Aspergilloma

What is Aspergilloma?

Aspergilloma and Chronic Cavitary Pulmonary Aspergillosis (CCPA) refer to situations where inactive, harmless organisms settle in pre-existing cavities in the lung tissue. These are just two conditions in a larger group known as Chronic Pulmonary Aspergillosis (CPA), which also includes chronic fibrotic pulmonary aspergillosis, aspergillus nodules, and subacute invasive aspergillosis. However, these conditions can sometimes get mixed up due to similarities in their symptoms and appearances in medical imaging, especially when comparing studies from different regions. This confusion also extends to their treatment as methods vary and there’s a lack of comprehensive, randomized studies.

Diagnosing and treating these long-lasting fungal infections is tricky. It’s difficult to distinguish them from other lung diseases just based on imaging results. Now, consider that CPA often develops in already diseased lungs, it’s challenging to determine whether the abnormalities shown in the images are caused by the fungus or the pre-existing lung disease.

Leading health organizations like the European Society for Clinical Microbiology and Infectious Diseases, the European Respiratory Society, and The Infectious Diseases Society of America have developed some consensus definitions for these conditions in order to streamline diagnosis and treatment:

Simple Aspergilloma refers to a single cavity in the lungs containing a fungal mass, and the patient has minor symptoms or none at all. Severe cases of Aspergilloma can develop into Chronic Cavitary Pulmonary Aspergillosis, presenting as multiple lung cavities, sometimes with fungal masses present, causing notable symptoms. Chronic Fibrosing Pulmonary Aspergillosis, another form of CPA, can result in severe fibrotic destruction of the lungs.

Additionally, an Aspergillus Nodule is an unusual type of CPA which presents as one or more nodules in the lung, which may mimic other diseases and can typically only be verified by examining a tissue sample. Subacute Invasive Aspergillosis is a form of invasive infection that develops over several months, particularly in patients with compromised immune systems.

However, these definitions aren’t exclusive. A patient’s health condition may evolve and fit into multiple categories over time. The exact causes contributing to this transition aren’t fully understood but may involve a mix of immune function, response to treatment, and the severity of preexisting lung diseases. This discussion will mainly focus on Pulmonary Aspergilloma and CCPA, including conditions such as aspergilloma, pulmonary mycetoma, and fungus ball, which describe the chronic presence of the Aspergillus species within pre-existing lung cavities.

What Causes Aspergilloma?

The Aspergillus fungus can be found pretty much everywhere in our environment. It’s a type of fungus that grows in damp places like soil, plants, and rotting vegetables. Despite needing a moist environment to thrive, the spores of this fungus disperse more easily in dry and dusty spaces like hay barns and compost piles. The most common type of this fungus that affects humans is Aspergillus fumigatus, though other types like A niger, A flavus, and A oxyzae can also cause diseases in humans.

This fungus can specifically cause lung diseases, including aspergilloma and CCPA, especially in people who already have certain lung conditions. Some of the risk factors for these diseases include:

* Lung tuberculosis (TB)
* Non-tuberculosis mycobacterial infection (NTM)
* Cystic fibrosis
* Chronic bronchiectasis
* Pneumoconiosis
* Pulmonary cavity after an infarction or radiation
* Sarcoidosis
* Lung cysts or bullae
* Chronic lung abscess
* Lung cancer
* Ankylosing spondylitis
* Allergic bronchopulmonary aspergillosis (ABPA)

But it’s not just lung conditions that make someone more likely to get these illnesses. People with other chronic health issues, or weakened immune systems are also at risk. This includes:

* Malnutrition
* Chronic obstructive pulmonary disease (COPD)
* Chronic liver disease
* After organ or stem cell transplants
* Chemotherapy
* Neutropenia
* Extended use of corticosteroids
* HIV
* Primary immunodeficiency syndromes

These lung diseases are most likely to occur in people with pre-existing lung diseases, but with a healthy immune system. People with leftover lung cavities from TB have the highest rate worldwide, with about 10% developing aspergilloma. Other high-risk groups include those with non-tuberculous mycobacteria, chronic obstructive pulmonary disease, and lung cancer. It’s also now recognized that SARS-CoV-2 pneumonitis can cause aspergilloma, with several cases reported.

