Aspergillosis refers to several forms of disease caused by a fungus in the genus Aspergillus. Aspergillosis fungal infections can occur in the ear canal, eyes, nose, sinus cavities, and lungs. In some individuals, the infection can even invade bone and the membranes that enclose the brain and spinal cord (meningitis ).
Aspergillosis is primarily an infection of the lungs caused by the inhalation of airborne spores of the fungus Aspergillus. Spores are the small particles that most fungi use to reproduce. Although virtually everyone is exposed to this fungus in their daily environment, it rarely causes disease. When Aspergillus does cause disease, however, it usually occurs in those individuals with weakened immune systems (immunocompromised) or who have a history of respiratory ailments. Because it does not present distinctive symptoms, aspergillosis is generally thought to be under-diagnosed and underreported. Furthermore, many patients with the more severe forms of aspergillosis tend to have multiple, complex health problems, such as AIDS or a blood disorder like leukemia, which can further complicate diagnosis and treatment.
Once considered particularly rare, the incidence of reported aspergillosis has risen somewhat with the development of more sophisticated methods of diagnosis and advances made in other areas of medicine, such as with the increased use of certain chemotherapeutic and corticosteroid drugs that are extremely useful in treating various types of cancer but that decrease the individual's immune response, making them more susceptible to other diseases like aspergillosis.
Our advanced ability to perform tissue and organ transplants has also increased the number of people vulnerable to fungal infections. Transplant recipients, particularly those receiving bone marrow or heart transplants, are highly susceptible to Aspergillus, which may be circulating in the hospital air.
Antibody— A specific protein produced by the immune system in response to a specific foreign protein or particle called an antigen.
Aspergilloma— A ball or mass made of Aspergillus fungi that can form in the lungs of patients with suppressed immune systems.
Bronchial lavage— A procedure that involves repeatedly washing the inside of the bronchial tubes of the lung.
Hemoptysis— Spitting up blood from the lungs or sputum stained with blood.
Immunocompromised— A state in which the immune system is suppressed or not functioning properly.
Meningitis— Inflammation of the membranes covering the brain and spinal cord, called the meninges.
Nebulizer— A device that produces an extremely fine mist that is readily inhalable.
Spores— The small, thick-walled reproductive structures of fungi.
Sputum— Mucus and other matter coughed up from the airways.
Aspergillosis can be a serious, potentially deadly threat for two primary reasons:
- Aspergillosis usually occurs in those individuals who are already ill or have weakened immune systems, such as patients who have undergone chemotherapy for cancer.
- None of the currently available antifungal drugs are reliably effective against Aspergillus.
Causes and symptoms
Airborne Aspergillus spores enter the body primarily through inhalation but can also lodge in the ear or eye. Normally functioning immune systems are generally able to cope without consequent development of aspergillosis.
It is important to make distinctions between the various forms of aspergillosis, as the treatment and prognosis varies considerably among types. Aspergillosis as a diagnosis refers to three general forms:
- Allergic bronchopulmonary aspergillosis (ABPA) is seen in patients with long-standing asthma, particularly in patients taking oral corticosteroids for a long period of time. This is usually the least serious and most treatable form.
- Aspergilloma refers to the mass formed when fungal spores settle into or colonize areas of the lung that have been pitted and scarred as a result of tuberculosis or prior pneumonia. There are several available treatments, although the success rate varies with each treatment.
- Invasive fungal infection refers to rare cases in which the fungus spreads throughout the body via the blood stream and invades other organ systems. Once established, invasive fungal infections are extremely difficult to cure and, as a result, the associated death rate is extremely high.
Aspergillosis can be quite difficult to diagnose because the symptoms, such as coughing and wheezing, if present at all, are common to many respiratory disorders. Furthermore, blood and sputum cultures are not very helpful. The presence of Aspergillus is so common, even in asthmatics, that a positive culture alone is insufficient for a diagnosis. Other, potentially more useful, screening tools include examining the sample obtained after repeatedly washing the bronchial tubes of the lung with water (bronchial lavage), but examining a tissue sample (biopsy) is the most reliable diagnostic tool. Researchers are currently attempting to develop a practical, specific, and rapid blood test that would confirm Aspergillus infection.
Signs of ABPA include a worsening of bronchial asthma accompanied by a low-grade fever. Brown flecks or clumps may be seen in the sputum. Pulmonary function tests may show decreased blood flow, suggesting an obstruction within the lungs. Elevated blood levels of an antibody produced in response to Aspergillus and of certain immune system cells may indicate a specific allergic-type immune system response.
A fungal mass (aspergilloma) in the lung usually does not produce clear symptoms and is generally diagnosed when seen on chest x rays. However, 70% or more of patients spit up blood from the lungs (hemoptysis ) at least once, and this may become repetitive and serious. Hemoptysis, then, is another indication that the patient may be suffering from an aspergilloma.
