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Objectives: Oral corticosteroid (OCS) as a part of appropriate medical therapy (AMT) (formerly maximal medical therapy) in chronic rhinosinusitis remains controversial. While the risks of OCS are well known, the benefit remains unclear due the absence of a standardized prescribing regimen. Consequently, it is difficult to characterize whether the risks of OCS and its ability to avert endoscopic sinus surgery (ESS) are helpful in AMT. When OCS is highly effective at averting surgery, the lesser risks of OCS would be justified because it can avoid the greater risks of ESS. When OCS is poorly effective at averting ESS, the risks of OCS would not be justified because many patients will be exposed to both risks. This study seeks to identify the threshold effectiveness of OCS at averting ESS that would minimize risk exposure to patients., Methods: A probabilistic risks-based decision analysis was constructed from literature reported incidences and impacts of adverse events of OCS and ESS. Monte Carlo analysis was performed to identify the minimum effectiveness required to avoid further intervention (MERAFI) for chronic sinusitis without nasal polyp (CRSsNP) and chronic sinusitis with nasal polyp (CRSwNP)., Results: The analysis showed MERAFI results of 20.8% (95% CI 20.7-20.9%) for CRSsNP and 16.8% (95% CI 16.7-16.9%) for CRSwNP., Conclusions: Given reported OCS effectiveness in the range of 34-71% in CRSsNP and 46-63% in CRSwNP, this analysis suggests that the inclusion of OCS in AMT may be the lower risk strategy., Level of Evidence: N/A Laryngoscope, 131:473-481, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: The role of the microbiome in the etiology of chronic rhinosinusitis (CRS) is still in debate. Reductions in richness and diversity have been implicated in CRS; however, limited knowledge exists regarding the impact of the severity of disease on the microbiome. The associations between constituents of the microbiome and the degree of mucosal inflammation and tissue eosinophilia are described., Methods: A cross-sectional study of CRS and non-CRS patients who underwent endoscopic sinus surgery was performed. Sinus mucosal biopsies were assessed for the degree of inflammation and tissue eosinophilia. Middle-meatal swabs were subjected to 16S rRNA gene sequencing, which quantified the prevalence, mean relative abundance, richness, and diversity. Comparisons between the microbiome at the genus level and degree of inflammation (absent, mild, moderate, severe) and tissue eosinophilia (absent, < 10, 10-100, > 100 per high-powered field) were performed., Results: Eight-nine patients (52.8 ± 14.21 years, 64.0% male) were assessed. Of those, 52 had CRS and 37 were controls. Corynebacterium and Staphylococcus were the most abundant genera in both the CRS (29% and 16%) and non-CRS groups (40% and 20%). Richness decreased in more severely inflamed patients (23.2 ± 13.9 vs. 18.1 ± 16.1 vs. 16.8 ± 12.3 vs. 14.7 ± 10.9; P < 0.01), as did diversity (1.4 ± 0.7 vs. 1.2 ± 1.0 vs. 1.2 ± 0.8 vs. 0.9 ± 0.7; P = 0.05). Richness was associated with higher tissue eosinophilia (23.2 ± 13.9 vs. 19.3 ± 17.2 vs. 15.9 ± 11.6 vs. 13.4 ± 6.6; P < 0.01)., Conclusion: The loss of richness and diversity seen in the CRS microbiome appears to be a product of severity of inflammation and tissue eosinophilia. Whether this dysbiosis is causative or a result of the disease with impaired epithelial integrity requires ongoing research., Level of Evidence: 4 Laryngoscope, 129:1265-1273, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: The Draf III frontal sinusotomy is an established surgical procedure with an important role in the surgical management of recalcitrant chronic rhinosinusitis (CRS). In 2012, the outside-in approach to the Draf III was described as a safe and efficient procedure. Smell recovery in inflammatory CRS is challenging, and to date there is limited evidence suggesting that Draf III improves patient-reported olfactory dysfunction from CRS., Methods: A consecutive series of patients who underwent an outside-in Draf III for inflammatory CRS by a single, tertiary rhinologist were reviewed. Patients were excluded if the Draf III was performed for noninflammatory conditions. Postoperatively, patients were maintained on long-term corticosteroid irrigations, and adherence was assessed. Prospectively collected data included patient demographics, a visual analogue scale for smell, overall Sinonasal Outcome Test Score (SNOT-22), global