Clinical Trials and Emerging Treatments for Chronic Aspergillosis

Last reviewed: 12 March 2026

Key points

  • Only a small number of antifungal drug classes are currently available to treat aspergillosis.
  • New treatments are needed because of drug resistance, side effects, drug interactions and the long-term burden of chronic disease.
  • Research is now exploring not only new antifungal drugs, but also inhaled therapies, biologics, immune-modulating treatments and combination approaches.
  • Most new drugs are first tested in invasive aspergillosis before being studied in chronic pulmonary aspergillosis (CPA) or allergic bronchopulmonary aspergillosis (ABPA).
  • Clinical trials are essential for showing whether new treatments are safe and effective.

Overview

Treatment options for aspergillosis have improved over time, but there are still important limitations. Only a small number of antifungal drug classes are available, some fungi develop resistance to existing medicines, and some patients cannot tolerate treatment because of side effects or drug interactions.

This is particularly important in chronic aspergillosis, where treatment may need to continue for months or years. Research is therefore focused not only on new antifungal drugs, but also on better drug delivery systems, immune-based treatments, biologic therapies and combinations of treatments.

Clinical trials are the main way that researchers test whether these new approaches are safe and effective.

New treatments usually move from laboratory research to clinical trials, then regulatory approval, and finally use in chronic aspergillosis.

Why new treatments are needed

New treatments for chronic aspergillosis are needed for several reasons:

  • the number of available antifungal drug classes is limited,
  • Aspergillus can develop resistance to azole antifungals,
  • some patients experience significant side effects or important drug interactions,
  • long-term treatment can be difficult to sustain,
  • chronic disease may continue to affect symptoms, lung function and quality of life even when treatment is helping.

Because chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA) and related conditions can behave differently, researchers are exploring a wider range of therapies than in the past.

How new treatments are developed

Before a new treatment can be used routinely, it must pass through several stages of development.

Stage Description
Basic research Scientists study the disease and identify targets that could be affected by a new drug or treatment approach.
Drug discovery Researchers screen chemical compounds or modify promising molecules to find potential treatments.
Pre-clinical studies Potential treatments are tested in laboratory systems and sometimes animal models to assess activity and safety.
Application to begin human trials Researchers apply to regulators and ethics committees for permission to test the treatment in people.

Clinical trial phases

Clinical trials are usually carried out in phases.

Phase Purpose
Phase 0 / Phase I Small studies, often in healthy volunteers, to understand how the treatment behaves in the body, including absorption, distribution and safe dose ranges.
Phase II Studies in patients with the disease to identify useful doses and gather early information on effectiveness and side effects.
Phase III Larger studies comparing the new treatment with existing care to assess effectiveness and safety more accurately.
Phase IV Post-marketing studies that monitor how the treatment performs in real-world use after approval.

Regulatory approval and NHS use

If a treatment performs well in trials, the manufacturer can apply for approval from a medicines regulator such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA).

In the United Kingdom, a treatment may also be assessed by the National Institute for Health and Care Excellence (NICE) to determine whether it should be funded for routine use in the NHS.

Even when a drug is not recommended for routine NHS use, doctors may sometimes apply for individual funding if they believe it could benefit a particular patient.

New antifungal drugs in development

Many new antifungal drugs are first developed for severe invasive fungal infections and may later be studied in chronic conditions such as CPA or ABPA.

Olorofim

Olorofim is a novel antifungal from a completely new class called the orotomides. It targets fungal pyrimidine synthesis, a pathway not affected by current azole, echinocandin or polyene antifungals.

Rezafungin

Rezafungin is an echinocandin designed to have a longer duration of action and improved pharmacokinetic properties compared with older drugs in the same class.

Ibrexafungerp

Ibrexafungerp belongs to a new group of antifungals called triterpenoids. It acts on fungal cell wall synthesis in a way that is similar to echinocandins, but its structure is different and it can be given orally.

Fosmanogepix

Fosmanogepix is a first-in-class antifungal that blocks production of a molecule needed for fungal cell wall construction and self-regulation.

Oteseconazole

Oteseconazole is one of the newer tetrazole agents designed to improve selectivity and reduce side effects compared with traditional azoles.

Encochleated Amphotericin B

This is a reformulated version of amphotericin B designed to improve delivery and reduce toxicity.

ATI-2307

ATI-2307 is an arylamidine antifungal that interferes with mitochondrial function in fungal cells.

Other emerging treatments for chronic aspergillosis

Although new antifungal drugs are an important area of research, scientists are also exploring other ways to treat chronic forms of aspergillosis such as chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). These approaches aim to improve treatment effectiveness, reduce side effects, or target the immune response to the fungus.

Inhaled antifungal treatments

One area of research is the development of antifungal medicines that can be delivered directly to the lungs using inhalers or nebulisers. Delivering medication directly to the lungs may allow higher drug concentrations at the site of disease while reducing side effects elsewhere in the body.

Examples being explored include inhaled or nebulised formulations of amphotericin B, itraconazole and voriconazole.

Immune-modulating therapies

In some patients with aspergillosis, the immune response to the fungus plays an important role in how the disease develops or persists. Researchers are studying treatments that help modify the immune response rather than directly killing the fungus.

Examples include therapies that may enhance antifungal immunity or reduce harmful inflammation.

Biologic therapies

Biologic drugs that target specific immune pathways are already used to treat severe asthma and allergic disease. Some of these medicines are now being studied or used in fungal-related airway disease.

Examples include drugs targeting immunoglobulin E (IgE) or eosinophilic inflammation, such as omalizumab, mepolizumab, benralizumab, dupilumab and tezepelumab. These may be particularly relevant in ABPA or severe asthma with fungal sensitisation (SAFS).

Combination therapies

Future treatment strategies may combine different approaches, for example antifungal medication together with biologic therapy, inhaled therapy or immune-modulating treatment. Combination treatment may improve outcomes in patients whose disease does not respond fully to a single treatment alone.

Research is ongoing to determine which combinations are most effective and safest for patients with chronic aspergillosis.

Why new treatments are often tested in invasive aspergillosis first

Many new antifungal drugs are first tested in patients with invasive aspergillosis before being studied in chronic forms of the disease such as chronic pulmonary aspergillosis (CPA) or allergic bronchopulmonary aspergillosis (ABPA).

There are several reasons for this:

  • Disease progression is faster. In invasive infections the illness progresses quickly, so researchers can more easily measure whether a new treatment is working.
  • Clearer treatment outcomes. Invasive infections often have well-defined clinical outcomes such as survival or clearance of infection.
  • Smaller studies can provide useful results. Because invasive infections are severe, treatment effects may be detected in smaller numbers of patients.

Chronic forms of aspergillosis usually progress more slowly. This means clinical trials often need to run for longer periods and include larger numbers of patients to demonstrate whether a treatment is effective.

Once a new antifungal drug has shown benefit in invasive disease, researchers may then study how it performs in chronic conditions such as CPA or ABPA.

Specialist centres such as the National Aspergillosis Centre contribute to research that helps evaluate new treatments for chronic forms of aspergillosis and improve care for patients living with these conditions.

How to find clinical trials

Clinical trials involving human participants must be registered publicly for ethical and regulatory reasons.

You can search for ongoing or completed studies at:

This database allows you to search for studies by disease, location, treatment or trial status.

