🔬 Charcot–Leyden Crystals in ABPA and Asthma

What are they? Why do they form? Do they matter?

If you live with Allergic Bronchopulmonary Aspergillosis (ABPA) or severe asthma, you may see the term Charcot–Leyden crystals in a sputum or pathology report.

They can sound worrying.

They are:

  • Not fungus

  • Not infection

  • Not cancer

They are a sign of a particular type of allergic inflammation in the airways.

🧬 What Are Charcot–Leyden Crystals?

Charcot–Leyden crystals are microscopic, needle-shaped structures found in mucus.

They are made from a protein called galectin-10, which is stored inside a type of white blood cell called an eosinophil.

Eosinophils are immune cells involved in:

  • Allergic asthma

  • ABPA

  • Severe asthma with fungal sensitisation

  • Parasitic infections

When eosinophils are activated and break down, they release galectin-10.
If enough of this protein accumulates in thick airway mucus, it crystallises into visible crystals.

So the crystals are made from your immune cells, not from Aspergillus.

🫁 Why Do They Appear in ABPA?

In ABPA:

  1. The immune system overreacts to Aspergillus fumigatus.

  2. This triggers a strong allergic (Type 2) immune response.

  3. Large numbers of eosinophils move into the airways.

  4. Eosinophils break down and release galectin-10.

  5. The protein crystallises inside mucus plugs.

The crystals are therefore a footprint of intense allergic inflammation, not fungal invasion.

🌡 Is Most ABPA Eosinophilic?

Yes — almost all classical ABPA is eosinophilic.

ABPA is fundamentally a Type 2 allergic condition, driven by immune pathways involving:

  • IL-4

  • IL-5

  • IL-13

  • IgE

  • Eosinophils

IL-5 in particular stimulates eosinophil production and survival.
Because of this, eosinophils are central to the disease process.

Historically, raised blood eosinophils have been part of diagnostic criteria.

However:

  • Eosinophil counts can fluctuate

  • Steroids can suppress blood levels

  • Eosinophils may still be present in airway mucus even if blood counts appear normal

So ABPA is biologically eosinophilic — even if a single blood test does not show a high count.

True non-eosinophilic ABPA would be unusual and would prompt clinicians to reconsider the diagnosis.

❓ Are Crystals Caused by Aspergillus Infection?

No.

They are caused by the immune reaction to Aspergillus — not by the fungus itself.

They can also be seen in:

  • Severe eosinophilic asthma

  • Parasitic infections

  • Other allergic lung conditions

They reflect eosinophil activity, not fungal growth.

🧠 Why Don’t All People with Asthma Develop These Crystals?

Asthma is not one single disease. It has different inflammatory patterns.

Type 2 (Eosinophilic) Asthma

This involves high eosinophils and allergic pathways.

Common in:

  • Allergic asthma

  • ABPA

  • Severe eosinophilic asthma

These patients can develop Charcot–Leyden crystals.

Non–Type 2 (Non-Eosinophilic) Asthma

This includes:

Neutrophilic asthma

Driven by neutrophils rather than eosinophils.

Paucigranulocytic asthma

Very few inflammatory cells present.

In these forms:

  • Eosinophils are low

  • Galectin-10 is not released in large amounts

  • Crystals are unlikely to form

🧱 Do Charcot–Leyden Crystals Make Mucus Plugs Worse?

Possibly.

Research suggests they may:

  • Increase mucus thickness

  • Contribute mechanically to airway blockage

  • Stimulate further inflammation

For many years they were thought to be harmless debris.
Modern studies suggest they may actively amplify inflammation when present in large amounts.

🎯 Do They Have a Purpose?

Eosinophils evolved mainly to help fight parasitic infections.

Galectin-10 probably has immune signalling roles inside cells.

However, when large amounts are released into thick airway mucus, crystallisation appears to be a by-product of excessive immune activity rather than a useful defence.

In ABPA and allergic asthma, they are more likely part of the problem than part of the solution.

💧 Can Their Formation Be Reduced?

Hydration alone does not stop them forming.

Drinking fluids helps:

  • Keep mucus less sticky

  • Support airway clearance

But it does not prevent eosinophils releasing galectin-10.

What reduces crystal formation?

Reducing eosinophilic inflammation:

  • Corticosteroids

  • Anti-IL-5 biologics

  • Anti-IL-4/IL-13 biologics

When eosinophil numbers fall:

→ Less galectin-10 is released
→ Fewer crystals form

Antifungal treatment in ABPA may indirectly help by reducing allergic stimulation, but the main driver is the immune response.

📊 Do They Change Treatment?

Not directly.

Doctors base treatment on:

  • Symptoms

  • Blood eosinophils

  • Total IgE

  • Imaging

  • Lung function

  • Exacerbation history

Crystals support the diagnosis of eosinophilic inflammation but do not determine treatment alone.

🔎 What Do They Tell Us?

Charcot–Leyden crystals tell us:

  • The airway inflammation is eosinophilic.

  • The immune response is strongly allergic.

  • Mucus plugging risk may be higher.

They are a marker of immune overreaction, not infection severity.

🧠 Key Points to Remember

  • They are made from proteins released by eosinophils.

  • They are not Aspergillus.

  • They do not mean invasive fungal infection.

  • Most classical ABPA is eosinophilic.

  • They are unlikely in non-eosinophilic asthma.

  • Reducing eosinophils reduces their formation.

  • Hydration helps clearance but does not prevent formation.

In simple terms:

Charcot–Leyden crystals are microscopic signs that the immune system is working too hard in the airways.

by GAtherton

Systemic fungal infections: why speed, diagnosis and stewardship matter

Systemic fungal infections — including aspergillosis, candidiasis, cryptococcosis, mucormycosis and pneumocystis pneumonia — are medical emergencies. When diagnosis or treatment is delayed, mortality rises sharply. This comprehensive review brings together current understanding of how these infections arise, why they are so difficult to diagnose, and what is needed to improve outcomes.

