Severe Asthma with Fungal Sensitisation (SAFS) for Expert Patients and non-Specialist Clinicians

Expert Information for Patients, GPs, and Specialist Nurses

🔎 What Is SAFS?

SAFS describes a clinical subgroup of patients with severe asthma who are sensitised to environmental fungi, particularly Aspergillus fumigatus, but who do not meet criteria for ABPA (i.e. no high total IgE or central bronchiectasis).

Fungal sensitisation may contribute to poor asthma control, airway inflammation, and increased exacerbations.

🧬 Pathophysiology

• IgE-mediated sensitisation to fungi in the airways

• Chronic airway inflammation exacerbated by fungal allergens

• Unlike ABPA, no eosinophilia, mucus plugging, or significant IgE rise

👥 Who Is at Risk?

SAFS affects adults or children with:

• Severe asthma (high-dose ICS + additional controller medication)

• Recurrent exacerbations or persistent symptoms

• Evidence of IgE sensitisation to fungi, especially A. fumigatus, Alternaria, Cladosporium

It may overlap with ABPA, and some patients may transition between the two.

⚠️ Common Symptoms

• Poor asthma control despite optimal treatment

• Frequent exacerbations

• Airflow limitation (FEV1 often <80%)

• Increased oral corticosteroid use

• Wheeze, cough, chest tightness

🧪 Diagnosis

SAFS is a diagnosis of exclusion in patients with severe asthma and fungal sensitisation, but without ABPA.

Required Features:

1. Severe asthma, typically on BTS Step 4–5 therapy

2. Positive fungal-specific IgE (skin prick or blood) to at least one fungus

   • Aspergillus fumigatus most common

3. No ABPA: i.e., total IgE <1000 IU/mL, no eosinophilia, no central bronchiectasis

Investigations:

• Skin prick testing or specific IgE blood test

• Total IgE to exclude ABPA

• CT chest to rule out ABPA or CPA

• Sputum culture for A. fumigatus (not required for diagnosis)

💊 Treatment

Antifungal Therapy:

• Itraconazole (first-line): 3–6 months may improve asthma control, reduce exacerbations

• Posaconazole (alternative)

• Liver function and drug levels must be monitored

The EVITA 3 and Fungal Asthma trials suggest modest benefit with antifungal therapy in SAFS.

Asthma Management:

• High-dose inhaled corticosteroids + LABA

• Leukotriene receptor antagonists

• Macrolides in selected patients (anti-inflammatory benefit)

• Biologics:

  • Omalizumab (anti-IgE)

  • Mepolizumab, Benralizumab (anti-IL-5)

  • Dupilumab (anti-IL-4/13)

🧾 Monitoring

• Asthma control questionnaires (ACT, ACQ)

• Exacerbation frequency

• Spirometry

• Fungal IgE titres (do not typically change with treatment)

• LFTs and drug levels if on antifungals

📚 More Information

• SAFS patients often benefit from review in a specialist asthma clinic or severe asthma network centre.

• Overlap with ABPA: patients should be periodically reassessed to detect transition to ABPA.

• Patient resources: aspergillosis.org, Asthma + Lung UK, BTS asthma guidelines

• Resource: SAFS