Cystic Fibrosis, CFTR Gene Variants, and Aspergillosis

Last reviewed: 8 April 2026

Some people with aspergillosis are told they have cystic fibrosis (CF), or that they carry a CFTR gene variant. This can be unexpected and may raise concerns about whether this explains their symptoms or diagnosis.

This article explains how cystic fibrosis and CFTR gene variants relate to Aspergillus-related lung disease, what current research shows, and—importantly—what conclusions should not be drawn.

Key points
Important reassurance
What is cystic fibrosis?
What is a CFTR gene variant?
How CFTR affects the lungs
How Aspergillus behaves in the lungs
ABPA and cystic fibrosis
CPA and cystic fibrosis
Modern CF treatments and Aspergillus
Does a CFTR variant explain symptoms?
What should patients take from this?
When to seek medical advice
Conclusion
References

Key points

Most people with aspergillosis do not have cystic fibrosis.
Most people with cystic fibrosis do not develop ABPA or CPA.
ABPA is linked to mucus and immune responses, not just infection.
CFTR variants may contribute to risk in some people, but are usually only one factor.
CPA is mainly driven by structural lung damage, not CFTR genetics.

Important reassurance

Most people with aspergillosis do not have cystic fibrosis, and most people with cystic fibrosis do not develop Aspergillus-related disease.

Although these conditions can overlap, they are usually separate. Genetic findings such as CFTR variants should be interpreted carefully and in context.

What is cystic fibrosis?

Cystic fibrosis is a genetic condition caused by changes in the CFTR gene. This gene regulates salt and water movement across cells.

When CFTR function is reduced:

mucus becomes thick and sticky
airways are harder to clear
microorganisms persist more easily

This creates an environment where bacteria and fungi can accumulate over time.

What is a CFTR gene variant?

CFTR variants range from severe mutations (causing cystic fibrosis) to mild or uncertain variants.

Carriers (with one variant):

are common in the general population
usually have no symptoms
may have subtle effects in some cases

These subtle effects may include reduced mucus clearance or increased susceptibility to airway inflammation.

How CFTR affects the lungs

CFTR dysfunction affects the lungs in several key ways:

Mucus dehydration: mucus becomes thick and difficult to clear
Impaired clearance: particles and microbes remain in the airways
Chronic inflammation: immune responses become exaggerated

This combination creates a “retention environment” where inhaled organisms—including Aspergillus—may persist.

How Aspergillus behaves in the lungs

Aspergillus is inhaled by everyone, but its effects vary depending on the lung environment.

Healthy lungs: spores are cleared
Impaired clearance: spores may persist
Sensitive immune system: allergic reactions may develop
Damaged lungs: chronic infection may develop

This explains why Aspergillus-related disease is diverse and depends heavily on underlying lung conditions.

ABPA and cystic fibrosis

ABPA is an allergic immune reaction to Aspergillus.

It is recognised in cystic fibrosis because:

mucus retention increases exposure to Aspergillus
immune responses can be exaggerated

However:

Many CF patients never develop ABPA
Most ABPA patients do not have CF

Some studies suggest CFTR variants may increase susceptibility, but this is not consistent across all research.

Key message: ABPA and CF can overlap, but one does not imply the other.

CPA and cystic fibrosis

CPA is a chronic fungal infection that develops in structurally damaged lungs.

The most important risk factor is:

pre-existing lung damage

This includes:

bronchiectasis
previous tuberculosis
COPD

Cystic fibrosis can lead to bronchiectasis, and therefore indirectly increase CPA risk.

However:

CPA is rarely driven directly by CFTR genetics
most CPA patients do not have CF

Key message: CPA is primarily a disease of lung structure, not genetics.

Modern CF treatments and Aspergillus

CFTR modulators (such as elexacaftor/tezacaftor/ivacaftor) have transformed CF care.

They:

improve CFTR function
thin mucus
improve clearance

Studies suggest:

reduced Aspergillus detection in some patients
fewer ABPA exacerbations in some cases

However:

ABPA still occurs
existing lung damage remains
immune responses are not fully corrected

Overall: these therapies improve risk but do not eliminate Aspergillus-related disease.

Does a CFTR variant explain symptoms?

No single factor explains complex lung disease.

Symptoms may result from:

underlying lung disease
infection
inflammation
environmental exposure

A CFTR variant may contribute, but is rarely the sole cause.

What should patients take from this?

CF and CFTR variants can sometimes contribute
ABPA has the strongest connection
CPA is mainly driven by lung damage
Most patients with aspergillosis do not have CF

When to seek medical advice

Seek advice if symptoms worsen, change, or include coughing up blood, fever, or chest pain.

Conclusion

Cystic fibrosis and CFTR gene variants can play a role in some patients with Aspergillus-related lung disease, particularly where mucus clearance is affected. However, they should not be overemphasised. In most cases, they are just one part of a broader clinical picture involving lung structure, immune response, and environmental exposure.

References

This article is for general information and does not replace advice from your clinical team.

by GAtherton

Asthma and Aspergillosis

How fungal spores interact with asthma and other lung diseases

Every day we inhale thousands of microscopic fungal spores from the environment. One of the most common fungi in the air is Aspergillus fumigatus. In healthy lungs these spores are removed quickly by the lungs’ natural defence systems and cause no illness.

