Aspergillosis Research Update: ICU Infections, Immune Defences and Antifungal Treatment
Published: July 2026
Medical research into aspergillosis continues to advance rapidly, with new studies appearing almost every week. Some confirm what doctors already suspected, while others introduce new ideas about how the body fights fungal infections or how treatment might improve in the future.
This week’s research includes a major international review of invasive aspergillosis in intensive care, encouraging real-world results for the antifungal drug isavuconazole, and two laboratory studies suggesting that specialised immune cells called macrophages may play an even greater role in protecting the lungs than previously appreciated.
None of these studies changes current treatment recommendations immediately. Together, however, they highlight an important direction in aspergillosis research: understanding not only how to kill the fungus, but also how to strengthen the body’s own immune defences.
A major international review confirms the burden of invasive aspergillosis in intensive care
A systematic review and meta-analysis combined results from 56 observational studies involving 15,385 intensive care patients. Among these patients, 2,381 cases of invasive pulmonary aspergillosis, or IPA, were identified.
The researchers estimated that IPA occurred in approximately 11.9% of the critically ill patients included in the studies. The estimated incidence increased to 15% among patients receiving mechanical ventilation.
Mortality among patients diagnosed with IPA was high:
- 59.6% overall mortality
- 61.9% mortality among mechanically ventilated patients
Factors associated with an increased risk of developing IPA included:
- immunosuppression;
- blood cancers and other malignancies;
- corticosteroid use before admission to intensive care;
- chronic lung, kidney, liver or heart disease;
- mechanical ventilation;
- vasopressor treatment;
- and renal replacement therapy.
What does this mean?
This study reinforces that invasive aspergillosis remains a serious complication in selected critically ill patients.
However, the results should not be interpreted as meaning that approximately one in eight people admitted to intensive care will develop aspergillosis. The authors state that the evidence predominantly reflects COVID-19-associated pulmonary aspergillosis, commonly known as CAPA.
Many of the identified risk factors, such as mechanical ventilation, vasopressor treatment and renal replacement therapy, are also signs that a patient is already extremely unwell. The study therefore identifies associations but cannot prove that these treatments independently cause aspergillosis.
The authors conclude that targeted screening and tailored antifungal strategies in high-risk patients deserve prospective evaluation. They do not claim that universal screening or preventive antifungal treatment has already been shown to improve survival.
Read the paper record on PubMed
Real-world evidence continues to support isavuconazole
Another study examined how well isavuconazole performs in routine clinical practice among people with blood cancers who develop serious invasive mould infections.
The retrospective study included 84 adults treated at two hospitals in China between 2022 and 2025:
- 62 had invasive aspergillosis;
- 14 had mucormycosis;
- 8 had mixed mould infections.
The main measure of success was assessed after six weeks. To count as successful treatment, the patient had to survive, show clinical or radiological improvement and avoid stopping treatment because of failure or toxicity.
The overall six-week treatment success rate was 59.5%. Among patients with aspergillosis, treatment success was higher, at 69.4%.
Only four patients experienced recorded drug-related adverse effects, and one stopped treatment because of vomiting.
What does this mean?
These findings are reassuring because they reflect routine clinical practice rather than the more controlled circumstances of a clinical trial.
The study found that patients receiving isavuconazole alone appeared to have better outcomes than those receiving combination antifungal treatment. However, this result must be interpreted cautiously.
Doctors commonly reserve combination therapy for patients who are more severely ill, have failed previous treatment, have mixed infections or are suspected of having resistant disease. The poorer outcomes in the combination-treatment group may therefore reflect the severity of the patients’ infections rather than harm caused by combining antifungal medicines.
This is known as confounding by indication. Because the patients were not randomly assigned to treatment, the study cannot establish that monotherapy is superior to combination treatment.
Overall, the study adds confidence that isavuconazole can be an effective and generally well-tolerated treatment for invasive aspergillosis in patients with haematological malignancies. It does not show that isavuconazole is better than other antifungal medicines, and it does not apply directly to chronic pulmonary aspergillosis, ABPA or Aspergillus bronchitis.
Read the paper record on PubMed
Could strengthening lung macrophages help prevent invasive aspergillosis?
Perhaps the most scientifically intriguing study this week did not test a new antifungal drug.
Instead, researchers investigated whether they could improve the ability of the lung’s own immune cells to eliminate Aspergillus fumigatus before infection became established.
The study focused on alveolar macrophages. These specialised immune cells live inside the air sacs of the lungs and are among the first cells to encounter inhaled Aspergillus spores.
Using a stem-cell transplant mouse model and an unusually low dose of Aspergillus spores intended to resemble everyday exposure, the researchers found that alveolar macrophages played a crucial role in protecting against invasive aspergillosis during the earliest stages of infection.
The researchers then tested whether macrophage function could be improved using macrophage colony-stimulating factor, or M-CSF.
M-CSF treatment:
- improved macrophage migration;
- enhanced phagolysosomal function;
- increased fungal killing;
- preserved lung tissue;
- reduced inflammatory cytokines;
- and protected mice against lethal invasive aspergillosis.
The researchers also tested primary human alveolar macrophages and found that M-CSF improved several of the same antifungal functions.
Importantly, the protective effect disappeared when alveolar macrophages were removed. This provides strong experimental evidence that the macrophages themselves were responsible for much of the benefit.
What does this mean?
This research suggests that tissue-resident macrophages may play an especially important role during the first hours after Aspergillus spores reach the lungs.
It also supports the wider idea of host-directed therapy: treatments designed to strengthen the patient’s immune response rather than attacking the fungus directly.
However, this study was carried out mainly in mice and has been published as a preprint. It has not yet completed formal peer review.
M-CSF is therefore not an established treatment for aspergillosis. Researchers would need to establish appropriate dosing, safety and effectiveness in people, particularly because stimulating immune activity after stem-cell transplantation could potentially affect inflammation, graft-versus-host disease and other immune processes.
Tuberculosis may affect immune defences as well as damaging the lungs
People who have previously had pulmonary tuberculosis are at increased risk of developing chronic pulmonary aspergillosis, or CPA.
The usual explanation is structural lung damage. Tuberculosis may leave behind cavities, scarring, bronchiectasis and damaged airways, creating an environment in which Aspergillus can persist.
A new laboratory study suggests that there may also be an immunological component.
The researchers studied a mycobacterial cell-wall molecule called lipoarabinomannan, or LAM. This molecule is known to interfere with some of the cellular pathways used by macrophages to respond to infection.
Bone-marrow-derived macrophages were exposed to two forms of LAM and then challenged with swollen Aspergillus fumigatus conidia.
Exposure to LAM:
- increased macrophage death;
- increased inflammatory cytokine release, particularly IL-1β;
- and reduced the ability of macrophages to kill Aspergillus conidia during the first six hours of infection.
The reduction in fungal killing was demonstrated using both colony-counting methods and time-lapse fluorescence microscopy.
What does this mean?
This study provides a plausible biological mechanism through which mycobacterial infection might interfere with early antifungal immune responses.
It does not, however, prove that this mechanism causes CPA after tuberculosis.
The experiments were conducted in laboratory-grown macrophages. They do not show that LAM remains present in the lungs for months or years after tuberculosis, nor that macrophages from people with previous tuberculosis behave in the same way.
The findings therefore do not replace the established structural explanation linking tuberculosis and CPA. Instead, they raise the possibility that lung damage and altered local immunity may work together.
Read the paper record on PubMed
A common theme emerges: macrophages matter
Although these studies examined different questions, two independent research groups reached complementary conclusions.
One study found that strengthening macrophage activity improved fungal killing and survival. The other found that disrupting macrophage activity reduced fungal killing.
Together, they support an emerging view that alveolar macrophages may be central to determining whether inhaled Aspergillus spores are cleared rapidly or allowed to develop into disease.
This does not reduce the importance of neutrophils, antifungal medicines or structural lung damage. Instead, it adds a more detailed understanding of what may happen during the earliest stages of fungal exposure.
Future advances in aspergillosis treatment may therefore involve both:
- better drugs that attack Aspergillus directly;
- and treatments that help the immune system respond more effectively.
What does this mean for people living with aspergillosis?
For most patients currently receiving treatment, these studies do not change day-to-day management.
Antifungal medicines remain the foundation of treatment for invasive and chronic Aspergillus infection. Patients should continue following the advice of their respiratory, infectious-diseases or specialist aspergillosis team.
These studies nevertheless provide encouraging evidence that aspergillosis research is progressing across several fronts:
- improving recognition of invasive aspergillosis in intensive care;
- evaluating how existing antifungal treatments perform in routine practice;
- understanding why some people are more vulnerable to Aspergillus than others;
- and exploring whether the immune system itself could become a future treatment target.
Progress is often gradual, and laboratory findings do not always lead to successful treatments. However, each study adds another piece to the puzzle and helps researchers move towards more effective and more personalised approaches to aspergillosis.
References
- Zhou Z, Luo B, Zhang X, et al. Incidence, mortality and risk factors of invasive pulmonary aspergillosis in critically ill patients during the COVID-19 era: a global systematic review and meta-analysis. Annals of Clinical Microbiology and Antimicrobials. Published 10 July 2026. PubMed. DOI.
- Zhang J, Xu M, Mao J, et al. Isavuconazole for invasive mold disease in patients with hematological malignancies: a multicenter real-world study from China on efficacy, safety, and competing risks. Antimicrobial Agents and Chemotherapy. Published 6 July 2026. PubMed. DOI.
- Sheta D, Mokhtari Z, Strobel M, et al. M-CSF-stimulated alveolar macrophages safeguard from invasive aspergillosis. bioRxiv. Preprint published 9 July 2026. DOI and preprint.
- Gonzales-Huerta LE, Williams TJ, Aljohani R, et al. Mycobacterial lipoarabinomannan negatively interferes with macrophage responses to Aspergillus fumigatus in vitro. PLOS ONE. 2026;21(7):e0351935. PubMed. DOI.
This article summarises newly published research for patients and non-specialist readers. It does not replace individual medical advice from a qualified healthcare professional.
Weekly Aspergillosis Research Update: COPD IPA Criteria, CPA Serology, ICU Galactomannan and Environmental Prevention
Week ending 6 July 2026
Overall summary
This week’s strongest theme is improved recognition and interpretation of Aspergillus disease in high-risk respiratory and immunocompromised patients.
The headline paper proposes COPD-specific diagnostic criteria for invasive pulmonary aspergillosis (IPA), addressing a long-standing gap between classic immunocompromised-host definitions and real-world respiratory practice. Other important papers focus on chronic pulmonary aspergillosis (CPA) serology, bronchoalveolar lavage galactomannan stewardship, endotracheal aspirate galactomannan in ICU patients, and environmental prevention of invasive fungal disease in paediatric cancer care.
Overall, this is a week of cautious progress: better criteria, better test interpretation, and better diagnostic systems — but several findings still require prospective validation.
High priority
Diagnostic criteria for invasive pulmonary aspergillosis in COPD patients
Denning DW, Rogers TR, Takazono T, Su X, Lagrou K, White PL, James DA, Bafadhel M, Lopez JB, Bulpa P, Chotirmall SH, et al.
American Journal of Respiratory and Critical Care Medicine. Published 1 July 2026.
DOI: 10.1093/ajrccm/aamag310
PMID: 42384914
This is the likely headline paper of the week. It proposes COPD-specific diagnostic criteria for IPA in non-ventilated hospitalised patients with COPD exacerbations. The criteria focus on patients with a hospitalised exacerbation plus at least two risk factors, such as systemic or high-dose inhaled corticosteroids, bronchiectasis, diabetes, cardiovascular disease, or prolonged antibiotic exposure.
Recommended investigation includes CT chest imaging, respiratory fungal microscopy and culture, preferably Aspergillus PCR, BAL or bronchoscopy galactomannan where available, serum galactomannan, and Aspergillus IgG. Diagnosis is supported by the combination of a high-risk COPD patient, compatible imaging, and any two positive Aspergillus tests, either from different samples or from different tests on the same respiratory sample.
Why it matters: COPD patients with IPA often do not fit classic EORTC/MSGERC host-factor definitions, which are strongest for haematology and transplant populations. This paper provides a respiratory-focused framework for a group in whom IPA may be missed, diagnosed late, or dismissed as colonisation.
