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Background: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient‐reported and clinically measured post‐operative outcome measures. Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient‐reported outcome measures included the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund–Kennedy endoscopic score (LKES). Results: A total of 115 patients were clustered into type 2 inflammatory, non–type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT‐22 (−28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between‐group differences in SNOT‐22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures. Conclusions: All CRS endotype clusters responded favorably to surgery and showed improvements in patient‐reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes. [ABSTRACT FROM AUTHOR]

Background: Multiple hypotheses are evolving that suggest several, potentially overlapping etiologies for olfactory dysfunction (OD) in chronic rhinosinusitis (CRS). Understanding inflammatory cytokine profiles of the olfactory cleft (OC) and their association with olfactory function is foundational for future clinical care and research. Methods: This cross‐sectional, case‐control study evaluates associations among OC mucus inflammatory proteins, psychophysical olfactory testing, and computed tomography (CT) analysis of the OC and sinuses. Normative reference intervals were determined for each protein and odds ratios (ORs) were used to compare proportions of altered expression between CRS without nasal polyposis (CRSsNP) and CRS without nasal polyposis (CRSwNP). Results: Case subjects with CRS (n = 151) and controls (n = 74) were evaluated. A majority of OC proteins tested were found within detectable ranges for cases and controls. The CRS cohort had significantly higher concentrations for 23 of 26 proteins. CRS cases with abnormal levels of C‐C motif chemokine ligand 2 (CCL2), CCL3, interleukin 5 (IL5), IL10, and IL13 associated with greater olfactory deficits. The prevalence of elevated IL5 and IL13 in anosmic patients was 64.6% and 62.5%, respectively (p < 0.004). CRS cases with the highest odds of elevated expression in CRSwNP were IL5 (OR = 10.83) and IL13 (OR = 8.36). However, both IL5 and IL13 were still elevated in approximately 14% of CRSsNP patients. The highest magnitude of correlation between the total percent of OC opacification was found to be with IL5 (r = 0.543; p < 0.001), whereas other moderate correlations were noted with immunoglobulin E (IgE), IL10, and IL13. Conclusion: This study confirmed that OC inflammatory proteins vary both by disease phenotype and in their association with OD. Type 2 inflammatory mediators are increased in CRS, especially within the CRSwNP group. However, a substantial proportion of CRSsNP also express type 2 inflammatory mediators. Further research is necessary to understand the complex roles OC mucous inflammatory proteins might play in defining endotype and in impacting CRS‐related OD. ©2021 ARSAAOA, LLC. [ABSTRACT FROM AUTHOR]

Background: Mechanisms of smell loss in chronic rhinosinusitis (CRS) are still unclear and likely multifactorial. Little attention has been given to olfactory cleft (OC) mucus proteins involved in odorant binding and metabolizing enzymes and their potential role in smell loss. Methods: Mucus from the OC was sampled from patients with CRS (n = 20) and controls (n = 10). Liquid chromatography and mass spectrometry were performed, followed by data processing so that protein groups could be identified, quantified, and compared. Hierarchical clustering and bioinformatic analysis were performed on significantly different proteins to explore for enrichment in known biologic pathways. Results: A total of 2514 proteins were found in OC mucus from all 30 subjects. Significant differences in protein abundance were found between CRS and controls, including both CRSsNP (n = 351 proteins; log2 fold change range: –3.88 to 6.71) and CRSwNP (n = 298 proteins; log2 fold change range: –4.00 to –6.13). Significant differences were found between patients with normosmia and those with dysosmia (n = 183; log2 fold change range: –3.62 to –2.16) and across groups of interest for a number of odorant binding proteins and metabolizing enzymes. Conclusion: OC mucous in CRS displays a rich and abundant array of proteins, many of which have been implicated in odorant transport and metabolization in animal studies. Significant differences in the olfactory mucus proteome were seen between CRS subtypes and controls, as well as between those with normal and abnormal olfaction. Further study should confirm these findings and explore the role individual proteins play in odorant transport and metabolization. ©2020 ARSAAOA, LLC. [ABSTRACT FROM AUTHOR]

Background: The Sinus Control Test (SCT) is a 4‐question, patient‐reported questionnaire that assesses disease control in chronic rhinosinusitis (CRS). This prospective, multicenter study examines SCT outcomes following endoscopic sinus surgery (ESS), further validating its use as a control instrument for CRS. Methods: Adults with CRS undergoing ESS were prospectively enrolled from 5 centers across North America. The SCT was administered at baseline and once 6 months after surgery. Quality of life and disease burden were evaluated using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and Lund‐Kennedy endoscopy scores. Linear regression was used to determine whether specific demographic, comorbidity, or disease severity measures were independently associated with changes in SCT scores postoperatively. Results: A total of 218 patients, 111 females (50.9%) and 107 males (49.1%), were enrolled, with mean ± standard deviation age of 50.1 ± 15.6 years. Mean SCT score improved from 8.9 ± 3.5 to 4.3 ± 3.7 postoperatively (p < 0.001). Preoperatively, 21.6% were uncontrolled, 71.5% partially controlled, and 6.9% controlled. Postoperatively, 6.0% were uncontrolled, 42.6% partially controlled, and 51.4% controlled (p < 0.001). Change in SCT score correlated independently with change in SNOT‐22 (r = 0.500, p < 0.001) and endoscopy scores (r = 0.310, p < 0.001). Endoscopy scores did not correlate with control status among patients with CRS without nasal polyposis (CRSsNP) nor between uncontrolled and partially controlled patients. Demographics and comorbidities were not associated with changes in SCT. Conclusion: Improvement in disease control following ESS as measured by the SCT correlated with improvements in SNOT‐22 and endoscopy scores. The SCT is an easily administered instrument that provides information complementary to existing patient‐reported and objective measures of disease severity. [ABSTRACT FROM AUTHOR]

Background: Olfactory dysfunction (OD) in chronic rhinosinusitis (CRS) is common. It is likely that numerous factors such as sex, race, age, allergies, asthma, smoking, and other comorbidities play a role in CRS‐related OD. In order to determine which aspects of OD are due solely to CRS and which are associated with other confounders, control populations are needed to allow appropriate risk assessments. Methods: Prospective, multi‐institutional enrollment of patients with CRS and control subjects without CRS was performed. Demographic information, comorbidities, and olfactory testing (Sniffin' Sticks) of threshold (T), discrimination (D), and identification (I) scores (TDI) was collected. Results: A total of 224 patients with CRS and 164 control subjects were enrolled. Olfaction was worse in CRS patients compared to controls (mean ± standard deviation (SD) TDI = 22.4 ± 9.5 vs 28.8 ± 7.0, respectively, p < 0.001). Only 27% of CRS patients were normosmic compared to 49% of controls (p < 0.001). When stratifying by nasal polyp (NP) status, CRSwNP patients had significant impairments in TDI, T, D, and I compared to controls with mean differences of 11.2, 3.3, 3.5, and 4.4 points, respectively (all p < 0.001). In contrast, CRSsNP patients only had impaired T when compared to controls with a mean difference of 2.2 points (p < 0.001). Multivariate modeling of TDI scoring showed that OD was driven by polyps, asthma, diabetes, and age. CRSsNP was not independently associated with worse TDI scores. Conclusion: OD in CRS patients is multifactorial. Independent drivers appear to be polyp status, asthma, diabetes, and age. OD in patients with CRSsNP is similar to controls with the exception of impaired thresholds. [ABSTRACT FROM AUTHOR]

Background: There is a striking lack of long‐term, prospective outcomes data for endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) using validated instruments. Our primary objective in this study was to report long‐term outcomes (>10 years) after ESS for CRS obtained by prospective data collection. Methods: An observational cohort (n = 59) of adult patients with CRS electing ESS was enrolled between 2004 and 2008. Long‐term, disease‐specific quality‐of‐life (QOL) outcomes, health utility values (HUV), revision surgery rate, development of asthma, and patient expectations/satisfaction with outcomes of ESS were examined using descriptive statistics and simple fixed‐effects linear modeling. Results: Fifty‐nine adult patients were followed for 10.9 years (±13.8 months), on average. Mean QOL significantly improved between baseline and 6 months and remained durable to 10 years. HUV improved to normal. A 17% revision surgery rate within the 10‐year follow‐up period was observed with a 25% revision rate in CRS with polyposis. New‐onset asthma after ESS occurred at a rate of 0.8%/year. Patient satisfaction with ESS outcomes was generally high. Conclusions: Ten‐year prospective outcomes of ESS for CRS demonstrate that the initial clinically significant improvements in QOL seen 6 months postoperatively are durable over the long term. Over 75% of patients reported clinically significant long‐term QOL and HUV improvement. HUV returned to normal. Revision surgery rate was 17% and worse postoperative endoscopy scores within 18 months of initial ESS were associated with higher likelihood of revision surgery. Most patients would pursue ESS again and recommend the procedure to other patients considering this treatment option. [ABSTRACT FROM AUTHOR]

