NEW BRUNSWICK, N.J. — Certain patients with severe asthma find little relief from their inhalers during an asthma attack. This has always puzzled doctors, but new research looks to have finally cracked the case. Study authors from Rutgers University report that people with the most severe form of asthma actually produce special substances in their airways during asthma attacks that block medicine from helping.
According to the research team, two distinct growth factors activate in severe asthma patients’ airways as they inhale corticosteroids. Growth factors are naturally occurring substances stimulating cell proliferation. Corticosteroids, meanwhile, are the standard emergency treatment for asthma attacks.
Over 25 million Americans have asthma – with five to 10 percent living with a severe form of asthma. While corticosteroids are quite reliable for decreasing swelling and irritation in the airways of people with moderate asthma, the very same treatments can fail among severe asthma patients in midst of an attack.
The study finds that when these severe asthma patients inhale corticosteroids, it appears to actually backfire in a sense – promoting the secretion of fibroblast growth factor (FGF) and granulocytic colony forming growth factor (G-CSF) in cells lining the airway.
“We believe this response explains why patients with severe asthma are unresponsive to such conventional therapy,” says study author Reynold Panettieri Jr., a professor of medicine at Rutgers Robert Wood Johnson Medical School and vice chancellor of Clinical and Translational Science, in a university release.
What’s going wrong with severe asthma patients’ genes?
Researchers collected samples of bronchial airway epithelial cells (BAECs) exposed to inhaled corticosteroids among three groups: patients with severe asthma, patients with moderate asthma, and healthy volunteers.
Then, the team conducted a genetic analysis to help ascertain what genes had been turned “on” in the BAECs. This led to the discovery that the FGF and G-CSF growth factors had only been expressed in the cells of the severe asthma patients.
Prof. Panettieri explains growth factors help regulate many cellular processes. In the specific scenario of a person with severe asthma suffering an asthma attack, this work indicates that the growth factors within the cells lining major connecting airways work to inhibit the corticosteroids. All in all, the study suggests different cellular pathways are at play when it comes to the cells of severe asthma patients, especially cells involved in inflammation.
These findings may pave the way for a new medicine that’s more capable of helping severe asthma patients. Study authors note that they conducted an additional study with mice. When the genetically modified rodents could not secrete those specific growth factors, corticosteroids proved effective, reversing airway inflammation and stopping tissue scarring.
“Our study has uncovered a potential mechanism to explain why patients with severe asthma are unresponsive to conventional therapy,” Prof. Panettieri concludes. “If we could uncover new approaches to treatment that directly affect that mechanism, we may be able to restore a sensitivity to the steroid and improve outcomes.”
The study is published in the journal Science Translational Medicine.