nasal function score, and a clinician-graded clinical outcome score., Results: One hundred and four patients (41.1% female) aged 54 ± 12 years underwent an outside-in Draf III. The median follow-up time was 30.6 months (range 12.2-72.1). The majority of patients rated their smell loss as moderate or worse preoperatively; however, this was significantly improved at postoperative review (71.2% vs. 27.6%; Kendall tau-b, P < 0.01). The SNOT-22 score improved after surgery (2.32 ± 1.09 vs. 0.78 ± 0.69, P < 0.0001). Medication adherence was significantly associated with improved clinical outcome score (Kendall tau-b, P < 0.004). Aspirin exacerbated respiratory disease was found to be a significant risk factor predicting poor clinical outcome on univariate analysis (Odds Ratio = 4.69 (1.03-21.2), P = 0.04)., Conclusion: The outside-in Draf III appears to facilitate sustained, meaningful improvement in several self-reported outcomes, including smell. However, further study and comparison to less aggressive surgery will be required to confirm its true benefit., Level of Evidence: Level 4 Laryngoscope, 129:25-30, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Polypoid edema of the middle turbinate is a marker of inhalant allergy. Extensive edematous changes may result in limited central nasal and sinus disease, which has been called central compartment atopic disease (CCAD). Radiologically, this is seen as soft tissue thickening in the central portion of the sinonasal cavity with or without paranasal sinus involvement. When the sinuses are involved, the soft tissue thickening spares the sinus roof or lateral wall (centrally limited). This centrally limited radiological pattern was assessed among chronic rhinosinusitis (CRS) patients and compared to allergy status., Study Design: Diagnostic cross-sectional study., Methods: This study included consecutive CRS patients without prior sinus surgery. Computed tomography (CT) scans of the paranasal sinuses were blindly assessed and allergy status was confirmed by serum or skin testing. Individual sinus cavities were defined as either centrally limited or diffuse disease. The radiological pattern that may predict allergy was determined, and its diagnostic accuracy was calculated., Results: One hundred twelve patients diagnosed to have CRS, representing 224 sides, were assessed (age 46.31 ± 13.57 years, 38.39% female, 41.07% asthma, Lund-Mackay CT score 15.88 ± 4.35, 56.25% atopic). The radiological pattern defined by centrally limited changes in all of the paranasal sinuses was associated with allergy status (73.53% vs. 53.16%, P = .03). This predicted atopy with 90.82% specificity, 73.53% positive predictive value, likelihood positive ratios of 2.16, and diagnostic odds ratio of 4.59., Conclusions: A central radiological pattern of mucosal disease is associated with inhalant allergen sensitization. This group may represent a CCAD subgroup of patients with mainly allergic etiology., Level of Evidence: 3b Laryngoscope, 128:2015-2021, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Ostiomeatal complex (OMC) occlusion may play a role in the pathogenesis of some chronic rhinosinusitis (CRS) subgroups, but its role in diffuse mucosal inflammation is strongly debated. The association between radiological OMC occlusion and its draining sinuses in patients with eosinophilic rhinosinusitis (ECRS) compared to non-ECRS is investigated., Study Design: Case-control study., Methods: Patients with CRS who underwent endoscopic sinus surgery were investigated. Preoperative computed tomography scans were evaluated. Structured histopathology reporting was performed. The study group was patients with high tissue eosinophil >10/high power fields (HPF), and the control group was patients with low tissue eosinophil ≤ 10/HPF. The radiological relationship of OMC occlusion to the draining sinuses was analyzed in each group., Results: Seventy patients with a mean age of 49.7 ± 14.1 years were analyzed. Forty-one (58.6%) patients had high tissue eosinophil >10/HPF. All patients with ECRS had maxillary disease, and there were 36.2% without OMC occlusion. There was no association of OMC occlusion to either the anterior ethmoid (ECRS: odds ratio [OR], 1.84; 95% confidence interval [CI], 0.24-14.14; P = .55; non-ECRS: OR, 1.57; 95% CI, 0.34-7.33; P = .56) or frontal sinuses (ECRS: OR, 0.67; 95% CI, 0.12-3.82; P = .65; non-ECRS: OR, 1.58; 95% CI, 0.45-5.54; P = .47). For patients with non-ECRS, maxillary sinus diseases was present in 96.2% of those with