Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: A randomized controlled trial

Patrick Mcelduff, P. A B Wark, Michael John Hensley, Nicholas Saltos, Michael James Boyle, Ruth Christine Toneguzzi, Jodie Louise Simpson, Patrick McElduff, Peter Gerard Gibson

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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 cortico-steroids 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.
    Original languageEnglish
    Pages (from-to)952-957
    Number of pages5
    JournalJournal of Allergy and Clinical Immunology
    Volume111
    Issue number5
    DOIs
    Publication statusPublished - 1 May 2003

    Keywords

    • Airway inflammation
    • Allergic bronchopulmonary aspergillosis
    • Asthma
    • Induced sputum
    • Itraconazole

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