Not all studies test new drugs. Some trials investigate diagnostics, biomarkers, new ways of using existing medicines, or observational registries that help researchers understand disease patterns over time.

If you are interested in taking part in a clinical trial, discuss this with your specialist respiratory team.

Common questions

Why are new treatments needed if antifungal drugs already exist?

Current antifungal drugs help many patients, but they do not work for everyone. Some fungi develop resistance, some patients experience side effects or interactions, and chronic disease can remain difficult to control.

Are all new treatments new antifungal drugs?

No. Research now includes new antifungal drugs, inhaled treatments, biologics, immune-modulating therapies and combination approaches.

Why are there more trials in invasive aspergillosis than CPA?

Invasive aspergillosis progresses more quickly, so trial results can often be measured sooner and with fewer patients. CPA usually changes more slowly, which makes trials longer and more difficult to run.

Can patients with chronic aspergillosis join clinical trials?

Sometimes, yes. Eligibility depends on the trial design, the type of aspergillosis, previous treatment and other health factors. Your specialist team can advise whether there may be suitable studies.

Do clinical trials always involve testing a completely new drug?

No. Some studies test new doses, new combinations, new formulations such as inhaled treatment, or new diagnostic approaches.

Further information

You may find these pages helpful:

More information about the medicine development process can be found through major medicines regulators, clinical trial registries, and specialist respiratory teams.

Author and review information

Author: Aspergillosis Website Editorial Team

Audience: Patients, carers, GPs and non-specialists

Last reviewed: 12 March 2026

by GAtherton

Clinical Trials and Emerging Diagnostics for Aspergillus Infections

How new diagnostic technologies may improve detection of Aspergillus lung infections

Last reviewed: March 2026
Author: Graham Atherton

Key points

  • Diagnosing Aspergillus lung infections can be challenging because symptoms often resemble other lung diseases.
  • Doctors usually combine CT scans, blood tests and microbiology tests to make a diagnosis.
  • Researchers are developing new diagnostics that detect fungal DNA, fungal molecules, or drug-resistant strains.
  • Emerging tools include PCR tests, antigen detection, rapid tests, sequencing technologies and artificial intelligence imaging.
  • This page focuses on Aspergillus infections rather than allergic conditions such as Allergic Bronchopulmonary Aspergillosis, Severe Asthma with Fungal Sensitisation, or Aspergillus bronchitis.
  • Many of these newer technologies are being studied in clinical trials and research programmes worldwide.

Table of contents

1. Important note: infection vs allergy

This article focuses on diagnosing Aspergillus infections of the lungs, particularly:

  • Chronic Pulmonary Aspergillosis
  • Aspergillus nodules
  • Aspergilloma (fungal ball)
  • Subacute invasive aspergillosis

These conditions involve the fungus growing in lung tissue or in pre-existing lung cavities.

This is different from allergic Aspergillus disease, such as:

  • Allergic Bronchopulmonary Aspergillosis (ABPA)
  • Severe Asthma with Fungal Sensitisation (SAFS)
  • Aspergillus bronchitis (which overlaps with airway disease rather than the classic cavity-forming infections discussed here)

In allergic disease, diagnosis focuses more on immune reactions, such as IgE antibodies, eosinophils, allergy testing and markers of Type 2 inflammation.

This page therefore focuses mainly on diagnostics for Aspergillus infection rather than allergy. A separate article can cover immune diagnostics in allergic Aspergillus disease.

2. Why better diagnostics are needed

Chronic Pulmonary Aspergillosis often develops in people who already have damaged lungs, for example from:

  • tuberculosis
  • Chronic Obstructive Pulmonary Disease
  • bronchiectasis
  • sarcoidosis
  • previous severe lung infections
  • lung surgery

Symptoms may include:

  • chronic cough
  • breathlessness
  • fatigue
  • weight loss
  • coughing up blood
  • chest discomfort

These symptoms are not specific, meaning they can occur in many other lung diseases.

Aspergillus is also very common in the environment, so detecting it in sputum does not always mean it is causing disease. Sometimes it may simply be present without invading tissue or causing progressive damage.

For these reasons, diagnosing chronic aspergillosis usually requires multiple tests interpreted together, rather than relying on one result alone.

3. How Aspergillus infections are diagnosed today

Doctors usually combine three main types of evidence.

Diagnostic method What it shows
CT scan Structural lung changes such as cavities, nodules or fungal balls
Blood tests The body's immune response to Aspergillus
Microbiology tests Evidence of the fungus itself

The most important blood test for many patients with Chronic Pulmonary Aspergillosis is Aspergillus IgG antibodies.

CT scans are also critical because they can reveal features such as:

  • lung cavities
  • fungal balls
  • nodules
  • thickened cavity walls
  • progressive lung destruction or scarring

Microbiology may include sputum culture, bronchoscopy samples, microscopy, molecular testing and antigen detection.

No single test is perfect. Doctors usually look at the whole picture: symptoms, scan findings, blood tests, microbiology, and how things change over time.

4. Detecting the immune response vs detecting the fungus

Some diagnostic tests detect how the body reacts to Aspergillus, while others try to detect the fungus itself.

Immune response tests

Examples include:

  • Aspergillus IgG antibodies
  • general inflammatory markers

These tests show that the immune system has encountered Aspergillus, but they do not always prove that the fungus is currently active, growing, or causing ongoing damage.

Direct fungal detection

Other tests look for components of the fungus itself.

Test What it detects
PCR Aspergillus DNA
Galactomannan Fungal cell wall molecules
Beta-D-glucan Fungal structural components
Culture Growth of the fungus in the laboratory

These tests can sometimes provide more direct evidence that fungal material is present.

Why not rely only on the immune response?

Immune-response tests are extremely useful, but they are indirect. They tell us what the body is doing, not necessarily what the fungus is doing at that moment.

Antibodies may remain raised for quite a long time, may change only slowly, and may vary from person to person. Some patients also produce weaker immune responses than others.

By contrast, tests that detect fungal DNA or fungal cell wall components may sometimes give a better sense that fungal material is actually present in the lungs.

The footprints analogy

A useful way to understand this difference is:

  • Immune response tests are like seeing footprints in the snow – they show that someone has been there.
  • Direct fungal tests are like seeing the person themselves – they show that the organism is present.

In practice, doctors usually combine both kinds of evidence to make the diagnosis more reliable.

5. Simple diagram: two ways of looking for Aspergillus disease

Two broad diagnostic approaches

Approach Examples Main question
Looking for the body's response Aspergillus IgG, inflammation markers Has the immune system reacted to Aspergillus?
Looking for the fungus itself PCR, galactomannan, Beta-D-glucan, culture Is fungal material present?
Looking for damage caused in the lungs CT scan Has Aspergillus or another disease caused structural lung change?

This is why diagnosis is usually based on a combination of evidence rather than any single test.

6. DNA testing (PCR diagnostics)

Polymerase Chain Reaction, usually shortened to PCR, detects the DNA of Aspergillus fungi.

These tests can be performed on samples such as:

  • sputum
  • bronchoscopy samples
  • lung tissue

Advantages of PCR include:

  • faster results than fungal culture
  • detection of very small amounts of fungus
  • possible detection even when cultures are negative

However, PCR also has challenges. It may detect fungal material even when it is not clearly causing disease, and methods are not yet fully standardised across all laboratories.

