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Patients with chronic rhinosinusitis (CRS) may have persistence of polyps, discharge, or edema after endoscopic sinus surgery (ESS). Inflammation in CRS can be classified into three endotypes, with the presence of polyps associated with the type 2 endotype. Here, we evaluate the endotypic underpinnings of discharge or edema without polyps after ESS.At a visit 6-12 months post ESS, patients underwent endoscopy and completed the CRS-PRO and SNOT-22. Luminex analysis of middle meatal mucus obtained at that visit was performed for IFN-γ, ECP, and IL-17a. Type 1, 2, and 3 endotypes were defined as greater than the 90th percentile expression of each marker, respectively, in controls. Wilcoxon rank-sum and chi-squared tests were used to compare cytokine levels and endotype prevalence between those with and without endoscopic findings.A total of 122 CRS patients completed a clinical exam (median: 8.2 months post ESS). Of the 122 patients, 107 did not have polyps on endoscopy. Of these 107 patients, 48 had discharge, 44 had edema, and 46 had neither discharge nor edema. Compared with those patients without any findings, patients with discharge or edema reported significantly worse severity as measured by CRS-PRO (10.5 vs. 7.0, p = 0.009; 12.0 vs. 7.0, p 0.001; respectively), and had higher post-ESS IFN-γ, ECP, and IL-17a. Patients with discharge had higher prevalence of only T1 and T3 endotypes, while patients with edema had higher prevalence of only the T3 endotype.Post-ESS discharge or edema in the absence of polyps was associated with higher patient-reported outcome severity and was more strongly associated with type 1 or 3 inflammation.

Mometasone-eluting stents (MES) have demonstrated improvement in short-term endoscopic outcomes and reduce short- to medium-term rescue interventions. Their effect on the local inflammatory environment, longer-term patient-reported outcomes, and radiographic severity have not been studied.Middle meatal mucus and validated measures of disease severity were collected before and 6 to 12 months after endoscopic surgery in 52 patients with chronic rhinosinusitis with nasal polyps (CRSwNPs). Operative findings, type 2 mediator concentrations, intraoperative variables, and disease severity measures were compared between those who did and those who did not receive intraoperative frontal MES.A total of 52 patients with CRSwNPs were studied; 33 received frontal MES and were compared with 19 who did not. Pre-endoscopic sinus surgery (ESS) middle meatus (MM) interleukin (IL) 13 and eosinophil cationic protein (ECP) were higher in the stented group (p 0.05), but pre-ESS clinical measures of disease severity were similar as were surgical extent and post-ESS medical management. Intraoperative eosinophilic mucin was more frequent in the stented group (58% vs 11%, p = 0.001). IL-5 (p 0.05) and IL-13 (p 0.001) decreased post-ESS in the stented group, but this was not observed in the nonstented group. Post-ESS IL-4 and IL-13 were higher in the nonstented vs stented group (p 0.05 for both).Although patients who received intraoperative frontal MES had significantly higher pre-ESS MM IL-13 and ECP, patients who received frontal MES had lower concentrations of IL-4 and IL-13 than those who did not at a median of 8 months post-ESS. However, these changes did not correspond to significantly different measures of symptomatic or radiographic disease severity.

Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti-phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS).To compare APA levels (anti-cardiolipin, anti-phosphatidylethanolamine (anti-PE), and anti-βPatient specimens were assayed for APA IgG, anti-dsDNA IgG and thrombin-anti-thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical-mechanical coagulometer.Anti-cardiolipin IgG in NP was 5-fold higher than control tissue (p .0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 µg/mL (36.7 s vs. 33.8 s, p = .024) and 600 µg/mL (40.9 s vs. 34.7 s, p = .0037). Anti-PE IgG antibodies were increased in NP (p = .027), but anti-B2GP IgG was not significantly higher (p = .084). All APAs correlated with anti-dsDNA IgG levels, which were also elevated (R = .77, .71 and .54, respectively, for anti-cardiolipin, anti-PE, and anti-B2GP; all p .001), but only anti-cardiolipin (R = .50, p = .0185) and anti-PE (R = 0.45, p = .037) correlated with TaT complex levels.APA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti-coagulant activity similar to those observed in anti-phospholipid syndrome, suggesting that they may have pro-coagulant effects in polyp tissue.

