Allergic Bronchopulmonary Aspergillosis (ABPA)

Aspergillus colonization in patients with ABPA prompts vigorous antibody (IgE and IgG) and cell-mediated immune responses (type I, III, and IV hypersensitivity reactions) to Aspergillus antigens, leading to frequent, recurrent asthma exacerbations. Over time, the immune reactions, combined with direct toxic effects of the fungus, lead to airway damage with dilation and, ultimately, bronchiectasis and fibrosis. The disorder is characterized histologically by mucoid impaction of airways, eosinophilic pneumonia, infiltration of alveolar septa with plasma and mononuclear cells, and an increase in the number of bronchiolar mucous glands and goblet cells.

Rarely, other fungi, such as Penicillium, Candida, Curvularia, Helminthosporium, and Drechslera, cause an identical syndrome called allergic bronchopulmonary mycosis in the absence of underlying asthma or cystic fibrosis.

Aspergillus is present intraluminally but is not invasive. Thus, ABPA must be distinguished from the following:

• Invasive aspergillosis, which occurs in immunocompromised patients

• Aspergillomas, which are collections of Aspergillus in patients with established cavitary lesions or cystic airspaces

• Aspergillus pneumonia, which is rare and occurs in patients who take low doses of prednisone long term (eg, patients with pneumonia, which is rare and occurs in patients who take low doses of prednisone long term (eg, patients withchronic obstructive pulmonary disease)

Overlap syndromes with ABPA and the other conditions have also been reported (1).

Symptoms are those of asthma or pulmonary cystic fibrosis exacerbations (ie, dyspnea, wheezing, and chest tightness), with the addition of cough productive of dirty-green or brown plugs of mucus and, occasionally, hemoptysis. Fever, headache, and anorexia are common systemic symptoms in severe disease. Signs are those of airway obstruction, specifically, wheezing and prolonged expiration on examination, which are indistinguishable from asthma exacerbations.

• History of asthma or cystic fibrosis

• Chest radiography or high-resolution CT

• Skin prick test with Aspergillus antigen

• Aspergillus precipitins in blood

• Positive sputum culture for Aspergillus species (or, rarely, other fungi)

• Serum IgE levels

• Blood eosinophil counts

The diagnosis is suspected in patients with asthma or cystic fibrosis with recurrent exacerbations, migratory (also called fleeting) or nonresolving infiltrates on chest radiographs (often due to atelectasis resulting from mucoid plugging and bronchial obstruction), evidence of bronchiectasis on imaging studies, sputum cultures positive for A. fumigatus, or notable peripheral eosinophilia.

Allergic Bronchopulmonary Aspergillosis

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By permission of the publisher. From Groll A, Walsh T. In Atlas of Infectious Diseases: Fungal Infections. Edited by GL Mandell and RD Diamond. Philadelphia, Current Medicine, 2000.

Allergic Bronchopulmonary Aspergillosis (Bronchiectasis)

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By permission of the publisher. From Coakley R, Boucher R, Fiel S, et al. In Bone's Atlas of Pulmonary and Critical Care Medicine. Edited by J Crapo. Philadelphia, Current Medicine, 2005.

Several criteria have been proposed for the diagnosis of ABPA (see table Diagnostic Criteria for Allergic Bronchopulmonary Aspergillosis), but in practice not all criteria are assessed in every case.

In general, when clinical suspicion for ABPA is high, a skin prick test with Aspergillus antigen is recommended. An immediate wheal-and-flare reaction on skin prick testing (or if skin prick testing is unavailable) should prompt further testing of serum total IgE, A. fumigatus–specific IgE, and A. fumigatus–specific IgG antibodies done via  enzyme-linked immunosorbent assay (ELISA) (or Aspergillus precipitins via immunodiffusion technique or similar). An elevated total IgE level > 1000 ng/mL (or 417 IU/mL) along with positive precipitins supports the diagnosis (1). The diagnosis can be established by detecting elevated A. fumigatus–specific IgE (> 0.35 kU/L) along with the presence of A. fumigatus–specific IgG antibodies. A. fumigatus–specific IgE is highly sensitive and A. fumigatus–specific IgG is highly specific for ABPA (2). Direct A. fumigatus–specific IgG measurement is preferred to Aspergillus precipitins (3). 

Sputum and bronchoscopic cultures for Aspergillus have a low sensitivity and specificity for the diagnosis of ABPA and are not included as diagnostic criteria.

Peripheral eosinophilia is common in untreated patients and ranges from about 10% to 25% of the differential count in patients who have not received oral glucocorticoids (4). Whenever test results diverge, such as when serum IgE is elevated but no A. fumigatus–specific immunoglobulins are found, testing should be repeated and the patient should be monitored over time to definitively establish or exclude the diagnosis.

• Systemic glucocorticoids

• Sometimes antifungal medications

Treatment is based on disease stage (see table Stages of Allergic Bronchopulmonary Aspergillosis). The mainstay of therapy is systemic (oral) glucocorticoids and protracted use of antifungal agents (azoles) which are glucocorticoid-sparing agents (1).

Stage I is treated with prednisone orally once a day for 2 to 4 weeks, then tapered over 4 to 6 months. Chest radiographs, blood eosinophil counts, and IgE levels should be checked quarterly for improvement, defined as resolution of infiltrates, Stage I is treated with prednisone orally once a day for 2 to 4 weeks, then tapered over 4 to 6 months. Chest radiographs, blood eosinophil counts, and IgE levels should be checked quarterly for improvement, defined as resolution of infiltrates,≥ 50% decline in eosinophils, and 33% decline in IgE. Patients who achieve stage II disease require annual monitoring only.

Patients with stage II ABPA who relapse (stage III) are given another trial of prednisone. Patients with stage I or stage III disease who do not improve with prednisone (stage IV) are candidates for antifungal treatment. Itraconazole orally twice a day for 16 weeks is recommended as a substitute for prednisone and as a glucocorticoid-sparing medication. Alternative antifungals (voriconazole, posaconazole, or inhaled amphotericin B) may be considered if Patients with stage II ABPA who relapse (stage III) are given another trial of prednisone. Patients with stage I or stage III disease who do not improve with prednisone (stage IV) are candidates for antifungal treatment. Itraconazole orally twice a day for 16 weeks is recommended as a substitute for prednisone and as a glucocorticoid-sparing medication. Alternative antifungals (voriconazole, posaconazole, or inhaled amphotericin B) may be considered ifitraconazole is ineffective or not tolerated. In patients with stage V disease, symptoms and complications are usually treated supportively.

Itraconazole therapy requires checking drug levels and monitoring liver enzymes, triglyceride, and potassium levels.Itraconazole therapy requires checking drug levels and monitoring liver enzymes, triglyceride, and potassium levels.

Emerging data indicate the clinical benefit of biologic therapies such as omalizumab, dupilumab, and mepolizumab in allergic bronchopulmonary aspergillosis (Emerging data indicate the clinical benefit of biologic therapies such as omalizumab, dupilumab, and mepolizumab in allergic bronchopulmonary aspergillosis (2).

All patients should be optimally treated for their underlying asthma or cystic fibrosis. In addition, patients taking long-term glucocorticoids should be monitored for complications, such as cataracts, diabetes mellitus, and osteoporosis, and possibly prescribed treatments to prevent bone demineralization and Pneumocystis jirovecii lung infection.