Why fungal infections are often missed

Unlike many bacterial infections, systemic fungal infections can be hard to confirm quickly. Fungal organisms are often present in low numbers, may be released intermittently into the bloodstream, and can be difficult to grow in standard cultures. As a result, no single test is usually sufficient, and clinicians often need a combination of imaging, cultures, antigen tests, molecular tests (PCR), and histopathology.

Because delay can be fatal, antifungal treatment is frequently started on clinical suspicion alone — especially in critically ill or immunocompromised patients. The paper emphasises that this approach is often necessary, but it must be paired with a clear diagnostic strategy.

Antifungal stewardship: knowing when to stop

A central message of the paper is that diagnostic tests are just as important for stopping treatment as for starting it. Antifungal drugs can be toxic, interact with many other medicines, and drive antifungal resistance if used unnecessarily.

The authors stress that:

  • Diagnostic results should be actively reviewed

  • Antifungal therapy should be stopped or stepped down if infection is not supported by evidence

  • This approach protects patients and preserves antifungal effectiveness

Antifungal resistance is a growing threat

Antifungal resistance is no longer rare. The review highlights:

  • Azole resistance in Aspergillus, including cryptic species

  • Rising resistance in several Candida species

  • The global spread of multidrug-resistant Candida auris

Because of this, the authors recommend that all clinically relevant fungal isolates are identified to species level and tested for antifungal susceptibility wherever possible. Making assumptions about drug sensitivity is increasingly unsafe.

Aspergillosis: a broad spectrum of disease

The paper clearly outlines the many forms of aspergillosis, ranging from:

  • Allergic disease (such as allergic bronchopulmonary aspergillosis)

  • Chronic pulmonary aspergillosis, often in people with underlying lung damage

  • Subacute and acute invasive disease, particularly in immunocompromised or critically ill patients

Importantly, the review notes that aspergillosis is not limited to severely immunocompromised people. Chronic and subacute forms often occur in individuals with structural lung disease who are otherwise immunocompetent.

Climate change and emerging fungal risks

One of the most forward-looking sections of the paper addresses how climate change and natural disasters are altering fungal disease patterns. Rising environmental temperatures, flooding, storms and environmental disruption are:

  • Increasing exposure to environmental fungi

  • Enabling fungi to adapt to higher temperatures

  • Contributing to outbreaks after natural disasters and trauma

  • Expanding fungal diseases into new geographic regions

The authors argue that fungal infections must be considered part of future public health and healthcare resilience planning.

Key take-home messages

  • Systemic fungal infections are time-critical medical emergencies

  • Diagnosis usually requires multiple tests, not a single result

  • Early antifungal treatment is often necessary — but must be reviewed

  • Diagnostics are essential for safe antifungal stewardship

  • Antifungal resistance is a real and growing problem

  • Climate change is reshaping fungal epidemiology and risk

Free access to the full article

Elsevier has provided free access to the full paper for a limited time (no registration required):

👉 https://authors.elsevier.com/a/1mZqR4qdNoJLH2
🗓️ Available until 28 March 2026

This article is recommended reading for patients wanting a deeper understanding of fungal disease, as well as clinicians, microbiology teams, and healthcare planners.

by GAtherton

Aspergillosis, immunity, and risk

Primary immune deficiencies and immune modifiers explained

A single, comprehensive explainer for expert patients, carers, and non-specialists

Why this article exists

Aspergillus is a mould that everyone breathes in every day. Most people clear it without difficulty.
A small number of people develop aspergillosis because the balance between the fungus, the lungs, and the immune system is disturbed.

This article explains:

  • Rare primary (inherited) immune deficiencies that are clearly linked to aspergillosis

  • Common immune “modifier” factors that can increase risk or severity but do not cause disease on their own

  • How these factors stack together in real life

Key reassurance up front

  • There are 500+ recognised primary immune deficiencies

  • Only ~20–30 are clearly linked to aspergillosis

  • Most people with aspergillosis do not have any inherited immune disorder

The unifying concept: three immune pathways to aspergillosis

Almost all immune–aspergillus relationships fall into three mechanisms. Understanding these matters more than memorising names.

1. Reduced ability to kill the fungus

Some immune cells fail to destroy Aspergillus spores effectively.
→ Risk of invasive aspergillosis, sometimes severe or life-threatening.

2. Lung damage over time

Repeated infections or inflammation damage airways or leave cavities.
→ Risk of chronic pulmonary aspergillosis (CPA) or aspergillomas.

3. Excessive allergic inflammation

The immune system over-reacts to Aspergillus rather than failing to fight it.
→ Allergic bronchopulmonary aspergillosis (ABPA) and severe fungal-sensitised asthma.

Many conditions overlap more than one pathway.

Section 1: Primary (inherited) immune deficiencies clearly linked to aspergillosis

Rare, high-impact, and sometimes life-changing when present

These are the conditions clinicians usually mean when they talk about “immune causes of aspergillus disease”.

