🎢 Life as a Patient

Living with chronic illness is often described as a journey, but that word can feel far too calm. In truth, it’s more like a modern roller coaster — fast, unpredictable, and full of twists that catch you off guard.

There are the high climbs, when medication works, energy returns, and hope builds quietly in your chest. Then there are the sudden drops, when symptoms flare, infections hit, or test results turn against you. But what really defines the experience are the loops and spirals — the disorienting moments that spin you upside down, when you’re not sure which way is forward, or how long it will take to steady yourself again.

Each turn tests your courage, your patience, and your ability to keep holding on. Sometimes you’re screaming inside while smiling on the outside. Other times, you find small moments of stillness even as the track twists beneath you — the deep breath between the storms.

And through it all, you learn:

To adapt rather than control.
To brace and breathe rather than fight every turn.
To appreciate those who stay beside you in the carriage, even when the ride is rough.

The roller coaster of illness is not one anyone chooses to board. But it teaches something profound — that strength isn’t about never being scared; it’s about showing up, again and again, when the world flips upside down.

by GAtherton

Living Between What My Body Needs and What the World Expects

Sometimes it feels as if people grow tired of hearing about illness or fatigue. They encourage us to “think positively,” as if mindset alone could repair the body or quiet exhaustion.

But chronic illness doesn’t work like that. It’s a daily negotiation between two inner voices — one saying, “You need to rest,” and the other whispering, “You still have responsibilities.” That constant tug-of-war leaves many of us feeling trapped between what our body needs and what life demands.

Even small things — such as changes in weather, sleep patterns, or stress — can tip the balance. We learn to pace ourselves, to weigh every decision, to ration energy. And still, the world around us often sees only the surface: “You look well.”

The Other Side of Positivity

For those who don’t live with chronic illness, this can be difficult to face. Often, people cling to optimism not because they’re unkind, but because they don’t want to confront the truth — that illness can be long-term, unpredictable, and out of anyone’s control.

Positivity can become a shield: a way of keeping the world steady and reassuring when faced with something that can’t be fixed. Saying “You’ll be fine” or “Stay strong” helps them feel hopeful, even if it leaves us feeling unseen.

Understanding that this comes from discomfort, fear, or helplessness rather than indifference can make those moments a little easier.

Where Real Connection Starts

Real empathy sits somewhere between positivity and honesty — where people can acknowledge pain without losing hope.

Most of the world won’t fully understand chronic fatigue or the mental gymnastics it takes to stay balanced until they experience it themselves. But by sharing what it’s really like, we give others the chance to learn — just as society learns to understand invisible struggles like dyslexia or digital exclusion.

Understanding begins when we listen without needing to fix. Sometimes the greatest kindness is simply to say, “That sounds hard — how are you managing today?”

by GAtherton

Aspergillus Saga — July 2024 to June 2025: Searching for the Invisible

In this compelling personal account, a patient describes her year-long journey battling what ultimately was identified as subacute invasive aspergillosis. She walks us through months of worsening symptoms, repeated rounds of antifungals, diagnostic uncertainty, and the pivotal decision to undergo lung surgery. The turning point: removal of a single lesion led to a rapid resolution of systemic infection signs, with follow-up therapy and monitoring guided by her infectious disease team. Her story highlights how, with very little precedent in medical literature, patients and clinicians sometimes must walk together on uncharted ground.

👉 Read the full article here:
“Aspergillus Saga – July 2024 to June 2025: Searching for the Invisible” Beauty for Ashes

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 Corticosteroid Mood Swings

Alison shared something that will resonate with many of us:

“Recognising that prednisone mood swings are very unpredictable is a good reminder as I feel like I am up and down so much of late. Yesterday’s swap to half hydrocortisone and half prednisone probably took a bit of adjusting too. Better day today though — I even got out to pick up my campervan that had been in for service. Felt really good to be driving it again and as the weather improves, I live in hope that I might get to use it this year!” 😊🤔

💭 Why mood can change on corticosteroids

Steroid medicines such as prednisone, prednisolone, and hydrocortisone affect many systems in the body — including brain chemistry.
When levels go up or down (for example when changing dose or type), it’s common to feel:

Irritable or anxious one day, low or tired the next
More emotional than usual — tears or frustration come quickly
Sleep disturbance, vivid dreams, or early waking
Short bursts of energy or restlessness, followed by a “crash”

These changes don’t mean you’re “losing control” — they reflect how sensitive the brain is to shifts in cortisol, the hormone steroids replace or supplement.

⚖️ Why switching between steroids can feel bumpy

Prednisone and hydrocortisone are both corticosteroids but have different potencies and timings:

Steroid	Approx. equivalent dose (anti-inflammatory)	Typical duration of action
Hydrocortisone	20 mg ≈ 5 mg prednisolone	Short-acting (6–8 hours)
Prednisone/Prednisolone	5 mg	Longer-acting (12–36 hours)

When switching or mixing them, the body’s rhythm of cortisol can temporarily feel off — like jet lag for your stress hormones. It often settles after a few days.

