in most cases. ABPA can be classified into five stages: acute, remission, exacerbation, steroid-dependent asthma, and fibrotic or end stage. Because of its rarity, there can be delays in diagnosis. Treatment has used oral corticosteroids and antifungal agents in addition to management of asthma or cystic fibrosis. The National Institute of Nursing Research held an invitational 2-day working group meeting on July 15-16, 2004 with biobehavioral, biological, and immunologic science experts to examine current knowledge of biobehavioral research and to provide recommendations for additional research. The focus was on biobehavioral methods of measurement and analysis with interdisciplinary/biobehavioral approaches. This article is an outcome of this meeting.     

Intracutaneous tests with recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis and Aspergillus allergy

Allergic bronchopulmonary aspergillosis (ABPA), an intensive inflammatory reaction to Aspergillus fumigatus, can cause irreversible lung damage in patients with cystic fibrosis (CF). The aim of this study was to assess if intracutaneous testing with recombinant A. fumigatus allergens (rAsp f ) allowed a reliable diagnosis of ABPA. Fifty patients with CF were tested, 12 suffering from ABPA, 21 with allergy to A. fumigatus, and 17 CF control patients not sensitized to A. fumigatus. All patients with ABPA reacted to at least one of the two intracellular A. fumigatus allergens rAsp f 4, a 30-kD protein of unknown biologic function, and rAsp f 6, a 23-kD manganese superoxide dismutase, at a concentration of 10(-2) microg/ml. The intracutaneous tests were negative or only marginally positive in the patients with allergy to A. fumigatus and completely negative in the CF control patients. The differential responses to the recombinant A. fumigatus allergens were in perfect agreement with our previous serologic results, so that rAsp f 4 and rAsp f 6 can be considered specific markers for ABPA. Early diagnosis of the disease might help to prevent irreversible lung damage and minimize possible steroid-mediated side effects as a consequence of an optimized control of the disease.     

变态反应性支气管肺曲霉病诊治的研究进展

变态反应性支气管肺曲霉病(allergic bronchopulmonary aspergillosis,ABPA)与烟曲菌感染引起的变态反应相关.ABPA可引起血清总IgE升高,外周血嗜酸粒细胞升高,肺浸润和中心性支气管扩张.若未得到有效治疗可发生肺组织结构的不可逆破坏,最终导致呼吸衰竭,故ABPA的早期诊断和早期治疗十分重要.ABPA的治疗取决于疾病的分期、临床表现、血清总IgE、肺功能和影像学检查,以往多以口服糖皮质激素治疗为主,目前普遍推荐口服糖皮质激素加抗真菌的联合治疗方案,以达到控制机体对烟曲菌抗原的过敏反应,清除寄生于气道内的烟曲菌的目的.本文将对近年ABPA诊治进展作一综述.