Background: Cognitive dysfunction in chronic rhinosinusitis (CRS) is often overlooked despite potentially broad implications. Earlier work has demonstrated decreased cognitive function in CRS patients at baseline. In this study we sought to prospectively evaluate the impact of initial, appropriate medical therapy on subjective and objective cognitive function, fatigue, and workplace productivity. Methods: Adult patients with CRS were prospectively enrolled and completed a robust battery of pretreatment quality‐of‐life and neurocognitive testing, before undergoing appropriate medical therapy with follow‐up testing at 6 weeks. Patient‐reported cognitive function was assessed using the Cognitive Failures Questionnaire (CFQ), whereas fatigue was measured with the Fatigue Severity Scale (FSS). Objective cognitive function was assessed using the Automated Neuropsychological Assessment Metrics (ANAM) platform and workplace productivity using the Clinical Trials version of the World Health Organization Health and Work Performance Questionnaire (ctHPQ). Results: Twenty‐seven patients were enrolled. Patients demonstrated posttreatment improvement scores on the FSS (4.32 ± 1.78 to 3.28 ± 1.65; p = 0.003), Pittsburgh Sleep Quality Index (8.62 ± 5.06 to 6.85 ± 4.11; p = 0.014), and CFQ (38.56 ± 16.40 to 33.04 ± 14.35; p = 0.046). Objective neurocognitive tests of mathematical processing and Stroop Reaction Test Block 3 improved after medical therapy (19.79 ± 5.61 to 21.3 ± 6.87; p = 0.029 and 43.06 ± 15.66 to 50.42 ± 19.34; p = 0.002, respectively). Measures of workplace productivity did not change significantly. Conclusion: Appropriate medical therapy improves several measures of cognitive dysfunction in patients with CRS. Sustainability of results should be evaluated with larger, prolonged studies. [ABSTRACT FROM AUTHOR]

Background: Olfactory‐specific quality of life (QOL) can be measured using the Questionnaire of Olfactory Disorders Negative Statements (QOD‐NS). Changes in the QOD‐NS after treatment can be difficult to interpret since there is no standardized definition of clinically meaningful improvement. Methods: Patients with chronic rhinosinusitis (CRS) completed the QOD‐NS. Four distribution‐based methods were used to calculate the minimal clinically important difference (MCID): (1) one‐half standard deviation (SD); (2) standard error of the mean (SEM); (3) Cohen's effect size (d) of the smallest unit of change; and (4) minimal detectable change (MDC). We also averaged all 4 of the scores together. Finally, the likelihood of achieving a MCID after sinus surgery using these methods, as well as average QOD‐NS scores, was stratified by normal vs abnormal baseline QOD‐NS scores. Results: Outcomes were examined on 128 patients. The mean ± SD improvement in QOD‐NS score after surgery was 4.3 ± 11.0 for the entire cohort and 9.6 ± 12.9 for those with abnormal baseline scores (p < 0.001). The MCID values using the different techniques were: (1) SD = 6.5; (2) SEM = 3.1; (3) d = 2.6; and (4) MDC = 8.6. The MCID score was 5.2 on average. For the total cohort analysis, the likelihood of reporting a MCID ranged from 26% to 51%, and 49% to 70% for patients reporting preoperative abnormal olfaction. Conclusion: Distribution‐based MCID values of the QOD‐NS range between 2.6 and 8.6 points, with an average of 5.2. When stratified by preoperative QOD‐NS scores the majority of patients reporting abnormal preoperative QOD‐NS scores achieved a MCID. [ABSTRACT FROM AUTHOR]

Background: In several inflammatory disorders, altered peripheral blood mononuclear leukocyte (PBML) glucocorticoid (GC) receptor isoform expression has been associated with GC resistance and disease severity. However, it is unclear if PBML GC receptor isoforms are expressed differentially and are associated with worsened disease severity in chronic rhinosinusitis (CRS). Methods: PBMLs were isolated from control (n = 8), CRS without nasal polyps (CRSsNP) (n = 8), atopic CRS with nasal polyps (CRSwNP) (n = 8), non‐atopic CRSwNP (n = 8), and allergic fungal rhinosinusitis (AFRS) (n = 8) patients. Demographics, atopic status, asthmatic status, 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores, Lund‐Kennedy nasal endoscopy scores, Lund‐Mackay sinus computed tomography (CT) scores, Kennedy Osteitis scores, and GC utilization 6 months postoperatively were collected. Intracellular immunostaining was then performed for functional GC receptor α (GCRα) and nonfunctional GC receptor β (GCRβ), followed by flow cytometry analysis of geometric mean fluorescent intensity (MFI) and the percentage of cells expressing each GC receptor isoform. Results: Compared to controls, each CRS subtype had decreased PBML GCRα and GCRα:GCRβ MFI expression, but no difference in GCRβ expression. Decreasing PBML GCRα in AFRS was associated with increasing Lund‐Mackay sinus CT scores (r = −0.880, p =0.004). No significant associations were found between GC receptor isoform expression and other clinical measures. Conclusion: CRS patients have reduced functional PBML GCRα expression and decreased GCRα:GCRβ compared to controls. Reductions in GCRα in AFRS are associated with worsening Lund‐Mackay sinus CT scores. The clinical implications of decreased functional GC receptor expression merits further investigation. [ABSTRACT FROM AUTHOR]

Background: Olfactory‐specific quality of life (QOL) can be measured using the Questionnaire of Olfactory Disorders–Negative Statements (QOD‐NS), which examines various aspects of olfactory dysfunction. It is unknown if certain factors of the QOD‐NS differentially impact QOL. Methods: Patients with chronic rhinosinusitis (CRS) completed the QOD‐NS, 22‐item Sino‐Nasal Outcome Test (SNOT‐22), Medical Outcomes Study Short Form 6‐D (SF‐6D) health utility measure, and Patient Health Questionnaire‐2 (PHQ‐2) depression screen. Exploratory factor analysis of the QOD‐NS was performed. Associations between QOD‐NS factors and other QOL metrics were analyzed before and after endoscopic sinus surgery (ESS). Results: Outcomes were examined on 132 patients. The QOD‐NS contains 4 distinct factors. There was no difference in associations between the different factors and baseline clinical characteristics. ESS had greatest effect size (d) on factors 2 and 4 (d = 0.29 and 0.27, respectively, p < 0.05). Postsurgical changes in the SF‐6D and SNOT‐22 had the strongest correlation with factor 2 scores (r = 0.29 and 0.34, respectively, p < 0.05), and changes in the PHQ‐2 had the strongest correlation to factor 3 (r = 0.24, p < 0.05). Abnormal QOD‐NS scores at baseline were associated with effect size increases of 50% to 100% (p < 0.05). Conclusion: The QOD‐NS measures 4 distinct factors. Eating‐related questions had the greatest improvement after ESS. Health utility and CRS‐specific QOL improvement most strongly associated with factor 2, while PHQ‐2 changes are most highly associated with factor 3, suggesting a differential impact of the factors of the QOD‐NS on varying aspects of QOL. [ABSTRACT FROM AUTHOR]

Background: Though many patients with chronic rhinosinusitis (CRS) describe disturbances in smell and taste, there have been no studies specifically assessing taste impairment in CRS. This study sought to objectively assess taste dysfunction in CRS patients and determine whether taste impairment correlates with olfactory dysfunction. Additionally, this investigation sought to determine the impact of taste dysfunction on quality of life (QOL) in CRS and identify the clinical factors that influence taste. Methods: Sixty‐eight CRS patients were prospectively enrolled and completed several QOL surveys in relation to taste, smell, overall sinus‐specific QOL, and depression. Validated taste strips were used to determine gustatory dysfunction pertaining to sweet, sour, salty, and bitter. Olfactory testing was assessed using the Sniffin’ Sticks Test while both Lund‐Kennedy and Olfactory Cleft Endoscopy Scoring (OCES) systems were used for endoscopic evaluation. Results: The overall prevalence of dysgeusia was 28%, with scores significantly lower for sour compared to other subgroups. No correlation was observed between taste scores and objective olfactory metrics including olfaction tests and OCES. Taste scores were better in younger patients (r = 0.28, p = 0.02), female patients (p = 0.004), and never smokers compared to former smokers (p = 0.01). Taste scores did not correlate with patient‐reported outcome measures or CRS disease severity metrics. Conclusion: Taste dysfunction is a common complaint in CRS. This cohort shows prevalence of gustatory loss to be about 28% using ideal normative values. This dysfunction correlated with male gender, smoking history, and older age. Taste dysfunction did not correlate with measured olfactory outcomes. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) significantly impacts olfaction. However, the relationship between objective olfaction and patient-reported olfactory-specific quality of life (QOL) is not well understood. Furthermore, objective olfactory testing can be time consuming, so we sought to determine if patient-reported olfactory QOL can be used as screening tool for olfactory dysfunction. Methods Olfactory dysfunction was evaluated in 109 patients with CRS using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) and the Sniffin' Sticks Test, assessing for olfactory threshold, discrimination, identification, and overall composite scores (TDI; composite score of threshold, discrimination, and identification). Regression analysis was performed to correlate olfactory metrics and patient and disease-specific factors with QOD-NS scores. Optimal QOD-NS scores to classify patients based upon objective olfactory function were established. Results Bivariate and multivariate regression analyses of QOD-NS and CRS-associated comorbidities, objective measures of disease, demographics, and CRS-specific QOL were performed. Non-white race, depression, and worse 22-item Sino-Nasal Outcome Test (SNOT-22) scores correlated with worse QOD-NS scores ( p < 0.005). Worse TDI scores correlated with worse QOD-NS scores, and discrimination had the strongest correlation ( p < 0.001). Mean ± standard deviation (SD) QOD-NS scores for normosmia, hyposmia, and anosmia were 44 ± 7.2, 35.7 ± 12.8, and 31.6 ± 10.7, respectively. Receiver operating characteristic curve analysis revealed an area under the curve of 0.770 ( p < 0.001), and a QOD-NS cutoff of 38.5 to have maximal Youden's index to define normal vs abnormal TDI score. Conclusion In CRS, QOD-NS correlates with non-white race, depression, SNOT-22, and TDI score, with discrimination having the strongest correlation. The QOD-NS also appears to be a feasible tool for olfaction screening. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) has significant impacts upon productivity, economic metrics, and medication usage; however, factors that are associated with these economic outcomes are unknown. Methods We evaluated olfactory dysfunction in 221 patients with CRS using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) and the 40-item Smell Identification Test (SIT) and assessed whether an association existed between these olfactory metrics and healthcare utilization, productivity, and medication usage over the preceding 90 days. Results After adjusting for CRS-associated comorbidities, objective measures of disease, demographics, and CRS-specific quality of life (QOL), patients with lower QOD-NS scores (worse patient-reported olfaction) had more missed days of normal productivity and employment, worse productivity levels, more hours of missed employment due to physician visits, more time caring for sinuses, greater distance traveled to medical appointment, more days of oral steroid use, and higher odds of being on disability insurance. Clinical olfaction, as measured by SIT, was associated with greater distance traveled to medical appointment and higher odds of being on disability insurance, but did not correlate with other productivity measures. Conclusion Impaired olfactory-specific QOL is associated with significantly worse economic and productivity metrics and increased medication usage even after adjusting for CRS-specific comorbidities, objective measures of disease, demographics, and severity of CRS-specific QOL. Future studies are warranted to determine if targeting the impaired olfactory-specific QOL noted in patients with CRS results in improved productivity and economic outcomes. [ABSTRACT FROM AUTHOR]

Background Vitamin D3 (VD3) is a steroid hormone with known antiproliferative properties. Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be VD3-deficient. Moreover, VD3 deficiency is associated with worse disease in patients with CRSwNP. One cell type thought to play a role in chronic rhinosinusitis (CRS) is the human sinonasal fibroblast (HSNF). The aim of this study was to investigate VD3 deficiency and HSNF proliferation in CRSwNP. Methods Blood and sinus tissue explants were collected at the time of surgery from patients with CRSwNP (n = 15). Control subjects (n = 12) were undergoing surgery for cerebrospinal fluid leak repair or to remove non-hormone-secreting pituitary tumors. Ex vivo HSNF proliferation was analyzed with flow cytometry using expression of fibroblast-specific protein (FSP) and the proliferation marker Ki67. Plasma levels of 25-hydroxyvitamin D3 (25VD3) were measured by enzyme-linked immunosorbent assay. In vitro analysis of HSNF proliferation after treatment with calcitriol (1,25VD3) was performed using carboxyfluorescein succinimidyl ester (CFSE) and analyzed with flow cytometry. Results In CRSwNP patients there was an inverse correlation between 25VD3 and proliferating HSNFs ( p = 0.0135). This correlation was not seen for control patients ( p = 0.3869). In vitro analysis showed that HSNFs from patients with CRSwNP had a higher proliferation index at baseline than HSNFs from control patients ( p < 0.01). When treated with 1,25VD3, there was a significant decrease in HSNF proliferation index in patients with CRSwNP ( p < 0.01), but not control patients. Conclusion VD3 deficiency is associated with increased HSNF proliferation in CRSwNP. Further investigation into how HSNFs and VD3 impact CRSwNP pathophysiology is warranted. [ABSTRACT FROM AUTHOR]

Background Ideal management of chronic rhinosinusitis (CRS) requires ongoing monitoring of disease and its control. Existing control instruments are limited in their correlation to patient reported outcomes, the need for endoscopy, or lack of validation from a multidisciplinary group. The goal of this study was to develop a patient-based Sinus Control Test (SCT) for determining CRS control. Methods A systematic literature review and focus groups consisting of 20 patients and 11 medical experts in CRS from various medical specialties were used to generate items. A draft 13-item questionnaire was administered to 50 patients with CRS in a prospective fashion. Patients were evaluated using the 22-item Sino-Nasal Outcome Test (SNOT-22) instrument, Lund-Mackay computed tomography (CT) score, and Lund-Kennedy endoscopy score. A rhinologist blinded to the questionnaire results also provided an overall control of the disease for each patient. A regression model was generated to identify which subset of items showed the greatest discriminate ability in relation to specialist's and patient's global rating of disease control. Results Four questions were included in the final questionnaire ( p < 0.05), each with a scale of 0 to 4, with an overall total score ranging from 0 to 16. Optimal classification resulted in patients with a score from 1 to 3 (well controlled), 4 to 11 (partially controlled), and 12 to 16 (uncontrolled). SCT scores correctly classified control levels 72% of the time when compared to physician's assessment. Conclusion The SCT is a simple, patient generated questionnaire that can measure the control of CRS without requirement of endoscopy or CT evaluation. [ABSTRACT FROM AUTHOR]

Background The 22-item Sino-Nasal Outcome Test (SNOT-22) is a commonly utilized outcome measure for chronic rhinosinusitis (CRS). However, what constitutes a normal score remains poorly defined. The goal of this study was to evaluate SNOT-22 scores in a control population without CRS and perform a systematic review and meta-analysis of 'normal' values. Methods Ninety-nine subjects without CRS were enrolled, with 95 fully completing the SNOT-22 questionnaire. Multivariable linear regression was used to determine whether demographic factors or medical comorbidities influence SNOT-22 scores in a population without CRS. A systematic literature search was performed, identifying studies that evaluated the SNOT-22 in a non-CRS population and estimates for SNOT-22 values were pooled. Results Thirty-six males and 59 females were included in the primary analysis with a mean age of 53.4 ± 17.3 years (range, 18-88 years). The mean SNOT-22 score was 16.4 ± 15.2. Asthma ( p = 0.003) and depression ( p = 0.002) were found to be independent predictors of higher SNOT-22 scores. Thirteen articles were identified in the literature search and 1 was provided via author correspondence, with 10 reporting sufficient data to be included in the meta-analysis. Weighted mean SNOT-22 score was 11 ± 9.4 (n = 1517). Our data differed significantly from published data (mean difference = 5.4; 95% confidence interval [CI], 3.4 to 7.5; p < 0.0001) likely owing to differences in comorbidities. Conclusion SNOT-22 scores vary in non-CRS populations depending upon the group queried. Asthma and depression are associated with higher SNOT-22 scores and should be considered when determining what constitutes a normal value. [ABSTRACT FROM AUTHOR]

Background After endoscopic sinus surgery (ESS), endoscopy is used to gauge surgical success and clinical outcomes. Prior studies have not examined this topic prospectively using validated outcome metrics across multiple institutions. Methods A multi-institutional, prospective study of patients with chronic rhinosinusitis (CRS) who underwent ESS completed the 22-item Sino-Nasal Outcome Test (SNOT-22), missed productivity, and medication usage questionnaires 6 months postoperatively. Lund-Kennedy endoscopy scoring (LKES) was performed with reviewers blinded to patient-reported data. A control cohort of non-CRS patients was recruited for comparison. Results Complete data was available on 183 CRS patients and 48 non-CRS control patients. Approximately 50% of patients achieve perfect or near perfect endoscopy (LKES 0 to 2) after ESS. Postoperative endoscopy correlated with total SNOT-22 scores ( r = 0.278, p < 0.001), with the strongest correlations to rhinologic and extranasal subdomains in the nasal polyp cohort. Improved postoperative endoscopy was associated with decreased antibiotic and oral steroid usage, but had little association with missed productivity. Among patients who achieved near perfect postoperative endoscopy, those with nasal polyps had SNOT-22 scores that were similar to non-CRS control patients (mean SNOT-22 scores 17.7 and 16.3, respectively). However, CRS patients without nasal polyps remained more symptomatic than non-CRS controls and CRS with nasal polyps patients despite nearly perfect endoscopy (mean SNOT-22 score 21.6). Conclusion Postoperative endoscopy correlates with SNOT-22 and medication usage in CRS patients. Polyp patients who achieve near perfect endoscopy have similar symptoms to healthy controls; however, nonpolyp patients with near perfect endoscopy still have rhinologic and extranasal symptoms that are worse than healthy controls. [ABSTRACT FROM AUTHOR]