🌞 Tips that may help

Keep a simple mood or energy diary — it helps you and your clinician see patterns.
Take doses at consistent times, usually in the morning, unless advised otherwise.
Build in gentle activity or time outdoors — small wins, like Alison’s campervan trip, really lift mood.
Avoid caffeine or alcohol spikes if feeling restless or irritable.
Tell your clinician if mood swings are severe or prolonged — dose adjustment or slower tapering may help.

💬 In Alison’s words

“Better day today.”
Sometimes that’s the victory — one step, one better day, one bit of normality returning.

by GAtherton

🌿 Why do I get thick, yellow mucus in the morning?

Many people with asthma, ABPA (allergic bronchopulmonary aspergillosis) or sinus problems notice that first thing in the morning they cough up or “hook out” very thick, sticky, yellow mucus from the back of the throat or nose.
It can feel like glue — stringy, rubbery, and slow to move.

The good news is:
👉 This doesn’t automatically mean that Aspergillus fungus is growing in your sinuses.

💧 Why it happens

At night, mucus naturally becomes thicker because:

You breathe more through your mouth while sleeping, which dries the nose and throat.
Mucus sits still instead of draining, so it concentrates and thickens.
If you already have sinus inflammation or allergies, your mucus glands make even more.
It often drains down the back of the throat (post-nasal drip), where it collects until morning.

This combination makes for a lumpy, sticky “plug” that only shifts once you’re up and moving around.

🧠 When might fungus be involved?

If the sinuses become colonised with Aspergillus or another fungus, there are usually extra clues, such as:

Blocked nose or pressure that doesn’t improve with sprays or rinses
One-sided pain or discharge
Dark, rubbery, or green-grey plugs rather than yellow mucus
Loss of smell
CT or endoscopy showing thick debris or “fungal balls”

If these are present, an ENT specialist can look directly into the sinuses and, if needed, take a small sample for fungal culture or order a CT scan.

🩺 What helps most people

You can often manage the morning mucus with simple measures:

Saline nasal rinses (like Sterimar, NeilMed, or salt-water sprays) — thin mucus and wash out allergens or fungal dust.
Warm fluids or gentle steam to moisten airways.
Topical nasal steroid sprays (if prescribed) — reduce swelling and mucus production.
Plenty of hydration through the day.
Avoid over-using decongestant sprays, which can make congestion worse in the long run.

If mucus stays thick, coloured, or difficult to clear for more than a few weeks — or you develop sinus pressure, pain, or smell loss — ask for a review by your ENT or respiratory team.

🟢 Key message

Thick yellow mucus in the morning is usually a sign of dryness and overnight build-up, not an active fungal infection.

Regular rinsing, good hydration, and controlling sinus inflammation usually keep things under control.

Fungal colonisation is much less common — and when it happens, there are usually other warning signs that your clinician can check.

by GAtherton

🌬️ When Breathlessness Gets Worse: Understanding What Might Be Happening

Many people with aspergillosis or ABPA (Allergic Bronchopulmonary Aspergillosis) find that their symptoms come and go — some days are better, some worse.
It can feel worrying when you suddenly become more breathless or wheezy, especially if you’ve been doing all the right things: airway clearance, antifungal treatment, and even starting a biologic injection.

This guide explains what might be happening and how you can begin to work out the cause.

💨 1. Why you might feel worse after airway clearance

Airway clearance helps move sticky mucus and plugs out of your lungs — but this can temporarily irritate or narrow the airways, especially if your chest is already inflamed.
You might feel tighter or more wheezy for a short time after a session.

Helpful tips

Use your bronchodilator (salbutamol or similar) before starting airway clearance.
Keep sessions short and gentle if you feel breathless afterward.
Talk to your respiratory physiotherapist about changing the timing or intensity of your airway clearance routine.
Nebulisers or inhalers after clearance can help calm things down again.

🧫 2. Could it mean the Aspergillus is becoming more active?

Sometimes it can — but not always.
Symptoms like breathlessness, cough, or fatigue can also be caused by inflammation, infection, or changes in medication.

Signs that might suggest Aspergillus activity is rising include:

More sputum, or thicker or darker plugs
More coughing or wheezing
Tiredness or mild fever
A drop in your usual lung function numbers (FEV₁)

These changes are only clues — to be sure, you need blood or sputum tests.

🧪 3. Tests that help you and your team understand what’s going on

Test	What it shows
Total IgE	Rises when allergic inflammation is active (monitored every few months).
Aspergillus-specific IgE / IgG	Shows how strongly your immune system is reacting to the fungus.
Eosinophil count	Measures allergic immune activity (should fall if your biologic is working).
Aspergillus culture or PCR (sputum)	Shows whether fungal growth has increased or returned.
Antifungal drug level (itraconazole, voriconazole, etc.)	Confirms whether your medication is at a helpful level in your bloodstream.

