Fungal Sensitisation Associated Asthma

Fungal sensitisation associated asthma is severe or poorly controlled asthma with IgE sensitisation to fungi (Aspergillus fumigatus, Alternaria, Cladosporium, Penicillium) that does not meet the criteria for allergic bronchopulmonary aspergillosis. Antifungal treatment may help in selected patients.

Pathophysiology. Inhaled fungal spores and mycelium trigger IgE-mediated type 2 inflammation and may colonise the airways. Persistent fungal colonisation in the lower airway sustains inflammation.

Severe asthma with fungal sensitisation is more common than allergic bronchopulmonary aspergillosis, and these patients have no bronchiectasis or mucus plugging on CT.

Fungal exposure is higher in damp housing, agricultural work and decaying vegetation, and in some countries rises in autumn.

• Severe or poorly controlled asthma with frequent exacerbations
• Allergic rhinitis, sinusitis and nasal polyps
• Expectoration of brown mucus plugs (less often than in allergic bronchopulmonary aspergillosis)
• Symptoms worse in damp environments or during autumn
• Blood eosinophilia
• Oral corticosteroid dependence

• Specific IgE to Aspergillus fumigatus over 0.35 kUA/L (or positive skin prick test to fungi), and to Alternaria, Cladosporium and Penicillium.
• Total IgE: under 1000 IU/mL (high levels suggest allergic bronchopulmonary aspergillosis).
• Exclude allergic bronchopulmonary aspergillosis: serum IgG to Aspergillus, eosinophil count, and high resolution CT for central bronchiectasis and high attenuation mucus.
• Sputum fungal culture and PCR to confirm colonisation.
• Asthma assessment: spirometry, fractional exhaled nitric oxide, adherence and technique review.

Differential diagnosis.

• Allergic bronchopulmonary aspergillosis
• Severe type 2 asthma without fungal sensitisation
• Chronic pulmonary aspergillosis and aspergilloma
• Eosinophilic granulomatosis with polyangiitis
• Cystic fibrosis
• Hypersensitivity pneumonitis

• Optimise usual asthma treatment: high dose inhaled corticosteroid with formoterol, long acting muscarinic antagonist and montelukast 10 mg at night, with technique and adherence review.
• Reduce exposure: repair damp, ventilate, avoid mouldy buildings, compost and decaying vegetation, and use masks in high risk work.
• Antifungal therapy for selected patients with persistent poor control: itraconazole 200 mg orally twice daily (with food, as capsules) for 3 to 6 months, with trough itraconazole level of 1 mg/L or more (reduce or stop if toxicity). Voriconazole is an alternative. Monitor liver enzymes, blood pressure, potassium and oedema.
• Interactions: itraconazole raises levels of budesonide and fluticasone, with adrenal suppression, so switch to beclometasone or ciclesonide during treatment.
• Biologic therapy (omalizumab by weight and IgE, or an anti-IL-5 agent) for severe disease with persisting exacerbations.
• Oral corticosteroid bursts for exacerbations: prednisolone 40 to 50 mg daily for 5 days.
• Treat upper airway disease: intranasal corticosteroid and saline irrigation.

Special groups.

• Patients on antifungal therapy: check drug interactions, since itraconazole interacts with many medicines (statins, calcium channel blockers, anticoagulants).

Monitoring. Symptom control, spirometry and exacerbation count every 3 months. Liver enzymes at 2 weeks, then monthly during antifungal therapy. Trough itraconazole level at 2 weeks. Total IgE and Aspergillus IgE yearly.

Referral and escalation. Refer to a severe asthma service for suspected fungal sensitisation with poor control. Urgent for haemoptysis, new infiltrate, or features of allergic bronchopulmonary aspergillosis.