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

Abstract

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.

Targeting IL-4 and IL-13 Receptors on Eosinophils in CRSwNP Patients: The Clinical Efficacy of Dupilumab

“…Nasal polyposis symptoms have a major impact on both social life and mental health. One of the most important consequences of the disease are sleep disturbances which will lead the patient to wake up already tired or to tire easily during the day [ 8 ]. The evaluation of the patient foresees a first diagnostic phase, with estimation of the sino-nasal symptomatology, objectifying the symptom with numerical values attributed by the patient himself; a subsequent phase in which social/occupational functioning, emotional consequences and overall satisfaction with care are assessed.…”