Antifungal Drug Improves Severe Asthma Symptoms

[Guest guest]

The results of Professor Denning's Fungal Asthma Sensitization Trial

(FAST) study were published in the Jan 2009 edition of the AMERICAN

JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE and shows dramatic

improvement of asthma with Iraconazole (Sporonox).

This study will be very helpful when approaching your physician or

your insurance company.

Below is a preview of the study results from MedPage Today and can be

accessed at

http://www.medpagetoday.com/AllergyImmunology/Asthma/12273

At the end of the article, you may contribute your own thoughts,

experience, questions, and knowledge to this story for the benefit of

all MedPage Today readers. Also, Graham Atherton is asking for

severe asthmatics in both UK & USA who would be prepared to share

their own experiences with antifungal treatment.

www.aspergillus.man.ac.uk

The complete article can be purchased directly from the journal for

$10 ar

http://ajrccm.atsjournals.org/cgi/reprint/179/1/11

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Action Points

Explain to interested patients that the study involved patients

with severe asthma symptoms who showed fungal sensitivity in skin-

prick tests.

Explain that the study was a randomized trial, the strongest kind

of research, but involved a relatively small number of patients.

Explain that itraconazole is FDA-approved for treating fungal

infections but not for reducing asthma symptoms in the absence of

overt fungal infection.

Explain that itraconazole can cause side effects, and that many

patients in the study dropped out because of adverse effects.

None of those in the trial had an overt clinical fungal infection.

But morning peak airflow, rhinitis symptoms, IgE levels, and quality

of life were all significantly improved following 32 weeks of oral

itraconazole compared with placebo.

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MANCHESTER, England, Dec. 29 -- Severe asthma symptoms were relieved

in patients who took the antifungal drug itraconazole (Sporanox),

showed a small randomized trial.

So reported W. Denning, M.D., of the University of Manchester,

and colleagues in the Jan. 1 issue of the American Journal of

Respiratory and Critical Care Medicine.

A small percentage of severely asthmatic patients show clear

sensitivity to Aspergillus fungi that persistently infect their

airways.

But up to 50% of patients with severe asthma are sensitized to

various fungal allergens without signs of clinical infection, Dr.

Denning and colleagues wrote.

They hypothesized that severely asthmatic patients with fungal

sensitivity may have subclinical infections that would benefit from

itraconazole therapy, prompting the clinical trial.

The researchers enrolled 58 severely asthmatic patients who showed

fungal sensitivity in skin-prick tests. They were randomized to

placebo or 200 mg of itraconazole twice daily.

Outcomes included scores on the seven-point Asthma Quality of Life

Questionnaire, forced expiratory volume in one second, morning and

evening peak expiratory flow, and serum IgE levels.

Assessments were reported on a modified intent-to-treat basis, which

excluded three patients randomized to itraconazole and one in the

placebo group who dropped out within the first four study weeks.

Key results, reported as means, were:

Change in quality of life score: +0.85 itraconazole, -0.01 placebo

(P=0.014)

Patients showing at least 0.75-point improvement in quality of life

score: 54% itraconazole, 18% placebo (P=0.013)

Change in total IgE: -27% itraconazole, +12% placebo (P=0.001)

Change in FEV1: -0.22 L itraconazole, -0.02 L placebo (P=0.22)

Change in morning peak flow: +20.8 L/min itraconazole, -5.5 L/min

placebo (P=0.028)

Change in evening peak flow: +16.8 L/min itraconazole, +8.9 L/min

placebo (P=0.74)

" The supposition is that antifungal therapy reduces allergen exposure

directly by killing viable filamentous fungi, " the researchers

concluded.

Dr. Denning and colleagues called the study " proof-of-concept "

research, but said it shows " a new treatment approach using anti-

fungal therapy in severe asthma is clinically useful. "

" We have much to understand about the daily interaction between fungi

and humans, " they added, noting that it was unclear where fungal

pathogens might have been hiding in their patients.

Colonization in the skin, the nose, or the gut -- not necessarily in

the airway -- might generate ongoing exposure to fungal antigens, the

researchers said.

Dr. Denning and colleagues said a high withdrawal rate was a

significant concern.

Of the study's original 58 participants, 17 did not complete the full

32 weeks of treatment. Eleven of the patients who dropped out were in

the itraconazole arm.

Adverse events or general ill health were cited by 10 patients as the

reason for withdrawal, including eight in the itraconazole arm.

Heffner, M.D., of Providence Portland Medical Center in

Portland, Ore., the past president of the American Thoracic Society,

said the findings supported a role for unrecognized fungal infections

in at least some severe asthma cases.

" Colonization with fungal species may generate immunologic responses

in patients with asthma that perpetuate airway inflammation and blunt

the effectiveness of drug therapy, " he said in a statement issued by

the society, which publishes the American Journal of Respiratory and

Critical Care Medicine.

" One can't help but wonder if antifungal therapy would benefit all

severe asthmatics regardless of sensitivity to fungi, " said Dr.

Heffner.

The study was supported by the Molton Trust and the Fungal Research

Trust.

Study authors reported relationships with Astellas, Merck, Pfizer,

F2G, AstraZeneca, Indevus, Basilea, Schering Plough, Nektar, Daiichi,

Sigma Tau, Gilead, York Pharma, Myconostica, Novartis, and

GlaxoKline.

Primary source: American Journal of Respiratory and Critical Care

Medicine

Source reference:

Denning D, et al " Randomized controlled trial of oral antifungal

treatment for severe asthma with fungal sensitization: the Fungal

Asthma Sensitization Trial (FAST) study " Am J Respir Crit Care Med

2009; 179: 11-18.