Itraconazole treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is a potentially fatal inflammatory disease due to the dual-type immune response provoked by the fungal antigens. Despite serious side effects long-term treatment with corticosteroids is often required. Itraconazole has been reported to be a useful steroid-sparing agent.


METHODS
In a retrospective follow-up of 21 CF patients from a total of 250 treated once or twice within a five-year study period (1994-98), 9 patients were treated with systemic glucocorticosteroids in combination with itraconazole and 12 patients were treated with itraconazole (200-600 mg/day) as monotherapy.


RESULTS
During treatment the percentage of Aspergillus fumigatus (AF)-positive sputum cultures significantly reduced (P < 0.05); precipitating antibodies to AF decreased significantly in all patients (P < 0.05); forced expiratory volume (FEV1) increased to pre-exacerbation level; total IgE levels decreased in 42% of patients on monotherapy and in 56% on combination therapy. Specific IgE (radioallergosorbant; RAST) level decreased in 6 of 21 patients. Eleven patients had transient increased levels of alanine transaminase (ALAT). One patient had isolated increase in alkaline phosphatase and another in aspartate transaminase (ASAT).


CONCLUSIONS
High dose itraconazole as monotherapy or in combination with systemic glucocorticosteroids seems effective in CF patients with ABPA. No hepatotoxicity was observed during long-term therapy.
CF Center, Department of Pediatrics, National University Hospital, Rigshospitalet, Copenhagen, Denmark.
M
M
Skov
N
N
Høiby
C
C
Koch
D000908:Antibodies, Fungal / Q000032:analysis; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D001232:Aspergillus fumigatus / Q000276:immunology / Q000302:isolation & purification; D003550:Cystic Fibrosis / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D007958:Leukocyte Count; D008099:Liver / Q000503:physiopathology; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology
D000908:Antibodies, Fungal; D000935:Antifungal Agents; D005938:Glucocorticoids; D017964:Itraconazole; D007073:Immunoglobulin E; D011239:Prednisolone