A. Phagocyte defects

Strongest association with invasive aspergillosis

  1. Chronic granulomatous disease (CGD)

  2. Autosomal recessive forms of CGD

  3. Severe congenital neutropenia

  4. Cyclic neutropenia

  5. Leukocyte adhesion deficiency type I

Typical pattern

  • Aspergillosis at a young age

  • Invasive lung disease ± spread beyond lungs

  • Often no other obvious risk factors

B. Hyper-IgE and severe allergy syndromes

Allergic, chronic, and cavity-associated disease

  1. STAT3 hyper-IgE syndrome

  2. DOCK8 deficiency

  3. PGM3 deficiency

  4. ZNF341 deficiency

  5. IL6ST deficiency

Typical pattern

  • Severe asthma and allergy

  • Thick mucus, recurrent infections

  • ABPA, later CPA or aspergillomas

C. Combined immunodeficiencies

Immune coordination problems

  1. Severe combined immunodeficiency (milder or surviving forms)

  2. Omenn syndrome

  3. ZAP-70 deficiency

  4. Major histocompatibility complex class II deficiency

  5. CD40 ligand deficiency (hyper-IgM syndrome)

Typical pattern

  • Broad infection susceptibility

  • Aspergillosis can behave aggressively

D. Defects of fungal recognition and innate signalling

Often dramatic or unexpected presentations

  1. CARD9 deficiency

  2. Dectin-1 (CLEC7A) complete deficiency

  3. MALT1 deficiency

Typical pattern

  • Severe or unusual aspergillosis

  • Lung, brain, or deep tissue involvement

  • Sometimes first presents in adulthood

E. Immune dysregulation syndromes

Mixed infection, inflammation, and autoimmunity

  1. CTLA-4 haploinsufficiency

  2. LRBA deficiency

  3. STAT1 gain-of-function mutations

  4. IPEX syndrome (FOXP3 deficiency)

Typical pattern

  • Inflammatory lung disease

  • Chronic or invasive aspergillosis emerging over time

F. Antibody deficiencies (indirect risk via lung damage)

  1. Common variable immunodeficiency

  2. X-linked agammaglobulinaemia

  3. Activated PI3K-delta syndrome

Important nuance
Antibodies do not normally kill Aspergillus.
Risk arises after years of lung damage, not early in life.

Section 2: Immune modifier-types that can amplify risk

Common, low-penetrance, and often invisible on routine testing

These are not immune deficiencies, but they can influence who struggles, how severely, and why disease persists.

Mannose-binding lectin (MBL) deficiency

  • Common (≈5–10% of population)

  • Affects fungal recognition and complement activation

  • Usually mild on its own

  • Becomes relevant with lung disease, steroids, or other immune issues

Partial fungal-recognition receptor variants

  • Heterozygous dectin-1 variants

  • Toll-like receptor polymorphisms (for example TLR2, TLR4)

Effect

  • Slower fungal recognition

  • Increased colonisation or allergic response

  • Act as risk amplifiers, not causes

Cytokine balance variants

Small genetic differences affecting immune “signal strength”, including:

  • Interleukin-6

  • Interleukin-10

  • Tumour necrosis factor-alpha

These modify:

  • Inflammation intensity

  • Tissue damage vs clearance balance

Allergy-biased (Th2-skewed) immunity

Not a disease, but a recognised immune tendency.

Features:

  • Asthma

  • Eczema

  • Nasal polyps

  • High immunoglobulin E levels

  • Eosinophilia

Strongly associated with:

  • Fungal sensitisation

  • ABPA

  • Difficult-to-control asthma

Impaired mucociliary clearance

A functional immune–mechanical issue.

Seen in:

  • Severe asthma

  • Bronchiectasis

  • Chronic sinus disease

Effect:

  • Aspergillus spores are not physically cleared

  • Prolonged immune exposure

  • Increased colonisation and allergy

Age-related immune change (immunosenescence)

  • Normal reduction in immune speed and coordination with age

  • Particularly relevant to chronic pulmonary aspergillosis

Not a disease, but an important modifier of outcome.

Airway epithelial vulnerability

Subtle weaknesses in:

  • Airway lining integrity

  • Antimicrobial peptide production

  • Local immune signalling

Can increase:

  • Fungal adherence

  • Chronic colonisation

  • Allergic sensitisation

Section 3: Risk stacking – how this works in real life

Aspergillosis rarely results from one single factor.

Instead, several modest risks align:

  • Mild MBL deficiency

  • Severe asthma

  • Corticosteroid exposure

  • Bronchiectasis

  • Age-related immune change

→ Together, they create real disease risk, even though none alone would.

This explains why:

  • Two people with similar scans can behave very differently

  • One patient relapses while another stabilises

  • “Why me?” often has no single answer

Section 4: When clinicians investigate immune causes

Testing is targeted, not routine. It is usually considered when there is:

  • Aspergillosis at a young age

  • Invasive or unusually severe disease

  • Disease without classic risk factors

  • Recurrent infections plus severe asthma or allergy

  • A family history of unusual infections

Section 5: Why identifying (or excluding) immune factors helps

Understanding immune contribution can:

  • Explain disease pattern and behaviour

  • Guide antifungal choice and duration

  • Inform long-term prevention strategies

  • Reduce future lung damage

  • Reassure patients when no immune defect is found

Key take-home messages

  • Aspergillus exposure is universal; immune causes are rare

  • Only ~20–30 inherited immune deficiencies are clearly linked to aspergillosis

  • Modifier-type immune factors are common and usually harmless alone

  • Aspergillosis often reflects risk stacking, not a single diagnosis

  • Understanding patterns matters more than labels

  • Specialist care improves precision and outcomes

by GAtherton

Antifungal Medicines: Dosing, Monitoring, and the Role of Specialist Care

A detailed reference for patients and non-specialist clinicians

1. Why antifungal treatment is different from most medicines

Oral antifungal medicines—especially azole antifungals—are essential for treating long-term fungal diseases such as chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis.

They differ from many common medicines because they:

  • Have a narrow margin between effectiveness and toxicity

  • Behave very differently between individuals

  • Are often taken for months or years, not days

  • Interact with many commonly prescribed drugs

For these reasons, antifungal treatment requires individualised dosing, monitoring, and specialist input, rather than a standard fixed dose.

2. What “pharmacokinetics” means (plain language)

Pharmacokinetics describes what the body does to a drug:

  1. Absorption – how well the drug enters the bloodstream from the gut

  2. Distribution – how effectively it reaches tissues such as the lungs

  3. Metabolism – how quickly the liver breaks it down

  4. Elimination – how the drug leaves the body

Differences at any of these stages explain why the same dose can be ineffective for one person and toxic for another.

3. Different generations of azole antifungals behave differently

Each generation of azole antifungal was designed to improve effectiveness, but chemical changes also altered how the body handles the drug.

