Asthma, Rhinitis, Other Respiratory Diseases
Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: A randomized controlled trial,☆☆

https://doi.org/10.1067/mai.2003.1388Get rights and content

Abstract

Background: Allergic bronchopulmonary aspergillosis (ABPA) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatu s, 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 fumigatu s, 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 fumigatu s (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.

Section snippets

Subjects

Eligible subjects with clinically stable ABPA were recruited from the Department of Respiratory and Sleep Medicine at John Hunter Hospital. The diagnosis of ABPA was based on the criteria of Patterson and Greenberger,1, 6 with a pre-existing diagnosis of asthma, positive immediate skin prick test response to A fumigatus (wheal >2 mm), increased serum total IgE level (>1000 IU/mL), and increased serum IgG and IgE antibody levels specific to A fumigatus . Subjects were further divided into those

Subject characteristics at baseline

Thirty-four subjects were screened, and 29 eligible subjects were randomized to receive either itraconazole (n = 15) or placebo (n = 14). There were 2 withdrawals from the itraconazole arm. One subject had nausea that developed within 2 weeks of starting treatment, and the subject's symptoms resolved 48 hours after ceasing the medication. The other subject was involved in a motor vehicle accident and withdrew because of injuries. In the placebo arm the subject who withdrew fell and broke her

Discussion

In this randomized, double-blind, placebo-controlled study we have shown that in subjects with clinically stable ABPA, the addition of 400 mg of itraconazole daily reduces airway inflammation, with a reduction in sputum eosinophils and a significant decrease in sputum ECP levels. In addition, there was evidence of a reduction in systemic immune activation in those treated with itraconazole, with significant decreases in total serum IgE and IgG antibodies to A fumigatus , together with fewer

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    Supported by NHMRC Australia.

    ☆☆

    Reprint requests: Peter G. Gibson, Airways Infection and Immunology Research, Department of Respiratory and Sleep Medicine, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, NSW, 2310, Australia.

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