A new scientific trail may have been discovered in the search for new treatments for asthma.
Researchers at two universities say they have potentially found a biological pathway that triggers asthma in a significant percentage of patients.
They say their research may help explain why current treatments don’t work well in some asthma cases, and also help develop new treatments for this chronic lung disease.
Their findings were published today in the Journal of Clinical Investigation (JCI).
One asthma expert interviewed by Healthline said it’s too early to tell if this particular research will lead to new therapies.
However, he credited the scientists for what they’ve discovered so far.
“They ask a very, very important question,” Dr. Norman H. Edelman, senior scientific advisor to the American Lung Association, told Healthline. “It opens up a really fascinating area of research.”
When Inflammation Isn’t the Problem
Asthma affects more than 25 million people, including 7 million children, in the U.S.
It accounts for 2 million emergency room visits as well as 1.5 million patient days of hospital inpatient care every year.
The researchers said 60 percent of asthma patients have an inflammatory or allergic component to their ailment.
The other 40 percent have trouble breathing in part due to abnormalities in their epithelial and smooth muscle cells.
For these patients current treatments aren’t effective.
So, scientists from Rutgers University and the Perelman School of Medicine at the University of Pennsylvania took a close look at these types of cases.
"There's a real need to understand the non-inflammatory aspects of asthma and with this study we're getting closer to that understanding,” said co-senior author Dr. Reynold A. Panettieri, Jr., vice chancellor of translational medicine and science at Rutgers, in a press release.
Goblets and Neuropeptides
The researchers homed in on the production of mucus secreting goblet cells in the lung epithelia of mice.
Increased goblet cell differentiation in the airways is a trademark of asthma.
From experiments in 2012, the researchers knew that transcription factors called Foxp1 and Foxp4, which can switch certain genes on and off, usually repress the production of these goblet cells.
The scientists noticed that mice lacking the Fox genes developed asthmalike symptoms, including the contraction of smooth muscle cells in the airway system.
Those mice did not show the signs of inflammation typically associated with asthma in humans.
The scientists also observed that a molecule called neuropeptide Y (NPY) was present in high levels in the mice without the Fox genes.
Researchers said their experiment showed NPY has a significant role in asthma by deleting not only NPY genes but the Fox genes as well.
They also tested NPY on human lung tissue. They noticed the tissue exposed to NPY developed hyperresponsiveness similar to what happened in the mice.
"These data strongly suggest that NPY can cause airway hyperresponsiveness in human lungs and could be a causative mechanism in human asthma," said Edward E. Morrisey, Ph.D., a professor of cell and developmental biology and director of the Penn Center for Pulmonary Biology, in a press release.
The Next Steps
The researchers noted pharmaceutical companies have already developed compounds that block NPY in conditions such as obesity and hypertension.
They said testing NPY inhibitors in people with asthma “would be worthwhile.”
They hope to replicate their mouse study in research involving larger animal models of asthma.
Edelman said the pathway the scientists discovered is an important step, but more research is definitely needed.
“The question is if this going on in humans,” said Edelman, a professor of preventive medicine, internal medicine, and public health at the State University of New York at Stony Brook.
He noted inflammatory systems are an ancient biological framework and are found in even the most basic of species.
He said asthma is unlike diseases in that an organism that can be targeted doesn’t cause it.
“It’s far more complex,” he said.
Edelman added biological pathways are adaptable. If one is blocked, another can open up.
Fortunately, he said, current asthma treatments work for most people in relieving asthmatic symptoms.
“For most people, asthma is a very manageable disease,” he said.