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Background: Biologic therapy targeting type 2 chronic rhinosinusitis with 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: A total of 37 patients were 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 × 10 9 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 × 10 9 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 × 10 9 cells/L predicts for poor response to current biologic therapy., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Key Points: Culturable bacterial colonization is similar between type 2 CRS phenotypes Staphylococcus aureus coinfection is similar between eosinophilic CRS and CCAD Patients with CCAD were younger, consistent with current knowledge of the disease., (© 2023 ARS-AAOA, LLC.)

Background: Prognostic implications of mucosal remodeling in chronic rhinosinusitis (CRS) remain unclear. Remodeling of respiratory mucosa in asthma is associated with greater medication use and decreased function. This study investigates the implications of mucosal remodeling on long-term clinical outcomes in patients with CRS., Methods: A case-control study of adult patients with CRS undergoing endoscopic sinus surgery (ESS) was performed. Mucosal remodeling was defined by squamous metaplasia, subepithelial fibrosis, and/or basement membrane thickening. The presence of remodeling changes were assessed relative to clinical and treatment outcomes at a minimum of 12 months postoperatively. Clinical outcomes were assessed at baseline and 12 months using a Nasal Symptom Score (NSS) and 22-item Sino-Nasal Outcome Test (SNOT-22). Treatment outcomes were assessed by oral corticosteroid usage (burst/continuous), topical corticosteroid irrigation frequency, and further surgical intervention., Results: A total of 110 patients (48.73 ± 14.75 years, 48.2% female) were assessed. Significant improvements where seen for the entire population, in both NSS (2.64 ± 1.06 to 1.34 ± 1.08, p < 0.001) and SNOT-22 (2.05 ± 0.96 to 1.06 ± 0.79, p < 0.001). Patients with remodeling (n = 88) were younger (47.2 ± 14.8 vs 54.7 ± 13.5 years, p = 0.03), but had similar symptom scores. Remodeling was seen in CRS with nasal polyposis (CRSwNP) (54.5%) and eosinophilic chronic rhinosinusitis (eCRS) (59.8%). Symptom improvement at 12 months was similar between remodeled and non-remodeled groups (NSS: Δ1.34 ± 1.20 vs Δ1.12 ± 1.31, p = 0.395; SNOT-22: Δ1.05 ± 0.91 vs Δ0.73 ± 0.95, p = 0.124); however, patients with remodeling had greater corticosteroid irrigation frequency (64.0% vs 31.6% daily use, Kendall's tau-b p = 0.004)., Conclusion: Established mucosal remodeling predicts a greater reliance on topical therapies to reach similar clinical endpoints as those without remodeling., (© 2016 ARS-AAOA, LLC.)

Background: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS)., Methods: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus., Results: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS., Conclusion: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed., (© 2016 ARS-AAOA, LLC.)

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., (© 2014 ARS-AAOA, LLC.)

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., (© 2014 ARS-AAOA, LLC.)

Background: Published randomized controlled trials (RCTs) on the efficacy of intranasal corticosteroid (INCS) in chronic rhinosinusitis (CRS) use either nasal delivery (nasal drop or nasal spray) or sinus delivery (sinus catheter or sinus irrigation) in patients with or without sinus surgery. This influences topical drug delivery and distribution. The effect of these factors on the published results of RCTs is assessed. This systematic review explores the strength of evidence supporting the influence of sinus surgery and delivery methods on the effectiveness of topical steroids in studies for CRS with meta-analyses., Methods: A systematic review was conducted of RCTs comparing INCS with either placebo or no intervention for treating CRS. Data were extracted for meta-analysis and subgroup analyses by sinus surgery status and topical delivery methods., Results: Forty-eight studies (3961 patients) met the inclusion criteria. INCS improved overall symptoms (standardized mean difference [SMD], -0.49; p < 0.00001) and the proportion of responders (risk ratio [RR], 0.59; p < 0.00001) compared with placebo. It decreased nasal polyp size with a greater proportion of responders (RR, 0.48; p < 0.00001) and prevented polyp recurrence (RR, 0.59; p = 0.0004) compared with placebo. Reduction of polyp size was greater in patients with sinus surgery (RR, 0.31; 95% confidence interval [CI], 0.20, 0.48) than those without (RR, 0.61; 95% CI, 0.46, 0.81; p = 0.009). Greater symptom improvement occurred when sinus delivery methods (SMD, -1.32; 95% CI, -2.26, -0.38) were compared with nasal delivery methods (SMD, -0.38; 95% CI, -0.55, -0.22; p < 0.00001)., Conclusion: INCS is effective for CRS. Prior sinus surgery and direct sinus delivery enhance the effectiveness of INCS in CRS.

