Aspergillosis, immunity, and risk

Primary immune deficiencies and immune modifiers explained

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

Why this article exists

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

This article explains:

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

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

  • How these factors stack together in real life

Key reassurance up front

  • There are 500+ recognised primary immune deficiencies

  • Only ~20–30 are clearly linked to aspergillosis

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

The unifying concept: three immune pathways to aspergillosis

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

1. Reduced ability to kill the fungus

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

2. Lung damage over time

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

3. Excessive allergic inflammation

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

Many conditions overlap more than one pathway.

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

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

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

A. Phagocyte defects

Strongest association with invasive aspergillosis

  1. Chronic granulomatous disease (CGD)

  2. Autosomal recessive forms of CGD

  3. Severe congenital neutropenia

  4. Cyclic neutropenia

  5. Leukocyte adhesion deficiency type I

Typical pattern

  • Aspergillosis at a young age

  • Invasive lung disease ± spread beyond lungs

  • Often no other obvious risk factors

B. Hyper-IgE and severe allergy syndromes

Allergic, chronic, and cavity-associated disease

  1. STAT3 hyper-IgE syndrome

  2. DOCK8 deficiency

  3. PGM3 deficiency

  4. ZNF341 deficiency

  5. IL6ST deficiency

Typical pattern

  • Severe asthma and allergy

  • Thick mucus, recurrent infections

  • ABPA, later CPA or aspergillomas

C. Combined immunodeficiencies

Immune coordination problems

  1. Severe combined immunodeficiency (milder or surviving forms)

  2. Omenn syndrome

  3. ZAP-70 deficiency

  4. Major histocompatibility complex class II deficiency

  5. CD40 ligand deficiency (hyper-IgM syndrome)

Typical pattern

  • Broad infection susceptibility

  • Aspergillosis can behave aggressively

D. Defects of fungal recognition and innate signalling

Often dramatic or unexpected presentations

  1. CARD9 deficiency

  2. Dectin-1 (CLEC7A) complete deficiency

  3. MALT1 deficiency

Typical pattern

  • Severe or unusual aspergillosis

  • Lung, brain, or deep tissue involvement

  • Sometimes first presents in adulthood

E. Immune dysregulation syndromes

Mixed infection, inflammation, and autoimmunity

  1. CTLA-4 haploinsufficiency

  2. LRBA deficiency

  3. STAT1 gain-of-function mutations

  4. IPEX syndrome (FOXP3 deficiency)

Typical pattern

  • Inflammatory lung disease

  • Chronic or invasive aspergillosis emerging over time

F. Antibody deficiencies (indirect risk via lung damage)

  1. Common variable immunodeficiency

  2. X-linked agammaglobulinaemia

  3. Activated PI3K-delta syndrome

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

Section 2: Immune modifier-types that can amplify risk

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

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

Mannose-binding lectin (MBL) deficiency

  • Common (≈5–10% of population)

  • Affects fungal recognition and complement activation

  • Usually mild on its own

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

Partial fungal-recognition receptor variants

  • Heterozygous dectin-1 variants

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

Effect

  • Slower fungal recognition

  • Increased colonisation or allergic response

  • Act as risk amplifiers, not causes

Cytokine balance variants

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

  • Interleukin-6

  • Interleukin-10

  • Tumour necrosis factor-alpha

These modify:

  • Inflammation intensity

  • Tissue damage vs clearance balance

Allergy-biased (Th2-skewed) immunity

Not a disease, but a recognised immune tendency.

Features:

  • Asthma

  • Eczema

  • Nasal polyps

  • High immunoglobulin E levels

  • Eosinophilia

Strongly associated with:

  • Fungal sensitisation

  • ABPA

  • Difficult-to-control asthma

Impaired mucociliary clearance

A functional immune–mechanical issue.

Seen in:

  • Severe asthma

  • Bronchiectasis

  • Chronic sinus disease

Effect:

  • Aspergillus spores are not physically cleared

  • Prolonged immune exposure

  • Increased colonisation and allergy

Age-related immune change (immunosenescence)

  • Normal reduction in immune speed and coordination with age

  • Particularly relevant to chronic pulmonary aspergillosis

Not a disease, but an important modifier of outcome.

Airway epithelial vulnerability

Subtle weaknesses in:

  • Airway lining integrity

  • Antimicrobial peptide production

  • Local immune signalling

Can increase:

  • Fungal adherence

  • Chronic colonisation

  • Allergic sensitisation

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

Aspergillosis rarely results from one single factor.

Instead, several modest risks align:

  • Mild MBL deficiency

  • Severe asthma

  • Corticosteroid exposure

  • Bronchiectasis

  • Age-related immune change

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

This explains why:

  • Two people with similar scans can behave very differently

  • One patient relapses while another stabilises

  • “Why me?” often has no single answer

Section 4: When clinicians investigate immune causes

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

  • Aspergillosis at a young age

  • Invasive or unusually severe disease

  • Disease without classic risk factors

  • Recurrent infections plus severe asthma or allergy

  • A family history of unusual infections

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

Understanding immune contribution can:

  • Explain disease pattern and behaviour

  • Guide antifungal choice and duration

  • Inform long-term prevention strategies

  • Reduce future lung damage

  • Reassure patients when no immune defect is found

Key take-home messages

  • Aspergillus exposure is universal; immune causes are rare

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

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

  • Aspergillosis often reflects risk stacking, not a single diagnosis

  • Understanding patterns matters more than labels

  • Specialist care improves precision and outcomes

by GAtherton

Latest Aspergillosis & Related Research Updates (Week 4).

Executive overview (what stands out this fortnight)

Key signals

  • Immune dysregulation—not just classic immunosuppression—continues to emerge as a central driver of invasive aspergillosis.

  • Allergic bronchopulmonary aspergillosis (Allergic Bronchopulmonary Aspergillosis) is appearing in atypical and early phenotypes, including absence of bronchiectasis.

  • Antifungal toxicity and pharmacokinetic variability remain clinically important.

  • Paediatric invasive aspergillosis evidence is improving.

  • Environmental and One Health studies continue to inform exposure risk.

  • Overlap with non-tuberculous mycobacteria and microbiome disruption is increasingly evident.

1. Immunocompromise, viral infection, and invasive aspergillosis
Immunocompromise and early-onset invasive pulmonary aspergillosis in viral pneumonia

Sun B et al., Frontiers in Public Health, 2026

Relevance

  • Directly informs understanding of early invasive pulmonary aspergillosis in severe viral pneumonia.
  • Extends COVID-associated pulmonary aspergillosis concepts to non-COVID viral infections.

Key points

  • Viral pneumonia causes early immune dysregulation, including lymphopenia.
  • Invasive aspergillosis may develop before classic intensive care risk factors.
  • Supports earlier fungal surveillance rather than late rescue testing.

Pulmonary cavitation as a late and self-limited complication of COVID-19 pneumonia

Osório M, Silveira M, Cureus, 2026

Relevance

  • Highlights post-viral structural lung damage as a substrate for aspergillosis.

Key points

  • Cavitation discussed alongside COVID-associated pulmonary aspergillosis and mucormycosis.
  • Fungal risk may persist after apparent clinical recovery.

2. Allergic disease and ABPA – expanding phenotypes
Triple autoimmune overlap: rheumatoid arthritis, systemic lupus erythematosus, and hypereosinophilic asthma with ABPA features

Frontiers in Immunology, 2026 (Case Report)

Relevance

  • Challenges rigid diagnostic frameworks for Allergic Bronchopulmonary Aspergillosis.
  • Supports emerging views that ABPA can occur before bronchiectasis develops.

