New Method Accurately Predicts Asthma Attacks Five Years in Advance

A major challenge in asthma care is the inability to reliably identify which patients are likely to experience severe exacerbations, even when their disease appears clinically stable. Existing clinical measures and biomarkers often fail to distinguish low-risk patients from those heading toward an attack. Researchers have now identified a blood-based metabolic signature that can predict asthma exacerbations years before they occur.

In research led by Mass General Brigham (Boston, MA, USA), in collaboration with Karolinska Institutet (Stockholm, Sweden), the team applied high-throughput metabolomics, a technology that measures small molecules circulating in the blood. By analyzing metabolic profiles from large asthma cohorts, the researchers examined how specific biochemical pathways relate to long-term asthma control and disease progression.

Rather than focusing on single biomarkers, the researchers evaluated interactions between entire classes of metabolites. They concentrated on sphingolipids, which play roles in inflammation and cell signaling, and steroids, which are closely linked to immune regulation and asthma therapy. This ratio-based approach allowed the team to capture biologically meaningful imbalances that are not apparent when metabolites are analyzed individually.

The analysis included data from more than 2,500 individuals across three long-term asthma cohorts, supported by decades of electronic medical records. The researchers found that the ratio of sphingolipids to steroids strongly predicted the risk of asthma exacerbations over five years. In some cases, the model distinguished between high- and low-risk patients by nearly a year in terms of time-to-first exacerbation.

The findings, published in Nature Communications, suggest that metabolic imbalance, rather than absolute metabolite levels, drives future asthma risk. A blood test based on sphingolipid-to-steroid ratios could help clinicians identify patients who appear stable but are metabolically primed for severe attacks. The researchers note that further validation, including prospective clinical trials and cost-effectiveness studies, is needed before the test can be implemented in routine care.

“One of the biggest challenges in treating asthma is that we currently have no effective way to tell which patient is going to have a severe attack in the near future,” said Jessica Lasky-Su, Associate Professor at Mass General Brigham and Harvard Medical School. “Our findings solve a critical unmet need. By measuring the balance between specific sphingolipids and steroids in the blood, we can identify high-risk patients with 90 per cent accuracy, allowing clinicians to intervene before an attack occurs.”

Related Links:
Mass General Brigham
Karolinska Institutet