Severe asthma with fungal sensitisation - SAFS

Aspergillosis is an infection caused by the fungus Aspergillus. Aspergillosis describes a large number of diseases involving both infection and growth of fungus as well as allergic responses. Aspergillosis can occur in a variety of organs, both in humans and animals. Watch a short video clip about aspergillus.
The most common sites of infection are the respiratory apparatus (lungs, sinuses) and these infections can be:


Patients with SAFS have troublesome asthma. They are adult male or females, with a mean age at diagnosis of ~50 years. Their pulmonary function measured by FEV1 or peak flow varies from 20-120% predicted, depending on how well their disease is controlled.


Many have significant nasal symptoms with runny nose, sneezing and hayfever- like symptoms. They do not produce plugs of sputum, like ABPA patients do, although CT scans may show some mucous in airways. Eosinophilia is common. Most are completely dependent on high dose inhaled corticosteroids, with intermittent courses of oral steroids required for exacerbations, and some on continuous oral steroids. Chronic persistent asthma symptoms which are poorly controlled by multiple medications is a common feature for SAFS. Admission to hospital for asthma exacerbations is also common. 
The criteria for defining SAFS are

  • Severe asthma (British Thoracic Society step 4 or worse)
  • Exclusion of ABPA ( total IgE <1000 IU/mL)
  • Evidence of sensitisation to one or more fungi, by skin prick test or RAST test

While some patients are sensitised to many fungi, the majority only react to one of two fungi. The commonest fungi that patients are sensitised to are A. fumigatus and C. albicans, with A. alternata, Trichopyton spp., Cladosporium herbarum, Penicillium chrysogenum and Botrytis cinerea. Skin test results are often not concordant with RAST results. RAST titres (to A. fumigatus) are much lower than titres in patients with ABPA.


Patients with SAFS are usually on multiple medications. Long-term inhaled and frequent courses of oral corticosteroids, usually control the patients worst symptoms, but have well known adverse events. These patients are usually already taking either short or long-acting beta-2 agonists, or leukotriene antagonists with some benefit. 
Antifungal therapy with itraconazole (200mg orally, twice daily) is beneficial in having a major effect on pulmonary and nasal symptoms. (Therapeutic drug monitoring is advised for itraconazole to optimize exposure to itraconazole, which may require switching between capsules and oral solution, and sometimes raising or lowering the dose). Fluconazole may be beneficial in those sensitised to Trichophyton spp. The required duration of antifungal therapy is uncertain.