Key points

  • ABPA considered despite normal chest imaging.
  • Diagnosis driven by immunological and eosinophilic markers.

Diagnosis of bronchopulmonary candidiasis—refractory airway hyperresponsiveness and severe pneumonia

Zhang D et al., Frontiers in Medicine, 2026

Relevance

  • Important differential diagnosis for suspected ABPA.

Key points

  • Bronchopulmonary candidiasis can closely mimic ABPA.
  • Normal Aspergillus serology does not exclude other fungal airway disease.

3. Rare immune defects and aspergillosis
Complete and partial forms of X-linked MCTS1 deficiency in patients with mycobacterial disease

Zhou Q et al., Journal of Human Immunity, 2026

Relevance

  • Expands the list of primary immunodeficiencies associated with Aspergillus infection.

Key points

  • Central nervous system aspergillosis identified as a rare but severe phenotype.
  • Suggests impaired cellular immunity as the underlying mechanism.

4. Antifungal therapy – toxicity, variability, and paediatrics
Voriconazole-associated peripheral polyneuropathy: A case report

González BJ et al., Archives of Argentine Pediatrics, 2026
(No PMC full text currently available)

Relevance

  • Highlights clinically important non-hepatic toxicity of azole therapy.

Key points

  • Peripheral neuropathy developed during voriconazole treatment.
  • Symptoms may be insidious and progressive.

RE: Factors affecting voriconazole pharmacokinetic variability in critically ill patients

Langbeen J et al., Critical Care, 2026

Relevance

  • Explains why fixed dosing of voriconazole is often unsafe.

Key points

  • Critical illness alters drug metabolism and clearance.
  • Drug–drug interactions are common.
  • Supports therapeutic drug monitoring and specialist pharmacy input.

Phase 2 clinical trial of posaconazole in paediatric invasive aspergillosis

Kang HJ et al., Antimicrobial Agents and Chemotherapy, 2026
(No PMC full text currently available)

Relevance

  • Rare prospective antifungal data in children.

Key points

  • Posaconazole showed acceptable safety.
  • Clinical responses were encouraging in a high-risk population.

5. Diagnostics, microbiology, and co-infection
Clinical characteristics, molecular diagnosis, and drug resistance profiles of nontuberculous mycobacteria infections

Wang K et al., Clinical and Translational Science, 2026

Relevance

  • Highly relevant to bronchiectasis patients where NTM and aspergillosis frequently coexist.

Key points

  • Molecular diagnostics improve species identification.
  • Resistance patterns complicate treatment strategies.

Impaired systemic antibody response against gut microbiota pathobionts in critical illness

Cho NA et al., Intensive Care Medicine Experimental, 2026

Relevance

  • Links immune–microbiome disruption to susceptibility to Aspergillus fumigatus.

Key points

  • Critical illness impairs antibody responses.
  • Loss of immune balance increases infection risk.

6. Pathogenesis and basic science
Arp2/3 complex contributes to actin-dependent uptake of Aspergillus terreus conidia

Mach N et al., PLOS One, 2026

Relevance

  • Improves understanding of early host–fungus interactions.

Key points

  • Epithelial cells actively internalise Aspergillus conidia.
  • Species differences may influence pathogenicity.

7. Environmental and One Health perspectives
Seasonal variation in Aspergillus abundance in captive penguin burrow sands

Takanobu S et al., Frontiers in Veterinary Science, 2026

Relevance

  • Demonstrates dynamic environmental exposure risk.

Key points

  • Clear seasonal peaks in Aspergillus burden.
  • Correlates with increased disease risk.

Mycotoxins – biomonitoring method including gliotoxin

Berger M et al., MAK Collection for Occupational Health and Safety, 2026

Relevance

  • Gliotoxin explored as a potential biomarker for invasive aspergillosis.

Key points

  • LC-MS/MS methods validated.
  • Currently research-grade rather than clinical.

by GAtherton

Latest Aspergillosis & Related Research Updates (Week 3).

January–February 2026

Search term is 'aspergillosis'.

This update highlights recent publications relevant to aspergillosis, allergic bronchopulmonary aspergillosis, nontuberculous mycobacterial lung disease, antifungal stewardship, diagnostics, and environmental fungal exposure. Papers are grouped by clinical theme, with key findings and clinical relevance highlighted.

1. Diagnostics, Molecular Methods & Imaging Innovation

Clinical Characteristics, Molecular Diagnosis, and Drug Resistance Profiles of Nontuberculous Mycobacteria Infections

Wang K, Xu D, Gao Y, Zhao W, Ma K
Clinical and Translational Science, 19(2):e70479, Feb 2026

Key highlights

  • Retrospective analysis using polymerase chain reaction melting curve technology to identify nontuberculous mycobacterial species.

  • Demonstrates rapid differentiation of clinically relevant species, with integrated resistance profiling.

  • Highlights marked heterogeneity in clinical presentation and antimicrobial resistance patterns.

Why this matters

  • Increasing relevance for patients with bronchiectasis, chronic obstructive pulmonary disease, and aspergillosis, where nontuberculous mycobacteria co-infection complicates diagnosis and treatment.

  • Supports the shift away from prolonged culture-only pathways toward faster molecular diagnostics.

Amplicon-based sequencing as a diagnostic tool for severe pneumonia in the ICU

Michel C, Imamura H, Yin N, et al.
Scientific Reports, 16(1):2845, Jan 2026

Key highlights

  • Amplicon-based sequencing applied directly to respiratory samples in intensive care.

  • Detects invasive aspergillosis alongside bacterial and viral pathogens.

  • Highlights limitations of current definitions of “proven invasive aspergillosis” when relying solely on histopathology.

Why this matters

  • Reinforces the diagnostic gap in critical care–associated pulmonary aspergillosis.

  • Supports broader adoption of molecular and microbiome-informed diagnostics in high-risk settings.

Deep learning detection and classification of fungal and non-fungal calcifications on paranasal sinus CT imaging

Yang Z, Choi I, Yun H, et al.
PLOS One, 21(1):e0340832, Jan 2026

Key highlights

  • Deep learning model distinguishes fungal ball (commonly aspergillosis) from non-fungal calcifications.

  • High diagnostic accuracy on routine sinus computed tomography scans.

  • Addresses a frequent diagnostic uncertainty in chronic rhinosinusitis.

Why this matters

  • Potential to reduce diagnostic delay and unnecessary surgery.

  • Particularly relevant for centres without ready access to specialist radiology expertise.

2. Invasive Aspergillosis: Expanding Risk Profiles & Clinical Phenotypes

Unmasking Invasive Pulmonary Aspergillosis: Insights From a Case Series at a Tertiary Care Center

Munasinghe K, Nanayakkara A, De Zoysa W, et al.
Cureus, 17(12), Jan 2026

Key highlights

  • Case series illustrating heterogeneous clinical presentations.

  • Emphasises delayed recognition outside classic immunocompromised populations.

  • Reinforces global incidence estimates of approximately 250,000 cases annually.

Why this matters

  • Supports growing recognition that invasive pulmonary aspergillosis occurs in broader patient groups, including those with chronic lung disease and critical illness.

Disseminated Invasive Aspergillosis in a Young Patient With Chronic Alcohol Use and Seemingly Preserved Immunocompetence

Khandwala K, Sawliha Syed H, Anwar S, et al.
Clinical Case Reports, 14(2), Jan 2026

Key highlights

  • Disseminated disease involving multiple organs.

  • Chronic alcohol use identified as a functional immunosuppressive state.

  • Challenges traditional “immunocompetent vs immunocompromised” dichotomy.

