Research Archives - Page 6 of 13 - Aspergillosis Patients & Carers Support

🫁 Understanding Chronic Cough in Aspergillosis

What the latest British Thoracic Society statement means for you

🌬️ Why This Matters

If you live with aspergillosis, Allergic Bronchopulmonary Aspergillosis (ABPA), or bronchiectasis, coughing can dominate your life. It’s tiring, painful, and socially awkward — especially when people assume it means infection.

Doctors used to see cough as just a symptom of another problem, but the British Thoracic Society (BTS) Clinical Statement on Chronic Cough in Adults (2023) recognises something new:

For many people, a cough can become a condition in its own right — caused by airway and nerve hypersensitivity, not just infection.

This matters for aspergillosis patients because fungal allergy and inflammation make the airways especially sensitive.

💡 What Is “Chronic Cough”?

A chronic cough is one lasting eight weeks or more.
It may be:

Dry – little or no mucus
Productive – thick sputum (common in bronchiectasis or chronic aspergillosis)
Triggered by dust, cold air, perfume, or strong scents

For people with aspergillosis, several overlapping causes may exist:

Fungal colonisation or infection
Allergic inflammation (ABPA)
Bronchiectasis and mucus retention
Reflux or post-nasal drip
Nerve hypersensitivity

This is why one treatment rarely fixes everything — different “treatable traits” must be addressed together.

🧬 Why It Happens

1️⃣ The Hypersensitive Cough Reflex

People with aspergillosis often develop overactive airway nerves — so normal irritants like dust, scent, or cold air trigger coughing fits.

This “cough reflex hypersensitivity” happens because:

Ongoing inflammation damages the airway lining.
Nerve endings in the throat and lungs become over-responsive.
Even mild triggers set off powerful reflexes.

This is a real physiological process, not psychological.
It’s why cough can continue even when infection is under control.

2️⃣ Treatable Traits – Finding the Real Drivers

Treatable Trait	What It Means	What Helps
Airway infection or colonisation	Persistent fungi or bacteria	Antifungal or antibiotic therapy, sputum tests
Allergic inflammation	ABPA or asthma-type airway swelling	Corticosteroids, biologics (e.g., mepolizumab, benralizumab)
Cough reflex hypersensitivity	Overactive airway nerves	Speech therapy, nerve-modulating medication
Airway clearance problems	Mucus that’s hard to shift	Physiotherapy, saline or mucolytic therapy
Reflux or postnasal drip	Acid or sinus drainage irritation	Reflux management, ENT care

Identifying these traits helps your clinician personalise treatment.

💊 Medications That Can Cause or Worsen Cough

The BTS statement highlights that some medicines can trigger or amplify chronic cough — especially in people with already-sensitive lungs.

🔹 ACE Inhibitors (Blood pressure or heart disease)

Examples: Ramipril, Lisinopril, Enalapril, Perindopril

Can cause a dry, tickly cough due to bradykinin build-up.
Happens in ~1 in 5 users, sometimes months after starting.
GP can switch to a similar drug (ARB – e.g., losartan) that doesn’t cause cough.

🔹 Beta Blockers (Heart or migraine medicines)

Examples: Atenolol, Propranolol, Bisoprolol

May tighten airways, worsening wheeze or cough.
Safer “lung-selective” versions exist but should still be monitored.

🔹 Inhalers

Examples: Fluticasone, Budesonide, Salbutamol

Can irritate the throat if used without a spacer or if technique is poor.
Always rinse or gargle after use, and ask your pharmacist to review inhaler technique.

🔹 Antifungal or Reflux Medicines

Antifungals (itraconazole, voriconazole) don’t directly cause cough, but reflux or nausea can trigger coughing indirectly.
PPIs (omeprazole, lansoprazole) usually help reflux-related cough, but long-term use should be reviewed regularly.

🔹 Other Drugs

Amiodarone, methotrexate, and some biologics can rarely cause cough due to lung inflammation.
Nasal sprays or lozenges with menthol/alcohol may irritate already-sensitive airways.