Background The objective of this work was to identify trends in chronic rhinosinusitis (CRS)-related publications for the past 3 decades. Methods Literature review was conducted using multiple terms, including sinusitis, chronic rhinosinusitis, chronic sinus disease, nasal polyposis, ethmoid sinusitis, frontal sinusitis, and maxillary sinusitis. Abstracts were divided into 3 decades: 1983 through 1992, 1993 through 2002, and 2003 through 2012. For each decade, we compared the total number of publications and journals, study design, use of validated outcome measures, quality of evidence, number of authors, country of origin, and clinical vs basic science. Results A total of 3406 abstracts were identified. There was a statistically significant increase in the number of publications with a 637% increase from 1983 through 1992 to 2003 through 2012 ( p < 0.05). Likewise, the number of journals with CRS-related publications significantly increased during the study period (117 to 350; p < 0.05). Prospective studies increased (15.30% to 28.90%, p < 0.05) and retrospective studies decreased (33.00% to 17.36%, p < 0.05). Cohort studies were the most common type of design study (18.70% to 32.46%). In studies reporting outcome measures, the use of validated measures significantly increased over time (2.56% to 49.70%, p < 0.05). Although, the quality of evidence for most clinical publications for all 3 decades were grade C, the number and percentage of grade A and grade B publications increased significantly over time (0.99% to 7.23%, p < 0.05; 6.9% to 10.44%, p < 0.05; respectively). Conclusion CRS-related publication quantity and quality have increased over the last 3 decades. [ABSTRACT FROM AUTHOR]

Background Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have deficiencies in circulating and sinonasal levels of the inactive form of vitamin D3, 25-hydroxycholecalciferol (25VD3). Moreover, CRSwNP patients have reduced epithelial cell-specific expression of 1α-hydroxylase; the enzyme responsible for the conversion of 25VD3 to its metabolically active form, 1α,25-dihydroxyvitamin D3 (1,25VD3). The objective of this work was to determine the impact of sinonasal 1α-hydroxylase levels combined from all cellular sources on subjective disease severity and to identify variables influencing its expression. Methods Blood and sinus tissue explants were collected at the time of surgery from control, chronic rhinosinusitis without nasal polyps (CRSsNP), CRSwNP, and allergic fungal rhinosinusitis (AFRS) patients. 1α-Hydroxylase was measured by immunostaining with flow cytometric analysis. Subjective disease severity was measured by the 22-item Sino-Nasal Outcomes Test (SNOT-22). 1,25VD3 and 25VD3 were measured by enzyme-linked immunosorbent assay (ELISA). Results Patients with CRSwNP or AFRS have reduced 1α-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Circulating 1,25VD3 levels were the same among all groups. No differences in sinonasal 1α-hydroxylase or 1,25VD3 were found between CRSwNP and AFRS. Gender, age, race, atopy, and systemic 25VD3 had no impact on sinonasal 1α-hydroxylase levels in any group. However, CRSwNP patients with asthma had higher 1α-hydroxylase than those without asthma. Total 1α-hydroxylase levels inversely correlated with SNOT-22 in CRSwNP, but not CRSsNP. Conclusion Patients with CRSwNP and AFRS both have reduced sinonasal 1α-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Reductions in intracellular 1α-hydroxylase combined from all sinonasal cell types were associated with more severe subjective disease severity in CRSwNP. [ABSTRACT FROM AUTHOR]

Background The objective of this work was to determine if specific chronic rhinosinusitis with nasal polyps (CRSwNP) populations are at risk for vitamin D3 (VD3) deficiency and if VD3 levels correlate with radiographic measures of disease severity or eosinophilia. Methods This study was a retrospective review of an academic rhinology practice. CRSwNP patients who had VD3 levels and CT scan within 6 months of each other were included. CT scans were graded using Lund-Mackay scoring (LMS) and peripheral eosinophil counts were measured. Demographic data including race, gender, age, body mass index, atopic status, and presence of asthma were collected. CRSwNP was subdivided into allergic fungal rhinosinusitis (AFRS), aspirin-exacerbated respiratory disease (AERD), and other CRSwNP. Multivariate analysis was performed to examine correlations and control for confounding factors. Results Insufficient VD3 levels were found in 55% of all CRSwNP patients. VD3 correlated with African American race because nearly 80% of all African Americans had insufficient VD3 levels. Lower VD3 levels also correlated with more severe mucosal disease on CT scans as measured by LMS. There was no correlation between VD3 levels and age, gender, body mass index, atopy, asthma, or CRSwNP subtype. Conclusion VD3 insufficiency/deficiency is common in CRSwNP patients, especially those of African American race. Lower levels of VD3 are associated with worse LMS on CT. The role of VD3 in CRSwNP warrants further investigation. [ABSTRACT FROM AUTHOR]

Background Recent research suggest that B and plasma cells may play an important role in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this study was to subcharacterize the B cell response in the sinus mucosa of control and CRS patients. Methods Representative tissue samples and peripheral blood samples were obtained from controls, CRS without nasal polyps (CRSsNP) and CRSwNP. Using single-cell suspension flow cytometry these samples were analyzed for overall and stage-specific B and plasma cell percentages. Results Both atopic and nonatopic CRSwNP patients showed an increase in local numbers of naive, active, and memory B cells compared to controls. CRSsNP patients only showed local elevations of naive B cells. Plasma cells were only significantly elevated in the sinus tissue of atopic CRSwNP patients. These local tissue increases did not correlate with increased numbers of circulating B cells. Conclusion This study provides further evidence of an important role of B cells in CRSwNP patients. The local increase appears to be independent of a systemic response. [ABSTRACT FROM AUTHOR]

Although numerous studies have focused on the nature and defensive role of surfactant in the lower airways, relatively little is known about its role in the upper airways. Decreased levels of the main component of surfactant — phospholip- ids — have been implicated in atrophic rhinitis. The lamellar body arrangement of phospholipids has now been demonstrated in both normal and diseased sinus tissue, resulting in the implication that these structures may play a crucial role in mucociliary clearance against inhaled pathogens, as well as in the regulation of mucous viscosity. Furthermore, they may be secreted from sinonasal ciliated epithelium. Surfactant proteins (SPs) make up a relatively smaller proportion of surfactant, but appear to have an important role in innate immunity. Altered levels of SPs have been observed in a number of respiratory tract diseases. These SPs may prove to play a significant role in chronic sinusitis. Demonstrated expression of SP-A and SP-D in diseased and normal sinus tissue may mean that these SPs are excreted into the airway-lining fluid of the sinuses. Additionally, initial contact and interaction between pathogens and SP-A and SP-D may occur relatively early after inhalation and deposition into the mucus of the respiratory tract. These findings may lead to potential therapeutic options for difficult-to-treat sinus disease in the future. [ABSTRACT FROM AUTHOR]

Background: The placebo effect observed in clinical trials evaluating medical treatments for chronic rhinosinusitis (CRS) is not well understood. This systematic review and meta‐analysis sought to characterize the placebo effect present within CRS outcomes. Methods: A systematic review of PubMed, Scopus, and Cumulated Index in Nursing and Allied Health Nursing (CINAHL) was performed. Randomized controlled trials (RCTs) evaluating medical treatments for CRS versus placebo were included. We assessed patient‐reported (sino‐nasal outcome test 22 [SNOT‐22], nasal obstruction, sense of smell, nasal obstruction visual analogue score [VAS], sense of smell VAS, anterior rhinorrhea, and postnasal drip) and objective (Lund–Mackay Computed tomography (CT) score, peak nasal inspiratory flow [PNIF], nasal polyp scores, 40‐item Smell Identification Test, serum IgE, and blood eosinophil levels) outcomes. Results: Twenty‐one RCTs were included, comprising 1437 patients (mean age 49.2 years). Biologics were the most common treatment investigated (n = 9). Eleven studies administered background steroids along with placebo. Following placebo administration, multiple patient‐reported outcomes significantly decreased, including SNOT‐22 (mean difference −9.49, 95% confidence interval [CI] [−11.26, −7.73]), nasal obstruction (−0.33 [−0.54, −0.13]), sense of smell (−0.22 [−0.33, −0.11]), nasal obstruction VAS (−2.47 [−2.87, −2.06]), and loss of smell VAS (−2.31 [−4.14, −0.47]) scores. For objective measures, significant changes occurred in Lund–Mackay CT score (−0.82, [−1.48, −0.16]) and PNIF (4.70, [4.76, 24.64]) with placebo. Placebo arms had the greatest impact when no background medications were used. Conclusions: Placebo treatments have a statistically and potentially clinically significant effect on patient‐reported and some objective CRS outcomes. Further investigation is required to fully understand placebo effect, which could improve assessment of RCTs and impact patient care. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including endoscopic skull surgery and risk of postoperative cerebrospinal fluid (CSF) leak, the association of Basic Smell Identification Test (BSIT) result improvement with endoscopic sinus surgery (ESS), and chronic rhinosinusitis (CRS) diagnosis.

Background: Current methods of quantifying inflammation in chronic rhinosinusitis (CRS) on computed tomography (CT) imaging focus on opacification of the paranasal sinuses and show limited correlation with patient-reported outcome measures. Objective: This study aimed to determine if quantifying CT opacification of the nasal cavity correlated with Sino-Nasal Outcomes Test scores (SNOT-22). Methods: Thirty patients with CRS were enrolled. Lund-Mackay and SNOT-22 scores were measured. Nasal cavity regions of interest (ROIs) were measured by 2 independent raters using ImageJ at 3 points on coronal CT scans: anteriorly at the lacrimal duct, at the approximate midpoint demarcated by the posterior aspect of the globe, and posteriorly at the transition from the hard to soft palate. Superior and inferior regions were defined based upon the root of the inferior turbinate. Percent opacification was calculated for each ROI. Analyses were conducted bilaterally and for the side with greater opacification (worse side). Results: Interrater reliability was strong for all ROIs. Lund-Mackay scores correlated with nasal blockage only (r =.495, P =.01) and did not correlate with nasal cavity ROI opacification. Inferior nasal cavity opacification for worse-sided anterior ROI and middle ROI correlated with SNOT-22 scores for nasal blockage (anterior r =.41, P =.03) (middle r =.42, P =.023) and runny nose (anterior r =.44, P =.02) (middle r =.38, P =.04). Posterior ROIs did not correlate with SNOT-22. Conclusions: Traditional CT scoring of sinus opacification does not correlate well with nasal cavity opacification or SNOT-22. Inferior nasal cavity inflammation provides unique correlations with SNOT-22 nasal questions and may guide targeted interventions in these regions. [ABSTRACT FROM AUTHOR]

Background: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness. Methods: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients. Results: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice. Conclusion: We suggest that physicians evaluate patients on an individual basis and closely monitor for improvement due to the high cost and unknown long‐term effects of biologics. [ABSTRACT FROM AUTHOR]

Background: The Questionnaire of Olfactory Disorders‒Negative Statements (QOD‐NS) is a valuable instrument in the measurement of olfactory‐specific quality of life (QOL). In the clinical setting, patients can be overwhelmed with the time required to complete questionnaires. Our objective was to develop a brief version of the QOD‐NS to streamline clinical care and research. Methods: QOD‐NS scores from 221 subjects were used to determine which subset of the 17 QOD‐NS questions best correlated with total and subdomain QOD‐NS scores. An initial pool of 11 questions was made by removing items with ρ < 0.80 to their respective subdomain scores. Next, 500 bootstrapped samples were taken. On each sampe, an all‐subsets regression was performed with total QOD‐NS scores and QOD‐NS subdomain scores as the outcomes. From this, our "top" and "bottom" 10 subsets were identified based on mean r2 value, representation in bootstrap analysis, and number of items. Results: All of our top subsets had excellent correlation with total and subdomain QOD‐NS scores (mean r2 > 0.90). Our top choice has 7 total questions, is representative of all subdomains, has a mean r2 = 0.92, and was represented in 323 of our 500 bootstrapped samples. The worst‐performing subset has 5 items, mean r2 = 0.81, and was represented in only 1 bootstrapped sample. Conclusions: Using less than half of the questions in the QOD‐NS, excellent correlations with both total and domain‐specific scores are achieved. A brief version of the QOD‐NS may prove useful in future clinical and research settings. [ABSTRACT FROM AUTHOR]

Background: Productivity loss and activity limitations due to chronic rhinosinusitis (CRS) are known to contribute to the significant economic and personal burden of disease. The purpose of this study was to assess productivity and activity impairment before and after endoscopic sinus surgery (ESS) for medically refractory CRS. Methods: This investigation was a prospective, multi‐institutional, observational cohort study. Patients diagnosed with medically refractory CRS completed the Work Productivity and Activity Impairment—Specific Health Problem (WPAI‐SHP) questionnaire before surgery and approximately 6 months after the procedure. Factors associated with minimal clinical important differences (MCIDs) for productivity and activity impairment were identified. Results: A total of 279 study participants were screened for inclusion, of whom 176 (63.1%) with postoperative follow‐up were included in the final cohort. Preoperative productivity and activity impairment were observed in 63.2% and 69.8% of the patients, respectively. Among these patients, postoperative improvement equaling at least 1 MCID was reported in both productivity (76.1%) and activity (76.4%) impairments. Multivariate regression identified sphenoidotomy (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.03‐17.02) as the only factor associated with increased likelihood of productivity improvement, whereas septoplasty during ESS (OR, 8.45; 95% CI, 2.33‐30.68) and migraine (OR, 0.35; 95% CI, 0.12‐0.96) were associated with differential odds of activity improvement. Conclusion: CRS is associated with a substantial burden on productivity and activity that significantly improves after treatment with ESS. These data may facilitate improved patient counseling and shared decision‐making regarding surgical management for CRS. [ABSTRACT FROM AUTHOR]

Background: Comparative effectiveness research between endoscopic sinus surgery (ESS) and biologic therapy for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a nascent field as new therapeutic modalities become clinically available. Methods: A prospective, multicenter cohort of CRSwNP patients, undergoing ESS between 2011 and 2019, were compared to phase‐3 biologic trial data. Patients undergoing ESS received baseline nasal endoscopy quantified via Lund‐Kennedy (LK) grading. Patients meeting inclusion criteria, modified from Dupilumab‐LIBERTY‐NP‐24&52, omalizumab‐POLYP‐1&2, and Mepolizumab‐SYNAPSE clinical trials, were included in this study. Baseline characteristics and outcome measures were compared between these cohorts at 24 weeks and 52 weeks, when possible. Results: A total of 111 CRSwNP patients met modified inclusion criteria. There were no statistically significant differences in baseline age, sex, asthma status, aspirin‐exacerbated respiratory disease status, smell identification, LK‐polyp score, and Lund‐Mackay computed tomography (CT) scores between ESS and biologic groups. At 24 weeks, ESS demonstrated significantly greater improvements in 22‐item Sino‐Nasal Outcome Test (SNOT‐22) compared to one (of two) dupilumab trials (p < 0.05) and both omalizumab trials (p < 0.001). ESS associated with significantly lower nasal polyp scores (NPS) compared to dupilumab (p < 0.001) and omalizumab (p < 0.001), despite comparable improvements in smell identification (p > 0.05). At 52 weeks, ESS resulted in statistically similar improvement in SNOT‐22 scores compared to dupilumab (p = 0.21), but NPS remained significantly lower in the ESS group compared to dupilumab (p < 0.001) and mepolizumab (p < 0.001). Conclusion: At 24 weeks and 52 weeks, ESS offers comparable SNOT‐22 improvements compared to dupilumab. ESS and dupilumab offer comparable improvement in smell identification at 24 weeks. Compared to omalizumab, ESS offers superior SNOT‐22 improvements. ESS offers significantly greater reductions in polyp size compared to omalizumab, dupilumab, and mepolizumab therapies. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced‐based review with recommendations (EBRR) for fundamental management principles of CF CRS. Methods: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence. Results: We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS). Conclusion: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder. [ABSTRACT FROM AUTHOR]

Background Fibroblasts are implicated in tissue remodeling and recruitment of inflammatory cells in chronic rhinosinusitis (CRS). Populations of fibroblasts remain unquantified in CRS subtypes. The objectives of this study were to measure fibroblast populations in subtypes of CRS, and to investigate the association between fibroblasts and disease severity. Methods Patients undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2011 to December 2014. Control subjects included patients undergoing endoscopic surgery for non-inflammatory conditions such as cerebrospinal fluid leak repair or non-hormone-secreting pituitary tumors. Patients completed 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires prior to surgery. Blood and tissue biopsies were taken during surgery. Percent of sinonasal fibroblasts was determined via flow cytometry by selecting fibroblast-specific protein (FSP)-positive and Mucin 1 (MUC1)-negative cells. Results A total of 69 patients were enrolled: control (n = 24), CRS without nasal polyps (CRSsNP) (n = 13), CRS with nasal polyps (CRSwNP) (n = 22), and allergic fungal rhinosinusitis (AFRS) (n = 10). Patients with CRSwNP had significantly more fibroblasts than both control ( p < 0.001) and CRSsNP ( p < 0.01). Patients with AFRS had the most fibroblasts when compared to control ( p < 0.0001), CRSsNP ( p < 0.0001), and CRSwNP ( p < 0.05). Atopy and asthma were not associated with increased fibroblasts in CRSwNP ( p = 0.21, p = 0.26, respectively). Increased fibroblasts correlated with subjective disease severity as measured by SNOT-22 for CRSwNP ( p = 0.003) and AFRS ( p = 0.048). Conclusion Sinonasal fibroblasts are increased in CRSwNP and AFRS compared to control and CRSsNP. Increased fibroblasts correlated with worse quality of life in CRSwNP and AFRS. [ABSTRACT FROM AUTHOR]

Background: Otologic symptoms consistent with Eustachian tube dysfunction (ETD) are common in patients with chronic rhinosinusitis (CRS), but can also occur independently of CRS as primary ETD. It is unclear if CRS+ETD is similar to primary ETD or how treatment outcomes compare. Methods: A systematic search of PubMed, CINAHL, Scopus, and Cochrane Library was conducted following Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA). Any study describing ETD in CRS was included. Primary ETD studies were limited to those with preoperative and postoperative Eustachian Tube Dysfunction Questionnaire (ETDQ‐7) scores in ETD treated only with Eustachian tube balloon dilation (ETBD). Results: Sixteen studies were included: nine studies with 1336 consecutive patients with CRS and seven studies with 161 patients with primary ETD. In studies with specific data, 225 (47.2%) patients with CRS had a score >14.5, consistent with ETD. In CRS+ETD, baseline mean ± standard deviation (SD) ETDQ‐7 score was 20.7 ± 8.4 and did not differ by polyp status. In primary ETD, mean ETDQ‐7 score was significantly higher than CRS+ETD (29.5 ± 8.1, p < 0.0001). Regarding treatment outcomes, CRS+ETD treated with endoscopic sinus surgery (ESS) alone resulted in mean ETDQ‐7 in the normal range (13.2 ± 5.3), with a mean change of −7.4 (95% confidence interval [CI], −10.82 to −3.99) (p < 0.00001). Patients with primary ETD treated with ETBD had postoperative ETDQ7 scores of 14.9 ± 7.5 with mean change of −13.9 (95% CI, −18.01 to −9.88), p < 0.00001. Conclusion: ETD is noted in approximately half of patients with CRS. Outcomes of CRS+ETD treated with ESS alone are similar to those of patients with primary ETD treated with ETBD. [ABSTRACT FROM AUTHOR]

Background Recent investigation has demonstrated that approximately 75% of patients with medically refractory chronic rhinosinusitis (CRS) report abnormal sleep quality, with strong correlation between worse sleep quality and more severe CRS disease severity. It remains unknown whether the treatment effect of endoscopic sinus surgery (ESS) for CRS results in appreciable sleep quality improvements. Methods Adult patients (aged ≥18 years) with a current diagnosis of recalcitrant chronic rhinosinusitis (CRS), who voluntarily elected ESS as the next treatment modality (n = 301), were prospectively evaluated within 4 academic, tertiary care centers using treatment outcome instruments: the Rhinosinusitis Disability Index, the 22-item Sinonasal Outcome Test, the 2-item Patient Health Questionnaire, and the Pittsburgh Sleep Quality Index (PSQI) both before and after ESS. Results Seventy-two percent (72%) of patients with CRS were found to have poor sleep (PSQI > 5) at baseline with a mean (standard deviation) global PSQI score of 9.4 (4.6). Surgery improved overall mean global PSQI scores (by 2.2 points), and all 7 subdomain scores of the PSQI. Similarly, the odds of good sleep quality (PSQI ≤ 5) in patients treated with sinus surgery increased significantly (odds ratio [OR] 5.94; 95% confidence interval [CI], 3.06 to 11.53; p < 0.001). Stepwise multivariate linear regression found that acetylsalicylic acid (ASA) intolerance (β [standard error], −1.94 [0.93]; 95% CI, −3.77 to −0.11; p = 0.038), history of prior sinus surgery (β [standard error], 1.10 (0.54); 95% CI, 0.03 to 2.16; p = 0.044), and frontal sinusotomy (β [standard error], −1.03 [0.62]; 95% CI, −2.26 to 0.20; p = 0.099) were found to significantly associate with improvement in PSQI sleep scores. Conclusion Among patients with CRS, reduced sleep quality, poor disease-specific quality of life, and greater disease severity were improved following ESS. [ABSTRACT FROM AUTHOR]

Objectives The primary human sinonasal epithelial cell culture (HSNEC) allows for in-vitro modelling of mucosal responses to topical therapy. Cultures grown from healthy donors may underestimate changes in individuals with chronic sinonasal disease thereby yielding inaccurate results with respect to this large patient population. The purpose of this study was to analyse HSNECs derived from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) to determine whether expected disease dependent variables salient to topical drug delivery persist in culture. Methods Cultures were grown from patients with CRSwNP. Ciliary beat frequency (CBF) (basal and stimulated), permeability ( trans and paracellular), inflammatory response, and glucocorticoid dose response were measured and compared with healthy controls. Key findings Methylcholine stimulated CBF was greater in CRSwNP versus controls (ΔCBF60min 7.25 ± 1.02 vs 0.89 ± 1.04 Hz, respectively). Paracellular permeability was greater in CRSwNP versus controls (basolateral dextran120min 18.97 ± 3.90 vs 11.31 ± 4.35 µg/ml, respectively). Lipopolysaccharide (0.1 mg/ml) stimulated interleukin-6 (IL-6) and IL-8 secretion was increased in CRSwNP versus controls (IL-6 Δbaseline 1738.72 ± 654.82 vs 1461.61 ± 533.51%, respectively; IL-8 Δbaseline 137.11 ± 0.83 vs 111.27 ± 0.67%, respectively). CRSwNP cultures were more sensitive than controls to dexamethasone (1 µg/ml) dependent IL-6 and IL-8 suppression. Conclusions HSNECs derived from patients with CRSwNP retained their primary phenotype with respect to ciliary function, epithelial permeability, irritant induced inflammatory cytokine secretion, and glucocorticoid dose response. [ABSTRACT FROM AUTHOR]

Introduction: There has been an explosion in the understanding of the mechanisms of chronic sinonasal inflammation. Multiple approaches to control and modify the inflammatory reaction in chronic rhinosinusitis have led to many new agents being introduced topically to the sinonasal cavities. This article aims to provide an evidence-based approach to the science behind topical management of sinonasal disease. Methods: The literature on delivery device, position, surgical state, and pharmaceutical and mechanical concepts of topical therapy to the paranasal sinuses is reviewed. Results: High-volume irrigation under positive pressure and in head-down positions is important for effective delivery and mechanical action of topical solutions. Unoperated paranasal sinuses appear to receive very limited topical therapy. Enhanced steroid therapy and surfactants appear to be the most promising pharmaceutical approaches. Future novel therapies may include enhancers of the innate immune system. The effect of antibiotic additives is difficult to establish as this might be treating a disease-modifying state rather than the underlying pathology. Conclusions: Topical therapies, applied after surgery, are likely to represent the mainstay of future management for chronic inflammatory rhinosinusitis. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To review developmental abnormalities and iatrogenic alterations in sinus anatomy that may predispose patients with congenital craniofacial malformations to chronic rhinosinusitis. Study design: Retrospective study. Methods: Seven patients with craniofacial malformations who were surgically treated by the senior author were included in the study. All were diagnosed with chronic rhinosinusitis refractory to medical management. Four patients had undergone previous corrective craniofacial surgery, and three of these patients developed iatrogenic sinus disease. Demographic data, diagnoses and anatomical abnormalities were included. Results: Abnormal sinus anatomy was present in all patients, most commonly skull base abnormalities and dehiscent lamina papyracea. All patients underwent successful endoscopic surgical management (n =7) for their chronic rhinosinusitis. Two patients had adjuvant external procedures. There were no complications and no recurrences after a mean follow up time of 15 months. Conclusions: Otolaryngologists should be aware of the possibility of chronic rhinosinusitis in patients with craniofacial malformations. Careful preoperative evaluation of radiographic studies should be performed as most of these patients will have abnormal sinus anatomy. In addition, patients who undergo surgery to correct their craniofacial malformations are susceptible to altered sinus anatomy that may predispose them to the development of iatrogenic chronic rhinosinusitis. [Copyright &y& Elsevier]

Background: The Questionnaire of Olfactory Disorders‐Negative Statements (QOD‐NS) is a 17‐item instrument measuring olfactory‐specific quality of life (QOL). However, in clinical research patients can be overwhelmed with multiple questionnaires. We recently developed the 7‐item brief QOD‐NS (B‐QOD). Our objective was to evaluate the psychometric properties of the B‐QOD in both the development (D) sample, and in a separate replication (R) sample. Methods: Testing on D (n = 203) and R (n = 281) samples included initial exploratory factor analysis (EFA), followed by internal reliability, information loss, and confirmatory factor analysis (CFA). Finally, incremental predictive utility analysis (IPUA) was performed by correlating the B‐QOD with the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) survey. Results: EFAs of both D and R demonstrated an underlying single‐factor structure (eigenvalue = 4.17 and 3.57, respectively) with comparable loading factors (R > 0.30 for both). B‐QOD also had good internal reliability in both D and R (Cronbach's alpha = 0.88 and 0.83, respectively). Also, there is minimal information loss with B‐QOD compared to QOD‐NS in both D and R (R = 0.98 and 0.96, respectively). CFA indicates that the B‐QOD single‐factor model has good overall fit as measured by the Comparative Fit Index (CFI) and the Standardized Root Mean Squared Residuals (SRMSR) in the D and R samples (CFI = 0.99 and 0.97; SRMSR = 0.035 and 0.053). IPUA shows that the QOD‐NS offers no additional predictive benefit of SNOT‐22 scores when compared with B‐QOD. Conclusion: The 7‐item B‐QOD captures a structurally coherent and reliable single dimension, with minimal information loss and excellent external predictive utility when compared to the QOD‐NS. [ABSTRACT FROM AUTHOR]