Clinical or diagnostic relevance: The criteria could help respiratory teams investigate hospitalised COPD patients who deteriorate unexpectedly or fail to respond to standard treatment. They may encourage earlier CT imaging and broader fungal testing rather than relying on a single sputum culture.
Limitations / cautions: These are proposed consensus criteria based on literature review and Delphi methodology, not externally validated diagnostic criteria. Further studies are needed to validate them and to improve performance data for fungal assays in COPD. There remains a risk of overdiagnosis from colonisation and underdiagnosis where good respiratory samples or bronchoscopy are unavailable.
Diagnostic performance of IgG against multiplex Aspergillus antigens (mx4) for identifying chronic pulmonary aspergillosis
Sehgal IS, Agarwal R, Muthu V, Prasad KT, Dhooria S, Singh M, Rudramurthy SM, Aggarwal AN, Garg M, Chakrabarti A.
Medical Mycology. Published 2 July 2026.
DOI: 10.1093/mmy/myag071
PMID: 42392187
This prospective diagnostic study compared a multiplex Aspergillus IgG assay, mx4-IgG, with standard A. fumigatus-IgG for diagnosing CPA. The mx4 antigen preparation includes extracts of A. fumigatus, A. flavus, A. niger, and A. terreus. Among 332 adults with suspected CPA, 230 had CPA and 102 were diseased controls with structural lung disease.
Against the primary reference standard, mx4-IgG had sensitivity of 83.0% and specificity of 73.5%, compared with 95.2% and 88.2% for A. fumigatus-IgG.
Why it matters: The study tests an attractive idea: that broader multiplex Aspergillus antigen testing might improve CPA diagnosis. However, the results suggest that mx4-IgG was not superior to standard A. fumigatus-IgG.
Clinical or diagnostic relevance: A. fumigatus-IgG should remain the first-line serological test for CPA based on these findings. A practical finding was that a hierarchical strategy using A. fumigatus-IgG followed by A. flavus-IgG identified 97.7% of CPA cases at the lowest reported cost, USD 24 per patient, and outperformed strategies incorporating mx4.
Limitations / cautions: This was a tertiary chest-clinic cohort with high CPA prevalence, so predictive values may differ in lower-prevalence settings. The abstract does not provide confidence intervals, ROC values, or detailed subgroup data. The subgroup most likely to benefit from A. flavus-IgG requires full-text review.
Medium priority
The clinical utility of bronchoalveolar lavage galactomannan result stewardship within a tertiary medical system
Apostolopoulou A, Hammond SP, Turbett SE, Fishman JA.
Medical Mycology. Published 1 July 2026.
DOI: 10.1093/mmy/myag069
PMID: 42384022
This retrospective quality-improvement study examined stewardship of elevated BAL galactomannan results in a tertiary medical system. The Transplant Infectious Disease team monitored all elevated BAL GM results and, 24 hours after a positive result, sent a standardised email to the primary team if the result appeared unaddressed in the clinical documentation.
Among 55 cases with BAL GM >1.0, 17 cases (31%) had antifungal therapy started after a single positive BAL GM result. The stewardship team contacted primary teams in 14 cases (25%), leading to a new start or change in antifungal therapy.
Why it matters: Fungal diagnostics are only useful if results are recognised and interpreted correctly. This paper highlights a practical gap in BAL GM interpretation and shows how specialist result stewardship may help close the loop.
Clinical or diagnostic relevance: The intervention is highly practical: monitor positive BAL GM results, check whether they have been acknowledged, and provide specialist infectious diseases or mycology input where needed. This could be relevant to transplant, haematology, ICU, and tertiary respiratory services.
Limitations / cautions: The study is small, retrospective, and a quality-improvement evaluation rather than a controlled before-and-after study. It shows that stewardship influenced management, but it does not prove improved survival, reduced harm, or reduced inappropriate antifungal prescribing.
Diagnostic utility of endotracheal aspirate galactomannan for invasive pulmonary aspergillosis in ICU patients
Kumar R, Gupta A, Kumar A, Rao Kordcal S, Baitha U, Singh G, Xess I, Madan K, Soneja M, Wig N.
medRxiv preprint. Published 1 July 2026.
DOI: 10.64898/2026.06.29.26356826
PPR: PPR1271604
This prospective observational cohort study assessed endotracheal aspirate galactomannan as a supportive diagnostic test for IPA in mechanically ventilated ICU patients. The study enrolled 120 medicine ICU patients in India, aged over 14 years and ventilated for more than 48 hours, meeting BM-AspICU entry criteria.
Forty-four patients (37%) were classified as probable IPA and 76 as colonisers or possible IPA. The optimal ETA GM cut-off was 1.097, giving sensitivity of 72.73%, specificity of 84.2%, positive likelihood ratio of 4.86, negative likelihood ratio of 0.35, and AUC of 0.844.
Why it matters: ETA sampling is less invasive and easier than bronchoscopy or BAL in ventilated ICU patients. A useful ETA GM test could support earlier recognition of IPA where BAL is unsafe, delayed, or unavailable.
Clinical or diagnostic relevance: ETA GM may be useful as an adjunct or triage tool in ventilated ICU patients with suspected IPA. A positive result may increase suspicion, but a negative result should not exclude disease.
Limitations / cautions: This is a preprint and may not yet have been peer reviewed. It is single-centre and uses a clinical classification reference standard rather than a perfect gold standard. ETA samples are vulnerable to the colonisation-versus-invasion problem, and the proposed cut-off needs external validation.
The underestimated role of environmental factors in the prevention of invasive fungal disease: experience from a European childhood cancer centre
Malvestiti S, Andresen F, Hufnagel M, Speckmann C, Strahm B, Feuchtinger T, Puzik A.
Mycoses. Published 1 July 2026.
DOI: 10.1111/myc.70204
PMID: 42367057
This retrospective single-centre before-and-after study examined invasive fungal disease incidence in high-risk paediatric cancer and transplant patients before and after relocation from an older 1990s building to a new facility with improved environmental protection standards. The study included 186 patients: 140 before relocation and 46 after relocation.
Antifungal prophylaxis followed local standards throughout, with adherence above 98%. Invasive fungal disease incidence fell from 25 cases in the older building (17.9%) to no cases after relocation (p=0.002). Most cases were pulmonary aspergillosis and occurred in HSCT recipients.
Why it matters: The study highlights environmental protection as an under-recognised component of fungal disease prevention. Pharmacological prophylaxis is important, but building design, air quality, and environmental controls may also strongly influence risk.
Clinical or diagnostic relevance: The findings are relevant to paediatric oncology, HSCT, adult haematology, transplant units, and hospitals undergoing refurbishment or ward relocation. Environmental protection should be part of fungal infection prevention planning.
Limitations / cautions: This is observational, retrospective, and single-centre. The post-relocation period was shorter than the pre-relocation period, and the post-relocation cohort was smaller. The abstract does not list the specific environmental measures, so the reduction should be interpreted as being associated with a prevention bundle rather than any single intervention.
Lower priority
Combination antifungal therapy and formulary optimization for progressive invasive pulmonary aspergillosis in a pediatric patient with acute myeloid leukemia: a case report
Khamis F, Al Busaidi A, Al Bahrani K, Al-Rashdi A.
Clinical Case Reports. Published 1 July 2026.
DOI: 10.1002/ccr3.73041
PMID: 42389035
This case report describes a paediatric AML patient with progressive or refractory IPA. Radiological improvement followed combination antifungal therapy and a switch to brand-name liposomal amphotericin B. The authors suggest that refractory IPA management may require attention not only to antifungal class escalation but also to formulation choice and individualised optimisation.
Why it matters: The case raises a practical stewardship issue: when IPA progresses despite apparently appropriate therapy, clinicians should reassess drug exposure, formulation, host immune recovery, resistance, drug interactions, and combination strategy.
Clinical or diagnostic relevance: This is most relevant to paediatric haemato-oncology, AML, prolonged neutropenia, refractory IPA, and formulary decisions.
Limitations / cautions: This is a single case report and should be treated as hypothesis-generating only. It does not prove superiority of one amphotericin formulation over another. Improvement could reflect combination therapy, immune recovery, timing, supportive care, or other factors.
What to highlight this week
- The COPD IPA diagnostic criteria paper is the headline item. It addresses a major diagnostic gap in respiratory practice, but should be described as a proposed consensus framework requiring prospective validation.
- The CPA serology study is an important negative study. Broader multiplex IgG testing was not better than standard A. fumigatus-IgG. The practical message is to keep A. fumigatus-IgG first-line while considering whether targeted reflex A. flavus-IgG deserves further evaluation in selected settings.
- BAL galactomannan stewardship offers a clear implementation message. Fungal diagnostics need interpretation pathways, not just laboratory reporting. A positive fungal biomarker should trigger documented clinical review.
- Endotracheal aspirate galactomannan in ICU patients is promising but not practice-changing yet. ETA GM may help where BAL is difficult, but results must be interpreted alongside clinical, radiological, and microbiological evidence.
- Environmental protection may substantially reduce invasive fungal disease risk in paediatric cancer and HSCT settings. However, the evidence is observational and bundled, so individual protective measures cannot be credited from the abstract alone.
- The paediatric AML case report is clinically thought-provoking but low-level evidence. It is best mentioned briefly as a reminder to reassess drug exposure, formulation, resistance, immune status, and combination strategy in refractory IPA.
Evidence note
This update is based on available evidence notes and abstracts for some papers. Full-text review may refine details, especially around methodology, subgroup findings, confidence intervals, and implementation implications.
Weekly Aspergillosis Research Update: June 29
COPD, autoimmune disease and new approaches to antifungal treatment
Published: 29 June 2026
Every week we review the latest research on aspergillosis and related fungal diseases, selecting the studies most likely to influence patient care and clinical practice. This week's research focuses on an increasingly important theme: recognising Aspergillus disease in patient groups where it has traditionally been overlooked.
The highlight is a large systematic review suggesting that allergic Aspergillus disease may be more common in people living with chronic obstructive pulmonary disease (COPD) than previously appreciated.
Featured Paper
COPD and Aspergillus: Is allergic aspergillosis more common than we thought?
For decades, allergic bronchopulmonary aspergillosis (ABPA) has been regarded primarily as a complication of asthma and cystic fibrosis. However, respiratory specialists have increasingly reported Aspergillus-related disease in patients with COPD.
A new systematic review and meta-analysis has now brought together the available evidence.
Paper: Ajayababu A, Antony A, Goyal B, Ray A. Prevalence of allergic bronchopulmonary aspergillosis/Aspergillus sensitization in chronic obstructive pulmonary disease: A systematic review and meta-analysis. Respiratory Investigation. 2026. PubMed PMID: 42361722
What did the researchers do?
The authors searched four major medical databases for studies reporting either:
- Allergic bronchopulmonary aspergillosis (ABPA)
- Aspergillus sensitisation (AS)
Among patients with COPD, the review identified 23 suitable studies, including:
- 1,529 patients for analysis of ABPA
- 3,505 patients for analysis of Aspergillus sensitisation
Pooling data from many studies provides a more reliable estimate than individual reports alone.
What did they find?
The results suggest Aspergillus-related disease is not rare in COPD.
The pooled prevalence was:
- ABPA: 2.1%
- Aspergillus sensitisation: 10.4%
Put another way:
- around 1 in 50 people with COPD may have ABPA
- approximately 1 in 10 have evidence of sensitisation to Aspergillus
Studies using Aspergillus-specific IgE as part of their diagnostic strategy detected more ABPA than studies using skin testing or total IgE alone. This suggests that the choice of diagnostic tests may influence how many patients are identified.
Why is this important?
Many symptoms of COPD overlap with Aspergillus-related disease, including:
- persistent cough
- breathlessness
- increased sputum production
- recurrent exacerbations
As a result, some patients may continue to receive repeated courses of antibiotics or steroids while an underlying Aspergillus-related condition remains unrecognised.
This study does not suggest that everyone with COPD should undergo routine fungal testing. However, it supports considering Aspergillus investigations in selected patients with:
- recurrent exacerbations despite optimal therapy
- unexplained eosinophilia or raised IgE
- bronchiectasis
- persistent mucus plugging
- radiological abnormalities that do not fit the expected pattern
Strengths and limitations
This is currently one of the largest reviews examining COPD and Aspergillus disease.