Why this matters

  • Reinforces the need for high clinical suspicion even when standard immune markers appear preserved.

  • Relevant for emergency, acute medical, and respiratory teams.

Intensification of Treosulfan–Fludarabine Conditioning With Thiotepa in Allogeneic Hematopoietic Stem Cell Transplantation

Tosoni L, Facchin G, Plos R, et al.
Transplant Direct, 12(2):e1896, Jan 2026

Key highlights

  • Real-world study in older or comorbid transplant recipients.

  • Reports four cases of invasive aspergillosis (three pulmonary, one cerebral).

  • Conditioning regimen was otherwise effective and tolerable.

Why this matters

  • Reinforces persistent invasive fungal infection risk despite modern conditioning approaches.

  • Supports ongoing need for antifungal prophylaxis and surveillance.

Infective Endocarditis Caused by Pan-Azole-Resistant Aspergillus fumigatus in a Lung Transplant Recipient

Ukai K, Kawashima M, Ikeuchi K
Transplant Infectious Disease, Jan 2026

Key highlights

  • Rare but severe manifestation: fungal endocarditis.

  • Pan-azole resistance significantly limited treatment options.

  • Occurred in a lung transplant recipient.

Why this matters

  • Adds to evidence of clinically catastrophic azole resistance.

  • Reinforces importance of resistance testing and antifungal stewardship.

3. Antifungal Toxicity & Stewardship

Voriconazole-associated peripheral polyneuropathy: A case report

González BJ, Ivarola P, Miranda M, et al.
Archivos Argentinos de Pediatría, 124(1), Feb 2026

Key highlights

  • Documents peripheral neuropathy linked to prolonged voriconazole exposure.

  • Emphasises reversibility only after early recognition and drug withdrawal.

Why this matters

  • Highly relevant for patients on long-term antifungal therapy for chronic pulmonary aspergillosis.

  • Supports routine neurological symptom surveillance.

Antifungal Stewardship: Time to Reappraise the Priorities toward Increasing Invasive Fungal Infections

Singh S
Annals of African Medicine, Jan 2026

Key highlights

  • Reviews stewardship challenges across aspergillosis, candidemia, and mucormycosis.

  • Highlights overuse, under-diagnosis, and limited access to diagnostics.

  • Calls for stewardship frameworks equivalent to antibacterial programmes.

Why this matters

  • Directly relevant to azole resistance, drug toxicity, and resource-limited settings.

  • Aligns with national and international fungal disease priorities.

4. Allergy, Mycotoxins & Inflammatory Pathways

Common inflammatory markers predict risk of ABPA development in children with cystic fibrosis

Crabtree HED, Malajczuk CJ, Ho HY, et al.
Journal of Cystic Fibrosis, Jan 2026

Key highlights

  • Identifies routinely measured inflammatory markers predictive of allergic bronchopulmonary aspergillosis.

  • Potential for earlier identification and intervention.

Why this matters

  • May support risk stratification in paediatric cystic fibrosis clinics.

  • Relevant for future screening and monitoring protocols.

Potential mechanisms and effects of AFB1-induced asthma

Yu Z, Gao M, Wu X, et al.
PLOS One, 21(1):e0341172, Jan 2026

Key highlights

  • Network toxicology and molecular docking suggest links between aflatoxin B1 exposure and:

    • Asthma

    • Allergic bronchial pulmonary aspergillosis

    • Lung malignancy in severe cases

Why this matters

  • Strengthens environmental and occupational health links to fungal allergy and chronic lung disease.

  • Supports broader discussion of mould exposure beyond infection alone.

Mycotoxins – Determination of aflatoxins, ochratoxin A, gliotoxin, and others in urine by LC–MS/MS

Berger M, Deharde M, Neuhoff J, et al.
MAK Collection for Occupational Health and Safety, 10(2), Jan 2026

Key highlights

  • Validated biomonitoring method for gliotoxin, aflatoxins, and ochratoxins.

  • Discusses potential use of urine biomarkers for early detection of invasive aspergillosis.

Why this matters

  • Provides methodological groundwork for future biomarker-driven diagnostics.

  • Particularly relevant for occupational and environmental exposure assessment.

Money and Microbes: A Global Systematic Review and Meta-Analysis of Currency Contamination

Appiah PO, Odoom A, Tetteh-Quarcoo PB, Donkor ES
Environmental Health Insights, Jan 2026

Key highlights

  • Identifies paper currency as a reservoir for microbial and fungal contamination.

  • Notes links to serious infections, including pulmonary aspergillosis.

Why this matters

  • Highlights overlooked environmental reservoirs of fungal exposure.

  • Relevant for public health messaging and infection control.

by GAtherton

Connecting patients, carers, clinicians and scientists to improve life with aspergillosis

World Aspergillosis Day (WAD) is an annual global event that brings together people who live with, care for, treat, and research long-term forms of aspergillosis — particularly chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA).

Each year, WAD creates a shared space where:

  • patients and carers can hear directly from specialists,

  • clinicians and scientists can learn from patient experience,

  • and everyone can explore how new research translates into better care.

🎥 Missed previous events?
Recordings from earlier World Aspergillosis Day meetings are available on our YouTube channel.

📅 NAC World Aspergillosis Day Meeting 2026

The National Aspergillosis Centre (NAC) will once again host a free online meeting:

🗓 Tuesday 3 February 2026
💻 Online via Microsoft Teams
👥 Open to patients, carers, clinicians, scientists, and anyone who lives or works with aspergillosis

🧬 This year’s theme:

“How can the genomics revolution help patients with chronic aspergillosis?”

Why genomics — and why now?

Modern molecular tests such as PCR and DNA sequencing are becoming faster, cheaper and more accurate. Because of this, the NHS is increasingly exploring how genomic technologies can be used to improve diagnosis, monitoring and treatment across many diseases — including aspergillosis.

This year’s WAD meeting will start an open discussion between patients and professionals about which genomic and molecular tests are likely to matter most for people with aspergillosis in the years ahead.

Topics will include:

  • 🧠 Is there a “gene for aspergillosis”?
    Should people be tested for genetic susceptibility?

  • 💊 Genes and voriconazole dosing
    Can testing the CYP2C19 gene help personalise antifungal treatment?

  • 🦠 Tracking antifungal resistance
    How molecular testing of Aspergillus strains can help hospitals monitor resistance.

  • 🔬 Aspergillus PCR at NAC
    How PCR is already used to diagnose and monitor chronic aspergillosis.

🗣️ Patient voices at the heart of the meeting

As always, patient experience will be central to the day.

This year will include new patient stories, including Alison, who will talk about how her aspergillosis treatment led to the development of adrenal insufficiency, and what that has meant for her care and daily life.

“I don’t know anything about genetics — is this for me?”

Absolutely yes.

You don’t need any background in genetics to take part. Everything will be explained clearly, step by step, with minimal jargon.

Planned discussion topics include:

  • What do my Aspergillus PCR test results actually mean?

  • Is there really a “gene for CPA”?

  • Why do genes matter for antifungal dosing?

In fact, the more questions you ask — especially the “silly” ones — the better. The discussion from the day will be used to create a new patient leaflet, designed to help people better understand their diagnosis and test results.

✅ Registration is now open

🎟 Book your free place via Eventbrite:
👉 www.eventbrite.co.uk/e/world-aspergillosis-day-tickets-1980707139373

💻 Joining via Microsoft Teams

The meeting will be held online using Microsoft Teams, which you can download here:
👉 www.microsoft.com/en-gb/microsoft-teams/group-chat-software

If you haven’t used Teams before, we recommend doing a test call in advance. If you run into any problems setting things up, we’re very happy to help.

