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Background: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. Objective: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. Methods: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. Results: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τ b = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm2, p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00–6.00] vs 6.00[6.00–6.75], p = 0.015). Other outcomes were similar. Conclusions: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations. [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: Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. Methods: A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. Results: 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = −8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = −2.37, p = 0.02). Conclusion: Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Respiratory epithelium is a key defense against inhaled pathogens. Vitamin D3 (VD) has been suggested to modulate airway inflammation; however, its effect on innate airway defenses, the physical barrier, mucociliary apparatus, and cytokine release remains unclear. Objective: To investigate the outcomes of VD application prior to challenge in an in vitro model of human sinonasal epithelium, through assessment of epithelial transepithelial resistance (TER), cilia beat frequency (CBF), and interleukin (IL)-6 release, and secondarily to determine whether topical VD is beneficial to patients with inflammatory sinonasal pathology. Methods: Primary human sinonasal epithelial cells from patients with eosinophilic chronic rhinosinusitis (eCRS) and healthy controls were cultured in air–liquid interface (ALI). Well-differentiated cultures from each patient were pretreated for 24 hours with 4 different VD doses. Toxicity was quantified at 24 hours in unchallenged ALI by lactate dehydrogenase (LDH) assay. Innate responses were assessed by measuring TER and CBF before and up to 24 hours after house dust mite Dermatophagoides pteronyssinus challenge. IL-6 release was evaluated 24-hour postchallenge. Results: Fifteen patients (53 ± 13.5 years, 60% females, 53% eCRS) representing 120 ALI wells were assessed. VD (0, 25, 50, 150 IU/mL) released less LDH than vehicle, indicating noncytotoxicity (0.15 ± 0.02; 0.15 ± 0.00; 0.14 ± 0.02; 0.11 ± 0.01 vs 0.17 ± 0.03, P =.004). VD increased TER for eCRS wells at 5 minutes (50 IU/mL: Δ6.76 ± 3.93 vs Δ3.87 ± 2.46, P =.04) and 24 hours (50 IU/mL: Δ0.88 ± 0.49 vs Δ0.40 ± 0.42, P =.02; 150 IU/mL: Δ1.06 ± 0.58 vs Δ0.47 ± 0.46, P =.01). CBF increased at 1 hour for eCRS wells (50 IU/mL: Δ0.62 ± 0.14 vs Δ0.41 ± 0.13, P =.001; 150 IU/ml: Δ0.60 ± 0.13 vs Δ0.38 ± 0.11, P <.001). IL-6 release was similar between normal and eCRS wells. Conclusion: Topical VD supplementation in eCRS patients may be beneficial for innate epithelial defenses. VD is noncytotoxic and does not adversely affect the physical barrier, mucociliary apparatus, or IL-6 release. Further studies should clarify its potential as a therapeutic agent. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that intrinsic cell dysfunction leads to dysregulated immune responses to environmental triggers in chronic rhinosinusitis (CRS). Although epidemiological and in vivo studies support this theory, in vitro studies are lacking. Methods: Epithelial cells from human sinonasal mucosa were cultured using an air–liquid interface culture model producing a well-differentiated phenotype. Specimens were characterized as chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyps and healthy control mucosa. Culture wells were exposed to house dust mite (HDM), diesel exhaust particles (DPM), or a combination (HDM + DPM) over 24 hours and responses in the 3 groups compared. Ciliary beat frequency (CBF) and transepithelial electrical resistance (TEER) were measured to assess mucociliary and barrier function, respectively. Interleukin-6 (IL-6) and 33 (IL-33) were measured after 24 hours. Results following challenge testing are expressed as fold change from baseline. Results: Baseline CBF was lower in CRSsNP compared with control (5.27 ± 0.51 Hz vs 5.88 ± 1.22 Hz, P =.003). HDM significantly reduced CBF and TEER in the CRSwNP group compared with its vehicle (CBF: 0.55 ± 0.25 vs 1.03 ± 0.22, P <.001; TEER: 0.54 [0.13] Ω cm2 vs 0.93 [0.5] Ω cm2, P =.001). In CRSwNP and CRSsNP, HDM induced an increase in IL-6 compared with its vehicle (CRSwNP: 81.11 [67.19] pg/mL vs 3.15 [44.64] pg/mL, P =.016; CRSsNP: 321.46 [182.04] pg/mL vs 21.54 [53.93] pg/mL, P =.004). Results are expressed as median (interquartile range) and in IL-33 in CRswNP (84.04 [69.96] pg/mL vs 16.62 [20.19] pg/mL, P =.025). Exposure to DPM did not affect CBF, TEER, and cytokine release in all groups. Conclusion: CRSwNP and CRSsNP cells exhibit altered responses particularly to HDM even after they have been removed from their host and cultured in vitro, suggesting an intrinsic cell dysfunction of the upper airway epithelium. [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]