Its strengths include:
- systematic literature search
- formal meta-analysis
- inclusion of more than 5,000 patients overall
However, the included studies differed considerably in patient populations, diagnostic methods and disease severity. This statistical heterogeneity means the true prevalence almost certainly varies between different clinical settings.
The review also demonstrates an association rather than proving that COPD itself causes ABPA.
What does this mean for patients?
The main message is one of greater awareness.
For patients with COPD whose symptoms remain difficult to explain despite appropriate treatment, clinicians may increasingly consider whether Aspergillus sensitisation or ABPA could be contributing to ongoing respiratory problems.
Earlier recognition has the potential to improve diagnosis and ensure that patients receive the most appropriate investigations and treatment.
Research in Brief
Invasive aspergillosis in autoimmune inflammatory rheumatic diseases
Paper: Liang P, Zhang X, Cai S, Hu Z, Dong L. Invasive aspergillosis in autoimmune inflammatory rheumatic diseases: epidemiology, risk factors, diagnosis, management and challenges. Annals of Medicine. 2026. PubMed PMID: 42343869
A comprehensive new review highlights the growing importance of invasive aspergillosis in people with autoimmune inflammatory rheumatic diseases such as rheumatoid arthritis and systemic vasculitis.
The increasing use of corticosteroids, biologic therapies and other immunosuppressive medications has expanded the population at risk. The authors note that invasive aspergillosis remains uncommon but carries a high mortality when diagnosis is delayed.
A particular challenge is that symptoms and imaging findings can resemble a flare of the underlying autoimmune disease, making diagnosis difficult. The review emphasises combining clinical assessment with microbiological tests, including galactomannan, PCR and bronchoalveolar lavage where appropriate, and careful interpretation of imaging findings.
Why it matters: Clinicians should maintain a high index of suspicion for invasive fungal disease in immunosuppressed patients who fail to respond as expected to conventional treatment.
Cerebral aspergillosis following influenza and ibrutinib therapy
Paper: Haraguchi M, Kimura M, Uruga H, Takahashi Y, Takaya H, Arisawa K, et al. Cerebral aspergillosis caused by Aspergillus flavus following seasonal influenza infection in a patient receiving ibrutinib for Waldenström's macroglobulinemia. Journal of Infection and Chemotherapy. 2026. PubMed PMID: 42331321
A Japanese case report describes successful treatment of cerebral aspergillosis caused by Aspergillus flavus in a patient receiving the Bruton tyrosine kinase inhibitor ibrutinib after seasonal influenza infection.
The patient developed both pulmonary and cerebral aspergillosis, underwent neurosurgical debridement and was successfully treated with isavuconazole.
Although this represents a single case, it reinforces growing evidence that BTK inhibitors and severe viral infections are emerging risk factors for invasive aspergillosis.
Why it matters: Patients receiving targeted therapies who develop persistent respiratory or neurological symptoms following influenza warrant careful assessment for opportunistic fungal infection.
Looking ahead: New ways to deliver antifungal drugs
Paper: Martins YA, Anselmo-Lima WT, Tamashiro E, Ho E, Valera FCP. Next-generation drug delivery systems for aspergillosis: Overcoming barriers in antifungal therapy. Biomedicine & Pharmacotherapy. 2026. PubMed PMID: 42361622
Another review this week explores next-generation drug delivery systems designed to improve treatment of aspergillosis.
Researchers are developing inhaled formulations, nanoparticles and targeted drug-delivery technologies that aim to increase antifungal concentrations directly within the lungs while reducing systemic side effects.
Most of these approaches remain experimental, but they offer possibilities for the future management of chronic pulmonary aspergillosis and other forms of pulmonary fungal disease.
What this week's research tells us
Although these papers address different aspects of aspergillosis, they all point in the same direction.
Increasingly, Aspergillus disease is being recognised in patient groups previously considered to be at relatively low risk, including people with COPD and those receiving modern immunosuppressive therapies.
At the same time, advances in diagnostics and drug delivery are creating opportunities for earlier diagnosis and more targeted treatment.
For patients, the message is reassuring but important: persistent or unexplained respiratory symptoms deserve careful evaluation, particularly when standard treatments are not achieving the expected improvement.
As awareness continues to grow, more patients may receive the correct diagnosis earlier in the course of their illness.
References
- Ajayababu A, Antony A, Goyal B, Ray A. Prevalence of allergic bronchopulmonary aspergillosis/Aspergillus sensitization in chronic obstructive pulmonary disease: A systematic review and meta-analysis. Respiratory Investigation. 2026. doi:10.1016/j.resinv.2026.101469. PubMed
- Liang P, Zhang X, Cai S, Hu Z, Dong L. Invasive aspergillosis in autoimmune inflammatory rheumatic diseases: epidemiology, risk factors, diagnosis, management and challenges. Annals of Medicine. 2026. doi:10.1080/07853890.2026.2685285. PubMed
- Haraguchi M, Kimura M, Uruga H, Takahashi Y, Takaya H, Arisawa K, et al. Cerebral aspergillosis caused by Aspergillus flavus following seasonal influenza infection in a patient receiving ibrutinib for Waldenström's macroglobulinemia. Journal of Infection and Chemotherapy. 2026. doi:10.1016/j.jiac.2026.103020. PubMed
- Martins YA, Anselmo-Lima WT, Tamashiro E, Ho E, Valera FCP. Next-generation drug delivery systems for aspergillosis: Overcoming barriers in antifungal therapy. Biomedicine & Pharmacotherapy. 2026. doi:10.1016/j.biopha.2026.119691. PubMed
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Catch Up on the Latest National Aspergillosis Centre Monthly Update
DNA Diagnostics, Adrenal Health, Damp Homes Research and Community Discussion
The National Aspergillosis Centre (NAC) Monthly Update brings together patients, carers, healthcare professionals and researchers to discuss the latest developments in aspergillosis care, research and day-to-day management.
Held on the first Friday of each month, these sessions combine expert presentations, research updates, practical information and community discussion. They provide an opportunity to learn about emerging developments in diagnosis and treatment while hearing directly from people living with aspergillosis and other chronic respiratory conditions.
In this month's update we discussed several important topics, including respiratory virus activity, corticosteroid management, adrenal insufficiency, new DNA-based diagnostic technologies and research into damp homes and mould exposure.
If you were unable to join us live, the full recording is available below.
Watch the Recording
Watch the full National Aspergillosis Centre Monthly Update using the embedded YouTube player below.
What Was Covered?
Respiratory Viruses and Seasonal Infections
The meeting opened with a discussion of current respiratory virus activity and the ongoing challenges that infections can present for people living with chronic respiratory disease.
Topics included seasonal trends, infection prevention and the importance of remaining aware of changing respiratory virus activity throughout the year.
Chapter: 24:30
Improving Corticosteroid Management
Corticosteroids remain an important treatment for many people with allergic and inflammatory lung conditions, including some forms of aspergillosis. However, long-term steroid use can also lead to significant side effects and complications.
This session explored current approaches to steroid management and the importance of balancing symptom control with minimising long-term risks.
Topics included:
- Why corticosteroids are used
- Monitoring treatment effectiveness
- Recognising steroid-related side effects
- Practical challenges faced by patients
Chapters: 25:30–58:00
Adrenal Insufficiency and Cortisol Replacement
A major focus of the meeting was adrenal insufficiency, a condition that can develop when prolonged corticosteroid treatment suppresses the body's natural cortisol production.
Discussion included:
- How adrenal insufficiency develops
- Common symptoms and warning signs
- Cortisol replacement therapy
- Managing illness and stress when adrenal function is reduced
- Questions raised by patients with lived experience
For many attendees this was one of the most relevant and practical discussions of the session.
Chapter: 27:00
New Approaches to Steroid Replacement Therapy
The meeting also explored newer approaches to cortisol replacement therapy that aim to more closely mimic the body's natural hormone rhythms.
Research in this area continues to develop and may improve quality of life for some patients in the future.
Chapter: 36:00
DNA-Based Bedside Diagnostics
One of the most exciting research topics discussed was the development of rapid DNA-based diagnostic technologies.
Traditional fungal diagnosis can sometimes take days or even weeks. New molecular approaches have the potential to identify pathogens much more quickly, helping clinicians make earlier and more informed treatment decisions.
The discussion explored:
- How DNA-based diagnostics work
- Why rapid diagnosis matters
- Current research developments
- Potential future applications in clinics and hospitals
Chapter: 58:00
How Rapid Genetic Testing Could Change Fungal Diagnosis
Advances in molecular biology and sequencing technology are opening the possibility of identifying fungal infections directly from patient samples without the need for lengthy culture-based methods.
Potential benefits include:
- Faster diagnosis
- Earlier treatment decisions
- Improved identification of difficult-to-detect infections
- More personalised approaches to care
Although many technologies remain under evaluation, this is one of the most rapidly developing areas of fungal medicine.
Chapter: 01:05:00
Damp Homes, Mould and Health Research
The second half of the update focused on growing evidence linking damp indoor environments and mould exposure to respiratory health problems.
This topic has received increasing attention following recent public health initiatives and growing awareness of housing-related health risks.
Discussion included:
- Current evidence linking damp homes and respiratory disease
- Ongoing research projects
- Challenges in measuring exposure
- Areas where further research is needed
Chapter: 01:55:00
Citizen Science Damp Homes and Health Project
Attendees also heard about the Citizen Science Damp Homes and Health Project, which aims to involve members of the public directly in collecting data and contributing to research.
Citizen science projects have the potential to improve understanding of real-world housing conditions and their impact on respiratory health.
Chapter: 01:56:00
Why Damp and Mould Matter for Respiratory Health
The meeting explored the ways in which damp environments can contribute to poor respiratory health, including increased exposure to mould spores, allergens and other environmental factors.
For people living with asthma, bronchiectasis and aspergillosis, understanding these risks can be an important part of managing their condition.
Chapter: 02:05:00
Patient Experiences and Open Discussion
As always, one of the most valuable aspects of the Monthly Update was the opportunity for attendees to share experiences, ask questions and support one another.
These discussions help connect people facing similar challenges while providing valuable insight into the real-world impact of living with aspergillosis.
Chapter Guide
- 00:00 Welcome and introductions
- 00:25 Community catch-up and discussion
- 24:30 Respiratory virus update and seasonal infections
- 25:00 Meeting agenda and topic selection
- 25:30 Improving corticosteroid management
- 27:00 Adrenal insufficiency and cortisol replacement
- 36:00 New approaches to steroid replacement therapy
- 43:00 Questions and discussion
- 58:00 DNA-based bedside diagnostics
- 01:05:00 How rapid genetic testing could change fungal diagnosis
- 01:20:00 Questions and patient discussion
- 01:31:00 Break and community discussion
- 01:55:00 Damp homes, mould and health research
- 01:56:00 Citizen Science Damp Homes and Health Project
- 02:05:00 Why damp and mould matter for respiratory health
- 02:20:00 Patient experiences and questions
- 02:30:00 Meeting summary and closing discussion
Why We Share These Updates
Not everyone can attend live events. Health issues, work commitments, caring responsibilities and geographical distance can all make participation difficult.
By recording and sharing our Monthly Updates, we hope to make expert information, research developments and community discussion accessible to as many people as possible.
The recordings also provide a valuable archive of emerging research, practical advice and patient experiences that can help people better understand and manage aspergillosis.
Join Future Monthly Updates
The National Aspergillosis Centre hosts regular online community meetings throughout the month, alongside the longer Monthly Update held on the first Friday.
Whether you are newly diagnosed, caring for someone with aspergillosis or have been living with the condition for many years, you are very welcome to join us.
For information about future events and resources, visit:
Weekly Aspergillosis Research Update: New Diagnostics, CAPA Evidence, and Why Azole Tolerance Matters
Last reviewed: 23 June 2026
Author: National Aspergillosis Centre Team
Audience: People living with aspergillosis, carers, healthcare professionals, and interested readers.
In one sentence: This week's aspergillosis research highlights a possible new bronchoscopic approach to aspergilloma management, growing use of PCR diagnostics, a major review of COVID-19-associated pulmonary aspergillosis, and new discoveries explaining how Aspergillus fumigatus may survive antifungal treatment.
