Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitization: The Fungal Asthma Sensitization Trial (FAST) Study

• Published in: American journal of respiratory and critical care medicine 2009-01, Vol.179 (1), p.11-18
• Main Authors: Denning, David W, O'Driscoll, B. Ronan, Powell, Georgina, Chew, Fiona, Atherton, Graham T, Vyas, Aashish, Miles, John, Morris, Julie, Niven, Robert M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antifungal Agents - blood; Antifungal Agents - therapeutic use; Asthma; Asthma - drug therapy; Asthma - microbiology; Asthma - physiopathology; Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; Female; Fungi; Good Manufacturing Practice; Humans; Intensive care medicine; Itraconazole - blood; Itraconazole - therapeutic use; Male; Medical sciences; Middle Aged; Pathogenesis; Patients; Pneumology; Quality of Life; Questionnaires; Respiratory Function Tests; Rhinitis; Steroids; Surveys and Questionnaires; Treatment Outcome; VOCs; Volatile organic compounds; Young Adult
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200805-737OC

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. To evaluate the response of SAFS to oral itraconazole. 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. 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. SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in about 60% of patients.