The assessment of immunologic and clinical changes occurring during corticosteroid therapy for allergic bronchopulmonary aspergillosis

Twenty-two patients with allergic bronchopulmonary aspergillosis have been treated and evaluated for a period ranging from two months to nine years. Twelve are available for periodic blood sampling. Data are presented suggesting the following: (1) Patients with allergic bronchopulmonary aspergillosis have high initial levels of total serum immunoglobulin E (IgE). These levels are significantly higher in those patients who had not been previously treated with prednisone for the control of asthma. (2) Treatment with alternate day prednisone (0.5 mg/kg given on alternate days) caused clinical and roentgenologic improvement as well as marked decreases in total serum IgE but does not necessarily prevent recurrence of the disease. (3) Total and specific IgE against Aspergillus antigen may increase prior to and during exacerbations of disease. (4) Specific IgG and IgE against Aspergillus antigen are increased in most patients with allergic bronchopulmonary aspergillosis and reflect disease activity as evidenced by x-ray and clinical exacerbations in some cases. (5) Lymphocyte transformation using Aspergillis antigen, as measured by the whole blood technic, is present in patients with allergic bronchopulmonary aspergillosis, but serial changes in lymphocyte transformation do not correlate with disease activity. (6) Precipitin reactions are present in patients with allergic bronchopulmonary aspergillosis, but presence or absence does not reflect disease activity in most cases.     

变应性支气管肺曲霉病七例临床特点分析

目的 探讨变应性支气管肺曲霉病( ABPA)的临床特征、影像学特点、诊断和治疗方法,以做到早期诊断及早期治疗.方法 回顾性分析解放军总医院2010年3月至2011年5月确诊的7例ABPA患者的临床资料.结果 7例中,男4例,女3例,平均年龄为(33±16)岁.在确诊ABPA前,曾被误诊为支气管哮喘(简称哮喘)6例,肺部感染3例,肺结核2例,支气管扩张1例.主要临床表现为咳嗽6例,咳痰5例,咯血4例(其中3例为黑褐色痰),喘息3例,气短3例,发热2例.7例外周血中总IgE均升高,中位数为3040 U/ml.7例外周血中嗜酸粒细胞比均升高,中位数为0.19.6例外周血中嗜酸粒细胞绝对值升高,中位数为1.84×109/L;6例曲霉皮肤点刺试验阳性;5例血清特异性烟曲霉IgE抗体升高,平均为(22±15) kU/L;4例血清特异性烟曲霉IgG抗体升高,平均为(108±96) mg,/L.胸部CT主要表现为双肺多发性斑片状影、中心型支气管扩张及支气管黏液栓形成.5例患者接受口服糖皮质激素(简称激素)联合抗真菌药物治疗.结论 ABPA主要临床特点为常有哮喘病史,胸部影像学显示游走性或固定性肺部浸润影或中心型支气管扩张,外周血中嗜酸粒细胞、血清总IgE水平和血清烟曲霉特异性IgE抗体均升高.对哮喘合并支气管扩张的患者应高度警惕ABPA的可能,应常规进行曲霉皮肤试验筛查,必要时行外周血总IgE及胸部CT检查,以提高ABPA的诊断率.口服激素联合抗真菌药物对ABPA治疗有效.对ABPA患者应注意规律随诊并监测病情的变化,防止病情复发加重.     

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 case of effective readministration of itraconazole for recurrent allergic bronchopulmonary aspergillosis]

A 67-year-old woman suffered from productive cough but not from bronchial asthma. Her peripheral blood showed eosinophilia, a high serum level of total immunoglobulin E (IgE), and elevated specific IgE and positive precipitating antibody against Aspergillus fumigatus. Her chest radiograph and computed tomography revealed infiltrative shadows but not central bronchiectasis. Fibreoptic bronchoscopy detected some mucous plugs which grew Aspergillus fumigatus on culture. We therefore made a diagnosis of allergic bronchopulmonary aspergillosis (ABPA). We treated her using only itraconazole. Her respiratory symptoms, eosinophilia, serum IgE level, and pulmonary infiltration gradually improved, but withdrawal of itraconazole exacerbated her respiratory symptom and laboratory data. Administration of itraconazole again resulted in improvement of her symptoms and laboratory data. We report a case of ABPA without bronchial asthma or central bronchiectasis and refer to our diagnostic rationale. Furthermore, we discuss the decrease of allergens by the eradication of Aspergillus fumigatus in the airway with itraconazole to reduce the allergic reaction and improve the clinical symptoms.     

