Corticosteroid inhalers are a common treatment for asthma, but strangely, patients with severe asthma don’t seem to respond well to it. In a new study, scientists have identified a mechanism that seems to block the drugs, and importantly, a potential way to bypass the problem.
People with persistent asthma are often prescribed inhaled corticosteroid drugs, which reduce inflammation and swelling of the airways to prevent asthma attacks and reduce their severity. But while they’re effective in people with mild to moderate asthma, these drugs don’t seem to grant the same relief to patients with severe asthma. Exactly why that’s the case has remained unknown.
For the new study, researchers at Rutgers University and Genentech investigated the problem. The team collected samples of bronchial airway epithelial cells (BAECs), which line the airways, from patients with moderate and severe asthma, as well as controls without the illness. Next, they conducted a genetic analysis to see which genes are turned on in the cells in response to the drugs.
The researchers found that the corticosteroids promote the secretion of two specific growth factors, called FGF and G-CSF, in the epithelial cells of patients with severe asthma. Growth factors like these usually perform important functions, but in this case, the team found that they block the action of the drugs.
“We believe this response explains why patients with severe asthma are unresponsive to such conventional therapy,” said Reynold Panettieri Jr., an author of the study.
The team says that the finding suggests that patients with severe asthma have different cellular pathways activated, which ultimately results in the drugs failing to work. Having identified the problem, the team tested a workaround that could restore their function. In tests in mice, the researchers blocked those growth factors before administering corticosteroids, and found that the drugs worked once again to reverse inflammation. This could open new paths to treatment for patients with severe asthma.
“Our study has uncovered a potential mechanism to explain why patients with severe asthma are unresponsive to conventional therapy,” said Panettieri. “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 research was published in the journal Science Translational Medicine.
Source: Rutgers University
