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.

Innate Immunity as a Contributing Factor for CRSwNP Aggregate Grade of Evidence: not applicable (Table X-11).

Ciliary Derangements as a Contributing Fac tor for CRSwNP Aggregate Grade of Evidence: C (Level 2: 1 study, Level 3: 2 studies; Table X-14).

X.C.13 Contributing Factors for CRSwNP: Epithelial Barrier Disturbance Because of limited data, CRSsNP and CRSwNP are com bined in Section IX.C.12 . X.C.14 Contributing Factors for CRSwNP: Ciliary Derangements CRSwNP has more pronounced ciliary dysfunction in some cases compared to CRSsNP, and there are several reasons that it manifests differently. In a recent whole transcriptomic sequencing study, cilia dysfunction and immune dysregulation are the 2 main gene ontology categories differentiating between CRSwNP patients and healthy controls. 1509 The nature of NPs physically disrupts MCC patterns. Additionally, histopathologic studies demonstrate that some regions of NPs do not have ciliated surfaces, which causes a disruption in flow of mucus in the sinonasal tract. 1510 Interestingly, explants from CRSwNP patients demonstrate a faster baseline CBF compared with con trol explants, suggesting that a local epithelial compen sation is occurring to account for “blocked” mucocil iary flow. This baseline increase is not observed in CRSsNP explants. 877,1511 Chronically increased CBF has a potential consequence of down-regulating endogenous stimulatory pathways, and the cell loses responsiveness to natural CBF stimulants and cannot be modulated normally. 842 Epithelial damage in CRSwNP has also been associated with squamous metaplasia, and abnormal or absent cilia are often associated with this metaplastic change. 180,181,851,912,913 Scanning electron microscopy con firms the abnormal architecture, with cilia in CRSwNP presenting as overly dense, lengthened, and untidy. Cilio genesis factors are correspondingly upregulated. 182 Other ciliogenesis-associated markers such as forkhead box j1 (Foxj1) and p73 isoform with an N-terminal transactivation domain (TAp73) are dysregulated in ciliated columnar cells inCRSwNP. 159,1512

X.C.15 Contributing Factors for CRSwNP: Immunodeficiency Little evidence exists examining the role of immunode ficiency in CRSwNP. A systematic review performed by Schwitzguebel et al. found that the prevalence of nasal polyposis varies between 13% and 60% of patients with CRS and documented immunoglobulin deficiencies. 1513 Tran Khai Hoan et al. examined a prospective case series and concluded that a link between IgG subclass deficiency and CRSwNP seemed unlikely. 1514 Two case-control studies have also examined this subject. Seppanen et al. compared CRS (including two thirds with CRSwNP) or RARS to ARS and controls. They demonstrated that low complement C4 levels were more associated with CRS or RARS than ARS and concluded that the isolated low IgG subclass alone had limited value in patient assessment. 937 Cui et al. performed a case-control study in Chinese adult patients. 804 They found that increased levels of C3 and mannose-binding lectin (MBL, a pattern-recognition molecule which can activate the lectin pathway of the complement system) might play a modulatory role in CRS development. This finding was especially true for MBL in CRSwNP com pared to CRSsNP. The study from Carr et al., in which 42% of CRS subjects were CRSwNP, demonstrated that patients with medically refractory CRS may have a high prevalence of low pre-immunization anti-pneumococcal titer and specific antibody deficiency (SAD). However, no correlation was identified specifically in CRSwNP. 943 Baraniuk and Maibach performed subgroup analysis and found that Ig subclass deficiencies were more prevalent in CRSsNP than CRSwNP although the small numbers of subjects per group precluded statistical significance. 1515 Subgroup analysis of a case-control study of 595 patients with CRS who were evaluated for humoral immunode ficiency with quantitative immunoglobulins and Strepto coccus pneumoniae antibody titers found no difference in nasal polyposis when stratifying by SAD severity. 952 Kashani et al. report a case series of 239 adults with CRS who were evaluated for SAD, with 27% sub-classified as CRSwNP. 946 In this study, the patients with CRSsNP with