OMC occlusion and 50% of those without (OR, 25.0; 95% CI, 2.77-226.08; P < .001)., Conclusions: OMC occlusion is not associated with draining sinuses for patients with ECRS. Simple surgical interventions directed at the OMC are unlikely to be of benefit to this CRS subgroup., Level of Evidence: 3b., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Due to the complexity and variety of the frontal recess and sinus anatomy, traditional Draf 2a frontal sinus surgery is challenging. The thickness of the nasofrontal beak and anterior–posterior dimensions of the frontal recess contribute to this complexity. Carolyn's window technique eliminates the limitation of anterior–posterior depth to facilitate a Draf 2a frontal sinusotomy. The approach is a 0° endoscope technique and provides an excellent view of the frontal sinus and recess. We describe Carolyn's window approach to frontal sinus surgery and the perioperative outcomes. Methods: Consecutive adult patients in whom Carolyn's window technique was applied for frontal sinus dissection as part of the endoscopic management of both inflammatory and neoplastic disease were assessed. The primary outcome was frontal sinus patency. Secondary outcomes were surgical morbidity, defined as early (<90 days) or late (>90 days). Results: Forty‐five patients (49.1 ± 17.9 years, 48.9% Female) were assessed. All patients had successful frontal sinus patency (100% [95CI: 92.1%–100%]). Morbidities were adhesion (4.8%), crusting (2.4%), pain (1.2%), and bleeding (1.2%) in the early postoperative period. There were no other morbidities in the early and late postoperative periods. Conclusion: Carolyn's window approach to frontal sinusotomy is a technique that evolves from previously described approaches. Successful frontal sinus patency with very low morbidities is achieved while still working with a 0° endoscope. The "axillectomy" performed simplifies frontal recess surgery by removing the anteroposterior diameter limitation and the dexterity required in angled endoscopy and instrumentation. The inferior‐based lateral wall mucosal flap and free mucosal grafting expedite the mucosal healing process. Laryngoscope, 133:2496–2501, 2023 [ABSTRACT FROM AUTHOR]

Background: Eosinophilic chronic rhinosinusitis is an often treatment‐resistant inflammatory disease mediated by type‐2 cytokines, including interleukin (IL)‐5. Mepolizumab, a monoclonal antibody drug targeting IL‐5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study's aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients. Methods: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four‐weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24. Results: Twenty patients (47.7 ± 11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64 ± 93.80 vs 41.74 ± 53.76 cells per 0.1 mm2; p =.035), eosinophil degranulation remained unchanged (5.79 ± 2.08 vs 6.07 ± 1.20, p =.662), and type‐2 cytokine levels increased in sinonasal tissue for IL‐5 (10.84 ± 18.65 vs 63.98 ± 50.66, p =.001), IL‐4 (4.48 ± 3.77 vs 9.38 ± 7.56, p =.004), IL‐13 (4.02 ± 2.57 vs 6.46 ± 3.99, p =.024) and GM‐CSF (1.51 ± 1.74 vs 4.50 ± 2.97, p =.001). Conclusion: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL‐5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type‐2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response. [ABSTRACT FROM AUTHOR]

Background The objective of this work was to review the literature concerning the distribution of topical therapeutics to the sinuses versus nasal cavity regarding: surgical state, delivery device, head position, and nasal anatomy and to provide evidence-based recommendations. Methods A systematic review was conducted using Medline, EMBASE, and Cochrane databases to perform a Medical Subject Heading search of the literature from 1946 until the last week of May 2012. Articles were independently reviewed and graded for level of evidence. All authors came to consensus on recommendations through an iterative process. Results Recommendations were made for: improved sinus delivery with high-volume devices and after standard sinus surgery. Recommendations were made against low-volume delivery devices, such as drops, sprays, or simple nebulizers as they do not reliably reach the sinuses. If large-volume devices are not tolerated, low-volume devices are recommended using the lying head back or lateral head low positions to improve nasal cavity distribution to the middle meatus or olfactory cleft. Conclusion Surgery, volume of device, head position, and nasal anatomy were shown to impact distribution to the sinuses. Recommendations are made based upon this evidence as to how to best maximize therapeutic distribution to the sinuses. [ABSTRACT FROM AUTHOR]