We hope you can join us for World Aspergillosis Day 2026 — to learn, to ask questions, and to help shape the future of aspergillosis care together.

by GAtherton

January–February 2026 Aspergillosis Papers (week 3)

Grouped by relevance and impact

🟥 HIGH IMPACT / PRACTICE-RELEVANT

(Most important for patients, clinicians, and services)

1. Chronic Pulmonary Aspergillosis (CPA): outcomes and mortality

Clinical Features and Mortality of Chronic Pulmonary Aspergillosis in Brazil
Open Forum Infectious Diseases, Jan 2026

Why this is important

  • Large multicentre cohort

  • Real-world data from TB-endemic, resource-limited settings

  • Directly relevant to global CPA burden, including post-TB disease

Key messages

  • CPA carries substantial long-term mortality

  • Tuberculosis is a major driver of CPA worldwide

  • Delayed diagnosis and limited antifungal access worsen outcomes

➡ This is one of the most important papers in the list for public health, service planning, and advocacy.

2. Invasive Aspergillosis in Intensive Care (including COVID-19)

Clinical spectrum of ICU-acquired invasive pulmonary aspergillosis according to SARS-CoV-2 infection
Eur J Clin Microbiol Infect Dis, Jan 2026

Why this is important

  • Large prospective multicentre ICU cohort

  • Builds on lessons from COVID-19 Associated Pulmonary Aspergillosis (CAPA)

Key messages

  • ICU-acquired aspergillosis remains common and deadly

  • COVID-19 patients are typically older and more severely ill

  • Early fungal testing in ICU is critical

➡ High relevance for intensivists, respiratory teams, and hospital policy.

3. Drug interactions in invasive aspergillosis

Concurrent administration of triazoles with chemotherapeutic and/or immunosuppressant agents
Mycopathologia, Jan 2026

Why this is important

  • Addresses real-world prescribing risk

  • Highly relevant to cancer, transplant, and haematology patients

Key messages

  • Triazole antifungals cause clinically dangerous drug–drug interactions

  • Requires specialist pharmacy oversight and monitoring

  • Not theoretical – directly affects patient safety

➡ High importance for clinicians and pharmacists, less so for patients directly, but critical for safe care.

🟧 MODERATE IMPACT / CLINICALLY INFORMATIVE

(Important, but narrower scope or smaller evidence base)

4. Aspergillosis beyond the “immunocompromised”

Pulmonary fungal infections in the immunocompetent host
Chest, Jan 2026 – Review

Why this matters

  • Challenges outdated assumptions

  • Useful for GPs and general physicians

Key messages

  • Serious fungal lung disease can occur without classic immune suppression

  • Chronic lung disease, viral infection, or exposure can be sufficient

  • Supports earlier fungal consideration when antibiotics fail

➡ Good educational review, especially for non-specialists.

5. Aspergillus species diversity and resistance

Beyond Fumigatus: a molecular portrait of clinical Aspergillus diversity
Antimicrobial Agents and Chemotherapy, Jan 2026

Why this matters

  • Advances understanding of non-fumigatus Aspergillus

  • Relevant to antifungal resistance

Key messages

  • Aspergillosis is caused by multiple species

  • Species identification may influence treatment success

  • Supports move toward precision mycology

➡ Important scientifically, indirect impact for patients (for now).

6. Minimally invasive treatment of aspergilloma

Minimally invasive management of a centrally located pulmonary aspergilloma
MMCTS, Jan 2026

Why this matters

  • Demonstrates evolving surgical approaches

  • Relevant to selected patients only

Key messages

  • Less invasive procedures may reduce surgical risk

  • Careful patient selection is crucial

➡ Clinically interesting, but case-based and niche.

🟨 LOW IMPACT / EARLY-STAGE / NICHE

(Useful context or future potential, limited immediate impact)

7. ABPA immunology and diagnostics (early-stage science)

Pathogen-specific IgE-reactive cytosolic allergenic epitopes of Aspergillus fumigatus
Ann Clin Microbiol Antimicrob, Jan 2026

Why this matters

  • Laboratory-based discovery research

Key messages

  • May improve future ABPA diagnostics

  • Potential foundation for targeted immunotherapy

➡ Promising but not practice-changing yet.

8. Voriconazole neurotoxicity (single case)

Voriconazole-associated peripheral polyneuropathy: A case report
Arch Argent Pediatr, Feb 2026

Why this matters

  • Highlights a rare but serious adverse effect

Key messages

  • Neurological symptoms on antifungals should not be ignored

  • Reinforces importance of monitoring during long-term therapy

➡ Low evidence level, but high awareness value.

9. Invasive aspergillosis in complex transplant oncology case

An Unforeseen Diagnosis After Liver Transplantation for Acute Liver Failure
Case Reports in Hepatology, Jan 2026

Why this matters

  • Illustrates diagnostic complexity in extreme immunosuppression

Key messages

  • Invasive aspergillosis can be rapidly fatal

  • Symptoms may be masked by other conditions

➡ Educational case, not generalisable.

10. Food enzyme safety (non-clinical)

Safety evaluation of the food enzyme aspergillopepsin I
EFSA Journal, Jan 2026

Why this matters

  • Addresses public concern rather than clinical disease

Key messages

  • Aspergillus-derived food enzymes are safe when regulated

  • Dietary exposure ≠ inhaled fungal spores

➡ Reassuring, but peripheral to aspergillosis care.

🔑 Overall “Most Important” Papers (Quick List)

Top tier

  1. CPA outcomes and mortality (Brazil cohort)

  2. ICU / COVID-19 associated invasive aspergillosis

  3. Triazole drug–drug interactions

Second tier
4. Fungal infection in immunocompetent hosts
5. Aspergillus species diversity & resistance

January–February 2026 Aspergillosis Papers – Source Links

🟥 High-impact / practice-relevant

  • Clinical Features and Mortality of Chronic Pulmonary Aspergillosis in Brazil: a Multicenter Cohort Study
    de Oliveira VF et al., Open Forum Infectious Diseases, Jan 2026
    🔗 https://pubmed.ncbi.nlm.nih.gov/41536616/

  • Clinical spectrum of ICU-acquired invasive pulmonary aspergillosis according to SARS-CoV-2 infection: a multicenter prospective cohort study
    Reizine F et al., European Journal of Clinical Microbiology & Infectious Diseases, Jan 2026
    🔗 https://pubmed.ncbi.nlm.nih.gov/41526761/

  • Concurrent Administration of Triazoles with Chemotherapeutic and/or Immunosuppressant Agents Known to Have Moderate-to-Severe Drug-Drug Interactions in Patients with Hematologic Malignancies Hospitalized for Invasive Aspergillosis
    Walsh TJ et al., Mycopathologia, Jan 2026
    🔗 https://pubmed.ncbi.nlm.nih.gov/41528615/

🟧 Moderate-impact / clinically informative

🟨 Lower-impact / niche / early-stage

  • Pathogen-specific IgE-reactive cytosolic allergenic epitopes of Aspergillus fumigatus for immunodiagnostic and immunotherapeutic applications against allergic aspergillosis
    Koundal P et al., Annals of Clinical Microbiology and Antimicrobials, Jan 2026
    🔗 https://pubmed.ncbi.nlm.nih.gov/41540426/

  • Voriconazole-associated peripheral polyneuropathy: A case report
    González BJ et al., Archivos Argentinos de Pediatría, Feb 2026
    🔗 https://pubmed.ncbi.nlm.nih.gov/40728252/

  • An Unforeseen Diagnosis After Liver Transplantation for Acute Liver Failure: Extranodal NK/T-Cell Lymphoma (includes invasive aspergillosis)
    Soares GL et al., Case Reports in Hepatology, Jan 2026
    🔗 https://pubmed.ncbi.nlm.nih.gov/41542139/

  • Safety evaluation of the food enzyme aspergillopepsin I from the genetically modified Trichoderma reesei strain DP-Nzq40
    EFSA Panel on Food Enzymes, EFSA Journal, Jan 2026
    🔗 https://pubmed.ncbi.nlm.nih.gov/41531469/

by GAtherton

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

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

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

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

📋 Clinical Trials of Interest

1. Phase III Olorofim Trial for Invasive Aspergillosis

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

2. Rezafungin in Chronic Pulmonary Aspergillosis (CPA)

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

3. Combination Trial: Ibrexafungerp + Voriconazole (SCYNERGIA)

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

4. PCR Diagnostic Study for Aspergillus fumigatus

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

🔎 What Else Is Ongoing?