Background: Poor sleep quality is common in chronic rhinosinusitis (CRS). Prior studies have demonstrated improvements in patient‐reported measures of sleep quality following endoscopic sinus surgery (ESS). The purpose of this study was to evaluate the effect of ESS on objective sleep parameters and identify any associations between specific objective measures and patient characteristics, comorbidities, and patient‐reported outcome measures (PROMs). Methods: Adults with CRS undergoing ESS were prospectively enrolled from 4 centers across North America. Any subject previously diagnosed with a known primary sleep disorder was excluded. Objective sleep indices were recorded using a portable sleep diagnostic device preoperatively and postoperatively. Patient‐reported outcome instruments were completed including the Pittsburgh Sleep Quality Index (PSQI) and the 22‐item Sino‐Nasal Outcome Test (SNOT‐22). Results: Thirty‐six patients (mean age 47 years, 56% male) completed baseline and postoperative sleep studies with mean ± standard deviation (SD) follow‐up 9.6 ± 7.7 months. Mean PSQI and SNOT‐22 before and after ESS was 10.2 ± 3.9 vs 7.8 ± 4.4 (p = 0.001); and 54.6 ± 14.6 vs 28.5 ± 15.3 (p < 0.001), respectively. Total sleep time, sleep latency, and awakenings after sleep onset did not change following ESS (all p > 0.5) despite improvements in PSQI and SNOT‐22. Changes in PSQI did not correlate with comorbidities or objective sleep indices (all p > 0.1). Conclusion: In this multicenter prospective cohort, objective sleep indices were not improved following ESS for CRS despite significant improvements in patient‐reported sleep quality and CRS‐specific QOL. [ABSTRACT FROM AUTHOR]

Background: Inflammatory profiles for patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) vary between North American and Asian populations. An elevated ethmoid‐to‐maxillary (E/M) opacification ratio on preoperative imaging is associated with certain postoperative outcomes in Asian populations and populations that are non‒type 2 dominant. In this study we explore this factor in North American/type 2‒based populations. Methods: Adult patients (n = 165) from a North American population with CRSwNP who underwent endoscopic sinus surgery (ESS) were prospectively enrolled into an observational, multi‐institutional study. The 22‐item Sino‐Nasal Outcome Test (SNOT‐22), Brief Smell Identification Test (BSIT), and Lund‐Kennedy (LK) endoscopic scores were obtained pre‐ and postoperatively. Patients were stratified according to increasing E/M ratios based on Lund‐Mackay (LM) scores. Results: On average, significant within‐subject postoperative improvement was found in all patients for SNOT‐22 total and domain scores, and also BSIT results (p ≤ 0.019). Preoperatively, elevated E/M ratio correlated with worse BSIT scores (r = −0.343, p < 0.001). Postoperatively, elevated E/M ratio correlated with BSIT improvement (r = 0.284, p = 0.002), but did not correlate with SNOT‐22 improvement or polyp recurrence. An elevated E/M ratio was associated with greater likelihood of reporting a minimal clinically important difference in BSIT scores (χ2 = 9.96, p = 0.041). Conclusion: Elevated E/M ratios were found to associated with worse baseline olfaction and an increased likelihood of achieving a clinically meaningful postoperative improvement in olfaction in this North American population with CRSwNP. Elevated E/M ratios did not predict postoperative changes in SNOT‐22 measures or polyp recurrence. This suggests that prognostic factors may vary according to geography and generalized inflammatory profiles (type 2 vs non‒type 2) in patients with CRS. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic rhinosinusitis (CRS) commonly experience both reduced quality of life (QOL) and olfactory dysfunction (OD). Literature on the impacts of appropriate medical therapy (AMT) for CRS on QOL and OD is limited, and the focused design of these studies may limit their applicability to usual clinical practice. Methods: Adults with symptomatic CRS were prospectively enrolled (November 2016 to October 2018) into an observational, multi‐institutional study. Individualized AMT was initiated using standard practice according to evidence‐based guidelines. Endoscopy examination (Lund‐Kennedy), olfactory function (Sniffin' Sticks) testing, and QOL survey responses (22‐item Sino‐Nasal Outcome Test [SNOT‐22], Questionnaire of Olfactory Disorders―Negative Statements [QOD‐NS]) were obtained at enrollment and follow‐up. Results: Baseline measures demonstrated heterogeneity of QOL and OD. After an average of 7.8 weeks, within‐subject median SNOT‐22 total improved by 39.5% (n = 39, p < 0.001) relative to baseline, including 50% (p = 0.014) improvement for item #21, "Sense of smell/taste." QOD‐NS improvement was also statistically significant (p = 0.044). Sniffin' Sticks score relative improvement of 10.9% (n = 33, p = 0.109) was not statistically significant and lacked correlation with SNOT‐22 total scores (R = −0.247, p = 0.165) or QOD‐NS total scores (R = −0.016, p = 0.930), but correlated moderately with endoscopy score (R = −0.436, p = 0.018). Conclusions: Participants with varied impacts of CRS, treated with individualized short‐term AMT, demonstrated significant improvements in CRS‐ and olfactory‐specific QOL measures, without corresponding improvement in clinically measured olfactory function. Olfactory function changes moderately correlated with endoscopy score changes, but lacked an association with QOL measurements. [ABSTRACT FROM AUTHOR]

Background: Surgical treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) has evolved over the last decade as rhinologists have increasingly used topical steroid therapies and altered surgical techniques. It is important to understand the changes in success rates of surgery and frequency of revision endoscopic sinus surgery (ESS) in CRSwNP. The aim of this study was to retrospectively review the revision surgical rate of CRSwNP patients by evaluating outcomes in a cohort from the Medical University of South Carolina (MUSC). Methods: Retrospective review of CRSwNP patients operated upon at the MUSC between 2002 and 2019 by a single surgeon was performed. Assessed factors included demographics, comorbidities, CRSwNP subtype, extent of surgery, and steroid rinse compliance. Logistic regression was performed to identify factors associated with revision surgery. Results: Among 338 patients with at least 6 months of follow‐up, 24.9% had revision surgery, with a mean follow‐up of 52.6 months. In patients with any person‐time measure, the revision rate was 5.58 per 100 person‐years. Independent risk factors associated with increased odds ratio (OR) for revision surgery were: younger age (OR, 1.1); prior surgery (OR, 3.3); longer follow‐up (OR, 1.1); and surgery before 2009 (OR, 2.4) (p < 0.05 for all). Conclusion: The revision surgery rate for CRSwNP was 24.9% among those with at least 6 months of follow‐up. Risk factors for higher revision rates included younger age, previous surgery, longer follow‐up, and surgery at the MUSC prior to 2009. As we enter an era of personalized medicine, it is important to consider patient‐ and surgeon‐specific factors, which impact revision surgery rates. [ABSTRACT FROM AUTHOR]

Background: Wide variations in revision endoscopic sinus surgery (ESS) rates for chronic rhinosinusitis with nasal polyposis (CRSwNP) have been reported. It is important to understand expected revision rates and factors that impact the need for revision. Methods: A literature search was conducted on PubMed, Scopus, and the Cochrane Database of Systematic Reviews. Following PRISMA guidelines, a systematic review and meta‐analysis was performed on studies that reported revision surgery data for CRSwNP patients. Results: Forty‐five studies with 34,220 subjects were meta‐analyzed, with an overall revision rate of 18.6% (95% confidence interval, 14.1%‐23.6%). Studies with extractable follow‐up data reported a mean revision rate of 16.2% over a weighted mean follow‐up of 89.6 months. Factors associated with increased revision rates included allergic fungal rhinosinusitis (28.7%), aspirin‐exacerbated respiratory disease (27.2%), asthma (22.6%), prior polypectomy (26.0%), and publication prior to 2008 (22.7%) (p < 0.05 for all). Conclusion: Although polyps can recur after ESS, reported long‐term ESS revision rates are approximately 14% to 24%. Identifying risk factors for revision surgery can help manage patient expectations and determine optimal personalized treatments. [ABSTRACT FROM AUTHOR]

