Efficacy and safety of nebulised amphotericin B (NAB) in severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA)

Abstract

Background and rationale: 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). Conclusion: 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.

• Asthma
• asthma pharmacology
• aspergillus lung disease
• allergic lung disease

Acknowledgements

The authors would like to acknowledge Mrs Sigrid Whiteside, medical statistician, for her contribution towards data analysis and help in graphical presentations. We would also like to acknowledge Dr Graham Atherton for all the help provided during analysis and Chris Harris who helped out with initial clerical work.

Declaration of interest

Dr Livingstone Chishimba has received travel and conference sponsorship from Astra Zeneca, GSK, Novartis, Astellas and Chiesi pharmaceuticals. He has received speaker fees from Chiesi. None of these activities have any relationship with design, conduct of study, analysis or publication of this study.

Prof David Denning holds founder shares in F2G Ltd, a University of Manchester spin-out company, and has current grant support from the National Institute of Allergy and Infectious Diseases, National Institute of Health Research, the European Union and the Fungal Infection Trust. He acts as a consultant to Trinity group, T2 Biosystems, GSK, Sigma Tau, Oxon Epidemiology as well as other companies over the last 5 years including Merck and Astellas. In the last 3 years, he has been paid for talks on behalf of Astellas, Gilead and Pfizer.

Dr Robert Niven Has received travel and conference sponsorship from Astra Zeneca, GSK and Novartis pharmaceuticals. None of these activities have any relationship with design, conduct of study, analysis or publication of this study.

Mrs Georgina Powell and Mr Philip Langridge have no interests to declare.