💬 If you suspect a medicine is contributing, don’t stop it suddenly — speak to your doctor or pharmacist first.
They can review interactions using the
👉 BNF Interactions Checker – NICE Medicines Guidance.

🔍 How Doctors Assess Chronic Cough

BTS recommends a structured pathway:

Basic tests: chest X-ray, spirometry, bloods (eosinophils, IgE), FeNO if available.
Further tests: CT scan, allergy or sputum studies if initial tests are abnormal.
Trait-based review: identifying overlapping issues — fungal, allergic, nerve-related, or reflux-related.
Specialist referral: to a Cough Clinic or Aspergillosis Centre if symptoms persist.

🧴 Pharmacists: Your Safety Specialists

Pharmacists — hospital or community — are crucial for managing long-term cough and medication safety:

Check for cough-inducing drugs or interactions.
Advise on best timing for antifungal and steroid doses.
Help switch to fragrance-free personal or cleaning products.
Liaise with your GP and consultant to fine-tune treatment.

🧭 Regular medication reviews every few months can prevent small problems becoming major triggers.

💬 How It Feels — and Why It’s Misunderstood

People with aspergillosis often describe:

“A tickle that turns into a spasm I can’t stop.”
“People think I’m ill, but it’s just the air or perfume.”

This happens because your airway nerves and immune cells are already primed.
Coughing doesn’t mean you’re infectious — it’s your body’s protective reflex in overdrive.

🩺 What Helps Most

Optimise your aspergillosis and ABPA treatment.
Cough-control physiotherapy or speech therapy for nerve-related cough.
Airway clearance techniques for mucus.
Identify and avoid irritants: perfume, smoke, strong detergents, cold air.
Ask about biologics if inflammation remains active despite steroids.
Use nerve-modulating medicines only under specialist advice.

🧘 Emotional Health Matters Too

Living with a chronic cough can cause anxiety, embarrassment, and isolation.
Support from counsellors, CBT therapists, or patient groups helps manage this stress — and can actually reduce cough frequency through better relaxation and breathing control.

🌱 Key Takeaway

Chronic cough in aspergillosis isn’t “just a symptom” — it’s often a mix of airway inflammation, fungal allergy, nerve hypersensitivity, and sometimes side effects of medicines.

The good news is that every contributing factor is treatable once identified — and cough can improve significantly with the right combination of medical, physical, and environmental care.

🔗 Trusted Resources

by GAtherton

🧬 Article 2: When Microbes Turn Hostile – The Evolutionary Pressures Behind Infection

Subtitle: Why stable colonisation sometimes shifts into active disease

Introduction

If microbes can live quietly in the lungs for years, why do they sometimes turn aggressive?
Evolutionary biology and microbiome research show that infection often develops because of environmental pressures — not by design, but as a by-product of survival in a changing ecosystem.

1. Antibiotic Pressure

Repeated antibiotic courses kill sensitive strains and leave behind resistant survivors.
These survivors often produce thicker biofilms and inflammatory molecules, which protect them but also damage airway tissue.
Over time, this selection creates harder-to-treat, more inflammatory strains.

2. Nutrient Competition

Airways are crowded ecosystems.
When nutrients run low, microbes compete by releasing toxins, proteases, and iron-scavenging molecules.
These harm competitors — and incidentally harm the lung.

3. Biofilms and Mutation

Within biofilms, bacteria and fungi evolve quickly.
Mutations can accumulate, producing hypermutator strains that are well adapted to chronic survival but also more inflammatory.

4. Host Factors

Changes in the body — reduced immunity, steroid use, diabetes, or viral infections — relax immune control.
Organisms that were previously contained can now proliferate.
Similarly, damaged or scarred airways provide sheltered niches where microbes thrive.

