Aspergillosis Research Highlights — Week in Review (Last 7 Days: Week 50)

Seven key publications: pathogenicity, diagnostics, resistance, treatment, maxillofacial disease, and ABPA in COPD.

1. Comparative Overview of A. fumigatus, A. flavus, and A. niger

Rafique et al., J Infect Public Health, 2025
DOI: 10.1016/j.jiph.2025.103070

What this adds

  • A major comparative review (2000–2025) of the three most clinically relevant Aspergillus species.

  • Highlights broad clinical spectrum: allergy → chronic disease → invasive aspergillosis.

  • Identifies species-specific concerns:

    • A. fumigatus: globally dominant, rapidly evolving triazole resistance.

    • A. flavus: important in warmer climates; high aflatoxin relevance.

    • A. niger: relatively lower virulence but significant in sinus disease.

  • Public health message: surveillance gaps persist, especially for non-fumigatus species.

Why it matters

A strong reference paper supporting the WHO prioritisation of Aspergillus, and reinforcing the need for:

  • Better diagnostics

  • Species-level identification

  • Environmental resistance monitoring

2. GFP Fusion Protein Proteolysis in A. fumigatus

Paul & Moye-Rowley, G3 (Bethesda), 2025
DOI: 10.1093/g3journal/jkaf295

What this adds

  • Fundamental molecular biology study revealing regulated degradation pathways of green fluorescent protein (GFP) fusion proteins inside A. fumigatus.

  • Demonstrates how the fungus controls protein turnover under stress conditions.

Why it matters

  • Advances tools for fungal cell biology.

  • Supports drug development by clarifying pathways involved in stress response and antifungal tolerance.

  • Reinforces WHO’s classification of A. fumigatus as one of the four most critical fungi to study.

3. ABPA in COPD: Case Series + Review

Ren et al., BMC Pulmonary Medicine, 2025
DOI: 10.1186/s12890-025-04027-8

What this adds

  • 11 COPD cases with confirmed Allergic Bronchopulmonary Aspergillosis — highlighting:

    • Under-recognition in COPD

    • Overlap with chronic bronchitis/bronchiectasis symptoms

    • Frequent misdiagnosis as recurrent infections or COPD exacerbations

  • Provides diagnostic guidance and a literature synthesis.

Why it matters

  • Significant implications for case finding across the UK.

  • Supports NAC messaging: ABPA is not only an asthma disease.

  • Reinforces need for:

    • IgE/IgG screening

    • Early CT imaging

    • Awareness among COPD teams and primary care

4. EL219: Next-Generation Polyene Antifungal

Youssef et al., AAC, 2025
DOI: 10.1128/aac.01400-25

What this adds

  • Animal model evidence that EL219, a modern polyene, is effective against:

    • Triazole-susceptible A. fumigatus

    • Azole-resistant isolates

    • Difficult species (A. lentulus, A. calidoustus)

Why it matters

  • Highly relevant to rising global antifungal resistance.

  • Early indication that EL219 may fill a clinical gap similar to (or complementary to) olorofim and fosmanogepix.

  • Suggests strong activity even in immunosuppressed models.

5. Misidentification & Triazole Resistance in Aspergillus tubingensis

Wang et al., JAMA Network Open, 2025
DOI: 10.1001/jamanetworkopen.2025.43630

What this adds

  • Large Southern California population study showing:

    • Frequent misidentification of A. tubingensis as A. niger.

    • Notable azole resistance rates in correctly identified isolates.

  • Stresses need for genomic sequencing or MALDI-TOF with updated libraries.

Why it matters

  • Strong evidence that misidentification leads to:

    • Inappropriate antifungal therapy

    • Poor outcomes

  • Supports calls for expanded diagnostic reference services such as MRCM.

6. 50-Year Review of Oral Fungal Infections in Thailand

Kosanwat et al., Clinical Oral Investigations, 2025
DOI: 10.1007/s00784-025-06685-8

What this adds

  • Longitudinal study: 29% of deep infections involved aspergillosis.

  • Mean age 62 → older adults most affected.

  • Many cases were mucormycosis, histoplasmosis, or aspergillosis presenting late.

Why it matters

  • Shows that oral/maxillofacial fungal disease remains under-recognised globally.

  • Relevant to dental teams → better imaging + biopsy protocols needed.

  • May help NAC/CARES identify referral pathways from dental medicine.

7. Management of Maxillary Sinus Aspergillosis with Implants

Khoury et al., Int J Oral Implantol, 2025

What this adds

  • Real-world 3–10 year follow-up of 11 patients.

  • Standardised approach:

    • Surgical clearance

    • Antifungal therapy

    • Successful implant-prosthetic rehabilitation

Why it matters

  • Demonstrates excellent long-term outcomes when sinus aspergillosis is properly treated.

  • Practical implications for:

    • ENT surgeons

    • Oral surgeons

    • Implant dentistry

  • Supports inclusion of aspergillosis in sinus disease differential diagnosis.

Cross-Cutting Themes Emerging This Week

1. Under-recognition and misidentification

  • ABPA in COPD

  • Misidentified A. tubingensis

  • Asymptomatic sinus disease

  • Oral/maxillofacial deep fungal infections

→ Key NAC message: We are missing cases in primary care, COPD clinics, ENT, and dentistry.

2. Antifungal resistance remains a central threat

  • Contemporary reviews of species-specific resistance patterns

  • EL219’s promise against resistant species

  • Misidentification leading to incorrect susceptibility assumptions

3. Need for better diagnostics and reference centres

  • Species-level identification is essential

  • Supports arguments for expansion of MRCM-style national services

4. The clinical spectrum is broad

From allergy (ABPA in COPD) → chronic sinus disease → deep oral infections → invasive pulmonary aspergillosis.
This reinforces the message: aspergillosis is multi-specialty, not confined to respiratory medicine.

Weekly NAC/MRCM Take-Home Messages

  • COPD teams should screen for ABPA more frequently—especially in patients with recurrent “infective exacerbations.”

  • Species-level identification is increasingly important; misidentification contributes to treatment failure.

  • New antifungals like EL219 show promise against resistant strains including A. lentulus.

  • Dental and ENT teams need better awareness: sinus and oral fungal infections remain overlooked but treatable.

