Published ahead of print on October 23, 2008, doi:10.1164/rccm.200805-737OC Am. J. Respir. Crit. Care Med., Volume 179, Number 1, January 2009, 11-18 A more recent version of this article appeared on January 1, 2009
Submitted on May 15, 2008 Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitisation (SAFS)David W. Denning1*,1 School of Translational Medicine, University of Manchester, Manchester, United Kingdom; North West Lung Centre, University Hospital of South Manchester, Manchester, United Kingdom, 2 Respiratory Medicine, Salford Royal Foundation NHS Trust, 3 Preston Royal Hospital, Preston, United Kingdom, 4 Respiraory Medicine, North Manchester General Hospital, 5 Department of Medical Statistics, University Hospital of South Manchester, Manchester, United Kingdom * To whom correspondence should be addressed. E-mail: ddenning{at}manchester.ac.uk.
Rationale: Some patients with severe asthma are immunologically sensitized to one or more fungi, a clinical entity recently categorized as SAFS. It is not known if SAFS responds to antifungal therapy.
Objectives: To evaluate the response of SAFS to oral itraconazole.
Methods: Patients with severe asthma sensitized to Key words: asthma • exacerbation • rhinosinusitis • forced expiratory volume (FEV1) • azole
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1 of 7 fungi by skin prick or specific IgE testing were recruited. All had total IgE <1000 IU/mL and negative Aspergillus precipitins. They were treated with oral itraconazole (200mg twice daily) or placebo for 32 weeks, with follow up for 16 weeks.
Measurements: The primary endpoint was change in the Asthma Quality of Life Questionnaire score (AQLQ), with rhinitis score, total IgE and respiratory function as secondary endpoints.
Main results: 58 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% CI) in AQLQ score was +0.85 (0.28, 1.41) in the antifungal group, compared with -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/min, p=0.028) in the antifungal group. Total serum IgE decreased in the antifungal (-51 IU/mL) but increased in placebo group (+30 IU/mL) (p=0.001). No SAEs were observed, but 7 patients developed adverse events requiring discontinuation, 5 in the antifungal group.
Conclusions: SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in ~60% of patients.
Clinical Trials Registry Information: ID# ISRCTN61552714 registered at www.controlled-trials.com.