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

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

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

🧠 What This Means for Patients

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

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

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

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

🗓 How to Use These Links

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

  • Who can participate

  • Locations and contact information

  • Detailed eligibility criteria

  • Sponsor and trial timelines

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

by GAtherton

How to Ask Fewer, Better Questions in Appointments

Focusing on what matters most to you—without feeling you’re wasting time

Many patients and carers worry about “asking too much” in clinic. Appointments are short, clinicians are busy, and you may already have a long list of questions in your head. The aim isn’t to stop asking questions—it’s to ask the right ones, at the right time, in the right way.

Here are practical strategies that help you stay focused, feel heard, and make the most of limited time.

1. Decide your Top 3 priorities before you go

Before the appointment, write down everything you’re thinking about. Then circle just three things that matter most right now.

Good priorities are usually:

  • A symptom that is new, worsening, or frightening

  • A treatment issue that affects daily life (side-effects, adherence, cost, function)

  • A decision you need to make soon

If it doesn’t change what happens in the next few weeks, it may not need airtime today.

If you remember only one thing: appointments are for decisions, not encyclopaedias.

2. Separate “need to know” from “nice to know”

It’s easy to mix curiosity with urgency.

Need to know (ask now):

  • Is this symptom important?

  • Is this treatment still right for me?

  • What should I do if X happens?

  • Are we monitoring the right things?

Nice to know (park for later):

  • Mechanisms, pathways, emerging research

  • Rare side-effects without symptoms

  • “What if” scenarios far in the future

Keep a “parking list” for later reading or discussion.

3. Frame questions around impact, not theory

Clinicians work best when questions are grounded in real life.

Instead of:

  • “I read a paper saying X might affect Y…”

Try:

  • “I’m noticing X in daily life—does that change what we do?”

  • “Is this symptom something you’d want to investigate?”

This signals relevance and helps clinicians triage quickly.

4. Ask one question at a time

Long, multi-part questions feel overwhelming and are easy to partially answer.

Break them down:

  • First: Is this important?

  • Then (if yes): What do we do about it?

  • Then (if needed): What should I watch for?

You’ll often find later questions become unnecessary once the first is answered.

5. Use the “Is this something we should…” test

This single phrase keeps questions concise and respectful of time:

  • “Is this something we should investigate?”

  • “Is this something that changes treatment?”

  • “Is this something I should worry about?”

A clear yes/no (or not yet) is often all you need.

6. Accept that not everything fits in one appointment

It’s okay—and normal—to say:

  • “I know we may not have time today—what should I prioritise?”

  • “Which of these matters most from your point of view?”

This shows partnership, not passivity.

If something needs more time, ask how best to handle it:

  • Another appointment

  • A nurse specialist

  • Written advice

  • Monitoring and review later

7. Bring written notes (but don’t read them all out)

A short list helps you stay focused under pressure.

Tip:

  • Highlight your top 3

  • Tick them off as they’re addressed

  • If time runs out, you still covered what mattered most

8. For carers: ask on behalf, not over

Carers often worry about dominating the conversation.

Helpful approaches:

  • Ask the patient first: “What do you most want answered today?”

  • Step in only if something important is being missed

  • Offer to follow up questions outside the appointment if possible

9. Reassure yourself: clinicians don’t expect perfection

You are not expected to:

  • Understand everything

  • Ask the “right” questions every time

  • Cover your entire condition in one visit

Good clinicians prefer:

a focused conversation
over
a rushed, overloaded one

10. A simple closing question that saves time

If time is tight, end with:

  • “Is there anything you think I should have asked but didn’t?”

This often surfaces the most important point of all.

The takeaway

You are not wasting time by asking questions—you’re wasting time by asking too many unfocused ones.

Clarity, prioritisation, and relevance help everyone:

  • You leave with answers that matter

  • Clinicians can make better decisions

  • Anxiety is reduced, not fuelled

by GAtherton

Learning About Aspergillosis (and Related Treatments)

How to stay curious, informed, and safe — without overload

Many people living with aspergillosis, or caring for someone who is, become highly motivated learners. You may read scientific papers, books, online articles, social media posts, AI summaries, and news stories about antifungal treatments, steroids, biologics, side-effects, immunity, mould exposure, diet, exercise, and wellbeing.

That curiosity is a strength. It helps you ask better questions, notice changes early, and feel more involved in your care.

At the same time, not all information is reliable, relevant, or helpful, and even good information can become harmful if it is over-interpreted or taken out of context. This article is about finding the balance: learning with confidence, without increasing anxiety or risk.

Why learning helps — and why it can sometimes backfire

The positives

  • Empowerment: Understanding your condition improves confidence.

  • Better conversations: Appointments are more productive when you share a common language.

  • Early awareness: You may recognise symptoms or side-effects sooner.

  • Reassurance: Knowledge can reduce uncertainty and fear.

The risks

  • Over-interpretation: A single paper or post can feel more important than it is.

  • Variable quality: Some research is weak, outdated, biased, or misapplied.

  • Loss of context: Lab studies or rare case reports may not apply to you.

  • Rising anxiety: Constant searching can amplify worry rather than reduce it.

  • Information overload: Too much input can make decisions harder, not easier.

A healthier approach to learning

1. Think in weight of evidence, not single findings

One article, story, or AI answer almost never changes medical care on its own.

When you read something new, ask:

  • Is this supported by more than one study?

  • Does it appear in guidelines or specialist practice?

  • Is it discussed cautiously, or presented as a breakthrough?

A useful rule of thumb:

The more dramatic the claim, the stronger the evidence needs to be.

2. Separate biological possibility from clinical reality

Many things are biologically plausible — immune pathways, hormones, inflammation, the microbiome — but that doesn’t mean they are proven or clinically relevant.

Helpful questions include:

  • Was this studied in people, or only in the lab?

  • Were the patients similar to me?

  • Did it improve symptoms or outcomes, not just blood tests?

Choosing trusted health information: practical guidance

Learning safely isn’t about reading less. It’s about choosing better sources and knowing how much weight to give them.

3. Start with sources that anchor practice

Your most reliable foundations are sources that:

  • Reflect clinical consensus, not speculation

  • Are written or reviewed by specialist teams

  • Change slowly because they are evidence-based

Examples include:

  • Specialist centre or hospital websites

  • National or international guidelines

  • Established patient organisations linked to clinical services

Examples:

    • NHS website
      A good starting point for clear, balanced information on symptoms, tests, treatments, and general health advice.
      Useful for understanding what is considered standard care in the UK.

