From flu to fungi: Different asthmas, different pathways

Understanding asthma's different pathways may allow individualized treatments.
Understanding asthma’s different pathways may allow individualized treatments.

Existing asthma drugs don’t work well in many people, and a major reason is becoming clear: Asthma isn’t just one disease, but a collection of diseases that cause airways to constrict and become twitchy. Different types of asthma have different triggers that exacerbate the disease, each setting off a different part of the immune system, and each needing a different pharmacologic approach.

In this week’s Nature Medicine, a team led by Dale Umetsu, MD, PhD, and Lee Albacker, PhD, of Boston Children’s Hospital’s Division of Immunology and Harvard Medical School, describe a type of asthma triggered by the fungus Aspergillus fumigatus, a common mold.

Existing asthma control drugs, like inhaled corticosteroids, target allergic asthma, via pathways involving adaptive immunity and a group of T cells, known as Th2 cells. However, the new work, in live mice and in human cell cultures, suggests that Aspergillus triggers asthma through a faster process involving the innate immune system. In both mice and humans, Aspergillus activates a different set of T cells, known as natural killer T cells (NKT cells).

NKT cells are known to be activated by various bacteria, but this is the first demonstration of their activation by a fungus (or, more specifically, a lipid molecule on its surface). While the asthma starts by non-allergic means, patients can later become sensitized to Aspergillus and develop chronic allergic reactions involving the Th2 system that make their respiratory disease more severe.

Some centers are using antifungal agents in asthma with some success. Asperamide B, the lipid that activates the NKT cells, might be another target, as might NKT cells themselves, if a successful targeting method could be found.

Meanwhile, Umetsu’s lab also has shown that influenza infection—which often spells hospitalization for children with asthma—activates a third group of immune cells called natural helper cells or innate lymphoid cells. These cells are not involved in allergic asthma. Fighting flu-induced asthma might mean developing drugs against the natural helper cells themselves, compounds these cells secrete or IL-33, the compound that activates natural helper cells when stimulated by influenza.

“Most existing therapies are good for allergic asthma, but they’re not effective in many patients, whose asthma may involve non-classical pathways,” says Umetsu. “We need to understand the specific pathways in each individual with asthma and when they are triggered, so we can give the right treatment at the right time.”

Read more in this press release and previous Vector post raising the possibility of a personalized medicine approach to asthma.