Researchers at Mass General Brigham and Karolinska Institutet have identified a new method to predict asthma exacerbations with a high degree of accuracy. The study is published in Nature Communications.
Asthma is one of the world's most common chronic diseases, affecting over 500 million people. Asthma exacerbations – commonly known as asthma attacks – are a major cause of disease morbidity and healthcare costs. Despite the prevalence of asthma, clinicians currently lack reliable biomarkers to identify which patients are at high risk for future attacks. Current methods often fail to distinguish between stable patients and those prone to severe exacerbations.
The study analysed data from three large asthma cohorts totalling over 2,500 participants, backed by decades of electronic medical records. Researchers used a high throughput approach called metabolomics to measures small molecules in the blood of individuals with asthma. They identified an important relationship between two classes of metabolites, sphingolipids and steroids, and asthma control. Specifically, they identified that sphingolipid to steroid ratios could predict exacerbation risk over a 5-year period. In some cases, the model could differentiate the time-to-first exacerbation between high- and low-risk groups by nearly a full year.
"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," says Jessica Lasky-Su, Associate Professor at the Channing Division of Network Medicine 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."
The team discovered that while individual metabolite levels provided some insight, the ratio between sphingolipids and steroids was the most powerful predictor of future health.
"We found that the interaction between sphingolipids and steroids drives the risk profile. This ratio approach is not only biologically meaningful but also analytically robust, making it highly suitable for development into a practical cost-effective clinical test, says Craig E. Wheelock, Principal Researcher at the Institute of Environmental Medicine at Karolinska Institutet."
The researchers believe these findings represent a significant step toward precision medicine for asthma. A clinical assay based on these ratios could be easily implemented in standard laboratories, helping doctors identify patients who appear stable but have underlying metabolic imbalances.
However, the researchers emphasise that the results need to be validated further before the test can be used in clinical practice. Among other things, more studies on asthma patients including direct clinical trials and cost-effectiveness analyses are required.
This study was a collaboration between Karolinska Institutet, Sweden, and Mass General Brigham, USA. The study was supported by funding from the National Heart, Lung, and Blood Institute (NHLBI), the Swedish Research Council, and the Swedish Heart-Lung Foundation.
Conflicts of interest: The researchers have applied for a patent for the method. Jessica Lasky-Su is a scientific advisor to Precion Inc. and TruDiagnostic Inc. Co-author Scott T. Weiss receives royalties from UpToDate and sits on the board of Histolix. The other authors have no relevant competing interests to declare.
Publication: "The ratio of circulatory levels of sphingolipids to steroids predicts asthma" , Yulu Chen, Pei Zhang, Mengna Huang, Priyadarishini Kachroo, Antonio Checa, Qingwen Chen, Kevin Mendez, Meryl Stav, Nicole Prince, Sofina Begum, Andrea Aparicio, Tao Guo, Rinku Sharma, Su H. Chu, Rachel S. Kelly, Julian Hecker, Ayobami Akenroye, Amber Dahlin, Scott T. Weiss, Michael McGeachie, Craig E. Wheelock, Jessica A. Lasky-Su, Nature Communications online 19 January 2026, doi: 10.1038/s41467-025-67436-7.
