ABPA – Allergic Broncho-Pulmonary Aspergillosis

Allergic broncho-pulmonary aspergillosis is a condition that causes the patient to develop an allergic response to the spores (conidia) of Aspergillus moulds. ABPA is predominantly found in patients with asthma, although this is not always the case. However, the condition can also affect those with cystic fibrosis and bronchiectasis. 

In people with fully functioning immune systems and healthy lungs, the inhaled spores are quickly cleared from the airways. In a case of ABPA, the disease begins because the fungal spores are not effectively cleared. The spores themselves are inactive and don’t cause disease right away. However, when they are not eliminated from the body they have time to become active, swell and produce long thread-like structures called hyphae which release harmful toxins. This triggers an overactive inflammatory immune response which causes symptoms.

There is as yet no complete cure for ABPA, so it is managed using steroids and antifungals in order to avoid any lung damage occurring. The fungus takes up residence in the lungs and grows in the air spaces deep within. The fungus does not invade the lung tissue itself (it is non-invasive) but sets up a permanent source for irritation and allergic reaction.

Sufferers of ABPA find anywhere that has increased levels of airborne mould spores can trigger severe asthmatic reactions – e.g. compost heaps, damp buildings and even the outside air in some places at particular times of the year. Avoiding over-exposure – staying indoors or using an N95/FFP2 facemask may be advisable when this is a problem for you.

CT scan of thorax of patient with severe ABPA. Taken from aspergillus.org

CT scan of thorax of patient with severe ABPA. Taken from aspergillus.org

Diagnosis

8 criteria for ABPA were initially proposed in 1977 and are still widely used today in diagnosing ABPA. These criteria are:

  • Episodic wheezing (asthma)
  • Eosinophilia (increase in the number of certain white blood cells which fight disease)
  • Immediate skin test reactivity to Aspergillus antigens
  • Precipitating (IgG) antibodies to Aspergillus
  • Elevated total IgE
  • Elevated Aspergillus-specific IgE
  • Central bronchiectasis (widening of the airways)
  • History of pulmonary infiltrates (seen on X-ray)

If a patient has all eight of the above, diagnosis is certain.
If a patient has seven, diagnosis for ABPA is highly likely.

If the patient has asthma, eosinophilia and a history of infiltrates then ABPA should be considered as possible and the other tests can be done to attempt to confirm.

If the patient has fewer than seven of the above diagnosis becomes less sure. If a quick answer is needed or preferred and if the health of the patient allows then biopsy provides a very good way of deciding the diagnosis.

Diagnosis for Cystic Fibrosis is a little different.

New diagnostic criteria

Whilst these criteria have been helpful in indicating ABPA, an expert working group – the International Society for Human and Animal Mycology (ISHAM), reviewed the literature and in 2013 proposed new diagnostic and classification criteria which aimed to improve accuracy in diagnosing ABPA.

The newly revised ISHAM diagnostic criteria are as follows:

Predisposing conditions:

  • Bronchial asthma
  • Cystic Fibrosis

Obligatory criteria (both should be present):

  • Positive type I skin test to Aspergillus antigens or elevated A.fumigatus specific IgE levels
  • Elevated total IgE levels (over 1000 IU/mL)

Two out of three of the following criteria should be present:

  • Serum precipitating IgG antibodies to Aspergillus fumigatus
  • Radiographic pulmonary opacities consistent with ABPA
  • Total eosinophil count over 500 cells/µL in steroid naïve patients

Despite there being no clear gold standard in terms of diagnosis, studies show that these criteria do seem to be more accurate in diagnosing ABPA than the original criteria.

Click this link to read the full ISHAM review – https://bit.ly/3q1rhFX

Staging

A few years after the original diagnostic criteria were proposed, stages of ABPA were also suggested. These were 1) acute, 2) remission, 3) exacerbation, 4) corticosteroid-dependent asthma and 5) fibrotic lung disease.

The ISHAM working group re-visited the traditional 5 stages of ABPA to define the stages more clearly. They introduced stage zero which describes a patient with controlled asthma who is asymptomatic for ABPA but is found to fulfil the diagnostic criteria upon investigation. The ISHAM group suggest that routinely investigating every asthmatic for ABPA would help in early diagnosis. The new stages were defined as 0) asymptomatic, 1) acute, 2) response, 3) exacerbation, 4) remission 5) difficult to control ABPA/asthma and 6) advanced.

