Switching off nerve cells eases asthma attacks

To stop an asthma attack, just numb some nerve cells.

Dulling nerve cells in mice’s lungs soothes irritated airways by easing inflammation and out-of-control coughing, researchers report online June 25 in Neuron.

“It’s a game changer,” says asthma researcher Christopher Evans of the University of Colorado Denver. He thinks targeting nerve cells could be a feasible therapeutic approach for asthma in humans.

In people with asthma, just a speck of pollen or a dust mite can trigger bouts of wheezing. Researchers thought that response was primarily an immune problem, Evans says. Usually, the immune system acts as a cellular bodyguard; it uses powerful weapons to fight dangerous bacteria and viruses. But sometimes the bodyguard pulls out the big guns too soon. In asthma and other allergic diseases, the immune system overreacts to minor threats — kind of like killing a mosquito with a bazooka. The resulting damage can include inflamed, mucus-clogged airways that make breathing difficult.

One type of asthma treatment uses steroids to calm the trigger-happy immune system. Another drug forces clenched airways to open. But that drug can wear off quickly, and long-term steroid use can cause infection.

Harvard University pain biologist Clifford Woolf and colleagues knew that pain-sensing nerve fibers line the lungs. When these fibers get a whiff of smoke or cayenne pepper, for example, they protect the lungs by triggering a cough reflex. People with asthma have especially sensitive pain fibers.

“So we thought, well, how can we target the pain fibers in the lung?” Woolf says. Turning them off could curb coughing, the team surmised. So Woolf’s team made asthmatic mice inhale a nerve-numbing drug, called QX-314, that’s related to the common anesthetic lidocaine.

The drug calmed the mice’s coughs, as expected, but the researchers were surprised to discover that it dialed down inflammation, too.

It’s a two-for-one effect, Woolf says. “We’re very excited about this because it’s a completely new treatment strategy.”

Numbed nerve cells no longer send out messages that rile up the immune system and trigger inflammation, the team found.

“It’s the first direct link I’ve seen between the nervous system and the immune system in asthma,” says molecular biologist Kirk Druey of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

But respiratory researcher Ulaganathan Mabalirajan of the Institute of Genomics and Integrative Biology in New Delhi cautions that the drug may not work for all types of asthma. “When you have inflammation, QX-314 works fantastically,” he says. But some people with asthma don’t have inflammation. 

Eventually, Woolf would like to tweak the drug so that it blocks the nerve cells’ immune system–provoking messages, while still allowing people to cough if they need to clear their throat. “But that’s going to be another story,” he says.