If you feel your symptoms are worsening, you can ask your GP or respiratory nurse if these blood tests can be arranged, even if your specialist clinic is hard to reach.

💉 4. When you’ve just started a biologic

Biologics such as Benralizumab, Mepolizumab, Omalizumab, or Dupilumab work by reducing inflammation in the lungs — but they take time.

What to expect

Most people don’t notice big changes after the first dose.
Benefits usually appear after 2–3 injections, sometimes longer.
You may start to notice less sputum, fewer wheezy days, and more energy over time.

If your breathing still feels difficult after a few doses, your team might review whether this biologic is the best one for you or whether something else is going on.

🧭 5. Keeping track between appointments

When clinic visits are months apart, self-monitoring helps fill the gap.

You can:

Keep a symptom diary — note breathlessness, cough, mucus colour, temperature, and how often you need rescue inhalers.
Record any oxygen readings if you use a pulse oximeter.
Note when you take antifungals and biologic injections.
Share this record at your next appointment — it helps your team see the bigger picture.

If you feel abandoned, remember you can still contact your hospital team or ask your GP for basic bloods. These can often be shared with your specialist for advice.

❤️ 6. When you feel alone

Many people with aspergillosis describe long stretches of “self-management.”
That’s why patient support networks (like NAC CARES) exist — to give you a space to talk, ask questions, and share what works.

No one should have to manage this alone.

🕊️ 7. Quick summary

Possible reason for feeling worse	What you can do
Airway irritation after clearance	Use bronchodilator first; ask physio about technique
Inflammation or allergic flare	Ask for IgE and eosinophil tests
Antifungal not at right level	Ask for a blood level check
Early days of biologic treatment	Give it more time; track symptoms
Infection or fungal regrowth	Ask for sputum culture or PCR

🌱 Remember:

Feeling worse doesn’t always mean you’re getting worse — but it’s always worth checking.
The right information (blood tests, drug levels, and a clear plan) can turn a worrying spell into a step forward.

by GAtherton

Understanding and Controlling Your Immune System

How your immune system works

Your immune system is your body’s built-in defence and repair network.
It protects you from infection, clears away damaged cells, and helps you heal after illness or injury. But it’s also connected to almost every part of the body — your brain, gut, hormones, and even mood.
When finely balanced, it keeps you healthy. When it becomes over- or under-active, it can cause inflammation, allergies, or long-term conditions such as ABPA or asthma.

🧠 1. Brain and nerves

Normal role: Immune cells in the brain (called microglia) keep nerve circuits healthy and remove damaged cells.
When things go wrong: Too much inflammation can cause fatigue, “brain fog,” anxiety, or depression — feelings many people experience during infection or flare-ups. Long-term inflammation is linked to memory problems and slower recovery after illness.

❤️ 2. Heart and blood vessels

Normal role: Immune cells repair vessel walls and help wounds heal.
When things go wrong: Chronic inflammation can thicken arteries (atherosclerosis) or cause rare problems like vasculitis, which affects blood flow. Balancing inflammation helps protect heart and circulation health.

🫁 3. Lungs and airways

Normal role: The immune system protects your lungs from germs, clears dust, and repairs tissue after irritation.
When things go wrong:
- In asthma or ABPA, the immune system overreacts to harmless triggers such as Aspergillus spores, pollen, or dust, causing airway swelling, mucus build-up, and breathlessness.
- In CPA, parts of the immune system struggle to clear fungal infection effectively, leading to chronic inflammation and tissue damage.
  Keeping the immune response balanced — not too weak, not too strong — is the key to long-term lung health.

🍽️ 4. Gut and digestion

Normal role: About 70% of your immune cells live in the gut, where they keep a healthy balance of bacteria and prevent harmful microbes leaking into the bloodstream.
When things go wrong: Stress, poor diet, or antibiotics can disrupt this balance, increasing inflammation.
A varied, fibre-rich diet and, in some cases, probiotics can help the gut “educate” the immune system.

💪 5. Muscles, joints, and repair

Normal role: Immune cells clear damaged tissue and stimulate repair after exercise or illness.
When things go wrong: If the immune system stays “switched on,” joints and muscles can ache or feel weak.
Fatigue in aspergillosis may be partly due to ongoing low-level inflammation.

🧬 6. Hormones and metabolism

Normal role: Hormones like cortisol and adrenaline help keep inflammation under control.
When things go wrong:
- Overactive inflammation can worsen insulin resistance, weight changes, and tiredness.
- Autoimmune problems can affect glands like the thyroid or adrenal glands (Addison’s disease).
  Managing stress, sleep, and diet all help the immune-hormonal balance.