Background: Endoscopic sinus surgery (ESS) is the surgical standard treatment for chronic rhinitis/rhinosinusitis and nasal polyposis. There is a reported complication rate of 5-10% associated with this type of surgery. Simulation has been advocated as a means to improve surgical training and minimize the rates of complication and medical error. This study aimed to show how a virtual reality ESS simulator was developed, with particular emphasis on achieving satisfactory photorealism and surgical verisimilitude., Methods: Sinus computed tomography scans were processed to create a triangle-based three-dimensional mesh model; this was incorporated into a spring-damper model of thousands of interconnected nodes, which is allowed to deform in response to user interactions. Dual haptic handpiece devices were programmed to simulate an endoscope and various surgical instruments. Textures and lighting effects were added to the mesh model to provide an accurate representation of the surgical field. Effects such as vasoconstriction in response to "virtual" decongestant were added., Results: The final simulated endoscopic view of the sinuses accurately simulates the moist and glossy appearance of the sinuses. The interactive tissue simulation system enables the user to interactively cut and remove tissue while receiving accurate haptic feedback. A working prototype of the simulator has been developed that leverages recent advances in computer hardware to deliver a realistic user experience, both visually and haptically., Conclusion: This new computer-based training tool for practicing ESS provides a risk-free environment for surgical trainees to practice and develop core skills. The novel use of customized precision force feedback (haptic) devices enables trainees to use movements during training that closely mimic those used during the actual procedure, which we anticipate will improve learning, retention, and recall.

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., (© 2013 ARS-AAOA, LLC.)

Background: Tissue eosinophilia in chronic rhinosinusitis (CRS) is a marker of inflammatory disorders recalcitrant to surgical intervention. Eosinophilic chronic rhinosinusitis (ECRS) is traditionally associated with asthma, polyps, aspirin sensitivity, high serum eosinophilia, and elevated immunoglobulin E (IgE). However, patients with ECRS may not present with these associations and there is a need to establish other surrogate markers. The objective of the study was to determine the associations between the histopathology, serology, and clinical characteristics in CRS patients., Methods: A cross-sectional study was undertaken of CRS patients undergoing surgery. Tissue eosinophilia and other pathological features were compared to traditional surrogate features of ECRS, as well as to symptoms, and to radiologic and endoscopic scores., Results: A total of 51 patients were assessed (47% female, mean age 46.6 ± 4.1 years). High tissue eosinophilia (>10 per high-power field [HPF]) was more prominent in polyps (84%) (χ(2) = 25.76; p < 0.01) but was also seen in nonpolyp patients (19%). Asthma was not associated with high tissue eosinophilia (p = 0.60), with 43% of nonasthmatics demonstrating high tissue eosinophilia. Serum eosinophilia predicted high tissue eosinophilia at >0.30 × 10(9)/L or 4.4% of leukocytes (sensitivity 52%, specificity 87%, receiver operating characteristic [ROC] p = 0.001), with low negative predictive value. Serum IgE was nonpredictive (p = 0.08)., Conclusion: The diagnosis of ECRS has unique prognostic implications. Traditional features of the ECRS phenotype are not necessarily reliable markers for the presence of tissue eosinophilia. Serum eosinophilia may be a good surrogate marker of tissue eosinophilia but of limited use. The routine use of structured histopathology reporting in CRS is suggested, to allow for the diagnosis of ECRS and to identify other prognostic markers., (Copyright © 2012 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.)