First-generation azoles (older drugs)

Examples

  • Ketoconazole

  • Fluconazole (limited activity against Aspergillus)

Key features

  • Variable absorption

  • Shorter half-life

  • Less reliable lung penetration

Clinical relevance

  • Rarely used now for chronic aspergillosis

Second-generation azoles (mainstay treatment)

Examples

  • Itraconazole

  • Voriconazole

  • Posaconazole

Key features

  • Excellent lung and tissue penetration

  • Highly variable metabolism between people

  • Strong interaction with liver enzymes

Clinical relevance

  • Very effective

  • Blood levels vary widely

  • Dose adjustment and monitoring are often essential

Newer azoles

Example

  • Isavuconazole

Key features

  • More predictable absorption

  • Long, stable half-life

  • Fewer extreme peaks and troughs

Clinical relevance

  • Often better tolerated long-term

  • Monitoring still important, but dosing may be more stable

4. Why the “right dose” matters so much

Too little antifungal

  • Infection not adequately controlled

  • Symptoms persist or worsen

  • Risk of antifungal resistance

  • Fewer future treatment options

Too much antifungal

  • Liver irritation or damage

  • Nausea, appetite loss

  • Neurological or visual side effects

  • Drug accumulation, especially with long-term use

The aim is always the lowest dose that effectively controls the fungus.

https://ars.els-cdn.com/content/image/3-s2.0-B9780123868824000189-f18-07-9780123868824.jpg

5. How clinicians know whether the dose is right

No single test determines this. The correct dose is identified when three elements align:

1️⃣ Blood level testing (therapeutic drug monitoring)

  • Measures how much drug is actually in the bloodstream

  • Helps identify:

    • Under-dosing

    • Target-range dosing

    • Toxic levels

2️⃣ Clinical response

  • Symptoms stabilise or improve

  • Fewer flare-ups or complications

  • Better day-to-day function

3️⃣ Safety monitoring

  • Liver and kidney blood tests

  • Review of side effects

  • Ongoing assessment of drug interactions

Only when effectiveness and safety are both acceptable is the dose considered “right”.

6. Why the right dose can change over time

A dose that was correct initially may later need adjustment because of:

  • Weight or body-composition changes

  • Age-related metabolic changes

  • New medications (including antibiotics or steroids)

  • Changes in liver or kidney function

  • Gradual drug accumulation during long-term therapy

Regular review is therefore expected and appropriate.

7. Is it sometimes impossible to find a stable dose?

Yes. For a minority of patients, a perfectly balanced dose cannot be found.

Reasons include:

  • Extremely fast or slow drug metabolism

  • A very narrow safety window

  • Long-term toxicity despite “acceptable” blood levels

  • Unavoidable interacting medications

  • Liver, kidney, or neurological vulnerability

  • Partial or full antifungal resistance

In these cases, the dose that controls the fungus and the dose that causes side effects may overlap.

This reflects biological limits, not treatment failure.

8. What clinicians do when a stable dose cannot be achieved

Options may include:

  • Switching to a different azole with different pharmacokinetics

  • Using modified dosing schedules (split dosing, slower titration)

  • Accepting a lower suppressive dose rather than full eradication

  • Considering non-azole antifungals where appropriate

  • Prioritising symptom control and quality of life

All are intentional, safety-focused decisions.

9. The central role of the specialist pharmacist

Specialist pharmacists are key to safe antifungal care, particularly for long-term azole therapy.

They play a critical role in:

Interpreting drug levels

  • Assessing whether a level is truly low or high

  • Accounting for dose timing and formulation

  • Preventing unnecessary or unsafe dose changes

Managing drug–drug interactions

Azoles interact with many common medicines, including:

  • Steroids and inhalers

  • Heart rhythm drugs

  • Blood thinners

  • Anti-epileptics

  • Pain medications

The specialist pharmacist:

  • Reviews the full medication list

  • Anticipates interactions before harm occurs

  • Advises on adjusting both interacting drugs

Individualising dosing

When standard doses do not work, they help design:

  • Non-standard doses

  • Split dosing schedules

  • Slow titration plans

  • Alternative azoles with different pharmacokinetics

Protecting patients during long-term treatment

They monitor:

  • Trends in liver and kidney tests

  • Signs of cumulative toxicity

  • Whether symptoms may be drug-related rather than disease-related

Coordinating care

They act as a bridge between:

  • Laboratory results

  • Clinical decision-making

  • Patient experience

https://www.omnicare.com/wp-content/uploads/omnicare-services-overview-02-expert-consultant.jpg

Their involvement often changes management, not just fine-tunes it.

10. Where antifungal drug level testing is done in the UK

In the UK, antifungal drug level testing is centralised.

  • Blood samples are taken locally

  • Samples are sent to specialist reference laboratories, most commonly the
    Mycology Reference Centre Manchester

  • Results are returned to the local clinical team for interpretation

Patients managed through specialist services such as the
National Aspergillosis Centre
benefit from integrated expertise in antifungal pharmacology, imaging, and long-term monitoring.

This process is routine and standard for antifungal care.

11. Key reassurance for patients

  • Dose changes are normal and expected

  • Side effects are often biology-driven, not your fault

  • Blood tests make treatment safer, not riskier

  • Switching drugs is a planned strategy, not giving up

12. One-paragraph summary

Antifungal medicines—particularly azole antifungals—have complex and highly variable behaviour in the body, with a narrow balance between effectiveness and toxicity. Safe use requires individualised dosing, therapeutic drug monitoring, symptom review, and long-term safety checks. Specialist pharmacists play a central role in interpreting drug levels, managing interactions, and tailoring treatment. For some patients, a perfectly balanced dose cannot be achieved, and alternative strategies are required. This reflects biological complexity, not failure, and the overarching aim is always effective fungal control with the best possible long-term safety and quality of life.

by GAtherton

Surgery for Chronic Pulmonary Aspergillosis (CPA): why it is sometimes considered – and often not

For people living with chronic pulmonary aspergillosis (CPA), the idea of surgery can raise difficult questions. Some patients are told surgery might offer a chance of cure; others are advised very firmly against it. Both positions can be correct, depending on the individual situation.

