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

Louise Munkholm Andreasson, Nanna Dyhre-Petersen, Morten Hvidtfeldt, Gustav Ørting Jørgensen, Anna Von Bülow, Ditte Kjærsgaard Klein, Lena Uller, Jonas Erjefält, Celeste Porsbjerg, Asger Sverrild

1 Citation (Scopus)

Abstract

BACKGROUND: Thymic 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 has been described sparsely.

OBJECTIVES: This study sought to investigate the association between AHR and levels of TSLP in serum, sputum, and bronchoalveolar lavage in patients with asthma with and without type-2 inflammation.

METHODS: A novel ultrasensitive assay was used to measure levels of TSLP in patients with asthma (serum, n = 182; sputum, n = 81; bronchoalveolar lavage, n = 85) and healthy controls (serum, n = 47). The distribution and association among airway and systemic TSLP, measures of AHR, type-2 inflammation, and severity of disease were assessed.

RESULTS: TSLP in sputum was associated with AHR independently of levels of eosinophils and fractional exhaled nitric oxide (ρ = 0.49, P = .005). Serum TSLP was higher in both eosinophil-high and eosinophil-low asthma compared to healthy controls: geometric mean: 1600 fg/mL (95% CI: 1468-1744 fg/mL) and 1294 fg/mL (95% CI: 1167-1435 fg/mL) versus 846 fg/mL (95% CI: 661-1082 fg/mL), 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, inhaled corticosteroid dose, and symptom score were not.

CONCLUSIONS: The 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.

Original languageEnglish
JournalThe Journal of allergy and clinical immunology
Volume153
Issue number4
Pages (from-to)988-997.e11
ISSN0091-6749
DOIs
Publication statusPublished - Apr 2024

Keywords

  • Airway hyperresponsiveness
  • asthma
  • blood
  • eosinophils
  • sputum
  • TSLP

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