Research Highlight of the Week
Why azole tolerance is more complex than resistance
The most important scientific theme this week is the growing recognition that Aspergillus fumigatus can sometimes survive antifungal treatment without possessing classic resistance mutations. Three separate studies suggest that iron availability, cellular stress responses, epigenetic regulation and long non-coding RNA may all influence how the fungus responds to azole drugs. These findings do not change treatment today, but they could shape future approaches to antifungal resistance monitoring and antifungal drug development.
Who Should Read This Update?
This update may be particularly relevant for:
- People living with chronic pulmonary aspergillosis (CPA)
- People with aspergilloma or a history of haemoptysis (coughing up blood)
- Patients receiving antifungal treatment such as itraconazole, voriconazole, posaconazole or isavuconazole
- Healthcare professionals interested in aspergillosis diagnostics and antifungal resistance
- Anyone following developments in fungal disease research
Key Points
- A study explored bronchoscopic removal of aspergilloma in selected patients with post-tuberculosis chronic cavitary pulmonary aspergillosis.
- Real-time polymerase chain reaction (PCR) testing may provide additional support when diagnosing invasive aspergillosis.
- A major review confirms that COVID-19-associated pulmonary aspergillosis (CAPA) remains a serious complication of severe COVID-19.
- New research suggests that antifungal treatment response is influenced by much more than simple resistance mutations.
- None of these findings should lead patients to change treatment without specialist medical advice.
Contents
- Overview
- A possible new approach for aspergilloma
- PCR testing and invasive aspergillosis
- COVID-19-associated pulmonary aspergillosis
- Why azole tolerance is more complex than resistance
- Also noted this week
- What this means for patients
- When to speak to your clinical team
- References
Overview
Research into aspergillosis continues to advance on several fronts. This week's papers range from practical clinical studies investigating new ways to manage aspergilloma, through to laboratory research exploring how Aspergillus fumigatus survives antifungal treatment.
While none of these studies are likely to change patient care immediately, they highlight important trends in the field. Researchers are working to improve diagnosis, develop new treatment approaches, and better understand why some infections persist despite treatment.
The strongest overall message this week is that aspergillosis research is moving beyond simple categories such as “susceptible” or “resistant”. Aspergillus fumigatus can adapt to stress, tolerate antifungal pressure, and sometimes survive long enough to acquire more stable resistance.
Most of the studies featured this week improve our understanding of aspergillosis rather than changing treatment directly. Nevertheless, several findings point towards future improvements in diagnosis, patient monitoring and antifungal therapy.
A Possible New Approach for Aspergilloma
One of the most clinically interesting papers this week investigated bronchoscopic removal of aspergilloma in patients with post-tuberculosis chronic pulmonary aspergillosis (CPA).
An aspergilloma, sometimes called a fungal ball, develops when Aspergillus grows within an existing cavity in the lung. These cavities can develop after conditions such as tuberculosis, sarcoidosis, or previous severe lung infections.
Post-tuberculosis chronic cavitary pulmonary aspergillosis refers to CPA developing in lung cavities left behind after previous tuberculosis.
Traditionally, treatment options include antifungal medication, surgery in carefully selected patients, and procedures such as bronchial artery embolisation to control significant bleeding.
This study explored whether bronchoscopy could be used to remove fungal material directly from affected cavities.
Why many patients will find this interesting: Antifungal treatment can help control chronic pulmonary aspergillosis, but it does not usually remove an established fungal ball. Surgery can sometimes be curative, but many patients are not suitable surgical candidates because of reduced lung function or other medical conditions. A successful bronchoscopic approach could eventually provide an additional option for selected patients.
Why is this important?
Many patients with chronic pulmonary aspergillosis are not suitable candidates for surgery because of reduced lung function or other health problems. A bronchoscopic approach could potentially offer a less invasive alternative in selected cases.
However, several important questions remain unanswered:
- Which patients benefit most?
- How often does the aspergilloma return?
- What is the risk of bleeding?
- Is antifungal treatment still required afterwards?
- How durable are the results over longer follow-up?
At present, this should be viewed as a promising specialist-centre approach rather than a new standard of care.
Evidence strength: Clinical interventional study.
Practice-changing now? No. Potentially important, but not yet routine management.
Bottom line: Bronchoscopic removal of aspergilloma is an interesting specialist approach that may eventually help some patients who are unsuitable for surgery, but it is not yet standard treatment.
Read more:
Investigating the efficacy and safety of bronchoscopic removal of aspergilloma in PTB-CCPA
PCR Testing May Help Diagnose Invasive Aspergillosis
Another paper examined the role of real-time polymerase chain reaction (PCR) testing in diagnosing invasive aspergillosis.
PCR detects fungal genetic material and can potentially identify infection more quickly than conventional culture methods.
Why is this important?
Diagnosing invasive aspergillosis remains challenging. No single test is perfect, and clinicians often need to combine information from:
- CT scans and other imaging
- Bronchoscopy findings
- Fungal culture
- Microscopy
- Galactomannan testing
- Clinical risk factors
PCR has been studied for many years, but its performance varies depending on the patient group, sample type, laboratory method and whether the patient has already received antifungal treatment.
This study supports the growing role of molecular diagnostics but does not suggest that PCR should replace existing tests. Instead, it reinforces the idea that combining several diagnostic approaches usually provides the most reliable diagnosis.
A key caution is that PCR detects fungal DNA. It does not always prove invasive disease. This is especially important in people with structurally abnormal lungs, where colonisation can complicate interpretation.
Evidence strength: Diagnostic utility study.
Practice-changing now? No. PCR may be a useful additional test but should always be interpreted alongside the wider clinical picture.
Bottom line: PCR is becoming an increasingly useful diagnostic tool, but it works best when combined with scans, biomarkers, culture results and clinical assessment.
Read more:
Utility of Real-Time PCR in the Diagnosis of Invasive Aspergillosis
Five Years of Evidence on COVID-19-Associated Pulmonary Aspergillosis
Researchers also published a major umbrella review examining evidence from 2020 to 2025 on COVID-19-associated pulmonary aspergillosis (CAPA).
CAPA emerged during the COVID-19 pandemic as an important complication affecting some patients with severe COVID-19, particularly those requiring intensive care.
What did the review find?
The review confirms that CAPA remains associated with:
- Severe illness
- Intensive care admission
- Mechanical ventilation
- High mortality
However, estimating exactly how common CAPA is remains difficult.
Different studies used different definitions, diagnostic methods and screening approaches, making direct comparison challenging. Bronchoscopy was also limited in many settings early in the pandemic, which affected how cases were detected and classified.
Studies have also differed because of:
- Different diagnostic criteria
- Changes in COVID-19 treatment over time
- Vaccination status
- Use of corticosteroids and immunomodulators
- Different intensive care unit screening practices
The review is valuable because it brings together several years of evidence, but it is unlikely to change current management directly.
Evidence strength: Umbrella review and meta-meta-analysis.
Practice-changing now? No. It reinforces awareness rather than introducing a new treatment approach.
Bottom line: CAPA remains a serious complication of severe COVID-19, but this review largely confirms what clinicians already suspected rather than changing current practice.
Read more:
Incidence, Mortality and Risk Factors in COVID-19-Associated Pulmonary Aspergillosis (CAPA)
Why Azole Tolerance Is More Complex Than Resistance
The most scientifically important theme this week comes from three studies investigating how Aspergillus fumigatus survives exposure to azole antifungal drugs.
For many years, discussions about antifungal treatment failure have focused heavily on resistance mutations, particularly changes involving the CYP51A gene. These mutations can make the fungus less susceptible to antifungal drugs such as itraconazole, voriconazole, posaconazole and isavuconazole.
However, these new studies suggest the situation may be considerably more complicated.
Researchers found that fungal survival may also be influenced by:
- Iron availability
- Mitochondrial function
- Epigenetic regulation
- Long non-coding RNA molecules
Why this matters for patients: Laboratory testing may sometimes suggest that an Aspergillus isolate is susceptible to treatment, yet the infection can still prove difficult to control. Researchers increasingly believe that fungal tolerance and stress-response mechanisms may help explain some of these situations. Understanding these processes could eventually lead to better resistance monitoring and more effective treatments.
Resistance vs Tolerance: What's the Difference?
Resistance and tolerance are related but different concepts.
Resistance usually refers to genetic changes that allow the fungus to continue growing despite exposure to an antifungal drug.
Tolerance refers to the ability of some fungal cells to survive drug exposure without necessarily having permanent resistance mutations.
This distinction matters because tolerance may allow the fungus to persist long enough to eventually acquire more stable resistance.
In simple terms, researchers are increasingly asking whether some cases of treatment failure occur because the fungus first becomes tolerant and only later becomes resistant.
The emerging model:
Azole exposure → Temporary tolerance → Fungal survival → Opportunity for resistance mutations → Stable resistance
Iron Starvation and Azole Tolerance
One study found that iron starvation may increase azole tolerance in Aspergillus fumigatus through effects on mitochondrial function.
Iron is essential for both humans and fungi. During infection, the immune system attempts to limit fungal access to iron as part of a defence strategy known as nutritional immunity.
The study suggests that when iron becomes scarce, the fungus may alter its metabolism in ways that help it survive antifungal stress.
This does not mean that iron supplements or dietary changes would affect antifungal treatment. The work is exploring complex biological processes occurring within infected tissues.
Instead, the study provides another clue about how the fungus adapts to hostile conditions inside the body.
Evidence strength: Mechanistic laboratory research.
Practice-changing now? No.
Epigenetics and the Development of Resistance
Perhaps the most influential paper this week examined an epigenetic mechanism that appears to promote azole tolerance and facilitate the later development of antifungal resistance.
Epigenetics refers to changes in gene activity that occur without altering the underlying DNA sequence itself.
In recent years, researchers have increasingly recognised that fungal adaptation is not driven solely by permanent genetic mutations. Instead, fungi can alter gene activity in response to environmental stress.
This study supports a model in which antifungal exposure may trigger a temporary tolerant state. That tolerant state may then allow some fungal cells to survive long enough to acquire permanent resistance mutations.
Importantly, this does not replace the existing understanding of CYP51A-mediated resistance. Instead, it expands it.
Rather than viewing resistance as a single event, researchers are increasingly seeing it as a process that may develop over time.
Evidence strength: Strong mechanistic evidence.
Practice-changing now? No, but potentially important for future resistance monitoring and antifungal development.
Long Non-Coding RNA and Antifungal Susceptibility
The third paper identified a long non-coding RNA that appears to influence triazole susceptibility in Aspergillus fumigatus.
Long non-coding RNAs are molecules that do not produce proteins themselves but can still influence how genes are switched on or off.
Although these molecules are increasingly recognised as important regulators of biological processes, their role in fungal antifungal susceptibility remains relatively unexplored.
The researchers found that altering the activity of a specific long non-coding RNA changed how the fungus responded to azole antifungal drugs in laboratory experiments and animal models.
This is still early-stage science and has no immediate impact on patient treatment. However, it provides another example of how fungal responses to antifungal drugs may be regulated by multiple biological pathways.
Evidence strength: Moderate to strong mechanistic evidence.
Practice-changing now? No.
Bottom line: These studies suggest that antifungal treatment response is influenced by much more than classic resistance mutations. Scientists are uncovering a complex network of stress responses, metabolic adaptations and gene regulation mechanisms that may help Aspergillus survive antifungal exposure. While this research will not change treatment today, it may eventually lead to better ways of predicting, preventing and overcoming antifungal resistance.
Also Noted This Week
Breakthrough Aspergillosis Despite Prophylaxis
A case report described tracheobronchial aspergillosis developing in a lung transplant recipient despite receiving combined antifungal prophylaxis. The infection involved Aspergillus calidoustus and Aspergillus niger.
While only a single case, it serves as a reminder that prophylactic treatment reduces risk but cannot eliminate it completely, particularly in highly immunosuppressed patients and where less common or resistant Aspergillus species may be involved.
Evidence strength: Case report. Clinically notable, but very low-level evidence.
Practice-changing now? No.
Read more:
View on PubMed |
Read via DOI
Therapeutic Drug Monitoring Remains Important
A bibliometric review highlighted growing interest in antifungal therapeutic drug monitoring (TDM).
Therapeutic drug monitoring means measuring antifungal drug levels in the blood to help ensure that treatment is high enough to be effective while minimising toxicity and drug interactions.
