Scientists at Rutgers University have solved a long-standing mystery of why asthma treatment does not work for patients with severe forms of the disease.
The Rutgers University study discovered that when severe asthma patients take treatment during an asthma attack, they produce special substances in their airways that prevent the treatment from working.
The team identified two growth factors – natural substances that stimulate cell proliferation – that activate in the airways of severe asthma patients when they inhale an asthma treatment called corticosteroids, which are used as an emergency medication during an asthma attack. The findings may help develop novel strategies to make asthma treatment more potent for severe patients.
The study’s findings are published in the journal Science Translational Medicine
Examining asthma treatment effectiveness
The American Lung Association estimates in the US, more than 25 million people have asthma, with between 5% and 10% having severe asthma and experiencing more frequent bouts of breathing problems than others.
Corticosteroids are administered to mitigate swelling and irritation in the airways of patients with moderate asthma; however, they often are ineffective for people with severe asthma.
The researchers uncovered that inhaling steroid medications, such as corticosteroids, promotes the secretion of two growth factors called fibroblast growth factor (FGF) and granulocytic colony forming growth factor (G-CSF) in airway lining cells known as the epithelium.
Reynold Panettieri Jr., the study’s author, a professor of medicine at Rutgers Robert Wood Johnson Medical School and vice chancellor of Clinical and Translational Science, said: “We believe this response explains why patients with severe asthma are unresponsive to such conventional therapy.”
The Rutgers scientists analysed samples of bronchial airway epithelial cells (BAECs) that had been exposed to inhaled corticosteroids from three groups: patients with severe asthma, those with moderate asthma, and health volunteers.
Through performing a genetic analysis, the researchers identified the genes that had been activated in the BAECS, finding that the FGF and G-CSF growth factors had only been expressed in the cells of the severe asthma patients.
Suppressing growth factors
Panettieri explained that growth factors are essential for regulating a range of cellular processes. When a patient with severe asthma suffers an asthma attack, the growth factors that line the major connecting airways oppose the action of the corticosteroids. The results suggest that various cellular pathways are instrumental in the cells of severe asthma patients, particularly ones involved in inflammation.
The team has potentially identified a strategy for making asthma treatment more effective for severe patients. In a mouse study, they found that if they blocked the cascade of chemicals that triggers the growth factors being secreted, the corticosteroids could reverse inflammation in the airways and prevent tissue scarring.
Panettieri concluded: “Our study has uncovered a potential mechanism to explain why patients with severe asthma are unresponsive to conventional asthma treatment. If we could uncover new approaches to treatment that directly affect that mechanism, we may be able to restore sensitivity to the steroid and improve outcomes.”
