Onderzoek naar de rol van neuroendocrine mechanismen bij bovenste luchtwegaandoeningen.

Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are highly prevalent disorders, affecting 30% and 5-15% of the general population, respectively. These conditions are characterized by pronounced nasal and sinonasal mucosal inflammation, leading to classic pathological features such as rhinorrhea, nasal congestion, loss of smell, and facial pain and pressure. Despite their significant impact on quality of life, current treatments remain disappointing, primarily due to a limited understanding of the underlying molecular mechanisms. Neurogenic inflammation, with nasal hyperreactivity (NHR) as a key clinical feature in the upper airways, is increasingly recognized in upper airway inflammatory conditions like AR and CRSwNP. However, the mechanisms leading to NHR are not yet fully understood. A deeper understanding of these neurogenic pathways and their manifestation as NHR could provide valuable insights for developing improved therapeutic strategies. Recent research has highlighted the airway epithelium as a potential key player in the pathology of AR and CRSwNP. Using single-cell RNA sequencing, novel epithelial cell types have been identified, including neuroendocrine cells—rare cells that function as chemoreceptors to monitor airway status. In the lower airways, neuroendocrine cells release neuromediators or cytokines that activate innate lymphoid cells and neurons, further promoting type 2 allergic responses. However, their role in upper airway diseases remains unexplored. Therefore, the overall aim of this research is to investigate the neurogenic mechanisms contributing to inflammation and NHR in AR and CRSwNP. Specifically, this includes studying whether neuroendocrine cell numbers are increased in these conditions, evaluating how the release of neuromediators is regulated, and determining how these mediators differ between AR, CRSwNP, and healthy controls. This work seeks to shed light on the neurogenic pathways driving these diseases and their implications for innovative treatment approaches.