This does not provide new clinical trial evidence, but it supports the growing importance of antifungal stewardship, pharmacokinetic monitoring, toxicity prevention and pharmacy-led optimisation of antifungal treatment.
Evidence strength: Bibliometric and service-focused review.
Practice-changing now? No, but relevant to service development and pharmacy practice.
Read more:
View on PubMed |
Read via DOI
Potential Future Drug Targets
A bioRxiv preprint investigated the mannitol biosynthesis pathway in Aspergillus fumigatus, focusing on mannitol-2-dehydrogenase as a possible antifungal target.
This is early preclinical research and does not affect current treatment. However, it is worth watching as part of wider efforts to identify fungal-specific metabolic vulnerabilities that could eventually support new antifungal strategies.
Evidence strength: Preclinical antifungal-target discovery.
Practice-changing now? No. Interesting, but very early.
Read more:
Search bioRxiv for this preprint
Why This Research Matters
- Diagnosis continues to improve through molecular testing.
- Researchers are exploring less invasive options for managing aspergilloma.
- COVID-19-associated pulmonary aspergillosis remains an important complication of severe COVID-19.
- Scientists are discovering new mechanisms that help Aspergillus survive antifungal treatment.
- Future antifungal therapies may target fungal stress responses as well as traditional resistance mechanisms.
What Researchers Will Be Watching Next
- Whether bronchoscopic aspergilloma removal can be replicated in larger studies and specialist centres.
- How PCR testing can be integrated most effectively into routine diagnostic pathways.
- Whether CAPA rates continue to change as COVID-19 evolves and vaccination remains widespread.
- How fungal tolerance contributes to treatment failure and acquired azole resistance.
- Whether new antifungal drugs can exploit pathways such as mannitol metabolism, stress adaptation and epigenetic regulation.
What This Means for Patients
This week's research illustrates how aspergillosis science is advancing in two important directions at the same time.
Firstly, researchers are developing better ways to diagnose and manage disease through improved testing and new interventional approaches.
Secondly, scientists are learning much more about the biology of Aspergillus itself, particularly how it survives antifungal treatment and adapts to stressful environments.
Although none of these studies should change individual treatment decisions today, they contribute to a growing body of knowledge that may improve diagnosis, monitoring and treatment options in the future.
The most immediate clinical relevance comes from studies investigating diagnosis and management. The laboratory studies are less likely to affect care in the short term but may contribute to future advances in treatment and resistance prevention.
For now, the main message is that aspergillosis remains a complex condition that requires specialist assessment and interpretation of test results within the wider clinical picture.
None of the papers discussed in this update support changing treatment without specialist medical advice.
When to Speak to Your Clinical Team
Contact your clinical team promptly if you experience:
- Significant haemoptysis (coughing up blood)
- Worsening breathlessness
- Persistent fever
- New or worsening chest pain
- Severe side effects from antifungal treatment
- New confusion or sudden deterioration
- A sudden worsening of your usual aspergillosis symptoms
Do not stop, reduce, or change antifungal treatment without discussing it with your healthcare team first.
If you cough up a large amount of blood, have severe breathlessness, chest pain, collapse, or feel acutely unwell, seek urgent medical help.
Evidence Strength Summary
| Topic | Evidence type | Clinical relevance | Practice-changing now? |
|---|---|---|---|
| Bronchoscopic aspergilloma removal in post-tuberculosis CPA | Clinical interventional study | Medium to high | No |
| Real-time PCR for invasive aspergillosis | Diagnostic utility study | Moderate | No |
| CAPA umbrella review | Evidence synthesis | High | No |
| Iron starvation and azole tolerance | Mechanistic study | Medium | No |
| Epigenetic azole tolerance | Mechanistic study | Medium to high | No |
| Long non-coding RNA and triazole susceptibility | Mechanistic study | Medium | No |
| Breakthrough tracheobronchial aspergillosis case report | Case report | Low to moderate | No |
| Antifungal therapeutic drug monitoring | Bibliometric/service review | Moderate for services | No |
| Mannitol pathway preprint | Preclinical target discovery | Low at present | No |
Frequently Asked Questions
What is azole tolerance in Aspergillus?
Azole tolerance describes the ability of some Aspergillus cells to survive exposure to antifungal drugs without possessing the classic resistance mutations normally associated with azole resistance. Researchers believe tolerance may sometimes contribute to persistent infection and could provide an opportunity for more stable resistance to develop later.
Can PCR diagnose aspergillosis?
Polymerase chain reaction (PCR) testing can help detect Aspergillus genetic material and may support diagnosis, particularly when combined with imaging, culture, galactomannan testing and clinical assessment. PCR alone cannot confirm invasive disease.
What is COVID-19-associated pulmonary aspergillosis (CAPA)?
COVID-19-associated pulmonary aspergillosis, or CAPA, is a form of aspergillosis that can occur in some patients with severe COVID-19, particularly those requiring intensive care treatment.
Can aspergilloma be removed without surgery?
Research is exploring bronchoscopic removal of aspergilloma in carefully selected patients. However, this remains a specialist procedure and is not currently considered standard treatment. Further studies are needed to determine which patients benefit most.
Does antifungal resistance mean treatment will stop working?
Not necessarily. Many patients respond well to antifungal treatment. Resistance is only one factor influencing treatment success. Drug levels, immune function, disease severity and fungal tolerance mechanisms may also influence outcomes.
Should I change my antifungal treatment because of these studies?
No. None of the studies discussed in this update support changing treatment without specialist medical advice. Patients should always discuss treatment decisions with their clinical team.
Weekly Aspergillosis Research Update – 15 June 2026
Key Points
- A large population study confirms that people who have survived tuberculosis (TB) have a substantially increased risk of developing chronic pulmonary aspergillosis (CPA).
- New UK data highlight the significant burden of Aspergillus-related chronic lung diseases in routine respiratory care.
- Research suggests that fungal balls (aspergillomas) are complex microbial ecosystems rather than simple collections of fungal growth.
- New diagnostic approaches using proteomics, DNA methylation and sequencing continue to show promise.
- Several studies explore improved diagnosis and treatment of aspergillosis in transplant recipients and other highly vulnerable patients.
Contents
- Tuberculosis Survivors and Aspergillosis Risk
- New UK Data on Aspergillus-Related Lung Disease
- Understanding Fungal Balls
- New Diagnostic Technologies
- Influenza-Associated Pulmonary Aspergillosis
- Transplantation and Immunotherapy Research
- What Does This Mean for Patients?
- References
Tuberculosis Survivors Face a Much Higher Risk of Pulmonary Aspergillosis
One of the most important studies published this week examined the long-term risk of pulmonary aspergillosis among people who have previously had tuberculosis (TB).
Researchers analysed nationwide health data and found that pulmonary aspergillosis occurred almost ten times more frequently in TB survivors than in matched controls. The incidence was 0.89 cases per 1,000 person-years among TB survivors compared with 0.09 cases per 1,000 person-years in the control group.
After adjusting for other risk factors, individuals with a history of TB remained nearly seven times more likely to develop pulmonary aspergillosis.
This finding reinforces a growing body of evidence showing that chronic pulmonary aspergillosis (CPA) is an important long-term complication of tuberculosis. Residual lung cavities and structural lung damage may provide an environment in which Aspergillus can establish chronic infection.
- Zo S, Lee KN, Han K, et al. Risk of Pulmonary Aspergillosis in Tuberculosis Survivors: A Nationwide Population-based Study.
International Journal of Antimicrobial Agents. 2026.
Patients who have previously had tuberculosis and continue to experience symptoms such as chronic cough, breathlessness, fatigue, weight loss or coughing up blood should discuss the possibility of CPA with their healthcare team.
New UK Data Highlight the Burden of Aspergillus-Related Lung Disease
A 10-year retrospective study from Imperial College Healthcare NHS Trust provides valuable insight into the scale of Aspergillus-related lung disease seen within a large UK respiratory service.
The researchers identified:
- 334 patients with serological allergic bronchopulmonary aspergillosis (sABPA)
- 145 patients with allergic bronchopulmonary aspergillosis (ABPA)
- 74 patients with chronic pulmonary aspergillosis (CPA)
- 38 patients with simple aspergilloma
- 11 patients with CPA-ABPA overlap disease
These figures demonstrate that Aspergillus-related conditions are encountered across a broad range of respiratory clinics and are not confined to specialist fungal centres.
- Venkatesan T, Nagi N, Nwankwo L, et al. Describing the Burden and Characteristics of Aspergillus-related Chronic Lung Disease at Imperial College Healthcare Trust: a 10-year Retrospective Study.
BMJ Open Respiratory Research. 2026.
The study highlights the importance of awareness among respiratory specialists, general physicians and primary care clinicians. Early recognition remains one of the biggest challenges in Aspergillus-related lung disease.
Fungal Balls Are More Complex Than Previously Thought
A fascinating multi-omics study examined fungal balls (aspergillomas) removed from patients with chronic pulmonary aspergillosis.
Traditionally, aspergillomas have been viewed as relatively simple accumulations of fungal material within pre-existing lung cavities. However, this research paints a much more complex picture.
The investigators found evidence that aspergillomas function as resilient microbial ecosystems involving interactions between Aspergillus species and bacteria, including organisms such as Pseudomonas aeruginosa.
The fungal communities also showed metabolic adaptations that may help them survive within the challenging environment of the lung cavity.
These findings may help explain why some aspergillomas remain difficult to eradicate and why bacterial co-infections can sometimes influence symptoms and treatment outcomes.
New Diagnostic Technologies Continue to Advance
Two veterinary studies published this week demonstrate the rapid development of advanced fungal diagnostic technologies.
Proteomics in Falcons
Researchers studying aspergillosis in falcons used plasma proteomics to identify potential biomarkers that may allow earlier diagnosis of infection.
Current diagnostic approaches often detect disease only after significant progression. The identification of blood-based biomarkers could eventually improve earlier detection and monitoring.
- Vieu S, Lozano C, Azmanis P, et al. Falcon Plasma Proteomics to Improve Avian Aspergillosis Diagnosis.
Journal of Proteomics. 2026.
DNA Methylation and Nanopore Sequencing in Chickens
A second study used host cell-free DNA methylation combined with nanopore sequencing to diagnose Aspergillus fumigatus infection in chickens with high accuracy.
Although these studies involve birds, they reflect wider trends in fungal diagnostics, where researchers are increasingly exploring:
- Proteomics
- Cell-free DNA analysis
- Next-generation sequencing
- Machine learning approaches
- Biomarker-based diagnostics
Future human diagnostics may rely less on culture-based testing and more on sophisticated molecular techniques that can identify disease earlier and more accurately.
Influenza and Aspergillosis: Understanding the Immune Response
A review published in Trends in Microbiology explores the mechanisms underlying influenza-associated pulmonary aspergillosis (IAPA).
Over the past decade, clinicians have recognised that severe influenza can predispose some patients to invasive Aspergillus infection.
The review discusses how viral infection can disrupt the delicate balance of immune responses in the lungs, creating conditions that allow Aspergillus to invade tissue.
The authors describe this balance as an inflammatory "rheostat" that regulates protection against infection while avoiding excessive tissue damage.
- Charrier Le Blan M, Biquand E, Briard B. Critical Role of the Inflammatory Rheostat in Influenza-associated Pulmonary Aspergillosis.
Trends in Microbiology. 2026.
While primarily relevant to critically ill hospitalised patients, the work improves our understanding of how viral infections and fungal infections interact.
Transplantation and Immunotherapy Research
Several studies this week focused on patients with severe immune suppression and organ transplantation.
Improved Diagnosis After Lung Transplantation
The GALACTBAS study suggests that galactomannan testing of tracheobronchial aspirates may improve detection of Aspergillus infection in lung transplant recipients.
The findings support the idea that some transplant-associated Aspergillus infections begin within the bronchial tree and may not always be detected early using traditional bronchoalveolar lavage (BAL) samples.
- Monforte A, Martín-Gómez MT, Berastegui C, et al. Diagnostic Value of Galactomannan in Tracheobronchial Aspirate for Aspergillus Infection in Lung Transplant Recipients.
Journal of Clinical Microbiology. 2026.
Kidney Transplant Patients
A prospective multicentre study found that invasive aspergillosis remained one of the most serious fungal complications after kidney transplantation, with mortality exceeding 40%.