5. Microbiome Collapse

The healthy lung microbiome helps regulate inflammation and suppress invaders.
When broad antibiotics or infections reduce diversity, opportunists like Pseudomonas or Aspergillus can expand unchecked.

6. Collateral Damage, Not Intent

Most microbes don’t “want” to be pathogenic — they’re simply adapting to survive.
Their survival strategies (biofilms, enzymes, toxins) cause collateral damage to airway tissue.
So, pathogenicity is often an accidental consequence of survival pressure.

7. Cycles of Stability and Flare-Ups

Chronic airway diseases often follow repeating cycles:

Stable colonisation – coexistence with minimal inflammation
Disruption – antibiotics, viral infection, or new strain
Flare-up – inflammation and tissue damage
Partial recovery – new stable community forms

Each cycle leaves the microbial ecosystem slightly altered — selecting for organisms that can survive stress and immune attack.

Evolutionary Summary

Pressure	Effect on Microbes	Result for Host
Antibiotics	Resistant, stress-adapted strains	Harder-to-treat infection
Nutrient limitation	Toxin and enzyme producers	Tissue damage
Immune suppression	Less control of microbes	Opportunistic growth
Microbiome loss	Opportunist expansion	Reduced resilience
Biofilm evolution	Genetic drift, persistence	Chronic inflammation

Key Takeaway

Microbes evolve under pressure from antibiotics, immune stress, and competition.
They don’t plan to harm the host — they adapt to survive.
Unfortunately, those same adaptations often make them more damaging and persistent.

This is why good airway care, careful antibiotic use, and microbiome-friendly approaches are essential to keep the system in balance.

👉 Read also: Colonisation vs Infection in Airways Disease
(Learn how to recognise the difference, when treatment is needed, and how to keep microbial balance.)

by GAtherton

🧬 From Scottish Discovery to American Pharmacy Shelf: The Story of Brensocatib

Sometimes a medicine begins life in one country but reaches patients first in another. The new bronchiectasis drug brensocatib is a perfect example — discovered in Scotland, yet first approved for use in the United States.
Here’s how that happens, and what it tells us about how new treatments make their way to patients.

1️⃣ Discovery in Dundee

At the University of Dundee, scientists in the Drug Discovery Unit (DDU) were studying how certain white blood cells called neutrophils can cause long-term lung damage.
They identified an enzyme, DPP1 (dipeptidyl peptidase I), that activates destructive substances inside these cells.
Blocking DPP1 could calm inflammation without wiping out the body’s defences.
Their research produced a promising new compound — later named brensocatib — which safely switched off this process in lab studies.

2️⃣ Partnering to Go Global

Turning an early discovery into a medicine is an enormous task.
It costs hundreds of millions of pounds and can take 10–15 years.
The Dundee team partnered with Insmed, a biotechnology company based in New Jersey, USA, which had the funding and international trial experience to move brensocatib into large clinical studies.

3️⃣ Worldwide Trials

Insmed led major trials involving hundreds of people with non-cystic fibrosis bronchiectasis in hospitals across North America, Europe, and Asia.
Results showed that brensocatib reduced flare-ups and improved quality of life.
Because Insmed’s main offices and regulatory team are in the U.S., they submitted their results first to the U.S. Food and Drug Administration (FDA).

4️⃣ U.S. Approval

In 2025, the FDA approved brensocatib — the first drug of its kind to treat bronchiectasis.
American patients can now access it while other countries complete their reviews.

5️⃣ What Happens Next in the UK

In the UK, every new medicine goes through two steps:

The Medicines and Healthcare products Regulatory Agency (MHRA) checks that it is safe and effective.
Then NICE (the National Institute for Health and Care Excellence) reviews how well it works for its cost and decides whether the NHS should fund it.

NICE is expected to make its decision on brensocatib in July 2026.
Even if approved, it may first be offered to those with the most severe or frequent flare-ups while more real-world data are gathered.

