Why Corticosteroids Poorly Control Severe Asthma

The approximate 1 in 10 asthma patients who have severe disease do not respond to mainstay corticosteroid treatment, even in high doses.

That could be because the immune response that occurs in the airways of severe asthma patients markedly differs from what is seen in mild-moderate disease, a team of researchers recently posited.

To test their theory, the investigators examined samples of lung cells from asthmatic participants in the National Institutes of Health’s (NIH) Severe Asthma Research Program.

“Our hope was that characterization of the nature of this immune response would identify targets for the development of new therapies against this very debilitating disease,” study author Anuradha Ray, PhD, a professor at the University of Pittsburgh School of Medicine, explained to Pharmacy Times in an e-mail.

The researchers found that severe asthmatics harbored significantly more interferon gamma-producing CD4+ T cells in their airways than those with milder asthma.

This human analysis helped the research team develop an animal model through which they induced an immune profile and airway hyper-reactivity poorly controlled by corticosteroids, similar to severe asthma patients.

Interestingly, mice that lacked the interferon gamma gene could not be induced to develop severe asthma.

Additionally, levels of leukocyte protease inhibitor (SLPI) levels decreased as interferon gamma levels rose. In follow-up experiments, the researchers found that boosting SLPI levels reduced airway hyper-reactivity.

In light of this finding, which was published in the Journal of Clinical Investigation the research team wants to uncover agents that can increase SLPI levels in severe asthma patients and potentially control their disease.

“New studies should be undertaken to determine whether treatment strategies using other broad-acting anti-inflammatories will correct the aberrant immune response identified by us in this study,” Dr. Ray told Pharmacy Times. “The key findings in this study should lead to the development of targeted therapies for severe asthma.”

The NIH awarded a 5-year, $8 million grant to Dr. Ray’s team to continue observing the immune response and genetic roots of severe asthma in 120 human patients and animal models.

The researchers noted that this project could address the unmet needs of severe asthma patients.