High Serum TSLP Is Characteristic of Late-Onset, Long-Duration, Eosinophilic Asthma

Background: Thymic stromal lymphopoietin (TSLP) is a master regulator of type 2 immune responses; however, the associations between serum TSLP and the characteristics of adult asthma have not been fully clarified. The aim of this study was to determine the characteristics of adult asthma with high serum TSLP and explore TSLP's association with the late-onset eosinophilic asthma phenotype. Methods: Baseline data of the TNH-Azma study (a real-world observational cohort study conducted in Japan on 1344 patients with asthma from 30 hospitals) was used and serum cytokines were measured. Patients were stratified into quartile groups based on the baseline serum TSLP levels, and their clinical characteristics were compared. Multivariable regression analyses were used to determine clinical variables associated with serum TSLP and cytokines associated with the late-onset eosinophilic asthma phenotype. Results: Patients with TSLP-high asthma were older, late-onset, eosinophilic, and less atopic; had a higher BMI; more smoking history; and more asthma–COPD overlap, sleep apnea syndrome (SAS), hypertension, and heart disease. They also exhibited lower lung function with worse asthma symptoms and were more frequently on oral corticosteroids. Multivariable regression analyses adjusted for age and sex demonstrated that a high TSLP level was positively associated with later asthma onset, longer asthma duration, hypertension, higher blood eosinophils, BMI, smoking history, use of biologics, SAS, and high Fres, and was negatively associated with pollinosis. Among the serum cytokines, TSLP exhibited the strongest association with late-onset, eosinophilic asthma. Conclusion: High serum TSLP is a distinctive feature of late-onset, long-duration, eosinophilic asthma. Patients with asthma with this feature may be a unique target population for specific asthma therapy.