S92 Nebulised Amphotericin in Allergic bronchopulmonary Aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS)

Abstract

Background and rationale Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) are debilitating lung diseases whose treatment is not yet fully established. Some published case reports/series suggest that nebulised amphotericin (liposomal) may have a role in the treatment of cystic fibrosis (CF) ABPA but little is known regarding its appropriateness in asthmatic ABPA and SAFS patients. We assessed the efficacy and safety of nebulised Amphotericin as second and third line therapy. Methods 20 adult asthmatics with SAFS (n = 11) and ABPA (n = 9) were treated with nebulised amphotericin between January 2011 and May 2013. All patients had either failed itraconazole (n = 8), voriconazole preceded by itraconazole (n = 5) or developed adverse events (AEs) to either agent (n = 7). 10 mg of Nebulised amphotericin B (Fungizone) was administered using a Pari LC plus nebulizer twice/day, preceded by salbutamol, under direct physiotherapist observation. We audited clinical, radiological and immunological response, including change in the Asthma Quality of Life Questionnaire (AQLQ-J) scores .We also examined Asthma Control Questionnaire (ACQ) scores, change in lung function (FEV1), change in IgE (total and specific) and healthcare utilization. Patients were followed up for 12 months during which they were evaluated at 2, 4, 6, 9 and 12 months. Results There were 20 patients analysed (SAFS, n = 11) and (ABPA n = 9), M: F = 8:12, median age 65.5 yrs (range = 24-78). The median duration of therapy was 30 days (IQR, 0.0-142). Clinical benefit was observed in 2 (10%) in which mean ACQ score improved from 6 to 2, overall mean AQLQ score improved by 0.95 and mean FEV1 improved by 1.2 L(63.1%). Seven (35%) failed the challenge due to adverse events (bronchospasm). 11 (55%) discontinued within 12 months of therapy due to delayed bronchospasm (n = 3, within 4 weeks), equipment problems/patient inconvenience (n = 4) and lack of clinical benefit (n = 4) (fig 1). There were no significant changes in immunological and radiological outcomes. Conclusion Our data suggests that the overall efficacy of nebulised amphotericin in this group of patients may be poor and is associated with high frequency of adverse events. However, the responses were excellent in 2 (10%) patients. It is not clear which patients are likely to respond. Further studies need to be conducted to establish the optimal dose range (dose, frequency), nebulizer type, pressures and identification of patients who may respond. (Figure Presented).