GAtherton

Differences between ABPA and CPA

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Allergic broncho pulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are two different types of aspergillosis. They are both chronic diseases but they differ in mechanisms and often presentation. Do you know the differences between the two?

This article will compare the biology, the symptoms and the diagnosis/treatment of the two diseases.

The Biology

An overview:

The ultimate cause of both ABPA and CPA is failed clearance of Aspergillus spores (conidia) from the lungs which leads to disease. However, the exact mechanism of how disease is caused in the two is quite different. The main difference is that ABPA is an allergic reaction to Aspergillus spores whereas CPA is an infection.

Let’s first look at ABPA. As previously said, ABPA is caused by an allergic reaction to Aspergillus spores. The reaction is exaggerated by co-morbid diseases like cystic fibrosis (CF) and asthma. As is described on the ABPA page, Aspergillus spores in and of themselves do not cause allergic reactions - hence they are unknowingly breathed in by everyone every day. In healthy people, the spores are quickly removed out of the lungs and body. A reaction occurs when the spores are not cleared out of the lungs, giving them time to grow and produce hyphae (long thread-like structures) that release harmful toxins. The body then produces an allergic immune response to the germinating spores and the hyphae. This allergic response involves inflammation. Inflammation is the result of lots of different immune cells rushing to the area at once to try and fight off the invaders. Whilst it is needed in an effective immune response, it also causes swelling and irritation of the airways, producing some of the main symptoms associated with ABPA such as coughing and shortness of breath.

Now let’s look at CPA. CPA, as mentioned above, is not characterised by an allergic reaction to Aspergillus spores. This disease is less clear cut than ABPA and is much less common. It is, however, caused by spores not being cleared effectively from the lungs. In this case, they set up residence in damaged lungs or cavities present within the lungs and begin to germinate there. Areas of damaged lung are much easier for infections to invade as there are fewer immune cells to fight them off (note that patients with CPA usually have a functioning immune system – ie. they are not immunocompromised). These cavities are usually the result of previous lung infections such as chronic obstructive pulmonary disorder (COPD) or tuberculosis (TB).

Some CPA patients have multiple underlying conditions. In a 2011 study, details of underlying conditions of 126 CPA patients in the UK were identified; it was found that tuberculosis, non-tuberculous mycobacterial infection and ABPA (yes, ABPA can be a risk factor for CPA) were the predominant risk factors for development of CPA (read the full study here - https://bit.ly/3lGjnyK). The Aspergillus infection can grow in damaged areas deep within the lungs and occasionally begin to invade the surrounding tissue. When this happens, immune cells in the surroundings areas usually fight off the infection and so it is prohibited from completely invading the lung tissue. This periodic spreading of the Aspergillus infection can, however, damage nearby blood vessels causing one of the main symptoms associated with CPA which is coughing up blood (haemoptysis).

Which immune cells are detected?

ABPA:

• As ABPA is predominantly an allergic infection, IgE antibody levels rise dramatically (>1000) as part of the body’s allergic immune response. IgE plays an important role in allergy as it stimulates other immune cells to release chemical mediators. These chemicals help to get the allergen out of your body and/or recruit other immune cells to help out as well. One of these well-known chemicals is histamine. Total IgE levels and Aspergillus-specific IgE levels are both raised in patients with ABPA.
• IgG antibodies to Aspergillus are also often elevated; IgG is the most common type of antibody and works by binding to the Aspergillus antigens which leads to their destruction.
• Eosinophils can be raised which work by releasing toxic chemicals that destroy the invading pathogen.

CPA:

• Raised levels of Aspergillus IgG antibodies are present
• IgE levels may be slightly elevated in CPA patients, but not as high as ABPA patients

Symptoms

Whilst there are overlaps in symptoms between the two diseases, some symptoms are more common with one type of aspergillosis.

ABPA is associated with allergic symptoms such as coughing and production of mucus. If you have asthma, ABPA will most likely result in worsening of your asthmatic symptoms (such as wheezing and shortness of breath). Fatigue, a fever and general feeling of weakness/illness (malaise) can also be present.

CPA is less associated with production of mucus and more with coughing and coughing up blood (haemoptysis). Symptoms such as fatigue, breathlessness and weight loss are also seen.

In a Facebook poll put out by the National Aspergillosis Centre, this question was posed separately to people with ABPA and CPA:

‘What aspect(s) of your current quality of life are you most concerned about and would like to improve the most?’

The top 5 answers for ABPA were:

• Fatigue
• Breathlessness
• Coughing
• Poor fitness
• Wheeze

The top 5 answers for CPA were:

• Fatigue
• Breathlessness
• Poor fitness
• Anxiety
• Weight loss/coughing/coughing up blood/side effects of anti-fungals (note these answers all got the same number of votes)

This is helpful in directly comparing symptoms reported from patients themselves.

Diagnosis/treatment

The ABPA page on this website describes the updated diagnostic criteria – see this link https://aspergillosis.org/abpa-allergic-broncho-pulmonary-aspergillosis/

Diagnosis for CPA depends on radiological and microscopic findings, patient history and laboratory tests. CPA can develop into different forms such as chronic cavitary pulmonary aspergillosis (CCPA) or chronic fibrosing pulmonary aspergillosis (CFPA) – diagnosis is slightly different for each depending on radiological findings. The most common feature found on a CT scan of a CPA patient is an aspergilloma (morphological appearance of a fungal ball). Whilst this is very characteristic of CPA it cannot alone be used to determine a diagnosis and requires a positive aspergillus IgG or precipitins test for confirmation. Lung cavities present for at least 3 months may be seen with or without an aspergilloma, that, along with serological or microbiological evidence, can indicate CPA. Other tests such as Aspergillus antigen or DNA, biopsy showing fungal hyphae on microscopy, Aspergillus PCR, and respiratory samples that grow Aspergillus in culture are also indicative. Together with symptoms described by the patient, a combination of these findings is required to make a sure diagnosis.

Treatment for both diseases usually involves triazole therapy. For ABPA, corticosteroids are often used to control the body’s response to the spores and itraconazole is the current first-line antifungal treatment. Biologics may be an option for those with severe asthma. See more about biologics here - https://aspergillosis.org/biologics-and-eosinophilic-asthma/.

For CPA, the first-line treatment is itraconazole or voriconazole and surgery may be suitable to remove an aspergilloma. Diagnosis and a treatment plan is made by a respiratory consultant.

Hopefully this has given you a clearer picture on the two diseases. The main takeaway is that ABPA is characterised by an allergic reaction to aspergillus spores whereas CPA is not.
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by GAtherton