However, in people with asthma—particularly severe asthma—the interaction between the lungs and Aspergillus can be very different. The fungus may trigger allergic inflammation, grow in mucus within the airways, or occasionally contribute to chronic lung disease.

Understanding this relationship helps explain several important conditions including:

Aspergillus sensitisation
Severe Asthma with Fungal Sensitisation (SAFS)
Allergic Bronchopulmonary Aspergillosis (ABPA)
Aspergillus bronchitis
Chronic Pulmonary Aspergillosis (CPA)

Although asthma is the most common condition linked to Aspergillus allergy, other lung diseases such as bronchiectasis, Chronic Obstructive Pulmonary Disease (COPD), and tuberculosis-related lung damage can also create environments where the fungus becomes important.

Why Asthma Creates a Favourable Environment for Aspergillus

Asthma is a disease of airway inflammation and hyper-reactivity. The bronchi narrow during attacks because the airway wall becomes swollen and the surrounding smooth muscle contracts.

Several features of asthma make it easier for Aspergillus spores to remain in the lungs.

Mucus production

Asthma often causes increased production of thick airway mucus.

Normally mucus traps inhaled particles and moves them upward toward the throat via the mucociliary escalator.

In asthma:

mucus becomes thicker
clearance becomes less efficient
spores remain trapped

This trapped environment allows fungal spores to persist in the airway mucus.

Allergic immune responses

Many asthma patients have Type-2 (T2) inflammation (50-70%), involving immune pathways driven by:

Immunoglobulin E (IgE)
Interleukin-4
Interleukin-5
Interleukin-13
eosinophils

These pathways respond strongly to fungal allergens. When the immune system recognises Aspergillus proteins it may trigger allergic inflammation in the airways.

Fungal sensitisation is increasingly recognised as an important contributor to severe asthma (PMID: 24735832).

Aspergillus Sensitisation

Many people with asthma develop allergic sensitisation to Aspergillus.

Sensitisation means the immune system produces antibodies against fungal proteins.

Features include:

positive Aspergillus skin test or IgE blood test
worsening asthma symptoms
increased exacerbations

Studies suggest 10–25% of patients attending severe asthma clinics show Aspergillus sensitisation (PMID: 24735832).

However, sensitisation alone does not necessarily cause lung damage.

Severe Asthma with Fungal Sensitisation (SAFS)

Some patients with severe asthma have fungal sensitisation but do not meet the criteria for ABPA.

This condition is known as Severe Asthma with Fungal Sensitisation (SAFS).

Typical features include:

severe or poorly controlled asthma
fungal allergy
moderate IgE elevation

A randomised controlled trial demonstrated that antifungal therapy may improve symptoms in some SAFS patients (PMID: 18948425).

Allergic Bronchopulmonary Aspergillosis (ABPA)

Allergic Bronchopulmonary Aspergillosis is the most important Aspergillus-related disease associated with asthma.

ABPA occurs when Aspergillus grows within airway mucus and triggers a strong allergic immune response.

Typical findings include:

very high total IgE levels
Aspergillus-specific IgE and IgG antibodies
eosinophilia
mucus plugs containing fungal hyphae
central bronchiectasis

ABPA occurs in approximately:

1–2% of all asthma patients
up to 10–15% of severe asthma patients

These figures come from global prevalence estimates of ABPA in asthma populations (PMID: 23210682/.

Modern diagnostic criteria for ABPA were updated by the International Society for Human and Animal Mycology (ISHAM) in 2024 (PMID: 38423624).

Asthma and Aspergillus Disease Pathway

Possible interactions between asthma and Aspergillus. Some patients develop allergic disease (ABPA) which may lead to airway damage such as bronchiectasis (NB Progression to CPA is very rare).

When ABPA Causes Bronchiectasis

Repeated inflammation from ABPA may damage airway walls and lead to bronchiectasis.

Bronchiectasis occurs when airways become:

permanently widened
distorted
unable to clear mucus effectively

Instead of being cleared from the lungs, mucus pools in the airways.

This retained mucus creates an environment where microorganisms—including fungi—can grow.

Aspergillus Bronchitis

In some patients with bronchiectasis or chronic lung disease, Aspergillus may persist in airway mucus and cause chronic airway infection rather than allergy.

Symptoms may include:

chronic cough
sputum production
repeated positive Aspergillus cultures

IgE levels are usually lower than in ABPA.

Chronic Pulmonary Aspergillosis (CPA)

Chronic Pulmonary Aspergillosis is a slowly progressive fungal infection of damaged lung tissue.

CPA usually develops in lungs containing:

cavities
severe structural damage

Common underlying diseases include:

tuberculosis
sarcoidosis
severe COPD

Globally, the most common cause of CPA is previous tuberculosis infection (PMID: 22271943).

Asthma alone rarely causes CPA, but severe bronchiectasis or ABPA-related lung damage may occasionally lead to it.

Aspergillosis and Immune Competence

Different forms of aspergillosis occur depending on lung damage and immune function.

Key Messages

Asthma is one of the most important diseases associated with Aspergillus-related lung conditions.
Many asthma patients develop fungal sensitisation.
A smaller proportion develop Allergic Bronchopulmonary Aspergillosis (ABPA).
Repeated inflammation from ABPA can lead to bronchiectasis.
Chronic pulmonary aspergillosis is rare in asthma alone but may occur if significant lung damage develops.