Risk Factors and Frequency for Aspergilloma

Chronic pulmonary aspergillosis (CPA) prevalence varies globally. In developed countries like the United States, it’s rare with less than one case for every 100,000 people. However, in some African countries, it can be much higher, up to 42.9 cases per 100,000 people. This high incidence is likely due to an increased number of lung cavities caused by tuberculosis in these regions, which are often resource-poor.

• About 25% of patients with CPA develop aspergilloma, a type of fungal lung infection.
• Worldwide, an estimated 18 out of every 100,000 people have CPA over a five-year period. This calculates to around 1.2 million patients globally.
• More cases of CPA are reported in Africa, the western Pacific, and Southeast Asia than elsewhere.
• In countries with a low prevalence of tuberculosis, the major risk factor for developing CPA is a lung disease called chronic obstructive pulmonary disease (COPD).
• Aspergilloma occurring without any pre-existing lung disease is quite rare, occurring in about 0.13% of cases.

It’s worth noting that although invasive aspergillus disease – a potentially life-threatening fungal infection – is more common in patients with weak immune systems, it’s not usually seen in patients with HIV.

Signs and Symptoms of Aspergilloma

When it comes to aspergillus-related diseases, certain people are more at risk. Those with a tendency for hypersensitivity can easily develop obstructive bronchopulmonary aspergillosis. Meanwhile, people with weakened immune systems are particularly vulnerable to invasive aspergillus infections, and those with existing lung diseases who have healthy immune systems tend to contract aspergilloma and other forms of Chronic Pulmonary Aspergillosis. That being said, these categories can overlap. For instance, a patient with aspergilloma can also have a hypersensitivity response similar to ABPA. Likewise, a chronic aspergilloma that doesn’t change for several months or years can lead to CCPA, CFPA, and even invasive infections.

Aspergilloma and CCPA can cause a wide range of symptoms, ranging from none at all to extremely severe bleeding in the lungs. It’s also possible that someone with aspergilloma will have symptoms related to their pre-existing lung disease, such as bullous emphysema, bronchiectasis, cavitary TB, cystic fibrosis, lung tumor, or sarcoidosis. The most common symptom is bleeding in the lungs, which happens in 54% to 87.5% of cases. Severe bleeding occurs in about 30% of patients. Factors such as the size of the aspergilloma, the complexity of the lesion, the preexisting lung disease, or previous minor bleeding do not predict the risk of severe bleeding. Rarely, patients might have a fever, although cough, chest pain, fatigue, and weight loss are more common in people with CCPA. If the fungus invades the surrounding lung tissue, it can cause recurring pneumonia, chronic cough, or pulmonary fibrosis.

Testing for Aspergilloma

Aspergilloma and CCPA, both lung conditions, are generally discovered through scan results, particularly for patients already dealing with other lung-related issues. These conditions can even be found by chance in people showing no symptoms. Once these conditions are identified through scans, additional tests can be carried out to help confirm the diagnosis. These can include testing for Aspergillus organisms in the lungs using a bronchoalveolar lavage (BAL), a blood or BAL test for a specific fungal component known as galactomannan, and a test for antibodies specific to Aspergillus in the serum.

Generally, people with a simple aspergilloma don’t have compromised immune systems and display little or no symptoms tied to the fungal mass in their lungs. Suspicion of aspergilloma often arises from chest X-ray or CT scan results in patients being evaluated for symptoms tied to other lung diseases such as TB lung cavities, bronchiectasis, tumors or chronic lung abscess. Specific symptoms like coughing blood, which can be due to the aspergilloma, can also cause the condition to be investigated.

Diagnostic tests usually start with a chest X-ray, which can highlight issues like cavitation, thickening, scarring and the potential presence of a mass within the cavity of the lung. CT scans, however, provide more detailed information and the following findings could be of importance:

* The appearance of a solid round lesion in the cavity
* The “halo” sign of inflammation in the cavity wall
* The air crescent sign, which separates the fungus ball from the wall in all or part of its circumference. This can also be present in other conditions like lung abscess, a hydatid cyst or a condition called granulomatosis with polyangiitis.
* Monod sign observed when the position of the fungus ball within the cavity changes when the patient’s position during imaging also changes.

