The Journal of Allergy and Clinical Immunology
Volume 111, Issue 5 , Pages 952-957, May 2003

Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: A randomized controlled trial2

    BMed, PhD, FRACP
  • Peter Alexander Blanch Wark

      Affiliations

    • Faculty of Health, University of Newcastle, Newcastle Australia
    • Department of Immunology and Infectious Diseases, John Hunter Hospital, Newcastle Australia
    • Medical School, University of Manchester, Manchester UK
    • Dr Wark is now with the Respiratory Cell and Molecular Biology Research Division, Southampton General Hospital, Southampton.
    • , MBBS, PhD, FRACP, FAFPHM
  • Michael John Hensley

      Affiliations

    • Faculty of Health, University of Newcastle, Newcastle Australia
    • Department of Immunology and Infectious Diseases, John Hunter Hospital, Newcastle Australia
    • Medical School, University of Manchester, Manchester UK
    • , MBBS, FRACP, FRCP, FRCPI, FCCP
  • Nicholas Saltos

      Affiliations

    • Faculty of Health, University of Newcastle, Newcastle Australia
    • Department of Immunology and Infectious Diseases, John Hunter Hospital, Newcastle Australia
    • Medical School, University of Manchester, Manchester UK
    • , MD, FRACP, FRCPA
  • Michael James Boyle

      Affiliations

    • Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle Australia
    • , Grad Dip Clin Epid
  • Ruth Christine Toneguzzi

      Affiliations

    • Faculty of Health, University of Newcastle, Newcastle Australia
    • Department of Immunology and Infectious Diseases, John Hunter Hospital, Newcastle Australia
    • Medical School, University of Manchester, Manchester UK
    • , BSc (Hons)
  • Jodie Louise Simpson

      Affiliations

    • Faculty of Health, University of Newcastle, Newcastle Australia
    • Department of Immunology and Infectious Diseases, John Hunter Hospital, Newcastle Australia
    • Medical School, University of Manchester, Manchester UK
    • , PhD
  • Patrick McElduff

      Affiliations

    • Airways Infection and Immunology Research Group, John Hunter Hospital, Newcastle Australia
    • , MBBS, FRACP
  • Peter Gerard Gibson

      Affiliations

    • Faculty of Health, University of Newcastle, Newcastle Australia
    • Department of Immunology and Infectious Diseases, John Hunter Hospital, Newcastle Australia
    • Medical School, University of Manchester, Manchester UK
    • Corresponding Author InformationReprint 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.

Received 16 July 2002; received in revised form 10 January 2003; accepted 15 January 2003.

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.

Key words: Itraconazole, allergic bronchopulmonary aspergillosis, airway inflammation, induced sputum, asthma

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2 Supported by NHMRC Australia.

PII: S0091-6749(03)80120-3

doi:10.1067/mai.2003.1388

The Journal of Allergy and Clinical Immunology
Volume 111, Issue 5 , Pages 952-957, May 2003

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