    • British National Formulary (BNF)
      The main UK reference for medicines.
      Particularly helpful for:

      • Medication side-effects

      • Drug interactions (including antifungals, steroids, and inhalers)

      • Practical prescribing information
        Side-effects are listed cautiously, so not everything applies to every person.

    • aspergillosis.org
      A specialist resource focused specifically on aspergillosis, written for patients, carers, and professionals.
      Helpful for understanding different forms of aspergillosis, investigations, treatments, and living with the condition.

    • European Lung Foundation – Aspergillosis resources
      Patient-focused information developed with respiratory specialists and patient representatives across Europe.
      Particularly useful for:

      • Plain-language explanations

      • Patient priorities and lived experience

      • Shared decision-making and questions to ask in clinic

    • Asthma + Lung UK (BLF)
      A trusted source for asthma and other lung diseases.
      Helpful for inhaler use, breathlessness, flare-ups, lifestyle advice, and living well with chronic lung conditions.

    • Aspergillosis Trust
      This website was created by patients who suffer from Aspergillosis. Please navigate around the website to read more about this disease, also the impact it has upon patients and their carers.

These sources may feel less exciting — but they set the safe boundaries of what is known.

4. Learn to spot interpretation versus evidence

Two people can read the same paper and draw very different conclusions.

Ask yourself:

  • Is this source presenting evidence, or interpreting it strongly?

  • Are limitations and uncertainty acknowledged?

  • Is the language careful or absolute?

Trusted sources often say:

“Evidence suggests…” or “We don’t yet know…”

Less reliable ones often say:

“This proves…” or “This explains everything.”

5. Use a simple credibility checklist

You don’t need to be a scientist to judge quality.

When reading anything, consider:

Who wrote it?
Clinical specialists, recognised organisations, or anonymous individuals?

Why was it written?
To inform and support — or to sell, persuade, or provoke?

What evidence is used?
Multiple studies and guidelines — or a single paper or personal story?

What tone is used?
Balanced and cautious — or dramatic and fear-based?

Several warning signs together should lower confidence.

6. Be cautious with “hidden” or “overlooked” explanations

Phrases that should trigger caution include:

  • “Doctors don’t tell you this…”

  • “The hidden cause…”

  • “The real reason…”

  • “One simple explanation…”

Conditions like aspergillosis are complex. Simple, universal explanations are rarely accurate.

7. Understand where research sits on the evidence ladder

Not all research carries the same weight.

Very roughly:

  1. Clinical guidelines and consensus statements

  2. Large clinical trials and systematic reviews

  3. Observational studies

  4. Case reports

  5. Laboratory or animal studies

  6. Opinions and anecdotes

Lower down the ladder does not mean “worthless” — but it does mean less certain and less likely to change care on its own.

8. Treat patient stories and forums as experience, not prediction

Patient experiences are invaluable for:

  • Feeling less alone

  • Understanding day-to-day challenges

  • Sharing coping strategies

They are not reliable predictors of:

  • What will happen to you

  • How common a problem is

  • Whether a treatment will help or harm you

A helpful distinction:

Stories help you feel understood. Evidence helps guide decisions.

9. Use AI tools wisely

AI can be excellent for:

  • Explaining terminology

  • Summarising broad topics

  • Helping you generate questions

AI cannot:

  • Replace specialist judgement

  • Fully understand your medical history

  • Balance risk in the way clinicians do

Treat AI as:

“A map to the topic,”
not
“An answer about me.”

10. Limit your sources — and give yourself permission to stop

Many people feel calmer once they:

  • Choose two to four trusted sources

  • Revisit those instead of endlessly searching

  • Accept that not every new paper needs action

Stopping is not giving up — it is protecting your wellbeing.

Bringing what you’ve learned into clinic

A good sign you’ve chosen reliable information:

  • You feel comfortable sharing it with clinicians

  • It leads to discussion, not confusion

  • It helps prioritise decisions

You might say:

  • “I’ve been reading from a specialist source — how relevant is this to me?”

  • “This helped me understand X, but I’m not sure how much weight to give it.”

When to pause or rebalance your learning

Consider stepping back if:

  • Searching increases anxiety every time

  • You feel pressure to solve everything yourself

  • Conflicting information leaves you stuck

  • Illness becomes the only thing you think about

Taking breaks from research is not disengagement — it is self-care.

The key message

Learning is a powerful tool. Used well, it supports confidence, partnership, and resilience. Used without guardrails, it can undermine peace of mind.

Aim for:

  • Curiosity with caution

  • Knowledge with context

  • Questions with balance

You don’t need to know everything.
You need to know what helps you live well and safely.

This article pairs with:
“Making the Most of Appointments: Asking Fewer, Better Questions” — a practical guide to deciding what to raise in clinic and how to use limited time effectively.

by GAtherton

Aspergillus Updates week 51

1. Immunodeficiency, rare syndromes & aspergillosis risk

Standing Still: A Case of Stiff Person Syndrome and Common Variable Immunodeficiency

Khazar et al., Cureus, 2025

Summary

  • Describes a rare coexistence of Stiff Person Syndrome (SPS) and Common Variable Immunodeficiency (CVID).

  • Highlights autoimmune–immunodeficiency overlap and diagnostic complexity.

Why it matters

  • CVID is a recognised risk factor for recurrent infections and chronic lung disease, including bronchiectasis and chronic pulmonary aspergillosis (CPA).

  • Reinforces the need for multisystem thinking when patients present with neurological and respiratory symptoms.

Limitations

  • Single case; no fungal infection reported.

  • Indirect relevance to aspergillosis but important for risk stratification.

Beyond Cystic Fibrosis: Recognising Shwachman–Diamond Syndrome in the Respiratory Clinic

Yang et al., Respirology Case Reports, 2025

Summary

  • Emphasises misdiagnosis of Shwachman–Diamond syndrome (SDS) as cystic fibrosis.

  • Includes discussion of allergic bronchopulmonary aspergillosis (ABPA) in the differential.

Why it matters

  • Reinforces that non-CF genetic syndromes can present with:

    • Bronchiectasis

    • Recurrent infection

    • ABPA-like features

  • Highly relevant to adult respiratory clinics and late diagnoses.

Clinical takeaway

  • ABPA should prompt consideration of underlying immune or genetic disease, not just asthma or CF.

2. Genetics & structural lung disease

Exome sequencing reanalysis identifies a novel CFAP54 variant in primary ciliary dyskinesia

Li et al., Frontiers in Medicine, 2025

Summary

  • Identifies a new likely pathogenic CFAP54 variant.

  • Expands the phenotypic spectrum of Primary Ciliary Dyskinesia (PCD).

Relevance to aspergillosis

  • PCD → impaired mucociliary clearance → chronic infection, bronchiectasis, and secondary fungal disease.

  • ABPA and CPA are increasingly recognised in non-CF bronchiectasis populations.

Strength

  • Genotype–phenotype correlation strengthens diagnostic confidence.

Limitation

  • Aspergillosis not a primary focus, but highly relevant to long-term respiratory outcomes.

3. Haematology, malignancy & invasive aspergillosis

Mixed-Phenotype Acute Leukemia Transforming into AML-M4

Alhayek et al., Cureus, 2025

Summary

  • Case of evolving leukemia complicated by pancytopenia, invasive pulmonary aspergillosis (IPA), and COVID-19.

Key points

  • Illustrates real-world stacked risk:

    • Neutropenia

    • Chemotherapy

    • Viral infection

    • IPA

Clinical relevance

  • Strong reminder that IPA often emerges during diagnostic or therapeutic transitions, not just during induction chemotherapy.