Background: Despite the tremendous burden of smell and taste dysfunction in patients with chronic rhinosinusitis (CRS), objective measures of smell and taste fail to fully account for eating‐related disruptions in CRS patient quality of life (QOL). In this study we sought to investigate the driving force behind impaired eating‐related QOL in CRS patients. Methods: Adult CRS patients were prospectively enrolled and answered a series of surveys relating to smell, taste, overall sinus‐specific QOL, and depression. Patients with both smell‐related and taste‐related eating complaints were considered to have impaired eating‐related QOL. Clinical demographics, objective chemosensory scores, and endoscopy scores were collected. Results: Seventy patients were enrolled and 23% showed impaired eating‐related QOL. In multivariable analyses, patients with aspirin‐exacerbated respiratory disease (AERD) showed 10.7 times higher odds of impaired eating‐related QOL (odds ratio [OR] 10.72; 95% confidence interval [CI], 1.09 to 105.09; p = 0.042); meanwhile, for every 1‐point increase in depression scores, the odds of impaired eating‐related QOL increased by 1.3 (OR 1.31; 95% CI, 1.10 to 1.57; p = 0.003). For every 1‐point decrease in orthonasal olfactory threshold, the odds of impaired eating‐related QOL increased by 1.9 times (OR 1.85; 95% CI, 1.14 to 3.00; p = 0.013). Symptom scores, polyp status, endoscopic scores, and other olfactory measures did not remain significant after adjusting for other variables in forward‐selection multivariable modeling. Conclusion: Disruptions in eating‐related QOL cannot be fully explained by objective smell or taste testing alone. We identified AERD and depression as independent risk factors for greater odds of impaired eating‐related QOL in CRS. Improved orthonasal threshold scores were independently associated with better eating‐related QOL. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have suggested that patients with chronic rhinosinusitis (CRS) report worse sleep quality than population norms. What remains unknown is whether these patients are actually experiencing measurable changes in objective sleep parameters. The goal of this study was to prospectively evaluate objective sleep measures in a cohort of patients with CRS. Methods: A prospective, multi‐institutional, case‐control study was designed to compare patients with CRS to nondiseased controls. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (EpSS). Home sleep studies were administered across all subjects and a battery of objective sleep measurements were recorded using a portable sleep diagnostic device. Regression models were used to control for any factors that differed across groups. Results: A total of 108 subjects were enrolled across 4 institutions, including 52 patients with CRS and 56 controls. Total PSQI scores were worse in patients with CRS when compared with controls (10.1 ± 4.3 vs 4.7 ± 2.5; p < 0.001). Similarly, daytime somnolence, as measured by the EpSS, was greater in patients with CRS (9.1 ± 5.3 vs 6.5 ± 3.7; p = 0.006). On home sleep studies, patients with CRS were found to have an increased number of awakenings during a night's sleep (8.6 ± 4.8 vs 6.3 ± 3.0; p = 0.004), lower average overnight oxygen saturation (93.2 ± 2.6% vs 94.3 ± 2.1%; p = 0.042), increased rapid eye movement sleep (REMS) latency (93.0 ± 67.1 vs 66.7 ± 35.3; p = 0.016), and spent a greater portion of the night snoring at >40 dB (24.7 ± 27.4% vs 14.6 ± 19.7%; p = 0.034). All differences except mean oxygen saturation remained significant after controlling for baseline differences. Conclusion: Differences in both patient‐reported and objective sleep measures exist between patients with CRS and controls. [ABSTRACT FROM AUTHOR]

Background: Genetic variation of the bitter taste receptor T2R38 has been associated with recalcitrant chronic rhinosinusitis (CRS). Specific T2R38 polymorphisms, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been identified as an independent risk factor for surgical intervention in CRS patients without polyps; however, the exact role of PTC tasting ability in clinical practice remains unknown. In this investigation we characterize PTC taste sensitivity in a tertiary care rhinology practice with pertinent clinical measures of disease and quality of life (QOL). Methods: Adult CRS patients were prospectively assessed for their ability to taste PTC and categorized as nontasters, tasters, or supertasters. Objective taste was assessed with strips for bitter, sweet, sour, and salty, whereas olfactory testing was measured with Sniffin’ Sticks. Correlation was performed between PTC tasting ability and patient demographics, endoscopy scores, validated QOL surveys, and both subjective and objective measures of taste and olfaction. Results: Sixty‐seven patients were enrolled. Fifty‐two percent were identified as nontasters, 34% as tasters, and 13% as supertasters. Nontasters were more likely to be non‐Hispanic (p = 0.018), white (p = 0.027), without nasal polyposis (p = 0.004), and nonasthmatics (p = 0.019). There were no other statistical differences in patients’ demographics, QOL measures, and subjective or objective olfactory and taste scores when compared with patients’ oral PTC‐sensing ability. Conclusion: Oral PTC‐sensing ability may serve as a convenient marker of increased disease severity in white CRS patients without polyps and vary among regional populations. PTC tasting ability appears to provide unique phenotypic information not obtained using other subjective or objective measures of smell and taste. [ABSTRACT FROM AUTHOR]

Rationale: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Methods: Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Results: Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. Conclusions: VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels. [ABSTRACT FROM AUTHOR]

Background Measuring quality outcomes is an important prerequisite to improve quality of care. Rhinosinusitis represents a high value target to improve quality of care because it has a high prevalence of disease, large economic burden, and large practice variation. In this study we review the current state of quality measurement for management of both acute (ARS) and chronic rhinosinusitis (CRS). Methods The major national quality metric repositories and clearinghouses were queried. Additional searches included the American Academy of Otolaryngology-Head and Neck Surgery database, PubMed, and Google to attempt to capture any additional quality metrics. Results Seven quality metrics for ARS and 4 quality metrics for CRS were identified. ARS metrics focused on appropriateness of diagnosis (n = 1), antibiotic prescribing (n = 4), and radiologic imaging (n = 2). CRS quality metrics focused on appropriateness of diagnosis (n = 1), radiologic imaging (n = 1), and measurement of patient quality of life (n = 2). The Physician Quality Reporting System (PQRS) currently tracks 3 ARS quality metrics and 1 CRS quality metric. There are no outcome-based rhinosinusitis quality metrics and no metrics that assess domains of safety, patient-centeredness, and timeliness of care. Conclusions The current status of quality measurement for rhinosinusitis has focused primarily on the quality domain of efficiency and process measures for ARS. More work is needed to develop, validate, and track outcome-based quality metrics along with CRS-specific metrics. Although there has been excellent work done to improve quality measurement for rhinosinusitis, there remain major gaps and challenges that need to be considered during the development of future metrics. [ABSTRACT FROM AUTHOR]

Background In these studies we examined the impact of environmental tobacco smoke (ETS) and active smoking on sinonasal dendritic cell (DC) subsets in controls or patients with chronic rhinosinusitis with nasal polyps (CRSwNP). In subsequent in-vitro investigations, we examined the influence of cigarette smoke extract (CSE) on human sinonasal epithelial cells' (HSNECs) ability to regulate DC functions. Methods Sinonasal tissue, blood, and hair were collected from patients undergoing sinus surgery. Smoking status and ETS exposure were determined by hair nicotine. DC subsets were examined by flow cytometric analysis. Monocyte-derived dendritic cells (moDCs) were treated with conditioned medium from non-smoked-exposed HSNECs (NS-HSNECs) or cigarette-smoke-extract-exposed HSNECs (CSE-HSNECs) to assess the impact of CSE exposure on HSNEC regulation of moDC functions. Results Control subjects who were active smokers displayed increased sinonasal moDC and myeloid dendritic 1 (mDC1) cells and reduced mDC2 cells, whereas, in CRSwNP patients, only moDC and mDC2 cells were altered. ETS was found to increase only moDCs in the CRSwNP patients. In vitro, CSE stimulated HSNEC secretion of the moDC regulatory products chemokine (C-C motif) ligand 20, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor. CSE exposure also promoted HSNECs to stimulate monocyte and moDC migration. moDCs treated with CSE-HSNEC media stimulated an increase in antigen uptake and expression of CD80 and CD86. Last, CSE-HSNEC-treated moDCs secreted increased levels of interleukin-10, interferon-γ, and thymic stromal lymphopoietin. Conclusion Active smoking, and to a lesser degree ETS, alters the sinonasal composition of DCs. A potential mechanism to account for this is that cigarette smoke stimulates HSNECs to induce moDC migration, maturation, and activation. [ABSTRACT FROM AUTHOR]

Background Endoscopic sinus surgery (ESS) has been shown to improve sleep in patients with chronic rhinosinusitis (CRS). However, it is unknown how this improvement compares with non-CRS control subjects' sleep, and medically treated CRS patients. Methods Patients meeting diagnostic criteria for CRS and controls from the same reference population were recruited from 4 academic centers. Patients chose either medical or surgical treatment. The Pittsburgh Sleep Quality Index (PSQI) was administered to patients before treatment and after 6 months, whereas controls received the PSQI at enrollment. Results The study population consisted of 187 cases (64 medical and 123 surgical) and 101 controls. Baseline PSQI scores for CRS patients (9.27 ± 4.76) were worse than for controls (5.78 ± 3.25), even after controlling for potential confounding factors such as asthma and allergy ( p < 0.001). There was no significant difference in baseline PSQI between patients choosing medical vs surgical treatment. The PSQI score in surgical patients improved from 8.36 ± 5.05 to 7.44 ± 5.09 ( p = 0.020). The PSQI score in medical patients demonstrated a nonsignificant increase with treatment from 8.71 ± 4.48 to 9.06 ± 4.80 ( p = 0.640). After controlling for allergy and asthma, 6-month PSQI scores in medical patients remained significantly higher than in controls ( p = 0.001), whereas a significant difference could not be demonstrated between surgical patients and controls ( p > 0.05). PSQI subdomain analysis mirrored the overall findings. Conclusion Patients with CRS report worse sleep compared with controls. Surgically treated CRS patients show significant improvement in PSQI scores, whereas those continuing with medical management fail to improve and remain worse than controls. [ABSTRACT FROM AUTHOR]