Aspergillosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Christeen Henen, M.D. [2]
Allergic Bronchopulmonary Aspergillosis (ABPA)
- Allergic bronchopulmonary aspergillosis is both a type I (atopic) and type III hypersensitivity response.
Type I Hypersensitivity
- Precipitating antibodies incite a type I acute hypersensitivity reaction that results in the release of immunoglobulin E (IgE) and immunoglobulin G (IgG).
- Immunoglobulin release induces mast cell degranulation, bronchoconstriction, and increased capillary permeability.
Type III Hypersensitivity
- Immune complexes and inflammatory cells are deposited within the bronchial mucosa leading to tissue necrosis and eosinophilic infiltrate, a type III reaction.
- The subsequent damage to the bronchial wall causes (proximal) bronchiectasis. Repeated acute episodes left untreated can result in progressive pulmonary fibrosis that is often seen in the upper zones and can give rise to a similar radiological appearance to that produced by tuberculosis.
Pulmonary Tissue Destruction
- Aspergillus is not usually cleared from the airways despite the immune response.
- Proteolytic enzymes are released by the immune cells, and toxins are released by the fungi. Together these result in bronchiectasis, most pronounced in the central parts of the airways.
- Repeated acute episodes result in progressive pulmonary fibrosis that is often prominent in the upper zones that is radiologically similar to tuberculosis.
Invasive Aspergillosis
Invasive Aspergillus infection almost always occurs in patients who are immunosuppressed with underlying lung disease, on an immunosuppressive drug therapy, or immunodeficiency. Aspergillus hyphae are histologically distinct from other fungi in that the hyphae have frequent septae, which branch at 45° angles. The hyphae are best visualized in tissue with silver stains. Although many species of Aspergillus have been isolated in nature, A fumigatus is the most common cause of infection in humans. A flavus and A niger are less common. Likely, this relates to the ability of A fumigatus, but not most other Aspergillus species, to grow at normal human body temperature. Human host defense against the inhaled spores begins with the mucous layer and the ciliary action in the respiratory tract. Macrophages and neutrophils encompass, engulf, and eradicate the fungus. However, many species of Aspergillus produce toxic metabolites that inhibit macrophage and neutrophil phagocytosis. Corticosteroids also impair macrophage and neutrophil function. Underlying immunosuppression (eg, HIV disease, chronic granulomatous disease, pharmacologic immunosuppression) also contributes directly to neutrophil dysfunction or decreased numbers of neutrophils. In individuals who are immunosuppressed, vascular invasion is much more common and may lead to infarction, hemorrhage, and necrosis of lung tissue. Persons with CNPA typically have granuloma formation and alveolar consolidation. Hyphae may be observed within the granulomata.
Aspergilloma
The most common place affected by aspergillomas is the lung. Aspergillus fumigatus, the most common species, is typically inhaled as small (2 to 3 micrometer) spores which do not affect people without underlying lung or immune system disease. However, people who have pre-existing lung problems, especially the cavities typically caused by tuberculosis, are at risk for developing aspergillomata. The fungus settles in a cavity and is able to grow free from interference because the immune system is unable to penetrate into the cavity. As the fungus multiplies, it forms a ball, which incorporates dead tissue from the surrounding lung, mucus, and other debris.[2]