Lennert Slobbe1, Eric Boersma, Bart J A Rijnders. 1. Department of Internal Medicine, Division of Infectious Diseases, Erasmus MC, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Abstract
BACKGROUND:Invasive pulmonary aspergillosis (IPA) is a leading cause of mortality in immunocompromised patients, with the highest risk observed in patients with acute leukaemia or lung transplantation. IPA-prophylactic strategies include administration of aerosolized amphotericin-B. Liposomal amphotericin-B (L-AmB) is one of the formulations available, although few data exist on safety and tolerability. METHODS: Data on tolerability, systemic toxicity and effects of aerosolized L-AmB on pulmonary function were recorded in a subgroup out of 271 haematological patients enrolled in aplacebo-controlled trial on the efficacy of aerosolized L-AmB for the prevention of IPA. Using an adaptive aerosol-delivery system, nebulization of L-AmB or placebo was performed during chemotherapy-induced neutropenia for 30 min/day on 2 consecutive days/week with a maximum of 6 weeks. RESULTS: Thirty-eight patients (41 episodes) received L-AmB, 39 patients (49 episodes) received placebo. Proportions of patients with >20% post-nebulization decline in forced expiratory volume in 1s (FEV(1)) or forced vital capacity (FVC) did not differ between groups. Also 26/38 L-AmB patients (68%) versus 31/39 patients (79%) on placebo had no significant decline during the entire treatment (p=0.20). Coughing was significantly more reported in L-AmB patients (p<0.0001). No differences were observed when baseline and post-nebulization serum levels of renal function and hepatic enzymes were compared. CONCLUSIONS: Short-term prophylactic nebulization of L-AmB was well tolerated and not associated with decline in pulmonary function or systemic adverse effects.
RCT Entities:
BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a leading cause of mortality in immunocompromised patients, with the highest risk observed in patients with acute leukaemia or lung transplantation. IPA-prophylactic strategies include administration of aerosolized amphotericin-B. Liposomal amphotericin-B (L-AmB) is one of the formulations available, although few data exist on safety and tolerability. METHODS: Data on tolerability, systemic toxicity and effects of aerosolized L-AmB on pulmonary function were recorded in a subgroup out of 271 haematological patients enrolled in a placebo-controlled trial on the efficacy of aerosolized L-AmB for the prevention of IPA. Using an adaptive aerosol-delivery system, nebulization of L-AmB or placebo was performed during chemotherapy-induced neutropenia for 30 min/day on 2 consecutive days/week with a maximum of 6 weeks. RESULTS: Thirty-eight patients (41 episodes) received L-AmB, 39 patients (49 episodes) received placebo. Proportions of patients with >20% post-nebulization decline in forced expiratory volume in 1s (FEV(1)) or forced vital capacity (FVC) did not differ between groups. Also 26/38 L-AmBpatients (68%) versus 31/39 patients (79%) on placebo had no significant decline during the entire treatment (p=0.20). Coughing was significantly more reported in L-AmBpatients (p<0.0001). No differences were observed when baseline and post-nebulization serum levels of renal function and hepatic enzymes were compared. CONCLUSIONS: Short-term prophylactic nebulization of L-AmB was well tolerated and not associated with decline in pulmonary function or systemic adverse effects.