  • Global reviews show growing public health significance of Aspergillus species—aligning with WHO priorities.

by GAtherton

⭐ Severe Asthma with Fungal Sensitisation (SAFS): The Hidden Burden Behind Difficult Asthma

Estimated prevalence: 15–30% of severe asthma patients show fungal sensitisation.

Severe Asthma with Fungal Sensitisation (SAFS) describes a group of patients with severe asthma who show sensitisation (allergy) to Aspergillus or other environmental moulds but do not meet criteria for ABPA. These patients often experience persistent inflammation, breathlessness, mucus production, and exacerbations that are not adequately controlled by standard asthma therapies.

Although SAFS is common in severe asthma clinics, it remains poorly recognised, frequently mislabelled, and rarely discussed in routine practice. Yet identifying SAFS is crucial because it opens the door to specific interventions — including antifungals or targeted biologics — that can improve symptoms and reduce hospital admissions.

⭐ How Common Is SAFS?

SAFS is more common than ABPA and CPA combined in asthma services.

Population Estimated prevalence
Moderate asthma ~5%
Severe asthma 15–30%
Patients with frequent exacerbations up to 40%
ABPA-negative patients with mucus plugging high likelihood

Across the UK, this represents tens of thousands of people.

⭐ Why SAFS Is Missed

1. The diagnosis is not widely understood

Unlike ABPA or CPA, SAFS lacks:

  • universally agreed diagnostic criteria

  • clear imaging features

  • a single confirmatory test

This leads to variability in thinking and detection.

2. Symptoms mimic uncontrolled asthma

SAFS patients typically experience:

  • severe breathlessness

  • wheeze

  • mucus production

  • airway plugging

  • poor response to inhalers

  • frequent steroid courses

These appear indistinguishable from “difficult” or “type 2–high” asthma.

3. IgE and eosinophils may be normal

Unlike ABPA:

  • total IgE may be modest

  • Aspergillus IgE may be borderline

  • eosinophils may fluctuate, especially with steroids or biologics

Clinicians are often looking for very high IgE levels — but SAFS patients usually don’t show them.

4. Sputum and CT scans appear non-specific

Typical imaging:

  • mucus plugging

  • small-airway thickening

  • variable, patchy inflammation

  • bronchiectasis may or may not be present

Radiologists often report these changes as:

  • “consistent with asthma”

  • “post-infective”

  • “non-specific inflammatory pattern”

5. The fungal link is overlooked

Many clinicians are unfamiliar with:

  • the role of mould exposure

  • sensitisation thresholds

  • the overlap between environmental allergy and airway disease

  • when antifungals are appropriate

This leads to delays in recognising fungal-driven asthma.

⭐ Who Is at Highest Risk?

1. Severe asthma patients unresponsive to maximal inhaled treatment

Particularly those with:

  • frequent exacerbations

  • nocturnal symptoms

  • long-term steroid use

  • persistently low lung function

  • mucus plugging events

2. Patients sensitised to Aspergillus or multiple moulds

Positive skin tests or specific IgE indicate airway allergy that can drive symptoms.

3. Patients with damp or mould exposure at home or work

An important environmental factor often overlooked.

4. ABPA-negative asthma patients with mucus plugging

A large proportion of these patients fit the SAFS profile.

5. Those with co-existing bronchiectasis

Bronchiectasis amplifies the inflammatory response to fungal exposure.

⭐ Specialties That Need Greater Awareness

  • Severe asthma services & biologics clinics
    (primary diagnostic opportunity)

  • General respiratory clinics

  • Primary care & urgent care
    (patients seen frequently with “persistent asthma symptoms”)

  • Radiology
    (important for identifying mucus plugging)

  • Allergy/Immunology
    (mould sensitisation is central to diagnosis)

  • Environmental health teams
    (exposure to mould and dampness often perpetuates symptoms)

The National Aspergillosis Centre can provide specialist input when diagnosis is unclear or response to treatment is suboptimal.

⭐ Red Flags Suggesting SAFS

1. Severe asthma poorly controlled despite maximal inhalers

Including biologics (omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab).

2. Sensitisation to Aspergillus fumigatus or multiple moulds

3. Repeated mucus plugging episodes

(or “sticky mucus” symptoms)

4. More than 2–3 steroid-treated exacerbations per year

5. Asthma + bronchiectasis

Even mild bronchiectasis increases fungal risk.

6. Symptoms triggered by damp/mould exposure

7. Persistent airway inflammation despite correct inhaler technique

⭐ Misdiagnoses That Delay Recognition

  • “Difficult asthma”

  • “Brittle asthma”

  • “Post-viral inflammation”

  • “Poor adherence to inhalers”

  • “Asthma–COPD overlap”

  • “Psychogenic dyspnoea”

  • “Recurrent chest infections”

SAFS is a diagnosis hiding in these labels.

⭐ The Cost of Missed SAFS Diagnosis

For patients:

  • persistent symptoms

  • steroid dependence

  • increased risk of ABPA

  • progressive airway damage

  • hospital admissions

  • poor quality of life

  • possible career and lifestyle impact

For healthcare systems:

  • repeated A&E visits

  • asthma admissions

  • high biologic usage without adequate response

  • unnecessary antibiotics

  • escalating steroid toxicity

  • missed environmental interventions

⭐ Conclusion

SAFS is one of the most common — yet least recognised — fungal-related lung conditions. Although it lacks the dramatic imaging changes of ABPA or CPA, its impact on patients is profound.

Recognising mould sensitisation in severe asthma, understanding the role of fungal allergens, and considering targeted therapies can transform disease control. For complex cases or when the diagnosis is uncertain, referral to the National Aspergillosis Centre is recommended.

Early identification and appropriate treatment reduce steroid use, exacerbations, and long-term airway damage.

by GAtherton

⭐ Aspergillus Bronchitis: The Overlooked Condition Hiding in Plain Sight

Estimated prevalence 1–2% in bronchiectasis and chronic airway disease clinics.

Aspergillus Bronchitis (AB) is a chronic, symptomatic infection of the airways caused by Aspergillus species in people with underlying lung disease. It sits between simple colonisation and chronic pulmonary aspergillosis (CPA), and is frequently overlooked or mislabelled as “recurrent infection,” “post-viral symptoms,” or uncontrolled bronchiectasis.

Unlike CPA, Aspergillus Bronchitis does not require cavities or major structural destruction — which makes it both easier to miss and surprisingly common among people with chronic airway disease.

