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Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitization

The Fungal Asthma Sensitization Trial (FAST) Study

¹ School of Translational Medicine, University of Manchester, and ² North West Lung Centre, University Hospital of South Manchester, Manchester; ³ Respiratory Medicine, Salford Royal Foundation NHS Trust, Salford; ⁴ Preston Royal Hospital, Preston, Lancashire; ⁵ North Manchester General Hospital, Manchester; and ⁶ Department of Medical Statistics, University Hospital of South Manchester, Manchester, United Kingdom

Correspondence and requests for reprints should be addressed to D. W. Denning, F.R.C.P., Education & Research Centre, University Hospital of South Manchester, Southmoor Road, Manchester M23 9LT, UK. E-mail: ddenning{at}manchester.ac.uk

Rationale: Some patients with severe asthma are immunologically sensitized to one or more fungi, a clinical entity categorized as severe asthma with fungal sensitization (SAFS). It is not known whether SAFS responds to antifungal therapy.

Objectives: To evaluate the response of SAFS to oral itraconazole.

Methods: Patients with severe asthma sensitized to at least one of seven fungi by skin prick or specific IgE testing were recruited. All had total IgE less than 1,000 IU/ml and negative Aspergillus precipitins. They were treated with oral itraconazole (200 mg twice daily) or placebo for 32 weeks, with follow-up for 16 weeks.

Measurements and Main Results: The primary end point was change in the Asthma Quality of Life Questionnaire (AQLQ) score, with rhinitis score, total IgE, and respiratory function as secondary end points. Fifty-eight patients were enrolled, of whom 41% had been hospitalized in the previous year. Baseline mean AQLQ score was 4.13 (range, 1–7). At 32 weeks, the improvement (95% confidence interval) in AQLQ score was +0.85 (0.28, 1.41) in the antifungal group, compared with a –0.01 (–0.43, 0.42) change in the placebo group (P = 0.014). Rhinitis score improved (–0.43) in the antifungal, and deteriorated (+0.17) in the placebo group (P = 0.013). Morning peak flow improved (20.8 L/minute, P = 0.028) in the antifungal group. Total serum IgE decreased in the antifungal group (–51 IU/ml) but increased in placebo group (+30 IU/ml) (P = 0.001). No severe adverse events were observed, but seven patients developed adverse events requiring discontinuation, five in the antifungal group.

Conclusions: SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in about 60% of patients.

Clinical trial registered with www.controlled-trials.com (ISRCTN61552714).

Key Words: Aspergillus • Cladosporium • Candida • Alternaria • Penicillium

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Some patients with severe asthma are sensitized to fungi. Studies with the antifungal agent itraconazole showed benefit in allergic bronchopulmonary aspergillosis. What This Study Adds to the Field The results of this randomized controlled trial showed a significant quality of life benefit, a fall in IgE, and a modest improvement in rhinitis and morning peak flow, but not FEV1, in patients with severe asthma sensitized to one of several common fungi after oral antifungal therapy.

 

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