Even so, PCR is one of the most important emerging tools in fungal diagnostics and is increasingly used in specialist centres.

7. Fungal antigen detection

Some tests look for molecules released by fungal cells. These are often called antigen tests.

Galactomannan

Galactomannan is a molecule found in the cell wall of Aspergillus.

It is already widely used in diagnosing invasive aspergillosis and is being studied more closely in chronic forms of disease as well.

Beta-D-glucan

Beta-D-glucan is a structural component found in the cell walls of many fungi.

Raised levels can suggest fungal infection somewhere in the body, although it is not specific for Aspergillus alone.

Researchers are interested in how these markers might be used alongside CT, antibody testing and PCR to improve accuracy.

8. Rapid diagnostic tests

Researchers are also developing rapid antigen tests that can detect fungal molecules within minutes.

These tests work in a similar way to a simple strip test and may offer:

  • quick results
  • minimal laboratory equipment
  • possible use in clinics with fewer resources

These tests are promising, but they still need careful evaluation to show how accurate and reliable they are in real patients with chronic Aspergillus disease.

9. Breath diagnostics

Fungi release small chemicals called volatile organic compounds. Some experimental devices aim to detect these compounds in exhaled breath.

If successful, breath testing could provide:

  • completely non-invasive testing
  • rapid screening
  • repeat testing over time without invasive procedures

This remains an early and experimental field, but it is attractive because it could make testing much easier for patients.

10. Sequencing technologies and the lung microbiome

Modern sequencing technologies can analyse all microbial DNA in a sample.

This means they may identify:

  • fungi
  • bacteria
  • viruses

These approaches may help doctors understand mixed infections and the broader lung microbiome, especially in people with bronchiectasis or complex chronic lung disease.

In the future, sequencing may help explain why some patients have persistent symptoms or repeated flares involving more than one organism.

11. Detecting antifungal resistance

Some strains of Aspergillus fumigatus have developed resistance to azole antifungal drugs.

Newer diagnostic tests can detect genetic mutations linked to drug resistance, especially in the CYP51A gene.

Earlier detection of resistance could help doctors:

  • choose effective antifungal drugs sooner
  • avoid ineffective treatment
  • improve long-term outcomes

This is an important area of research because antifungal resistance is a growing international concern.

12. Artificial intelligence and CT imaging

Artificial intelligence is increasingly being explored as a way to analyse CT scans more precisely.

These systems may eventually help doctors:

  • detect subtle lung changes earlier
  • measure cavity size or progression more consistently
  • monitor disease over time
  • compare scans more accurately

Artificial intelligence is unlikely to replace expert radiologists or specialist teams, but it may become a useful support tool.

13. Flowchart: how doctors diagnose chronic Aspergillus infection

Typical diagnostic pathway

Symptoms
persistent cough, breathlessness, fatigue, weight loss, coughing up blood

↓

CT scan
looking for cavities, fungal balls, nodules, scarring or progressive damage

↓

Blood tests
especially Aspergillus IgG and general inflammatory markers

↓

Microbiology
sputum, bronchoscopy, culture, PCR, antigen tests

↓

Clinical interpretation
combining symptoms, imaging, blood tests and microbiology

↓

Diagnosis and follow-up
deciding whether this is infection, colonisation, another lung condition, or mixed disease

This flowchart is simplified, but it shows the basic principle: diagnosis depends on combining evidence.

14. The future diagnostic pathway

In the future, diagnosing Aspergillus infection may involve several rapid tests used together.

A possible pathway could look like this:

Symptoms → CT scan → fungal antigen test → PCR confirmation → resistance testing

This approach could allow:

  • faster diagnosis
  • more personalised treatment
  • earlier detection of complications
  • better treatment monitoring

The aim is not necessarily to replace older tests, but to make the whole diagnostic process earlier, clearer and more precise.

15. Common questions patients ask

Why can Aspergillus infection take time to diagnose?

Because no single test can confirm the disease on its own. Doctors usually need to combine scan findings, blood tests, microbiology and the clinical history.

Why do some tests detect antibodies while others detect the fungus?

Antibody tests show how the immune system has reacted. Molecular and antigen tests try to show whether fungal material is present. Both are useful, but they answer slightly different questions.

Why is a CT scan so important?

A CT scan shows whether there is structural lung damage such as cavities, nodules or fungal balls. This helps doctors judge whether Aspergillus is likely to be causing disease rather than simply being present.

Are these new diagnostics available now?

Some are already used in specialist centres, but many are still being evaluated in clinical trials and research studies.

Will these newer tests replace existing blood tests?

Probably not completely. More likely, they will be used alongside existing tests to improve accuracy and speed.

16. When to seek medical advice

You should seek medical advice if you have symptoms such as:

  • persistent cough
  • worsening breathlessness
  • unexplained fatigue
  • weight loss
  • coughing up blood
  • new or worsening chest pain

These symptoms can have many causes, but they should be assessed properly, especially if you already have underlying lung disease.

17. References

  • Denning DW, Cadranel J, Beigelman-Aubry C, Ader F, Chakrabarti A, Blot S, Ullmann AJ, Dimopoulos G, Lange C; European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016 Jan;47(1):45-68. doi: 10.1183/13993003.00583-2015. PMID: 26699723.
  • Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax. 2015 Mar;70(3):270-7. doi: 10.1136/thoraxjnl-2014-206291. Epub 2014 Oct 29. PMID: 25354514.
  • Takazono T, Izumikawa K. Recent Advances in Diagnosing Chronic Pulmonary Aspergillosis. Front Microbiol. 2018 Aug 17;9:1810. doi: 10.3389/fmicb.2018.01810. PMID: 30174658; PMCID: PMC6107790.

Author and review information

This page is intended for patients, carers, and non-specialist clinicians. It provides general educational information and should not replace individual medical advice.

by GAtherton

Weekly Aspergillosis Research Update – Week 10, 2026

Focus: chronic aspergillosis, allergic Aspergillus disease, and long-term lung damage

This week’s papers are especially relevant to people living with Allergic Bronchopulmonary Aspergillosis (ABPA), allergic bronchopulmonary mycosis, and Chronic Pulmonary Aspergillosis (CPA). The strongest themes are the potential value of Immunoglobulin E (IgE) as a marker of future lung decline, the growing role of biologic therapies in steroid-sparing care, and improved tools for diagnosing CPA in people with previous tuberculosis.

Acute invasive aspergillosis papers are included lower down for context, but this update prioritises chronic and longer-term disease.

Chronic and allergic Aspergillus disease

High total serum IgE level at diagnosis was associated with a progressive decline in lung function in asthmatic patients with allergic bronchopulmonary mycosis

Kodama Y, Takaoka S, Nakashima T, Matsunaga K, Terada K, Yamashita Y, Masumitsu H, Miyasaka A, Muraoka T, Masumoto N, Kaneko T, Watanabe M, Tsurikisawa N.
Allergy Asthma Clin Immunol. 2026 Mar 8. doi: 10.1186/s13223-026-01024-2.

PMID: https://pubmed.ncbi.nlm.nih.gov/41796390/

Why this matters

This is one of the most important chronic-disease papers in this batch. It suggests that very high total IgE at diagnosis may not just reflect current disease activity, but may also predict future lung damage.

Key points

  • Patients with allergic bronchopulmonary mycosis (ABPM), including many with Allergic Bronchopulmonary Aspergillosis (ABPA), who had higher IgE levels at diagnosis showed a more progressive decline in lung function over time.

