xRead - Nasal Obstruction (September 2024) Full Articles

20426984, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.22741 by Stanford University, Wiley Online Library on [01/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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International consensus statement on rhinosinusitis

frequency, and anti-bactericidal activity. 612 The evidence showed the T2R38 genotype PAV/PAV or PAV/PAV T2R38 are less susceptible to gram-negative bacterium sinonasal infection than PAV/AVI or AVI/ AVI patients. 612 TAS2R38 polymorphisms have been associated with an increased risk of CRS. 611 These findings indicate the potential role of T2R in the pathogenesis of CRSsNP. Innate Immune Cell and Epithelial Derived Cytokines. The proportion of macrophage, mast cells, fibroblast and basophils in the sinonasal tissue in CRSsNP are similar to that in healthy subjects. Patients with CRSsNP demon strate local neutrophilic inflammation. However, there are conflicting data suggesting whether a local eosinophilia is present. The expression levels of epithelial-derived innate cytokines in most CRSsNP patients were similar to that in healthy subjects. In summary, the evidence demonstrating key epithe lial innate immune mediators are differentially expressed is relatively sparse with no cohesive picture yet formed (Tables IX-13 through IX-15). Additional work in this area will shed meaningful light on the pathophysiology of CRSsNP. IX.C.12 Contributing Factors for CRS: Epithelial Barrier Disturbance Because of limited data, CRSsNP and CRSwNP are com bined in this analysis. Sinonasal mucosa functions as a mechanical and immunological barrier to a range of exogenous agents that may initiate and contribute to mucosal inflamma tion. When the mechanical barrier fails, immunologi cal activation of epithelial receptors can lead to the dys regulated secretion of pro-inflammatory cytokines and chemokines with resultant cellular injury, chronic inflam mation and tissue remodeling. CRS has been described through the immune barrier hypothesis as a disease borne from dysfunctional sinonasal mucosa and altered cellu lar and immunological responses. 835 Different patterns of upstream epithelial defects have been characterized in the phenotypes of CRS and more recently with geographical variances in the immunological responses identified in the same phenotypic class of disease. 836 There are 2 components of the mechanical barrier; res piratory mucus and, in health, a relatively impermeable epithelial barrier. The function of mucus is to trap foreign material and cilial motility propels it toward the nasophar ynx. Nasal mucus consists of water, glycoproteins and intrinsic antimicrobial agents including antioxidants and antiproteases. 837 Mucin glycoproteins are key components and 2 forms exist; secreted gel-forming mucins that are responsible for its viscoelastic properties and membrane

bound mucins that bind pathogens. In conjunction with effective ciliary function, mechanical elimination of pathogens and nasal irritants occurs. Alteration in the expression of secreted and membrane-bound mucins has been reported in adult CRS patients when compared to control patients. 838,839 No differences have been identified between the pediatric CRS and control populations, sug gesting that these alterations may possibly be related to the duration of the disease process. 837 Cilial function is critical in the mechanical clearance of nasal mucus. Genetic and acquired defects are associated with a high incidence of sinonasal inflammation and CRS 840–843 in disease conditions such as cystic fibrosis and primary ciliary dyskinesia. Beneath the mucus reside the epithelial cells, which are linked by tight and adherenz junctions. Tight and adherent junctions comprise the apical junctional complex (AJC), creating a relatively impermeable barrier. Disruption of proteins in the AJC can result in a "leaky" barrier, and thus allow the entry of pathogenic microbes, allergens or antigens into the underlying tissue. 844 Alterations in this epithelial barrier have been recognized in other Type 2 inflammatory diseases including atopic dermatitis, asthma and eosinophilic esophagitis, 845 and both cell-intrinsic and extrinsic mechanisms have been described. 846 It remains controversial in the setting of CRS as to whether the epithelium is inherently dysfunctional or disruption is a consequence of exogenous factors, however, studies have demonstrated increased barrier permeability in both nasal epithelial cell cultures and tissue samples within CRSwNP patients. 847–849 In both CRSwNP and CRSsNP, the epithelium is known to be structurally and functionally abnormal, which may be crucial in the development and progression of CRS. For example, the epithelium in CRSwNP appears to respond inappropriately to physical insults or common pathogens and this can lead to aberrant epithelial dam age including hyperplasia with an increase of poorly pro liferated basal cells forming multiples layers or squamous metaplasia. 159,180,850 Furthermore, goblet cell hyperplasia with excessive mucus production, abnormalities in cilia architecture and function can be found in hyperplasia or squamous metaplasia of the nasal epithelium. 182,851,852 A recent study from single-cell transcriptomes of epithelial cells from the non-polyp and polyp demonstrated that in humans for the emerging paradigm of stem cell dysfunc tion altering the set point of barrier tissues, where basal cells form "memories" of chronic exposure to the type 2 immunity environment, shifting the entire cellular ecosys tem away from productive differentiation and propagat ing disease. 853 These pathological findings are similar to that seen in asthma where the epithelium damage and more mucus-producing cells than normal make the airway