💷 What Dundee Gained from Its Discovery

Although Dundee handed over development to a U.S. company, the university continues to benefit in several ways:

Financial return: Dundee receives upfront payments, milestone fees for each stage of progress, and royalties on global sales.
These funds support new drug discovery projects, student training, and research facilities.
Scientific impact: Brensocatib’s success highlights the strength of the Drug Discovery Unit’s model, showing that UK universities can produce world-class medicines.
Future partnerships: Dundee’s achievement attracts new collaborations and investment, ensuring that more early discoveries have a route to reach patients.

So while the drug is made and sold by Insmed, Dundee’s scientists — and their reinvested funding — continue to play a role in future breakthroughs.

🏭 Manufacturing: Turning Discovery into a Real Medicine

Once a new drug is approved, it still has to be produced safely, at scale, and consistently.
This is often a completely separate operation from the research or licensing stage.

For brensocatib, the chemical process that makes the active ingredient was developed by Dundee and Insmed scientists early on, but large-scale manufacturing is now carried out by specialist pharmaceutical plants under strict international standards known as Good Manufacturing Practice (GMP).

Because brensocatib is a small-molecule oral drug (a tablet, not an injection), it’s made in high-tech chemical manufacturing facilities, not hospitals or biologics plants.
These sites are often in Europe, the U.S., or Asia, depending on where the supply chains, raw materials, and quality-control systems are strongest.

Manufacturing is expensive — it must ensure every tablet is identical in purity, strength, and safety — but it’s also where economies of scale help keep the cost manageable once global production ramps up.

For the NHS and NICE, manufacturing details matter too, because:

They affect cost-effectiveness (how much the NHS will pay per course of treatment).
They influence availability — whether the company can supply enough medicine to meet demand once approved in the UK.

So, while the discovery began in Dundee and the approval started in the U.S., manufacturing is the bridge that makes it real — transforming a scientific idea into a medicine that can be prescribed to patients worldwide.

🌍 Why This Matters

This journey shows how scientific discovery is global.
A breakthrough can start in a Scottish laboratory, be developed with American funding, tested around the world, manufactured across several continents, and eventually come back to help patients in the UK.
It’s a reminder that international collaboration — between researchers, funders, manufacturers, and regulators — is what turns good science into real treatments.

by GAtherton

🧩 NAC Aspergillosis Research Digest Aspergillosis (October 2025: week 44)

Highlights

Pulmonary aspergillosis in chronic lung disease can be severe and life-threatening, especially in patients with underlying interstitial lung conditions. Prompt diagnosis and subtype-targeted treatment are crucial for better outcomes (7).
Advanced sinus imaging in dogs improves veterinary precision for diagnosing and treating fungal infections such as aspergillosis (1).
Poultry farms in Turkey are best protected against aspergillosis outbreaks through consistent hygiene and environment management (3).
Pediatric liver transplant patients remain at high risk of deadly fungal infections, so ongoing immune and drug monitoring is vital (2).
New antifungal agents such as isavuconazole are yielding positive results in children, adults, and drug-resistant cases (10).
Agricultural fungicide use is driving azole resistance in Aspergillus, prompting urgent "One Health" responses across medicine and farming (8).
Research is underway to determine the best antifungal prophylaxis for heart transplant recipients (6).
Case studies show severe treatment challenges for aspergillosis in post-tuberculosis and cancer patients (5), (9).

Pulmonary Aspergillosis in Lung Disease

Recent research examined the prevalence and outcomes of aspergillosis among patients with interstitial lung disease (ILD) and chronic respiratory disorders. The study highlights three major forms:

Invasive Pulmonary Aspergillosis (IPA): Occurs in roughly 2% of hospitalised ILD patients, presenting with symptoms such as fever, persistent cough, and rapid decline in lung function. Those prescribed steroids or immunosuppressants and showing certain lung scan features are at greater risk. Estimated 3-month mortality can reach 50%.
Chronic Cavitary Pulmonary Aspergillosis (CPA): Represents about 0.6% of cases in target populations, with slower onset but significant respiratory impairment over time. Mortality is lower than IPA but remains notable.
Allergic Bronchopulmonary Aspergillosis (ABPA): Occurs in about 3% of studied patients, typically with a better prognosis, though delayed care can worsen outcomes.