  • This raises the possibility that baseline IgE could help identify patients at higher risk of long-term airway damage.

  • It supports the idea that some patients may need closer monitoring and earlier treatment escalation rather than waiting for repeated flare-ups.

Relevance

For patients and clinicians, this paper reinforces that IgE is not just a number to follow during treatment. A very high starting IgE may signal the need for more careful long-term planning, especially in people with asthma, mucus plugging, recurrent exacerbations or bronchiectasis.

Biologics Use in Eosinophilic Lung Disease: Controversies and Consensus

Pérez de Llano L, Rivas DD, Pavord I, Aslam MMS, Lugogo N.
J Allergy Clin Immunol Pract. 2026 Mar;14(3):583-596.e12. doi: 10.1016/j.jaip.2026.01.022.

PMID: https://pubmed.ncbi.nlm.nih.gov/41786384/

Why this matters

This review is highly relevant to current ABPA care because biologics are increasingly being used to reduce reliance on oral corticosteroids, especially in people with severe asthma and recurrent eosinophilic inflammation.

Key points

  • The review discusses biologics including omalizumab, mepolizumab, benralizumab, dupilumab and tezepelumab.

  • It highlights growing evidence that biologics may help some patients with ABPA by reducing steroid burden, improving asthma control and lowering exacerbation frequency.

  • The authors also stress that evidence in ABPA is still developing and remains less robust than in severe eosinophilic asthma.

Relevance

This is a useful overview of where the field is heading. For many patients with ABPA, the major clinical problem is not only fungal sensitisation but the long-term harm caused by repeated steroid courses. Biologics are becoming an increasingly important part of steroid-sparing strategy, though patient selection remains crucial.

Differential Diagnosis of Eosinophilic Lung Diseases

Emmi G, Bass J, Baratella E, Akuthota P, Loscocco GG.
J Allergy Clin Immunol Pract. 2026 Mar;14(3):542-557. doi: 10.1016/j.jaip.2026.01.027.

PMID: https://pubmed.ncbi.nlm.nih.gov/41786383/

Why this matters

ABPA is still often missed, mislabelled or diagnosed late. This review is useful because it places ABPA in the wider context of eosinophilic lung disease, where several conditions can look similar.

Key points

  • The paper compares ABPA with other eosinophilic lung diseases such as chronic eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis, and drug-related eosinophilic lung disease.

  • It emphasises the importance of combining history, imaging, blood eosinophils, total IgE, fungal sensitisation and radiology.

  • The review underlines how easily overlap can occur, especially in people with severe asthma.

Relevance

For patients, this matters because getting the diagnosis right affects treatment. Not every eosinophilic lung disease is ABPA, and not every worsening in an asthma patient with high eosinophils is due to fungus. For clinicians, it is a helpful reminder to keep a broad differential diagnosis.

Chronic Pulmonary Aspergillosis

Performance of the LDBio Aspergillus ICT lateral flow assay and western blot for diagnosing chronic pulmonary aspergillosis in post-tuberculosis patients: a prospective study from South India

Samaddar A, Pramanik P, Voleti H, Akshata JS, Nagarathna S, Thennarasu K, Nagraja C.
Microbiol Spectr. 2026 Mar 6:e0384725. doi: 10.1128/spectrum.03847-25.

PMID: https://pubmed.ncbi.nlm.nih.gov/41789940/

Why this matters

This is the key CPA paper in this week’s list. It focuses on a major real-world problem: how to diagnose CPA more effectively in people left with lung damage after tuberculosis.

Key points

  • The study found that the LDBio Aspergillus immunochromatographic test (ICT) performed well in diagnosing CPA in post-tuberculosis patients.

  • Western blot also performed strongly, and combining the tests improved diagnostic confidence.

  • The results support the use of simpler, more accessible serology in settings where advanced imaging or specialist fungal laboratories may be limited.

Relevance

CPA after tuberculosis remains underdiagnosed worldwide. This paper is especially important because it supports the use of practical, lower-complexity diagnostics that may help identify patients earlier. That has implications far beyond India, particularly in regions where post-tuberculosis lung disease is common.

Host susceptibility and chronic disease risk

Oncostatin M receptor deficiency as a novel candidate genetic cause of autosomal recessive hyper-IgE syndrome

Andersen S, Assing K, Jensen J, Rasmussen LD, Laursen CB, Dellgren CD, Hinke DM, Degn SE, Mogensen TH.
J Hum Immun. 2026 Mar 3;2(3):e20250119. doi: 10.70962/jhi.20250119.

PMID: https://pubmed.ncbi.nlm.nih.gov/41783139/

Why this matters

Some patients develop chronic or severe Aspergillus disease because of an underlying immune problem that may not be obvious at first. This paper adds a possible new genetic explanation.

Key points

  • The authors describe a patient with very high IgE, eczema, bone fractures and Chronic Pulmonary Aspergillosis (CPA).

  • They identified a rare variant in the oncostatin M receptor (OSMR) gene.

  • The paper proposes OSMR deficiency as a possible new cause of autosomal recessive hyper-IgE syndrome.

Relevance

Although rare, studies like this help explain why a small number of people develop unusual susceptibility to chronic fungal disease. Over time, this kind of work may improve genetic diagnosis, immune work-up and personalised management in patients with recurrent or unexplained Aspergillus disease.

Important diagnostic lesson

Peripheral T-cell lymphoma-NOS presenting with cavitary lung lesions mimicking invasive aspergillosis

Lopez Ventosa J, Rodriguez A, Garcia N, Tirado M, Nieves Rivera J.
BMJ Case Rep. 2026 Mar 4;19(3):e268805. doi: 10.1136/bcr-2025-268805.

PMID: https://pubmed.ncbi.nlm.nih.gov/41781006/

Why this matters

Although this is not a chronic aspergillosis paper, it is worth noting because it highlights a key problem in lung medicine: cavities and positive biomarkers do not always equal Aspergillus infection.

Key points

  • A patient with cavitary lung lesions and a positive serum galactomannan was initially treated for presumed aspergillosis.

  • Tissue biopsy did not support fungal infection.

  • The final diagnosis was peripheral T-cell lymphoma.

Relevance

This is a valuable reminder that malignancy, tuberculosis and other diseases can mimic CPA or invasive aspergillosis, and that tissue diagnosis remains important when the picture does not fit cleanly.

Acute invasive aspergillosis: important context papers

How to safely discontinue antifungal treatment in invasive pulmonary aspergillosis? - Clinical considerations in haematology

Stemler J, Sprute R, Koehler P, Cornely OA.
Clin Microbiol Infect. 2026 Mar 6:S1198-743X(26)00106-0. doi: 10.1016/j.cmi.2026.03.001.

PMID: https://pubmed.ncbi.nlm.nih.gov/41796963/

25 years of improvement in mortality in invasive aspergillosis in haematology patients: will it be sustained or is it under threat?

Maertens JA, Vanbiervliet Y, Mercier T, Aerts R, Lagrou K, Slavin MA.
J Antimicrob Chemother. 2026 Mar 4;81(4):dkag077. doi: 10.1093/jac/dkag077.

