AN INSIGHTFUL study has revealed that a subset of patients with asthma has elevated levels of thymic stromal lymphopoietin (TSLP) in the airways, a finding associated with severe disease, type 2 inflammation, mucus plugging, and airway remodelling, according to new research.
TSLP is an epithelial-derived cytokine that plays a central role in initiating type 2 immune responses in asthma. While inhibition of TSLP is known to improve asthma outcomes, the clinical significance of airway TSLP levels has not been well defined. This study aimed to clarify how airway TSLP relates to asthma severity, immune profiles, and structural lung changes.
Investigators measured TSLP protein levels in sputum samples from 137 patients with mild-to-moderate asthma, 397 patients with moderate-to-severe asthma, and 95 healthy controls. The upper 95th percentile of sputum TSLP in healthy individuals was 1.6 pg/mL. Levels above this threshold were observed in 16% of patients with mild-to-moderate asthma and in 33.5% of those with moderate-to-severe disease.
Elevated Airway TSLP Common in Type 2-High Asthma
Elevated airway TSLP was most frequently identified in patients with severe asthma displaying features of type 2 inflammation, including eosinophilia. Gene expression analysis of sputum cells showed that high TSLP levels were associated with strong activation of type 2 immune pathways and reduced expression of type 1 inflammatory signals. Although there was substantial overlap between patients with high TSLP and those with eosinophilic inflammation, the two groups were not identical, suggesting TSLP may represent a distinct biological marker.
Importantly, high airway TSLP was also linked to structural lung abnormalities on CT imaging. Patients with elevated TSLP demonstrated increased expression of the mucus-associated gene MUC5AC and higher scores for mucus plugging, air trapping, and airway remodelling, features associated with persistent airflow limitation and poor disease control.
Airway TSLP as a Biomarker for Severe Asthma
The authors conclude that elevated airway TSLP identifies a biologically distinct, type 2-high asthma endotype that persists despite corticosteroid treatment. These findings support the use of anti-TSLP and other type 2-targeted biologics in selected patients and highlight the potential role of airway TSLP as a biomarker for severe asthma with structural lung involvement.
Reference
Khanna K et al. High airway TSLP in asthma associates with type 2 inflammation, mucus plugging and airway remodeling. J Allergy Clin Immunol. 2025; doi: 10.1016/j.jaci.2025.11.014