Emerging Immunotherapies
Another review evaluated growing evidence supporting the use of immune-enhancing treatments such as:
- Interferon-gamma (IFN-γ)
- Anti-programmed death-1 (anti-PD-1) therapies
These approaches aim to strengthen antifungal immunity alongside standard antifungal treatment in selected patients with severe invasive mould infections.
Although still considered specialist therapies, interest in immunomodulation continues to grow.
What Does This Mean for Patients?
Several themes emerge from this week's publications:
- Previous tuberculosis remains one of the most important risk factors for chronic pulmonary aspergillosis.
- Aspergillus-related lung diseases continue to be under-recognised outside specialist centres.
- Fungal balls are biologically complex and involve interactions between fungi, bacteria and the lung environment.
- Diagnostic technology is advancing rapidly, particularly in biomarker and sequencing-based approaches.
- Research into immune-based treatments continues to expand alongside antifungal drug development.
Although many of these studies are early-stage or aimed primarily at researchers and specialists, together they show a field that is continuing to improve our understanding of how Aspergillus causes disease and how it might be diagnosed and treated more effectively in the future.
When to Seek Medical Advice
Patients with known lung disease should seek medical advice if they experience:
- Persistent or worsening breathlessness
- New or worsening cough
- Unexplained weight loss
- Fatigue that is worsening over time
- Coughing up blood (haemoptysis)
- New chest pain
- Persistent fever or night sweats
Individuals who have previously had tuberculosis should be particularly aware that chronic pulmonary aspergillosis can develop months or years after apparent recovery from TB.
References
- Zo S, Lee KN, Han K, et al. Risk of Pulmonary Aspergillosis in Tuberculosis Survivors: A Nationwide Population-based Study.
International Journal of Antimicrobial Agents. 2026. - Venkatesan T, Nagi N, Nwankwo L, et al. Describing the Burden and Characteristics of Aspergillus-related Chronic Lung Disease at Imperial College Healthcare Trust: a 10-year Retrospective Study.
BMJ Open Respiratory Research. 2026. - Liu C, Ribeiro MM, Yang J, et al. Multi-omics Profiling of Fungal Balls in Chronic Pulmonary Aspergillosis Patients Reveals Microbiome Dynamics and Metabolic Adaptations.
mBio. 2026. - Vieu S, Lozano C, Azmanis P, et al. Falcon Plasma Proteomics to Improve Avian Aspergillosis Diagnosis.
Journal of Proteomics. 2026. - Drag MH, Hvilsom C, Poulsen LL, et al. MethylSense: High Accuracy Machine Learning-Based Diagnostics for Aspergillus fumigatus Infection in Chickens Using Host Cell-free DNA Methylation and Nanopore Sequencing.
Journal of Clinical Microbiology. 2026. - Charrier Le Blan M, Biquand E, Briard B. Critical Role of the Inflammatory Rheostat in Influenza-associated Pulmonary Aspergillosis.
Trends in Microbiology. 2026. - Monforte A, Martín-Gómez MT, Berastegui C, et al. Diagnostic Value of Galactomannan in Tracheobronchial Aspirate for Aspergillus Infection in Lung Transplant Recipients.
Journal of Clinical Microbiology. 2026. - Serris A, Guihot A, Joffre J, et al. Emerging Evidence for Anti-PD-1 and IFN-γ as Adjunctive Immunotherapy in Invasive Mold Infections.
mBio. 2026.
Author: Graham Atherton, National Aspergillosis Centre (NAC)
Clinical Review: National Aspergillosis Centre Clinical Team
Last Reviewed: 15 June 2026
For Patient Education Only: This article is intended for educational purposes and should not replace professional medical advice.
Professional Aspergillosis Update: May 2026
Audience: respiratory physicians, infectious diseases physicians, clinical microbiologists, haematologists, pharmacists, specialist nurses, laboratory scientists and researchers with an interest in aspergillosis.
Contents
Key messages
- Isavuconazole therapeutic drug monitoring may have a selective role. Although isavuconazole is usually more predictable than voriconazole, real-world pharmacokinetic variability remains clinically relevant in some patients.
- Posaconazole prophylaxis should not automatically be avoided with midostaurin. The interaction is real, but clinical consequences may often be manageable with careful monitoring.
- Surrogate azole susceptibility testing has limits. Voriconazole gradient diffusion testing may help screen for broader azole resistance, but it should not replace direct susceptibility testing where treatment decisions depend on the result.
- Invasive fungal sinusitis remains a high-mortality emergency in haematological malignancy. Early tissue diagnosis, ENT involvement and multidisciplinary management remain central.
- Non-fumigatus Aspergillus species are becoming more important research targets. New CRISPR-Cas9 tools for Aspergillus calidoustus may support future work on virulence and antifungal resistance.
Top papers this month
1. Isavuconazole pharmacokinetics and pharmacodynamics in real-world practice
Guidi M, Couchepin J, Reinhold I, Kronig I, Neofytos D, Schreiber PW, André P, Buclin T, Lamoth F.
Characterization of isavuconazole pharmacokinetics and pharmacodynamics in a real-life cohort.
JAC Antimicrobial Resistance. 2026;8(3):dlag071.
PMID: 42088097
Why this paper was selected
Isavuconazole is increasingly used for invasive aspergillosis because of its favourable safety profile and generally more predictable pharmacokinetics compared with voriconazole. This study provides important real-world evidence that clinically relevant interpatient variability still occurs and that therapeutic drug monitoring may have a role in selected patients.
Key findings
- Isavuconazole showed relatively predictable pharmacokinetics overall.
- Clinically relevant variability in drug exposure was still observed between patients.
- Therapeutic drug monitoring identified patients with atypically low or high exposure.
- Exposure relative to fungal minimum inhibitory concentration may be more informative than plasma concentration alone.
- No strong concentration-dependent toxicity signal was observed within the exposure range studied.
Clinical significance
This paper challenges the assumption that isavuconazole therapeutic drug monitoring is rarely useful. While the findings do not justify universal routine monitoring, they support selective monitoring in complex patients, particularly where there is treatment failure, suspected malabsorption, significant drug interactions, unusual body composition, long-term therapy, or infection with isolates showing elevated minimum inhibitory concentrations.
Implications for practice
Classification: Important but not yet practice changing.
The study supports a more individualised approach to isavuconazole use. It also reinforces the direction of travel in antifungal stewardship: interpreting drug exposure alongside fungal susceptibility rather than considering plasma concentrations in isolation.
Evidence assessment
Evidence quality: Moderate. The real-world dataset and pharmacokinetic-pharmacodynamic modelling strengthen the evidence base, but the observational design limits causal inference and definitive exposure targets were not established.
Editorial assessment
This is one of the most clinically relevant antifungal pharmacology papers in this update. It does not establish mandatory isavuconazole monitoring, but it provides a strong argument for selective therapeutic drug monitoring in high-risk or complex aspergillosis patients.
2. Managing posaconazole and midostaurin interactions in FLT3-mutated AML
Joisten CS, Mellinghoff SC, Seidel D, Müller C, Müller-Ohrem C, Kreuzer K-A, Frenzel LP, Simon F, Hallek M, Koehler P, Cornely OA, Stemler J.
Clinical impact of potential drug-drug interactions between midostaurin and posaconazole in FLT3-mutated AML.
Antimicrobial Agents and Chemotherapy. 2026;70(6):e01951-25.
PMID: 42118097
Why this paper was selected
Posaconazole prophylaxis is central to prevention of invasive aspergillosis in patients undergoing intensive acute myeloid leukaemia treatment. Midostaurin is metabolised through CYP3A4, and posaconazole is a potent CYP3A4 inhibitor. This study addresses a common real-world dilemma: whether this interaction should alter antifungal prophylaxis practice.
Key findings
- The pharmacokinetic interaction between posaconazole and midostaurin was confirmed.
- Clinical toxicity appeared less severe than theoretical concerns might suggest.
- Many patients were able to receive both agents without major treatment-limiting toxicity.
- Individual variability in exposure and tolerability remained important.
- The findings support continued attention to monitoring rather than automatic avoidance of posaconazole.
Clinical significance
This paper is important because it addresses an immediate bedside decision. Avoiding posaconazole because of interaction concerns may leave high-risk acute myeloid leukaemia patients vulnerable to invasive aspergillosis. The study suggests that the interaction is clinically manageable in many patients when appropriate monitoring and multidisciplinary oversight are in place.
Implications for practice
Classification: Important but not yet practice changing.
The paper supports continued use of posaconazole prophylaxis where clinically indicated, with careful monitoring for toxicity and close collaboration between haematology, infectious diseases, microbiology and pharmacy teams.
Evidence assessment
Evidence quality: Moderate. The study is clinically relevant and real-world, but observational. It does not establish definitive dose-adjustment protocols or replace existing guideline recommendations.
Editorial assessment
The key message is that proven antifungal prophylaxis should not be abandoned solely because of theoretical interaction concerns. The interaction is real, but careful monitoring is generally preferable to withholding protection against invasive aspergillosis in a very high-risk group.
3. Can voriconazole susceptibility predict isavuconazole or posaconazole susceptibility?
Vahedi-Shahandashti R, Nickel A-S, Eisele D, Lass-Flörl C; ISHAM Working Group Member of Intrinsic Antifungal Resistance.
Can voriconazole gradient diffusion testing results be extrapolated to isavuconazole and posaconazole in Aspergillus spp.? Comparative analysis with CLSI broth microdilution and cyp51A gene sequencing.
Antimicrobial Agents and Chemotherapy. 2026;70(6):e01813-25.
PMID: 42138696
Why this paper was selected
Azole resistance in Aspergillus species is a growing problem, but not all laboratories can perform comprehensive susceptibility testing for every triazole. This paper asks whether voriconazole gradient diffusion testing can be used as a practical surrogate marker for broader azole susceptibility.
Key findings
- Voriconazole susceptibility often correlated with broader azole susceptibility patterns.
- Elevated voriconazole minimum inhibitory concentrations frequently corresponded with reduced isavuconazole susceptibility.
- Prediction of posaconazole susceptibility was less reliable.
- Discordant susceptibility profiles occurred, particularly among resistant isolates.
- cyp51A sequencing helped explain many resistance patterns but did not account for all phenotypes.
Clinical significance
The study supports voriconazole gradient diffusion testing as a useful first-line screening approach, especially where full reference testing is not immediately available. However, it also highlights a critical limitation: susceptibility to one triazole cannot be assumed to guarantee susceptibility to another.
Implications for practice
Classification: Important but not yet practice changing.
Voriconazole gradient diffusion testing may help identify isolates that require further investigation, but it should not replace direct isavuconazole or posaconazole susceptibility testing where treatment decisions depend on accurate results.
Evidence assessment
Evidence quality: Moderate to high for a laboratory diagnostic study. The use of CLSI broth microdilution and cyp51A sequencing strengthens the analysis, but clinical outcome data were not assessed.
Editorial assessment
This is a practical paper for clinical mycology laboratories. The main message is that surrogate azole testing can support screening and stewardship, but definitive treatment decisions should still be based on agent-specific susceptibility testing and molecular resistance analysis where available.
4. Invasive fungal sinusitis in haematological malignancy
Athni TS, Strauch CB, Kovac V, Arbona-Haddad E, Villa IP, Gupta S, Aleissa MM, Liakos AD, Tong A, Vedula RS, Maxfield AZ, Bergmark RW, Sherman AC.
Invasive fungal sinusitis in patients with hematological malignancies: a 20-year study from a tertiary academic US hospital system.
Open Forum Infectious Diseases. 2026;13(6):ofag304.
PMID: 42238379
Why this paper was selected
Invasive fungal sinusitis is a severe but less commonly discussed manifestation of invasive mould disease. In haematological malignancy, delayed recognition can lead to orbital, intracranial and fatal complications. This 20-year cohort provides useful long-term clinical insight.
Key findings
- Aspergillus species and Mucorales were the dominant pathogens.
- Mortality remained substantial despite modern antifungal therapy and supportive care.
- Early imaging, endoscopic assessment, tissue biopsy and histopathology remained central to diagnosis.
- Successful management frequently required combined medical and surgical approaches.
- Multidisciplinary care involving haematology, infectious diseases, ENT, microbiology and radiology was essential.
