People suffering from severe asthma have their airways inflamed and constricted, which in turn impairs their breathing capabilities, making it impossible to improve the condition even with high doses of corticosteroids, the standard treatment to address typical asthma, according to Anuradha Ray, professor of medicine at the Pitt School of Medicine.
“About 10 percent of asthma patients have a severe form of the disease, but they account for up to half of asthma costs in the U.S. and Europe. That’s because these patients frequently need to go to the emergency room or be hospitalized when they have an acute asthma episode,” said Ray in a press release.
In this study, the research team assessed lung cell samples collected from patients also enrolling in the Severe Asthma Research Program (SARP), a program by the National Heart, Lung, and Blood Institute of the National Institutes of Health that is designed to improve the understanding of what causes severe asthma.
Researchers observed that the CD4 T-cells, immune cells, in the airways of asthmatics with the severe form of the disease secreted different inflammatory proteins in comparison to those in mild disease — specifically, interferon gamma. The assessment of human samples assisted them in developing a mouse model of the condition by introducing both an allergen and a bacterial product capable of inducing an airway hyper-reactivity and an immune profile that was poorly controlled by corticosteroids and similar to severe asthma patients.
When mice without the interferon gamma gene were subjected to the severe asthma model, they noticed that the mice could not be induced to develop severe asthma. Thanks to computer modeling they identified connections between interferon gamma and asthma-associated genes and they learned that when interferon gamma levels rise, the amount of secretory leukocyte protease inhibitor (SLPI) decreases. Further, they realized that boosting SLPI levels decreased airway hyper-reactivity in the mouse model.
“We’d like to better understand why severe asthma occurs in most people right from the start. We also want to find agents that can raise SLPI levels for clinical use,” concluded Anuradha Ray.
