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HEPA filters & heat to reduce exposure to allergens

Patients with forms of aspergillosis like ABPA can be highly allergic to fungal and many other airborne allergens. For some, relief can be found by ensuring the levels of airborne allergens in the home are as low as possible—this means removing as much dust as possible and removing sources of dust in the home.

Fungal spore fragments can be extremely small so air filters and vacuum cleaners have to have HEPA-grade filtration systems in order to be effective. NB there are some air cleaning systems that do not use filtration as a means to remove particles, instead they use heat (see bottom of page).

For those that use HEPA filters it is important that the correct grade of HEPA filtration is provided:

HEPA (High-Efficiency Particulate Air) filters are classified into different grades based on their filtration efficiency. The most commonly used classification is from ISO 29463 (based on EN 1822-1), which divides HEPA filters into E (Efficiency), H (High Efficiency), and U (Ultra-Low Penetration Air - ULPA) categories.

HEPA Filter Grades and Their Uses

Key Uses of Different HEPA Grades

1. E10-E12: Used in standard HVAC systems, air purifiers, and vacuum cleaners.
2. H13-H14: Common in hospitals, clean rooms, and biosafety labs where high air purity is needed.
3. U15-U17 (ULPA): Found in pharmaceutical manufacturing, semiconductor industries, and nuclear facilities.

For medical conditions like ABPA, HEPA H13 or H14 filters are recommended in home air purifiers and hospital settings to reduce airborne Aspergillus spores.

Heat-based filtration

Some domestic air purifiers use heat-based filtration to neutralize airborne contaminants. These typically work by heating air to a high temperature to kill bacteria, viruses, mould spores, and other pathogens before cooling them down and releasing them into the room.

Types of Heat-Based Air Cleaners

1. Thermodynamic Sterilization (TSS) Air Purifiers

   • Uses a ceramic core heated to ~200°C (392°F) to destroy airborne microorganisms.
   • No filters, so there’s no need for replacements.
   • Example: Airfree air purifiers (popular in allergy-sensitive households).

2. Hybrid Heat & Filtration Systems

   • Combines heat sterilization with HEPA filters or activated carbon.
   • Example: Some high-end medical-grade air purifiers integrate thermal disinfection.

Advantages

✔ Kills mold, bacteria, and viruses rather than just trapping them.
✔ No filter replacements (TSS models).
✔ Silent operation (as some don’t use fans).

Disadvantages

❌ Limited particle filtration—doesn’t remove dust, pet dander, or allergens like a HEPA filter does.
❌ Slower purification compared to fan-driven systems.

Best Use Cases

• Allergy and asthma sufferers (e.g., ABPA) who want a maintenance-free solution.
• People sensitive to mold and bacteria in humid environments.
• Homes with immunocompromised individuals needing sterile air.

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How the UK evaluates new drugs for use in the NHS

The UK evaluates expensive drugs for cost-effectiveness primarily through the National Institute for Health and Care Excellence (NICE) and other bodies like the Scottish Medicines Consortium (SMC). The evaluation is based on clinical effectiveness, cost-effectiveness, and impact on NHS resources.

Key Aspects of Evaluation

1. Cost-Effectiveness Analysis (CEA) using QALYs

• NICE uses the Quality-Adjusted Life Year (QALY) as a measure to assess whether a drug provides sufficient health benefits relative to its cost.
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• If the ICER is below £20,000–£30,000 per QALY, the drug is typically considered cost-effective.
• For certain severe or rare diseases, NICE may allow a higher cost per QALY threshold (e.g., up to £100,000 for very rare conditions under the Highly Specialised Technologies (HST) program).

2. Budget Impact Test

• If a drug is expected to cost the NHS more than £20 million per year, NICE may negotiate with the manufacturer for a Managed Access Agreement (MAA) or phased introduction to spread costs.

3. Clinical Evidence & Real-World Data

• NICE considers clinical trial data, real-world effectiveness, and patient-reported outcomes.
• The NHS Commercial Medicines Directorate may negotiate confidential pricing agreements (e.g., rebates or discounts).

4. NHS England & Special Cases

• For cancer drugs, the Cancer Drugs Fund (CDF) allows faster access while gathering more real-world data.
• The Innovative Medicines Fund (IMF) supports non-cancer drugs with promising early data but uncertain long-term benefits.

5. Scotland & Wales

• The Scottish Medicines Consortium (SMC) and the All Wales Medicines Strategy Group (AWMSG) perform similar cost-effectiveness evaluations for their health systems.

