Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation

Abstract

BackgroundThymic stromal lymphopoietin (TSLP) is released from the airway epithelium in response to various environmental triggers, inducing a Type-2 inflammatory response, and is associated with airway inflammation, airway hyperresponsiveness (AHR) and exacerbations. TSLP may also induce AHR via a direct effect on airway smooth muscle and mast cells, independently of Type-2 inflammation, although association between airway TSLP and AHR across asthma phenotypes only has been described sparsely. ObjectiveTo investigate the association between AHR and levels of TSLP in serum, sputum and BAL in patients with asthma with and without Type-2 inflammation. MethodsA novel ultra-sensitive MSD S-plex assay was used to measure levels of TSLP in patients with asthma (serum n=182, sputum n=81, BAL n=85) and healthy controls (serum n=47). The distribution and association between airway and systemic TSLP, measures of AHR, Type-2 inflammation and severity of disease were assessed. ResultsTSLP in sputum was associated with AHR independently of levels of eosinophils and fractional exhaled nitric oxide, ρ=0.49, p=0.005. Serum TSLP (geo.mean (95% CI)) was higher in both eosinophil-high and eosinophil-low asthma compared to healthy controls: 1600 fg/ml (1468-1744) and 1294 fg/ml (1167-1435) vs. 846 fg/ml (661-1082), but did not correlate with the level of AHR. Increasing age, male sex and eosinophils in blood were associated with higher levels of TSLP in serum, whereas lung function, ICS dose and symptom score were not. ConclusionThe association between TSLP in sputum and AHR to mannitol irrespective of markers of type-2 inflammation further supports a role of TSLP in AHR that is partially independent of eosinophilic inflammation.