Allergic Bronchopulmonary Aspergillosis (ABPA)

For unclear reasons, colonization in these patients 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

• 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)

Although the distinction can be clear, overlap syndromes have been reported.

Symptoms are those of asthma or pulmonary cystic fibrosis exacerbation, with the addition of cough productive of dirty-green or brown plugs 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, which are indistinguishable from asthma exacerbation.

• History of asthma

• Chest x-ray or high-resolution CT

• Skin prick test with Aspergillus antigen

• Aspergillus precipitins in blood

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

• IgE levels

• Blood eosinophil count

The diagnosis is suspected in patients with asthma or cystic fibrosis with recurrent exacerbations, migratory or nonresolving infiltrates on chest x-ray (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 (see table Diagnostic Criteria for Allergic Bronchopulmonary Aspergillosis), but in practice not all criteria are assessed in every case.

Several diagnostic criteria exist. In general, when clinical suspicion for ABPA is high, a skin prick test with Aspergillus antigen is recommended. If skin prick testing is performed, an immediate wheal-and-flare reaction suggests the diagnosis. Regardless of skin testing results, further testing of serum total IgE, A. fumigatus–specific IgE, and A. fumigatus–specific IgG antibodies done via ELISA (or Aspergillus precipitins via immunodiffusion technique or similar) should be performed. An elevated total IgE level greater than 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.

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.

• PrednisonePrednisone

• Sometimes antifungal drugs

Treatment is based on disease stage (see table Stages of Allergic Bronchopulmonary Aspergillosis).

Stage I is treated with prednisone 0.5 to 0.75 mg/kg orally once a day for 2 to 4 weeks, then tapered over 4 to 6 months. Chest x-ray, blood eosinophil count, and IgE levels should be checked quarterly for improvement, defined as resolution of infiltrates, Stage I is treated with prednisone 0.5 to 0.75 mg/kg orally once a day for 2 to 4 weeks, then tapered over 4 to 6 months. Chest x-ray, blood eosinophil count, 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.

Stage II patients who relapse (stage III) are given another trial of prednisone. Stage I or III patients who do not improve with prednisone (stage IV) are candidates for antifungal treatment. Itraconazole 200 mg orally twice a day for 16 weeks is recommended as a substitute for prednisone and as a corticosteroid-sparing drug. Also, merging data address the use of biologic therapies such as omalizumab as steroid-sparing drugs. Symptoms and complications for stage V patients are usually treated supportively. Stage II patients who relapse (stage III) are given another trial of prednisone. Stage I or III patients who do not improve with prednisone (stage IV) are candidates for antifungal treatment. Itraconazole 200 mg orally twice a day for 16 weeks is recommended as a substitute for prednisone and as a corticosteroid-sparing drug. Also, merging data address the use of biologic therapies such as omalizumab as steroid-sparing drugs. Symptoms and complications for stage V patients are usually treated supportively.

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

All patients should be optimally treated for their underlying asthma or cystic fibrosis. In addition, patients taking long-term corticosteroids 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.