Severe Asthma With Fungal Sensitization May Respond to Oral Antifungal Therapy

Laurie Barclay, MD

December 26, 2008

December 26, 2008 — Approximately 60% of patients with severe asthma with fungal sensitization (SAFS) respond to antifungal therapy, according to the results of a randomized controlled trial reported in the January 1, 2009, issue of the American Journal of Respiratory and Critical Care Medicine.

"Some patients with severe asthma are immunologically sensitized to one or more fungi, a clinical entity categorized as...SAFS," write David W. Denning, FRCP, from the University of Manchester, United Kingdom, and colleagues from the Fungal Asthma Sensitization Trial Study. "It is not known whether SAFS responds to antifungal therapy."

The goal of this study was to assess the response of patients with SAFS to treatment with oral itraconazole. Participants had severe asthma and were sensitized to at least 1 of 7 fungi based on skin prick or specific immunoglobin E (IgE) testing. In all participants, total IgE levels were less than 1000 IU/mL and Aspergillus precipitins results were negative.

Patients were randomly assigned to treatment with oral itraconazole, 200 mg twice daily, or placebo for 32 weeks, and they were followed up for 16 weeks. Change in the Asthma Quality of Life Questionnaire (AQLQ) score was the main outcome measure, and rhinitis score, total IgE, and respiratory function were secondary endpoints.

Among the 58 participants, 41% had been hospitalized in the previous year, and mean AQLQ score at baseline was 4.13 (range, 1 - 7). Mean improvement in AQLQ score at 32 weeks was +0.85 (95% confidence interval [CI], 0.28 - 1.41) in the antifungal group vs change of −0.01 (95% CI, −0.43 to 0.42) in the placebo group (P = .014). In a similar fashion, rhinitis score improved in the antifungal group and worsened in the placebo group (−0.43 vs +0.17; P = .013).

In the antifungal group, morning peak flow improved (20.8 L/minute; P = .028) and total serum IgE levels decreased (−51IU/mL), whereas total serum IgE levels increased in the placebo group (+30 IU/mL; P = .001).

Although there were no severe adverse events, 7 patients discontinued the study because of adverse events, including 5 in the antifungal group.

"SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in about 60% of patients," the study authors write.

Limitations of this study include small sample size, imprecise definition of fungal sensitization and fungal allergy, and recruitment lower than the initial target.

"The primary aim of this proof-of-concept study was to contribute key data to the long-standing debate about whether there is any direct link between fungal exposure and asthma," the study authors conclude. "Our data are most consistent with an important and poorly understood relationship. Our study results indicate that a new treatment approach using antifungal therapy in severe asthma is clinically useful, and that we have much to understand about the daily interaction between fungi and humans."

The Molton Trust and the Fungal Research Trust, both UK studies, supported this study. Some of the study authors have disclosed various financial relationships with Astellas, Merck, Pfizer, F2G, AstraZeneca, Indevus, Basilea, Vicuron (now Pfizer), Schering Plough, Nektar, Daiichi, Sigma Tau, Gilead, York Pharma, Myconostica, Ltd, Novartis, and/or GlaxoSmithKline.

Am J Respir Crit Care Med. 2009;179:11-18.