PMID: https://pubmed.ncbi.nlm.nih.gov/41790511/

Invasive aspergillosis in liver transplant recipients in France (2007-21): a nationwide, retrospective, matched case-control study

Le Hyaric C, Melenotte C, Lefebvre F, Saliba F, Botterel F, El-Domiaty N, Dumortier J, Persat F, Do R, Pasquier G, Camus C, Gangneux JP, Kamar N, Iriart X, Monsel A, Fekkar A, Conti F, Vuotto F, Loridant S, Durand F, Bonnal C, Barbaz M, Chesnay A, Vignals C, Lefranc M, Guerin R, Moniot M, Weil D, Bellanger AP, Decaens T, Maubon D, Lebossé F, Artzner T, Morel G, Letscher-Bru V, Herbrecht R, Ader F, Lortholary O, Lefort A, Guichon C, Danion F.
Lancet Microbe. 2026 Mar 2:101272. doi: 10.1016/j.lanmic.2025.101272.

PMID: https://pubmed.ncbi.nlm.nih.gov/41785881/

Treatment Monitoring and Outcome Prediction in Invasive Aspergillosis using Immunologic Markers

Pereira A, Scott J, Sarlea A, Sprute R, Aerts R, Lass-Flörl C, Mikulska M, Sedik S, Garcia-Vidal C, Gangneux JP, Giacobbe DR, Prattes J, Grothe J, Biswas S, Monzo-Gallo P, Bassetti M, Maertens J, Kumar V, Koehler P, Cunha C, Netea MG, Carvalho A, Hoenigl M.
J Infect Dis. 2026 Mar 4:jiag140. doi: 10.1093/infdis/jiag140.

PMID: https://pubmed.ncbi.nlm.nih.gov/41778487/

by GAtherton

Using AI Safely When You Have Aspergillosis

Artificial intelligence (AI) tools (for example, ChatGPT and other “medical chatbots”) can help people living with aspergillosis understand information, prepare for appointments, and feel more confident asking questions.

Used well, AI can be like a helpful explainer.
Used badly, it can be misleading — especially for conditions like aspergillosis where treatment decisions are complex.

This page explains what is safe, what is not safe, and how to use AI in a way that supports (not replaces) your clinical team.

Who is this page for?

This guidance is for people affected by:

  • Chronic Pulmonary Aspergillosis (CPA)

  • Allergic Bronchopulmonary Aspergillosis (ABPA)

  • Severe Asthma with Fungal Sensitisation (SAFS)

  • Aspergillus bronchitis

  • Other long-term Aspergillus-related lung problems

A simple rule that keeps you safe

AI should improve your understanding — it should not change your treatment.

If an AI tool suggests starting, stopping, or changing medication, do not act on it without speaking to your clinician.

What AI is good for

AI tools are usually helpful for:

Explaining medical words in plain language

Examples:

  • “What is Aspergillus Immunoglobulin G (IgG)?”

  • “What does ‘eosinophils’ mean?”

  • “What is a CT scan finding such as ‘cavity’ or ‘bronchiectasis’?”

Understanding medicines (general information)

AI can explain:

  • What a medicine is for

  • How it works in the body

  • Common side effects (in general terms)

  • Why monitoring is needed

This can be helpful for antifungal medicines such as itraconazole, voriconazole, posaconazole, and isavuconazole.

Preparing for appointments

AI can help you create a list of questions, for example:

  • “What monitoring do I need while on antifungals?”

  • “What symptoms should prompt urgent review?”

  • “How do we judge whether treatment is working?”

Summarising research articles

If you paste a paragraph from a paper (or describe it), AI can often translate it into patient-friendly language.
(Always remember: AI can sometimes get details wrong — see below.)

Organising your story

Many people find it useful to ask AI to format:

  • A timeline of symptoms

  • A list of medicines and dates

  • A short “what I want from this appointment” summary

This can make consultations more productive.

What AI is NOT safe for

AI should not be used for:

Diagnosis

Aspergillosis diagnosis usually depends on a careful combination of:

  • Symptoms and clinical history

  • Imaging (often computed tomography, CT)

  • Blood tests

  • Sputum tests / microbiology

  • Sometimes bronchoscopy results

AI cannot reliably “diagnose” from symptoms or a single test result.

Treatment decisions

Do not use AI to decide:

  • Whether you should start or stop antifungals

  • Steroid doses or tapering plans

  • Whether you “should” try biologics (for example, omalizumab)

  • Whether a side effect is safe to ignore

These decisions must be individualised and clinician-led.

Urgent situations

If you have worsening breathlessness, fever, chest pain, or coughing blood (haemoptysis), seek medical advice urgently.
AI is not an emergency service.

Why aspergillosis needs extra caution

Aspergillosis care can be complicated because:

  • Some antifungal medicines have important drug interactions

  • Blood levels may need monitoring (therapeutic drug monitoring)

  • Side effects can overlap with symptoms of lung disease

  • Different Aspergillus-related conditions can look similar but need different management

AI tools can also:

  • Over-generalise from asthma guidance

  • Confuse chronic disease with invasive disease

  • “Hallucinate” (invent) facts, references, or confident-sounding explanations

  • Be out of date

Privacy and confidentiality: what not to share with AI

To protect your privacy, avoid typing in:

  • Your full name

  • Date of birth

  • NHS number

  • Home address

  • Phone number

  • Identifiable clinic letters or reports (unless anonymised)

A safer way to write questions

Instead of pasting an entire letter, use a summary like:

“Adult with chronic lung disease, on itraconazole 200 mg daily, recent CT shows cavities, asking about monitoring and side effects.”

That’s usually enough for education and planning questions.

A safe “4-step” way to use AI

  1. Ask AI to explain (terms, tests, general concepts)

  2. Ask AI to help you prepare questions

  3. Discuss those questions with your clinician

  4. Only change treatment after clinical advice

A quick safety checklist

Before trusting an AI answer, ask:

  • Is this general education, or is it telling me what I should do?

  • Does it recommend changing my medicine or dose?

  • Does it mention checking interactions or monitoring?

  • Does it conflict with my current plan?

  • Is this situation urgent?

If any answer worries you: pause and ask your care team.

Example prompts patients can use safely

You can copy/paste these into an AI tool:

  • “Explain Chronic Pulmonary Aspergillosis (CPA) in plain language.”

  • “What questions should I ask about long-term itraconazole treatment?”

  • “What monitoring is commonly recommended for antifungal medicines?”

  • “Can you help me write a one-page symptom and medication summary for my clinic appointment?”

  • “Here is a paragraph from a research paper — can you summarise it in patient-friendly language and list any uncertainties?”

Tip: If you want a more cautious response, add:
“Please be conservative and tell me what you’re unsure about.”

Signs an AI answer may be unreliable

Be cautious if the AI:

  • Sounds very confident but gives no clear reasoning

  • Gives exact doses or taper schedules

  • Claims “this is definitely ABPA/CPA” from limited information

  • Provides references you cannot find elsewhere

  • Dismisses side effects, interactions, or monitoring

  • Encourages you to delay medical care

Final reminder

AI can be a helpful tool for understanding and preparing — but it is not a substitute for a specialist team.

If you are unsure, or something feels wrong, it is always reasonable to contact your clinician, specialist nurse, or GP.

Medical disclaimer

This page is for general information only and is not medical advice. Always follow the guidance of your healthcare team, especially regarding diagnosis, medicines, and urgent symptoms.

by GAtherton

Why Can Aspergillus Infection Be Hard to Clear — Even When Tests Say It’s “Sensitive”?

