There Is No ‘One Size Fits All’ Approach to Treat Severe Asthma

Asthma is a debilitating condition that affects millions of people each year.

A group of scientists led by immunologists and pulmonologists used advanced tools of immunology, molecular biology and unbiased computational and bioinformatic approaches to characterize immune profiles of patients with severe asthma.

These findings invite a new appreciation for the complexity of disease mechanisms and can lead to improved treatments.

“We started this study to better understand immune mediators of inflammation in asthma,” said lead author Matthew Camiolo, M.D., Ph.D., clinical instructor of medicine at Pitt.

“We found that despite being grouped broadly as ‘clinically severe,’ these asthma patients actually had very different and distinct immune profiles.”

And while current standards of treatment — inhaled immunosuppressive corticosteroids, such as beclomethasone and budesonide — are effective in most patients, clinical markers that can help identify those who are likely to be resistant to treatment are lacking.

For patients who do not respond to standard corticosteroid treatment or respond to it poorly, there is no ‘one size fits all’ approach to treat severe disease.

To characterize immune cells within the airways of severe asthma patients, the researchers used mass cytometry, RNA-sequencing and machine learning, and established a novel algorithm that links immune cells to cellular pathways potentially related to disease pathogenesis.

The research team found that lung aspirates from one group of patients were enriched with T cells polarized to fight infections, while the other group had a much lower level of T cells.

At the same time, the second group had an increased number of innate immune cells expressing an inflammatory molecule IL-4 — a cytokine known to be elevated in asthma.

“We have identified two clusters of severe asthma patients with very similar biomarkers but with strikingly distinct immune profiles and associated biological pathways,” said senior author Anuradha Ray, Ph.D., professor of medicine and immunology at Pitt.

“These findings identify new targets for therapy, which are distinct in the two subgroups of severe asthma patients who otherwise would be indistinguishable based on biomarker profiles.”

“We believe that the cell types expressing IL-4 in the airways of one of the groups have not been previously identified in humans in any setting,” Ray added.

Researchers are optimistic that these findings will enhance precision medicine approaches to treating severe asthma patients.

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Sources:

Matthew J. Camiolo, Xiaoying Zhou, Timothy B. Oriss, Qi Yan, Michael Gorry, William Horne, John B. Trudeau, Kathryn Scholl, Wei Chen, Jay K. Kolls, Prabir Ray, Florian J. Weisel, Nadine M. Weisel, Nima Aghaeepour, Kari Nadeau, Sally E. Wenzel, Anuradha Ray. High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status. Cell Reports, 2021; 35 (2): 108974 DOI: 10.1016/j.celrep.2021.108974

Materials provided by University of Pittsburgh. Note: Content may be edited for style and length.

University of Pittsburgh. “There is no ‘one size fits all’ approach to treat severe asthma.” ScienceDaily. ScienceDaily, 13 April 2021. <www.sciencedaily.com/releases/2021/04/210413170708.htm>

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