BAFungal diseases in patients with asthma

SAFS can be a troublesome asthma. Patients are often 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. Presentation: Many have significant nasal symptoms with runny nose, sneezing and hay fever- like symptoms. They do not produce plugs of sputum, like ABPA patients do, although CT scans may show some mucous in airways. ABPA is a hypersensitivity reaction rather than a true infection. – The pathogenesis of ABPA is not completely understood, but specific IgE-mediated type I hypersensitivity reactions, specific IgG-mediated type III hypersensitivity reactions, and abnormal T-lymphocyte cellular immune responses have all been implicated. – It most commonly occurs in patients with asthma or cystic fibrosis. Diagnosis – Patients with ABPA usually present with episodic wheezing, occasional productive cough Eosinophilia is common feature of SAFS. 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 Diagnosis and Diagnostic Criteria Criteria Used for the Diagnosis of ABPA Rosenberg-Patterson criteria A = Asthma R = Roentgenographic fleeting pulmonary opacities T = Skin test positive for Aspergillus (type I reaction, immediate cutaneous hyperreactivity) E = Eosinophilia P = Precipitating antibodies (IgG) in serum I = IgE in serum elevated (>1,000 IU/mL) C = Central bronchiectasis S = Serums A fumigatus-specific IgG and IgE (more than twice the value of pooled serum samples from patients with asthma who have Aspergillus hypersensitivity) Minor criteria

  1. Positive presence of Aspergillus in sputum
  2. Expectoration of brownish black mucus plugs
  3. Delayed skin reaction to Aspergillus antigen (type III reaction) The presence of six of eight major criteria makes the diagnosis almost certain.

The disease is further classified as ABPA-S or ABPA-CB on the absence or presence of central bronchiectasis, respectively Minimal ABPA-CB (Central Bronchiectasis)

  1. Asthma
  2. Immediate cutaneous hyperreactivity to Aspergillus antigens
  3. Central bronchiectasis
  4. Elevated IgE
  5. Raised A fumigatus-specific IgG and IgE Minimal ABPA-S (Serum)

 

  1. Asthma
  2. Immediate cutaneous hyperreactivity to Aspergillus antigens
  3. Transient pulmonary infiltrates on chest radiograph
  4. Elevated IgE
  5. Raised A fumigatus-specific IgG and IgE

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. Treatment: 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.

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