Background: Biologic therapy targeting type 2 chronic rhinosinusitiswith nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control. Methods: A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control. Results:Atotal of 37 patientswere included (age 47.8±12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 109 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 109 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002). Conclusion: Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of =5.75 × 109 cells/L predicts for poor response to current biologic therapy. [ABSTRACT FROM AUTHOR]

Key Points: Culturable bacterial colonization is similar between type 2 CRS phenotypesStaphylococcus aureus coinfection is similar between eosinophilic CRS and CCADPatients with CCAD were younger, consistent with current knowledge of the disease [ABSTRACT FROM AUTHOR]

Colloquially, many patients simply refer to any form of sinonasal symptoms as "sinus" or "sinusitis", but often patients simply have a rhinitis reaction. PATIENTS AND METHODS Study design A cross-sectional study was performed of patients presenting with sinonasal symptoms to an otolaryngologist. Only those with a final diagnosis of either rhinitis or CRS were included and all patients underwent nasal endoscopy and CT. [Extracted from the article]

Background: Delivery of topical pharmacotherapy to the paranasal sinuses remains integral to the management of chronic rhinosinusitis. The frontal sinus remains a difficult access site for irrigations, often limited by its position relative to the nostril and ethmoid sinus. In view of the previous demonstration of improved frontal sinus irrigation with Draf III vs Draf IIa, in this work we sought to evaluate topical access of Draf IIb relative to Draf IIa and Draf III modification of the frontal sinus outflow tract. Methods: Unfixed human cadaver heads were dissected using Draf IIa, Draf IIb, and Draf III frontal sinusotomies. Draf IIa, Draf IIb, and Draf III frontal sinusotomies were performed in progressive sequence on each cadaver head. Nasal irrigation fluid access to the frontal sinus was tested after each successive frontal sinus intervention. Irrigations were performed using Frankfort horizontal and vertex positioning. Blinded reviewers were then asked to evaluate nasal irrigation access based on an ordinal scale. Results: Eight cadaveric specimens (age, 78 ± 12.3 years; 62.5% female) were assessed. The greatest distribution scores were recorded by Draf III, then IIb, and then IIa (90.7% vs 81.3% vs 50.1%; p < 0.001). Similarly, the rate of lavage was greatest with Draf III (50% vs 12.5% vs 12.5%). Vertex positioning and increasing volume trended toward improved distribution but did not reach statistical significance. Conclusion: Adequate delivery of topical therapy to the paranasal sinuses by nasal irrigation remains critical in the postoperative state. Although increasing the dimensions of the frontal recess improves nasal irrigation delivery, the Draf III procedure provides the optimal delivery of pharmacotherapy in those with frontal sinus disease. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS), in particular with nasal polyps (CRSwNP), has been linked with skewed T‐helper 2 and immunoglobulin E (IgE)‐mediated allergic responses. The role of atopy in CRS, however, remains unclear. Correlations between immunological allergic markers and patient‐reported outcomes measures (PROMs) were investigated. Methods: A cross‐sectional study of adult patients with CRS undergoing endoscopic sinus surgery was conducted. Immunological allergic markers included automated immunoassay testing for serum‐specific IgE to common allergens (house dust mite, grass, mold, animal epithelia) and total IgE. PROMs were assessed using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22). Patients were defined as atopic based on either a positive specific IgE or elevated total IgE (>160 kU/L). Results: A total of 446 patients (45.7% female, age 49.05 ± 14.96 years) were recruited, of which 42.8% had asthma, 51.6% had CRSwNP, and 63.0% had eosinophilic CRS. Positive allergen sensitization was detected in 52.9% patients. Total IgE levels were elevated in 28.0% with mean IgE level of 161 ± 269 kU/L. Atopy was associated with younger age at the time of surgery, CRSwNP, asthma, and eosinophilic CRS (eCRS). Atopy was also associated with increased severity in nasal symptom score (13.1 ± 6.4 vs 11.9 ± 6.0, p = 0.04), as well as worse scores in the loss of smell/taste (χ2(1) = 5.97, p = 0.02) and need to blow nose (χ2(1) = 4.26, p = 0.04) questions in the CRS population. In the CRSwNP population, there was no significant association between atopy and PROMs. Conclusion: Comorbid atopy in CRS is associated with additional symptom burden, reflected mainly within the nasal symptom quality of life markers. Atopy assessment in CRS is important to ensure appropriate and successful treatment of the disease. [ABSTRACT FROM AUTHOR]

