Why asthma often comes back—even with powerful drugs

Biological drugs (biologics) have become an important tool in the treatment of severe asthma.

"They help most patients to keep their symptoms under control, but exactly how these drugs affect the immune system has so far remained unknown," says Valentyna Yasinska, consultant in pulmonary medicine at Karolinska University Hospital and doctoral student at Karolinska Institutet's Department of Medicine in Huddinge.

In a new study published in the scientific journal Allergy, researchers at Karolinska Institutet have explored what happens to the immune cells of patients being treated with biologics. By analyzing blood samples from 40 patients before and during treatment, they found that instead of disappearing during treatment, certain types of immune cell - which play a key part in asthma inflammation - actually increased.

"This suggests that biologics might not attack the root of the problem, no matter how much they help asthma patients during treatment," says Jenny Mjösberg, professor of tissue immunology at Karolinska Institutet's Department of Medicine in Huddinge. "Continued treatment might be necessary to keep the disease under control."

The study is based on data from patients with severe asthma sourced from the BIOCROSS study. The researchers used advanced methods such as flow cytometry and single-cell sequencing to determine the properties and function of the immune cells.

"We were surprised to find that blood levels of inflammatory cells increased rather than decreased," says Lorenz Wirth, doctoral student at the same department at Karolinska Institutet. "This could explain why inflammation of the airways often returns when the treatment is tapered or discontinued. It is important that we understand the long-term immunological effects of these drugs."

Little is still known about the long-term effects of biologics like mepolizumab and dupilumab since they are relatively new, having been prescribed to asthmatics for less than ten years.

The next stage of the study will be to analyse samples from patients with a long treatment history and to study lung tissue to see how the immune cells are affected in the airways.

The study was financed by grants from the EU (Horizon 2020), the Swedish Heart-Lung Foundation, the Centre for Innovative Medicine, the Swedish state, the Torsten Söderberg Foundation, Karolinska Institutet and the ChAMP Consortium.

Any conflicts of interest are reported in the published paper.