Allergic bronchopulmonary aspergillosis
- Praveen Akuthota, MD
Praveen Akuthota, MD
- Assistant Professor of Medicine
- Harvard Medical School
- Peter F Weller, MD, FACP
Peter F Weller, MD, FACP
- Editor-in-Chief — Infectious Diseases
- Section Editor — Tropical Medicine
- William Bosworth Castle Professor of Medicine
- Harvard Medical School
- Professor of Immunology and Infectious Diseases
- Harvard T. H. Chan School of Public Health
- Section Editors
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
- Peter J Barnes, DM, DSc, FRCP, FRS
Peter J Barnes, DM, DSc, FRCP, FRS
- Editor-in-Chief — Pulmonary, Critical Care, and Sleep Medicine
- Section Editor — Asthma
- Professor of Medicine
- National Heart and Lung Institute, Imperial College, London
- Deputy Editors
- Helen Hollingsworth, MD
Helen Hollingsworth, MD
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor of Medicine
- Boston University School of Medicine
- Anna R Thorner, MD
Anna R Thorner, MD
- Deputy Editor — Infectious Diseases
- Assistant Clinical Professor of Medicine (Part-time)
- Harvard Medical School
Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction, often in patients with asthma or cystic fibrosis (CF), that occurs when bronchi become colonized by Aspergillus species [1-4]. Repeated episodes of bronchial obstruction, inflammation, and mucoid impaction can lead to bronchiectasis, fibrosis, and respiratory compromise .
The pathophysiology, diagnosis, and treatment of ABPA will be reviewed here. General issues related to bronchiectasis are discussed separately. (See "Clinical manifestations and diagnosis of bronchiectasis in adults" and "Treatment of bronchiectasis in adults".)
The pathogenesis of allergic bronchopulmonary aspergillosis (ABPA) remains incompletely understood [5,6]. There is no relation between the intensity of exposure to airborne Aspergillus spores and rates of sensitization to the fungus as measured by skin testing . Although all spores that are inhaled in sufficient quantities can behave as allergens, the normally low level of IgG against fungal antigens in the circulation and the low antifungal secretory IgA in bronchoalveolar fluid suggest that healthy individuals are able to effectively eliminate fungal spores [8,9]. In contrast, exposure of atopic individuals to fungal spores or mycelial fragments results in the formation of IgE and IgG antibodies.
T cells also play an important role in ABPA. There are increases in Th2 CD4+ cell responses to Aspergillus antigens both in the bronchoalveolar lymphoid tissue and systemically . Aspergillus-responsive T cells generate cytokines interleukin (IL)-4, IL-5, and IL-13, which in turn account for the increases in eosinophilia and IgE in ABPA. In one study, T cell clones specific to the Asp f 1 antigen of A. fumigatus were established from the peripheral blood of three patients with ABPA . The majority of these clones were CD4+ cells of the Th2 phenotype, which produce IL-4 and IL-5 . The response to the Asp f 1 antigen was HLA restricted, being mediated exclusively by either HLA-DR2 or HLA-DR5 and was restricted to specific T cell receptor V-beta chains . In addition, there is increased sensitivity of B cells, T cells, NK cells, and eosinophils to IL-4 .
In another study, the costimulatory molecule OX40 ligand was crucial for driving Th2 responses to A. fumigatus in the CD4+ cells of patients with cystic fibrosis (CF) and ABPA . Heightened Th2 reactivity in these patients correlated with lower mean serum vitamin D levels.
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- CLINICAL FEATURES
- Staging system
- Radiographic features
- - High-resolution computed tomography
- Pulmonary function testing
- ABPA versus conventional asthma
- ABPA in cystic fibrosis
- ABPA and pulmonary eosinophilia
- ABPA and bronchiectasis
- Antifungal agents
- - Approach to antifungal therapy
- Duration of therapy
- Other interventions
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS