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Background: Local sinonasal inflammation resulting from altered T-cell immune signaling is a contributor to the pathogenesis of chronic rhinosinusitis (CRS). CRS patients experience negative impacts on quality of life (QOL) and suffer from comorbidities linked to systemic inflammation. However, systemic inflammatory profiling to evaluate the association between systemic inflammation and QOL in CRS has not been performed. Our objectives were to compare local and systemic inflammatory gene expression in patients with CRS to determine if systemic markers of inflammation associate with disease severity and disease-specific QOL., Methods: A prospective observational study was conducted comparing 16 patients with CRS to 10 controls. Inflammatory gene expression in the anterior ethmoid tissues and peripheral blood of patients was measured using multiplex gene expression analysis and correlated to disease severity (computed tomography and nasal endoscopy) and disease-specific QOL (22-item Sino-Nasal Outcome Test [SNOT-22] and Rhinosinusitis Disability Index) using linear regression analyses., Results: Patients with CRS showed significant increases in the expression of ctla4 and jak1 in sinonasal tissue and blood (p < 0.05), whereas the gene expression of hla-dqa1, hla-dqb1, and dusp4 was significantly decreased in patients with CRS compared to controls (p < 0.05). Soluble and local ctla4 and jak1 showed a significant positive correlation with clinical markers of disease severity and disease-specific QOL (p < 0.05)., Conclusion: Local and systemic gene expression involved in T-cell immune signaling was found to be significantly altered in the blood and sinonasal tissues of patients with CRS compared to controls and significantly correlated to disease severity and QOL in patients with CRS., (© 2019 ARS-AAOA, LLC.)

Background: The Rhinosinusitis Disability Index (RSDI) consists of multiple subdomains shown to be useful in studying chronic rhinosinusitis (CRS). The objective of this study was to determine if RSDI subdomain scores are associated with selection of treatment modality (endoscopic sinus surgery [ESS] or continued medical management [CMM]) in subjects with CRS., Methods: Patients with CRS were prospectively enrolled into a multi-institutional cohort study. Following an initial period of medical management, patients elected to undergo treatment with either ESS or CMM. Baseline RSDI total and subdomain scores were compared between patients electing different treatment modalities., Results: A total of 684 subjects were enrolled with 122 (17.8%) electing CMM and 562 (82.2%) electing ESS. When compared to patients undergoing CMM, patients electing ESS exhibited significantly higher mean baseline RSDI total scores (mean ± standard deviation [SD]: 48.1 ± 24.9 vs 40.1 ± 24.1; p = 0.001) and subdomain scores (emotional: 13.2 ± 9.1 vs 10.4 ± 8.3; p = 0.001; functional: 15.3 ± 8.9 vs 12.6 ± 8.4; p = 0.002; and physical: 19.6 ± 9.3 vs 17.1 ± 9.6; p = 0.007). Emotional subdomain scores were found to be the most associated with choice of treatment modality., Conclusion: Patients with CRS electing ESS had worse baseline RSDI total and subdomain scores compared to those electing CMM. Although both rhinologic and nonrhinologic symptoms contributed to the selection of treatment modality, emotional symptoms appeared to exhibit the greatest influence on patient-centered treatment decisions., (© 2015 ARS-AAOA, LLC.)

Background: Cathelicidin (LL-37) is an endogenous innate immune peptide that is elevated in patients with chronic rhinosinusitis (CRS). The role of LL-37 in olfactory epithelium (OE) inflammation remains unknown. We hypothesized that: (1) LL-37 topically delivered would elicit profound OE inflammation; and (2) LL-37 induced inflammation is associated with increased infiltration of neutrophils and mast cells., Methods: To test our hypothesis we challenged C57BL/6 mice intranasally with increasing concentrations of LL-37. At 24 hours tissues were examined histologically and scored for inflammatory cell infiltrate, edema, and secretory hyperplasia. In separate experiments, fluorescently conjugated LL-37 was instilled and tissues were examined at 0.5 and 24 hours. To test our last hypothesis, we performed tissue myeloperoxidase (MPO) assays for neutrophil activity and immunohistochemistry for tryptase to determine the mean number of mast cells per mm(2) ., Results: LL-37 caused increased inflammatory cell infiltrate, edema, and secretory cell hyperplasia of the sinonasal mucosa, with higher LL-37 concentrations yielding significantly more inflammatory changes (p < 0.01). Fluorescent LL-37 demonstrated global sinonasal epithelial binding and tissue distribution. Further, higher concentrations of LL-37 led to significantly greater MPO levels with dose-dependent increases in mast cell infiltration (p < 0.01)., Conclusion: LL-37 has dramatic inflammatory effects in the OE mucosa that is dose-dependent. The observed inflammatory changes in the olfactory mucosa were associated with the infiltration of both neutrophils and mast cells. Our biologic model represents a new model to further investigate the role of LL-37 in OE inflammation., (© 2015 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is a highly prevalent inflammatory condition, with significant effects on morbidity and quality of life, yet little is known about its pathogenesis. Preliminary evidence suggests there is a heritable component to the multifactorial etiology of CRS; however, our understanding of this genetic susceptibility is limited., Methods: Using an extensive genealogical database linked to medical records, the risk of CRS with nasal polyps (CRSwNP) and without polyps (CRSsNP) was calculated for relatives and spouses of adult probands (1638 CRSwNP and 24,200 CRSsNP patients diagnosed between 1996 and 2011) and were compared to random population controls matched 5:1 on sex and birth year from Cox regression models., Results: First-degree relatives (1stDRs) of CRSwNP patients demonstrated a 4.1-fold increased risk (p < 10(-3) ) of carrying the same diagnosis, whereas second-degree relatives (2ndDRs) demonstrated a 3.3-fold increased risk (p < 0.004), compared to controls. In CRSsNP patients, 1stDRs were at 2.4-fold increased risk (p < 10(-15) ), whereas 2ndDRs were at 1.4-fold increased risk (p < 10(-15) ) of the same diagnosis. Third-degree relatives (3rdDRs) had a slight increased risk at 1.1-fold (p < 10(-7) ). Spouses of CRSsNP patients, who likely share environmental circumstances, exhibited a 2-fold increased risk (p < 10(-15) ). No increased risk was observed in spouses of CRSwNP patients., Conclusion: In the largest population study to date, a significant familial risk is confirmed in CRSwNP and CRSsNP, which may have a shared genetic and environmental component. Further understanding of the genetic basis of CRS and its interplay with environment factors could clarify disease etiology and lead to more effective targeted treatments., (© 2015 ARS-AAOA, LLC.)