🔬 Emerging Research for Aspergillosis

Aspergillosis is a complex group of diseases caused by the Aspergillus fungus. Ongoing research is uncovering new ways to diagnose, treat, and prevent these conditions—offering hope for improved care and long-term outcomes. This page outlines current areas of promising research relevant to patients, carers, and healthcare professionals.

⏱️ Has Research Accelerated Over Time?

Yes. Over the last 40 years, research into aspergillosis and fungal infections has significantly accelerated due to:

• Rising awareness of fungal diseases in immunocompromised patients
• Improved diagnostic technology (e.g. PCR, lateral flow tests, next-gen sequencing)
• New drug development in response to growing azole resistance
• Greater investment from both academic institutions and industry
• Dedicated centres like the UK National Aspergillosis Centre driving specialist research
• Fungal infections gaining WHO recognition as emerging public health threats

In the 1980s and 1990s, progress was relatively slow. Since the early 2000s—and especially after the COVID-19 pandemic revealed the risks of fungal co-infection—momentum has increased markedly.

1. 🧪 Antifungal Drug Development

Resistance to azole antifungals is a growing concern. Several new antifungal agents are in development:

🔸 Olorofim (F2G)

• First-in-class orotomide antifungal
• Shows activity against Aspergillus, including azole-resistant strains
• Currently in phase III trials for invasive and chronic pulmonary aspergillosis

🔸 Ibrexafungerp and Fosmanogepix

• New antifungals with different mechanisms of action
• Potentially effective in combination or for resistant cases

🔸 Inhaled Antifungals

• Trials of inhaled itraconazole, posaconazole, and PC945 (opelconazole) for direct delivery to the lungs
• Aim: higher local drug concentrations with fewer side effects

2. 🧬 Biologics and Immune Modulation

🧭 What’s Next in Biologic Therapies for Severe Asthma?

Several next-generation biologics are under development, aiming to:

• Broaden coverage for patients who don’t respond to existing biologics
• Target upstream pathways (beyond IL‑5, IL‑4/13, or IgE)
• Offer once-yearly dosing or dual-target activity

Examples include:

• Depemokimab: A long-acting anti-IL‑5 antibody in phase 3 trials (GSK)
• CSJ117: An inhaled anti-TSLP monoclonal antibody fragment (Novartis)
• RG6354: Targeting IL-33 pathway, an upstream trigger in type 2 and non-type 2 asthma
• Dual Biologics: Exploratory research combining two targets (e.g., IL‑5 + IL‑4 or TSLP + IL‑13)

These developments may also benefit subsets of aspergillosis patients with severe asthma or ABPA who have not fully responded to current biologics. Research is exploring biologic therapies that reduce allergic inflammation or modulate immune response, particularly for ABPA (Allergic Bronchopulmonary Aspergillosis) and overlapping asthma subtypes.

✅ Biologics Currently in Use for ABPA

Omalizumab (Xolair) – Anti-IgE

• Target: IgE antibody—blocks allergic immune response to Aspergillus antigens.
• Evidence: Studies show significant reductions in exacerbations, IgE, steroid use, and improved lung function.
• Clinical Use: Widely used off-label in ABPA patients with raised IgE and asthma features.

Mepolizumab (Nucala) – Anti–IL‑5

• Target: IL‑5 cytokine—reduces eosinophil inflammation.
• Use: Steroid-sparing and symptom control in eosinophilic ABPA.

Benralizumab (Fasenra) – Anti–IL‑5 Receptor

• Target: IL‑5Rα—causes rapid eosinophil depletion.
• Use: Clearing mucus plugs and reducing flares; often used after mepolizumab failure.

Dupilumab (Dupixent) – Anti–IL‑4Ra

• Target: IL‑4/IL‑13 pathway—type 2 inflammation.
• Use: Shown to reduce IgE levels and ABPA exacerbations.

Tezepelumab (Tezspire) – Anti‑TSLP

• Target: TSLP—broadly suppresses upstream allergic inflammation.
• Evidence: Early reports suggest benefit in ABPA patients, though data are limited.

