Background: Allergic bronchopulmonary aspergillosis (ABPA) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatus, causing an intense systemic immune response and progressive lung damage. Objective: We sought to determine whether treatment with the antifungal agent itraconazole reduced eosinophilic airway inflammation in subjects with ABPA. Methods: A randomized, double-blind, placebo-controlled trial was performed in stable subjects with ABPA (n=29). Subjects received 400 mg of itraconazole per day (n=15) or placebo (n=14) for 16 weeks. All subjects were reviewed monthly with history, spirometry, and sputum induction to measure airway inflammation, serum total IgE and IgG levels to A fumigatus, and blood eosinophil counts. Results: By using regression analysis in a random-effects model, subjects receiving itraconazole had a decrease in sputum eosinophils of 35% per week, with no decrease seen in the placebo arm (P<.01). Sputum eosinophil cationic protein levels decreased with itraconazole treatment by 42% per week compared with 23% in the placebo group (P<.01). Itraconazole reduced systemic immune activation, leading to a decrease in serum IgE levels (310 IU/mL) compared with levels seen in the placebo group (increase of 18 IU/mL, P<.01) and a decrease in IgG levels to A fumigatus (15.4 IU/mL) compared with levels seen in the placebo group (increase of 3.7 IU/mL, P =.03). There were fewer exacerbations requiring oral corticosteroids in those treated with itraconazole compared with in the placebo group (P=.03). Conclusion: Itraconazole treatment of subjects with stable ABPA reduces eosinophilic airway inflammation, systemic immune activation, and exacerbations. These results imply that itraconazole is a potential adjunctive treatment for ABPA.
Journal of Allergy and Clinical Immunology Vol. 111, Issue 5, p. 952-957