When recognised and treated (usually with antifungal therapy for several months), symptoms often improve significantly. But because awareness remains low, most patients cycle through unnecessary antibiotics, repeated exacerbations, and worsening airway disease before the real cause is identified.

⭐ What Exactly Is Aspergillus Bronchitis?

Aspergillus Bronchitis is defined by:

  • chronic productive cough

  • sputum growing Aspergillus species repeatedly

  • airway inflammation

  • symptoms lasting over 3 months

  • underlying airway disease (bronchiectasis, CF, COPD, prior TB, ABPA)

  • response to antifungal therapy

Unlike ABPA:

  • there is no allergic response,

  • IgE is usually normal,

  • eosinophils are normal or mildly elevated.

Unlike CPA:

  • there are no cavities on imaging,

  • IgG may be normal or only slightly elevated,

  • disease is confined to the airways, not lung tissue.

This places AB in a “grey zone” — often invisible unless specifically looked for.

⭐ Why Aspergillus Bronchitis Is Missed

1. Symptoms mimic common chronic airway disease

Typical AB symptoms include:

  • daily productive cough

  • worsening sputum thickness

  • breathlessness

  • fatigue

  • repeated “chest infections”

  • slow-to-clear mucus

  • crackles or wheeze

These resemble:

  • bronchiectasis exacerbations

  • COPD flare-ups

  • chronic infection with Pseudomonas or NTM

  • post-viral cough

  • uncontrolled asthma

Without fungal awareness, clinicians default to bacterial explanations.

2. Sputum grows multiple organisms — Aspergillus is dismissed

In bronchiectasis, sputum frequently grows:

  • Haemophilus

  • Pseudomonas

  • Staphylococcus

  • Streptococcus

  • NTM

When Aspergillus appears, it’s often labelled:

  • “colonisation”

  • “contaminant”

  • “not clinically relevant”

But repeated isolation with persistent symptoms is highly suggestive of AB.

3. IgE/IgG results may be normal

Many clinicians expect high IgE or IgG to “confirm Aspergillus disease.”
But in Aspergillus Bronchitis:

  • IgE is usually normal

  • IgG can be normal or borderline

This leads to false reassurance.

4. Radiology rarely shows overt features

CT scans in AB may show:

  • mucus plugging

  • mild bronchial wall thickening

  • small nodules

  • progression of bronchiectasis

But they do not show the cavities of CPA or classic features of ABPA.

Therefore radiologists often report scans as “no significant change” or “stable bronchiectasis.”

5. Antibiotics appear to help — temporarily

Patients often improve slightly with:

  • amoxicillin

  • doxycycline

  • macrolides

  • ciprofloxacin

This gives clinicians the impression of bacterial disease, but symptoms soon return.

6. Lack of awareness

Many specialists (even in respiratory clinics) are unaware that Aspergillus Bronchitis:

  • exists as a distinct clinical entity

  • can be disabling

  • responds to antifungals

  • predicts progression to CPA if untreated

This leads to significant diagnostic delay.

⭐ Who Is at Highest Risk?

1. Bronchiectasis

The largest risk group.
Aspergillus Bronchitis may account for 1–2% of all bronchiectasis patients, and up to 5–10% in severe or frequent exacerbator groups.

2. Cystic Fibrosis (CF)

These patients frequently grow Aspergillus but not all have ABPA — some have Aspergillus Bronchitis.

3. COPD and chronic productive cough

Especially those with:

  • frequent mucus plugging

  • repeated “infective exacerbations”

  • progressive sputum production

4. Post-TB airway damage

Chronic airway deformity, scarring, and bronchiectasis from old TB predispose to fungal infection.

5. Post-COVID structural disease

A new and growing risk group, especially after prolonged ICU ventilation.

6. ABPA patients

Some patients develop Aspergillus Bronchitis during steroid-dominated treatment or after stopping antifungals.

⭐ Which Specialities Need Greater Awareness?

  • Respiratory medicine
    (especially bronchiectasis clinicians and severe asthma teams)

  • Infectious Diseases
    (frequent respiratory presentations with chronic airway infection)

  • Radiology
    (to recognise subtle but progressive airway changes)

  • Primary care
    (“recurrent chest infection” or “persistent cough” patients)

  • Physiotherapy & airway clearance teams
    (excessive sputum with fungal elements)

  • Cystic Fibrosis services

The National Aspergillosis Centre is the ideal referral destination when diagnosis is uncertain or symptoms persist despite typical management.

⭐ Red Flags Suggesting Aspergillus Bronchitis

1. Chronic (>3 months) productive cough + repeated Aspergillus in sputum

Even 2 positive sputums in the right clinical context should raise suspicion.

2. Bronchiectasis patient not improving on repeated antibiotics

3. Thick, tenacious mucus with black, grey, or brown plugs

4. Worsening CT bronchiectasis or mucus plugging

5. Absence of features typical for ABPA (normal IgE, no fleeting infiltrates)

6. Asthma or COPD patient with new persistent sputum

7. Partial response to antibiotics but rapid relapse

8. Unexplained fatigue and breathlessness in someone with airway disease

⭐ The Cost of Missed Aspergillus Bronchitis

If AB is not recognised early, consequences include:

  • repeated exacerbations

  • accelerating bronchiectasis

  • long-term airway damage

  • chronic inflammation

  • steroid overuse

  • unnecessary antibiotics

  • repeated hospitalisations

  • progression to CPA in some patients

For health systems, missed diagnosis leads to:

  • higher admission rates

  • inappropriate long-term antibiotic use

  • avoidable CT scans and investigations

  • greater long-term burden of CPA

But antifungal therapy — when appropriately used — can offer marked symptom improvement and reduce exacerbation frequency.

⭐ Conclusion

Aspergillus Bronchitis is a distinct, treatable form of chronic airway disease seen in people with bronchiectasis, asthma, COPD, CF, and post-TB lung damage. Yet lack of awareness means many patients are repeatedly misdiagnosed with bacterial infections or unexplained chronic cough.

Recognising red flags, reviewing sputum results carefully, and considering antifungal therapy can dramatically improve outcomes. Early referral to specialist centres such as the National Aspergillosis Centre is recommended for complex cases or uncertain diagnosis.