Objectives Chronic rhinosinusitis (CRS) affects approximately 12% of the population and leads to increased health care utilization and indirect costs exceeding $20 billion annually in the United States. The Lund‐Mackay score (LMS) measures radiographic disease severity for CRS but poorly correlates with symptom scores. The association between LMS and health care utilization in CRS patients has not yet been investigated. The study aimed to assess the association between health care utilization and CRS radiographic severity using LMS. Methods CRS patients enrolled in a clinical registry were evaluated. Nasal endoscopy findings and LMS were recorded for patients with sinus CT imaging. Patient symptom scores, demographic characteristics, and health care utilization measures were collected. The relationship between these factors and LMS was examined. Results A total of 556 patients met inclusion criteria. Mean age was 45.3 years, 53.4% were male, and 41.7% had nasal polyps. There was no difference in sex, smoking history, 22‐item Sino‐nasal Outcome Test scores, or past medical history factors between patients with high (≥8, n = 410) and low (

Background: Acute exacerbations of chronic rhinosinusitis (AECRS) are associated with significant morbidity and decreased quality of life. There are sparse data assessing the real-world impact of biologics on AECRS. Objectives: We sought to determine the impact of type 2‐targeting biologics on the frequency of medication use for AECRS episodes. Methods: Antibiotic and/or systemic corticosteroid courses for AECRS were identified in a retrospective study from November 2015 to February 2020, at a single academic health system. The estimated yearly rates for antibiotic and corticosteroid courses were evaluated before and after initiation of type 2 biologics. Results: One-hundred and sixty-five patients with chronic rhinosinusitis (CRS) had received either omalizumab (n = 12), mepolizumab (n = 42), benralizumab (n = 44), dupilumab (n = 61), or reslizumab (n = 6). Seventy percent had CRS with nasal polyps, and 30% had CRS without nasal polyps. All the patients had asthma. When all the biologics were combined, the estimated yearly rate for antibiotics for AECRS decreased from 1.34 (95% confidence interval [CI], 1.12‐1.59) to 0.68 (95% CI, 0.52‐0.88) with biologic use (49% reduction, p < 0.001). Those with frequent AECRS (three or more courses of antibiotics in the 1 year before biologic use) had a larger degree of reduction, with an estimated yearly rate of 4.15 (95% CI, 3.79‐4.55) to 1.58 (95% CI, 1.06‐2.35) with biologic use (n = 27; 62% reduction; p < 0.001). Within the total cohort, the estimated yearly rate for systemic corticosteroids for AECRS decreased from 1.69 (95% CI, 1.42‐2.02) to 0.68 (95% CI, 0.53‐0.88) with biologic use (60% reduction; p < 0.001). Conclusion: Type 2‐targeting biologics reduced medication use for AECRS. This suggested that biologics may be a therapeutic option for patients with frequent AECRS.

BACKGROUND The chronic rhinosinusitis patient-reported outcome (CRS-PRO) measure is a 12-item measure with previously demonstrated validity in chronic rhinosinusitis (CRS) patients receiving medical therapy. This study establishes the factor structure, responsiveness, and convergent validity of the CRS-PRO following endoscopic sinus surgery (ESS). METHODS Northwestern CRS Subject Registry patients had pre-ESS, 3-month (n = 111; CRS without nasal polyps [CRSsNP] = 60, CRS with nasal polyps [CRSwNP] = 51), and 6-month (n = 86; CRSsNP = 47, CRSwNP = 39) post-ESS assessments where patients completed the CRS-PRO, 22-item Sino-Nasal Outcome Test (SNOT-22), and four Patient-Reported Outcomes Measurement (PROM) Information System (PROMIS) short forms (general health measures). Patients had pre-ESS objective testing (endoscopic and radiographic assessment). Factor analysis was conducted using principal axis factoring with varimax rotation on the baseline CRS-PRO. The clinically important difference (CID) was estimated using both distribution-based and anchor-based methods. RESULTS Factor analysis found the CRS-PRO comprised the "rhino-psychologic," "facial discomfort," and "cough" factors, which were responsive to ESS and correlated with the other PROMs. The changes observed in the CRS-PRO at 3 months had strong correlation with the corresponding changes in SNOT-22 (r = 0.792, p < 0.0001) and moderate correlations with changes in PROMIS fatigue and sleep domains. These changes had a very large effect size (Cohen's d 1.44) comparable to the longer SNOT-22 (Cohen's d 1.41) with slightly larger effect sizes observed in CRSwNP compared to CRSsNP patients. Similar convergent validity and responsiveness were observed in the 6-month data. The CRS-PRO CID was estimated to be between 5.0 and 7.5 (midpoint 6.0) using distribution-based and anchor-based methods. CONCLUSION This study demonstrates the validity and responsiveness of the CRS-PRO in subjects receiving ESS.

