The nasal basal cell population shifts toward a diseased phenotype with impaired barrier formation capacity in allergic rhinitis.

BACKGROUND: The integrity of the airway epithelium is guarded by the airway basal cells that serve as progenitor cells and restore wounds in case of injury. Basal cells are a heterogenous population, and specific changes in their behavior are associated with chronic barrier disruption-mechanisms that have not been studied in detail in allergic rhinitis (AR). OBJECTIVE: We aimed to study basal cell subtypes in AR and healthy controls. METHODS: Single-cell RNA sequencing (scRNA-Seq) of the nasal epithelium was performed on nonallergic and house dust mite-allergic AR patients to reveal basal cell diversity and to identify allergy-related alterations. Flow cytometry, immunofluorescence staining, and in vitro experiments using primary basal cells were performed to confirm phenotypic findings at the protein level and functionally. RESULTS: The scRNA-Seq, flow cytometry, and immunofluorescence staining revealed that basal cells are abundantly and heterogeneously present in the nasal epithelium, suggesting specialized subtypes. The total basal cell fraction within the epithelium in AR is increased compared to controls. scRNA-Seq demonstrated that potentially beneficial basal cells are missing in AR epithelium, while an activated population of allergy-associated basal cells is more dominantly present. Furthermore, our in vitro proliferation, wound healing assay and air-liquid interface cultures show that AR-associated basal cells have altered progenitor capacity compared to nonallergic basal cells. CONCLUSIONS: The nasal basal cell population is abundant and diverse, and it shifts toward a diseased state in AR. The absence of potentially protective subtypes and the rise of a proinflammatory population suggest that basal cells are important players in maintaining epithelial barrier defects in AR.

Multiple reasons underlaying uncontrolled disease in the majority of chronic rhinosinusitis patients.

Background: Up to 40% of patients with chronic rhinosinusitis (CRS) remain uncontrolled despite guidelines of care being available, with an enormous socio-economic impact. The reasons for uncontrolled disease can be arbitrarily divided into disease-related, diagnosis-related, treatment-related, and patient-related factors. The relative contribution of each factor in uncontrolled CRS remains speculative. This explorative study aimed at determining the factors responsible for uncontrolled CRS in a tertiary care center, thereby identifying the most commons reasons for uncontrolled disease in CRS. Methods: Patients with uncontrolled CRS (n = 187) were asked to fill out a questionnaire and underwent a clinical examination at the outpatient clinic of the University Hospital of Leuven, Belgium. Two independent physicians evaluated the (multiple) reason(s) for uncontrolled disease. Results: In uncontrolled CRS, 66% of patients showed two or more reasons for uncontrolled disease according to the physicians' evaluation. Disease-related factors (70%) were most often considered the reason for uncontrolled disease, followed by treatment- (45%), patient- (42%), and diagnosis- (32%) related factors. Conclusion: In case of uncontrolled CRS, the different contributing factors to the uncontrolled nature need to be carefully addressed during diagnostic and therapeutic actions in order to define strategies to improve CRS care. Most uncontrolled CRS patients have multiple reasons contributing to their disease status, with disease-related factors being the most common factor.

Mometasone furoate and fluticasone furoate are equally effective in restoring nasal epithelial barrier dysfunction in allergic rhinitis.

Tight junction defects (TJ) have been associated with a defective epithelial barrier function in allergic rhinitis (AR). Intranasal corticosteroids are potent drugs frequently used to treat AR and are shown to restore epithelial integrity by acting on TJs and by reducing type 2 cytokine production. However, the effect of different classes of intranasal corticosteroids on the epithelial barrier has not been studied. Therefore, we compared the effect of 2 intranasal corticosteroids, ie, fluticasone furoate (FF) and mometasone furoate (MF) on epithelial barrier function. Both FF and MF similarly increased trans-epithelial electrical resistance of primary nasal epithelial cell cultures from AR patients. In a house dust mite-induced allergic asthma mouse model, FF and MF had similar beneficial effects on fluorescein isothiocyanate-dextran 4 kDa mucosal permeability, eosinophilic infiltration and IL-13 levels. Both molecules increased mRNA expression of the TJ proteins occludin and zonula occludens-1, thereby restoring epithelial barrier function. Lastly, we showed that long-term FF treatment also increased expression of occludin in AR patients compared to controls. In conclusion, both FF and MF effectively restore epithelial barrier function by increasing expression of TJ proteins in AR patients.