Biomarkers for Severe Asthma: Lessons From Longitudinal Cohort Studies

Severe asthma (SA) is a heterogeneous disease characterized by uncontrolled symptoms, frequent exacerbations, and lung function decline. The discovery of phenotypes and endotypes of SA significantly improves our understanding of its pathophysiology and allows the advent of biologics blocking multiple molecular targets. The advances have mainly been made in type 2-high asthma associated with elevated type 2 inflammatory biomarkers such as immunoglobulin E (IgE), interleukins (IL)-4, IL-5, and IL-13. Previous clinical trials have demonstrated that type 2 biomarkers, including blood/sputum eosinophils and the fraction of exhaled nitric oxide (FeNO), were correlated to severe airway inflammation, persistent symptoms, frequent exacerbations, and the clinical efficacy of these biomarkers in predicting treatment outcomes of type 2-targeting biologics. However, it is well known that type 2 inflammation is partially attributable to the pathogenesis of SA. Although some recent studies have suggested that type 2-low and mixed phenotypes of asthma are important contributors to the heterogeneity of SA, many questions about these non-type 2 asthma phenotypes remain to be solved. Consequently, many efforts to investigate and find novel biomarkers for SA have also made in their methods. Many cross-sectional experimental studies in large-scale cohorts and randomized clinical trials have proved their value in understanding SA. More recently, real-world cohort studies have been in the limelight for SA research, which is unbiased and expected to give us an answer to the unmet needs of the heterogeneity of SA.