This article explains when surgery may be considered, why it is often avoided, and what “success” or “cure” really means in CPA.

Why is surgery even considered in CPA

CPA usually develops in lungs that are already damaged (for example, by tuberculosis, chronic obstructive pulmonary disease, bronchiectasis, sarcoidosis, or prior infections). Antifungal medicines are therefore the mainstay of treatment.

However, surgery may be considered in a small and carefully selected group of patients, most commonly when:

1. Disease is localised to one area of the lung

If the aspergillus infection is confined to a single cavity or one lobe, and the rest of the lungs are relatively healthy, it may be technically possible to remove the affected area.

2. Recurrent or life-threatening haemoptysis (coughing up blood)

Large-volume or repeated bleeding is one of the strongest reasons surgery is considered. In some cases, surgery is viewed as a way to prevent catastrophic bleeding, rather than to eradicate infection.

3. A simple aspergilloma

Patients with a simple aspergilloma (a single fungal ball in a cavity, minimal surrounding disease, and preserved lung function) are the group most likely to benefit.

4. Failure or intolerance of antifungal therapy

If antifungal drugs cannot be taken long term due to side effects, drug resistance, or lack of response—and the disease remains localised—surgery may be discussed.

Why surgery is often not recommended

Although surgery can sound appealing, CPA surgery is high-risk and not suitable for most patients.

1. CPA is often widespread

Many patients have a disease affecting both lungs or multiple lobes. Removing one area does not treat the remaining infection.

2. Underlying lung reserve is limited

CPA commonly occurs in people with reduced lung function. Removing lung tissue can lead to:

  • Long-term breathlessness

  • Oxygen dependence

  • Reduced quality of life

Even if the operation itself is technically successful.

3. Surgery carries significant risks

Compared with many other lung operations, CPA surgery has higher complication rates, including:

  • Prolonged air leaks

  • Serious infections

  • Bleeding

  • Bronchopleural fistula (abnormal airway–pleural connection)

  • Need for prolonged hospitalisation or intensive care

4. Surgery does not address the underlying vulnerability

CPA reflects an ongoing susceptibility of the lung environment. Removing one fungal focus does not remove the underlying reason aspergillus was able to grow in the first place.

What is the “success rate” of surgery?

Success depends heavily on patient selection and surgical expertise.

In specialist centres:

  • Operative mortality (risk of death around the time of surgery):
    Typically reported between 1–5%, but higher in complex diseases.

  • Major complication rates:
    Often 15–40%, depending on disease extent and lung health.

  • Symptom improvement:
    Many patients selected for surgery experience reduced haemoptysis and improved local control of disease.

These figures are why surgery is only offered after careful multidisciplinary discussion, usually involving respiratory physicians, infectious disease specialists, thoracic surgeons, and radiologists.

Is surgery a “cure” for CPA?

This is one of the most misunderstood points.

Short answer: sometimes, but often not in the long term

  • In a simple aspergilloma, surgery can be genuinely curative if:

    • The disease is completely removed

    • There is no other active CPA elsewhere

    • The patient’s lungs remain stable

  • In chronic cavitary or fibrosing CPA, surgery is rarely a true cure. Instead, it may:

    • Control bleeding

    • Remove a particularly problematic area

    • Reduce fungal burden

Even after apparently successful surgery, some patients still require:

  • Long-term antifungal therapy

  • Ongoing monitoring with scans and blood tests

Recurrence of aspergillus infection elsewhere in the lungs can occur months or years later.

Why are many patients managed medically instead

For most people with CPA, long-term antifungal therapy offers:

  • Disease stabilisation

  • Symptom control

  • Lower risk than surgery

While antifungals do not usually “cure” CPA either, they can:

  • Slow or halt progression

  • Reduce inflammation and symptoms

  • Improve quality of life

This is why surgery is best seen as a highly selective tool, not a standard treatment.

How decisions about surgery are made

If surgery is discussed, your team will usually consider:

  • Extent and pattern of CPA on imaging

  • Lung function tests

  • General fitness and other medical conditions

  • History of haemoptysis

  • Response and tolerance to antifungal treatment

  • Your own priorities and acceptable trade-offs

Importantly, being told surgery is not advised does not mean your care is being limited—it usually reflects a judgement that risks outweigh benefits in your specific case.

Key messages for patients

  • Surgery for CPA is uncommon and highly selective

  • It is most useful in localised disease or severe bleeding

  • Complication rates are significant

  • A guaranteed or permanent “cure” is not typical, except in carefully chosen cases

  • Long-term medical management remains the safest and most effective option for most patients

If surgery has been mentioned—or ruled out—in your case, it is reasonable to ask your team:

  • What specific problem would surgery aim to solve for me?

  • What risks apply to my lungs and overall health?

  • Would antifungal treatment still be needed afterwards?

These discussions are an important part of shared decision-making in CPA care.

by GAtherton

What’s New in Aspergillosis Clinical Trials (Last ~4 Months)

An overview for patients and non-specialist readers — 19 January 2026

Over the past four months, research into aspergillosis — including chronic, allergic, and invasive forms — has continued across a range of clinical trials. These studies include treatments, diagnostics, and better ways to understand who gets sick and how best to manage it.

Below is a summary of the most relevant trials now active, recruiting, or updated recently. Whenever possible, we link to the official ClinicalTrials.gov record so you can see the details, eligibility criteria, locations, and contact information.

📋 Clinical Trials of Interest

1. Phase III Olorofim Trial for Invasive Aspergillosis

Study title: Olorofim Aspergillus Infection Study
Condition: Invasive aspergillosis (IA)
What it’s testing: A new antifungal drug called olorofim compared with liposomal amphotericin B followed by standard care.
Status: Active — not currently recruiting new patients but ongoing through 2026.
Official record: Olorofim Aspergillus Infection Study on ClinicalTrials.gov
Last updated: January 4, 2026
Why this matters: Olorofim is a completely new class of antifungal designed for patients whose infection is difficult to treat with standard drugs. It may offer an alternative for those with drug-resistant or treatment-intolerant infections.