Maybe you have been told that your ABPA is at a particular stage and you aren’t sure what this means, to see descriptions of each stage refer to the table below;

Stage Definition Features
0 Asymptomatic Controlled asthma, asymptomatic ABPA
1 Acute Acute to subacute symptoms of ABPA
1a With mucoid impaction Documented mucoid impaction on chest radiograph, CT or bronchoscopy
1b Without mucoid impaction No documented mucoid impaction on chest radiograph, CT or bronchoscopy
2 Response With treatment there is improvement in symptoms, clearance of radiographic opacities and at least a 25% decline in IgE by 8 weeks
3 Exacerbation Exacerbation of the disease (increase in IgE levels by 50%, clinical worsening), likely in patients with aspergilloma or HAM (high-attenuation mucus)
4 Remission No ABPA exacerbations over 6 months after stopping therapy, IgE levels measured every 3-6 months for the first year and then annually but remain higher than normal
5 Difficult to control ABPA/asthma  
5a Treatment-dependent Patient requires repeated courses of steroids or azoles for control of ABPA
5b Glucocorticoid-dependent Patient requires glucocorticoids for control of asthma
6 Advanced Widespread bronchiectasis and/or fibrosis with type II respiratory failure and/or cor pulmonale (condition that causes the right side of the heart to fail)

Genetics

Some studies suggest that there could be a genetic risk factor for ABPA, although cases of ABPA in siblings or children of parents with ABPA are very rare. One study does report a familial link of 5% (which is relatively high) but this study was based in India where aspergillosis is known to be more common due to the environment. It is well known that asthma runs in families and asthma can be a pre-disposing condition for ABPA, but there is thought to be a further genetic risk required to cause ABPA because not all asthmatics develop ABPA despite being exposed to the same environment as those that do, meaning there is likely a genetic element involved as well.

Studies show that there are some specific genes, mainly associated with cells of the immune system, that are commonly affected in ABPA patients compared to people without ABPA. One such gene is that which codes for a molecule called major histocompatibility complex (MHC) II. This molecule presents antigens (such as Aspergillus antigens) on its surface so that other immune cells can destroy them. If this gene is mutated then the antigens aren’t presented as well to the other immune cells and aren’t destroyed as effectively. Consequently, there could be an inherited genetic risk if mutations in these genes are passed on, but further research is needed in this area to work out what this risk involves and how high of a risk it is.

If you want to find out more, this study gives an overview of some of the genetic factors involved in ABPA – https://bit.ly/2ZNawmO

Ultimately, if you have ABPA you don’t need to worry about your family as the risk of inheriting this disease is extremely low.

Treatment

Treatment consists of long term use of steroids (e.g. prednisolone) to reduce inflammation and lung damage. There are several potential difficulties with the use of steroid drugs for long periods but their use is vital to prevent the disease progressing.

We can often reduce the amount of steroids taken by ABPA patients by giving the patient an antifungal medication such as itraconazole (e.g. Sporanox, but there are now several brand names). This seems to keep the symptoms under control and some people can stop taking steroids completely for periods of time.

Another way to reduce the need for steroids is to reduce inflammation via other means. A biologic drug could be beneficial for patients that have been taking treatment and haven’t seen improvements to their health, or have seen continuing deterioration. For patients with ABPA, omalizumab might be given. This drug works by inhibiting IgE, an antibody produced by the immune system that causes inflammation and triggers other immune cells to release chemicals such as histamine. Patients with ABPA have too much IgE and inflammation of the airways ensues. This drug reduces IgE levels and hence can ease inflammation and asthmatic symptoms.

It is known that many asthmatics have fungal sensitivity, a proportion of these having ABPA, some possibly undiagnosed. The number of those diagnosed with severe asthma and admitted to the hospital is growing constantly.

Young people with Cystic Fibrosis frequently also suffer from ABPA, imposing further complications in their treatment.

Prognosis

There is no current cure for ABPA, but the management of inflammation and scarring using itraconazole and steroids usually succeeds in stabilising the symptoms for many years.

ABPA can very rarely progress to CPA.

This is a relatively ‘young’ illness (first reported in 1952) with a long period of infection so it takes time for the long term results of improvements in care to become apparent. Identification of a fungal element in other severe asthmas suggests ABPA may well be much more common that was thought. ABPA is starting to lose its image of a rare and unusual infection and hopefully that will lead to increased awareness and improved management of the disease.

Further Information

 
Updated by Katy McGuinness – Nov 2021