Background Episodic or recurrent sinonasal symptoms are often suspected as 'sinus' in origin. With normal sinus radiology between events, the diagnosis of recurrent acute rhinosinusitis (RecARS) is made. However, other conditions can produce episodic symptoms. In this study we analyze acutely performed computed tomography (CT) in a population with suspected or self-diagnosed 'sinus' disease. Methods Patients referred to a tertiary clinic for suspected RecARS were assessed. Sinus changes were defined by CT (initial assessment) and during the acute event, by a semiurgent CT performed during the symptomatic episode. Mucosal thickening, ostiomeatal compromise, and severe septal deformity were recorded. Symptom profile was assessed during both time-points with the 22-item Sino-Nasal Outcome Test (SNOT-22). Results Forty-eight patients (49.5 ± 14.7 years of age, 70.8% female) were assessed. At presentation, 75% were resolute in a diagnosis of 'sinus.' Baseline Lund-Mackay scores were <6 (median 0 [interquartile range 1]). Ostiomeatal compromise was 6.8% left and 4.5% right at baseline. Of the patients who returned for acute CT (n = 27), SNOT-22 and subdomains were similar to baseline. Septal deviation was similar (13.6% vs 15.3%). Acutely, ostiomeatal compromise was 0% left and 7.4% right (n = 2). Of these 2 patients with ostiomeatal compromise, 1 was diagnosed with RecARS (4%) and the other with triptan-responsive migraine, with incidental sinus changes. Final diagnosis was rhinitis (47%), headache/migraine (37%), and facial pain otherwise undefined (12.5%). Conclusion Patients with a history of "recurrent acute sinusitis" and normal CT scans between episodes rarely have abnormal CT findings during acute exacerbations of symptoms. Antibiotics and surgical intervention are often inappropriate in this population. [ABSTRACT FROM AUTHOR]

Background Vitamin D deficiency is associated with many inflammatory respiratory disease states. However, serum vitamin D concentrations may not reflect tissue-specific availability. In this study we sought to assess the local expression of genes essential in vitamin D regulation in chronic rhinosinusitis (CRS). Methods A cross-sectional study of adult patients undergoing endoscopic sinus surgery was performed. Patients were defined as having CRS with polyps (CRSwNP) or without polyps (CRSsNP), or normal sinus mucosa. Sinus mucosal biopsies were assessed using quantitative polymerase chain reaction to determine expression of genes encoding the vitamin D receptor ( VDR), 25-hydroxylase ( CYP2R1), 1α-hydroxylase ( CYP27B1), and 24-hydroxylase ( CYP24A1). Expression levels correlated with serum 25(OH)D [sum 25(OH)D2 and 25(OH)D3], the 22-item Sinonasal Outcome Test (SNOT-22), and Nasal Symptom Score (NSS). Separate analyses were performed for patients grouped by tissue eosinophilia. Results Thirty-one patients were assessed (age 49.47 ± 18.14 years, 48.4% female), including 8 CRSsNP, 10 CRSwNP, and 13 controls. CRSsNP and CRSwNP mucosa exhibited decreased CYP27B1 compared with controls (0.0437 [Interquartile range (IQR) 0.0999] vs 0.3260 [IQR 2.9384] vs 0.6557 [IQR 1.1005], p = 0.039), whereas CYP24A1 was upregulated (0.8522 [IQR 1.3170] vs 1.2239 [IQR 4.4197] vs 0.1076 [IQR 0.1791], p = 0.025). CYP24A1 was upregulated in both non-eosinophilic CRS and eosinophilic CRS (1.1337 [IQR 2.3790] vs 0.9555 [IQR 3.2811] vs 0.1076 [IQR 0.1791], p = 0.033). Significant correlations were observed between NSS and CYP2R1 ( r = −0.432, p = 0.022), CYP24A1 ( r = 0.420, P = 0.026), and VDR ( r = 0.425, p = 0.024), although no correlations with serum 25(OH)D were observed. Conclusions The local regulation of vitamin D in sinonasal tissue during CRS may be independent of serum 25(OH)D levels. Vitamin D may be dysregulated at multiple levels, with decreased transcription of the metabolic gene CYP27B1 and increased transcription of the catabolic gene CYP24A1 observed. [ABSTRACT FROM AUTHOR]

