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)
For an unknown reason, patients with allergic bronchopulmonary aspergillosis develop a hypersensitivity response, both a type I response (atopic, with formation of immunoglobulin E or IgE) and a type III hypersensitivity response (with formation of immunoglobulin G or IgG). The reaction of immunoglobulin E with Aspergillus antigens results in mast cell degranulation with bronchoconstriction and increased capillary permeability. Immune complexes (a type III reaction) and inflammatory cells are then deposited within the mucous membranes of the airways, leading to necrosis (tissue death) and an eosinophilic infiltrate. Type 2 T helper cells secreting interleukin 4 and interleukin 5, and attraction of neutrophils by interleukin 8 seem to play an important role.[citation needed]
In spite of this pronounced immune reaction, the fungus is not cleared from the airways. 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 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.
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]