🌬️ Inhaled Antifungal Treatments for Chronic Pulmonary Aspergillosis (CPA)

Updated: October 2025

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💡 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.

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💊 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

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🔬 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.

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🧾 Current and recent clinical trials

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

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⚠️ 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).

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🧭 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?

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🏥 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

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🗝️ 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.