Scientists solve the long-standing mystery: Why do some asthma patients respond poorly to treatment?

Identifying growth factors produced in patients with severe asthma could lead to new therapies, according to a study involving researchers at Rutgers

Patients with the most severe asthma produce special substances in their airways when they take medications during an asthma attack that block treatment, according to a study in which Rutgers researchers collaborated with researchers from Genentech, a member of the Roche Group.

Reporting in the diary Science Translational Medicinescientists have said two different so-called growth factors naturally occurring substances that stimulate cell proliferation is activated in the airways of patients with severe asthma as they inhale corticosteroids used as emergency treatment during an asthma attack.

The discovery was made when researchers investigate a lasting mystery in the treatment of asthma: why do some patients who suffer the most from the 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 irritation in the airways of people with moderate asthma, often do not work for those with severe asthma. Patients with severe asthma experience more frequent bouts of breathing problems than others.

The researchers found that the use of inhaled steroids in patients with severe asthma promotes the secretion of growth factors – fibroblast growth factor (FGF) and granulocyte colony-forming growth factor (G-CSF) – in airway cells known as epithelium.

“We believe this answer explains why patients with severe asthma do not respond to such conventional therapy,” said author Reynold Panettiere Jr., Rutgers professor of medicine at Robert Wood Johnson Medical School and vice chancellor of clinical and translational science.

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 were “involved” in BAECs, the researchers were able to see that FGF and G-CSF growth factors were expressed only in the cells of patients with severe asthma.

Growth factors are important in regulating various cellular processes, Panettiere said. In the case of an asthma attack in patients with severe asthma, the growth factors identified in the cells that cover the main connecting airways act directly against the action of corticosteroids. The results of the study suggest that different cellular pathways work in the cells of patients with severe asthma, especially those involved in inflammation.

Here’s how researchers imagine a new drug may work: In a study in mice, researchers found that if they blocked the cascade of chemicals that eventually triggered the secretion of growth factors, corticosteroids effectively reversed airway inflammation and even prevented the formation of airways. tissue scars.

“Our study revealed a potential mechanism to explain why patients with severe asthma do not respond to conventional therapy,” Panettiere said. “If we can find new treatment approaches that directly affect this mechanism, we may be able to restore steroid sensitivity and improve outcomes.”

Other Rutgers researchers on the Genentech-led paper include Cynthia Cosiol-White, an assistant professor in the pharmacology department at 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 article are from Genentech in South San Francisco, California, and Texas A&M University in Houston, Texas.

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