In patients with lowered immune systems who are at risk for developing invasive aspergillosis, the physician may use a combination of blood culture with visual diagnostic techniques, such as computed tomography scans (CT) and radiography, to arrive at a likely diagnosis.
The treatment method selected depends on the form of aspergillosis. ABPA can usually be treated with many of the same drugs used to treat asthma, such as systemic steroids. Long-term therapy may be required, however, to prevent recurrence. Antifungal agents are not recommended in the treatment of ABPA. In cases of aspergilloma, it may become necessary to surgically remove or reduce the size of a fungal mass, especially if the patient continues to spit up blood. In aspergillosis cases affecting the nose and nasal sinuses, surgery may also be required.
In non-ABPA cases, the use of antifungal drugs may be indicated. In such cases, amphotericin B (Fungizone) is the first-line therapy. The prescribed dose will depend on the patient's condition but usually begins with a small test dose and then escalates. Less than one-third of patients are likely to respond to amphotericin B, and its side effects often limit its use. For patients who do not respond to oral amphotericin B, another option is a different formulation of the same drug called liposomal amphotericin B.
For patients who fail to respond or who cannot tolerate amphotericin B, another drug called itraconazole (Sporanox), given 400-600 mg daily, has also been approved. Treatment generally lasts about 3 months. Giving itraconazole can produce adverse reactions if prescribed in combination with certain other drugs by increasing the concentrations of both drugs in the blood and creating a potentially life-threatening situation. Even antacids can significantly affect itraconazole levels. As a result, drug levels must be continually monitored to ensure that absorption is occurring at acceptable levels.
Two other methods of treatment are being studied: direct instillation of an antifungal agent into the lungs and administration of antifungals using a nebulizer. Instilling or injecting amphotericin B or itraconazole directly into the lung cavity or into the fungal ball (aspergilloma) itself has been helpful in stopping episodes of hemoptysis, but not in preventing future recurrences. Furthermore, many patients with aspergillomas are poor risks for surgery because their lung function is already compromised. As a result, instillation of a fungal agent should only be considered in those who have significant hempotysis.
A popular method of treating some respiratory disorders is to add a liquid drug to another carrier liquid and aerosolize or produce a fine mist that can be inhaled into the lungs through a device called a nebulizer. However, this has not yet been shown to improve the patient's condition in cases of aspergillosis, possibly because the drug is not reaching the aspergilloma.
At this point, preventative therapy for aspergillosis is not suggested for susceptible individuals, primarily because overuse of the drugs used to fight fungal infections may lead to the development of drug-resistant aspergillosis against which current antifungal drugs are no longer effective.
The likelihood of recovery from aspergillosis depends on any underlying medical conditions, the patient's general health, and the specific type of aspergillosis. If the problem is based on an allergic response, as in ABPA, the patient will likely respond well to systemic steroids.
Patients who require lung surgery, especially those who have problems with coughing up blood, have a mortality rate of about 7-14%, and complications or recurrence may result in a higher overall death rate. However, by treating aspergilloma with other, non-surgical methods, that risk rises to 26%, making surgery a better option in some cases.
Unfortunately, the prognosis for the most serious form, invasive aspergillosis, is quite poor, largely because these patients have little resilience due to their underlying disorders. Death rates have ranged from about 50% in some studies to as high as 95% for bone-marrow recipients and patients with AIDS. The course of the illness can be rapid, resulting in death within a few months of diagnosis.
Fungal infection by Aspergillus presents a major challenge, particularly in the patient with a suppressed immune system (immunocompromised). Hospitals and government health agencies continually seek ways to minimize exposure for hospitalized patients. Practical suggestions are minimal but include moving leaf piles away from the house. Unfortunately, overall avoidance of this fungus is all but impossible because it is present in the environment virtually everywhere. Research efforts are being directed at enhancing patients' resistance to Aspergillus rather than trying to eliminate exposure to the fungus. Given the growing number of people with immune disorders or whose immune systems have been suppressed in the course of treating another disease, research and clinical trials for new antifungal agents will be increasingly important in the future.
American College of Allergy, Asthma, and Immunology. 85 West Algonquin Road, Suite 550, Arlington Heights, IL 60005. 〈http://allergy.mcg.edu〉.
"Lung, Allergic and Immune Diseases: Mold Allergy: Prevention Techniques." National Jewish Medical and Research. 〈http://nationaljewish.org/main.html〉.
Office of Rare Diseases (ORD) at National Institutes of Health, Bldg. 31,1BO3, Bethesda, MD 20892-2082. (301) 402-4336 〈http://rarediseases.info.nih.gov/ord〉.
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