The Development of Nasal Polyp Disease Involves Early Nasal Mucosal Inflammation and Remodelling

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by both a chronic inflammation and tissue remodelling; as indicated by extracellular matrix protein deposition, basement membrane thickening, goblet cell hyperplasia and subepithelial edema, with reduced vessels and glands. Although remodelling is generally considered to be consequence of persistent inflammation, the chronological order and relationship between inflammation and remodelling in polyp development is still not clear. The aim of our study was therefore to investigate the pathological features prevalent in the development of nasal polyps and to elucidate the chronological order and relationship between inflammation and remodelling, by comparing specific markers of inflammation and remodelling in early stage nasal polyps confined to the middle turbinate (refer to as middle turbinate CRSwNP) obtained from 5 CRSwNP patients with bilateral polyposis, mature ethmoidal polyps from 6 CRSwNP patients, and normal nasal mucosal tissue from 6 control subjects. Middle turbinate CRSwNP demonstrated significantly more severe epithelial loss compared to mature ethmoidal polyps and normal nasal mucosa. The epithelial cell junction molecules E-cadherin, ZO-1 and occludin were also expressed in significantly lower amounts in mature ethmoidal polyps compared to healthy mucosa. Middle turbinate CRSwNP were further characterized by significantly increased numbers of subepithelial eosinophils and M2 type macrophages, with a distinct lack of collagen and deposition of fibronectin in polyp part. In contrast, the turbinate area of the middle turbinate CRSwNP was characterized by an increase in TGF-β activated myofibroblasts expressing α-SMA and vimentin, an increase in the number of pSmad2 positive cells, as well as increased deposition of collagen. These findings suggest a complex network of processes in the formation of CRSwNP; including gross epithelial damage and repair reactions, eosinophil and macrophage cell infiltration, and tissue remodelling. Furthermore, remodelling appears to occur in parallel, rather than subsequent to inflammation.

Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers

“…Also, subjects were allocated to a phenotype during office endoscopy before surgery, and the clinical differentiation might be unclear in some cases were polyps were only observed during surgery. In cases of middle turbinate-confined polypoid oedema, the phenotype might not be clear-cut during office endoscopy, and it has been shown that early stage nasal polyps already show eosinophilic inflammation 15,23 . The production of Th17-family derived cytokines IL-17A and IL-22 correlated modestly as was shown by the principal components analysis.…”

Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited

“…In CRSwNP, epithelial cell disruption is extensive in whole nasal tissue samples 88 and excess mucus can be explained by goblet cell hyperplasia and mucin hypersecretion. 89 BM thickening relates to disease severity and duration, along with the presence of underlying asthma 90 and seems to be independent of the degree of eosinophilic inflammation.…”

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

“…Reductions of the tight junction proteins claudin-1 and occludin in CRS tissues were reported in another study 50 . The group of Bachert reported that ZO-1, occludin and E-cadherin were all reduced in mature polyps removed from CRSwNP patients 51 . Moreover, aquaporin 5, a marker of epithelial differentiation, was significantly reduced in sinonasal samples of CRSwNP subjects compared to CRSsNP or controls 52 .…”

“…More recent studies found similar evidence for increased EMT in allergic rhinitis 42, 43 . Several studies have demonstrated ongoing EMT in CRS 37, 47, 49–51 . Two studies have demonstrated ongoing EMT in eosinophilic esophagitis 62, 124 .…”