Last reviewed: April 2026
Audience: Patients, carers, GPs, specialist nurses, and healthcare professionals
Key Points (Summary)
- Invasive pulmonary aspergillosis (IPA) can closely mimic other serious infections, including miliary tuberculosis, particularly in highly immunocompromised patients.
- Metagenomic next-generation sequencing (mNGS) is emerging as a valuable diagnostic tool in complex or unclear cases, though it is not yet widely available.
- Bruton tyrosine kinase (BTK) inhibitors are associated with a measurable risk of invasive fungal infections, with aspergillosis the most frequently reported.
- Host genetics (e.g. toll-like receptor variants) may influence susceptibility to invasive fungal disease, but this is not yet used clinically.
- Azole antifungal drugs remain high-risk for drug–drug interactions, particularly in patients receiving cancer therapies.
- Basic science research continues to identify new fungal targets and pathways, which may inform future treatments.
Contents
- Diagnosis and difficult cases
- Treatment-related risk and immunosuppression
- Genetics and susceptibility
- Asthma and Aspergillus sensitisation
- Drug interactions
- Emerging research and future treatments
- What this means for patients
- When to seek medical advice
Diagnosis and difficult cases
When aspergillosis looks like something else
A case report
(Ji H et al., 2026 – full text)
describes a patient with acute leukaemia who developed widespread “miliary” lung nodules—an imaging pattern classically associated with tuberculosis.
Despite this, the final diagnosis was invasive pulmonary aspergillosis (IPA).
Clinical interpretation
- Radiological appearances in immunocompromised patients can be non-specific.
- Aspergillosis may present without classic features such as halo signs or cavitation.
- Coinfection (e.g. TB + fungal disease) can further complicate interpretation.
This reinforces an important principle in clinical practice: lack of response to treatment should prompt reconsideration of the diagnosis.
The emerging role of mNGS
In this case, metagenomic next-generation sequencing (mNGS) helped establish the diagnosis by detecting fungal DNA directly from clinical samples.
Strengths of mNGS
- Broad pathogen detection (fungi, bacteria, viruses)
- Useful in culture-negative infections
- Can identify unexpected pathogens
Current limitations
- Limited availability outside specialist centres
- Cost and turnaround time
- Interpretation challenges (distinguishing infection from colonisation)
Bottom line: mNGS is promising, but currently complements rather than replaces standard diagnostics (culture, PCR, antigen testing).
Treatment-related risk and immunosuppression
BTK inhibitors and invasive fungal infection
A systematic review and meta-analysis
(PMID: 41954633)
including over 23,000 patients found that:
- Aspergillosis was the most commonly reported invasive fungal infection
- Central nervous system involvement was reported in a subset
Why BTK inhibitors increase risk
- They impair B-cell signalling
- They affect macrophage and neutrophil function
- This reduces the body’s ability to control fungal spores
Clinical implications
- Risk stratification is important
- Some patients may require antifungal prophylaxis
- Early recognition of symptoms is critical
This aligns with increasing recognition that modern targeted therapies can have unintended immunological effects.
Genetics and susceptibility
The role of innate immunity
A systematic review
(PMID: 41962654)
examined toll-like receptor (TLR) polymorphisms and fungal infection risk.
TLRs are part of the innate immune system and are responsible for recognising fungal components such as:
- β-glucans
- Cell wall proteins
Key insight
- Certain genetic variants were more frequently reported in patients with invasive aspergillosis
Important context:
- This does not yet translate into routine testing
- It may become relevant in the future for personalised risk prediction
Asthma and Aspergillus sensitisation
A 12-week prospective study
(PMID: 41949214)
found that:
- ~29% of asthma patients were sensitised to Aspergillus fumigatus
- No significant short-term differences in outcomes were seen compared to non-sensitised patients
Interpretation
- Sensitisation alone does not necessarily indicate active disease
- Clinical context remains critical
Important distinction:
- Sensitisation = immune response to Aspergillus
- ABPA (Allergic Bronchopulmonary Aspergillosis) = a specific inflammatory disease requiring treatment
Drug interactions
Itraconazole and erlotinib interaction
A case report
(PMID: 41953502)
demonstrated increased exposure to erlotinib when co-administered with itraconazole.
Mechanism
- Itraconazole inhibits CYP3A4
- This reduces drug metabolism
- Drug levels rise, increasing risk of toxicity
Clinical message
- Always review medications when starting antifungals
- Particular caution is needed in cancer, transplant, and multi-morbid patients
Useful tool:
Antifungal Interactions Checker
Emerging research and future treatments
Epigenetic regulation in Aspergillus fumigatus
A study
(PMID: 41928566)
identified the role of HosA in regulating fungal growth and virulence.
This type of work helps identify:
- Potential drug targets
- Mechanisms of antifungal resistance
New experimental antifungal compounds
A review
(Full text (PMC))
discusses sodium new houttuyfonate (SNH), which has shown activity in animal models of invasive aspergillosis.
Important caution:
- This is early-stage research
- It is not available as a treatment
What this means for patients
- Aspergillosis can sometimes be difficult to diagnose, especially if symptoms overlap with other conditions.
- If treatment is not working, your medical team may need to review or repeat tests.
- Some medications (especially for cancer or immune conditions) can increase risk of fungal infection.
- Antifungal medications are effective but require careful monitoring for interactions.
- New research is promising, but most advances take time to reach routine care.
When to seek medical advice
Seek medical attention urgently if you have:
- Worsening breathlessness
- Persistent fever
- Coughing up blood
- New chest pain
- Symptoms not improving with treatment
If you are immunocompromised, symptoms may progress quickly and should be assessed promptly.
References
- Ji H et al. Front Fungal Biol, 2026
- Srisurapanont K et al. Blood Adv, 2026
- Pereira Staiger MF et al. Clin Microbiol Infect, 2026
- Yokota H et al. Case Rep Oncol Med, 2026
- Chauhan NK et al. Monaldi Arch Chest Dis, 2026
- Zhou Z et al. Virulence, 2026
- Fang L et al. Front Pharmacol, 2026
Author & Review
This article is part of the Aspergillosis.org weekly research update series. It is intended for general educational purposes and reflects a structured summary of recent research.
Disclaimer: This content is not a substitute for medical advice. Always consult your healthcare team for individual care decisions.
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