Joshua Mezrich, MD

Preventing Environmentally Triggered Asthma Flareups

While it has long been known that certain environmental hazards can affect airway disease such as asthma, the way in which some of these toxins cause harm has been unclear. Joshua Mezrich, MD, is researching polycyclic aromatic hydrocarbons, toxic chemicals released into the environment by fossil fuel combustion. A primary route of human exposure to these chemicals is tobacco smoke. He hopes that his investigation will identify an entirely new target for intervention, both before and after environmental exposures, to prevent worsening of airway disease.

“If you can identify people at risk of developing disease before they do so, you might be able to minimize their exposure, or treat them before they develop the disease.”
“It’s possible that if people are exposed to toxins over a long period, they could alter the immune system,” says Dr. Mezrich. “We are exposed to many of these toxins through pollutants such as cigarette smoke and diesel fuel, all of which are associated with aggravating asthma.”

He is focusing on the receptor through which these hydrocarbons work, known as Aryl Hydrocarbon Receptor (AHR). He screened many small compounds to see which ones activate AHR strongly, and found a few that were not previously known to do so. One of the compounds was designed as a cancer drug that blocks growth of blood vessels in tumors. Dr. Mezrich found the compound activates AHR and helps regulate the immune response. “Although it did not work well against cancer, clinical tests showed it was tolerated, so it could be tested safely for asthma,” he notes.

“If we can prove one of the mechanisms of airway disease involves activation of AHR by environmental exposures, it would open up new ways of regulating this process,” Dr. Mezrich says. He suggested that an inhaled treatment could be developed to modulate the effects of toxins that cause problems in airway disease.

He also hopes to be able to identify which people are at risk from toxic exposures, by looking at their activation of AHR in response to these exposures. “If you can identify people at risk of developing disease before they do so, you might be able to minimize their exposure, or treat them before they develop the disease,” he says. “We hope this research will be very translatable.”