Diagnostic strategies involve serology, antigen testing, and imaging to distinguish subtypes and select appropriate antifungal therapy. The study urges multidisciplinary care and more effective protocols for immunosuppressed patients (7).

Veterinary and Animal Health

Advanced radiological mapping now allows veterinarians to better diagnose and treat sinus aspergillosis across various breeds. This enhances surgical accuracy and supports targeted case management (1).
Poultry studies highlight aspergillosis as a leading fungal threat, with hygiene as the most effective control tactic (3).

Human Health: Transplant, Immunosuppression, and Infection

Children undergoing liver transplants require ongoing immune suppression, which increases susceptibility to severe fungal infections like aspergillosis. This underscores the value of rigorous therapeutic monitoring (2).
Current protocols are evaluating which antifungal drugs work best in heart transplant recipients to prevent invasive fungal infections (6)

Clinical Complications and Case Reports

Case studies spotlight life-threatening adrenal crisis and aspergillosis in children recovered from TB and adults with leukaemia. Timely diagnosis and combined therapies are essential for recovery (5), (9)
Transplant patients are vulnerable to bacterial and fungal sinus infections, presenting significant diagnostic challenges (4).

Drug Resistance and Novel Treatments

The rise of azole-resistant Aspergillus, driven by agricultural fungicide use, is making some forms of aspergillosis harder to treat. Integrated medical and environmental interventions are needed to slow resistance (8)
New medications, such as isavuconazole, are being adopted for severe and resistant cases in paediatric and adult populations with positive early results (10).

Reference List

by GAtherton

🌬️ Inhaled Antifungal Treatments for Chronic Pulmonary Aspergillosis (CPA)

Updated: October 2025

💡 Why are inhaled antifungals being developed?

For people living with Chronic Pulmonary Aspergillosis (CPA), treatment usually involves long courses of oral antifungal tablets such as itraconazole, voriconazole, or posaconazole.
These medicines circulate through the whole body to reach the lungs — but sometimes they cause side-effects, interact with other drugs, or fail to reach high enough levels in thick mucus, cavities, or scarred areas of lung tissue.

Inhaled antifungal therapy aims to solve this problem by delivering medicine directly to the lungs using a nebuliser or inhaler device.
This can potentially mean:

✅ Higher drug levels exactly where infection is active
⚡ Faster local action
🚫 Fewer whole-body side-effects
🧩 Fewer drug interactions

This approach is especially promising for patients with localized lung disease, such as CPA or aspergillus bronchitis, where the fungus lives in damaged parts of the lung.

💊 Current inhaled antifungal options (used off-label)

🧪 Nebulised Amphotericin B

At the moment, nebulised amphotericin B is the only inhaled antifungal used in hospitals, although it is off-label for CPA.

It is more commonly used to prevent infection in people who have had a lung transplant or who are severely immunocompromised.
In some specialist centres, it may be used as maintenance therapy or an add-on for CPA if other antifungals have not worked or cannot be tolerated.

Advantages

High concentration in lung tissue
Minimal effects on other organs (especially the kidneys)

Drawbacks

Possible airway irritation (cough, tight chest, wheezing)
Requires specialist supervision and appropriate nebuliser equipment

🔬 New treatments in development

💨 Opelconazole (also called PC-945)

Opelconazole is a new inhaled triazole antifungal developed by Pulmocide Ltd in the UK.
It works in the same way as existing azole antifungals — by blocking the fungal enzyme CYP51 — but has been specially designed to stay in the lungs and minimise side-effects elsewhere.