CT scans help in further understanding the thickness of the cavity wall, structural changes, and inflammation of the area surrounding the aspergilloma, and how close the aspergilloma is to blood vessels. The high parts of either lung are the most usual locations but the top segment of the lower lobe can also be affected.

For CCPA, radiographic findings typically show consolidation areas with one or multiple cavities of varying thicknesses, containing aspergilloma. Thickening of the tissue lining the lungs (pleura) is common.

The finding of Aspergillus organisms in sputum is not necessarily diagnostic because these fungi are found everywhere and can be present in the airway without causing disease. Nevertheless, in patients with characteristic radiographic findings, the organisms’ detection from a BAL can further support the diagnosis. Conversely, the absence of organisms in the culture does not rule out a diagnosis.

The presence of antibodies specific to the fungus Aspergillus in the blood provides strong evidence of CPA when characteristic radiographic features are also present. However, patients from Pakistan, where both A flavus and A fumigatus are common, may test negative unless species-specific tests are used. On the other hand, the galactomannan antigen test, which looks for a key component of the fungal cell wall, has high specificity.

It’s important to note that Aspergilloma and CCPA can co-occur with active lung diseases such as cancer and other types of infectious conditions. Therefore, other potential conditions should be examined when evaluating patients who are presumed to have Aspergilloma and CCPA.

Treatment Options for Aspergilloma

The standardized treatment for Chronic Pulmonary Aspergillosis (CPA) has yet to be established due to the unpredictable nature of the infection and limited understanding of treatment methods. The primary goals of treatment are to reduce symptoms, prevent bouts of hemoptysis (coughing up blood), and halt the progression to pulmonary fibrosis (scarring of lung tissue).

About 10% of simple aspergillomas, a type of lung disease caused by a fungal infection, can get better on their own, but many can lead to severe hemoptysis. It’s also challenging to predict the severity of hemoptysis based on symptoms, aspergilloma size, and co-existing lung diseases.

Surgical removal of the aspergilloma, once thought of as the best treatment, can carry high risks, and antifungal therapy has often been seen as limited. The skill level and experience of the medical team can significantly influence the outcome. Even though guidelines have been established, the ideal treatment method, particularly for patients without symptoms, remains disputed. For patients who are asymptomatic with a single, stable aspergilloma, the Infectious Diseases Society of America suggests a wait-and-watch approach. If symptoms develop, including hemoptysis, removal is advised provided there are no contraindications to surgery. In patients who are considered high-risk or unwilling to undergo surgery, prolonged use of antifungal drugs called triazoles is recommended.

Despite surgical removal being considered the go-to treatment, not all aspergilloma patients are eligible for surgery due to overall poor health and extensive disease. For these patients, triazole and echinocandin therapy (types of antifungal treatments) have shown promise.

Alternative antifungal therapy should be considered for patients who don’t respond or cannot tolerate triazole therapy. In patients with hemoptysis who are not suitable for surgery and are unresponsive to antifungal therapy, antifungal agents can be delivered directly into the cavity in the lung where the aspergilloma is located. This can be performed using an endobronchial tube or a percutaneous catheter. However, this method is only seen as a temporary treatment and it’s not without complications, including pneumothorax (collapsed lung) and cough. In addition, a new non-surgical approach involving the transbronchial removal of the aspergilloma has begun to show promise.

In case of mild to moderate hemoptysis, oral tranexamic acid, a drug that helps with blood clotting, can be tried. If massive hemoptysis occurs, embolization (clotting) of the bronchial artery has been successful in 50%-90% of cases. However, recurrences of hemoptysis are also expected to be high. These patients should then be started on antifungal therapy. In more rare cases, embolization of other arteries may be required to control hemoptysis. The decision to proceed with surgery should be taken seriously and must be determined on a case-by-case basis, taking into consideration the overall health condition of the patient, the experience of the surgical team, and various symptoms and factors. Depending on these variables, several surgical procedures can be considered, such as removal of a lobe of the lung (lobectomy) or a lung segment (segmentectomy) among others.

