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.