A blood biomarker-based score may help identify individuals at considerable risk for asthma exacerbations, addressing a persistent gap in clinical risk stratification. In a study published in Nature Communications, a metabolomics-derived model showed strong predictive performance across multiple cohorts, with the potential to inform early intervention and treatment optimization.

Researchers from the Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, used metabolomic profiling to identify predictive biomarkers, with findings suggesting that sphingolipid and steroid profiles may support clinically actionable risk stratification.

“Asthma exacerbations are a major healthcare burden and cause of disease morbidity, leading to progressive loss of lung function, airway remodeling, and enhanced disease severity. The heterogeneity of asthma complicates identifying individuals at high risk for future exacerbations, and there are no current clinical tests or biomarkers that effectively identify those at risk for asthma exacerbations, making this a critical unmet need,” the authors wrote.

Metabolic Signals

The study included three cohorts, totaling 2513 individuals with asthma. Researchers identified sphingolipid-to-steroid ratios as key discriminators of the risk for asthma exacerbation.

Cortisone-based sphingolipid ratios showed the best performance. The strongest were Cer(d18:1/20:1): cortisone, HexCer(d18:1/24:1): cortisone, Sphinganine(d18:0): cortisone, and SM(d18:1/20:0): cortisone. These ratios separated high- and low-risk patients for up to 366 days, and the predictive accuracy was strong, with areas under the curve of 0.901 and 0.893.

Model Performance

“We derive and replicate a simple 5-year predictive model of asthma exacerbations using 21 sphingolipid-to-steroid ratios that outperform current clinical measures,” the authors wrote.

The authors noted that overall, androgen, glucocorticoid, and progestogen metabolites were inversely associated with asthma diagnosis and exacerbation and positively associated with forced expiratory volume in 1 second and forced vital capacity. The score could be used as a monitoring tool in clinical practice, including assessment of treatment response and disease control.

Sphingolipids, which are derived from sphingosine, are complex lipids that are found in cell membranes. Steroids, also known as lipids, are a well-established class of hormones. Sphingolipids, particularly ceramides, modulate steroidogenesis, linking these pathways to the regulation of inflammatory and metabolic processes.

“Alterations in sphingolipid/steroid ratios may reflect imbalances in hormonal regulation and lipid signaling, both of which are critical in the inflammatory and immune processes underlying asthma.”

Similarly, reduced ceramide levels early in life are linked to abnormal lung development and an increased risk for asthma. Steroid deficiencies are also associated with lung inflammation and an increased risk for asthma.

Clinical Utility

In practice, using sphingolipid and steroid levels could be easy because “these molecules are readily amenable to clinical assay development because they are abundant and stable, and the analytical methods for their quantification are relatively straightforward and inexpensive. If these ratios can accurately predict exacerbation risk within the next 6 months, that would enable the implementation of preventative measures to protect against an exacerbation,” the researchers added.

This story was translated from MediQuality, part of the Medscape Professional Network.