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. [ABSTRACT FROM AUTHOR]

Background Eosinophilic chronic rhinosinusitis (eCRS) is linked with skewed T-helper 2 or immunoglobulin E (IgE)-mediated allergic responses, with differing diagnosis, prognosis, and management to non-eCRS. Objective The association between biomarkers and eCRS was investigated to assess the predictors of eCRS. Methods A cross-sectional study of adult patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery was conducted. eCRS was defined by histopathological assessment showing >10 eosinophils/high-power field on sinus mucosal biopsy. Blood tests were performed preoperatively and assessed for a full blood count including eosinophils and a white cell count (WCC) as well as biochemical markers of inflammation and atopy including Immunoglobulin E (IgE), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ImmunoCAP testing for serum-specific IgE. Comparisons between eCRS and non-eCRS patients were performed. Results 345 patients (48.1% female, age 48.72 ± 15.06 years) were recruited, with 206 (59.7%) identified as eCRS, 41% with asthma and 47% CRS with nasal polyps. eCRS patients were more likely to have asthma (P < .01) and nasal polyps (P < .01). Blood eosinophils were significantly elevated in eCRS (0.42±0.34 vs 0.17±0.13 × 109/L, P < .01) as were eosinophils as a ratio of WCC (6.21 ± 4.48 vs 2.55 ± 1.84, P < .01). ESR was decreased when compared with non-eCRS (8.1±7.87 vs 10.65±11.91, P = .03). Receiver operating characteristic curve analysis predicted high tissue eosinophilia at blood eosinophil levels above 0.24 × 109/L (sensitivity 70.9%, specificity 78.4%, area under the curve [AUC]: 0.792, P < .01). eCRS was predicted at eosinophil above 4.27% of total WCC (sensitivity 64.1%, specificity 88.5%, AUC 0.797; P < .01; positive predictive value 89.2%, negative predictive value 62.4%, positive likelihood ratio 5.57, and diagnostic odds ratio 13.71). There was no significant association among WCC, CRP, IgE, or ImmunoCAP testing. Conclusion eCRS is associated with elevated blood eosinophils (>0.24 × 109/L), eosinophil ratio (>4.27% of total WCC), and lower ESR when compared with non-eCRS. [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: Eosinophilic chronic rhinosinusitis (eCRS) is an inflammatory endotype of CRS. Contemporary treatment includes creation of a "neo‐sinus" cavity and postoperative corticosteroid irrigations. Not all patients gain control with local therapy. This study aims to determine, in patients with polyp recurrence, the most common sinuses involved. Methods: A prospective case‐series was conducted on consecutive adult (≥18 years) post‐FESS eCRS patients followed for a minimum of 12 months. All patients had a neo‐sinus cavity created surgically and used corticosteroid irrigations daily for 3‐6 months, then tapered to disease control. Sinus cavities were assessed by endoscopy on last follow‐up. Polyp recurrence was defined as a score of 5 or 6 in the MLMES in ≥3 sinus cavities. Patient‐reported outcomes based on SNOT22 and NSS, frequency of corticosteroid irrigations, and courses of systemic antibiotics and corticosteroid were collected. The pattern of sinus involvement was analyzed. Result: A total of 342 sinus cavities were assessed (mean ± standard deviation, 54.9 ± 13.4 years, 43.2% female). Polyp recurrence occurred in 4.3% (6.4% of patients, n = 7 unilateral) of sinus cavities. Frontal and ethmoid sinus cavities were most affected in those with polyp recurrence, compared to the maxilla and sphenoid (100% vs 100% vs 53% vs 53%, p < 0.01). Although those patients with polyp recurrence utilized more systemic corticosteroids courses per year (0.4 ± 0.4 vs 0.1 ± 0.3, p < 0.01), the use of corticosteroid irrigations was similar (% >4/week; 66.7% vs 48.9%, p = 0.13). Prior surgery was more common in patients with polyp recurrence (86.7% vs 53.5%, p = 0.01). Conclusion: The frontal and ethmoid sinuses were most affected in those patients with polyp recurrence. Whether the disease is more active in this location or topical therapy has limited access requires further evaluation. [ABSTRACT FROM AUTHOR]