Advances in the Knowledge of the Underlying Airway Remodeling Mechanisms in Chronic Rhinosinusitis Based on the Endotypes: A Review

Abstract

Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa that affects up to 10% of the population worldwide. CRS is the most representative disease of the upper respiratory tract where airway remodeling occurs, including epithelial damage, thickening of the basement membrane, fibrosis, goblet cell hyperplasia, subepithelial edema, and osteitis. CRS is divided into two phenotypes according to the presence or absence of nasal polyps: CRS with nasal polyp (CRSwNP) and CRS without nasal polyps (CRSsNP). Based on the underlying pathophysiologic mechanism, CRS is also classified as eosinophilic CRS and non-eosinophilic CRS, owing to Type 2 T helper (Th2)-based inflammation and Type 1 T helper (Th1)/Type 17 T helper (Th17) skewed immune response, respectively. Differences in tissue remodeling in CRS are suggested to be based on the clinical phenotype and endotypes; this is because fibrosis is prominent in CRSsNP, whereas edematous changes occur in CRSwNP, especially in the eosinophilic type. This review aims to summarize the latest information on the different mechanisms of airway remodeling in CRS according to distinct endotypes.

DNMTs Are Involved in TGF-β1-Induced Epithelial–Mesenchymal Transitions in Airway Epithelial Cells

“…Its importance is widely investigated in recalcitrant cases. In CRS, tissue remodeling appears in various forms, including EMT, subepithelial fibrosis, goblet cell hyperplasia, hypertrophy of bronchial myocytes, submucosal angiogenesis, and increased extracellular matrix deposition, depending on the type of inflammation [ 10 ]. Among them, EMT is a consistent phenomenon in the mucosal epithelium of CRS regardless of the type of inflammation or presence of nasal polyps.…”

“…Tissue remodeling refers to the structural change that is caused by a persistent inflammatory response. Airway remodeling is characterized by inflammatory cell infiltration, basement membrane thickening, angiogenesis, goblet cell hyperplasia, edema, and fibrosis [ 10 ]. Tissue remodeling can be associated with pathological changes in CRS in the respiratory epithelium, lamina propria, and submucosa.…”

Biologics for severe uncontrolled chronic rhinosinusitis with nasal polyps: a change management approach. Consensus of the Joint Committee of Italian Society of Otorhinolaryngology on biologics in rhinology

“…However, further research demonstrated that immunologic profile is much more complex, demonstrating that there is some overlap and endotypes may coexist in the same patient. In fact, non-eosinophilic inflammation dominated by Th1/Th17 pathways may be associated with CRSwNP and CRSsNP patients may express a Type 2 cytokine profile [12][13][14][15] . Because studies on endotyping provided full insight into the underlying cellular and molecular inflammatory mechanisms associated with CRS 16 , the EPOS 2020 group 1 came into the decision to change the management approach to CRS.…”

miR-29b Regulates TGF-β1-Induced Epithelial–Mesenchymal Transition by Inhibiting Heat Shock Protein 47 Expression in Airway Epithelial Cells

“…Moreover, the concept of tissue remodeling has been well established in lower respiratory diseases, such as asthma, that share similar pathological mechanisms with refractory CRS. According to current evidence, tissue remodeling in CRS shows characterized clinical features based on the endotype and continuously occurs during ongoing inflammation [15]. Kao et al reported further evidence that CRS mucous, regardless of phenotype, demonstrated dysregulations of biological processes related to tissue remodeling using proteomic analysis [16].…”