🔍 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.

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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).

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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.

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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.

• OA FungiScope study (Mycoses 2025) ·

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.)

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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.