High airway thymic stromal lymphopoietin in asthma is associated with type 2 inflammation, mucus plugging, and airway remodeling

Background: Inhibition of thymic stromal lymphopoietin (TSLP) improves asthma control, but the relationships between airway TSLP levels and clinical and immunologic features of asthma are unclear. Objective: We sought to determine associations between airway TSLP, disease control, and airway remodeling in asthma. Methods: We measured TSLP protein in sputum from patients with mild-to-moderate asthma (University of California San Francisco cohort, n = 137), patients with moderate-to-severe asthma (Severe Asthma Research Program-3 cohort, n = 397), and healthy controls (n = 95). We explored how sputum TSLP levels relate to measures of lung function and exacerbations, airway inflammation, and lung image–based measures of mucus plugging and airway remodeling. Results: The upper 95th percentile value for sputum TSLP concentration in healthy controls was 1.6 pg/mL; 16% of the University of California San Francisco cohort and 33.5% of the Severe Asthma Research Program-3 cohort had TSLP concentrations above this value. High sputum TSLP levels occurred most often in patients with severe asthma showing clinical traits typical of type 2 inflammation. There was considerable overlap between subgroups with high levels of TSLP and eosinophilic inflammation. High sputum TSLP levels were associated with a strong sputum cell gene expression profile for type 2 immune responses and a weak expression for type 1 responses. High sputum TSLP levels were also associated with high sputum MUC5AC expression and high scores for mucus plugging, air trapping, and other measures of airway remodeling on computed tomography lung scans. Conclusion: High levels of airway TSLP in asthma are associated with more severe asthma with predominantly type 2 airway immune responses and with mucus plugging, air trapping, and airway remodeling.