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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Orlandi et al.

1 study from Iran found an association between CRSsNP and vitamin D deficiency. The authors discuss how cul tural differences, specifically dressing style (which in turn affects the amount of sun-exposed skin and vitamin D syn thesis), can affect systemic vitamin D levels. Given the lim ited population studied, results of this investigation may not be generalizable to other geographic regions. Investigations looking at local sinonasal vitamin D levels further support the lack of association between CRSsNP and vitamin D deficiency. Two studies from the same group found no association between CRSsNP and decreased sinonasal VD3 levels 719 or sinonasal 1,25VD3 levels. 715 Cigarette smoke exposure also decreased local 25VD3 levels in sinonasal tissues. 719 A separate study looked at sinonasal tissue dendritic cell infiltrate levels and its relationship with systemic vitamin D levels given the role of vitamin D as a potent steroid hormone that acts on immune cells. CD209 + dendritic cells were found to inversely correlate with vitamin D3 levels. Unlike CRSwNP patients, there was no increase in CD209 + dendritic cell infiltrate in sinonasal tissue of CRSsNP patients. 717 Studies have also looked at vitamin D metabolism as it pertains to CRS. It has been shown that CRSsNP sinonasal epithelial cells have the ability to convert 25VD 3 to1,25VD 3 . 719,723 In contrast to CRSwNP patients, CRSsNP patients do not demonstrate reduced sinonasal 1 α hydrox ylase levels. 715 When looking at gene expression, a sep arate study similarly found that sinonasal vitamin D receptor (VDR) gene expression was not reduced in CRSsNP patients. However, in this same study, cytochrome P450 family 27 subfamily B member 1 gene expression (CYP27B1, the gene encoding 1 α hydroxylase) was lower in the sinonasal mucosa of CRSsNP compared to controls, despite having normal systemic 1,25VD3 levels suggesting that the local regulation of vitamin D may be independent of serum 1,25VD3. 724 A separate study similarly found a 2-fold down-regulation of CYP27B1 expression in CRSsNP patient compared to controls. When examining the effect of cigarette smoke exposure, CYP27B1 expression was fur ther downregulated in all study groups including CRSsNP patients. 719 Vitamin D Deficiency as a Contributing Fac tor for CRSsNP In summary, 2 statements can be made about Vita min D in CRSsNP: 1. CRSsNP is not associated with systemic 25VD3 deficiencies. Aggregate Grade of Evidence: C (Level 4: 11 studies; level 5: 2 studies).

2. Smoke exposure in CRSsNP patients can lower systemic and local 25VD3 levels. Aggregate Grade of Evidence: N/A (Level 4: 1 study).

IX.C.7 Contributing Factors for CRSsNP: Superantigens Studies on Staphylococcus aureus (SA) and its superanti gens have mainly focused on CRSwNP. It has been shown that CRS patients with and without polyps have sig nificantly increased SA nasal carriage rates and biofilm formation compared to healthy subjects. The presence of SA biofilm has been associated with the presence of superantigen specific IgE. 728,729 However, within the sinus tissue, no SE-IgE antibodies could be detected in 20% CRSsNP subjects, whereas they could be demonstrated in about 50% of the CRSwNP patients. In line with these findings, serum specific IgE to Staphylococcal entero toxin B (SEB) was significantly increased in CRSwNP patients compared with the controls, but not in CRSsNP patients. 730 A recent study differentiating type 2 from non-type 2 CRSsNP showed that IgE formation to S. aureus entero toxins (SE-IgE) was exclusively present in type 2 CRSsNP and associated with increased tissue IgE and markers of eosinophilic inflammation, but less pronounced com pared to CRSwNP. 731 In summary, unlike for type 2 dis ease including CRSwNP, there is no evidence supporting a prominent role of superantigens in the etiology or patho genesis of on non-type 2 CRSsNP. With these studies, there is limited data available that supports any role for superantigens in the pathophysiology ofCRSsNP.

Superantigens as a Contributing Factor for CRSsNP Aggregate Grade of Evidence: C (Level 3: 2 studies; Table IX-9).