Objectives/hypothesis: Drilling in modified endoscopic Lothrop procedure (MELP) is traditionally described as commencing from the frontal recess (FR). This is challenging when the FR is involved by tumor, inflammatory disease, or scarring. The outside-in MELP, where the limits of the sinusotomy are first defined and the FR is addressed last, is described., Study Design: Case-control study., Methods: Patients undergoing MELP, using the standard or outside-in approach, for inflammatory disease or endoscopic skull base surgery were assessed. Data were collected on demographics, disease characteristics, and FR involvement. Operative time was calculated from intraoperative video recording. Time points recorded were times to frontal sinus and recess connected for outside-in MELP and completion of Lothrop cavity for both groups. Perioperative complications (infection, skin breach or contusion, surgical emphysema, orbital bleeding, cerebrospinal fluid leak, and intracranial complications) were recorded., Results: Thirty patients (67% female) with a mean age ± standard deviation of 56.0 ± 10.8 years underwent MELP (24 outside-in, six standard). Time for Lothrop completion was shorter for outside-in MELP (30.60 ± 14.10 minutes vs. 69.66 ± 64.52 minutes, P = .002). Among outside-in MELP, mean time to frontal sinus floor discovery was 8.41 ± 6.29 minutes, to recess connected 26.50 ± 12.45 minutes, and were similar regardless of pathology. The time for Lothrop cavity completion was shorter for tumor cases (24.63 ± 6.49 minutes) than for chronic rhinosinusitis without polyps (35.87 ± 20.18 minutes) and chronic rhinosinusitis with polyps (34.62 ± 11.56 minutes) (P = .05). One patient had skin edema. No other complications were recorded., Conclusions: The outside-in MELP is technically feasible and safe. Its advantage is a wide approach to the frontal sinus with development of the Lothrop cavity en route resulting in short predictable operative times. Defining the limits of the dissection early provides a robust and efficient approach., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Background: Topical corticosteroid is used as part of a comprehensive medical treatment for chronic rhinosinusitis (CRS) without polyps. Nevertheless, there is insufficient evidence to show a clear overall benefit. Trials studying the efficacy of topical corticosteroid use various delivery methods in patients who have or have not had sinus surgery, which directly impacts on topical delivery and distribution., Objectives: To assess the effects of topical steroid in patients with CRS without nasal polyps and perform a meta-analysis of symptom improvement data, including subgroup analysis by sinus surgery status and topical delivery methods., Search Strategy: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 9 July 2010., Selection Criteria: All randomised trials in which a topically administered corticosteroid was compared with either a placebo, no treatment or alternative topically administered corticosteroid for the treatment of CRS without polyps in patients of any age., Data Collection and Analysis: Two authors reviewed the search results and selected trials meeting the eligibility criteria, obtaining full texts and contacting authors where necessary. We documented our justification for the exclusion of studies. Two authors extracted data using a pre-determined standardised data form., Main Results: Ten studies (590 patients) met the inclusion criteria. The trials were of low (six trials) and medium (four trials) risk of bias. The primary outcome was sino-nasal symptoms. When compared to placebo, topical steroid improved symptom scores (standardised mean difference -0.37; 95% confidence interval (CI) -0.60 to -0.13, P = 0.002; five trials, n = 286) and had a greater proportion of responders (risk ratio 1.69; 95% CI 1.21 to 2.37, P = 0.002; four trials, n = 263). With a limited number of studies, the subgroup analyses of patients who had received sinus surgery versus those who had not was not significant (P = 0.35). Subgroup analyses by topical delivery method revealed more benefit when steroid was administered directly to the sinuses than with simple nasal delivery (P = 0.04). There were no differences between groups for quality of life and adverse events., Authors' Conclusions: Topical steroid is a beneficial treatment for CRS without polyps and the adverse effects are minor. It may be included in a comprehensive treatment of CRS without polyps. Direct delivery of steroid to the sinuses may bring more beneficial effect. Further studies comparing different topical drug delivery methods to the sinuses, with appropriate treatment duration (longer than 12 weeks), are required.

Background: Monoclonal antibody therapies have a growing role in treating refractory airway disease. Objective: The review aimed to summarize the response of respiratory mucosa to monoclonal antibody treatments in inflammatory airway conditions. Design: We conducted a systematic review including risk of bias assessment. Data sources: MEDLINE, EMBASE and PubMed from 1 January 2000 to 16 November 2019 were searched. Eligibility criteria: Eligible studies assessed the immunological and histological response of airway mucosa to monoclonal antibody therapy compared with baseline or a comparison group in patients with respiratory diseases (asthma, chronic rhinosinusitis and allergic rhinitis). Any prospective interventional studies, including randomized controlled trials (RCTs) and single‐arm trials, were eligible. Results: There were 4195 articles screened, and full‐text analysis produced n = 11 studies with extractable data. Nine were RCTs, and two were single‐arm trials. These studies focused on asthma (n = 9 articles), chronic rhinosinusitis (n = 1) and allergic rhinitis (n = 1). Five monoclonal antibody drugs were assessed (omalizumab, mepolizumab, dupilumab, benralizumab and tralokinumab). Risk of bias was low (n = 6) or unclear (n = 3) in the RCTs and moderate in the single‐arm trials. Omalizumab reduced the mucosal concentration of its target, IgE. Dupilumab reduced the concentration of one of its targets, IL‐13, but not IL‐4. Omalizumab, mepolizumab and benralizumab reduced tissue eosinophil cell density. Dupilumab decreased mucosal eosinophil granule proteins. Tralokinumab did not affect airway mucosa. Conclusions: Knowledge of the expected biological response of monoclonal antibody therapy on biomarkers in disease tissue provides an important supplement to data about clinical outcomes. An understanding of the biological effect is essential to identify likely responders, reasons for treatment failure and necessary adjustments to monoclonal antibody treatment. Further investigation into the effect of monoclonal antibody therapy on disease mucosa and more precise endotyping are required to move closer to achieving personalized medicine. [ABSTRACT FROM AUTHOR]