Example: Cost-Effectiveness Evaluation of Omalizumab in the UK

Omalizumab (Xolair) is a monoclonal antibody used for severe allergic asthma and chronic spontaneous urticaria (CSU). Its cost-effectiveness for NHS use was evaluated by NICE based on clinical benefit, quality of life improvement, and economic impact.

1. How is the benefit of Omalizumab calculated?

A. Clinical Benefits (Health Gains)

• Clinical trials show reduced asthma exacerbations, hospitalizations, and improved symptom control.
• Fewer oral corticosteroid (OCS) bursts, reducing side effects (osteoporosis, diabetes risk).
• Improved quality of life due to fewer symptoms and better lung function.

B. Quality-Adjusted Life Years (QALY) Calculation

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• Without treatment: Patients may experience frequent asthma attacks, reliance on oral corticosteroids, and reduced quality of life (e.g., QALY score = 0.50).
• With Omalizumab: Patients have fewer exacerbations, reduced hospital stays, and improved daily function (e.g., QALY score = 0.72).
• QALYs gained = 0.72 - 0.50 = 0.22**

**NOTE that for Omalizumab initial ICER calculation would have been £8000/26000 (ie. cost of drug) divided by 0.22 (QALY gained) which equals £40-100 000 ie. well above the usual approval threshold of £20-30 000. NHS presumably negotiated a way around that problem to allow approval of Omalizumab.

2. Cost-Effectiveness of Omalizumab

A. NHS Cost Evaluation

• Omalizumab cost: ~£8,000–£26,000 per patient per year (depending on dosage).
• Cost savings: Fewer hospitalizations, ICU admissions, and OCS-related complications.
• NICE’s ICER threshold is £20,000–£30,000 per QALY.

B. NICE Decision on Cost-Effectiveness

• For severe allergic asthma: Approved, as the ICER was ~£28,000 per QALY, within the acceptable NHS threshold.
• For chronic urticaria: Initially not approved due to an ICER > £50,000 per QALY, but later funded under special circumstances.

3. Special NHS Funding Mechanisms

• Managed Access Agreements (MAA): Discounted pricing for eligible patients.
• Real-World Data Collection: Continued monitoring of benefits via the Severe Asthma Registry.

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ABPA & CPA: Patient priorities

We have launched a new section that lists the commonest symptoms reported by our patient groups and offers tips on how to manage them.

In Their Words: CPA & ABPA

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I Have ABPA and feel worse if I sleep with windows open

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How the NHS funds medications

 Scotland, Wales, and Northern Ireland offer free prescriptions to all residents.

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Chronic pulmonary aspergillosis – a guide for the general physician

This collaborative article reviews chronic pulmonary aspergillosis (CPA) from the perspective of a multidisciplinary team comprising of respiratory physicians, radiologists, mycologists, dietitians, pharmacists, physiotherapists and palliative care specialists. The review synthesises current knowledge on CPA, emphasising the intricate interplay between clinical, radiological, and microbiological aspects. We highlight the importance of assessing each patient as a multidisciplinary team to ensure personalised treatment strategies and a holistic approach to patient care.

Link to review

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Thinking about joining a clinical trial? What are your concerns?

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Biologics & ABPA - what are they and what can they do?

Biologic medications (also known as biologics) are a class of drugs derived from living organisms or their cells. These treatments are used for various conditions, especially those involving the immune system, such as autoimmune diseases, cancers, and chronic inflammatory disorders. Here’s a breakdown of biologics:

1. What Are Biologics?

• Biologics are large, complex molecules made using biotechnology. They can be derived from living organisms such as bacteria, yeast, or animal cells.
• Unlike traditional medications (chemically synthesized), biologics are produced through genetic engineering or cell culture techniques.

2. Types of Biologic Drugs:

• Monoclonal Antibodies (mAbs): These are engineered antibodies designed to target specific proteins or cells, such as tumor cells or immune system components. Examples include drugs like adalimumab (Humira) for rheumatoid arthritis and rituximab (Rituxan) for certain cancers.
• Interferons: Proteins that modify immune system activity. They are used for conditions like multiple sclerosis and hepatitis C.
• Vaccines: Biologic drugs used to stimulate the immune system to protect against infectious diseases (e.g., the flu vaccine, COVID-19 vaccines).
• Cell and Gene Therapies: These involve altering genes or using stem cells to treat genetic disorders or cancers. CAR T-cell therapies are an example for cancer treatment.