2. Rezafungin in Chronic Pulmonary Aspergillosis (CPA)

Study title: Rezafungin for Treatment of Chronic Pulmonary Aspergillosis
Condition: Chronic pulmonary aspergillosis
What it’s testing: A long-acting echinocandin antifungal (rezafungin) that might reduce dosing frequency.
Status: Recruiting / active
Official record: Rezafungin CPA Trial on ClinicalTrials.gov
Why this matters: Current CPA treatments can require daily medication and prolonged therapy. Rezafungin’s once-weekly dosing could help reduce burden and hospital visits.

3. Combination Trial: Ibrexafungerp + Voriconazole (SCYNERGIA)

Study title: Evaluate Safety and Efficacy of Ibrexafungerp With Voriconazole in Invasive Pulmonary Aspergillosis
Condition: Invasive pulmonary aspergillosis
What it’s testing: Whether combining two antifungals works better than standard therapy alone.
Status: Active (ongoing)
Official record: SCYNERGIA Combination Trial on ClinicalTrials.gov
Why this matters: Some patients don’t respond well to single-agent treatment. Combination therapy may help in severe cases, especially where resistance is a concern.

4. PCR Diagnostic Study for Aspergillus fumigatus

Study title: PCR for Aspergillus Fumigatus in Blood and Bronchoalveolar Lavage Fluid
Condition: Aspergillosis (diagnostic focus)
What it’s testing: A blood and lung fluid PCR test to improve early detection of aspergillosis.
Status: Recruiting
Official record: PCR Aspergillus fumigatus Diagnostic Trial on ClinicalTrials.gov
First posted: 2 January 2026
Why this matters: Early diagnosis increases the chance of successful treatment. A reliable PCR test could allow clinicians to start antifungal therapy sooner.

🔎 What Else Is Ongoing?

There are other studies that include aspergillosis patients or Aspergillus exposure as part of broader research, such as:

  • All-of-Us Research Program fungal infection analysis — large observational work looking at fungal disease patterns in hundreds of thousands of people in the U.S., including aspergillosis. (Not a clinical trial per se but relevant to understanding how aspergillosis affects populations.)

  • Historic or related trials — e.g., older isavuconazole comparisons (e.g., NCT00412893) exist but are not newly updated.

🧠 What This Means for Patients

  • New antifungal drugs like olorofim and rezafungin are being tested in late-stage studies — these could expand treatment options in the future.

  • Combination therapies (e.g., ibrexafungerp + voriconazole) are being assessed to tackle difficult or resistant infections.

  • Improved diagnostics (e.g., PCR tests for Aspergillus fumigatus) are now being studied to help clinicians diagnose infections earlier and more accurately.

  • Not all trials are about treatment — some focus on better ways to detect infection or understand disease patterns, which are important for prevention and clinical practice.

🗓 How to Use These Links

Clicking a trial link takes you to the official ClinicalTrials.gov page, where you can often see:

  • Who can participate

  • Locations and contact information

  • Detailed eligibility criteria

  • Sponsor and trial timelines

If you have questions about joining a trial or how it applies to you specifically, always discuss this with your healthcare team.

by GAtherton

Indoor Damp, Ventilation & Aspergillosis

What a Major UK Evidence Review Means for Patients and Professionals

Why this paper matters

This large UK Health and Safety Executive (HSE) review examined whether microorganisms inside buildings (homes, offices, workplaces) can harm health — and what actually helps reduce risk.

Although it does not focus on a single disease, its findings are highly relevant to people living with aspergillosis, asthma, bronchiectasis, and other chronic lung conditions, as well as the professionals who support them.

Link to paper

The short answer (for everyone)

Yes — indoor environments can significantly affect lung health.
And ventilation and moisture control are central to reducing risk, especially for people vulnerable to fungal exposure.

What the review confirms (in plain language)

1. Indoor fungi are common — and not harmless

High confidence evidence

Many buildings contain airborne and surface fungi, especially when dampness is present.
The fungi most often found indoors include:

  • Aspergillus

  • Penicillium

  • Cladosporium

  • Alternaria

For aspergillosis patients, this matters because:

  • Aspergillus is not just an “outdoor mould”

  • Ongoing exposure can worsen symptoms, trigger inflammation, or complicate recovery

  • Even low levels may be problematic for sensitised or immunocompromised people

2. Dampness is a major driver of fungal exposure

High confidence

Damp buildings — whether due to leaks, condensation, or poor airflow — consistently show:

  • Higher mould growth

  • More fungal spores in the air

  • Stronger links to respiratory symptoms

Important point for patients:

You do not need to see black mould for damp to be affecting your lungs.
Mould smell (“musty odour”) is one of the strongest warning signs.

3. Ventilation is the most important protective factor

High confidence

Ventilation:

  • Dilutes fungal spores, bacteria, and viruses

  • Reduces moisture build-up

  • Lowers exposure for occupants

This applies to:

  • Homes

  • Flats

  • Offices

  • Other non-industrial indoor spaces

⚠️ The review highlights a key modern problem:
Energy-efficient, airtight buildings can unintentionally trap damp and fungi if ventilation is inadequate.

For aspergillosis patients, this means:

  • A “warm” home is not always a “healthy” home

  • Reduced airflow can increase fungal exposure even without visible mould

4. Indoor air also spreads infections

High confidence

Respiratory viruses (e.g. influenza, COVID-19) spread mainly through indoor air, especially when ventilation is poor.

This is relevant for aspergillosis patients because:

  • Viral infections can destabilise lung disease

  • Recovery may be slower

  • Secondary infections are more likely

Ventilation therefore protects against both fungal and viral risks.