The removal of a simple aspergilloma is considered a final treatment. Complex aspergillomas and CCPA require longer courses of antifungal therapy, and a cure is sometimes not achievable. The goal in these cases is to manage the disease and reduce instances of hemoptysis. Progress should be monitored regularly with chest CT scans. As the disease stabilizes or improves, the frequency of these scans can be reduced. Blood tests for antibodies to Aspergillus should also be performed regularly.

What else can Aspergilloma be?

When a doctor notices a lesion, or abnormal area, in the lung, there are several potential causes for this. These may include:

• Primary lung cancer, which starts in the lung itself
• Metastatic disease, where cancer from another part of the body has spread to the lung
• Aspergilloma, a fungal growth
• Hydatid cyst, a parasitic infection
• A lung abscess, which is a pus-filled cavity in the lung

If a patient has CCPA, a lung disease caused by a specific type of fungus, there are also several possible conditions that can cause similar symptoms. It could be:

• Active tuberculosis, a serious infectious lung disease
• Non-tuberculous mycobacteria, a group of bacteria that can cause lung infection
• Histoplasmosis, another type of fungal infection
• Coccidioidomycosis, a disease caused by inhaling certain types of fungus spores
• Actinomycosis, a rare chronic disease caused by a specific type of bacteria
• A tumor or cancer (neoplasm)

Dealing with lung lesions and CCPA requires further tests to confirm the right diagnosis among these possibilities.

What to expect with Aspergilloma

Predicting the outlook for aspergilloma and CCPA is difficult due to the unpredictable nature of these conditions, potential associated lung diseases, and the patient’s general health status. Around 10% of simple aspergilloma cases get better on their own. Newly available antifungal medicines such as triazole and echinocandin have shown benefits for about 65% of treated patients with symptoms.

Similar positive results have been seen when antifungal medicines are directly inserted into the cavity where the fungus grows. It’s important to note, however, that while these treatments may relieve symptoms, it doesn’t necessarily mean they’ll extend one’s life. Additionally, the long-term impacts of these treatments on prognosis are still unknown.

In cases where there’s heavy bleeding (massive hemoptysis), the mortality rate has been reported to be as high as 38% historically. However, it’s unclear if this figure is still relevant with modern treatment strategies for aspergilloma and CCPA.

After successful bronchial artery embolization – a procedure to stop the bleeding – recurrence of bleeding can be seen in 19% to 55% of the cases. More investigation is needed to understand the impact of new antifungal medications and non-surgical management on the overall outlook for aspergilloma and CCPA.

Possible Complications When Diagnosed with Aspergilloma

Hemoptysis, or coughing up blood, is the most common and feared complication in some lung diseases. Some complications come from the lung disease itself while others are the result of the antifungal medication used for treatment. These can be administered systemically (through the body) or locally, directly into the affected cavity within the lung. There are also potential complications that can occur during or after surgery. These risks should be considered when assessing the patient’s overall health before surgery.

The progression of simple aspergilloma and CCPA, two types of lung diseases, isn’t well understood. These diseases can either go unnoticed or cause further extensive and invasive lung damage.

Preventing Aspergilloma

Aspergilloma and Chronic Cavitary Pulmonary Aspergillosis (CCPA) are more common in areas with low resources due to their association with pre-existing TB lung cavities. In these areas, diagnosing and treating these conditions is often challenging due to limited resources. Regardless of where they are diagnosed, patients with these conditions may have few management options due to resource availability and the experience level of the medical professionals involved in their care. Clinical options may also be restricted due to the patient’s overall health and lung function.

If the selected treatment strategy is antifungal therapy, it can often require long treatment courses. This can significantly affect costs and monitoring of potential side effects. Furthermore, once treatment begins, it’s important to understand that close monitoring over several years will be necessary to assess how the treatment is working. Deciding to pursue surgery should take into account the experience of the surgical team.

Despite these challenges, the management of aspergilloma and CCPA has improved over the past decade due to new antifungal treatments and diverse surgical and non-surgical therapy strategies. However, due to these conditions’ low prevalence, especially in developed regions, many doctors have limited experience. Part of this lack of experience is due to outdated studies and a lack of fresh clinical research. This, along with differing opinions regarding therapy and monitoring strategies, complicates the diagnosis and management of these complicated infections.