Melody Duvall

About 10 percent of people with asthma have severe asthma, a form of the disease that is not controlled by current medications. Many of these patients are prescribed increased dosages of corticosteroids – a medication intended to reduce inflammation in the airways – but continue to experience daily symptoms and recurrent infections. New research led by a team of BWH investigators suggests a reason why corticosteroids may actually aggravate severe asthma. Their insights appear online this month in Science Immunology.

“Our findings point to an interesting and pivotal role for a certain type of white blood cells, known as natural killer cells, in the asthmatic airway and suggest that continually giving high doses of corticosteroids may actually be making things worse for patients with severe asthma,” said Bruce Levy, MD, chief of the Division of Pulmonary and Critical Care Medicine at BWH.

Elliot Israel

Asthma affects an average of one out of every eight Americans at some point in their lives, but severe asthma is relatively rare. In order to better understand severe asthma, seven U.S. asthma research centers joined forces to collect and share patient samples as part of the Severe Asthma Research Program-3 (SARP-3) Study funded by the National Heart, Lung and Blood Institute of the National Institutes of Health.

Levy and Elliot Israel, MD, the division’s director of Clinical Research and director of BWH’s Asthma Research Center, are the co-principal investigators of the Boston-based site of the study. Study participants, recruited from the Asthma Research Center, gave blood, sputum and exhaled breath samples as well as tissue samples from deep in the lungs.

By examining specimens that originate in close proximity to the source of severe asthma from a relatively large number of patients, researchers were able to gain insights that had not been possible before.

Bruce Levy

Lead author Melody Duvall, MD, PhD, a postdoctoral research fellow in the Levy lab, joined by Levy, Israel and other colleagues, examined immune cells in samples from patients with severe asthma, patients with nonsevere asthma and healthy control subjects.

They focused on a prominent type of white blood cells: lymphocytes. One important family of innate lymphocytes in the lung are known as natural killer cells, which are pivotal for both mounting an immune response and helping to resolve inflammation. In patients with severe asthma, however, natural killer cells are disabled from resolving inflammation, and become outnumbered by other types of immune cells that provoke it. Treatment with corticosteroids for severe asthma appeared to further suppress the ability of these cells to help clear inflammation.

The team found evidence that molecules called lipoxins may help NK cells resolve inflammation. Further studies of their therapeutic potential are ongoing. On the clinical side, Israel and Christopher Fanta, MD, of Pulmonary and Critical Care Medicine and director of the Partners Asthma Center, will lead a new, multidisciplinary clinical center for patients with severe asthma, opening this May.