Clinical significance
This study reinforces that invasive aspergillosis is not solely a pulmonary disease. Sinonasal invasive fungal disease remains an emergency in profoundly immunocompromised patients. Distinguishing aspergillosis from mucormycosis is particularly important because antifungal treatment choices differ substantially.
Implications for practice
Classification: Important but not practice changing.
The paper reinforces existing best practice: early suspicion, urgent ENT involvement, tissue diagnosis, prompt antifungal therapy and multidisciplinary management.
Evidence assessment
Evidence quality: Moderate. The long observation period and detailed clinical experience are strengths, but the retrospective single-system design limits causal conclusions.
Editorial assessment
This paper is a useful reminder that early recognition remains one of the strongest determinants of outcome in invasive fungal disease. Persistent or atypical sinus symptoms in high-risk haematology patients should prompt urgent assessment rather than routine treatment as uncomplicated bacterial sinusitis.
Important development
5. Invasive mould infections in transplant recipients
Sudhaharan S, Pamidimukkala U, Bojja S, Raju DSB, Kk R, Gopal PSS.
Invasive mold infections among transplant recipients: a single-center observational study.
Journal de Mycologie Médicale / Journal of Medical Mycology. 2026;36(2):101629.
DOI: 10.1016/j.mycmed.2026.101629
Why this paper was selected
Transplant recipients remain a key high-risk population for invasive aspergillosis and other invasive mould infections. This observational study provides contemporary real-world data on presentation, diagnosis, microbiology, treatment and outcomes in a transplant centre.
Key findings
- Aspergillus species remained the predominant mould pathogen.
- Pulmonary disease was the most common presentation.
- Diagnosis required multimodal assessment combining clinical, radiological and mycological data.
- Invasive mould infections remained associated with substantial morbidity and mortality.
- Earlier diagnosis was associated with more favourable outcomes.
Clinical significance
The study confirms rather than changes current understanding. Its main value is as a contemporary reminder that invasive aspergillosis remains a major threat in transplantation despite advances in prophylaxis, diagnostics and antifungal treatment.
Implications for practice
Classification: Important but not practice changing.
The findings support ongoing vigilance, rapid investigation pathways, early multidisciplinary input and antifungal stewardship in transplant programmes.
Evidence assessment
Evidence quality: Moderate. Real-world applicability is useful, but the single-centre observational design and modest sample size limit generalisability.
Editorial assessment
This paper does not introduce a new management strategy, but it reinforces an enduring message: invasive aspergillosis outcomes in transplant recipients remain strongly dependent on early recognition and timely treatment.
Research horizon
6. CRISPR-Cas9 gene editing in Aspergillus calidoustus
Hollomon JM, Dahlstrom KM.
CRISPR-Cas9-mediated targeted gene deletion in Aspergillus calidoustus, a non-model environmental mold.
Microbiology Spectrum. 2026;14(6):e03899-25.
PMID: 42112836
Why this paper was selected
Most molecular understanding of pathogenic Aspergillus species comes from Aspergillus fumigatus. This study establishes a CRISPR-Cas9 gene-editing system for Aspergillus calidoustus, an emerging opportunistic mould with clinical relevance and reduced susceptibility to some antifungals.
Key findings
- The authors successfully developed a CRISPR-Cas9 platform for targeted gene deletion in A. calidoustus.
- The system provides a method for functional genetic studies in a previously less tractable species.
- The platform may support future research into virulence, environmental adaptation, antifungal resistance and novel drug targets.
Clinical significance
There is no immediate clinical application. However, the study is important as enabling science. As non-fumigatus Aspergillus species are increasingly recognised in clinical practice, tools that allow their biology to be studied directly may become increasingly valuable.
Implications for practice
Classification: Early-stage research requiring further validation.
This paper does not alter clinical management, diagnostics or guidelines. Its value lies in supporting future translational research.
Editorial assessment
This is a foundational research paper. It will not change patient care today, but it may help build the scientific infrastructure needed to understand emerging mould pathogens and their resistance mechanisms over the next decade.
Clinical pearl
7. Primary traumatic cutaneous aspergillosis caused by Aspergillus terreus
Ing SK, Lee YH, Tan YY, Aziz MBA, Chang AKW.
Primary traumatic cutaneous aspergillosis of the hand caused by Aspergillus terreus following a mould-contaminated penetrating injury.
Medical Mycology Case Reports. 2026;52:100798.
PMID: 42237979
Why this case was noted
This case report describes primary traumatic cutaneous aspergillosis of the hand caused by Aspergillus terreus following a mould-contaminated penetrating injury.
Clinical take-home points
- Aspergillosis is not always acquired through inhalation.
- Direct traumatic inoculation can cause localised Aspergillus infection.
- Persistent or atypical wounds following mould-contaminated trauma should prompt consideration of fungal infection.
- Tissue sampling is essential for diagnosis.
- Species-level identification matters because Aspergillus terreus is intrinsically resistant to amphotericin B.
Editorial assessment
This is not a practice-changing paper, but it is a useful educational case. It broadens clinical awareness beyond pulmonary aspergillosis and highlights the importance of early tissue diagnosis when wounds behave unexpectedly after contaminated trauma.
Overall editorial summary
The May 2026 literature contains several papers that are useful for clinicians and laboratory professionals working in aspergillosis and invasive mould disease. The strongest clinical themes are antifungal stewardship, drug exposure, azole resistance, and the continued importance of early diagnosis in high-risk populations.
The isavuconazole pharmacokinetic-pharmacodynamic study and the midostaurin-posaconazole interaction paper are particularly relevant because they address practical treatment decisions. The azole susceptibility study is highly relevant to clinical mycology laboratories and reinforces the need for careful interpretation of surrogate resistance testing. The invasive fungal sinusitis and transplant studies reinforce a familiar but important message: outcomes remain closely linked to early recognition, tissue diagnosis where appropriate, and multidisciplinary management.
Finally, the CRISPR-Cas9 paper and traumatic cutaneous aspergillosis case illustrate the breadth of modern aspergillosis research, from molecular tools for emerging moulds to unusual clinical presentations outside the respiratory tract.
References
- Guidi M, Couchepin J, Reinhold I, Kronig I, Neofytos D, Schreiber PW, André P, Buclin T, Lamoth F. Characterization of isavuconazole pharmacokinetics and pharmacodynamics in a real-life cohort. JAC Antimicrobial Resistance. 2026;8(3):dlag071. PMID: 42088097
- Joisten CS, Mellinghoff SC, Seidel D, Müller C, Müller-Ohrem C, Kreuzer K-A, Frenzel LP, Simon F, Hallek M, Koehler P, Cornely OA, Stemler J. Clinical impact of potential drug-drug interactions between midostaurin and posaconazole in FLT3-mutated AML. Antimicrobial Agents and Chemotherapy. 2026;70(6):e01951-25. PMID: 42118097
- Vahedi-Shahandashti R, Nickel A-S, Eisele D, Lass-Flörl C; ISHAM Working Group Member of Intrinsic Antifungal Resistance. Can voriconazole gradient diffusion testing results be extrapolated to isavuconazole and posaconazole in Aspergillus spp.? Comparative analysis with CLSI broth microdilution and cyp51A gene sequencing. Antimicrobial Agents and Chemotherapy. 2026;70(6):e01813-25. PMID: 42138696
- Athni TS, Strauch CB, Kovac V, Arbona-Haddad E, Villa IP, Gupta S, Aleissa MM, Liakos AD, Tong A, Vedula RS, Maxfield AZ, Bergmark RW, Sherman AC. Invasive fungal sinusitis in patients with hematological malignancies: a 20-year study from a tertiary academic US hospital system. Open Forum Infectious Diseases. 2026;13(6):ofag304. PMID: 42238379
- Sudhaharan S, Pamidimukkala U, Bojja S, Raju DSB, Kk R, Gopal PSS. Invasive mold infections among transplant recipients: a single-center observational study. Journal de Mycologie Médicale / Journal of Medical Mycology. 2026;36(2):101629. DOI: 10.1016/j.mycmed.2026.101629
- Hollomon JM, Dahlstrom KM. CRISPR-Cas9-mediated targeted gene deletion in Aspergillus calidoustus, a non-model environmental mold. Microbiology Spectrum. 2026;14(6):e03899-25. PMID: 42112836
- Ing SK, Lee YH, Tan YY, Aziz MBA, Chang AKW. Primary traumatic cutaneous aspergillosis of the hand caused by Aspergillus terreus following a mould-contaminated penetrating injury. Medical Mycology Case Reports. 2026;52:100798. PMID: 42237979
Article information
Prepared for: aspergillosis.org professionals section
Intended audience: healthcare professionals and researchers
Article type: monthly professional literature update
Coverage period: May 2026
Last reviewed: June 2026
Clinical Trials Update: Progress in ABPA and Invasive Aspergillosis Research
Date reviewed: 8 June 2026
Clinical research into aspergillosis continues to move forward, although there have been relatively few major new trial launches in recent weeks. The most significant developments involve two areas:
- Growing evidence supporting biologic treatment for Allergic Bronchopulmonary Aspergillosis (ABPA).
- Progress towards completion of a major international trial of a new antifungal drug for invasive aspergillosis.
Contents
- ABPA: More Evidence for Dupilumab
- Olorofim Trial Moves Towards Completion
- Why These Studies Matter
- What We Didn't Find This Month
- Common Questions
- When to Seek Medical Advice
ABPA: More Evidence for Dupilumab
One of the most encouraging developments in recent years has been the emergence of biologic therapies for ABPA. Researchers continue to publish and present results from the Phase II LIBERTY ABPA AIRED study, which investigated the biologic drug dupilumab.
Dupilumab works by blocking two important inflammatory pathways (Interleukin-4 and Interleukin-13) that contribute to allergic inflammation in asthma and ABPA.
Additional scientific presentations and publications appearing during 2025 and 2026 continue to show consistent benefits for many patients:
- Improved lung function.
- Fewer severe respiratory exacerbations.
- Reduced need for oral corticosteroids.
- Better asthma control.
- Improved quality of life.
- Reductions in total Immunoglobulin E (IgE) and Aspergillus-specific IgE levels.
Although biologics are not suitable for everyone with ABPA, these results continue to strengthen the evidence that targeted immune therapies may offer an alternative to long-term steroid treatment for some patients.
For people living with ABPA, this remains one of the most promising areas of current research.
Olorofim Trial Moves Towards Completion
The other major development concerns olorofim, a novel antifungal medication being developed for difficult-to-treat invasive fungal infections.
The large international Phase III OASIS trial has been comparing olorofim with standard treatment in patients with invasive aspergillosis.
Recent updates suggest that recruitment has now effectively closed and that the study is entering its final follow-up and analysis phase.
This is an important milestone because it usually means researchers have enrolled enough participants and are now collecting the final outcome data needed to determine whether the treatment works and how safe it is.
However, the most important information is still awaited:
- The primary trial results have not yet been published.
- No peer-reviewed Phase III paper is currently available.
- The effectiveness of olorofim compared with current standard treatments remains under formal evaluation.
If the final results are positive, olorofim could become an important additional treatment option for patients with invasive aspergillosis, particularly those whose infections are resistant to existing antifungal drugs or who cannot tolerate current therapies.
Why These Studies Matter
Research into aspergillosis has traditionally lagged behind many other respiratory and infectious diseases. It is therefore encouraging to see progress occurring in two key areas:
- Allergic disease (ABPA) – where biologics are offering the possibility of reducing steroid dependence.
- Invasive disease – where new antifungal drugs may help address drug resistance and treatment failure.
These studies also reflect a broader trend towards more personalised treatment approaches, matching therapies to the specific type of aspergillosis and the underlying immune response of the patient.
What We Didn't Find This Month
While there has been progress in ongoing studies, we did not identify any major new:
- ABPA clinical trials.
- Chronic Pulmonary Aspergillosis (CPA) treatment trials.
- Severe Asthma with Fungal Sensitisation (SAFS) interventional studies.
- Aspergillus bronchitis treatment trials.
- Major environmental intervention studies.
- Newly terminated or withdrawn aspergillosis drug-development programmes.
This is not unusual. Large clinical trials often take several years to complete, and periods of data analysis between recruitment and publication can be lengthy.
Common Questions
Is dupilumab available for ABPA?