Understanding these interactions helps guide diagnosis and treatment for people living with asthma and Aspergillus-related disease.

Looking further into the future - could we control lung damage, preserve healthy lung tissue better?

Can Lungs Repair Themselves?

What New Research Means for People with CPA (and Other Aspergillosis)

A recent scientific discovery has helped researchers understand how certain lung cells decide whether to focus on repairing damage or defending against infection. The work, highlighted by the Mayo Clinic and published in Nature Communications, describes a molecular “switch” inside specialised lung cells that influences this balance.

For people living with Chronic Pulmonary Aspergillosis (CPA) — and also those with Allergic Bronchopulmonary Aspergillosis (ABPA) — this kind of research is relevant. But it needs careful explanation.

This is not about rebuilding destroyed lungs.
It is about understanding how to better protect and preserve the lung tissue that remains.

The Discovery: A “Repair vs Defence” Switch

Researchers identified a regulatory circuit in alveolar type II (AT2) cells — specialised cells that:

Produce surfactant (which keeps air sacs open)
Act as a reserve “repair” population in the lung
Can regenerate other essential lung cells after injury

The study showed that these cells operate under tight control. When infection is present, they prioritise defence. When injury needs healing, they can switch into repair mode.

The key insight is that this switch is biologically regulated. It is not random. That means, in theory, it may one day be possible to influence it.

What “Repair” Means — and What It Does Not Mean

When we talk about lung repair in this context, we must be very clear.

It does not mean:

Lung cavities caused by CPA will close in the foreseeable future
Established fibrosis will melt away
Bronchiectasis will reverse
Severely distorted lung architecture will rebuild

CPA cavities represent major structural remodelling — destruction of alveoli, scarring, altered blood supply, and thickened pleura. Reconstructing that complex architecture is biologically extremely challenging and not currently realistic within the next decade.

What repair does realistically mean

In chronic lung disease, “repair” is more likely to mean:

Supporting survival of remaining alveoli
Preventing excessive fibrotic signalling
Helping lung lining cells recover more efficiently after inflammation
Reducing cumulative injury from repeated infection
Slowing progression of structural change

In other words:

Not rebuilding what is gone — but better protecting what remains.

For many people with CPA, this is a crucial distinction.

Why Preservation Is a Major Goal in CPA

CPA usually develops in lungs already weakened by conditions such as tuberculosis, non-tuberculous mycobacteria, chronic obstructive pulmonary disease, or severe pneumonia.

Over time, CPA can lead to:

Expanding cavities
Progressive scarring
Reduced gas exchange
Reduced exercise tolerance

Many patients have limited lung reserve. Even small additional losses of functioning lung tissue can significantly increase breathlessness or fatigue.

If future therapies could slow the rate of progression — even modestly — that would meaningfully affect long-term outcomes.

Flattening the decline curve is not trivial. It changes quality of life.

Why This Also Matters in ABPA

In ABPA, repeated inflammatory episodes can lead to:

Airway remodelling
Mucus plugging
Development or progression of bronchiectasis

Better control of inflammatory signalling — combined with improved epithelial recovery — could reduce long-term airway damage.

Again, this is about preservation rather than reversal.

Where Development Has Reached

The current research is still laboratory-based. It used advanced techniques such as:

Single-cell sequencing
Imaging of lung tissue
Preclinical models of injury

No human treatments based on this discovery are yet available.

However, the significance lies in identifying:

A defined molecular pathway
A controllable regulatory mechanism
A clearer understanding of why repair fails in chronic inflammation

That foundational knowledge is what eventually allows targeted drug development.

The Balance Challenge in Aspergillosis

There is an additional complexity in fungal lung disease.

Any attempt to promote repair must not weaken antifungal defence.

The immune system must:

Control Aspergillus
Avoid causing excessive inflammatory damage

Future therapies would need to strike that balance carefully.

What This Means for Patients Now

This discovery does not change current treatment.

The most effective preservation strategies today remain:

Consistent antifungal therapy when indicated
Careful inflammatory control
Biologic therapies where appropriate
Airway clearance
Vaccination and infection prevention
Avoiding damp and mould exposure
Pulmonary rehabilitation

These measures are already forms of lung preservation.

A Realistic and Hopeful Perspective

It is unlikely that cavities from CPA will be repaired in the near future.

It is realistic that within the next 5–10 years we may see improved strategies aimed at:

Slowing structural progression
Supporting endogenous repair cells
Reducing fibrotic signalling
Improving recovery after exacerbations

For people living long-term with CPA or ABPA, even incremental preservation could significantly affect independence and quality of life.

The science is still early — but understanding how the lung decides to repair itself is an important step forward.

Reference

Sawhney, A.S., Deskin, B.J., Cai, J. et al. A molecular circuit regulates fate plasticity in emerging and adult AT2 cells. Nat Commun 16, 8924 (2025). https://doi.org/10.1038/s41467-025-64224-1

by GAtherton

Can blood tests help predict if chronic pulmonary aspergillosis will come back?