3. Conditions Treated by Biologics:

• Autoimmune Disorders: Such as rheumatoid arthritis, Crohn’s disease, and psoriasis.
• Cancer: Biologics like monoclonal antibodies and immune checkpoint inhibitors target cancer cells.
• Infections: Some biologics, including vaccines, protect against infections like hepatitis, flu, and COVID-19.
• Chronic Inflammatory Conditions: Such as asthma and inflammatory bowel disease (IBD).

4. Advantages of Biologics:

• Targeted Action: Biologics can target specific parts of the immune system or cells involved in disease, leading to more effective treatments with fewer side effects compared to traditional drugs.
• Personalized Treatments: Some biologics can be customized based on a patient's genetics, improving outcomes for certain conditions.

5. Limitations and Side Effects:

• Expensive: Biologics tend to be more expensive than traditional medications due to the complex production process.
• Injection or Infusion: Many biologics are administered through injections or intravenous infusions rather than oral tablets.
• Immune System Effects: Since biologics modify immune system function, they can increase the risk of infections and other immune-related side effects.

Examples of Biologic Medications:

• Humira (adalimumab) for autoimmune diseases.
• Keytruda (pembrolizumab) for cancer treatment.
• Enbrel (etanercept) for rheumatoid arthritis.

Biologics are reshaping the treatment landscape, particularly in conditions where traditional medications were less effective.

In the case of Allergic Bronchopulmonary Aspergillosis (ABPA), biologic medications are increasingly being explored and used as part of treatment, particularly for patients with more severe or resistant forms of the disease. ABPA is an allergic reaction to the fungus Aspergillus, which can lead to airway inflammation and lung damage. Biologic medications, often aimed at modulating the immune system, help in managing this complex condition, especially when conventional treatments like corticosteroids fail to control symptoms or lead to significant side effects.

How Biologics Help in ABPA Treatment:

1. Targeting Immune System Pathways:
   • Biologics used in ABPA primarily work by targeting specific immune system pathways that drive the inflammatory response triggered by the Aspergillus fungus.
   • For example, biologics that target interleukin-5 (IL-5), such as mepolizumab (Nucala), can help reduce eosinophil levels, a type of white blood cell involved in allergic reactions and inflammation in ABPA. Dupixent, another biologic, targets IL-4 and IL-13, which are cytokines involved in the inflammatory cascade in ABPA, potentially improving lung function and reducing exacerbations .
   • Omalizumab (Xolair) acts directly on the patients IgE antibodies, preventing them triggering allergic inflammation
2. Reducing Steroids - For ABPA patients who require long-term corticosteroid use, biologics may offer an alternative, reducing dependence on steroids and lowering the risk of long-term steroid side effects (e.g., osteoporosis, diabetes, and weight gain).
   • Biologics can provide a more targeted approach, addressing the underlying immune mechanism, rather than just suppressing the overall immune response with steroids .
3. Clinical Evidence:
   • In trials, biologics like mepolizumab have shown improvements in asthma control and reduced exacerbations, suggesting potential benefits for ABPA patients with significant asthma components.
   • Dupilumab has also demonstrated potential benefits in patients with ABPA and associated asthma, showing improvements in lung function and reduction in eosinophil levels, thus addressing both the underlying inflammation and allergic reactions .
4. Safety and Efficacy:
   • While biologics are typically used in cases where standard treatments (steroids, antifungals) are not sufficient or appropriate. These medications are generally well-tolerated, but they do carry risks, such as increased susceptibility to infections due to immune system modulation** .

Summary:

Biologic therapies represent an option for patients with ABPA, particularly those with severe symptoms or who struggle with long-term steroid use. By targeting specific immune pathways, biologics help reduce inflammation and improve lung function without the broad immunosuppression of steroids. Drugs like mepolizumab and dupilumab are showing encouraging results, though their use in ABPA is still being refined and evaluated in clinical trials.

If you're exploring biologics for ABPA treatment, consulting with a specialist in pulmonary or immunologic disorders is crucial, as the benefits and risks of these drugs need to be carefully balanced for each individual patient.

**One common concern is whether these treatments could increase susceptibility to viral infections, particularly respiratory viruses.

Immune Modulation and Viral Infections: Omalizumab (Anti-IgE): Omalizumab reduces IgE levels, which are primarily involved in allergic reactions, not antiviral immunity. Studies show that it may actually decrease the frequency of respiratory viral infections by reducing inflammation and preventing exacerbations triggered by viruses. In clinical trials, omalizumab was not associated with increased viral infection rates and has been shown to lower asthma exacerbations caused by viral infections.