Background Effective mucus lavage and delivery of topical pharmaceuticals are central to successful management of chronic rhinosinusitis (CRS). The frontal sinus remains difficult to penetrate with topical therapies. This study evaluates the benefit of Draf III frontal dissection compared to traditional Draf IIa for distribution of topical therapies. Methods Fresh human cadaver heads were dissected sequentially with Draf IIa frontal sinusotomy and then Draf III procedures. Each cavity was irrigated with pediatric (120 mL) and adult (240 mL) irrigation bottles with 1/1000 10% fluorescein-labeled free water in 2 fixed positions (vertex and Frankfort horizontal). An endoscope at a fixed position within the frontal sinus recorded frontal sinus and frontal recess penetration. The images then underwent blinded evaluation of fluid distribution scored as 0 to 4 (nasal cavity only, frontal recess, medial one-half, lateral one-half, and lavage). Ordinal distribution score was analyzed with Kendall's tau-b. Results Eight specimens (age 76 ± 11.2 years; 50% female) were assessed. Draf III was superior to Draf IIa in ability to achieve frontal sinus distribution of irrigation (90.6% vs 50.1%, p < 0.001). Vertex head position improved distribution (90.6% vs 50.1%, p < 0.001), was synergistic with Draf III (100% with 87.5% lavage, p < 0.001), but was unable to overcome Draf IIa (81.2% with 25% lavage, p < 0.001). Irrigation volume trended toward improved distribution with larger volume irrigations. Conclusion Successful treatment of sinonasal disease may require postoperative delivery of topical therapies. Draf III frontal sinusotomy achieves superior topical access, and access to the frontal sinus with Draf IIa appears limited, despite large volumes and positioning. [ABSTRACT FROM AUTHOR]

Background Although remodeling changes of the lower airway are well described, similar changes in the upper airway are less well known. Remodeling changes of the upper airway in chronic rhinosinusitis (CRS) relevant to different phenotypes and endotypes and their clinical characteristics are investigated. Methods A cross-sectional study of adult patients with CRS was performed. Mucosal samples were taken during endoscopic sinus surgery (ESS). Histopathological analysis included eosinophil count, eosinophil activation (eosinophilic mucin), and remodeling changes. Mucosal damage was defined as ulceration, edema, and hypertrophic changes. Patient-reported outcomes (PROMs) were assessed using a Nasal Symptom Score (NSS) and Sino-Nasal Outcome Test (SNOT-22). Patients were subgrouped by presence of polyps (CRSwNP/CRSsNP) or tissue eosinophilia (>10/high power field). Subgroup analysis was performed when both eosinophilic chronic rhinosinusitis (eCRS) and eosinophil activation (eCRSwEA) were coexistent. Analysis between subgroups, pathology, and PROMs was also performed. Results A total of 259 patients (age 48.5 ± 15.6 years, 45% female) were recruited; 53% CRSwNP, 51% eCRS. Remodeling changes were present in 85%, higher in both CRSwNP (90%, p = 0.006) and eCRS (91%, p = 0.004). Mucosal damage changes were common in eCRS (ulceration 18%, p = 0.003; edema 98%, p < 0.001; hypertrophic changes 25%, p = 0.007). NSS was worse in CRSwNP compared to CRSsNP (2.84 ± 1.1 vs 2.29 ± 1.1, p < 0.001) and eCRSwEA (2.95 ± 0.16 vs 2.51 ± 0.11, p = 0.04). 'Loss of sense of smell or taste' was worse in patients with evidence of mucosal damage ( p = 0.006). Conclusion Remodeling features are present in CRS. Tissue eosinophilia and evidence of eosinophil activation is closely associated with remodeling features of CRS, associated mucosal damage and clinical symptoms. [ABSTRACT FROM AUTHOR]

Background Nasal polyposis is a common development in chronic rhinosinusitis (CRS), and sinus mucosa and polyp tissue have been used interchangeably in studies investigating CRS. However, potential differences may exist between these 2 tissue types, which have not been entirely characterized. Methods A cross-sectional study of CRS with nasal polyposis (CRSwNP) patients undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies and corresponding polyp tissue were obtained from the same sinus cavity via flow cytometry, single-cell suspensions identified type 2 innate lymphoid cells (ILC2s), CD4 and CD8 T cells, activated CD4 and CD8 T cells, plasma cells, plasmacytoid dendritic cells (pDCs), regulatory T cells, T follicular helper cells, B cells, and immunoglobulin A (IgA)+ and IgG+ B cells. Cells were measured as a percentage of CD45+ cells. Paired nonparametric comparisons between sinus and polyp tissue were performed. Results Ten patients (50% female; age 48 ± 16 years) were recruited. Significantly elevated ILC2 levels were found in polyp tissue compared to sinus mucosa (0.12 [0.07 to 0.23] vs 0.07 [0.04 to 0.16], p = 0.02), as well as plasma cells (2.25 [0.84 to 3.68] vs 1.18 [0.74 to 2.41], p = 0.01); pDCs (0.15 [0.12 to 0.50[ vs 0.04 [0.02 to 0.17], p = 0.03); activated CD8 T cells (29.22 [17.60 to 41.43] vs 16.32 [10.07 to 36.16], p = 0.04) and IgG+ B cells (6.96 [0.06 to 11.82] vs 1.51 [0.38 to 5.13], p = 0.04). Other cell populations showed no significant differences. Conclusion Polyps have a similar cellular composition to that of mucosa. Higher levels of ILC2s, plasma cells, pDCs, activated CD8 T cells, and IgG+ B cells in polyp tissue may be reflective of cell populations driving nasal polyp development. The cellular machinery of CRS is present in polyps and representative of the disease process. This pilot study strongly suggests that a larger study would provide significant insights into the relationship of sinus mucosa to pathogenesis of nasal polyps. [ABSTRACT FROM AUTHOR]

Background The histological features of osteitis in chronic rhinosinusitis (CRS) in animal studies induced by bacterial inoculation into maxillary sinuses revealed inflammatory involvement of the underlying bone matrix and/or the Haversian system; however, human studies do not mention these findings. The objective of this study was to investigate the inflammatory characterization of osteitis in CRS. Method A prospective study of primary CRS patients undergoing sinus surgery was conducted (August 2012 to April 2013). Bone-mucosa samples were taken from a predetermined site that correlated to a computed tomography location. Radiological bone thickness was measured. A blinded histopathological assessment included inflammatory infiltrate of bone, periosteal reaction, presence of osteoblasts or osteoclasts, fibrosis, and the percentage of new woven bone to total bone thickness, together with an overall opinion of whether neo-osteogenesis was present. Results Twenty-two primary CRS patients (age 45.8 ± 15.6 years; 59.1% female) were recruited. CRS with polyps accounted for 59.1% of patients. The bony thickness measured radiologically was a median 1.72 (interquartile range [IQR], 2.38; range, 0.3-12.14) mm. No samples (0%) had evidence of inflammatory infiltrate of bone; 90.9% had both osteoblasts present and new woven bone formation. Woven bone was greater with periosteal reaction (80.83% ± 9.25% vs. 47.50% ± 29.37%; p = 0.006), greater with osteoclasts present (80.00% ± 12.58% vs 59.00% ± 28.52%; p = 0.03), and greater when fibrosis was present (69.75% ± 24.14% vs 25.00% ± 7.07%; p = 0.003). Conclusion Most primary CRS patients demonstrated evidence of new woven bone formation. True 'osteitis' with inflammatory infiltrate of the bone was not observed. 'Osteitis' is likely a process of neo-osteogenesis and bone remodeling, rather than bone inflammation in primary CRS. [ABSTRACT FROM AUTHOR]

Background The influence of the microbial community on inflammatory subtype in chronic rhinosinusitis (CRS) has been proposed. Superantigen mechanisms potentially create a T helper 2 (Th-2)/eosinophilic dominated inflammation as a product of local flora rather than an intrinsic mucosal process. The associations between culturable bacteria and the histopathology and clinical features of CRS patients are described. Methods A cross-sectional study involving patients with CRS undergoing surgery was undertaken. Middle meatal swabs were performed at surgery for microbiological evaluation. Mucosal biopsies were taken and a blinded histopathological profile was performed. Disease specific quality of life and nasal symptom scores were recorded. The presence of culturable organisms and particular pathogens were compared with histopathology and clinical outcomes. Results A total of 95 patients were assessed (48.4% female, mean age 45.6 ± 14.0 years), of which 47.3% had a culturable organism. Tissue eosinophilia (>10/high-power field [HPF]) was found in 46.1% of these patients and 30.3% had neutrophilic infiltrate, with the presence of neither Gram-positive organisms, Gram-negative organisms, nor species correlating to pathology subtype. A culturable pathogen was a predictor of subepithelial fibrosis (χ2 = 6.36, p = 0.04) and Gram-negative bacteria had the strongest association (χ2 = 18.82, p < 0.01). There were no other significant associations with other clinical outcomes. Conclusion The culturable bacterial community has little impact on histopathology in CRS. While more sensitive tests may detect bacteria in the sinuses, the impact of the simple 'culturable' bacteria on the underlying pathologic process is limited. Changes, such as subepithelial fibrosis, suggest colonization may lead to undesirable local mucosal damage and remodeling. [ABSTRACT FROM AUTHOR]