Many patients ask:

“If my lab report says the fungus is sensitive to the antifungal drug, why is my condition not improving quickly?”

This is a very reasonable question.

The short answer is: fungi are biologically adaptable, and we are still learning how they adjust inside the lung.

Recent research involving scientists working with the National Aspergillosis Centre (NAC), including work led by Dr. Weaver and colleagues, is helping us understand this better.

You can read the scientific abstract here:
🔗 https://pubmed.ncbi.nlm.nih.gov/41673015/

1️⃣ What Does “Sensitive” Mean in the Lab?

When Aspergillus is tested against a drug (such as itraconazole or voriconazole), laboratories measure the minimum inhibitory concentration (MIC).

This tells us the drug level needed to stop fungal growth in a controlled lab setting.

If the MIC is low, the fungus is labelled “sensitive.”

But the laboratory environment is very different from a lung cavity.

2️⃣ The Lung Is Not a Uniform Environment

In chronic pulmonary aspergillosis (CPA), the fungus often lives inside:

  • Cavities

  • Scarred lung tissue

  • Fungal balls

  • Thick mucus

Within these areas there can be:

  • Low oxygen

  • Variable iron levels

  • Uneven drug penetration

  • Different levels of immune activity

This means that different parts of the same infection can behave differently at the same time.

3️⃣ New Research: Fungi Have Fine-Tuned Control Systems

Recent work from researchers collaborating with NAC, including Prof. Bowyer’s group, has shown that Aspergillus contains additional regulatory elements in its genome called long non-coding RNAs (lncRNAs).

These do not make proteins.
Instead, they help fine-tune how nearby genes behave under stress.

In laboratory studies, some of these regulatory elements appear to influence how the fungus responds to antifungal drugs — even when there is no classic resistance mutation.

This suggests:

  • Aspergillus can adjust how strongly certain pathways (like ergosterol production) are activated.

  • These adjustments may help the fungus survive stressful conditions.

  • This survival does not always show up as “resistance” in standard lab testing.

This does not mean the drug does not work.
It means the biological response can be more subtle and layered than we previously understood.

4️⃣ Resistance vs Tolerance — An Important Difference

Resistance

  • Caused by stable genetic mutations.

  • The drug becomes much less effective.

  • MIC levels rise clearly.

Tolerance

  • The fungus survives but grows slowly.

  • MIC may still appear “sensitive.”

  • The fungus adapts temporarily to stress conditions.

The new regulatory findings may help explain tolerance — not necessarily resistance.

5️⃣ Why This Matters for CPA

CPA is a chronic condition.

Inside lung cavities:

  • Drug levels may vary.

  • Oxygen levels fluctuate.

  • Stress signals are ongoing.

This environment encourages survival strategies.

Research like the Weaver study helps us understand why:

  • Treatment response may be gradual.

  • Cultures can be intermittently positive.

  • Stability may be the goal rather than rapid clearance.

6️⃣ How Could This Research Help in the Future?

It is important to be realistic: this research is still at an early stage.

However, understanding these regulatory systems opens new possibilities.

Instead of thinking only about killing the fungus directly, future approaches might aim to:

  • Weaken its survival responses.

  • Reduce its ability to enter protective stress states.

  • Make existing antifungal drugs work more effectively.

For example, research in fungal biology has already shown that interfering with certain stress-buffering pathways can increase azole effectiveness in laboratory models.

In the longer term, this type of work could lead to:

🔹 Better Diagnostics

Tests that detect not only resistance mutations, but also stress-adapted or tolerance states.

🔹 More Personalised Treatment

Identifying strains that rely heavily on stress adaptation and adjusting therapy accordingly.

🔹 Combination Strategies

Using antifungal drugs together with agents that reduce fungal stress tolerance, helping prevent persistence.

These ideas are still under investigation, and no lncRNA-based treatments exist yet.
But this research expands the way scientists think about fungal treatment.

7️⃣ Encouraging News

The important message is this:

NAC is actively involved in research that improves our understanding of how Aspergillus behaves under treatment.

This work:

  • Does not suggest current treatments are ineffective.

  • Does not mean patients are resistant.

  • Does highlight why long-term management can be complex.

  • Represents steady progress in understanding fungal biology.

Understanding these regulatory systems is a step toward:

  • Better diagnostics

  • More personalised treatment strategies

  • Improved long-term outcomes

A Reassuring Perspective

If progress feels slow, it is not because you or your clinicians have failed.

It reflects the adaptable survival biology of a fungus living in a complex lung environment.

And importantly, NAC and its research partners — including groups such as Dr. Weaver’s — are working to understand this biology in order to improve care.

by GAtherton

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

Can Lungs Repair Themselves?

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

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

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

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

The Discovery: A “Repair vs Defence” Switch

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

  • Produce surfactant (which keeps air sacs open)

  • Act as a reserve “repair” population in the lung

  • Can regenerate other essential lung cells after injury

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

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

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

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

It does not mean:

  • Lung cavities caused by CPA will close in the foreseeable future

  • Established fibrosis will melt away

  • Bronchiectasis will reverse

  • Severely distorted lung architecture will rebuild

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

What repair does realistically mean

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

  • Supporting survival of remaining alveoli

  • Preventing excessive fibrotic signalling

  • Helping lung lining cells recover more efficiently after inflammation

  • Reducing cumulative injury from repeated infection

  • Slowing progression of structural change

In other words:

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

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

Why Preservation Is a Major Goal in CPA

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

Over time, CPA can lead to:

  • Expanding cavities

  • Progressive scarring

  • Reduced gas exchange

  • Reduced exercise tolerance

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

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

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

Why This Also Matters in ABPA

In ABPA, repeated inflammatory episodes can lead to:

  • Airway remodelling

  • Mucus plugging

  • Development or progression of bronchiectasis

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

Again, this is about preservation rather than reversal.

Where Development Has Reached

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

  • Single-cell sequencing

  • Imaging of lung tissue

  • Preclinical models of injury

No human treatments based on this discovery are yet available.

However, the significance lies in identifying:

  • A defined molecular pathway

  • A controllable regulatory mechanism

  • A clearer understanding of why repair fails in chronic inflammation

That foundational knowledge is what eventually allows targeted drug development.

The Balance Challenge in Aspergillosis

There is an additional complexity in fungal lung disease.

Any attempt to promote repair must not weaken antifungal defence.

The immune system must:

  • Control Aspergillus

  • Avoid causing excessive inflammatory damage

Future therapies would need to strike that balance carefully.

What This Means for Patients Now

This discovery does not change current treatment.

The most effective preservation strategies today remain:

  • Consistent antifungal therapy when indicated

  • Careful inflammatory control

  • Biologic therapies where appropriate

  • Airway clearance

  • Vaccination and infection prevention

  • Avoiding damp and mould exposure

  • Pulmonary rehabilitation

These measures are already forms of lung preservation.

A Realistic and Hopeful Perspective

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

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

  • Slowing structural progression

  • Supporting endogenous repair cells

  • Reducing fibrotic signalling

  • Improving recovery after exacerbations

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

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

Reference

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

by GAtherton

🧬 Could Antibody-Driven Dissolving of Charcot–Leyden Crystals Help ABPA?

Researchers have recently discovered that Charcot–Leyden crystals (CLCs) — the needle-shaped structures formed from the eosinophil protein galectin-10 — are not just debris.