Dupilumab is already licensed for several allergic and eosinophilic conditions, including some forms of severe asthma. Its use specifically for ABPA varies between countries and healthcare systems. Decisions about treatment remain highly individual and should be discussed with a specialist team.
What is a Phase III trial?
Phase III studies are large clinical trials designed to determine whether a new treatment works and how safe it is compared with existing treatments. Positive Phase III results are often required before regulatory approval.
Could olorofim be used for CPA?
Research has explored olorofim in a variety of fungal diseases, but the current Phase III programme focuses on invasive aspergillosis. Further evidence would be needed before routine use in Chronic Pulmonary Aspergillosis.
When might the OASIS results be available?
There is currently no confirmed publication date. As recruitment appears to have finished, the next major milestone will be release of the primary efficacy and safety results.
When to Seek Medical Advice
Clinical trial news is exciting, but it should not replace advice from your healthcare team.
Seek medical attention if you experience:
- Worsening breathlessness.
- New or worsening haemoptysis (coughing blood).
- Persistent fever.
- Sudden deterioration in asthma control.
- Significant side effects from antifungal or biologic treatments.
If you are interested in taking part in clinical research, speak with your specialist team about studies that may be available in your area.
Key Takeaway: The strongest current momentum in aspergillosis research remains in biologic treatments for ABPA and new antifungal therapies for invasive aspergillosis. While no major new trials have appeared this month, ongoing studies continue to move closer to delivering results that could influence future care.
Last reviewed: 8 June 2026
Aspergillosis Research Update: Week Ending 8 June 2026
Key Points
- This was a relatively quiet week for aspergillosis research, with few major new clinical studies.
- A review explored whether positive parasite blood tests in people with Allergic Bronchopulmonary Aspergillosis (ABPA) may represent true infection or immune cross-reactivity.
- Chronic Pulmonary Aspergillosis (CPA) continues to gain recognition as an important complication following tuberculosis.
- Researchers are investigating home monitoring technologies and microsampling approaches.
- Antifungal resistance remains an important area of global surveillance.
- A major review examined Aspergillus species beyond Aspergillus fumigatus.
Contents
- Can ABPA Be Confused with Parasitic Infections?
- Can Tuberculosis Lead to CPA?
- Could Home Blood Testing Help Aspergillosis Patients?
- What Is Antifungal Resistance?
- Are There Aspergillus Species Other Than Aspergillus fumigatus?
- New Aspergillus Research
- Other Interesting Publications
- What Does This Mean for Patients?
- When Should Patients Seek Medical Advice?
This week was dominated by review articles rather than major new clinical trials. While there were no obvious practice-changing breakthroughs, several useful papers provide updated summaries of important topics including ABPA diagnosis, Chronic Pulmonary Aspergillosis (CPA), antifungal resistance and future monitoring technologies.
These reviews help clinicians and researchers understand where the field currently stands and identify areas where further research is needed.
Can ABPA Be Confused with Parasitic Infections?
Our research highlight this week is a review by Mewara and colleagues examining the relationship between Allergic Bronchopulmonary Aspergillosis (ABPA) and parasitic worm (helminth) infections. Read the paper on PubMed.
ABPA and some parasitic infections can trigger remarkably similar immune responses, including:
- Very high Immunoglobulin E (IgE) levels
- Raised eosinophils
- Allergic inflammation
- Positive antibody tests
This can occasionally create diagnostic uncertainty. The authors discuss whether positive parasite blood tests in some patients with ABPA represent genuine infection, previous exposure or immune cross-reactivity caused by overlapping allergic responses.
Are parasitic infections common in the UK?
For most patients living in the UK, USA, Canada and much of Europe, parasitic worm infections remain relatively uncommon. However, doctors may consider them in people who have:
- Lived abroad
- Travelled extensively
- Worked overseas
- Been exposed to contaminated soil or freshwater in higher-risk regions
One parasite of particular interest is Strongyloides stercoralis, which can persist silently for many years and may become dangerous if someone receives high-dose steroids or other immunosuppressive treatments.
Take-home message: A positive blood test rarely tells the whole story. Symptoms, scans, blood tests and clinical history all contribute to making the correct diagnosis.
Can Tuberculosis Lead to CPA?
A large scoping review examining lung disease after tuberculosis highlighted the growing recognition of Chronic Pulmonary Aspergillosis (CPA) as an important and potentially treatable complication. Read the review on PubMed.
The review identified evidence that antifungal treatment can improve:
- Symptoms
- Radiological findings
- Markers of inflammation
Tuberculosis remains one of the most important risk factors for CPA worldwide.
Many people continue to experience symptoms after completing tuberculosis treatment, including:
- Breathlessness
- Persistent cough
- Fatigue
- Weight loss
- Haemoptysis (coughing up blood)
Increasingly, researchers recognise that some of these patients may have treatable Aspergillus-related disease rather than simply permanent lung damage.
Not all ongoing symptoms after tuberculosis are simply due to old lung damage. Some patients may have treatable Chronic Pulmonary Aspergillosis.
Could Home Blood Testing Help Aspergillosis Patients?
A review of respiratory biomarkers and patient-centred microsampling explored technologies that may eventually make monitoring chronic respiratory diseases easier and more convenient. Read the review on PubMed.
Areas under investigation include:
- Finger-prick blood testing
- Home sample collection
- Microsampling technologies
- Remote monitoring
- Personalised treatment optimisation
These approaches are particularly attractive for patients with long-term conditions who require regular monitoring.
Although still developing, they align closely with the wider move towards patient-centred care and remote monitoring.
What Is Antifungal Resistance?
A review from Japan examined azole-resistant Aspergillus species and their implications for patient care. Read the review on PubMed.
Azole antifungal drugs remain central to treatment for:
- Chronic Pulmonary Aspergillosis (CPA)
- Aspergillus bronchitis
- Invasive aspergillosis
The review highlights the continuing importance of:
- Fungal culture
- Susceptibility testing
- Therapeutic drug monitoring
- Clinical review when treatment is not working as expected
Resistance remains relatively uncommon in many patient groups but continues to be monitored closely worldwide.
Are There Aspergillus Species Other Than Aspergillus fumigatus?
Most patients are familiar with Aspergillus fumigatus, the species most commonly associated with lung disease.
However, a major review published in Clinical Microbiology Reviews examined the black aspergilli, including the Aspergillus niger complex. Read the review on PubMed.
While less common causes of lung disease, these fungi can also be associated with:
- Ear infections
- Nail infections
- Chronic pulmonary disease
- Rare invasive infections
The review serves as a useful reminder that Aspergillus is a large family of related fungi rather than a single organism.
New Aspergillus Research
One of the few original research studies highlighted this week investigated how Aspergillus fumigatus builds and repairs its cell wall. Read the study on PubMed.
The researchers explored how fungal growth is affected by antifungal drugs that target cell wall synthesis.
Although this laboratory work is unlikely to affect patient care immediately, it improves our understanding of how antifungal drugs work and may help identify future treatment targets.
Other Interesting Publications
- Fosmanogepix: A review of an emerging antifungal drug that may play a future role in treating resistant fungal infections. PubMed.
- ABPA and Eosinophilic Granulomatosis with Polyangiitis (EGPA): A rare case report describing overlapping eosinophilic disease and ABPA. PubMed.
- Hyper-IgE Syndrome and Pulmonary Aspergillosis: A case report highlighting fungal infection in a rare inherited immune disorder. PubMed.
What Does This Mean for Patients?
While this was not a week of major breakthroughs, the research reinforces several important messages:
- Diagnosing ABPA can sometimes be complicated because different conditions can produce similar immune responses.
- CPA remains an important and potentially treatable complication after tuberculosis.
- Future monitoring technologies may allow more care to take place at home.
- Antifungal resistance continues to be monitored closely worldwide.
- Research into Aspergillus biology continues to support the development of future treatments.
When Should Patients Seek Medical Advice?
Patients should contact their healthcare team if they experience:
- Increasing breathlessness
- Coughing up blood
- Persistent fever
- Unexplained weight loss
- New chest pain
- A significant increase in sputum production
- New or worsening treatment side effects
Anyone with a history of living or travelling in regions where parasitic infections are common should mention this to their healthcare team before starting high-dose steroid treatment.
Review Information
Last reviewed: 8 June 2026
Prepared for: Aspergillosis.org Weekly Research Update
Audience: Patients, carers and non-specialist readers
This article summarises recently published research. Research findings may take years to influence routine clinical practice and should not replace personalised medical advice from your healthcare team.
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Help Us Improve Our Damp Homes and Health Questionnaire
We are asking patients, carers and members of the public to help us improve a draft questionnaire for our new UK Citizen Science project on damp homes, mould and health.
Draft 1 of questionnaire download here: Health Effects of Indoor Mould Questionnaire
Key points
- We are developing a questionnaire for a Citizen Science project about damp homes, mould and health.
- Before using it in the study, we want feedback from people who may complete it.
- We are not just asking people to check spelling or grammar.
- We want to know whether the questionnaire asks the right questions, is easy to understand, and collects useful information.
- Your comments can help shape the final version of the study.
Why are we doing this project?
Damp homes and indoor mould are common problems in the UK. Many people worry that dampness, condensation and mould may affect their breathing, allergies, infections, fatigue or general wellbeing.
Our Citizen Science project aims to learn more about the links between homes, indoor mould and health by working directly with patients, carers and householders.
Citizen Science means that members of the public are not just research subjects. They help shape the research, collect information, and improve the questions being asked.
What is the questionnaire for?
The questionnaire is designed to collect information about:
- the type of home someone lives in
- signs of damp, condensation or mould
- heating and ventilation
- previous water damage, leaks or flooding
- respiratory symptoms and other health problems
- whether symptoms seem to change in different environments
- how damp or mould affects everyday life and wellbeing
This information will help researchers understand whether there are patterns between housing conditions and health. It will also help guide the next stages of the project, including possible home sampling and laboratory analysis.
Why do we need feedback?
A questionnaire can look clear to researchers but feel very different to the people completing it.
Patients and householders may notice:
- questions that are confusing
- questions that are too difficult to answer
- important topics that are missing
- sections that feel repetitive
- questions that need a “Don’t know” option
- places where more explanation is needed
This is why your feedback is so important.
What sort of comments are we looking for?
We are especially interested in comments on the following areas.
1. Is the questionnaire easy to understand?
Please tell us if any wording is unclear, too technical, or open to different interpretations.
2. Are any important questions missing?
For example, should we ask more about:
- previous mould exposure in other homes
- roof leaks, plumbing leaks or flooding
- diagnosed respiratory conditions
- asthma, allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis or other lung conditions
- steroid treatment or immune-suppressing medicines
- whether symptoms improve away from home
- whether symptoms changed after moving house
3. Is the questionnaire too long?
Long questionnaires can be tiring, especially for people living with chronic illness. We want to collect enough information to make the study useful, but not so much that people give up before finishing.
4. Are any questions difficult to answer accurately?
Some people may not know exact details about their home, heating system, building age or past water damage. We want to identify questions where people may need clearer options, such as “Not sure” or “Don’t know”.
5. Are any questions sensitive?
Questions about housing, health and personal circumstances can sometimes feel sensitive. Please tell us if any question needs a clearer explanation of why it is being asked.
The most important question
One of the most useful questions we can ask is:
If this study could answer one question about damp homes, mould and health, what would you most like to know?
This helps us understand what matters most to patients, carers and householders.
How to send us your comments
Click here for a short Google Form where you can send your feedback.
The feedback form will ask questions such as:
- How easy was the questionnaire to understand?
- Were any questions unclear or confusing?
- Do you think any important questions are missing?
- Were any questions unnecessary or repetitive?
- Was the questionnaire too long, too short, or about right?
- If this study could answer one question about damp homes, mould and health, what would you most like to know?
- Do you have any other comments or suggestions?
You do not need to answer every question. Any feedback is helpful.
This is not a grammar exercise
We are not mainly asking people to proofread the questionnaire.
What we really want to know is:
Does this questionnaire help us collect the information needed to understand whether damp homes and mould may be affecting health, and are we asking the right questions?
Thank you
Thank you for helping us improve this questionnaire. Your comments will help us design a better study and make sure the project reflects the experiences and priorities of the people affected by damp homes and mould.
By sharing your views at this early stage, you are helping shape research that could improve understanding of indoor mould, housing conditions and health.
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