Invasive fungal infections in haematologic diseases: evidence, challenges, and practice

Cho et al., Blood Research, 2025 – Review

Summary

  • Comprehensive overview of invasive aspergillosis, candidiasis, and mucormycosis.

  • Covers diagnostics, antifungal resistance, and treatment strategies.

Strengths

  • Practical, guideline-aligned.

  • Emphasises individualised risk assessment and early treatment.

Gap

  • Limited discussion of long-term survivors and post-IPA chronic complications (e.g. CPA).

4. Imaging & diagnostics

CT Pulmonary Angiography in invasive pulmonary aspergillosis

Tian, Future Microbiology, 2025

Summary

  • Explores the role of CT pulmonary angiography (CTPA) in detecting angioinvasion.

Why it matters

  • Vascular occlusion and infarction are hallmarks of IPA.

  • CTPA may improve diagnostic confidence when standard CT is equivocal.

Limitations

  • Case-based evidence.

  • Needs integration into diagnostic algorithms.

Sequential serum galactomannan as an outcome marker

Többen et al., Int J Infect Dis, 2025

Summary

  • Registry-based exploratory analysis of serial galactomannan (GM).

Key finding

  • Trends in GM may correlate with treatment response, not just diagnosis.

Clinical importance

  • Supports GM as a monitoring biomarker, though interpretation remains complex.

Caution

  • Not reliable in all patient groups (e.g. non-neutropenic, antifungal pre-exposure).

5. Chronic pulmonary aspergillosis & structural disease

Molecular epidemiology of Aspergillus species in CPA (South India)

Spruijtenburg et al., Medical Mycology, 2025

Summary

  • Describes species diversity and genetic variation in CPA patients.

Why it matters

  • Highlights:

    • Geographic variation

    • Potential antifungal resistance implications

  • Supports species-level identification in CPA.

Strength

  • Strong laboratory–clinical interface.

Advanced pulmonary sarcoidosis

Spagnolo et al., Seminars in Respiratory and Critical Care Medicine, 2025

Summary

  • Reviews complications of advanced sarcoidosis, including:

    • Bronchiectasis

    • Pulmonary hypertension

    • Chronic pulmonary aspergillosis

Key point

  • CPA should be actively considered, not viewed as rare, in fibrotic sarcoidosis.

Rezafungin OPAT for chronic pulmonary aspergillosis

Law et al., JAC Antimicrobial Resistance, 2025

Summary

  • First real-world case of rezafungin used via outpatient parenteral therapy for CPA.

  • Includes a health-economic assessment.

Why this is important

  • CPA treatment options are limited.

  • Weekly dosing may:

    • Reduce hospital burden

    • Improve quality of life

Caution

  • Single case; echinocandins are not standard CPA therapy.

  • Best viewed as salvage or niche use.

6. Tracheobronchial & atypical aspergillosis

Tracheobronchial Aspergillosis Mimicking Pseudotumour

Castillo Gamboa et al., Clinical Case Reports, 2025

Summary

  • Rare presentation of tracheobronchial aspergillosis masquerading as malignancy.

Clinical lesson

  • Endobronchial disease can be missed or mislabelled.

  • Supports biopsy and fungal testing when appearances are atypical.

7. Immunology, inflammation & host–pathogen interaction

PANoptosis in pathogen infection and systemic disease

Cai et al., Cell Biology and Toxicology, 2025 – Review

Summary

  • Reviews PANoptosis (pyroptosis, apoptosis, necroptosis) in infections.

Relevance

  • Aspergillus is discussed as a trigger of complex inflammatory cell death pathways.

  • May help explain:

    • Severe tissue damage

    • Dysregulated inflammation in IPA

Translational value

  • Still mechanistic; clinical applications remain distant.

PD-1 / PD-L1 immune checkpoint in fungal infections

Zheng et al., Virulence, 2025 – Review

Summary

  • Explores immune exhaustion in ABPA, CPA, and IPA.

Key insight

  • Checkpoint pathways may:

    • Contribute to chronic infection persistence

    • Become future adjunctive immunotherapies

Important caution

  • Immune checkpoint modulation carries significant risk in fungal disease.

8. Antimicrobial stewardship & prophylaxis

Procalcitonin-guided antibiotics in RSV and influenza

Hessels et al., BMJ Open Respiratory Research, 2025

Finding

  • Reduced antibiotic use without increased fungal infection risk.

Relevance

  • Important reassurance that stewardship does not increase IPA risk in viral respiratory infections.

Letermovir prophylaxis post-HSCT

Kimura et al., J Infect Chemother, 2025

Key result

  • Letermovir did not increase invasive aspergillosis or candidemia risk.

Clinical reassurance

  • Supports ongoing antiviral prophylaxis strategies in transplant patients.

9. Experimental antifungals

Berberine suppresses Aspergillus fumigatus growth

Wang et al., ACS Infectious Diseases, 2025

Summary

  • Demonstrates antifungal activity via:

    • Mitochondrial fragmentation

    • Reactive oxygen species

    • Hog1-MAPK activation

  • Reduced fungal burden in a murine IPA model.

Important caution

  • Pre-clinical only.

  • Not a supplement recommendation for patients.

Overall themes & take-home messages

Key trends this week

  • Increasing recognition of rare immunodeficiency and genetic syndromes behind chronic lung disease.

  • Better understanding of non-classical aspergillosis presentations.

  • Strong interest in immune modulation, biomarkers, and novel therapies.

  • Continued need for early diagnosis, especially in haematology and advanced lung disease.

For clinical practice

  • Think beyond labels (asthma, CF, cancer).

  • Revisit diagnoses when disease behaves atypically.

  • CPA and ABPA remain under-recognised but increasingly documented across conditions.

If you’d like, I can:

  • Turn this into a NAC weekly research digest

  • Produce patient-safe summaries of selected papers

  • Extract figures and learning points for teaching or the Knowledge Hub

by GAtherton

🌍 THE MICROBIOME REVOLUTION

How gut and lung microbiota are transforming the way we diagnose, treat and understand infection in aspergillosis

https://media.springernature.com/full/springer-static/image/art%3A10.1038%2Fs41698-020-00138-z/MediaObjects/41698_2020_138_Fig1_HTML.png
https://www.cell.com/cms/10.1016/j.heliyon.2024.e24032/asset/c18ec70a-98da-43b9-8114-e20cf6cf2ab6/main.assets/gr3_lrg.jpg

For decades, infection was seen through a simple lens:

Find the organism → treat the organism → infection cured.

But modern microbiome research has shown that this view is too narrow—especially for chronic lung diseases such as aspergillosis, bronchiectasis, ABPA, SAFS and CPA.

We now understand that the:

  • lungs,

  • gut,

  • sinuses,

  • skin, and even

  • CPA cavities

contain complex microbial ecosystems (bacteria, fungi, viruses, archaea) that interact dynamically with each other and with your immune system.

Rather than being passive passengers, these microbes shape inflammation, immunity, symptoms, resistance, treatment response and overall wellbeing.

This is why microbiome science is truly revolutionising how clinicians think about infection.

🧬 1. What is a microbiome?

A microbiome is the entire community of microorganisms living in a particular environment, plus all the genes, chemicals, signals and interactions that exist between them.

Healthy microbiomes are:

  • diverse

  • stable

  • environmentally balanced

  • dominated by harmless or beneficial species

Disease-associated microbiomes are:

  • less diverse

  • unstable

  • dominated by a few harmful organisms

  • deeply involved in inflammation

This imbalance is called dysbiosis.

🫁 2. The lung microbiome: complex, dynamic, and vital

The lungs are not sterile—they contain a delicate, low-density microbiome.