In laboratory studies, specially designed antibodies can dissolve these crystals.

This has raised two important questions:

  1. Could dissolving the crystals reduce airway inflammation?

  2. Could dissolving them make mucus plugs easier to clear?

Here is what we currently know.

1️⃣ Could dissolving crystals reduce airway inflammation?

What we know

Laboratory and animal studies have shown:

  • Charcot–Leyden crystals can activate immune cells (especially macrophages).

  • They can stimulate inflammatory pathways (including inflammasome signalling).

  • In mouse models, antibodies targeting galectin-10 dissolved the crystals.

  • When crystals were dissolved, airway inflammation decreased.

This suggests that the crystals themselves may amplify inflammation, rather than simply mark it.

What this means biologically

In ABPA and eosinophilic asthma:

  • Eosinophils release galectin-10.

  • Galectin-10 crystallises.

  • Crystals may trigger further immune activation.

  • That leads to more inflammation → more eosinophils → more crystals.

Dissolving the crystals could theoretically interrupt this feedback loop.

How likely is this to help inflammation in humans?

Moderately plausible, but not yet proven.

The biological mechanism is strong.
The animal data are encouraging.
But no human clinical trials have yet shown reduced inflammation through crystal dissolution.

If developed successfully, this approach could:

  • Reduce airway immune activation

  • Lower exacerbation risk

  • Potentially reduce steroid dependence

But at present, it remains investigational.

2️⃣ Could dissolving crystals make mucus plugs easier to cough up?

This is more speculative — but still biologically reasonable.

Why mucus plugs are so thick in ABPA

ABPA mucus plugs contain:

  • Gel-forming mucins

  • DNA from inflammatory cells

  • Dead cells

  • Fungal fragments

  • Eosinophil proteins

  • Charcot–Leyden crystals

The crystals are:

  • Rigid

  • Needle-shaped

  • Structurally stable

When embedded in mucus, they likely increase:

  • Mechanical stiffness

  • Plug density

  • Resistance to deformation

From a physics perspective:

Removing rigid crystalline structures from a gel should reduce stiffness and improve flow.

Do we have direct evidence?

No.

There are currently:

  • No human studies measuring mucus clearance after crystal dissolution

  • No trials showing improved plug expectoration from crystal-targeting therapy

So while it is plausible that dissolving crystals could soften plugs, this has not yet been demonstrated in patients.

3️⃣ How strong is the overall case?

Outcome Evidence strength Likelihood
Reduced inflammation Strong biological rationale + animal data Moderately promising
Easier mucus clearance Biophysical plausibility only Possible but unproven

Inflammation reduction is the more evidence-supported target.
Improved plug clearance is plausible but currently theoretical.

4️⃣ How does this compare to existing treatments?

Current therapies (e.g., anti-IL-5 biologics) reduce eosinophils upstream.

That leads to:

  • Less galectin-10 release

  • Fewer crystals forming

  • Reduced inflammation

  • Often improved mucus plugging

So biologics already indirectly reduce crystal burden.

A crystal-dissolving antibody would act downstream, targeting the structural product directly.

This could theoretically:

  • Accelerate resolution of existing plugs

  • Reduce residual inflammatory signalling

But again, this remains in early research stages.

5️⃣ Practical take-home message

At present:

  • Dissolving Charcot–Leyden crystals reduces inflammation in animal models.

  • It is biologically plausible that this could also soften mucus plugs.

  • There is no human clinical proof yet.

  • No approved therapy currently targets the crystals directly.

The concept is scientifically credible — but still under development.

🔭 The Bigger Picture

ABPA is increasingly understood as a condition driven by:

  • Eosinophils

  • Allergic immune signalling

  • Abnormal mucus biology

  • Structural plug formation

Crystal-targeting therapies may eventually become part of a more precise approach to treating eosinophilic airway disease.

But for now, they remain a promising research direction rather than a clinical option.

by GAtherton

Systemic fungal infections: why speed, diagnosis and stewardship matter

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

Why fungal infections are often missed

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

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

Antifungal stewardship: knowing when to stop

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

The authors stress that:

  • Diagnostic results should be actively reviewed

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

  • This approach protects patients and preserves antifungal effectiveness

Antifungal resistance is a growing threat

Antifungal resistance is no longer rare. The review highlights:

  • Azole resistance in Aspergillus, including cryptic species

  • Rising resistance in several Candida species

  • The global spread of multidrug-resistant Candida auris

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

Aspergillosis: a broad spectrum of disease

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

  • Allergic disease (such as allergic bronchopulmonary aspergillosis)

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

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

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

Climate change and emerging fungal risks

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

  • Increasing exposure to environmental fungi

  • Enabling fungi to adapt to higher temperatures

  • Contributing to outbreaks after natural disasters and trauma

  • Expanding fungal diseases into new geographic regions

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

Key take-home messages

  • Systemic fungal infections are time-critical medical emergencies

  • Diagnosis usually requires multiple tests, not a single result

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

  • Diagnostics are essential for safe antifungal stewardship

  • Antifungal resistance is a real and growing problem

  • Climate change is reshaping fungal epidemiology and risk

Free access to the full article

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

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

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

by GAtherton

Weekly Aspergillosis Update (2–9 February 2026)(Week 5).

This week’s papers cluster around: (1) ICU/viral-pneumonia–associated invasive pulmonary aspergillosis (IPA),
(2) tuberculosis (TB)–chronic pulmonary aspergillosis (CPA) overlap,
(3) diagnostic criteria and emerging detection approaches, and
(4) antifungal drug interaction risk.

Top highlights (quick take)

  • CAPA criteria matter: case rates vary substantially depending on which definition is used (AspICU vs ISHAM vs EORTC).
  • Viral illness + immune dysfunction = early IPA risk: data add to the “risk stacking” story (including SFTS and broader viral pneumonia).
  • TB–CPA remains a major clinical challenge: CPA can be misread as TB relapse; delayed recognition worsens outcomes.
  • Safety: rifapentine can markedly reduce voriconazole exposure (important in TB–aspergillosis co-infection).

1) ICU, Viral Pneumonia & CAPA / IPA


Decoding CAPA: A Comparative Study of Aspicu, Isham, and Eortc Criteria in Critical COVID-19 Patients Requiring Mechanical Ventilation (Preprint)

Taleb C, Lelubre C, Biston P, Piagnerelli M. Preprints.org. 04 Feb 2026. PPR: PPR1150994

  • What they did: compared CAPA classification using AspICU, ISHAM and EORTC-style criteria in ventilated COVID-19 patients.
  • Key point: CAPA “incidence” changes materially depending on the criteria applied; distributions differed across COVID-19 waves.
  • Why it matters: reinforces that audits, research comparisons and ICU protocols must state which definition is used (and why).


Characteristics of T-lymphocyte subsets in patients with severe fever with thrombocytopenia syndrome complicated with invasive pulmonary aspergillosis: a retrospective study

Xu Y, Liu Y, Qian Y, et al. Front Immunol. 09 Feb 2026. PMCID: PMC12876148

  • What they found: SFTS patients complicated by IPA showed marked T-cell subset abnormalities and high reported secondary IPA rates.
  • Clinical takeaway: another example of viral immune dysregulation predisposing to IPA—analogous to influenza-associated IPA and CAPA.
  • Practice relevance: supports heightened fungal vigilance in severe viral syndromes with immune suppression features.


