Research Into Plasma Proteins Yields Potential Biomarkers for Asthma Severity

An international team of researchers has identified plasma proteins that appear to be biomarkers for asthma disease severity, independent of type-2 inflammation.

The report offers the potential to better understand the disease, as well as possible new therapeutic targets. The study was published in the European Respiratory Journal.

Asthma is a very common respiratory condition, but it also varies widely from individual to individual, noted corresponding author Maria Sparreman Mikus, PhD, of the Karolinska Institute, in Sweden, and colleagues. Not only do individuals’ symptoms and triggers vary, so too do their responses to treatments. Yet, Mikus said physicians’ ability to personalize care for patients with asthma is constrained.

“Currently available type-2 asthma biomarkers, such as blood eosinophils, total serum IgE or fraction of exhaled nitric oxide (FeNO), do not adequately enable endotyping which is required for personalized treatment,” the authors wrote.

In hopes of finding biomarkers that would enable clinicians to better tailor care to individual patients, the investigators turned to a proteomics panel created by the ChAMP (Centre for Allergy Research highlights Asthma Markers of Phenotype) consortium and focused on 177 proteins with potential involvement in airway or systemic inflammation. The authors hoped that panel might help identify plasma protein associations with asthma severity and/or oral corticosteroid (OCS) treatment response. They also wanted to find out whether specific protein profiles could be used to differentiate unique molecular subgroups of asthma patients.

The authors used a cohort of 525 people in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group and 142 people from the BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) Consortium, the latter of which were used as a validation cohort.

Among the 525 patients in the U-BIOPRED group, about half (263) were nonsmokers who had severe asthma; 95 were current or previous smokers with severe asthma; 76 were nonsmokers with mild-to-moderate asthma; and the remaining 91 patients were healthy controls.

The proteomic panel identified 110 proteins in the U-BIOPRED group that were significantly different in patients with severe asthma versus those with mild-to-moderate asthma or no asthma. A comparison of the U-BIOPRED and BIOAIR cohorts found 10 proteins that were elevated in severe asthma patients in both cohorts.

The authors then looked at the results of a 2-week, placebo-controlled OCS trial in BIOAIR, as well as objective OCS measures in the BIOPRED group. While the data showed that OCS treatment led to a decrease in most proteins, it did not completely erase differences between severe and mild-to-moderate OCS.

“Consensus clustering of U- BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, hsCRP (high-sensitivity C-reactive protein), and BMI (body mass index), but not Type-2 inflammatory biomarkers,” Mikus and colleagues wrote. “The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.”

The authors concluded that their findings offer important new insights that could eventually lead to changes in treatment for patients.

“Taken together, we present a platform that is able to suggest novel biomarker candidates for molecular phenotyping, particularly relevant to non-Type-2 asthma,” the investigators wrote. “The panel may also aid discovery of future pharmacotherapeutic targets by exposing previously unexplored pathways.”

Reference

Mikus MS, Kolmert J, Andersson LI, et al. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to type-2 inflammation. Eur Respir J. Published November 4, 2021. doi:10.1183/13993003.00142-2021