Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitisation (SAFS).

Author(s): Denning DW, O'Driscoll BR, Powell G, Chew F, Atherton GT, Vyas A, Miles J, Morris J, Niven RM

Affiliation(s): School of Translational Medicine, University of Manchester, Manchester, United Kingdom; North West Lung Centre, University Hospital of South Manchester, Manchester, United Kingdom.

Publication date & source: 2008-10-23, Am J Respir Crit Care Med., [Epub ahead of print]

Publication type:

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 >/=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.