Identification of growth factors produced in patients with severe asthma could lead to new therapies, reveals a study involving Rutgers scientists
Patients with the most severe form of asthma produce special substances in their airways when they take medications during asthma attacks that block the effect of treatment, according to a study in which Rutgers scientists collaborated with researchers from Genentech, a member of the Roche group.
Reporting in the journal Science of Translational Medicinescientists have said two different so-called growth factors - natural substances that stimulate cell proliferation - activated in the airways of patients with severe asthma while inhaling corticosteroids used as emergency treatment during an asthma attack.
The discovery came as researchers investigated an enduring mystery in the treatment of asthma: why do some patients who suffer the most from disease often have the least success with conventional rescue treatments?
Of the more than 25 million people in the United States with asthma, between 5 percent and 10 percent suffer from severe asthma, according to the American Lung Association. Corticosteroids used to reduce swelling and airway irritation in people with moderate asthma often do not work in those with severe asthma. Patients with severe asthma have more frequent attacks of breathing problems than others.
Researchers have found that the use of inhaled steroids in patients with severe asthma stimulates the secretion of growth factors - fibroblast growth factor (FGF) and granulocyte colony-forming growth factor (G-CSF) - in airway mucosal cells known as epithelium.
“We believe this answer explains why patients with severe asthma do not respond to such conventional therapies,” said author Reinold Panettieri Jr., Rutgers professor of medicine at Robert Wood Johnson Medical School and vice rector for clinical and translational sciences.
The researchers compared samples of bronchial airway epithelial cells (BAECs) that were exposed to inhaled corticosteroids and were collected from three groups: those with severe asthma, those with moderate asthma, and healthy volunteers.
By conducting genetic analysis to determine which genes are “involved” in BAEC, the scientists were able to see that FGF and G-CSF growth factors are expressed only in the cells of patients with severe asthma.
Growth factors are important for regulating various cellular processes, Panettieri said. In the case of asthma attacks in patients with severe asthma, the growth factors identified in the cells lining the main connecting airways act directly against the action of corticosteroids. The findings of the study suggest that different cell pathways are at work in the cells of patients with severe asthma, especially those involved in inflammation.
Here’s how researchers imagine the new drug could work: In a study on mice, scientists found that if they blocked a cascade of chemicals that eventually cause growth factor secretion, corticosteroids effectively reversed airway inflammation and even prevented scarring.
“Our study revealed a potential mechanism that explains why patients with severe asthma do not respond to conventional therapy,” Panetieri said. “If we could discover new treatment approaches that directly affect this mechanism, maybe we could restore steroid sensitivity and improve results.
Other Rutgers researchers working under Genentech include Cinthia Koziol-White, assistant professor of pharmacology at the Robert Wood Johnson School of Medicine, and William Jester Jr., chief operating officer of the Institute of Translational Medicine and Science. Additional authors in the paper are from Genentech in South San Francisco, California, and the Texas A&M University in Houston, Texas.