Mepolizumab and Benralizumab (Anti-IL-5): These biologics target IL-5, which reduces eosinophil counts. Eosinophils play a minor role in viral defense, but their reduction does not seem to impair the body's ability to fight viruses significantly. Data suggest that mepolizumab and benralizumab do not increase the incidence of viral infections and can reduce asthma exacerbations, including those triggered by viruses.

Dupilumab (Anti-IL-4/IL-13): Dupilumab inhibits IL-4 and IL-13 signaling, key cytokines in allergic inflammation. It is not associated with increased viral infection susceptibility in clinical trials. It may enhance antiviral defenses by reducing Th2-skewed inflammation, potentially allowing the body to mount a better response to viruses.

Evidence from Studies: Studies have consistently shown that biologics can reduce asthma exacerbations, many of which are triggered by viral infections, suggesting they do not compromise the immune system's ability to fight viruses. No significant increase in viral infections has been observed in large clinical trials for these medications, and they are generally considered safe in this context.

Conclusion: Biologic medications for asthma do not appear to increase vulnerability to viral infections. In fact, they may reduce the risk of virus-induced asthma exacerbations by controlling airway inflammation. However, patients with severe asthma or comorbid conditions should always consult their healthcare provider regarding potential risks.

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Olorofim - a promising new antifungal candidate for aspergillosis treatment.

Olorofim represents a significant advancement in treating aspergillosis, particularly for patients who cannot tolerate or do not respond to existing antifungal therapies. Here’s why it’s important:

1. Novel Mechanism of Action

• Olorofim is the first antifungal in a new class called orotomides. It inhibits dihydroorotate dehydrogenase, an enzyme essential for fungal pyrimidine biosynthesis.
• This mechanism is entirely distinct from existing antifungal classes (azoles, polyenes, and echinocandins), making it effective against strains resistant to current treatments​

2. Broad Spectrum and Potency

• It has demonstrated activity against azole-resistant Aspergillus species and other difficult-to-treat moulds, addressing a major gap in antifungal therapy​
• This includes rare and often lethal fungal infections like Scedosporium, Lomentospora, and Fusarium, as well as chronic conditions like Chronic Pulmonary Aspergillosis (CPA) and invasive aspergillosis.

3. Oral Administration

• Unlike many current treatments that require intravenous administration (e.g., amphotericin B), olorofim is taken orally, improving convenience and accessibility for patients needing long-term therapy.

4. Targeting Unmet Needs

• Aspergillosis, particularly invasive aspergillosis, has high morbidity and mortality rates, especially in immunocompromised patients (e.g., those with cancer, transplant recipients).
• Current treatments face challenges like resistance, toxicity, and drug-drug interactions. Olorofim addresses these limitations by offering a safer and more tolerable alternative​

5. Regulatory Recognition

• The drug has been granted Breakthrough Therapy Designation and Orphan Drug Status by the FDA and EMA, underscoring its potential to meet urgent medical needs​
  pharmaphorum GlobeNewswire

Future Implications

Olorofim's availability for treating Chronic Pulmonary Aspergillosis (CPA) depends on its successful progression through clinical trials and regulatory approval. Here's a summary of its current status and potential timeline:

1. Current Status:
   • Olorofim is in Phase 3 clinical trials (OASIS trial) for invasive fungal diseases, including invasive aspergillosis, a related but more acute condition than CPA.
   • Although the drug has shown promising results in earlier studies, the FDA recently issued a Complete Response Letter, indicating that additional clinical data is required before it can be approved in the U.S.​​
   • CPA is not explicitly listed as a primary indication in current trials, but success in related aspergillosis treatments could lead to future trials or off-label use for CPA.
2. Timeline to Approval:
   • If the ongoing Phase 3 trial and additional studies satisfy regulatory agencies, olorofim could receive an approval within 2–3 years for its initial indications (e.g., invasive aspergillosis).
   • For CPA specifically:
     • Additional trials may be needed to confirm efficacy and safety, potentially extending approval timelines by 3–5 years.
     • Off-label use might occur sooner, depending on clinician judgment and availability in regions with less restrictive policies.

Given the high unmet need in CPA and the novelty of olorofim’s mechanism, it is closely watched by both the medical community and regulators. If you're a patient with CPA, keeping in touch with your healthcare provider about ongoing trials and compassionate use programs may help you access new treatments sooner.

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UK National RSV vaccination program launched

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