Fungal infections can trigger and exacerbate asthma

(Medical Xpress)—A common fungal infection can trigger asthma and make it much worse by way of a route not targeted by existing asthma drugs, report researchers at Boston Children's Hospital. Their findings, published online by Nature Medicine on September 1, have implications for some patients with severe asthma who may be chronically exposed to fungi and can become highly sensitized.

The findings from this mouse study explain why existing don't work well in fungal-associated asthma. "As we understand the different pathways to asthma, we can develop better therapies," says senior investigator Dale Umetsu, MD, PhD, of Boston Children's Division of Immunology and also a professor at Harvard Medical School. "Most existing therapies are good for , but they're not effective in many patients, whose asthma may involve non-classical pathways."

When Umetsu and colleagues exposed the mice to the fungus Aspergillus fumigatus, a mold common in the indoor and outdoor environment, they developed airway hyperreactivity, the cardinal feature of asthma, within just a few days. Since allergic responses in mice typically take 10 to 14 days to develop, this finding suggested that the fungus triggers an immediate, .

Traditional asthma-control drugs, such as , act on pathways involving Th2 cells, a type of T cell in the that is important in allergy. However, the new study shows, in mice and in human cell cultures, that Aspergillus directly activates a recently discovered group of T cells, known as natural killer T cells (NKT cells), via a lipid molecule on its surface, asperamide B. In live mice, asperamide B alone was enough to induce airway hyperreactivity.

Umetsu and colleagues first showed in 2006 that NKT cells can trigger asthma in people in the absence of Th2 cells. The cells have been shown to be activated by various bacteria, but this is the first demonstration of their activation by a fungus.

Although Aspergillus and NKT cells initiate asthma through non-allergic means, patients can become sensitized to the fungus and develop chronic allergic reactions that make their respiratory disease more severe. Previous studies indicate that 28 percent of patients with asthma and 45 percent of patients with severe asthma become sensitized to Aspergillus.

Umetsu's investigations support the growing idea that asthma is a collection of different disease processes that all cause airways to become twitchy and constricted. In 2011, for example, his lab showed that influenza infection—which often requires asthmatic children to be hospitalized—exacerbates asthma by activating not Th2 cells or NKT cells, but yet another group of immune cells called natural helper cells or innate lymphoid cells.

"We need to understand the specific asthma pathways present in each individual with asthma and when they are triggered, so we can give the right treatment at the right time," Umetsu says.

Some academic research groups are using antifungal agents in asthma, with some success, Umetsu notes. In the future, he would like to target NKT cells in patients with severe asthma if a successful targeting method could be found.

More information: dx.doi.org/10.1038/nm.3321

Related Stories

The pathway to asthma winds through toll-like receptor 4

Aug 15, 2013

In a report that appears online in the journal Science, Dr. David Corry of Baylor College of Medicine and colleagues describe a molecule called toll-like receptor 4 that plays a key role in prompting the in ...

Study shows how flu infections may prevent asthma

Dec 13, 2010

In a paper that suggests a new strategy to prevent asthma, scientists at Children's Hospital Boston and their colleagues report that the influenza virus infection in young mice protected the mice as adults against the development ...

Children with allergy, asthma may be at higher risk for ADHD

Aug 13, 2013

The number of children being diagnosed with attention-deficit disorder (ADHD), allergy and asthma is increasing in the United States. And according to a new study, there might be a link between the growth of these three conditions.

Recommended for you

Guidelines presented for diagnosing focal liver lesions

8 hours ago

(HealthDay)—Focal liver lesions (FLLs) are mostly benign, and can be diagnosed based on knowledge of their presentation, associated clinical and laboratory features, and natural history, according to clinical ...

Factors tied to neck, back pain improvement identified

13 hours ago

(HealthDay)—Observational registry-based research can inform patients and physicians about prognosis for subacute or chronic neck or low back pain, according to a study published in the Aug. 1 issue of ...

User comments