Aspergillosis 

  • Author: Eloise M Harman, MD; Chief Editor: Zab Mosenifar, MD   more...
 
Updated: Sep 16, 2011
 

Background

Aspergillus species are ubiquitous molds found in organic matter. Although more than 100 species have been identified, the majority of human illness is caused by Aspergillus fumigatus and Aspergillus niger and, less frequently, by Aspergillus flavus and Aspergillus clavatus. The transmission of fungal spores to the human host is via inhalation. Also see the eMedicine articles Aspergillosis (dermatology focus), Aspergillosis (pediatric focus), and Aspergillosis, Thoracic (radiology focus).

Aspergillus may cause a broad spectrum of disease in the human host, ranging from hypersensitivity reactions to direct angioinvasion. Aspergillus primarily affects the lungs, causing 4 main syndromes, including allergic bronchopulmonary aspergillosis (ABPA), chronic necrotizing Aspergillus pneumonia (or chronic necrotizing pulmonary aspergillosis [CNPA]), aspergilloma, and invasive aspergillosis. However, in patients who are severely immunocompromised, Aspergillus may hematogenously disseminate beyond the lung, potentially causing endophthalmitis, endocarditis, and abscesses in the myocardium, kidney, liver, spleen, soft tissue, and bone. Aspergillus is second to Candida species as a cause of fungal endocarditis. Aspergillus -related endocarditis and wound infections occur in the context of cardiac surgery.

ABPA is a hypersensitivity reaction to A fumigatus colonization of the tracheobronchial tree and occurs in conjunction with asthma and cystic fibrosis (CF). Allergic fungal sinusitis may also occur alone or with ABPA. Bronchocentric granulomatosis and malt worker's lung are 2 hypersensitivity lung diseases that are caused by Aspergillus species, but they are rare.

An aspergilloma is a fungus ball (mycetoma) that develops in a preexisting cavity in the lung parenchyma. Underlying causes of the cavitary disease may include treated tuberculosis or other necrotizing infection, sarcoidosis, CF, and emphysematous bullae. The ball of fungus may move within the cavity but does not invade the cavity wall; however, it may cause hemoptysis.

CNPA is a subacute process usually found in patients with some degree of immunosuppression, most commonly that associated with underlying lung disease, alcoholism, or long-term corticosteroid therapy. Because it is uncommon, CNPA often remains unrecognized for weeks or months and can cause a progressive cavitary pulmonary infiltrate.

Invasive aspergillosis is a rapidly progressive, often fatal infection that occurs in patients who are severely immunosuppressed, including those who are profoundly neutropenic, those who have received bone marrow or solid organ transplants, and patients with advanced AIDS[1] or chronic granulomatous disease. This infectious process is characterized by invasion of blood vessels, resulting in multifocal infiltrates, which are often wedge-shaped, pleural-based, and cavitary. Dissemination to other organs, particularly the central nervous system, may occur.

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Pathophysiology

Aspergillus causes a spectrum of disease, from colonization to hypersensitivity reactions to chronic necrotizing infections to rapidly progressive angioinvasion, often resulting in death. Rarely found in individuals who are immunocompetent, invasive Aspergillus infection almost always occurs in patients who are immunosuppressed by virtue of underlying lung disease, 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.

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Epidemiology

Frequency

United States

Although allergy to Aspergillus, as manifested by a positive skin test reaction to Aspergillus antigen, is present in approximately 25% of people with asthma and 50% of patients with CF, ABPA is much less common. From surveys and an ABPA registry, 0.25-0.8% of people with asthma and approximately 7% of patients with CF are estimated to have ABPA. The incidence of ABPA in people with asthma who are steroid-dependent or have associated central bronchiectasis is higher, estimated at 7-10%.

CNPA is rare. Frequently undetected in life and found at autopsy, the frequency of chronic necrotizing Aspergillus pneumonia may be underestimated.

The frequency of invasive aspergillosis reflects disease states and treatments that result in prolonged neutropenia and immunosuppression. Invasive aspergillosis is estimated to occur in 5-13% of recipients of bone marrow transplants, 5-25% of patients who have received heart or lung transplants, and 10-20% of patients who are receiving intensive chemotherapy for leukemia. Although it has been described in individuals who are immunocompetent, invasive aspergillosis is exceedingly uncommon in this population.

Aspergilloma is not rare in patients with chronic cavitary lung disease and CF. In one survey of patients with cavitary lung disease due to tuberculosis, 17% developed aspergilloma.

International

The incidence of ABPA in people with asthma appears to be higher in Great Britain compared with the United States.

Mortality/Morbidity

Invasive aspergillosis is associated with significant mortality, with a rate of 30-95%.

Chronic necrotizing Aspergillus pneumonia has a reported mortality rate of 10-40%, but rates as high as 100% have been noted because it often remains unrecognized for prolonged periods.

Aspergilloma is associated with hemoptysis, which may be severe and life threatening.

ABPA may cause problems with asthma control. Repeated episodes of ABPA may cause widespread bronchiectasis and resultant chronic fibrotic lung disease.

Age

The age distribution of aspergillosis is consistent with that of the various comorbid conditions with which it is associated.

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Contributor Information and Disclosures
Author

Eloise M Harman, MD  Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, University of Florida College of Medicine

Eloise M Harman, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American Medical Women's Association, American Thoracic Society, Phi Beta Kappa, and Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Oleh Wasyl Hnatiuk, MD  Program Director, National Capital Consortium, Pulmonary and Critical Care, Walter Reed Army Medical Center; Associate Professor, Department of Medicine, Uniformed Services University of Health Sciences

Oleh Wasyl Hnatiuk, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H  Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD  Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society

Disclosure: Nothing to disclose.

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