This study from the National Aspergillosis Centre (NAC) looked at people with chronic pulmonary aspergillosis (CPA) who had completed antifungal treatment and asked a simple question:

Can blood tests tell us who is more likely to relapse after treatment stops?

What the researchers did

Doctors reviewed patients with CPA who had:

Taken antifungal treatment for at least 6 months
Stopped treatment because they were clinically stable

They then followed these patients to see who stayed well and who relapsed, and compared this with their blood test results at the time treatment stopped.

What they found

About 1 in 4 patients had a relapse after stopping treatment
People whose Aspergillus IgG blood test was still high at the end of treatment were much more likely to relapse
Patients whose IgG level had fallen to a lower level did not relapse in this study
Signs of Aspergillus allergy or sensitisation also increased relapse risk
CT scan appearances and treatment length alone were not reliable predictors

Why this matters for patients

This means that:

Blood tests may help doctors decide when it is safe to stop treatment
Some people may need closer follow-up or longer treatment
Follow-up can be more personalised, rather than “one size fits all”

Importantly, a relapse does not mean treatment failed — it reflects how persistent this infection can be in damaged lungs.

Key takeaway

A simple blood test at the end of treatment may help predict who needs closer monitoring for CPA relapse.

This research supports a more individualised approach to long-term CPA care.

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

⭐ Chronic Pulmonary Aspergillosis: Why Diagnosis Is Missed and Who Needs to Be More Aware

With estimated prevalence of 3–4 cases per 100,000 population, and far higher rates in high-risk groups.

Chronic Pulmonary Aspergillosis (CPA) is a slowly progressive fungal lung disease affecting an estimated 3–4 per 100,000 people in the UK, with higher estimates in global settings with greater TB prevalence. Despite this, many clinicians will go through entire careers without confidently recognising it — not because it is extremely rare, but because it almost always hides inside other long-term lung diseases.

The UK is unusual in having a nationally commissioned specialist service — the National Aspergillosis Centre (NAC), based at Wythenshawe Hospital, Manchester — offering funded diagnostics, multidisciplinary review, and long-term antifungal management. But only a fraction of expected CPA cases are ever referred. Most are simply never diagnosed.

This article explains why diagnoses are missed, who is at highest risk, which specialities need to be more alert, and the red flags that should trigger testing or referral.

⭐ How Common Is CPA? The Numbers Behind the Problem

The UK prevalence is estimated at 3–4 per 100,000 people — approximately 2,000–2,500 people with CPA at any given time.

But the risk is far higher in specific groups:

Risk Group	Estimated CPA prevalence
Post-TB lung disease	6–10% in those with residual cavities
Severe COPD (GOLD III–IV)	1–3%
Bronchiectasis	1–3%
NTM disease	3–10%
Sarcoidosis with fibrosis	1–2%
Immunosuppression (steroids/biologics)	Unknown, but rising

Using these figures, the true UK caseload could exceed 4,000–6,000 individuals, yet NAC receives ~500–1,000 referrals, highlighting a large diagnostic gap.

⭐ Why CPA Is So Often Missed

1. Symptoms mimic common chronic lung diseases

CPA presents with:

Persistent cough
Breathlessness
Fatigue
Weight loss
Recurrent “chest infections”
Haemoptysis

These overlap almost perfectly with:

COPD
bronchiectasis
post-TB changes
long COVID
NTM infection
repeatedly “slow to clear” pneumonia

Because symptoms are non-specific, clinicians rarely think fungal.

2. Interpretation of imaging is inconsistent

CPA shows:

one or more cavities
pleural thickening
nodules
progressive changes over months
fungal balls

Common reporting pitfalls:

labelled “post-infective scarring”
misinterpreted as malignancy
seen but not compared longitudinally
incidental CT findings not acted upon

Radiology is one of the biggest missed opportunities for early detection.

3. IgG testing is not routinely requested

Aspergillus IgG is the key diagnostic biomarker — but it is:

often confused with IgE
not available in some hospitals
omitted from workups for recurrent infection
unfamiliar to non-respiratory clinicians

Without IgG, CPA is rarely diagnosed.

4. Short-term improvement with antibiotics is misleading

Patients with CPA may temporarily feel better after:

broad-spectrum antibiotics
steroids
physiotherapy

This transient improvement creates false reassurance.

5. CPA spans multiple specialisms — and no one owns it

Diagnosis requires combined expertise across:

respiratory medicine
infectious diseases
radiology
microbiology
immunology

When no one speciality takes responsibility, patients get lost.

⭐ Which Patients Are at High Risk?

CPA almost always develops on a background of existing lung damage.

1. Post-TB lung disease (PTLD)

Globally the largest CPA population.
Residual cavities are the strongest predictor.

Specialities needing awareness:

TB teams
ID physicians
Radiologists
Community TB nurses
Public health TB programmes

2. COPD (especially severe / emphysema)

Millions of people are potentially at risk.
Recurrent infections + bullae/cavities = fertile ground for CPA.

Specialities:

COPD clinics
Pulmonary rehab
Acute medicine (frequent admissions)

3. Bronchiectasis

Damaged airways enable persistent Aspergillus colonisation and inflammation.

Specialities:

Bronchiectasis MDTs
Severe asthma & NTM clinics
Respiratory physiotherapy

4. Sarcoidosis and ILD

Fibrosis and traction bronchiectasis develop cavities over time.

