Severe Asthma With Fungal Sensitization May Respond to Oral Antifungal Therapy

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Severe Asthma With Fungal Sensitization May Respond to Oral

Antifungal Therapy

http://www.medscape.com/viewarticle/585975

Laurie Barclay, MD

Medscape - USA

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

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

& #8722;0.01 (95% CI, & #8722;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 ( & #8722;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 ( & #8722;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 GlaxoKline.

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