In laboratory and early human studies, opelconazole has shown:

Strong activity against Aspergillus fumigatus
High and lasting drug levels in the lungs
Very low blood levels (reducing risk of toxicity and drug interactions)
Good tolerability in early trials

Although not yet licensed, it has been used compassionately in small numbers of patients with difficult-to-treat lung aspergillosis at centres such as Manchester and London.

🧾 Current and recent clinical trials

Trial ID	Treatment	Condition	Purpose / Summary	Status
NCT06447402	Nebulised Amphotericin B vs Saline	Chronic Pulmonary Aspergillosis	Tests whether regular nebulised amphotericin can help prevent CPA relapse compared with saline.	Recruiting
NCT03656081	Itraconazole ± Nebulised Liposomal Amphotericin B	CPA	Compares oral itraconazole alone versus itraconazole plus inhaled amphotericin for symptom and scan improvement.	Completed – results pending
NCT05238116	Inhaled Opelconazole + Standard Therapy	Refractory Invasive Pulmonary Aspergillosis	Phase 3 trial evaluating safety and added benefit of inhaled opelconazole. UK, EU, and US sites.	Recruiting
NCT05037851	Inhaled Opelconazole (PC-945)	Post-Lung Transplant Prophylaxis	Assesses prevention of fungal infection after transplant. Found well tolerated.	Completed
PubMed 34058036	Nebulised Amphotericin B vs Oral Itraconazole	Pulmonary Aspergilloma (CPA subset)	Six-month open study found similar improvement rates between inhaled amphotericin and oral itraconazole.	Completed

👉 You can look up any of these studies on ClinicalTrials.gov by entering the trial ID (e.g. NCT06447402).

⚠️ Things to keep in mind

Not yet routine — Inhaled antifungals are available only in research or specialist centres.
Limited evidence — Most data come from transplant or invasive aspergillosis studies, not chronic infection.
Delivery challenges — Damaged or scarred areas of lung may be hard for inhaled drugs to reach.
Possible side-effects — Coughing or mild bronchospasm are common; pre-treatment with an inhaler may help.
Monitoring still needed — Even with inhaled therapy, your care team will continue to check symptoms, lung scans, and blood markers (such as Aspergillus IgG).

🧭 Questions to ask your specialist

If you are interested in this type of therapy, you could ask:

Does my centre offer nebulised amphotericin as part of CPA care?
Are there any clinical trials nearby (for example NCT06447402 or NCT05238116)?
Could an inhaled antifungal be used with my current oral treatment?
What are the side-effects and how are they monitored?
What nebuliser device is required and how often would I use it?

🏥 UK research centres involved

Current UK involvement is mainly through:

National Aspergillosis Centre, Wythenshawe Hospital (Manchester)
Royal Brompton and Harefield Hospitals (London)
UK transplant centres participating in Pulmocide’s opelconazole studies

🗝️ Key takeaway

Inhaled antifungal medicines are an exciting development that could make CPA treatment safer and more targeted in the future.
For now, they are mainly available through clinical trials or specialist centres, but the early results are promising — especially for those who have struggled with oral antifungal side-effects or limited success.

If you’re interested, speak to your CPA specialist or the National Aspergillosis Centre team about ongoing research and eligibility.

by GAtherton

🧬 The Story of Brensocatib: A New Way to Calm Lung Inflammation

What Is Brensocatib?

Brensocatib is a new type of anti-inflammatory medicine being developed to protect the lungs from long-term damage caused by overactive immune cells, especially neutrophils.
It is being tested by the company Insmed in people with bronchiectasis, but it may also help those with aspergillosis and other chronic lung diseases where inflammation is a major problem.

Brensocatib is taken as a once-daily tablet—not an injection.

Why Was It Developed?

In conditions like ABPA (Allergic Bronchopulmonary Aspergillosis) and CPA (Chronic Pulmonary Aspergillosis), inflammation is often persistent.
The lungs attract neutrophils, which are immune cells that normally destroy germs.
However, when too many neutrophils gather, they release enzymes that damage healthy lung tissue, thicken mucus, and make infection easier for fungi and bacteria.