Early identification prevents airway deterioration — and reduces the likelihood of progression to CPA.

by GAtherton

⭐ Allergic Bronchopulmonary Aspergillosis (ABPA): Why Diagnosis Is Missed and Who Needs to Be More Aware

With estimated prevalence of 1–2% in asthma clinics and up to 10% in severe asthma services.

Allergic Bronchopulmonary Aspergillosis (ABPA) is a chronic immune reaction to Aspergillus that affects people with asthma or cystic fibrosis. It causes airway inflammation, mucus plugging, recurrent exacerbations, and bronchiectasis if untreated.

Despite being treatable, ABPA remains heavily underdiagnosed, even in countries with advanced respiratory services. Many people are told for years that they have “difficult asthma” or “recurrent chest infections,” only for ABPA to be diagnosed much later, often with significant lung damage already present.

The UK National Aspergillosis Centre (NAC) provides specialist expertise, yet only a small proportion of expected ABPA cases reach specialist review.

This article explains why ABPA is missed, which patients are at risk, which specialities need to be more alert, and the red flags that should prompt testing or referral.

⭐ How Common Is ABPA?

ABPA is more common than most clinicians realise:

Population Estimated prevalence
General asthma 1–2%
Severe asthma clinics 3–10%
Cystic fibrosis 5–15%
Bronchiectasis (non-CF) 1–4%

Across the UK, this equates to an estimated 15,000–25,000 people living with ABPA — but only a small minority ever receive the correct diagnosis.

⭐ Why ABPA Is Often Missed

1. ABPA looks like “difficult asthma”

Typical symptoms — wheeze, cough, mucus, breathlessness — mimic:

  • severe asthma

  • eosinophilic asthma

  • uncontrolled asthma despite treatment

Patients may be repeatedly stepped up through inhalers, oral steroids, and biologics before ABPA is even considered.

2. Exacerbations are mistaken for infections

Many ABPA flare-ups are treated as:

  • pneumonia

  • viral infection

  • “chest infection”

  • post-viral asthma worsening

Without fungal-specific thinking, the diagnosis is rarely made.

3. IgE and eosinophils fluctuate

IgE is a cornerstone of ABPA diagnosis, but:

  • systemic steroids suppress IgE

  • biologics (benralizumab, mepolizumab, dupilumab) reduce eosinophils

  • flare-ups produce temporary spikes

  • baseline ranges vary between labs

Clinicians often overlook ABPA in patients on biologics because eosinophils are normal — despite the underlying fungal allergy still being active.

4. Radiology findings get mislabelled

ABPA causes:

  • mucus plugging

  • “tram lines” and bronchial thickening

  • fleeting infiltrates

  • upper lobe bronchiectasis

These are often:

  • labelled “infection”

  • attributed to asthma airway remodelling

  • not compared across time

  • missed on CT unless specifically looked for

5. Inconsistent awareness across specialities

Some clinicians are unfamiliar with:

  • ISHAM diagnostic criteria

  • interpreting IgE/IgG results

  • the relationship between asthma and fungal allergy

  • the overlap between ABPA and bronchiectasis

This leads to diagnostic delay or misdiagnosis.

6. ABPA evolves into chronic disease if untreated

Repeated inflammation → mucus plugging → bronchiectasis → fibrosis.
By the time a diagnosis is made, airway damage can be permanent.

⭐ Who Is at Highest Risk?

1. Asthma patients with repeated exacerbations

Especially those who:

  • fail maximal inhaler therapy

  • require multiple steroid courses

  • have sudden, dramatic mucus plugging events

  • experience episodic “flares” with no clear cause

2. Severe asthma clinic patients

Prevalence is up to 10%, especially those with:

  • high IgE

  • eosinophilia

  • sensitisation to multiple allergens

  • steroid dependence

3. Bronchiectasis patients

Bronchiectasis often coexists with ABPA and can worsen flares.

4. Patients with mucus plugging (“finger-in-glove” signs)

These striking CT appearances strongly suggest ABPA but are often misattributed to infection.

5. People with CF (Cystic Fibrosis)

5–15% develop ABPA at some stage.

⭐ Which Specialities Need Greater Awareness?

  • Severe asthma services & biologics clinics
    (highest yield group for ABPA detection)

  • Respiratory medicine
    (diagnosis often falls here but is highly variable)

  • General practice
    (sees frequent “exacerbations”)

  • Emergency departments & acute medical units
    (manage acute mucus plugging, chest tightness)

  • Paediatric respiratory medicine
    (early recognition prevents chronic damage)

  • Cystic Fibrosis services

  • Radiology
    (fleeting infiltrates and mucus plugging often give the earliest clues)

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

⭐ Red Flags Suggesting ABPA

1. Asthma with repeated, unexplained exacerbations

Especially if poorly responsive to normal treatment.

2. High total IgE (>500–1000 IU/mL)

Or rising IgE over time.

3. Eosinophilia (unless suppressed by treatment)

4. Positive Aspergillus sensitisation

(Skin prick test or specific IgE)

5. Bronchiectasis, particularly central or upper lobe

6. Fleeting pulmonary infiltrates

7. Mucus plugging on CT (“finger-in-glove” appearance)

8. ABPA flare triggered by stopping antifungals

9. Asthma + Aspergillus in sputum

⭐ The Cost of Missed ABPA Diagnosis

Failure to diagnose ABPA leads to:

  • progressive airway damage

  • permanent bronchiectasis

  • steroid dependence

  • hospital admissions

  • repeated infections

  • respiratory failure in advanced stages

  • reduced quality of life

  • avoidable healthcare expenditure

Delayed diagnosis increases the risk of progression to CPA, a far more serious chronic fungal infection requiring long-term antifungal therapy.

Early recognition, correct treatment, and referral to specialist centres like the National Aspergillosis Centre dramatically improve long-term outcomes.

⭐ Conclusion

ABPA is not rare — especially within severe asthma clinics, bronchiectasis services, and CF units. Yet it remains significantly underdiagnosed because its symptoms mirror those of common respiratory conditions, and because key investigations like IgE, IgG, and CT interpretation are inconsistently used.

A structured approach — recognising red flags, performing appropriate testing, and referring complex cases to the National Aspergillosis Centre — can reduce the burden of avoidable airway damage and improve the lives of thousands of patients.

