Type 2-low Asthma: Epidemiology, Multiomics, and Emerging Therapies

Type 2-low (T2-low) asthma, characterized by low blood and sputum eosinophils and low fractional exhaled nitric oxide (FeNO), remains a major unmet need because of frequent corticosteroid insensitivity and a lack of targeted therapies. This review summarizes recent advances in its epidemiology, multiomics, and therapeutic landscape.

T2-low inflammation is highly prevalent, affecting approximately 14%-39% of adults with current asthma and up to 60% of children. Its pathogenesis reflects complex non-T2 mechanisms, including IL-17 signaling, innate immune activation through IL-1β and IL-33, and neutrophilic inflammation. Heterogeneity is further shaped by systemic factors such as obesity and immunosenescence and by environmental exposures such as ozone. Among available therapies, long-term macrolides and the anti-TSLP biologic tezepelumab have shown significant efficacy in reducing exacerbations, whereas other pathway-specific interventions have yielded inconsistent clinical benefits. Emerging metabolic approaches, including GLP-1 receptor agonists, may offer additional promise. Progress in T2-low asthma will require mechanism-based classification and clinically deployable biomarkers to align targeted therapies with specific biological drivers.