Researchers realised that if they could turn down the destructive part of neutrophil activity—without turning off the immune system completely—they might be able to break the cycle of inflammation and infection.

How Brensocatib Works

Brensocatib blocks a switch inside the bone marrow called DPP1 (dipeptidyl peptidase-1).
DPP1’s job is to “activate” enzymes inside newly formed neutrophils before they enter the bloodstream.

By blocking DPP1, brensocatib stops neutrophils from producing harmful enzymes such as neutrophil elastase.
These neutrophils can still travel to the lungs and fight infection, but they cause less collateral damage.

👉 In short: brensocatib reduces lung injury caused by over-active immune cells, not by suppressing immunity itself.

Not a Biologic – A Different Type of Treatment

It’s important to understand that brensocatib is not a biologic.

Feature	Biologic drugs (e.g. mepolizumab, dupilumab)	Brensocatib
Made from	Complex proteins or antibodies	Small chemical molecule
How it’s given	Injection or infusion	Oral tablet
What it targets	Specific immune pathways (e.g. IL-5, IL-4)	Enzyme activation in neutrophils
Purpose	Block inflammatory signals	Reduce tissue-damaging enzymes
Typical use	Severe asthma, ABPA, autoimmune diseases	Bronchiectasis, chronic airway inflammation

So, while biologics act by targeting immune messengers in the bloodstream, brensocatib works deeper—at the level of neutrophil development.
The two approaches are different but potentially complementary.
Some people in future may benefit from a combination, depending on their pattern of inflammation.

The Development Story

Early research (2010s): Scientists found that blocking DPP1 prevented lung injury in animal studies.
Insmed’s discovery: Brensocatib was developed as an oral, selective DPP1 inhibitor.
Phase 2 WILLOW trial (2020): In people with bronchiectasis, brensocatib significantly reduced flare-ups and lowered airway inflammation.
Phase 3 ASPEN trial (2022–2025): A large international study now nearing completion; results are expected soon.

If successful, brensocatib could become the first approved DPP1 inhibitor for long-term inflammatory lung disease.

Why This Matters for Aspergillosis Patients

People living with aspergillosis often also have bronchiectasis, where inflammation causes persistent mucus, infection, and breathlessness.
Current treatments such as steroids, antifungals, and biologics can help, but each has limits.

Brensocatib could:

Reduce airway inflammation without steroid side-effects
Protect lung tissue from further damage
Possibly lower the number of flare-ups or infections
Work safely alongside antifungals or biologics

It represents a new way of calming inflammation—by modifying neutrophil behaviour rather than blocking the immune system.

What Happens Next

The ASPEN Phase 3 results are expected soon. If positive, Insmed plans to apply for approval in the UK, EU, and USA.
Researchers are also studying brensocatib in:

COPD (Chronic Obstructive Pulmonary Disease)
Cystic fibrosis
Nontuberculous mycobacterial (NTM) infections

If licensed, it could mark the first new oral anti-inflammatory class for chronic lung disease in decades.

Key Take-Home Messages

Brensocatib reduces harmful lung inflammation by blocking the enzyme DPP1.
It is a small-molecule tablet, not a biologic injection.
It aims to protect the lungs by preventing damage from overactive neutrophils.
It may offer a steroid-sparing option for chronic airway diseases like bronchiectasis and aspergillosis.
It’s currently in final clinical trials, with results expected soon.

💬 Find Out More

National Aspergillosis Centre – aspergillosis.org
Insmed’s brensocatib research
ClinicalTrials.gov – search “brensocatib”

by GAtherton

🧩 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

🧠 Understanding Regulatory T Cells (Tregs) in Aspergillosis

How our immune system’s “brakes” help balance allergy and infection

🏅 2025 Nobel Prize in Medicine: Celebrating a Breakthrough in Immune Regulation

On 6 October 2025, the Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for discovering regulatory T cells (Tregs) and the FOXP3 gene — the master switch that controls immune tolerance.