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

🌐 Promoting the NHS National Aspergillosis Centre (NAC)

Nationally Commissioned Service • Specialist Advice • Remote MDT • Patient Support

Chronic and allergic aspergillosis remain significantly under-recognised across the UK — despite their substantial burden on respiratory, infectious disease, and immunology services.

As the NHS England–commissioned National Aspergillosis Centre (NAC), based at Wythenshawe Hospital (Manchester University NHS Foundation Trust), we provide national expertise, remote support, and shared-care pathways for clinicians managing these complex conditions.

📊 Why This Matters

Chronic pulmonary aspergillosis (CPA) affects an estimated 3–4 per 100,000 people in the UK, with far higher rates in those with:

  • Previous tuberculosis

  • COPD

  • Non-tuberculous mycobacterial (NTM) lung disease

  • Sarcoidosis

  • Bronchiectasis

Allergic bronchopulmonary aspergillosis (ABPA) may affect:

  • 2.5% of adult asthmatics

  • Up to 15% of people with cystic fibrosis

Yet both conditions are frequently undiagnosed or misdiagnosed, leading to delayed treatment and avoidable morbidity.

🏥 How NAC Supports Clinicians Across the UK

As the nationally commissioned centre for chronic aspergillosis, we offer:

🩺 Specialist clinical care

Face-to-face and remote clinics with structured long-term follow-up in partnership with local teams.

👥 National Aspergillosis MDT via Teams Remote Communication

A dedicated MDT where clinicians can refer and discuss complex diagnostic or therapeutic cases.

📧 Consultant-led advice & guidance

Available via phone & email, including:

  • Diagnostic support

  • Interpretation of IgE/IgG and fungal microbiology

  • Antifungal prescribing advice

  • Case planning for ABPA, CPA, SAFS and Aspergillus bronchitis

🔬 Access to advanced diagnostics

Including Aspergillus-specific IgE/IgG, culture, imaging, and molecular testing (e.g. antifungal resistance).

💬 Patient support & education (NAC CARES)

Moderated online groups, weekly patient meetings, webinars, and comprehensive educational resources — helping patients understand their condition and remain safely supported close to home.

🤝 We Welcome Collaboration

We’d be pleased to connect with respiratory, ID, immunology, and internal medicine teams to discuss:

  • Shared-care pathways

  • Diagnostic support

  • Service guidance

  • Virtual or in-person educational sessions

  • Case-specific MDT referrals

📄 Further information

Referral pathways, service scope and patient resources:
👉 https://mft.nhs.uk/wythenshawe/services/infectious-diseases/national-aspergillosis-centre/

Dr Chris Kosmidis
Clinical Lead, NHS National Aspergillosis Centre
Manchester University NHS Foundation Trust

by GAtherton

**Adrenal Insufficiency & Steroid Tapering:

A Complete Patient Guide**

People taking long-term steroids (prednisolone, methylprednisolone, hydrocortisone, dexamethasone) can develop adrenal insufficiency because their adrenal glands “go to sleep” and stop making cortisol.
During tapering, the body must slowly “wake up” again — and this needs careful monitoring.

This guide explains the symptoms, tests, warning signs, and emergency precautions to keep you safe.

⭐ 1. Why adrenal insufficiency happens

Long-term steroid use suppresses the HPA axis (hypothalamus–pituitary–adrenal system).
When daily steroid doses are reduced, your body must produce more of its own cortisol. This takes time.

If the steroid reduction is too quick, or the body is under stress, low cortisol symptoms appear.

⭐ 2. Symptoms to watch for during steroid tapering

These are early signs that your body may not be keeping up with the reduction.

✔ Early, mild symptoms

  • Fatigue / sudden exhaustion

  • Muscle weakness

  • Dizziness when standing

  • Nausea or reduced appetite

  • Flu-like aching

  • Low mood, anxiety, irritability

  • Brain fog

  • Feeling unusually cold

  • Worsening joint or muscle pain

These often improve if the taper is slowed or paused.

⭐ 3. More serious symptoms of low cortisol

These symptoms suggest steroid levels are too low and the taper needs urgent review:

  • Vomiting

  • Persistent dizziness

  • Very low blood pressure

  • Severe fatigue (unable to function normally)

  • Salt cravings

  • Ongoing nausea preventing eating

  • Faintness or near-collapse

These require medical advice (same day).

⭐ 4. Emergency symptoms — possible adrenal crisis

Call 999 or go to A&E immediately if you develop:

  • Severe vomiting or diarrhoea

  • Collapse or inability to stand

  • Severe dehydration

  • Confusion

  • Sudden severe abdominal or back pain

  • Pale, clammy skin

  • Rapid breathing

  • Loss of consciousness

This is a medical emergency.
Patients normally receive 100 mg hydrocortisone IM/IV, but patients allergic to hydrocortisone require a pre-agreed emergency alternative — your endocrinologist must document this clearly.

⭐ 5. Symptoms that mean you may need a temporary “stress dose” of steroids

Your cortisol requirement increases during physical stress.
If you have adrenal suppression, your body cannot produce this extra cortisol.

You may need a temporary increase in dose if you have:

✔ Illness

  • Fever

  • Chest infection

  • Flu-like illness

  • COVID

  • Urinary infection

  • Gastroenteritis

  • Diarrhoea

  • Persistent nausea

✔ Physical stress

  • Injury

  • Significant fall

  • Severe pain

  • Dental surgery

  • Medical or surgical procedures

✔ Emotional stress

  • Bereavement

  • Panic attacks

  • Trauma

If vomiting prevents taking steroids → seek emergency help immediately.

⭐ 6. Tests used to monitor adrenal function during tapering

Doctors rely on a combination of symptoms and laboratory tests.

✔ Morning cortisol (8–9 am)

A key test to assess recovery.

Typical interpretation:

  • > 400–500 nmol/L → likely normal function

  • 150–350 nmol/L → recovering / borderline

  • < 100 nmol/L → adrenal insufficiency

(Exact thresholds vary.)

✔ ACTH level

Shows whether the pituitary is trying to stimulate the adrenals.

  • Low ACTH → still suppressed

  • High ACTH → trying to wake adrenals

  • Normal ACTH + low cortisol → gland slow to respond

✔ Short Synacthen Test (SST)

Gold standard.
A small ACTH injection tests whether your adrenal glands can produce cortisol.