In health, microbes drift in and out through:

  • breathing

  • micro-aspiration

  • mucociliary clearance

The “healthy lung microbiota” remains balanced because airflow and immune regulation prevent any single species from dominating.

In disease (aspergillosis, bronchiectasis, ABPA, SAFS, CPA), the situation changes:

  • thick mucus traps microbes

  • reduced airflow produces stagnant zones

  • inflammation increases microbial stickiness

  • biofilms form

  • pathogens dominate

  • microbial diversity drops

  • chronic inflammation becomes self-sustaining

This drives persistent symptoms even when cultures appear negative.

🍽️ 3. The gut microbiome: our “second immune system”

https://www.researchgate.net/publication/330336693/figure/fig3/AS%3A714099797270528%401547266067017/Proposed-schematic-representation-of-how-the-gut-microbiome-is-regulated-Risk-factors.jpg
https://www.researchgate.net/publication/326442483/figure/fig1/AS%3A11431281250325630%401717821322668/Interaction-between-gut-microbiota-and-immune-system-Gut-microbiota-metabolites-and.tif
https://pub.mdpi-res.com/cells/cells-13-01436/article_deploy/html/images/cells-13-01436-g001.png?1724759089=&utm_source=chatgpt.com

The gut contains trillions of bacteria, fungi and viruses.
Far from being limited to digestion, the gut microbiome influences:

  • immune development

  • inflammation control

  • IgE responses

  • eosinophils

  • energy levels

  • weight regulation

  • steroid responsiveness

  • susceptibility to infection

  • mental wellbeing

Up to 70% of your immune system is shaped by gut microbes.

This means:

Gut health directly affects lung health, including risk and severity of aspergillosis-related disease.

🔄 4. The Gut–Lung Axis: how the two microbiomes talk to each other

The gut and lungs are connected through a biochemical “highway” known as the gut–lung axis.

How the gut affects the lungs

Gut bacteria produce metabolites such as:

  • short-chain fatty acids (SCFAs) — e.g., butyrate

  • tryptophan metabolites

  • bile-acid derivatives

These travel in the bloodstream and regulate:

  • airway inflammation

  • Th2/Th17 immune responses

  • IgE and eosinophils

  • neutrophil activity

  • mucus production

  • tolerance to allergens (including fungal allergens)

  • steroid responsiveness

Low SCFA levels are linked to:

  • more severe asthma

  • worse fungal sensitisation

  • increased ABPA flares

  • poorer lung function

  • difficulty clearing infection

How lung disease affects the gut

Chronic respiratory disease increases:

  • gut permeability (“leaky gut”)

  • microbiota disruption

  • systemic inflammation

  • digestive symptoms

  • fatigue

  • candida overgrowth

Steroids and antibiotics worsen this further.

This creates a self-reinforcing circle of inflammation and dysbiosis.

🧱 5. Biofilms: microbial fortresses driving persistent disease

Biofilms are communities of microbes encased in a sticky protective matrix.

In aspergillosis and bronchiectasis, biofilms:

  • make organisms up to 100–1000× more resistant to treatment

  • protect microbes from the immune system

  • allow bacteria and fungi to communicate and collaborate

  • swap resistance genes

  • support mixed infections (e.g., Aspergillus + Pseudomonas)

  • cause chronic symptoms even with “negative” cultures

Biofilms also change the immune system’s behaviour, driving long-term inflammation.

🔬 6. What microbiome research has revealed so far

A. Infection is rarely a single organism

Microbiomes show that infections are polymicrobial ecosystems, not isolated pathogens.

B. Diversity = resilience

Higher microbial diversity is linked to:

  • better lung stability

  • fewer flare-ups

  • lower inflammation

Low diversity correlates with:

  • severe disease

  • CPA progression

  • ABPA flares

  • worse bronchiectasis outcomes

C. Microbiome patterns can predict future illness

Research shows that flare-ups often follow:

  • a drop in diversity

  • an increase in dominant pathogens

  • changes in fungal–bacterial interactions

D. Treatment responses are microbiome-dependent

The presence of certain bacteria can make Aspergillus:

  • grow faster

  • form stronger biofilms

  • resist antifungals

  • provoke more inflammation

🫁🌱 7. What patients can do to support their lung microbiota

Just as dietary fibre supports gut microbes, there are practical steps that support a healthier lung microbial ecosystem.

These steps do not introduce microbes into the lungs; instead, they improve the environment the microbiota lives in.

⭐ 1. Keep airways clear — the foundation of lung microbial health

Biofilms and harmful microbes thrive in stagnant mucus.

Effective clearance techniques:

  • Active Cycle of Breathing Techniques (ACBT)

  • Autogenic drainage

  • Oscillating devices (Flutter, Acapella, Aerobika)

  • Nebulised saline (3–7%)

  • Huffing and controlled coughing

Clearer airways → more airflow → better microbial balance.

⭐ 2. Hydration

Hydration thins mucus, improves ciliary function, and weakens biofilms.

⭐ 3. Use inhalers correctly & control inflammation

Inflamed, narrowed airways promote dysbiosis.

Good control of:

  • asthma

  • ABPA

  • eosinophilia
    reduces microbial imbalance.

⭐ 4. Improve sinus health

The sinuses drip microbes into the lungs all day long.

Sinus care (saline rinses, nasal steroids) supports lung microbiota stability.

⭐ 5. Avoid unnecessary antibiotics

Antibiotics disrupt:

  • lung microbiota

  • gut microbiota

  • fungal–bacterial balance

  • biofilm behaviour

Use them when needed — but avoid repeated unnecessary courses.

⭐ 6. Exercise

Exercise increases airflow and clearance, helping shift the lung microbiome toward a healthier, more diverse state.

⭐ 7. Reduce smoke and indoor pollutants

Pollutants:

  • paralyse cilia

  • thicken mucus

  • promote pathogenic microbes

  • reduce diversity

HEPA filtration, ventilation, and smoke avoidance all help.

⭐ 8. Manage reflux (GORD)

Micro-aspiration introduces stomach contents into the lungs, disrupting the lung microbiota.

Treating reflux supports lung microbial homeostasis.

⭐ 9. Support your gut microbiota

A healthy gut → more SCFAs → improved lung immunity → a more balanced lung microbiome.

Helpful for gut health:

  • fibre-rich foods

  • diverse diet

  • fermented foods (if tolerated)

  • avoiding unnecessary antibiotics

  • reducing alcohol

  • managing stress

🩺 8. What this means for the future of aspergillosis care

Within 5–10 years, we may routinely use:

  • microbiome sequencing in clinic

  • AI-designed “ecosystem maps” of the lungs

  • targeted therapies for mixed infections

  • inhaled agents that break down biofilms

  • gut-directed therapies to help lung disease

  • personalised airway clearance plans

  • microbial diversity scores to predict flares

This could:

  • reduce exacerbations

  • minimise antibiotic and antifungal exposure

  • improve quality of life

  • slow CPA progression

  • improve steroid responsiveness

  • reduce hospital admissions

🧠 9. Key takeaways

  • You have two important microbiomes that matter for aspergillosis:
    the lung microbiome and the gut microbiome.

  • They communicate through the gut–lung axis.

  • Dysbiosis (imbalance) increases inflammation and worsens fungal disease.

  • Biofilms make infections far more resistant and persistent.

  • Patients can support their lung microbiota through lifestyle steps, especially:

    • airway clearance

    • hydration

    • exercise

    • sinus care

    • avoiding unnecessary antibiotics

    • supporting gut health

  • Microbiome science is transforming future diagnosis and treatment strategies.

by GAtherton