Pathogenesis of nasal polyposis

Abstract

Summary Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition that affects a large proportion of the population world-wide and is associated with high cost of management and significant morbidity. Yet, there is a lack of population-based epidemiologic studies using current definitions of CRSwNP, and the mechanisms that drive pathogenesis in this disease remain unclear. In this review, we summarize the current evidence for the plethora of factors that likely contribute to CRSwNP pathogenesis. Defects in the innate function of the airway epithelial barrier, including diminished expression of antimicrobial products and loss of barrier integrity, combined with colonization by fungi and bacteria likely play a critical role in the development of chronic inflammation in CRSwNP. This chronic inflammation is characterized by elevated expression of many key inflammatory cytokines and chemokines, including IL-5, thymic stromal lymphopoietin and CCL11, that help to initiate and perpetuate this chronic inflammatory response. Together, these factors likely combine to drive the influx of a variety of immune cells, including eosinophils, mast cells, group 2 innate lymphoid cells and lymphocytes, which participate in the chronic inflammatory response within the nasal polyps. Importantly, however, future studies are needed to demonstrate the necessity and sufficiency of these potential drivers of disease in CRSwNP. In addition to the development of new tools and models to aid mechanistic studies, the field of CRSwNP research also needs the type of robust epidemiologic data that has served the asthma community so well. Given the high prevalence, costs and morbidity, there is a great need for continued research into CRS that could facilitate the development of novel therapeutic strategies to improve treatment for patients who suffer from this disease.

Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease

“…However, as recently summarized, there are conflicting reports regarding expression levels of specific inflammatory mediators in CRS, which may in part be secondary to different types of specimens and/or methodology used for analysis (19). As a result, the first goal of our present study was to measure mediators simultaneously in a given type of sinonasal tissue specimen and characterize these inflammatory signatures in controls, CRSsNP, and CRSwNP.…”

“…It has been suggested that CRSsNP is driven by a predominant type 1 inflammatory response, whereas CRSwNP is characterized by an enhanced type 2 response (16)(17)(18). However, there are conflicting reports regarding expression levels of specific mediators in CRS, and thus a more comprehensive analysis is warranted (19). Dysregulation of arachidonic acid metabolism and altered platelet function are thought to specifically contribute to AERD pathogenesis, but additional studies are needed to further investigate potential roles that other mediators may play in this severe form of polypoid sinus disease (20,21).…”

The nasal microbiome: opening new clinical research avenues for allergic disease

“…Discovery of new pathways by studying the interplay between the immune system and the microbial communities Nasal epithelium and mucosal cells including submucosal mixed seromucinous glands produce a large group of proteins and peptides with antimicrobial functions. These cells possess multiple pattern recognition receptors such as Toll-like receptors (TLRs) and bitter taste receptors [18]. T-helper 2-type inflammation in AR, asthma, and eosinophilic CRS has been associated with downregulation of innate immunity elements like human beta-defensin 2(hBD-2), antileukoproteinase, immunoglobulin J chain, surfactant protein-A (SP-A), and TLRs [11,18,19].…”

“…These cells possess multiple pattern recognition receptors such as Toll-like receptors (TLRs) and bitter taste receptors [18]. T-helper 2-type inflammation in AR, asthma, and eosinophilic CRS has been associated with downregulation of innate immunity elements like human beta-defensin 2(hBD-2), antileukoproteinase, immunoglobulin J chain, surfactant protein-A (SP-A), and TLRs [11,18,19]. Microbial products are ligands for these innate immune receptors, which are found on inflammatory granulocytes like basophils and eosinophils.…”

Combinations of Interleukin-10 Gene Promoter Polymorphisms with -1082A, -819T, -592A Minor Allele are Associated with Sinonasal Polyposis

“…Sinonasal polyposis is often accompanied by allergic rhinitis, allergy, aspirin susceptibility and asthma [1]. SP has been implicated in many immunological pathways and is a localized manifestation of systemic disorders [2,3]. SP cases frequently accompanied by T helper (Th) type 1-, Th2-, or Th17-biased inflammatory processes regulated by increased expression levels of a number of cytokines with pro-and anti-inflammatory activities [4].…”