Scientists Have Solved a Long-Running Puzzle: Why Do Some Asthma Patients Fail to Respond to Treatment?

A study led by Rutgers scientists found that identifying growth factors produced in individuals with severe asthma could lead to novel medicines.

According to a study conducted by Rutgers scientists in collaboration with researchers at Genentech, a member of the Roche Group, patients with the most severe form of asthma produce special substances in their airways when taking medicine during an asthma attack that prevents the treatment from working.

Two different so-called growth factors – naturally occurring substances that stimulate cell proliferation – activate in the airways of severe asthma patients as they inhale corticosteroids used as an emergency treatment during an asthma attack, according to a study published in the journal Science Translational Medicine.

Researchers uncovered the discovery while looking at a long-standing puzzle in asthma treatment: why do some of the most severely afflicted patients have the least success with standard rescue treatments?

According to the American Lung Association, between 5% and 10% of the more than 25 million persons in the United States who have asthma have severe asthma. Corticosteroids, which are used to reduce swelling and irritation in the airways of people with mild asthma, frequently fail to help those with severe asthma. Patients with severe asthma have more respiratory issues on a regular basis than others.

Inhaled steroids enhance the release of growth factors such as fibroblast growth factor (FGF) and granulocytic colony-forming growth factor (G-CSF) in airway lining cells known as the epithelium, according to researchers.

“We believe this response explains why patients with severe asthma are unresponsive to traditional medication,” stated author Reynold Panettieri Jr., a professor of medicine and vice-chancellor of Clinical and Translational Science at Rutgers Robert Wood Johnson Medical School.

Researchers analyzed samples of bronchial airway epithelial cells (BAECs) from three groups: those with severe asthma, those with moderate asthma, and healthy volunteers who had been exposed to inhaled corticosteroids.

The scientists discovered that the FGF and G-CSF growth factors were only expressed in the cells of patients with severe asthma after doing a genomic study to establish which genes had been turned “on” in the BAECs.

According to Panettieri, growth factors are vital for controlling a range of cellular activities. When a patient with severe asthma has an asthma attack, the growth factors found in the cells lining the major connecting airways operate directly against the corticosteroids. The findings show that various cellular pathways, notably those implicated in inflammation, are an action in the cells of people with severe asthma.

Here’s how a new drug might operate, according to the researchers: Corticosteroids significantly reversed airway inflammation and even avoided tissue scarring in mice when scientists stopped the chemical cascade that ultimately promotes the secretion of growth factors.

Panettieri remarked, “Our research has found a potential mechanism to explain why people with severe asthma are unresponsive to traditional medication.” “If we can find novel therapy options that directly alter that process, we might be able to restore steroid sensitivity and improve outcomes.”

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Author: Muhammad Asim

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