Their work revealed how the immune system prevents itself from attacking the body’s own tissues. This discovery has since guided the development of immune-modulating therapies now used in cancer, autoimmune, and allergic diseases.

This Nobel recognition highlights how understanding Tregs can lead to smarter, safer therapies — including future immune-based treatments for Allergic Bronchopulmonary Aspergillosis (ABPA) and Chronic Pulmonary Aspergillosis (CPA), where immune balance is disrupted.

🔍 What Are Regulatory T Cells?

Regulatory T cells (Tregs) are a specialised group of white blood cells (lymphocytes) that act as the “brakes” of the immune system.
They prevent excessive inflammation and protect the body from overreacting to harmless particles such as dust, pollen, or Aspergillus spores.

Tregs work by releasing interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), two powerful calming signals that suppress over-active helper T cells (Th2 and Th17) and reduce allergic or inflammatory damage.

🦠 Aspergillus and the Immune System

Everyone inhales Aspergillus spores daily.
In healthy people, the immune system quickly clears them. But in individuals with asthma, allergies, or lung damage, the immune response can become unbalanced:

Form of Aspergillosis	Main Immune Problem	Treg Function
Allergic Bronchopulmonary Aspergillosis (ABPA) / Severe Asthma with Fungal Sensitisation (SAFS)	The immune system over-reacts to Aspergillus allergens, causing inflammation, mucus plugging, and airway obstruction	Too few or weak Tregs → loss of immune control
Chronic Pulmonary Aspergillosis (CPA)	Ongoing fungal growth with persistent inflammation and fibrosis	Excess local Treg activity may dampen antifungal defence
Invasive Aspergillosis (IA)	Profound immune weakness (e.g., after chemotherapy, corticosteroids, or organ transplant)	Tregs can further suppress protective antifungal responses

⚖️ The Delicate Balance

The immune system must balance acceleration and braking:

Too little Treg control → allergic inflammation and tissue damage.
Too much Treg control → poor antifungal clearance and chronic infection.

The ideal is immune equilibrium — strong enough to fight Aspergillus, but calm enough to prevent lung injury.

💊 Treatments That Influence Regulatory T Cells

Several therapies already used for aspergillosis or severe asthma may influence Treg activity:

Therapy	Possible Effect on Tregs
Corticosteroids (e.g., prednisolone)	Reduce inflammation and may increase IL-10-producing Tregs
Biologic therapies (omalizumab, mepolizumab, dupilumab)	Indirectly restore Treg–Th2 balance by blocking overactive allergy pathways
Vitamin D supplementation	Promotes stable and functional Tregs; deficiency linked with severe ABPA
Healthy gut microbiome (dietary fibre, probiotics)	Gut–lung axis supports Treg generation via short-chain fatty acids
Low-dose interleukin-2 (IL-2) therapy (research stage)	Expands Tregs selectively — now in early clinical trials for allergic and autoimmune disease

🔬 Current Research Directions

Researchers are studying:

Differences in Treg profiles between ABPA, SAFS, CPA, and healthy lungs
How biologic therapies and antifungal drugs affect the Treg–Th2–Th17 balance
Whether IL-2-based immune modulation could calm allergic flares without immunosuppression
The influence of the airway microbiome on lung Treg activity

These studies aim for personalised immune therapy, tailoring treatment to each patient’s immune pattern.

💬 Take-Home Message

Regulatory T cells are the peacekeepers of the immune system.
Their discovery — now honoured by the 2025 Nobel Prize — transformed our understanding of allergy, infection, and autoimmunity.

In aspergillosis, restoring Treg balance could one day:

Calm allergic inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)
Limit lung scarring and fibrosis in Chronic Pulmonary Aspergillosis (CPA)
Support better fungal control without harmful over-suppression

By understanding these immune “brakes,” researchers hope to keep both Aspergillus and the immune system under control — balanced, not overactive.

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.

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.)

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