5. Post-COVID or post-influenza structural disease

Emerging risk group, especially in patients with:

ventilatory lung injury
persistent CT abnormalities
chronic steroid exposure

6. Chronic steroid or immunomodulator use

While invasive aspergillosis is linked to profound immunosuppression, CPA often affects those with milder, chronic immune dysfunction:

systemic steroids
high-dose inhaled steroids
biologics affecting eosinophils
poorly controlled diabetes
chronic kidney disease
malnutrition

⭐ Which Specialities Need to Be More Alert?

Respiratory Medicine – primary detection, but awareness varies greatly
Infectious Diseases – especially post-TB and persistent infection clinics
Radiology – key to spotting early changes
Primary Care – sees patients repeatedly with “ongoing chest infections”
Emergency & acute medicine – haemoptysis presentations
Bronchiectasis and NTM services – strong overlap
Severe asthma and biologics teams – ABPA → CPA evolution
TB clinics – highest prevalence globally, often least recognised

The National Aspergillosis Centre should be the referral point for any complex or uncertain case.

⭐ Red Flags: When to Suspect CPA

1. Cavities on CT (thin-, thick-walled, evolving, or multiple)

Especially with pleural thickening.

2. Haemoptysis

CPA is one of the most common causes of haemoptysis in people with cavities.

3. Symptoms lasting >3 months

Chronic cough, fatigue, weight loss, breathlessness.

4. “Recurrent infections” that never fully resolve

5. Post-TB patient with any new or worsening symptoms

6. Bronchiectasis patient with new cavity or Aspergillus culture

7. High or rising Aspergillus IgG

8. ABPA patient who deteriorates off antifungals

⭐ The Cost of Missed Diagnoses

When CPA is not recognised early, the consequences are severe:

irreversible lung damage
repeated hospitalisations
emergency haemoptysis events
prolonged antifungal therapy with more toxicity
reduced quality of life
avoidable deaths

For systems like the NHS, late diagnosis increases costs:

unplanned admissions
repeated CT imaging
prolonged antibiotics
intensive care during haemoptysis
complex surgery (lobectomy/pneumonectomy)

Early referral to specialist centres like the National Aspergillosis Centre prevents many of these harms.

⭐ Conclusion

CPA is not rare within the populations most likely to develop it.
Missed diagnoses are common, predictable, and preventable.

By increasing awareness across Respiratory, Infectious Diseases, Radiology, Primary Care, TB services, and severe asthma pathways — and by using simple tools such as Aspergillus IgG and careful CT interpretation — clinicians can dramatically reduce the diagnostic delay that damages lungs, quality of life, and survival.

The UK is fortunate to have the National Aspergillosis Centre as a nationally commissioned referral service. Recognising CPA early and referring appropriately has the power to save lives, reduce system costs, and improve long-term outcomes.

by GAtherton

🌿 Biologics when ABPA and CPA overlap: What Patients Need to Know

Understanding how they work, when they’re helpful, and when extra care is needed

Biologic medicines (such as omalizumab, mepolizumab, benralizumab, dupilumab and newer options like tezepelumab) are increasingly used to treat Allergic Bronchopulmonary Aspergillosis (ABPA) and severe asthma. They can be life-changing for some people.

However, their place in Chronic Pulmonary Aspergillosis (CPA) — especially in people who have both ABPA and CPA together — is more complicated and needs careful specialist supervision.

This article explains what we know so far.

🌟 1. ABPA and CPA are different conditions — but some people have both

ABPA is mainly an allergic reaction to Aspergillus in the airways.
CPA is a chronic fungal infection that causes cavities, scarring, and long-term lung damage.
Some people start with ABPA and later develop CPA, or the two conditions overlap.
The 2024 international ABPA guidelines now recognise this overlap as real and important.

Because biologics target allergy pathways rather than fungal infection, treatment decisions must look at both sides of the disease.

🌿 2. Biologics in ABPA: the evidence is strong and growing

Biologics can help patients with ABPA or severe asthma by:

reducing steroid use
improving breathing
decreasing mucus plugging
lowering flare-ups
improving quality of life

Biologics most commonly used in ABPA include:

Biologic	Target	Notes
Omalizumab	IgE	Well established, helps many ABPA patients
Mepolizumab	IL-5	Helps eosinophilic inflammation
Benralizumab	IL-5Rα	Similar to mepolizumab; long-acting
Dupilumab	IL-4Rα	Very promising for allergic disease; growing evidence for ABPA
Tezepelumab	TSLP	Very new; limited ABPA data so far

For many people with ABPA, biologics are safe and effective when monitored.

⚠️ 3. Biologics and CPA: much less evidence

CPA is caused by persistent fungal infection and structural lung damage.
Biologics do not treat fungal infection, and they do not prevent cavities.
In CPA, the mainstay of treatment is still:
- antifungal medication (usually itraconazole, voriconazole or posaconazole)
- careful imaging (CT scans)
- airway clearance
- sometimes surgery or bronchoscopy

There is no strong evidence that biologics help CPA itself.

🔄 **4. What about patients who have both ABPA and CPA?**

This is where things become more complex.

