🧩 NAC Aspergillosis Research Digest Aspergillosis (October 2025: week 43)

Highlights

  • Post‑transplant GVHD & IFI risk: In paediatric liver transplant recipients with GVHD, invasive fungal infection (aspergillosis/candidiasis) was the dominant cause of death; paper advocates PK‑guided monitoring of JAK inhibitors and tacrolimus for safer immunosuppression. (Pediatr Transplant; free full text) PMID: 41039701 | PMCID: PMC12491760
  • Inhaled opelconazole: In‑vitro + clinical data suggest negligible drug–drug interaction (DDI) risk for the investigational inhaled triazole opelconazole, supporting development for pulmonary aspergillosis. (JAC) PMID: 41105437
  • Isavuconazole DDI mapping: PBPK modelling compares isavuconazole with other azoles and proposes model‑informed dosing for anticancer drugs—useful in haem‑onc co‑prescribing. (CPT:PSP) PMID: 41104611
  • CAR‑T fungal infections: Registry analysis after CD19 CAR‑T for B‑cell lymphoma reports invasive aspergillosis as the commonest mould IFI (11/32). (CMI) PMID: 41109429
  • Air pollution & IPA: Two multicentre cohorts link higher fine particulate (PM2.5) exposure before admission with invasive pulmonary aspergillosis in severe pneumonia. (EBioMedicine) PMID: 41106023
  • Mechanisms of resistance/virulence: A bioRxiv preprint identifies a long non‑coding RNA (afu‑182) that modulates triazole susceptibility and virulence in A. fumigatus. (Preprint) PPR: PPR1101933
  • Burden estimates (Poland): National modelling updates burden for IA, CPA, ABPA, SAFS—useful for service planning and advocacy. (Sci Rep; open) PMID: 41087447 | Full text

Diagnostics

  • Dental/ENT interface: In a retrospective implant‑centred series, chronic sinusitis and aspergillosis were histopathologically confirmed in a subset of sinus augmentation candidates; authors discuss when 3D imaging is warranted pre‑procedure. (Int J Oral Maxillofac Implants) PMID: 41105467
  • Environmental surveillance: Post‑hurricane housing study identified Aspergillus spp. in water‑impacted homes, contextualising environmental exposure risk for ABPA/CPA. (Sci Rep; open) PMID: 41087584

Therapeutics & stewardship

  • Opelconazole (inhaled triazole) DDI profile appears favourable (see above). Consider future role for adjunct/targeted lung delivery once efficacy data mature. PMID: 41105437
  • Isavuconazole PBPK‑based recommendations may aid co‑administration with anticancer agents; still requires centre‑specific DDI checks and, where available, TDM. PMID: 41104611
  • Novel antifungal target: A selective acetyl‑CoA synthetase inhibitor shows antifungal activity in Nat Commun—early‑stage discovery but potentially relevant to future azole‑resistant IA/CPA. (Nat Commun; open) PMID: 41087359

Epidemiology & special populations

  • CAR‑T recipients: IA predominance among mould IFIs underscores the need for surveillance, rapid diagnostics (GM/PCR), and early therapy in post‑CAR‑T care pathways. PMID: 41109429
  • Air quality: Association between PM2.5 and IPA suggests including environmental history in risk assessments for severe pneumonia patients. PMID: 41106023
  • Veterinary reservoir: Review from Turkey highlights aspergillosis as a major poultry disease—relevance for occupational exposures and broader One‑Health messaging. (Vet Med Sci; open) PMID: 40988581

Surgery & case‑based learning

  • CPA with infected bulla: Case report supports surgical resection as an option in selected CPA phenotypes with localised disease. (Clin Case Rep; open) PMID: 41103592

Guidance / practice notes

  • For post‑transplant GVHD, ensure PK monitoring (tacrolimus, JAK inhibitors) and early IFI screening (GM/LFA ± PCR) to balance GVHD control against infection risk. PMID: 41039701
  • In CAR‑T and severe pneumonia pathways, include combined diagnostics (BAL GM, Aspergillus PCR ± culture) and rapid initiation of active triazoles where IA is probable.
  • Consider air quality and environmental exposures (post‑disaster housing, poultry) in patient education and prevention.

References & links

  • Sawada K et al. PK Monitoring of JAK Inhibitor and Tacrolimus in post‑LT GVHD. Pediatr Transplant. 2025. PMID: 41039701 | PMCID: PMC12491760
  • Cass LMR et al. Opelconazole DDIs. J Antimicrob Chemother. 2025. PMID: 41105437
  • Goosen TC et al. Isavuconazole DDI PBPK. CPT: Pharmacometrics Syst Pharmacol. 2025. PMID: 41104611
  • Bouvier A et al. IFIs after CD19 CAR‑T. Clin Microbiol Infect. 2025. PMID: 41109429
  • Zhou H et al. PM2.5 & IPA. EBioMedicine. 2025. PMID: 41106023
  • Poudyal NR et al. lncRNA afu‑182 & azole susceptibility. bioRxiv. 2025. Preprint
  • Tamagawa K et al. Lung resection in CPA with infected bulla. Clin Case Rep. 2025. PMID: 41103592
  • Vélez‑Torres LN et al. Aspergillus in water‑impacted homes. Sci Rep. 2025. PMID: 41087584
  • Krzyściak PM et al. Burden of serious mycoses in Poland. Sci Rep. 2025. PMID: 41087447
  • Alhassani ANA et al. Aspergillosis in poultry (Turkey). Vet Med Sci. 2025. PMID: 40988581

 

by GAtherton

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

🧬 Focus Review — Chronic Aspergillosis (October 2025)

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

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

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

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

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

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

  • Read full paper on PubMed

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

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

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

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

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

  • Read full paper on PMC

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

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

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

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

  • This approach helps avoid unnecessary treatments and invasive tests.

  • Read full paper on Frontiers

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

by GAtherton

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

Revised ISHAM-ABPA working group guidelines (2024)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Epidemiology & Clinical Cohorts

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

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

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

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

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

Invasive aspergillosis in ICU settings (2025 review)

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

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

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

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

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

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

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

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

  • Review (ScienceDirect).

Diagnostics: Biomarkers, Molecular, Imaging & Novel Methods

GM antigen & Aspergillus IgG negative “escape” cases

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

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

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

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

Molecular diagnosis, qPCR & NGS advances (2025 review)

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

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

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

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

Microscopy, GM, PCR comparative pilot (2025)

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

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

  • Study (ScienceDirect). ERS Publications

Emerging spectroscopy / imaging techniques (TERS)

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

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

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

Therapeutics, Resistance & New Drugs

Olorofim (F901318) — Phase IIb results (2025)

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

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

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

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

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

Review of olorofim in aspergillosis

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

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

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

  • epocrates.com

Pipeline and alternative antifungals

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

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

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

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

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

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

Azole resistance & clinical implications

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

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

  • Nature Communications 2024 · Review PubMed.

Therapeutic drug monitoring & combination strategies

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

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

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

Immunology, Host Responses & Biologics

Immunopathogenesis review (2023)

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

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

  • OA review (Front Immunol 2023).

Biologics in ABPA / severe asthma

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

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

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

  • ISHAM ABPA paper · PubMed.

by GAtherton