Serum immunoglobulin levels in pulmonary allergic aspergillosis and certain other lung diseases, with special reference to immunoglobulin E

A study of serum immunoglobulin concentrations was made with serum obtained from patients with hypersensitivity lung diseases and from other patients with pulmonary disease of various types. Serum immunoglobulin E (IgE) was measured by a radioimmunoassay technic and demonstrated marked elevations in patients with the clinical and laboratory findings of pulmonary allergic aspergillosis, especially during the acute phase of pulmonary infiltration. In contrast, serum IgE levels were not elevated in patients with pigeon breeders' disease, farmer's lung or with pulmonary infiltrates and eosinophilia associated with polyarteritis nodosum. The serum IgE level in the acute cases of pulmonary allergic aspergillosis was sufficiently high to detect by routine gel double diffusion analysis using anti-IgE. This may constitute a useful diagnostic aid in recognizing the disease.     

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.     

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。     

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.     

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.     

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.     

9例变应性支气管肺曲菌病误诊为肺结核临床分析

目的探讨变态反应性支气管肺曲菌病(ABPA)的临床特点及误诊为肺结核的原因。方法分析9例误诊为肺结核的ABPA的临床表现、发病、影像学表现、诊断和治疗的特点及误诊原因。结果 9例病例均有慢性咳嗽、咳痰,5例有胸闷、喘息,所有病例长时间的误诊。胸部CT显示:单侧和(或)两侧片状浸润影,呈游走,中心性支气管扩张,外周血嗜酸粒细胞增高,血清总IgE高,烟曲菌抗原皮内试验呈速发反应阳性。9例患者用激素及伊曲康唑治疗后症状改善,X线影像学明显吸收。结论 ABPA与肺结核有相似的临床表现和胸部X线影像学表现,临床医生应提高对ABPA的认识。     

Uncertain areas in the diagnosis of allergic bronchopulmonary aspergillosis in patients with asthma

Background and objectiveThe prevalence of allergic bronchopulmonary aspergillosis (ABPA) in patients with bronchial asthma remains unknown. We evaluated the roles of various laboratory tests in the diagnosis of ABPA, including, skin prick test (SPT) for Aspergillus fumigatus (Af), and serum Af specific IgE and IgG antibody measurement.MethodsA total of 50 asthma patients with more than 1000 cell/μL of peripheral blood eosinophils were prospectively collected between January 2007 and September 2011. Evaluations using SPT for Af, serum total IgE and specific IgE antibody to Af by CAP system, IgG antibody to Af by enzyme immunoassay (EIA) or CAP system were performed according to the essential minimal criteria for the diagnosis of ABPA – asthma, immediate cutaneous reactivity to Af, elevated total IgE, and raised Af specific IgE and IgG.ResultsAmong 50 patients, three patients (6.0%) were diagnosed as ABPA, of whom each confirmed five items of the essential minimal diagnostic criteria for the diagnosis of ABPA. Six patients (12.0%) showed negative responses to Af in SPT, but positive responses in specific IgE by CAP system. Eight patients (16.0%) showed negative responses to IgG to Af by CAP system, but positive responses by enzyme immunoassay (EIA).ConclusionsSPT and serum IgE to Af measurement by CAP system should be performed simultaneously. It is reasonable to set up cut-off values in Af specific IgE/IgG by CAP system for the differentiation of ABPA from Af sensitised asthma patients.     

Allergic bronchopulmonary aspergillosis. Apropos of 30 cases

Thirty cases of allergic bronchopulmonary aspergillosis (ABPA) were treated between 1967 and 1981. Developing in patients with a history of chronic asthma (28 of the 30 cases), the initial manifestations of ABPA developed after long periods (an average of 29 years after the onset of the asthma). Chest radiography demonstrated recurrent labile infiltrates in 28 cases, segmental or lobar atelectasis in 7, and proximal bronchiectasis in 16 cases. A circulating eosinophilia was a constant finding, but this varied with time. Immunologic investigations gave positive skin tests, 19 of the 30 patients only presenting a cutaneous reaction delayed until the 6th hour. Total IgE, determined in 18 cases, varied between 600 and 9400 IU/ml (RIST), with identification of specific IgE for Aspergillus in all cases, though to varying degrees. Serial measurements of total IgE levels showed co-existence of an acute progression of the affection and elevated total IgE in 3 cases, but no correlation was found between serum IgE levels and the severity or chronicity of the disease. Physiopathologic features included immediate and partially delayed hypersensitivity to Aspergillus fumigatus. The frequency of ABPA during the course of mucoviscidosis suggests, by analogy, that a local factor may exist which favorizes Aspergillus fumigatus proliferation in patients with ABPA alone.     

Elevated total serum immunoglobulin E (>1000 IU/mL): implications?