Used when:

  • taper reaches low doses

  • symptoms appear

  • deciding if steroids can be stopped

✔ Electrolytes (U&Es)

Low cortisol may cause:

  • Low sodium

  • High potassium (less common in steroid-induced insufficiency)

✔ Blood pressure monitoring

Low cortisol → low BP, dizziness, faintness.

✔ Glucose levels

Low-normal glucose and shakiness may occur during withdrawal.

✔ Clinical symptom review

Symptoms are sometimes more sensitive than tests.

Doctors track:

  • fatigue

  • appetite

  • dizziness

  • illness triggers

  • salt cravings

  • mental state

  • recovery after small dose increases

⭐ 7. How tapering decisions are made

Tapering depends on:

  • how long steroids have been taken

  • current dose

  • symptoms

  • test results

  • presence of illness

  • rate at which symptoms develop

  • allergy restrictions (pred/hydrocortisone allergy requires specialist handling)

General principles (not schedules):

  1. Higher doses can reduce more quickly.

  2. Taper slows dramatically near physiological levels
    (~4–6 mg pred-equivalent).

  3. If symptoms appear → pause, slightly increase, or slow taper.

  4. SST is used near the end to confirm recovery.

⭐ 8. When to contact your medical team

Same day advice needed

  • worsening dizziness

  • persistent nausea

  • new vomiting

  • symptoms appear with each taper step

  • fainting

  • new severe fatigue

  • any infection (urinary, chest, flu)

Urgent / A&E

  • collapse

  • severe vomiting/diarrhoea

  • confusion

  • severe abdominal pain

  • unable to take oral steroids

  • suspected adrenal crisis

⭐ 9. What patients should do to stay safe

  • Carry a Steroid Emergency Card at all times

  • Keep emergency instructions from your endocrinologist

  • Know your Sick Day Rules

  • Ensure A&E or ambulance crews know about corticosteroid allergy

  • Keep a written record of tapering plan

  • Never stop steroids suddenly

  • Be cautious during illness

  • Know your emergency steroid plan (alternative if allergic to hydrocortisone)

⭐ Final reassurance

Adrenal insufficiency during tapering is common, manageable, and often reversible.
By monitoring symptoms, using regular blood tests, and following specialist guidance, tapering can be done safely.

You are not alone — your endocrine team will guide every step, especially if allergies (to prednisolone or hydrocortisone) make your case more complex.

With careful observation and a clear emergency plan, serious complications are rare and preventable.

by GAtherton

🧩 NAC Aspergillosis Research Digest — Focus: Chronic Aspergillosis (October 2025: week 42)

🧬 Focus Review — Chronic Aspergillosis (October 2025)

Here are peer-reviewed papers on chronic aspergillosis published in the last month:

1. Improving Diagnostic Sensitivity Using Species-Specific IgG (Sep 2025)

  • This study investigated better blood tests to diagnose CPA by measuring IgG antibodies not just to Aspergillus fumigatus but also to other common Aspergillus species.

  • They found adding antibodies against non-fumigatus species identified more CPA cases that would have been missed by the standard A. fumigatus test alone.

  • The treatment results were similar regardless of which Aspergillus species was involved.

  • This means broader antibody testing improves diagnosis without changing expected outcomes.

  • Read full paper on PubMed

2. Prevalence and Impact of Bacterial Co-infections in CPA (April 2025)

  • This study looked at how often bacterial infections occur alongside CPA and their effect on patients.

  • About 21% of CPA patients had bacterial co-infections.

  • However, having a bacterial co-infection did not significantly change mortality rates compared to those without.

  • This highlights the need to assess for bacteria but suggests it may not worsen long-term outcomes.

  • Read full paper on PMC

3. Non-invasive Monitoring Using Serology and HRCT Imaging (June 2025)

  • Researchers combined blood antibody tests and high-resolution chest CT scans to identify active Aspergillus infections in chronic lung disease patients.

  • This method distinguished active infections from colonization without invasive procedures.

  • It supports using combined non-invasive tests to decide who needs further invasive diagnostics or antifungal treatment.

  • This approach helps avoid unnecessary treatments and invasive tests.

  • Read full paper on Frontiers

In short: these studies improve how doctors diagnose and monitor CPA — by expanding antibody testing beyond classic targets, recognizing the role but limited impact of bacterial co-infections, and using combined non-invasive testing strategies to guide management safely and effectively.

by GAtherton

🔍 Aspergillosis: Recent Highlights & Key Publications October 2025 (Week 41)

Revised ISHAM-ABPA working group guidelines (2024)

  • Scope & criteria: Codifies ABPA diagnosis around mandatory Aspergillus sensitisation (specific IgE or SPT) plus total IgE ≥ 500 IU/mL, with supporting features (Aspergillus-specific IgG/precipitins, eosinophilia, imaging with central bronchiectasis/mucus plugging). Distinguishes ABPA vs. ABPM (other fungi) and sets clinical states (acute, response, exacerbation, remission).

  • Treatment pathways: For acute ABPA, permits oral corticosteroids or itraconazole as first-line; combination is reasonable in severe disease or frequent relapsers. Provides steroid-sparing strategies (itraconazole/voriconazole/posaconazole) and practical taper schedules.

  • Biologics & monitoring: Positions omalizumab/mepolizumab/dupilumab for recurrent/exacerbation-prone ABPA. Recommends multidimensional response criteria (symptoms, exacerbations, lung function, IgE kinetics, radiology) rather than IgE alone.

  • Paper (Eur Respir J) · PubMed · OA summary (PMC).

BTS Clinical Statement on Aspergillus-Related Chronic Lung Disease (2025)

  • Who it’s for: UK-focused guidance to help respiratory teams manage CPA, aspergilloma, chronic airway disease with Aspergillus, and allergic phenotypes in secondary care.

  • CPA approach: Emphasises radiology over time (HRCT), microbiology/Aspergillus-IgG, and exclusion of mimics (NTM, malignancy). Advises long-term azoles (with TDM & LFTs), and when to consider surgery (haemoptysis/aspergilloma).

  • Service model: Encourages early referral/MDT (radiology, mycology, thoracic surgery, interventional radiology), signposts NAC pathways, and sets pragmatic follow-up intervals (clinical, radiology, serology).

  • BTS page · News item · (access via Thorax from BTS page).

Consensus guidelines for invasive aspergillosis (ECMM/ISHAM CAPA; 2021)

  • Definitions: Introduces proven/probable/possible CAPA using clinical + mycological evidence (BAL/TA culture or PCR, GM thresholds, imaging).