5. Surfaces matter too — but air matters more

Medium–high confidence

  • Fungal material and microbes accumulate in dust, carpets, soft furnishings, and damp surfaces

  • Toilets and bathrooms can generate contaminated aerosols

  • Good hygiene helps, but cannot compensate for poor ventilation

For patients:

Cleaning alone will not solve a damp or ventilation problem.

What actually helps (evidence-based)

Strongest evidence

✔️ Adequate ventilation (natural or mechanical)
✔️ Fixing leaks and moisture sources
✔️ Removing mould-damaged materials
✔️ Preventing condensation on cold surfaces

Moderate evidence

✔️ HEPA air filtration (helpful but not a substitute for ventilation)
✔️ UV air disinfection (context-specific)
✔️ Touch-free fittings in shared buildings

⚠️ No single measure works on its own — combined approaches are needed.

Why this matters specifically for aspergillosis patients

This review strongly supports what many patients already experience:

  • Symptoms may persist despite treatment if exposure continues

  • Indoor environments can drive inflammation and relapse

  • “Just take your medication” is not enough if housing conditions are harmful

Importantly, the review recognises that:

  • Health effects vary by individual vulnerability

  • Those with asthma, bronchiectasis, aspergillosis, or immune suppression are more sensitive

  • There are no universally safe mould levels for everyone

What non-specialists should take from this

For GPs and clinicians

  • Damp and poor ventilation are legitimate medical risk factors

  • Persistent respiratory symptoms may be environment-driven

  • Asking about housing conditions is clinically relevant

For housing, environmental health & social care

  • Mould and damp are health hazards, not cosmetic defects

  • Ventilation failures can directly affect chronic disease

  • Energy efficiency must be balanced with respiratory health

For patients and carers

  • You are not “overreacting” if your home affects your breathing

  • Ventilation and moisture control are part of disease management

  • Evidence supports advocating for safer living conditions

Bottom line

This major UK review confirms that indoor dampness and poor ventilation increase exposure to fungi — including Aspergillus — and worsen respiratory health.
For people living with aspergillosis, building conditions are not secondary issues: they are part of the disease environment.

by GAtherton

Sinusitis in Patients with ABPA

When to suspect it, when to investigate, and when to refer

Why this matters

Patients with allergic bronchopulmonary aspergillosis (ABPA) are usually managed as having a lung disease. Diagnosis, monitoring, and treatment focus appropriately on the chest, immunology, and asthma control.

However, ABPA occurs within a single continuous airway, extending from the nose and sinuses to the lungs. Disease in the upper airway can coexist with, exacerbate, or complicate lower airway inflammation — yet sinus disease is not routinely assessed in ABPA care pathways.

This article outlines:

  • What is known about sinus disease in this context

  • Which symptoms should raise suspicion

  • When investigation or ENT referral should be considered

  • What GPs and non-specialists can reasonably do

The united airway: a brief reminder

The upper and lower airways share:

  • Type 2 (eosinophilic) inflammation

  • Immunoglobulin E–mediated immune responses

  • Common triggers, including allergens and fungi

Chronic rhinosinusitis is common in asthma and severe asthma, and treatment of sinus disease can improve lower airway outcomes in some patients.
ABPA sits within this same inflammatory spectrum, even though its management is lung-centred.

Sinus disease in ABPA: what is (and isn’t) known

What we know

  • Chronic rhinosinusitis is common in patients with asthma and severe asthma

  • Sinus disease may be symptomatic or relatively silent

  • ABPA guidelines do not mandate routine ENT review or sinus imaging

  • ENT involvement, therefore, varies widely between centres

What we do not know

  • Whether routine ENT assessment improves ABPA outcomes

  • Which ABPA patients benefit most from sinus intervention

  • The optimal timing for ENT referral in ABPA

As a result, clinical judgement remains central.

Symptoms that should prompt consideration of sinus disease

Sinusitis in ABPA patients does not always present with classic “blocked nose and facial pain”.
Key symptoms include:

Common but often overlooked

  • Persistent post-nasal drip

  • Foul, bitter, metallic, or “infected” taste in the mouth

  • Throat clearing, chronic cough

  • Thick or sticky mucus sensation

  • Symptoms are worse on waking or lying flat

More typical sinonasal features

  • Nasal blockage or congestion

  • Facial pressure or fullness

  • Reduced or altered sense of smell

  • Nasal crusting or discharge

Contextual clues

  • Poor durability of response to steroids or antifungals

  • Recurrent “flares” without clear chest triggers

  • Coexisting severe asthma or nasal polyps

  • Symptoms are worse in damp or mould-affected housing

A persistent foul taste in the mouth is a recognised symptom of chronic sinus disease, usually due to post-nasal drainage of inflamed secretions.

Damp homes and sinus disease

Living in damp or mould-affected environments is associated with:

  • Higher rates of chronic rhinosinusitis

  • Upper airway irritation and inflammation

  • Allergic sensitisation to fungal spores

In most cases, this results in inflammatory or allergic sinusitis, not invasive fungal infection.
Fungal involvement may act as an immune trigger, even when not labelled as “fungal sinusitis”.

Fungal sinusitis: rare vs under-recognised

It is important to distinguish between entities:

Type Frequency Key point
Invasive fungal sinusitis Rare Usually immunocompromised; dramatic presentation
Fungal ball (mycetoma) Uncommon Usually obvious on CT
Allergic fungal rhinosinusitis Likely under-recognised Requires active suspicion

Allergic fungal rhinosinusitis overlaps biologically with ABPA:

  • IgE-mediated

  • Eosinophilic inflammation

  • Thick allergic mucin

It is not routinely sought, so it may be under-diagnosed in at-risk groups.

