xRead - Nasal Obstruction (September 2024) Full Articles

20426984, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.22741 by Stanford University, Wiley Online Library on [01/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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International consensus statement on rhinosinusitis

reported an inverse correlation between 25VD3 and total IgE, though this was not statistically significant. 720 Passive or active cigarette smoke exposure appears to decrease both systemic and local sinus tissue levels of 25VD3. This finding was consistent across CRSwNP and control patients. 719 Invitro studies also support the role of VD3 in CRSwNP pathogenesis. Studies demonstrate that human sinonasal epithelial cells constitutively express 1 α hydroxylase and epithelial cells convert 25VD3 to 1,25VD3 in a dose depen dent manner, but that CRSwNP epithelial cells appear to have lower levels of 1 α hydroxylase and are less effi cient at 25VD3 activation. 719,723 Similarly, when looking at sinonasal CYP27B1 expression (gene encoding 1 α hydrox ylase), this was lower in CRSwNP patients compared to controls. 724 Additionally, reduction in 1 α hydroxylase was shown to be associated with worse subjective disease sever ity (based on SNOT22 scores). 715 When investigating the effects of exogenous insults with smoke extract, epithe lial cell conversion of 25VD3 into active 1,25VD3 became impaired, but addition of 1,25VD3 to smoke exposed cells inhibited their secretion of pro-inflammatory cytokines (IL-6, IL-8, CCL20), alluding to its potential to influence immune tolerance. 719 CRSwNP patients have 25VD3 deficiencies that correlate with increased numbers of systemic and local dendritic cells, and increased human sinonasal fibroblast (HSNF) proliferation. 717,718,1417 Additionally, low 25VD3 correlates with increases in pro-inflammatory cytokines and in vitro studies demonstrate that adding various forms of vita min D appear to suppress fibroblast proliferation and production of pro-inflammatory cytokines. 1418–1422 There also appears to be a synergistic effect of inhibiting pro inflammatory cytokines and inhibiting fibroblast prolifera tion when budoesonide was added to 1,25VD3 or tacalcitol compared to monotherapy. 1423,1424 Vitamin D Deficiency as a Contributing Fac tor for CRSwNP In summary, the following statements can be made about vitamin D in CRSwNP: 1. Systemic 25VD3 deficiency is common in CRSwNP and correlates with subjective disease severity, and severity of sinus mucosal and sinus bone involvement in CRSwNP. Aggregate Grade of Evidence: C (Level 4: 13 studies). 2. Local sinonasal VD3 metabolism dysfunction in CRSwNP may contribute to a pro-inflammatory

state and appears to be independent of serum 25VD3 levels in CRSwNP. Aggregate Grade of Evidence: C (Level 4: 2 studies; Table X-8).

X.C.8 Contibuting Factors for CRSwNP: Superantigens Staphylococcus aureus (SA) has been found colonizing the airways in up to 90% of patients with CRSwNP, with the highest prevalence in patients with comorbid asthma and aspirin sensitivity. 1374 In these patients, SA also grows intramucosally and even intracellularly 1425–1427 and releases over 600 proteins into the mucosa. 1428 Staphylo coccal enterotoxins (SEs) are superantigens that stimulate T cells via binding to the T cell receptor Vß chain indepen dent of the antigen-binding site, causing polyclonal activa tion of T cells with massive cytokine release. In about 60% of CRSwNP, evidence of superantigen effects on the T cell receptor V-beta expansion in both CD4 + andCD8 + lym phocytes was noted. 1429 The presence of Vß skewed T cells in CRSwNP tissue has recently been confirmed, demon strating that these cells produce type 2 cytokines such as IL-4, IL-5, and IL-13. 1430,1431 The findings of superantigens in CRSwNP and its association with eosinophilic inflam mation were independently confirmed by others. 1432–1434 The first description of a possible role of superantigens and IgE-antibodies to superantigen in CRSwNP dates back to 2001. 1374 The presence of IgE specific to SEs was associated with increased levels of total IgE and eosinophilic inflam mation in CRSwNP. SEs can function by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SE IgE in anti-SE IgE-Fc ε RI complexes. 1435 Stimulation of mucosal tissue with SEB, the best studied superantigen, over 24 hours induced a significant increase of IL-1ß, TNF- α , IFN- γ , IL-2, IL-4, IL-5, IL-10, and IL-13 in CRSwNP and healthy patients, with this increase signifi cantly greater in NPs compared to controls. 1436 Recently it was shown that SA presence within CRSwNP tissue was associated with a higher spontaneous production of IL-5 by the tissue, which could be reduced by antibiotics and bac teriophages directed against the bacteria, 1428 indicating a direct impact of S. aureus on type 2 inflammation. At the sametime, S.aureus, via components of its cell wall, down regulates IP-10 and other Th1 cell-recruiting chemokines (eg, CXCL9 and CXCL11), counteracting the SE induced Th1 cell recruitment. This effect translated into inhibition