Immunocompromise and early-onset invasive pulmonary aspergillosis in viral pneumonia: a retrospective cohort study

Sun B, Shen J, Dong M, et al. Front Public Health. 02 Feb 2026. PMCID: PMC12852324

  • Theme: early IPA can emerge in viral pneumonia in the setting of immunocompromise (not only classic neutropenia).
  • Why it matters: backs the “risk stacking” concept—viral lung injury + immune dysfunction (often steroids) can accelerate IPA risk.
  • Use: helpful citation for ICU pathways and education materials.


The COVID-19 pandemic: an underlying factor for increased Stenotrophomonas maltophilia infections—A literature review and case study analysis (Review)

Pompilio A, Di Bonaventura G. Front Microbiol. 06 Feb 2026. PMCID: PMC12867275

  • What’s relevant to aspergillosis: notes co-detection of Stenotrophomonas maltophilia in COVID-19 patients with invasive aspergillosis.
  • Why it matters: underlines polymicrobial complexity in ICU; prompts questions about dysbiosis and pathogen interactions in severe disease.


Pulmonary Cavitation as a Late and Self-Limited Complication of COVID-19 Pneumonia: A Case Report

Osório M, Silveira M. Cureus. 02 Feb 2026. PMCID: PMC12852039

  • Clinical reminder: post-COVID cavitation has a broad differential including CAPA and mucormycosis; requires careful exclusion of fungal disease.
  • Why it matters: useful for follow-up imaging discussions and MDT differential diagnosis teaching.

2) TB–CPA overlap & antifungal pharmacology


Clinical features, diagnostic test performance, treatment and outcome of pulmonary tuberculosis patients with chronic pulmonary aspergillosis in China: a retrospective, observational study

Li J, Wu N, Mei C, et al. Front Cell Infect Microbiol. 06 Feb 2026. PMCID: PMC12864492

  • Main message: CPA in TB patients is common and can be mistaken for TB relapse; diagnostic delay is consequential.
  • Why it matters: strong global relevance—TB remains one of the biggest drivers of CPA burden.
  • Use: good reference for post-TB lung disease pathways and CPA awareness materials.


A clinically significant interaction between voriconazole and rifapentine: a case report and review of evidence

Chen T, Chen X, Zhang Q. Front Med (Lausanne). 09 Feb 2026. PMCID: PMC12875967

  • What happened: TB–aspergillosis co-infection complicated by rifapentine–voriconazole interaction.
  • Key point: rifapentine (a potent enzyme inducer) can substantially reduce voriconazole exposure → risk of treatment failure.
  • Why it matters: high-impact safety message; supports use of therapeutic drug monitoring and/or alternative strategies in TB co-treatment.

3) Diagnostics & detection methods


Combined Biospectroscopy with Multivariate Analysis for the Differential Diagnosis of Leptospirosis Disease: A Pilot Study

Zambrano A, Trilleras J, Arana Rengifo V, et al. ACS Omega. 09 Feb 2026. PMCID: PMC12878783

  • Why it’s here: includes a small aspergillosis group among comparator infections.
  • What it suggests: biospectroscopy + multivariate modelling may separate infections via biochemical “fingerprints” (early-stage concept).
  • Bottom line: promising research direction, but not near-term clinical practice.


Research progress on the current status of respiratory pathogen infections and their detection methods (Review)

Zhu F, Peng M, Chen A, Zhu Q. Front Microbiol. 09 Feb 2026. PMCID: PMC12876234

  • Scope: broad overview of respiratory pathogen detection, including invasive and allergic aspergillosis concepts.
  • Useful for: background reading for non-specialists and training materials (diagnostic modalities and limitations).

4) Aspergillus biology, pathology & wider fungal immunology


Characterization of a bZIP Transcription Factor ZipD in Aspergillus flavus

Jeong D, Cho H, Park H. Mycobiology. 06 Feb 2026. PMCID: PMC12865826

  • What it is: basic science on gene regulation (ZipD) in Aspergillus flavus.
  • Why it matters: contributes to long-term understanding of fungal stress responses and potential future targets.


Mechanistic Insights into Calcium Oxalate Crystals in Aspergillosis of the Maxillary Sinus

Trimukhe A, Bhatt K, Mridha AR, et al. Head Neck Pathol. 02 Feb 2026. PMID: 41627592

  • Key message: calcium oxalate crystal deposition is a mechanistic contributor to local inflammation/tissue injury in sinus aspergillosis.
  • Clinical relevance: useful for ENT/pathology audiences; supports recognition of crystals as an important clue.


Adjunctive GM-CSF therapy enhances host defense against systemic Candida auris infection in immunosuppressed mice

Mattos E, Das Gupta K, Quintanilla D, et al. Front Immunol. 06 Feb 2026. PMCID: PMC12862068

  • Why included: host-directed immunotherapy concepts often discussed alongside invasive aspergillosis.
  • Takeaway: GM-CSF improved antifungal host defense in a preclinical model—supporting interest in adjunctive approaches (not clinical guidance).


The therapeutic potential of high-dose inhaled nitric oxide for antimicrobial effects: a narrative review and future directions (Review)

Berra L, Kamenshchikov N, Tal A, et al. Intensive Care Med Exp. 05 Feb 2026. PMCID: PMC12872992

  • Scope: experimental antimicrobial strategy, mainly ICU-focused.
  • Relevance: future-facing adjunct discussion rather than current aspergillosis practice.

5) Case reports & broader context (selected)


Case Report: Triple autoimmune overlap: rheumatoid arthritis, systemic lupus erythematosus, and hypereosinophilic asthma with systemic manifestations

Front Immunol. 02 Feb 2026. PMCID: PMC12852425

  • Aspergillosis relevance: ABPA considered in complex eosinophilic/asthma phenotypes; reminder that ABPA can present atypically (e.g., without classic bronchiectasis early on).
  • Use: supports education on diagnostic nuance in asthma/eosinophilic lung disease.


HIV-associated neurological infections in a Brazilian tertiary care center: clinical-epidemiological features and predictors of in-hospital mortality

Ramos L, Ninomiya D, Sequeira M, et al. Rev Inst Med Trop Sao Paulo. 02 Feb 2026. PMCID: PMC12858172

  • Context: opportunistic infection landscape in advanced HIV; useful epidemiological background (limited direct aspergillosis focus).

Note: This page summarises research and does not replace clinical guidance. If you are a patient and have concerns about symptoms or treatment, contact your clinical team.

by GAtherton

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

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

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

What the researchers did

Doctors reviewed patients with CPA who had:

  • Taken antifungal treatment for at least 6 months

  • Stopped treatment because they were clinically stable

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

What they found

  • About 1 in 4 patients had a relapse after stopping treatment

  • People whose Aspergillus IgG blood test was still high at the end of treatment were much more likely to relapse

  • Patients whose IgG level had fallen to a lower level did not relapse in this study

  • Signs of Aspergillus allergy or sensitisation also increased relapse risk

  • CT scan appearances and treatment length alone were not reliable predictors

Why this matters for patients

This means that:

  • Blood tests may help doctors decide when it is safe to stop treatment

  • Some people may need closer follow-up or longer treatment

  • Follow-up can be more personalised, rather than “one size fits all”

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

Key takeaway

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

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

by GAtherton