🩸 7. Blood and bone marrow

Normal role: The immune system is built in the bone marrow, producing white cells, red cells, and platelets.
When things go wrong: Excessive inflammation raises blood markers such as CRP or eosinophils, often seen during ABPA flare-ups or infection.
Monitoring these levels helps your specialist adjust treatment safely.

🦴 8. Skin and mucous membranes

Normal role: Acts as the body’s first barrier, with immune cells ready to seal wounds or fight germs.
When things go wrong: Eczema, psoriasis, and slow-healing wounds can occur when immune balance is disturbed — sometimes as side effects of steroids or other medications.

⚖️ 9. The balance between defence and tolerance

The most important job of your immune system is to tell friend from foe — to destroy invaders but leave your own body unharmed.

If it overreacts, you get allergies or autoimmune disease.
If it underreacts, infections can take hold more easily.
In aspergillosis, both problems can occur together: too little defence against fungus, but too much inflammation once the fungus is detected.

🧩 How Medicine Is Learning to Control the Immune System Better

In the past, we only had blunt tools — like steroids — to “calm” inflammation. These saved lives but also caused side effects.
Today, science is learning to control the immune system more precisely, using targeted treatments, cell therapies, and even lifestyle tools that work with your body’s own defences.

🎯 1. Targeted biologic drugs

These are antibodies made in the lab that block one specific immune signal instead of suppressing everything.

Examples used in asthma and ABPA:

Mepolizumab and benralizumab block interleukin-5 (IL-5), reducing eosinophil-driven inflammation.
Dupilumab blocks IL-4 and IL-13 pathways, calming allergic inflammation.

Other biologics (like infliximab, tocilizumab, and omalizumab) target immune messengers involved in arthritis, eczema, or autoimmune disease.

💉 2. Vaccines and immune training

Vaccines “teach” the immune system to respond safely and efficiently.
New approaches — such as mRNA vaccines — can be updated quickly and may in future be used to retrain the immune system in chronic diseases, allergies, and even cancer.

⚙️ 3. Immune cell therapies and genetic repair

Researchers can now rebuild parts of the immune system:

CAR-T cell therapy modifies a patient’s own T cells to find and destroy cancer.
T-reg therapy expands the body’s natural “peacekeeping” cells to prevent autoimmune attack.
Gene editing (CRISPR) aims to correct inherited immune problems or fine-tune overactive responses.

🧠 4. Neuro-immune and stress control

Because the brain and immune system constantly talk, therapies that reduce stress or stimulate specific nerves can influence inflammation.

Vagus nerve stimulation devices can reduce gut and joint inflammation.
Mindfulness, relaxation, and gentle exercise lower stress hormones and improve immune balance — especially in asthma or ABPA, where stress can trigger flares.

🌿 5. Microbiome and metabolic balance

Your gut bacteria, diet, and metabolism shape immune health.

A high-fibre, plant-based diet produces short-chain fatty acids that calm inflammation.
Probiotic and prebiotic therapies are being studied to restore immune tolerance.
Metabolic drugs such as metformin are showing anti-inflammatory effects beyond diabetes care.

🧩 6. Re-teaching immune tolerance

The ultimate goal is to re-educate the immune system so it stops attacking harmless things.

Allergen immunotherapy exposes the body to small, increasing doses of allergens to reduce sensitivity.
Nanoparticle and peptide therapies are being developed to signal to immune cells that “this is safe,” switching off allergic or autoimmune responses without weakening defences.

👤 7. Personalised immune medicine

Every person’s immune system behaves differently.

New blood and genetic tests (“immune phenotyping”) help doctors match patients to the best biologic or antifungal treatment.
Artificial intelligence is being used to model individual immune systems — predicting who will respond best to certain drugs.
In the future, “immune profiles” may be as common as cholesterol or blood pressure checks.

💬 Living with Aspergillosis: What This Means for You

You’re not powerless. Understanding your immune system helps you work with your doctors to find the best balance of antifungal, biologic, and anti-inflammatory treatments.
Lifestyle still matters. Stress control, exercise, nutrition, and infection avoidance (e.g. clean air, low mould exposure) all influence immune stability.
New hope. Research is rapidly advancing — turning immune control from a guessing game into a precise science.
The same breakthroughs that transformed cancer and autoimmune care are now informing treatments for allergic and fungal lung disease.

🩺 In summary

Your immune system touches every part of your body — lungs, gut, brain, hormones, and skin.
In aspergillosis, it can become both under-protective and over-reactive, creating the delicate balance specialists are trying to restore.
Modern medicine is learning to tune the immune system like an orchestra, not silence it — calming inflammation when it harms you, and strengthening defence when you need it most.

The future of aspergillosis care lies in immune precision — treating not just infection, but the whole system that responds to it.

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