  • ICU nuance: Acknowledges non-neutropenic ICU patients (COVID/influenza) can develop IA with atypical imaging and lower fungal burdens; endorses combined biomarker strategies (BAL GM/PCR ± serum GM).

  • Therapy: Positions voriconazole/isavuconazole as first-line; L-AmB where resistance or intolerance suspected. Flags early initiation on high suspicion to improve outcomes.

  • Paper (Lancet Infect Dis) · PubMed · ECMM guideline hub.

Epidemiology & Clinical Cohorts

Marseille 2-year retrospective cohort — CPA & ABPA insights (2025)

  • Design: Single-centre retrospective study applying ESCMID CPA criteria and modified ISHAM ABPA criteria to consecutive referrals.

  • Findings: High rate of diagnostic overlap (allergy + chronic infection features). Delays to diagnosis common, especially where IgG negative/indeterminate but GM/BAL/PCR positive.

  • Implication: Supports multimodal testing (serology, GM/PCR, serial imaging) and repeat sampling in indeterminate cases; highlights value of centre-based MDT.

  • PubMed · (preprint/alt copies if needed: SSRN/other listing, ResearchGate record).

Invasive aspergillosis in ICU settings (2025 review)

  • Epidemiology: IA increasingly reported in severe viral pneumonias (COVID, influenza); mortality ~40–50% depending on definition and antifungal timing.

  • Diagnostics: BAL GM outperforms serum GM in non-neutropenic ICU; PCR adds sensitivity but needs pre-test probability framing to avoid over-calling colonisation.

  • Care points: Advocate protocolised screening (e.g., twice-weekly BAL GM/PCR in high-risk ventilated patients) and earlier empiric therapy when criteria met.

  • Open access review (Frontiers, 2025) · (alt listing: ResearchGate record).

Review: Invasive aspergillosis — scope & new species (2024)

  • Landscape: Expands on non-fumigatus Aspergillus species, cryptic species with distinct susceptibility patterns, and emerging hosts (advanced COPD, cirrhosis, ICU).

  • Resistance: Summarises azole resistance mechanisms (cyp51A variants, TR34/L98H, TR46/Y121F/T289A) and notes environmental selection via triazole fungicides.

  • Practice: Reinforces susceptibility testing and situational use of L-AmB or isavuconazole where resistance is likely.

  • Review (ScienceDirect).

Diagnostics: Biomarkers, Molecular, Imaging & Novel Methods

GM antigen & Aspergillus IgG negative “escape” cases

  • Problem: In suspected CPA/airway disease, Aspergillus-IgG can be false-negative early or in immunomodulated hosts.

  • Finding: High GM titres (especially BAL) can help “rescue” such cases, prompting treatment or further invasive sampling.

  • Clinical use: In IgG-negative but high-suspicion scenarios, pair BAL GM + PCR and repeat serology; avoid reliance on single negative IgG.

  • OA study (2025) · PubMed. (See also general GM/BDG performance review: Medicine 2024).

Molecular diagnosis, qPCR & NGS advances (2025 review)

  • Performance: qPCR improves sensitivity vs culture/microscopy; specificity hinges on contamination control and clinical context.

  • Best practice: Combine qPCR with GM/BDG in high-risk patients; consider cycle thresholds and duplicate positivity to support true infection.

  • NGS: Useful for broad pathogen screens or resistant/cryptic species; needs standardisation and careful interpretation.

  • OA review (Front Cell Infect Microbiol, 2025). British Thoracic Society

Microscopy, GM, PCR comparative pilot (2025)

  • Design: Head-to-head assay comparison across serum/BAL/sputum against a composite clinical reference.

  • Takeaway: No single test is definitive; dual-modality (e.g., BAL GM + PCR) yields best balance. Microscopy remains specific but insensitive.

  • Study (ScienceDirect). ERS Publications

Emerging spectroscopy / imaging techniques (TERS)

  • What it is: Tip-enhanced Raman spectroscopy mapping conidial wall components (melanin, polysaccharides, proteins) at nanoscale.

  • Why it matters: Potential to differentiate strains or track resistance-linked wall changes; currently preclinical, not diagnostic.

  • AIP Applied Physics Letters (2025) · arXiv preprint.

Therapeutics, Resistance & New Drugs

Olorofim (F901318) — Phase IIb results (2025)

  • Population: Refractory invasive mould disease (including azole-resistant Aspergillus), many salvage scenarios.

  • Efficacy: Global response ~29% (D42) and ~27% (D84); when counting stable disease, success rises to ~75% (D42) and ~63% (D84).

  • Safety: Transaminase elevations ~10%, mostly reversible with dose interruption/adjustment; no treatment-related deaths reported.

  • Use case: Salvage/compassionate therapy where standard options fail or resistance limits choices; monitor LFTs and DDIs.

  • PubMed · Lancet Infect Dis abstract. (Trial record: NCT03583164).

Review of olorofim in aspergillosis

  • MoA: Inhibits dihydroorotate dehydrogenase (DHODH), blocking de novo pyrimidine synthesis (novel class, no cross-resistance with azoles/echnocandins/AmB).

  • Signals: Case series in azole-resistant disease (incl. CGD) report clinical/radiologic remission; combination strategies under study.

  • Caveats: Access via trials/managed access; need phase III data and resistance surveillance under use pressure.

  • epocrates.com

Pipeline and alternative antifungals

  • Fosmanogepix (Gwt1 inhibitor): Oral/IV; activity against Candida/Aspergillus; CNS penetration promising; phase II positive signals.

  • Rezafungin (long-acting echinocandin): Weekly IV dosing enables OPAT; emerging real-world data in invasive disease and step-down.

  • Ibrexafungerp (tricohalose class/β-glucan): Oral; Aspergillus data limited (better for Candida), but combinations explored.

  • New azoles (isavuconazole real-world/TDM): Use where voriconazole intolerance or QT issues exist.

  • (See contemporary reviews; real-world rezafungin data below.)

Rezafungin (real-world, 2025) — OPAT-friendly weekly echinocandin; emerging safety/utility data.

Azole resistance & clinical implications

  • Drivers: Agricultural triazoles select environmental cyp51A mutations; patients can acquire primary resistant strains.

