Pathogenesis of Nasal Polyposis: Current Trends

Abstract

Chronic Rhinosinusitis (CRS) is characterized by edema of the sub-epithelial layers, but, only specific types of CRS are developing polyps. Nasal polyposis may develop under different pathogenetic mechanisms rendering the typical macroscopic classification of CRS, with or without nasal polyps, rather deficient. Currently, we approach nasal polyposis, in terms of diagnosis and treatment, according to its endotype, which means that we focus on the specific cells and cytokines that are participating in its pathogenesis. It appears that the molecular procedures that contribute to polyp formation, initiating with a Th-2 response of the adaptive immune system, are local phenomena occurring in the sub-epithelial layers of the mucosa. Several hypotheses are trying to approach the etiology that drives the immune response towards Th-2 type. Extrinsic factors, like fungi, Staphylococcus superantigens, biofilms, and altered microbiome can contribute to a modified and intense local reaction of the immune system. Some hypotheses based on intrinsic factors like the elimination of Treg lymphocytes, low local vitamin-D levels, high levels of leukotrienes, epithelial to mesenchymal transition (EMT) induced by hypoxia, and altered levels of NO, add pieces to the puzzle of the pathogenesis of nasal polyposis. Currently, the most complete theory is that of epithelial immune barrier dysfunction. Intrinsic and extrinsic conditions can damage the epithelial barrier rendering sub-epithelial layers more vulnerable to invasion by pathogens that trigger a Th-2 response of the adaptive immune system. Th2 cytokines, subsequently, induce the accumulation of eosinophils and IgE together with the remodeling of the stroma in the sub-epithelial layers leading, eventually, to the formation of nasal polyps.

Remodeling of Paranasal Sinuses Mucosa Functions in Response to Biofilm-Induced Inflammation

“…199 In general, dysregulated and intense local immune response, triggered by extrinsic factors (fungi, staphylococcal superantigens, biofilms, and imbalanced microbiota) and intrinsic factors like (i) induced by hypoxia EMT, (ii) depletion of Treg lymphocytes, (iii) low local vitamin-D levels, (iv) high levels of leukotrienes, and (v) altered levels of NO have been associated with pathogenesis of nasal polyposis. 201 Nevertheless, it appears that the damage of the epithelial barrier, regardless form intrinsic or extrinsic etiology, is a precondition increasing the susceptibility of subepithelial layers to invasion by pathogens that trigger a Th-2-skewed response. Subsequently, Th2 cytokines induce the accumulation of eosinophils and IgE, as well as remodeling of the sub-epithelial stroma, resulting in the formation of nasal polyps.…”

“…Subsequently, Th2 cytokines induce the accumulation of eosinophils and IgE, as well as remodeling of the sub-epithelial stroma, resulting in the formation of nasal polyps. 201 Pseudocyst formation, involving edema formation with albumin accumulation and collagen depletion within the extracellular matrix, is a typical remodeling feature of the mucosa in CRSwNP. 136 Damage to the epithelial barrier results in an influx of inflammatory cells, tissue swelling, and fibrin deposition.…”

Intranasal alpha-adrenergic receptor agonists and corticosteroids as medical treatments for nasal congestion

“…Nasal polyps are eventually formed when the sub-epithelial stroma is remodelled. It is again linked to inflammatory conditions that cause nasal congestion, such as chronic rhinosinusitis, asthma, and aspirin-exacerbated respiratory disease (AERD) [6].…”

The Inhibition Effect and Mechanism of Staurosporine Isolated from Streptomyces sp. SNC087 Strain on Nasal Polyp

“…The nasal polyp (NP) mucosa is mostly composed of respiratory epithelium, and the submucosal layer shows significant swelling, with the infiltration of inflammatory cells, particularly eosinophils [2]. The exact cause of NPs is not fully understood, but there have been reports suggesting a potential association with allergic reactions, inflammation, epithelial immune barrier dysfunction, and genetic factors [1,3,4]. While the precise underlying mechanisms remain unclear, these factors are believed to play a role in the development of NPs.…”