Some 10 to 15 percent of people with asthma have severe disease that medications can’t control. A deep-dive multicenter study finds differences in these patients’ immune systems that may explain why increased dosages of corticosteroids don’t help — and could lead to steroids doing more harm than good. Findings appear online this week in Science Immunology.
The researchers, led by Elliot Israel, MD, and Bruce Levy, MD, of the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital, pooled samples from patients at seven U.S. asthma research centers as part of the NHLBI-funded Severe Asthma Research Program-3 (SARP-3) Study.
“It was a unique opportunity to home in on an in-depth characterization of the immunology of the severe asthma airway using bronchoscopy samples obtained from patients across the country,” says first author Melody Duvall, MD, PhD, a research fellow in the Levy lab and a physician in Boston Children’s Hospital’s Division of Critical Care Medicine.
Duvall, Levy and colleagues examined immune cells in samples from patients with severe asthma, patients with non-severe asthma and healthy control subjects. They found that in severe asthma, certain immune cells in the lung known as natural killer (NK) cells are unable to do their job of helping to resolve inflammation. Treating patients’ cells with steroids — the mainstay of asthma therapy — appeared to impair them even further. Patients’ NK cells also become outnumbered by other types of immune cells that provoke inflammation.
“Our findings point to an interesting and pivotal role for natural killer cells in the asthmatic airway and suggest that continuously giving high doses of corticosteroids may actually be making things worse,” says Levy.
On the other hand, the researchers noted that naturally occurring molecules called lipoxins preserved NK cells’ ability to resolve inflammation — suggesting a potential new path toward treating asthma. Overall, the research adds to the growing idea that asthma is a collection of different disease processes that may require customized treatments.
Read more in this press release.