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Understanding Aspergillosis.

What is Aspergillosis and how is it caused?

Aspergillosis is a disease caused by Aspergillus, which is a variety of mould found in the air, soil, rotting plants, leaves and compost. We all breathe in Aspergillus fungal spores every day and for the vast majority of people, these spores are harmless. However, they can cause problems for those with immune deficiencies, or lung conditions such as severe asthma, bronchiectasis, cystic fibrosis, COPD and TB.

Diseases caused by Aspergillus fungal infections are called aspergillosis and can take several forms. The severity of aspergillosis is determined by various factors. The conditions range from allergy-type illness, to life-threatening generalised infections. One of the most important factors is the state of the person’s immune system.

Chronic forms of aspergillosis, suffered by people with a normal immune system, are the results of the fungus gaining a foothold in the body. It slowly grows and irritates the surface of delicate tissues that it comes into contact with (such as the lungs or sinuses). This causes them to change in a way that impacts upon a person’s health. Delicate tissue in the lungs helps us to breathe, by allowing the efficient exchange of gases to and from the blood supply. This runs just below the membranes – but, the fungal irritation causes it to inflame, thicken and scar. This compromises that important functionality of the lungs.

Types

Aspergillus Infections

IA invasive aspergillosis
CPA chronic pulmonary aspergillosis
FRS fungal rhinosinusitis

Allergies to Aspergillus infections

ABPA allergic bronchopulmonary aspergill
SAFS severe asthma with fungal sensitivity
Fungal sensitisation from a damp home

Symptoms

Symptoms vary depending upon the type of aspergillosis a person has. Somebody with an aspergilloma (a fungal ball in the lung) may have few symptoms or just a cough, but another may cough up large quantities of blood and require urgent medical attention. It’s not the same for everyone, but people with aspergillosis can experience:

Weight loss ● fatigue ● fever ● cough

Coughing blood (haemoptysis) ● Breathlessness ● mucous plugs ● lung cavities

Diagnosis

Early diagnosis makes treatment easier and improves outcomes. Aspergillosis is difficult to diagnose though. We know that the diagnostic odyssey, which is the (long) time taken from initial disease recognition or symptom onset to diagnosis, is real. People with aspergillosis have told us that they are repeatedly misdiagnosed, or not listened to.

We surveyed 128 people with aspergillosis and 60% told us that from the first visit to their GP, they waited 1-5 year for a diagnosis. (See Fig.1.)

Treatment

It is important to reduce or prevent inflammation, so steroids are typically prescribed. Triazole antifungals such as itraconazole, voriconazole, or posaconazole are also used. Although they cannot eradicate the infection, they do reduce symptoms quite markedly, in many cases. However these drugs are expensive and can cause unpleasant side effects.

Drug interactions particularly with the triazole drugs, may provide an additional challenge during the treatment of aspergillosis. Online tools are available to check for antifungal interactions. See useful resources.(1)

Some people with aspergillosis will find themselves on antibiotics from time to time, as secondary bacterial infections are common.

How people with aspergillosis feel

“My breathing difficulties became so severe, that I had to give up my job and simply concentrate on staying alive.”(2)
“Going from desperate for information to being terrified of information.”
“Went from a fit, working man, to struggling to cope day-to-day and living on benefits.”
“I often have low energy levels, severe wheezing, difficulty with breathing and doing everyday tasks.”
“The worst fear is not knowing how long the medication will keep working.”

The future – people with aspergillosis want

• More research and new antifungal drugs with fewer side effects.
• Better awareness among healthcare professionals.
• Earlier diagnosis of new cases to enhance quality of life, improve outcomes and reduce mortality.
• An understanding that aspergillosis is a hidden condition, people can be very ill but look well.
• Removing geographical barriers to treatment – people are often too ill to travel to specialist centres like the one at Wythenshawe, Manchester.
• More collaboration, communication and compassion from healthcare workers.

How can GPs, practice nurses and community pharmacists help?

All of these frontline healthcare professionals can contribute to earlier diagnosis of aspergillosis, by thinking of fungal lung infections sooner if they notice patients who:

1.  have repeat courses of antibiotics, that are failing to clear lung infections. Antibiotics won’t work on fungal infections, they will only work on bacterial infections. Having repeat courses of antibiotics when not needed could contribute to antibiotic resistance, which we all need to help to reduce.
2. have asthma exacerbations, despite using inhalers correctly.
3. are using more salbutamol inhalers than expected.

Triazole antifungals – side effects and interactions

Also these healthcare professionals can check for side effects from triazole antifungals. These medicines can cause hepatotoxicity (liver damage) and peripheral neuropathy (nerve damage). Itraconazole may also cause cardiac failure and peripheral oedema (fluid retention and swelling), while voriconazole therapy is associated with severe photosensitivity and temporary visual impairment.(1) It is always a balance between risks and benefits of medicines. Healthcare professionals, especially pharmacists, can help monitor these to ensure the benefits are greater than the risks of side effects.

All of these healthcare professionals can look up interactions between antifungals and the patient’s other medications. Patients can also check for interactions themselves. (See link in useful resources below.) Interactions causing low levels of antifungals could potentially lead to Aspergillus resistance to antifungals. It’s important to avoid this, to keep antifungals working to help manage the condition more easily. Certain medicines interactions can cause increased levels, potentially leading to toxicity from the antifungal or the other medicine. This increases the risk of unwanted, or harmful side effects.

Flag-up any concerns with the patient’s GP, referring them to the Pharmaceutical Journal article (referenced below) for more detailed information. Alternatively advise them to contact the National Aspergillosis Centre to discuss the case (tel. 0161 291 5811).

Useful resources

• Online antifungal interactions database and Android app (via Google play): www.antifungalinteractions.org
• Aspergillosis Trust, patient and carers advocacy group: www.aspergillosistrust.org
• Aspergillosis patients and carers website https://aspergillosis.org/
• Aspergillosis Trust raises funds for research for the Fungal Infection Trust (FIT) www.fungalinfectiontrust.org/

References
(1) Bazaz R, Denning D. Aspergillosis: causes, types and treatment. Pharm J. 2019;303(7927):38-43. doi:10.1211/pj.2019.20206738
(2) Chapman M. Living with allergic bronchopulmonary aspergillosis. Breathe. 2019;15(2):108-109. doi:10.1183/20734735.0170-2019

Learn more about the disease here

Content written by Helen Findon, National Aspergillosis Centre, University of Manchester. Jill Fairweather, Aspergillosis Trust. Sandra Hicks, Aspergillosis Trust.

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