What GPs and non-specialists can reasonably do

1. Take upper airway symptoms seriously

Especially in ABPA or severe asthma patients with:

  • Persistent post-nasal symptoms

  • Foul taste

  • Recurrent unexplained deterioration

2. Examine the nose and throat

  • Look for polyps, discharge, and crusting

  • Note mouth breathing or altered voice quality

  • Check dentition (to exclude dental causes)

3. Consider imaging when symptoms persist

  • CT sinuses (not plain X-ray) is the imaging of choice

  • Particularly appropriate if symptoms last >8–12 weeks or recur

4. Refer to ENT when:

  • Symptoms are persistent or progressive

  • CT shows significant sinus disease

  • There is a poor response to standard medical therapy

  • There is diagnostic uncertainty

Referral does not imply surgery — ENT input may be diagnostic or medical.

What this article is not saying

  • It does not suggest that all ABPA patients need an ENT referral

  • It does not claim that sinus treatment improves ABPA outcomes

  • It does not override existing guidelines

It does suggest that earlier consideration of the upper airway is reasonable in selected patients.

Key take-home points for clinicians

  • The airway functions as a single inflammatory system

  • Sinus disease may be subtle, under-reported, or atypical

  • A foul taste in the mouth is a meaningful symptom

  • Damp or mould exposure increases sinus disease risk

  • ENT referral is appropriate when symptoms persist or recur

  • Evidence gaps remain — but clinical vigilance is justified

In summary

ABPA is managed as a lung disease, but patients live with a whole airway.
Recognising when sinus disease may be contributing can help explain persistent symptoms and guide appropriate referral — without over-investigation or over-treatment.

by GAtherton

ABPA and Work: What a Patient Poll Tells Us About Employment, Health, and Real-World Impact

An article for patients, GPs, and non-specialist healthcare professionals

Allergic bronchopulmonary aspergillosis (ABPA) is often discussed in terms of lung function, immunology, and imaging. Far less often do we talk about its impact on everyday life, particularly on a person’s ability to work.

A poll run within the National Aspergillosis Centre patient community asked a simple but powerful question:

Who is still able to work while living with ABPA – and who has had to stop or retire?

The responses provide an important insight into the functional and socioeconomic burden of ABPA.

Key findings from the poll (patient-reported)

  • Working full time: 17%

  • Working part time (days or hours): 18% combined

  • Not working: 30%

  • Retirement age: 21%

  • Retired early for health reasons: 12%

  • Currently on sick leave / full-time carer / pre-diagnosis: small but notable groups

Even allowing for the informal nature of a social media poll, the overall pattern is clear.

What this tells us

1. Sustained full-time work is uncommon in ABPA

Fewer than one in five respondents were able to work full time. Even among those still working, many described reduced hours, flexible arrangements, or fragile employment dependent on day-to-day health.

ABPA is often incompatible with predictable, high-demand working patterns.

2. ABPA frequently leads to work loss or early retirement

A substantial proportion of respondents were either:

  • No longer working at all, or

  • Retired earlier than planned specifically because of health

This is particularly striking given that ABPA often affects people during their working years and may coexist with asthma, bronchiectasis, or long-term steroid use.

3. “Retirement age” can hide health-forced exit

Some respondents selected “retirement age,” but accompanying comments revealed that many:

  • Left work earlier than expected

  • Changed careers or reduced responsibilities years before retirement

  • Worked through ill health until they no longer could

This matters when interpreting employment statistics: health-driven work loss may be underestimated.

4. Unpaid work and instability are often overlooked

The poll also highlighted:

  • People currently on prolonged sick leave

  • Full-time unpaid carers

  • Individuals still awaiting diagnosis but already struggling to work

These groups are frequently invisible in employment data, yet represent significant personal and societal impact.

Why ABPA affects the ability to work

For patients and non-specialists, it is important to understand that work difficulties in ABPA are not simply due to “asthma symptoms.”

Common contributors include:

  • Chronic breathlessness and cough

  • Severe fatigue and post-exertional exhaustion

  • Recurrent chest infections

  • Steroid side-effects (muscle weakness, bone disease, mood changes, diabetes risk)

  • Unpredictable flare-ups requiring rest, antibiotics, or hospital care

  • Cognitive and emotional burden of long-term illness

Together, these make consistent attendance, physical work, and high cognitive load difficult to sustain.

Implications for patients

  • Difficulty working is not a personal failure

  • Many others with ABPA face similar challenges

  • Adjustments, reduced hours, or stopping work altogether may be medically appropriate

  • Asking for support is reasonable and justified

Implications for GPs and non-specialist clinicians

  • Employment status should be considered a key outcome of disease control

  • Fit notes, occupational health input, and benefits documentation are part of holistic care

  • ABPA is a fluctuating condition – patients may cope for periods and then deteriorate

  • Statements such as “lung function is stable” do not always reflect real-world functioning

Understanding the work impact helps clinicians better support patients in consultations, reports, and advocacy.

Implications for systems and policy

This poll reinforces that ABPA carries a significant socioeconomic burden, including:

  • Reduced workforce participation

  • Early retirement

  • Increased reliance on health and social support systems

Any assessment of disability, employment capability, or long-term planning must take into account:

  • Variability over time

  • Treatment burden

  • Side-effects of necessary medications

In summary

This patient poll sends a consistent message:

ABPA commonly limits the ability to work, often leading to reduced hours, unstable employment, or early exit from the workforce.

For patients, this experience is shared and valid.
For clinicians, it is a reminder that ABPA is not just a radiological or immunological diagnosis, but a life-limiting condition with real-world consequences.

by GAtherton

Season’s Greeting

As the year draws to a close, we would like to send warm wishes to everyone in the aspergillosis community — patients, families, carers, clinicians, nurses, scientists, and all professionals working to improve care and understanding.

Living with aspergillosis, or supporting those who do, often requires resilience, patience, and compassion. Throughout this year, we have seen remarkable strength from patients, dedication from healthcare teams, and generosity of spirit across our wider community.

At this time of reflection and renewal — whether you mark Christmas, another festival, or simply the turning of the year — we hope you find moments of rest, comfort, and connection. May the days ahead bring steadier health where possible, renewed energy, and continued progress in care, research, and support.
Thank you for being part of this community.

With warmest wishes for peace, kindness, and hope — now and into the New Year.

by GAtherton