Biologics may help the allergic part (ABPA), but:

they do not treat fungal infection
they do not stop fungal cavities from progressing
they may reduce inflammation that normally helps the body contain infection

If antifungal treatment is interrupted or not strong enough, fungal activity may increase while the allergic symptoms improve — so regular monitoring is essential.

Specialist centres (like the NAC) now emphasise:

✔️ Continue antifungals if CPA is active
✔️ Watch cavities with regular CT scans
✔️ Monitor Aspergillus IgG/IgE and fungal cultures
✔️ Check whether symptoms are from allergy, infection, or both
✔️ Make joint plans between asthma/airway doctors and mycology specialists

❓ 5. Are some biologics better than others for ABPA/CPA overlap?

There is no official guidance yet, but early observations suggest:

⭐ Most promising for ABPA:

Dupilumab seems particularly effective for allergic disease (IgE, mucus, airflow), though still off-label for ABPA.

⭐ Increasing interest:

Tezepelumab works outside the eosinophil pathway and may be useful in some asthma types, but research in ABPA is only just starting.

⭐ Useful in selected cases:

Anti-IL-5 biologics (mepolizumab, benralizumab) help airway eosinophils but may not help every ABPA patient.

⚠️ Uncertain in CPA:

None of the biologics treat fungal infection or cavities directly.
Their role in active CPA remains unclear and requires careful oversight.

🧭 6. What this means for patients

If you have ABPA only, biologics may be an excellent option — especially if:

steroids cause side-effects
your asthma is uncontrolled
you have frequent flare-ups
your IgE levels are very high
mucus plugging or wheezing continues despite treatment

If you have CPA or cavities, treatment needs to be more cautious:

antifungal medication usually needs to continue
biologics may still help if the allergic component is significant
CT scans must be repeated to make sure cavities are not progressing
specialists must weigh benefits vs. risk for each patient individually

💬 7. Summary

Biologics can be extremely helpful for ABPA.
They do not treat CPA, and cannot replace antifungal medicines.
In patients with both ABPA and CPA, the approach must be personalised.
Dupilumab and (possibly) tezepelumab are emerging biologics with promise, but evidence is still developing.
Decisions should always be made with a specialist centre such as the National Aspergillosis Centre (NAC).

by GAtherton

🌬️ Inhaled Antifungal Treatments for Chronic Pulmonary Aspergillosis (CPA)

Updated: October 2025

💡 Why are inhaled antifungals being developed?

For people living with Chronic Pulmonary Aspergillosis (CPA), treatment usually involves long courses of oral antifungal tablets such as itraconazole, voriconazole, or posaconazole.
These medicines circulate through the whole body to reach the lungs — but sometimes they cause side-effects, interact with other drugs, or fail to reach high enough levels in thick mucus, cavities, or scarred areas of lung tissue.

Inhaled antifungal therapy aims to solve this problem by delivering medicine directly to the lungs using a nebuliser or inhaler device.
This can potentially mean:

✅ Higher drug levels exactly where infection is active
⚡ Faster local action
🚫 Fewer whole-body side-effects
🧩 Fewer drug interactions

This approach is especially promising for patients with localized lung disease, such as CPA or aspergillus bronchitis, where the fungus lives in damaged parts of the lung.

💊 Current inhaled antifungal options (used off-label)

🧪 Nebulised Amphotericin B

At the moment, nebulised amphotericin B is the only inhaled antifungal used in hospitals, although it is off-label for CPA.

It is more commonly used to prevent infection in people who have had a lung transplant or who are severely immunocompromised.
In some specialist centres, it may be used as maintenance therapy or an add-on for CPA if other antifungals have not worked or cannot be tolerated.

Advantages

High concentration in lung tissue
Minimal effects on other organs (especially the kidneys)

Drawbacks

Possible airway irritation (cough, tight chest, wheezing)
Requires specialist supervision and appropriate nebuliser equipment

🔬 New treatments in development

💨 Opelconazole (also called PC-945)

Opelconazole is a new inhaled triazole antifungal developed by Pulmocide Ltd in the UK.
It works in the same way as existing azole antifungals — by blocking the fungal enzyme CYP51 — but has been specially designed to stay in the lungs and minimise side-effects elsewhere.

In laboratory and early human studies, opelconazole has shown:

Strong activity against Aspergillus fumigatus
High and lasting drug levels in the lungs
Very low blood levels (reducing risk of toxicity and drug interactions)
Good tolerability in early trials

Although not yet licensed, it has been used compassionately in small numbers of patients with difficult-to-treat lung aspergillosis at centres such as Manchester and London.

🧾 Current and recent clinical trials

Trial ID	Treatment	Condition	Purpose / Summary	Status
NCT06447402	Nebulised Amphotericin B vs Saline	Chronic Pulmonary Aspergillosis	Tests whether regular nebulised amphotericin can help prevent CPA relapse compared with saline.	Recruiting
NCT03656081	Itraconazole ± Nebulised Liposomal Amphotericin B	CPA	Compares oral itraconazole alone versus itraconazole plus inhaled amphotericin for symptom and scan improvement.	Completed – results pending
NCT05238116	Inhaled Opelconazole + Standard Therapy	Refractory Invasive Pulmonary Aspergillosis	Phase 3 trial evaluating safety and added benefit of inhaled opelconazole. UK, EU, and US sites.	Recruiting
NCT05037851	Inhaled Opelconazole (PC-945)	Post-Lung Transplant Prophylaxis	Assesses prevention of fungal infection after transplant. Found well tolerated.	Completed
PubMed 34058036	Nebulised Amphotericin B vs Oral Itraconazole	Pulmonary Aspergilloma (CPA subset)	Six-month open study found similar improvement rates between inhaled amphotericin and oral itraconazole.	Completed

👉 You can look up any of these studies on ClinicalTrials.gov by entering the trial ID (e.g. NCT06447402).

