Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation
(2024) In Journal of Allergy and Clinical Immunology 153(4). p.11-997- 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... (More)
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.
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- author
- Andreasson, Louise Munkholm ; Dyhre-Petersen, Nanna ; Hvidtfeldt, Morten ; Jørgensen, Gustav Ørting ; Von Bülow, Anna ; Klein, Ditte Kjærsgaard ; Uller, Lena LU ; Erjefält, Jonas LU ; Porsbjerg, Celeste and Sverrild, Asger
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Airway hyperresponsiveness, asthma, blood, eosinophils, sputum, TSLP
- in
- Journal of Allergy and Clinical Immunology
- volume
- 153
- issue
- 4
- pages
- 11 - 997
- publisher
- Elsevier
- external identifiers
-
- pmid:38081546
- scopus:85181840022
- ISSN
- 0091-6749
- DOI
- 10.1016/j.jaci.2023.11.915
- language
- English
- LU publication?
- yes
- id
- c936492a-031d-42d4-8c05-4c2b166c3f04
- date added to LUP
- 2024-02-08 13:57:41
- date last changed
- 2024-11-07 17:53:20
@article{c936492a-031d-42d4-8c05-4c2b166c3f04,
abstract = {{<p>Background: </p><p>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.</p>}},
author = {{Andreasson, Louise Munkholm and Dyhre-Petersen, Nanna and Hvidtfeldt, Morten and Jørgensen, Gustav Ørting and Von Bülow, Anna and Klein, Ditte Kjærsgaard and Uller, Lena and Erjefält, Jonas and Porsbjerg, Celeste and Sverrild, Asger}},
issn = {{0091-6749}},
keywords = {{Airway hyperresponsiveness; asthma; blood; eosinophils; sputum; TSLP}},
language = {{eng}},
number = {{4}},
pages = {{11--997}},
publisher = {{Elsevier}},
series = {{Journal of Allergy and Clinical Immunology}},
title = {{Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation}},
url = {{http://dx.doi.org/10.1016/j.jaci.2023.11.915}},
doi = {{10.1016/j.jaci.2023.11.915}},
volume = {{153}},
year = {{2024}},
}