Study finds nearly 5 million asthmatics worldwide could benefit from antifungal therapy

An estimated 4,837,000 asthmatics with allergic bronchopulmonary aspergillosis (ABPA) could benefit substantially from antifungal treatment, say researchers from the University of Toronto and Manchester University.

Their work, published today in the journal Medical Mycology, has also re-estimated the total number of asthmatics worldwide – to reveal a staggering 193 million sufferers. Twenty-four million asthma sufferers live in the United States, 20 million each in India and China, and seven million in the United Kingdom.

Clinical studies have shown that oral antifungal drugs significantly improve symptoms and asthma control in asthmatics with ABPA, treatment endorsed by the Cochrane Collaboration. This is the first time that a global estimate of ABPA numbers has been made.

In national league tables of asthma rates in adults, only Australia and Sweden have a higher prevalence than the UK. In global league tables of ABPA occurrence, New Zealand tops the list with a 3.5% rate in new patients attending chest clinics at hospitals. The rates were 2.6% in Cape Town, 2.3% in Saudi Arabia, 2.5% in China and 0.7% in an older study from Ireland. No population-based studies have been done.

In addition to standard asthma therapy, the antifungal therapy used is itraconazole – now a generic, inexpensive antifungal – with a response rate of 60%. The researchers also found that antifungal therapy also benefits patients with severe asthma sensitized to fungi, called SAFS.

Alternatives include voriconazole and posaconazole, which have 75-80% response rates. In a recent assessment of voriconazole and posaconazole for both ABPA and SAFS, 75% of patients were able to stop taking oral corticosteroids, a major benefit, and 38% of patients had their asthma severity downgraded on antifungal therapy.

Allergic bronchopulmonary aspergillosis (ABPA) is a chronic pulmonary eosinophilic hypersensitivity reaction resulting in airflow obstruction and bronchiectasis. Disease results from an exaggerated allergic response to several fungal species, particularly Aspergillus fumigatus, which accounts for nearly 90% of cases. The exact mechanism is unknown; however, several host factors and specific IgE-mediated type-I, IgG-mediated type-III, and (under investigation) cell-mediated type-IV hypersensitivity reactions are thought to contribute to the pathogenesis of this disorder.

First described by Hinson and colleagues in 1952, ABPA is a disease nearly exclusively seen in those with underlying obstructive or bronchiectatic airways disorders. Among those with asthma, a recent epidemiologic study by Novey and colleagues estimated that ABPA occurs between 0.25% and 11%. However, the reported prevalence of ABPA in this population has varied widely and may be greater than 20% among those with poorly controlled asthma.

While asthma is the most common and best understood contributing factor, ABPA is also prominent among those with cystic fibrosis and other underlying bronchiectatic diseases. The reported prevalence of ABPA among those with cystic fibrosis also varies and is estimated to occur in 1%-15% of patients. Although less described, other associated conditions include allergic rhinitis, allergic fungal sinusitis, bronchocentric granulomatosis, atopic dermatitis, and contact dermatitis. A familial occurrence pattern has been described but is not well understood. Associations with hyper-IgE syndrome and chronic granulomatous diseases have been described. These underlying etiologies are important to identify because concurrent steroid treatment may precipitate invasive fungal infections.


Professor David Denning, professor of medicine and medical mycology at the University of Manchester and Director of the University Hospital of South Manchester’s National Aspergillosis Centre, led the study into the total number of asthmatics worldwide. He said the study results implied that asthma admissions and deaths could be avoided with more extensive use of antifungal therapy.

“We were surprised by the number of patients with ABPA, and by the lack of community based studies done,” he said. “Our National Aspergillosis Centre treats hundreds of these patients each year, generally with major improvement, and so a conscious program to seek out ABPA from all asthmatics is required.”

Allergic Bronchopulmonary Aspergillosis (ABPA)
Overview

Allergic Bronchopulmonary Aspergillosis (ABPA) is an allergic or hypersensitive reaction to a fungus known as Aspergillus fumigatus. This is a fungi found in the soil.

Although most of us are frequently exposed to Aspergillus, a reaction to it is rare in people with normal immune systems. However, in certain people, the immune system overreacts to the antigens of Aspergillus fumigatus found in the lungs. This may damage the airways and result in permanent lung damage.

ABPA most commonly affects people with asthma or cystic fibrosis. Many people with ABPA also suffer from allergic conditions such as atopic dermatitis (eczema), urticaria (hives), allergic rhinitis (hay fever) and sinusitis.


Symptoms & Diagnosis

Symptoms
If you have asthma, the first noticeable symptoms of ABPA are usually progressive worsening of your asthma symptoms such as wheezing and shortness of breath.

Other symptoms of ABPA include:
•  Cough with brownish flecks or bloody mucous
•  Fever
•  General weakness or malaise


Diagnosis

Diagnosis for ABPA is determined by health history, x-rays or CT scans, allergy skin testing and/or blood tests.

Professor Donald Cole of the Dalla Lana School of Public Health at the University of Toronto was the senior author of the study and contributed his expert epidemiological knowledge to the development of the model and provided a ‘reality’ check of the model’s estimates.

To view the paper entitled, Global burden of asthma in adults and ABPA, click here: (http://www.ncbi.nlm.nih.gov/pubmed/23210682)

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