📊 Real-World Effectiveness

UK-based retrospective study (2014–2022):

• 74 ABPA patients treated with biologics
• 65% showed ≥50% reduction in steroid use after 12 months
• 35% switched due to lack of effect or side effects

📌 Summary Table of Biologics

Biologic	Target	Use in Aspergillosis	Key Benefits
Omalizumab	IgE	ABPA with raised IgE	↓ Exacerbations, ↓ steroids, ↑ FEV₁
Mepolizumab	IL‑5	Eosinophilic ABPA	Steroid-sparing, symptom control
Benralizumab	IL‑5Rα	Refractory cases	Mucus clearance, eosinophil depletion
Dupilumab	IL‑4/IL‑13	Mixed allergic/eosinophilic ABPA	↓ IgE, ↓ flares
Tezepelumab	TSLP	Emerging, broad asthma-ABPA	Broad inflammation control

3. 🧫 Diagnostic Advances

Improved diagnostics aim to detect disease earlier and more accurately:

• Lateral flow tests (e.g., Aspergillus-specific LFD) for rapid diagnosis
• PCR testing and galactomannan assays in blood, sputum, or BAL
• Aspergillus-specific IgG and IgE testing to distinguish CPA, ABPA, and colonisation
• Next-generation sequencing (NGS) for strain typing and resistance detection

4. 🌡️ Non-Pharmacological Research

🌀 Airway Clearance and Physiotherapy

• Trials assessing flutter devices, oscillating PEP, and manual physiotherapy in chronic aspergillosis and bronchiectasis

🥦 Nutrition and Gut-Lung Health

• Increasing interest in the role of dietary fibre, gut microbiome, and short-chain fatty acids in immune defence and lung inflammation

💨 Air Quality and Exposure

• Home-based studies evaluating the impact of HEPA filters, spore counts, and environmental remediation

5. 🛡️ Preventative Strategies

🫁 Lung/Nasal Coatings (Experimental)

• Early research into coating the lungs or nasal passages to prevent infection
• Not yet in human trials for aspergillosis, but promising in animals for viral and bacterial prevention

💉 Vaccines

• No approved vaccines yet, but exploratory work is underway for high-risk populations

6. 🧫 Clinical Trials in Aspergillosis

A wide range of clinical trials are currently underway or recently completed, focusing on new antifungals, biologics, and non-pharmacological interventions:

🧪 Antifungal Trials

• Rezafungin – A long-acting echinocandin administered once weekly, currently in trials for prevention and treatment of invasive fungal infections, including those caused by Aspergillus species
• Olorofim (F2G) – Phase III trials for CPA and invasive aspergillosis
• PC945 (Opelconazole) – Inhaled triazole for CPA and prophylaxis in immunocompromised patients
• Fosmanogepix and Ibrexafungerp – Investigated in resistant and invasive fungal disease

🧬 Biologic Trials

• Tezepelumab and Dupilumab – Trials involving patients with ABPA and severe asthma
• Depemokimab (GSK) – Phase III trials for long-acting IL‑5 blockade

🌡️ Other Trials

• Airway clearance studies – Use of physiotherapy and flutter/PEP devices in chronic pulmonary aspergillosis
• Gut microbiome and fibre supplementation – Exploring anti-inflammatory potential in lung disease

These trials often recruit patients from UK centres including the National Aspergillosis Centre, and are registered on databases such as ClinicalTrials.gov.

7. 🤝 Patient Support and Outcomes Research

📊 Real-World Evidence

• Registries and observational studies (e.g., LIFE, FungiScope) gathering long-term data on patients with CPA, ABPA, SAFS, and invasive disease

👥 Quality of Life and Patient-Reported Outcomes

• Surveys and tools to measure impact of fatigue, breathlessness, mental health, and medication side effects
• Aim: improve personalised care and support services

🧭 Where to Find Updates

• ClinicalTrials.gov – searchable by “aspergillosis”
• Aspergillosis.org – for patient-friendly research summaries
• National Aspergillosis Centre (UK) – involved in many UK-based studies
• Journal of Fungi, Medical Mycology, Clinical Infectious Diseases – leading sources of peer-reviewed studies

📢 Final Word

Research into aspergillosis is accelerating across drug development, diagnostics, prevention, and patient support. While not all options are available yet, many are in trials or early clinical use. Staying informed and involved—whether through trial participation or feedback—helps shape better care for all.

Updated July 2025 – suitable for patients, clinicians, and advocacy groups.

 

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