In this study, we will investigate the effect of tezepelumab on the epithelial barrier function of the upper and lower airways in patients suffering from severe asthma with and without chronic rhinosinusitis with nasal polyps. This will be achieved by analysis of epithelial barrier function upon challenge with various harmful substances (e.g. cigarette smoke extract, allergens) in cultured primary respiratory tract epithelial cells. Furthermore we will assess changes in clinical parameters, cellular composition and inflammatory mediators.
The primary objective of the proposal is to investigate the effect of Tezepelumab on the epithelial barrier function of upper and lower airways. To that aim, epithelial cells from the upper and lower airways will be cultured to investigate the change in barrier function during Tezepelumab treatment in patients suffering from severe asthma in presence or absence of chronic rhinosinusitis with nasal polyps. In addition, mucus plugging will be quantified by computer tomography before and after Tezepelumab therapy. These data will be supplemented by cellular and mediator analyses as well as microbiome analyses. Thus, our study will unravel the molecular mechanisms and benefits underlying therapy with Tezepelumab in patients suffering from severe asthma with or without nasal polyps. Objectives Primary objective: Effect of Tezepelumab treatment on the barrier function of upper and lower airways in patients suffering from severe asthma with and without CRSwNP. This will be achieved by analysis of epithelial barrier function upon challenge with various harmful substances (e.g. cigarette smoke extract, allergens, and rhinovirus) in cultured primary respiratory tract epithelial cells using the xCELLigence system for continuous monitoring of barrier function.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
20
injection with Tezepelumab every 4 weeks
Medical University of Vienna
Vienna, Austria, Austria
Change in cell index
Changes in normalized cell index in response to barrier-damaging substances in cultured primary epithelial cells of the different disease entities using the xCELLigence system for continuous monitoring of barrier function.
Time frame: 6 months
Change in mucus plugging
The extent of air-trapping, bronchial wall thickening and mucus plugging per pulmonary segment will be scored independently by two thoracic radiologists.
Time frame: 6 months
Change in marker expression immune cell subsets
Cellular composition and marker expression on cells derived from Bronchoalveolar lavage (BAL), nasal polyps and blood as assessed by a multi-colour mass cytometry panel
Time frame: 6 months
Change in inflammatory mediators
(Inflammatory) mediator expression in BAL, lung tissue, nasal mucosa, polyp tissue (e.g. OLINK explorer)
Time frame: 6 months
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