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. [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]

Background Osteitis is a feature of chronic rhinosinusitis (CRS) and often associated with recalcitrant disease. Radiological characteristics of osteitic sinus changes are commonly reported in practice but the clinical and pathologic significance is poorly defined. The objective of this study was to correlate the Kennedy Osteitis Score (KOS) to clinico-histologic features of CRS. Methods A cross-sectional study of CRS patients undergoing sinus surgery was conducted. Osteitis was scored radiologically using the KOS. Associations between osteitis and histopathology, symptoms, 22-item Sino-Nasal Outcomes Test (SNOT-22), endoscopy, computed tomography (CT) mucosal score, and seromarkers were assessed. Interobserver correlation coefficient was performed. Additionally, the KOS was correlated to an alternate Global Osteitis Score. Results A total of 88 patients were assessed (45.5% female, age 50.3 ± 13.6 years); 45 (51.1%) patients had osteitis. Patients with KOS >0, had greater endoscopy score (6.1 ± 2.9 vs 4.4 ± 3.6, p = 0.03) and CT score (14.0 ± 6.0 vs 10.1 ± 5.7, p < 0.01) than those without osteitis. There was no difference in symptom score (2.4 ± 1.3 vs 2.4 ± 1.1, p = 0.89) and SNOT-22 (2.0 ± 1.0 vs 1.9 ± 1.1, p = 0.56) in patients with and without osteitis. KOS was higher in patients with tissue eosinophilia >10/high-power field (HPF) (median 3.0 [IQR, 1.0-5.3] vs 0.0 [0.0-4.0], p = 0.03) and serum eosinophilia >0.3 × 109/L (4.0 [2.0-7.0] vs 1.0 [0.0-4.0], p < 0.01). Importantly, this was also true for those without prior surgery. The interobserver correlation coefficient was good ( R = 0.86, p < 0.001). There was a significant correlation between the KOS and the Global Osteitis Score ( R = 0.93, p < 0.001). Conclusion The KOS is a simple, easy, and reproducible scale in assessing osteitic bones in patients with CRS and can predict measures of severity in eosinophilic rhinosinusitis. [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 Many chronic rhinosinusitis (CRS) treatment regimes revolve around 'one-off' maximal medical therapy (MMT) protocols, and although many patients initially respond, long-term control is unpredictable. The value of imaging, endoscopy, and patient progress after MMT for CRS is assessed. Methods Symptomatic CRS patients with computed tomography (CT)-confirmed disease were recruited at a tertiary rhinology clinic. All patients received at least a 3-week oral prednisone course as part of their MMT. Pretreatment and posttreatment nasal symptoms scores (NSS), quality of life (22-item SinoNasal Outcomes Test [SNOT-22]), and CT (Lund-Mackay [LM]) scores were recorded along with post-MMT endoscopy status. Results A total of 86 patients (38% female, age 46 ± 13 years) met inclusion criteria. Pre-MMT and post-MMT LM scores were 10.9 ± 5.3 and 8.3 ± 5.5 (change 2.6 ± 3.8, p < 0.001). Median follow-up after their initial post-MMT assessment was 6.3 (interquartile range [IQR] 17) months. At initial post-MMT review, 43 (50%) were symptomatic with persistent radiologic disease ('symptomatic CRS'), 12 (14%) were asymptomatic with no radiologic disease ('resolved CRS'), 21 (24%) were asymptomatic with persistent radiologic disease ('asymptomatic CRS'), and 10 (12%) were symptomatic with no radiologic disease ('alternate diagnosis'). Pre-MMT NSS and SNOT-22 were similar among groups. The 'asymptomatic CRS' group had the highest age (52 ± 11 years, p = 0.07). The 'alternate diagnosis' group had the lowest initial LM scores (5.2 ± 2.9, p = 0.001). Of the 'asymptomatic CRS' patients, 43% relapsed between 3 and 23 months (median 6; IQR 4.4 months) post-MMT and 29% eventually underwent surgery. Conclusion Although MMT for CRS achieved symptomatic relief in 38% patients, objective evidence of disease was associated with clinical relapse. The concepts of 'response' to medical therapy and the need to 'control' long-term inflammatory burden need to be balanced. [ABSTRACT FROM AUTHOR]