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Targeting Epithelium Dysfunction and Impaired Nasal Biofilms to Treat Immunological, Functional, and Structural Abnormalities of Chronic Rhinosinusitis

Journal

Publisher

MDPI
DOI: 10.3390/ijms241512379

Keywords

polyps; eosinophilic; type 2 inflammation; biofilm; nitric oxide; microbiome; biomarkers; mucociliary clearance; cystic fibrosis; primary ciliary dyskinesia; immunodeficiencies; granulomatosis

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Chronic rhinosinusitis (CRS) is a common and heterogeneous disorder with complex underlying mechanisms. CRS is a broad syndrome involving multiple immunological features, including interactions between genes, the microbiome, exosomes, the epithelial barrier, and environmental exposures. The main pathophysiological feature is epithelial barrier disruption, accompanied by microbiome alterations and unpredictable immunoreactions. CRSwNP is characterized by fibrosis and mild inflammation, often associated with Th1 or Th17 immunological profiles. CRSsNP is associated with moderate or severe eosinophilic inflammation. Diagnosis is based on clinical, endoscopic, and imaging findings. Different CRS endotypes are studied through biomarkers from blood, nasal secretions, biopsies, and exhaled air. Management aims to maintain clinical control through nasal douching, steroids, antibiotics, biologics, or surgical procedures in severe cases.
Chronic rhinosinusitis (CRS) with (CRSwNP) or without (CRSsNP) nasal polyps is a prevalent and heterogeneous disorder existing as a spectrum of clinical conditions with complex underlying pathomechanisms. CRS comprises a broad syndrome characterized by multiple immunological features involving complex interactions between the genes, the microbiome, host- and microbiota-derived exosomes, the epithelial barrier, and environmental and micromilieu exposures. The main pathophysiological feature is an epithelial barrier disruption, accompanied by microbiome alterations and unpredictable and multifactorial immunologic overreactions. Extrinsic pathogens and irritants interact with multiple epithelial receptors, which show distinct expression patterns, activate numerous signaling pathways, and lead to diverse antipathogen responses. CRSsNP is mainly characterized by fibrosis and mild inflammation and is often associated with Th1 or Th17 immunological profiles. CRSwNP appears to be associated with moderate or severe type 2 (T2) or Th2 eosinophilic inflammation. The diagnosis is based on clinical, endoscopic, and imaging findings. Possible CRS biomarkers from the peripheral blood, nasal secretions, tissue biopsies, and nasally exhaled air are studied to subgroup different CRS endotypes. The primary goal of CRS management is to maintain clinical control by nasal douching with isotonic or hypertonic saline solutions, administration of nasal and systemic steroids, antibiotics, biologic agents, or, in persistent and more severe cases, appropriate surgical procedures.

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