Atopic eczema, allergic broncho‐pulmonary aspergillosis, helminthic infections and rare primary immunodeficiencies are known to elevate total serum immunoglobulin E (IgE) above 1000 IU/mL. However, of 352 patients with IgE >1000 IU/mL seen in our hospital over a 5‐year period, less than 50% had these conditions. Markedly elevated IgE levels in the rest of the patients were associated with asthma, allergic rhinitis and food allergy, instances where the test is of limited diagnostic utility.     

Allergic bronchopulmonary aspergillosis.

A case of allergic bronchopulmonary aspergillosis (ABPA) is presented, followed by a discussion of the clinical characteristics, pathogenesis, diagnosis, and management of this disease. Special emphasis is given to clinical pearls and pitfalls for the practicing allergist. ABPA is a hypersensitivity response to Aspergillus antigens in the lung and is distinct from other forms of Aspergillus pulmonary disease. Episodic bronchospasm, expectoration of mucous plugs, and fleeting pulmonary infiltrates are common manifestations of the disease. Several diagnostic schemes for ABPA have been described with varying criteria, which uniformly includes asthma and positive immediate skin-prick test to Aspergillus fumigatus. The mainstay of treatment for ABPA is corticosteroids, which are normally effective.     

The spectrum of pulmonary aspergillosis.

Aspergillus species can produce a wide range of pulmonary disorders. Classically, pulmonary aspergillosis has been categorized into invasive, saprophytic, and allergic forms, all of which differ in their manifestations and therapy. More recently, however, other types of infection by this fungus have been recognized that do not fit into these traditional categories; an example is semi-invasive (chronic necrotizing) aspergillosis. In fact, these forms have features that are intermediate between those of the invasive and saprophytic types. The various types of aspergillosis can be regarded as constituting a continuous spectrum, ranging from invasive disease in the severely immunosuppressed patient to hypersensitivity reactions such as allergic bronchopulmonary aspergillosis (and bronchocentric granulomatosis) in the hyperreactive patient. Between these extremes are chronic necrotizing disease seen in midly immunocompromised hosts, and the noninvasive aspergilloma, which is due to saprophytic growth within a previously diseased area of lung in an otherwise normal host. Other intermediate forms may be encountered, their behavior being determined by the host immune status in combination with the underlying lung morphology. The radiographic and clinical features of these various forms of pulmonary aspergillosis are reviewed, including the more recently reported forms of infection such as Aspergillus tracheobronchitis and aspergillosis associated with acquired immunodeficiency syndrome and cystic fibrosis. The proposed concept of a disease spectrum is emphasized.     

Specific IgG antibodies (total and subclasses) against Saffron pollen: a study of their correlation with specific IgE and immediate skin reactions

Saffron (Zaaferan), botanical name Crocus sativus, is the most expensive spice in the world. It is derived from the dried stigma and pistil of the purple saffron crocus flowers. Iran is the largest saffron producer accounting for more than 80% of the world's production. Saffron contains an aeroallergen that causes reactive respiratory allergic reactions in atopic subjects. IgG antibody to allergens in the serum of allergic patients is not routinely measured. In this study in order to find out more about mechanism of allergy against saffron pollen, specific antibodies (IgE and IgG, total and subclasses) in atopic subjects were assayed. We used an ELISA assay for measuring specific IgE and IgG against saffron pollen extract in the sera of 38 atopic subjects (test group) and 20 non allergic subjects (control group). The optical densities were compared between allergic subjects and non-allergic individuals. The prick test with saffron pollen extract was used to evaluate the cutaneous and specific antibody responses in the allergic subjects. The correlation was determined by statistical analysis. Specific saffron pollen IgE and IgG subclasses were found significantly higher in the allergic subjects than the control group. The immediate skin reaction was found positive in 70% of the test group. We report here, the existence of a positive correlation between specific IgE and skin reaction by prick test in atopic subjects (R= 0.433). A negative correlation between specific IgE and IgG4 subclass was also found (R= -0.576). These data may be useful to understand the mechanism of allergy to saffron and may help in clarifying clinical manifestations and to prevent IgE production as well as therapeutic application.     

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.     

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.     

Allergic bronchopulmonary candidiasis

A patient had an illness consistent with allergic bronchopulmonary candidiasis. She had asthma, fleeting pulmonary infiltrate, immediate skin reactivity and precipitating antibody against Candida albicans, elevated total serum IgE concentration, elevated IgE and IgG antibody activity against C albicans, and two positive sputum cultures for C albicans. Serial serologic studies showed a significant decrease of serum IgE levels and IgE antibody activity after corticosteroid treatment.