xRead - Nasal Obstruction (September 2024) Full Articles

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368

International consensus statement on rhinosinusitis

epithelial barrier more permeable and more sensitive to infectious pathogens. The polypoid form of CRS and a Type 2 cytokine milieu have been associated with significantly decreased levels of AJC proteins including Zona Occludin-1 (ZO-1), claudin-1, E-cadherin, and desmoglein-1 and -2 847,849,854,855 aswell as diminished intrinsic protective anti-protease activity. 807,856 A range of exoproteins from bacteria including S. aureus , and P. aeruginosa 857–860 can disrupt epithelial tight junc tions, potentially allowing pathogenic bacterial invasion and underlying tissue damage. 846 Bacterial proteins are not the only exogenous compounds with the potential to disrupt epithelial TJs in ALI models; air pollution-related particulate matters, 861 cigarette smoke extract 862 andnasal mucus itself 863 have all been implicated. The activity of proteases and their equilibrium with pro tease inhibitors have been implicated in both direct epithe lial disruption and stimulation of cell surface protease activated receptors, specifically in Type 2 skewed endo types of CRSwNP. These enzymes may originate from aero-allergens such as house dust mite or pollen, 864 fungi 629,865 and bacteria including S. aureus and P. aeruginosa . 860,866,867 Protease disrupts ZO-1 and occludin in tight junctions 868 and decreased levels of the protease inhibitors Cystatin A and serine protease inhibitor Kazal type 5 (SPINK5) at both a transcriptional and metagenomic level have been reported in CRS patients. 869 It has also been recognized that activated neutrophil-secreted proteases lead to epithelial degradation, 859 in addition to upregulat ing proteins involved in nasal mucus secretion. 869 Taken together, these studies suggest that mucociliary dysfunction may play a role in the pathogenesis of CRS broadly, whereas intrinsic or acquired abnormalities in sinonasal mucosa leading to a porous epithelial barrier are more closely linked to CRSwNP (Table IX-16). Proper MCC is of paramount importance in eradicating pathogens and debris from the sinonasal tract. Cilia beat in a directional fashion to move mucus to the sinus nat ural ostia and ultimately to the nasopharynx/oropharynx, where it can be cleared by expectoration or swallowing. 872 A variety of cholinergic, adrenergic, and peptidergic path ways are involved in the regulation of ciliary beating, and ciliary beat frequency (CBF) can be dynamically modu lated for maximal efficiency of mucociliary transport. Sub stances that are introduced to the surface of the respiratory epithelium bind to receptors that have potent downstream effects on CBF. 873–875 During infection, CBF increases to stimulate mucus clearance 612,876,877 as well as to IX.C.13 Contributing Factors for CRSsNP: Ciliary Derangements

Innate Immunity Activity Normal

Normal

Normal

Increased

RT-PCR Tissue TLSP There was no significant difference in the level of TSLP mRNA between CRSsNP and controls. IHC Tissue TLSP TSLP protein levels were significantly

RT-PCR IHC Tissue TSLP There was no significant difference in the level of TSLP mRNA between CRSsNP and controls. RT-PCR ELISA

Tissue TSLP There was no significant difference in the level of TSLP mRNA between CRSsNP and controls.

increased in CRSsNP compared with controls.

Type of Innate Immunity Findings

Study Year Study Groups (size) Tissue Technique Hong 162 2018 CRSsNP (20) Nasal tissue

Nasal polyps

Nasal tissue

Nasal polyps

Nasal tissue

Nasal polyps

Nasal tissue

Nasal polyps

Epithelia cells

Nagarkar 833 2013 CRSsNP (60)

Boita 834 2011 CRSsNP (5)

CRSwNP (90) Control (16)

CRSwNP (86)

Control (47)

Lam 831 2012 CRSsNP (18)

CRSwNP (12) Control (7)

CRSwNP (10) Control

TABLE IX-15 (Continued) TSLP