title: Efficacy and safety of nebulised amphotericin B (NAB) in severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA).
abstract: OBJECTIVE
  Antifungal therapy for severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) remains poorly studied. We assessed the efficacy and safety of NAB as second and third line therapy in SAFS and ABPA.
  
  
  METHODS
  21 adult asthmatics with SAFS (n = 11) and ABPA (n = 10) who had either failed itraconazole (n = 8), voriconazole proceeded by itraconazole (n = 5) or developed adverse events (AEs) to either agent (n = 7) were treated with 10mg of NAB (Fungizone) twice daily. We audited clinical and immunological response, using the Asthma Quality of Life Questionnaire (AQLQ-J) scores, asthma control, FEV1, healthcare utilisation and IgE. Patients were followed up for 12 months.
  
  
  RESULTS
  Twenty-one patients were treated (SAFS, n = 11) and (ABPA, n = 10), M: F = 8:12, median age 65 years (range, 24-78). The median duration of therapy was 30 days (0-1825). Clinical benefit was observed in three (14.3 %) in which overall mean AQLQ-J score improved by + 2.9, mean FEV1 improved by 0.5 L and there was improvement in overall asthma control. Seven (33%) failed initial dose (bronchospasm). Eleven (52.4%) discontinued within 12 months of therapy due to delayed bronchospasm (n = 3, within 4 weeks), equipment problems (n = 2, within 4 weeks) and lack of clinical benefit (n = 4, within 16 weeks).
  
  
  CONCLUSIONS
  Our data suggest that the overall efficacy of NAB in this group of patients is poor and associated with bronchospasm. However, the excellent response in 3 patients, suggest it may be considered when other alternatives have been exhausted. Overcoming the initial bronchospasm may improve tolerability.
authors.affiliation: Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, The University of Manchester , Manchester , UK .
authors.forename: Livingstone
authors.initials: L
authors.lastname: Chishimba
authors.forename: Philip
authors.initials: P
authors.lastname: Langridge
authors.forename: Georgina
authors.initials: G
authors.lastname: Powell
authors.forename: Robert M
authors.initials: RM
authors.lastname: Niven
authors.forename: David W
authors.initials: DW
authors.lastname: Denning
mesh_terms: D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000188:drug therapy* / Q000453:epidemiology*; D001249:Asthma / Q000453:epidemiology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011788:Quality of Life; D065819:Voriconazole / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D000666:Amphotericin B; D065819:Voriconazole
keywords: Asthma; allergic lung disease; aspergillus lung disease; asthma pharmacology