⚠️ Things to keep in mind

Not yet routine — Inhaled antifungals are available only in research or specialist centres.
Limited evidence — Most data come from transplant or invasive aspergillosis studies, not chronic infection.
Delivery challenges — Damaged or scarred areas of lung may be hard for inhaled drugs to reach.
Possible side-effects — Coughing or mild bronchospasm are common; pre-treatment with an inhaler may help.
Monitoring still needed — Even with inhaled therapy, your care team will continue to check symptoms, lung scans, and blood markers (such as Aspergillus IgG).

🧭 Questions to ask your specialist

If you are interested in this type of therapy, you could ask:

Does my centre offer nebulised amphotericin as part of CPA care?
Are there any clinical trials nearby (for example NCT06447402 or NCT05238116)?
Could an inhaled antifungal be used with my current oral treatment?
What are the side-effects and how are they monitored?
What nebuliser device is required and how often would I use it?

🏥 UK research centres involved

Current UK involvement is mainly through:

National Aspergillosis Centre, Wythenshawe Hospital (Manchester)
Royal Brompton and Harefield Hospitals (London)
UK transplant centres participating in Pulmocide’s opelconazole studies

🗝️ Key takeaway

Inhaled antifungal medicines are an exciting development that could make CPA treatment safer and more targeted in the future.
For now, they are mainly available through clinical trials or specialist centres, but the early results are promising — especially for those who have struggled with oral antifungal side-effects or limited success.

If you’re interested, speak to your CPA specialist or the National Aspergillosis Centre team about ongoing research and eligibility.

by GAtherton

Chronic Pulmonary Aspergillosis (CPA) – Information For Family and Friends

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WHAT IT IS
CPA (Chronic Pulmonary Aspergillosis) is a long-term lung infection caused by the Aspergillus fungus. It often develops where lungs are already damaged (e.g., TB, COPD, bronchiectasis, sarcoidosis) and may form cavities, sometimes with fungal balls (aspergillomas).

WHAT IT'S NOT

Not contagious – you can't catch CPA.
Not poor hygiene – spores are everywhere in the air.
Not the patient's fault – flare-ups or setbacks happen because of the illness, not something they did wrong.

WHY AREN'T OTHERS AFFECTED?
Most people remove spores without trouble. CPA appears when lungs are already damaged or the immune system can't fight the fungus well – after past infections, chronic lung disease, or weakened defences. It's not about choices; it's lung history and chance.

TYPICAL SYMPTOMS

Persistent cough (sometimes with blood)
Breathlessness
Fatigue and low energy
Weight loss
Recurring chest infections

WORST SYMPTOMS

Coughing up blood – can be small streaks or larger amounts; sudden and frightening; urgent if heavy.
Severe fatigue – can stop even simple tasks; not just ‘tiredness’.

TREATMENT

Long-term antifungal medication
Regular scans and blood tests
Surgery in selected cases

THE REALITY
CPA is a serious, long-term condition. On bad days, people may not be able to do much at all. Symptoms can dominate daily life and limit social plans – cancelled arrangements are the illness talking, not them. It can also make people feel grumpy or irritable – not because they don't care, but because constant symptoms, tiredness, and limits on daily life are frustrating and exhausting. There’s often a mental load too – always thinking about avoiding dust, damp, or mould spores, and sometimes feeling overcautious about activities like going on boats, visiting old buildings, or anywhere that might harbour moisture or mould. This risk-checking is a form of self-protection, even if it means missing out.
It’s important to mention the mood swings and fatigue caused not only by the disease but also by the medication. For some, constant hand tremors are also part of daily life — these are often misunderstood by others.

LOOKING AHEAD

With effective treatment – Many people can keep the infection stable for years, control symptoms, and stay independent.
Risks – CPA can slowly progress, and severe flare-ups (like coughing large amounts of blood) may need urgent treatment.
Change over time – The illness can be stable for long periods, but it often needs lifelong monitoring and treatment changes. Support from specialists helps keep people well for longer.

ENVIRONMENTAL TRIGGERS & PROTECTION
Some people with CPA need to avoid environments with high levels of dust or fungal spores. This includes gardening, composting, building work, or damp/mouldy places. Wearing a protective mask during these activities can help reduce risk. Avoiding these triggers is about preserving lung health – not being fussy or antisocial.

HOW FRIENDS AND FAMILY CAN BEST HELP

Respect limits – breathlessness, fatigue, or coughing up blood can stop plans at short notice; it's not a choice.
Minimise exposure risks – avoid inviting them to dusty, damp, or mouldy places.
Offer practical help – driving to appointments, carrying shopping, or helping at home during flare-ups.
Be patient with mood changes – grumpiness can come from exhaustion and constant vigilance against triggers.
Talk openly about safety – if you suggest an outing, ask “Would this feel safe for you?”
Stay connected – even if they can't join in physically, a call or small gesture keeps them included.

