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.
Provision of informed consent prior to any study specific procedures
Age 18-99 years and willing to participate in the study
Have a recorded clinical diagnosis of asthma (ICD-10 Code: J45)
Undergo severe asthma treatment according to GINA/DAL treatment step 4 or 5
Bronchiectasis, pulmonary fibrosis, emphysema, primary ciliary dyskinesia
Cystic fibrosis, any known parasitic infections and lung cancer
Single group
Tezepelumab
Druginjection with Tezepelumab every 4 weeks
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.
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.
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
Change in inflammatory mediators
(Inflammatory) mediator expression in BAL, lung tissue, nasal mucosa, polyp tissue (e.g. OLINK explorer)
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