Background Osteitic bone is a feature of chronic rhinosinusitis (CRS), potentially playing a role in pathogenesis. Although seen after previous endoscopic sinus surgery (ESS), it is also a de novo feature in patients without prior interventions. In these patients, osteitis is associated with high tissue and serum eosinophilia. However, the impact of osteitis on prognosis is unclear. This study investigates the clinical and endoscopic outcomes between patients with and without osteitis after primary ESS. Methods A prospective study of a cohort of previously unoperated patients with CRS undergoing ESS was performed. The sinuses were scored radiologically for osteitis using the Global Osteitis Score (GOS) and Kennedy Osteitis Score (KOS) preoperatively and were also scored dichotomously for the presence or absence of osteitis. Disease-specific quality of life (22-item Sino-Nasal Outcomes Test [SNOT-22]), nasal symptom score (NSS), endoscopic score (Lund-Kennedy), and clinical outcomes-including oral steroid use, frequency of nasal steroid irrigation, and infective exacerbations-were collected at baseline and 1 year postsurgery. The presence and extent of osteitis was assessed relative to clinical outcome. Results Fifty-three patients were included (41.5% female, age 47.4 ± 13.8 years), 42.9% of which had radiologic osteitis. There was no significant association between the presence or severity of osteitis at the time of surgery and SNOT-22, NSS, or endoscopy scores at 12 months postsurgery. However, the presence of osteitis was associated with the need for a course of oral steroid postsurgery (odds ratio [OR]=4.17; p = 0.026). High tissue eosinophilia could not predict this alone ( p = 0.55). There was no significant relationship between osteitis and the frequency of steroid irrigations or infective exacerbations. Conclusion Osteitis in CRS is associated with the degree of eosinophilia and as a independent process it was associated with the need for a course of systemic corticosteroid over a 12-month period, but did it not affect overall disease control. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is a heterogeneous disease defined by epithelial inflammation. The link between measures of traditional disease severity and markers of epithelial inflammation is poorly understood as prior research has focused on presence of polyps or degree of eosinophilia. The expression of 3 epithelial derived cytokines implicated in initiation of T-helper 2 (Th2) inflammation and an eosinophil chemoattractant were compared with clinical measures used in CRS. Methods Sinus mucosal samples from CRS patients undergoing sinus surgery were analyzed for interleukin-25 (IL-25), IL-33, thymic stromal lymphopoietin (TSLP), and eotaxin-3 messenger RNA (mRNA) expression by quantitative polymerase chain reaction (PCR). Tumor patients undergoing surgery transnasally with normal sinus mucosa were controls. Gene expression was compared with symptom, radiology, and endoscopy scores, serological markers, presence of reactive airways disease (RAD), and atopy. Results Thirty-seven patients (38% female, mean age 48 ± 15 years), 12 CRS with nasal polyps (CRSwNP), 18 CRS without nasal polyps (CRSsNP), and 7 controls were recruited. CRSwNP phenotype predicted elevated IL-25, IL-33, and eotaxin-3 levels. Increased eotaxin-3 correlated with poorer computed tomography (CT) ( p = 0.004) and endoscopic scores ( p = 0.049). Increased IL-25 correlated with poorer CT scores ( p = 0.012) and raised serum eosinophils ( p = 0.006). No associations with RAD, atopy, and symptom measures were found. No associations for IL-33 and TSLP were found. Conclusion Inflammatory mediators of the epithelium in CRS has some correlation with traditional measures of disease burden. Certain epithelial profiles may predict highly dysfunctional epithelial barriers and prospective evaluation of the clinical outcomes from interventions is required. Future endotyping of the epithelium in CRS may be able to provide prognostic information. [ABSTRACT FROM AUTHOR]