MORE INFORMATION & SUPPORT
National Aspergillosis Centre (UK): https://mft.nhs.uk/wythenshawe/services/infectious-diseases/national-aspergillosis-centre/
Patient information & community: https://aspergillosis.org

by GAtherton

📘 What is CPA? (Chronic Pulmonary Aspergillosis)

Patient handout for A&E staff who are not aware of aspergillosis.

What is CPA?

CPA is a chronic fungal infection of the lungs caused by Aspergillus, most often in people who already have damaged lungs from conditions like tuberculosis, COPD, lung cancer, or sarcoidosis.

Unlike ABPA, CPA is a true infection, not an allergic reaction. It is not contagious but can slowly destroy lung tissue if not treated.

Symptoms

Chronic cough, often with mucus
Coughing up blood (haemoptysis)
Fatigue, low-grade fever
Unexplained weight loss
Breathlessness
Recurrent chest infections not responding to antibiotics

Diagnosis

CT scan of the chest showing cavities, nodules, or fungus balls (aspergillomas)
Aspergillus IgG antibody (usually raised)
Positive sputum PCR or culture for Aspergillus
Exclude TB and malignancy

Treatment

Long-term antifungal therapy (e.g. itraconazole, voriconazole, posaconazole)
Monitor blood levels and liver function
Surgery or embolisation if severe bleeding occurs
Supportive care: oxygen, nutrition, physiotherapy

Key Points for A&E:

✅ CPA is a progressive fungal infection, not a typical bacterial pneumonia
✅ May present with haemoptysis, respiratory distress, or systemic illness
✅ Review current antifungal treatment and potential drug interactions
✅ Consider urgent chest CT and specialist referral if patient is unwell

📍 For specialist support:

National Aspergillosis Centre (NAC)
🏥 Wythenshawe Hospital, Manchester University NHS Foundation Trust
🌐 NAC homepage on MFT website https://mft.nhs.uk/wythenshawe/services/infectious-diseases/national-aspergillosis-centre/
🌐 www.aspergillosis.org

📞 Daytime contact: 0161 291 2891 or 0161 291 4362
📞 Urgent out-of-hours: Call Wythenshawe switchboard on 0161 998 7070
📢 Ask for the on-call Infectious Diseases Consultant

by GAtherton

Contents

Key points

Important reassurance

What is cystic fibrosis?

What is a CFTR gene variant?

How CFTR affects the lungs

How Aspergillus behaves in the lungs

ABPA and cystic fibrosis

CPA and cystic fibrosis

Modern CF treatments and Aspergillus

Does a CFTR variant explain symptoms?

What should patients take from this?

When to seek medical advice

Conclusion

References

How fungal spores interact with asthma and other lung diseases

Why Asthma Creates a Favourable Environment for Aspergillus

Mucus production

Allergic immune responses

Aspergillus Sensitisation

Severe Asthma with Fungal Sensitisation (SAFS)

Allergic Bronchopulmonary Aspergillosis (ABPA)

Asthma and Aspergillus Disease Pathway

When ABPA Causes Bronchiectasis

Aspergillus Bronchitis

Chronic Pulmonary Aspergillosis (CPA)

Aspergillosis and Immune Competence

Other Lung Diseases Linked to Aspergillus

Bronchiectasis

COPD

Tuberculosis

Key Messages

Further reading

Can Lungs Repair Themselves?

What New Research Means for People with CPA (and Other Aspergillosis)

The Discovery: A “Repair vs Defence” Switch

What “Repair” Means — and What It Does Not Mean

It does not mean:

What repair does realistically mean

Why Preservation Is a Major Goal in CPA

Why This Also Matters in ABPA

Where Development Has Reached

The Balance Challenge in Aspergillosis

What This Means for Patients Now

A Realistic and Hopeful Perspective

Reference

What the researchers did

What they found

Why this matters for patients

Key takeaway

Why is surgery even considered in CPA

1. Disease is localised to one area of the lung

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

3. A simple aspergilloma

4. Failure or intolerance of antifungal therapy

Why surgery is often not recommended

1. CPA is often widespread

2. Underlying lung reserve is limited

3. Surgery carries significant risks

4. Surgery does not address the underlying vulnerability

What is the “success rate” of surgery?

Is surgery a “cure” for CPA?

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

Why are many patients managed medically instead

How decisions about surgery are made

Key messages for patients

⭐ How Common Is CPA? The Numbers Behind the Problem

⭐ Why CPA Is So Often Missed

1. Symptoms mimic common chronic lung diseases

2. Interpretation of imaging is inconsistent

3. IgG testing is not routinely requested

4. Short-term improvement with antibiotics is misleading

5. CPA spans multiple specialisms — and no one owns it

⭐ Which Patients Are at High Risk?

1. Post-TB lung disease (PTLD)

Specialities needing awareness:

2. COPD (especially severe / emphysema)

Specialities:

3. Bronchiectasis

Specialities:

🔄 **4. What about patients who have both ABPA and CPA?**