  • Practice changes: Where resistance prevalence is ≥10%, consider empiric L-AmB or isavuconazole until susceptibility known; always request AFST when feasible.

  • Nature Communications 2024 · Review PubMed.

Therapeutic drug monitoring & combination strategies

  • TDM: Essential for voriconazole/posaconazole (target troughs, avoid toxicity). Isavuconazole TDM less routine, but consider in extremes.

  • Combinations: Azole + echinocandin in refractory disease or high burden IA; AmB-based combos when resistance suspected. Evidence heterogeneous—use in expert-guided salvage.

  • (Covered within recent IA/therapy reviews above.)

Immunology, Host Responses & Biologics

Immunopathogenesis review (2023)

  • Pathways: Th2-skewed responses drive ABPA/SAFS (IgE/eosinophilia); defects in phagocyte function (neutropenia, CGD, high-dose steroids) predispose to invasive disease.

  • Mediators: Roles for IFN-γ, IL-5/IL-13, mucus hypersecretion, and airway remodelling; supports biologic targeting in allergic phenotypes.

  • OA review (Front Immunol 2023).

Biologics in ABPA / severe asthma

  • When to use: Relapsing ABPA, frequent steroid bursts, or steroid toxicity despite azole therapy.

  • Agents & effects: Omalizumab (anti-IgE) reduces exacerbations/steroid need; mepolizumab/benralizumab (anti-IL-5/IL-5R) tackle eosinophilia; dupilumab (anti-IL-4Rα) addresses Th2 axis and mucus/plugging.

  • Integration: Keep antifungal therapy for fungal burden; use biologics to control inflammation/exacerbations and spare steroids; monitor IgE dynamics and radiology.

  • ISHAM ABPA paper · PubMed.

by GAtherton

Side Effects, New Medicines, and Safety Reporting: What Every Patient Should Know

Modern medicines, including antifungals used for aspergillosis, can be life-saving. But they can also have powerful side effects. One patient recently described developing nerve damage (neuropathy) while on treatment, but never mentioned it to their doctor, because they didn’t know it could be a side effect. Sadly, by the time it was recognised, the damage was permanent.

This story shows why patients and doctors need to work together in partnership to spot and report side effects early — especially when medicines are new and real-world safety data is still limited.

1. From passive role to partnership

In the past, healthcare was one-way: the doctor gave instructions, the patient followed. Today the NHS encourages shared responsibility:

  • Doctors bring their expertise about the illness and treatments.

  • Patients bring their daily experience of living with the condition.

  • Together they can make safer, better-informed decisions.

This partnership is essential for powerful drugs like antifungals, where side effect monitoring depends on both sides working together.

2. Why side effect statistics can be misleading

Leaflets list side effects as “common” or “rare,” often with percentages. But these figures don’t always reflect real life because:

  • Trials are limited – only a few thousand people take part, often younger and healthier than typical NHS patients.

  • Under-reporting is common – doctors and patients often fail to report side effects, especially mild ones.

  • Bias exists – severe or unusual reactions are reported more often than everyday ones.

👉 Bottom line: leaflets tell us what can happen, not always how often it happens.

3. The Yellow Card system

The UK’s main tool for detecting safety issues is the Yellow Card Scheme, run by the MHRA.

  • Anyone can report: doctors, nurses, pharmacists, patients, or carers.

  • Reports are vital: patterns in these reports may reveal risks not seen in trials.

  • Action is taken: if needed, leaflets are updated, warnings issued, or drugs restricted/withdrawn.

You can report suspected side effects at yellowcard.mhra.gov.uk.

4. Why reporting matters

Poor reporting leads to harm:

  • Delayed warnings – e.g. photosensitivity with voriconazole took years to be recognised.

  • Biased safety data – drugs may seem safer than they are.

  • Preventable harm – patients may suffer permanent injury before action is taken.

For new medicines (marked with a ▼ black triangle in the BNF and leaflets), the MHRA asks for all side effects to be reported, no matter how small.

5. Extra protections for new medicines

When a drug is new, safety systems are stronger than usual:

  • Black triangle (▼) – signals “additional monitoring” so all suspected ADRs should be reported.

  • Specialist prescribing – new antifungals are usually limited to centres like NAC.

  • Closer monitoring – frequent blood tests, drug levels, eye or skin checks depending on risk.

  • Risk Management Plans – agreed with regulators, spelling out what to watch for.

  • Post-marketing studies – Phase 4 trials track safety in real-world patients.

These safeguards are extensive, but not fool-proof. Rare or long-term effects may still emerge only after years of wider use.

6. The NHS challenge

Despite the systems:

  • Only a small percentage of doctors file Yellow Card reports each year.

  • Most GPs never prescribe brand-new drugs — so reporting falls heavily on specialist centres like NAC.

  • Under-reporting risks harm, increases NHS costs, and erodes trust.

7. Who sets the rules?

Several organisations provide guidance on reporting and safety:

  • MHRA (UK regulator): runs Yellow Card, monitors new and established drugs, and issues safety updates.

  • BNF (British National Formulary): highlights side effects, black triangle drugs, and links to reporting tools.

  • GMC (General Medical Council): obliges doctors to report serious ADRs and all reactions to ▼ drugs.

  • EMA (European Medicines Agency): operates EudraVigilance, pooling reports from across Europe.

  • Global standards: the UK follows international rules (ICH E2B) so data is shared worldwide.

8. What patients can do

You are central to this safety net:

  • Be observant – notice anything new or unusual.

  • Keep a record – note when it started, how often, and any changes with medication.

  • Report promptly – tell your team and consider submitting a Yellow Card yourself.

  • Ask questions – “What side effects should I look out for? Which are urgent? How will we monitor this drug?”

  • Use trusted sources – NHS.uk, bnf.nice.org.uk, NAC, or your pharmacist.

9. The reality of side effects

For many, side effects are not “minor inconveniences.” They can mean:

  • Permanent disability (e.g. nerve or vision damage).

  • Loss of independence or mobility.

  • Social isolation and depression.

That’s why side effect monitoring is not just bureaucracy — it’s about protecting real lives.

Key message

The systems around new medicines are extensive but not fool-proof. That’s why patients and doctors must work as partners.

👉 If you notice something new, strange, or worrying while on antifungal medication — however small — tell your healthcare team and consider reporting it. Your report may be the missing piece that protects you and others.

by GAtherton