I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

Purpose of review Adequate visualization during endoscopic sinus surgery (ESS) is one of the most critical aspects of performing well tolerated and successful surgery. The topic of visualization encompasses a broad spectrum of preoperative and intraoperative manoeuvres the surgeon can perform that aid in the understanding of the patient's anatomy and in the delivery of efficient surgical care. Recent findings Preoperative considerations to improve visualization include optimization of haemostasis through management of comorbidities (e.g. hypertension, coagulopathies), medication management (e.g. blood thinners) and systemic versus topical corticosteroids. New technologies allow preoperative visual mapping of surgical plans. Advances in knowledge of intraoperative anaesthesia have encouraged a move toward noninhaled anaesthetics to reduce bleeding. High definition cameras, angled endoscopes, 3D endoscopes and more recently augmented reality, image-guided surgery, and robotic surgery, represent the state of the art for high-quality visualization. Topical interventions, such as epinephrine, tranexamic acid and warm isotonic saline, can help to reduce bleeding and improve the operative field. Surgical manoeuvres, such as polyp debulking, septoplasty, carefully controlled tissue manipulation and a consistent repeatable approach remain fundamental to appropriate intraoperative surgical visualization. Summary This chapter delineates medical, technical and technological means - preoperatively and intraoperatively - to achieve optimized visualization of the surgical field in ESS.

Inverted papillomas (IP) are the most common sinonasal tumor with a tendency for recurrence, potential attachment to the orbit and skull base, and risk of malignant degeneration into squamous cell carcinoma (SCC). While the overall rate of recurrence has decreased with the widespread adoption of high-definition endoscopic optics and advanced surgical tools, there remain challenges in managing tumors that are multiply recurrent or involve vital neurovascular structures. Here, we review the state-of-the-art diagnostic tools for IP and IP-degenerated SCC, contemporary surgical management, and propose a surveillance protocol.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease of the upper airways. AZD1981 is a selective antagonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 and other type 2 cells, including innate lymphoid cells type 2, eosinophils, and basophils.To evaluate the efficacy of AZD1981 in reducing nasal polyp size when added to intranasal corticosteroids in adult patients with CRSwNP.Eighty-one subjects (18-70 years of age) with CRSwNP were recruited and screened for trial eligibility from allergy and otolaryngology clinics from a single tertiary care site between June 2016 and August 2019. Eligible patients were randomized in a double-blind fashion to receive either AZD1981 (n = 22) or placebo (n = 21) orally three times a day for 12 weeks, added to intranasal corticosteroids. The primary endpoint was a change in nasal polyp score (NPS) at 12 weeks. Secondary endpoints included improvement in sinus computed tomography using Lund Mackay scoring, symptoms using visual analog scale, quality of life using Sino Nasal Outcome Test-22, and the Brief Smell Identification Test.Forty-three patients met the inclusion criteria and were enrolled. At 12 weeks, there was no difference in NPS change in the AZD1981 arm (mean 0, standard error 0.34, n = 15) compared with placebo (mean 0.20, standard error 0.36, n = 17); mean difference -0.20 (95% confidence interval: -1.21, 0.81; p = .69). No significant differences were observed for Lund Mackay score, symptoms, quality of life, or smell test. AZD1981 was well tolerated except for one case of hypersensitivity reaction.In patients with CRSwNP, the addition of AZD1981 to intranasal corticosteroids did not change nasal polyp size, radiographic scores, symptoms, or disease-specific quality of life.

The 22-item Sino-Nasal Outcome Test (SNOT-22) and 12-item Patient Reported Outcomes in Chronic Rhinosinusitis (CRS-PRO) instrument are validated patient-reported outcomes measures in CRS. In this study we assess the correlation of these with type 2 (T2) biomarkers before and after endoscopic sinus surgery (ESS).Middle meatal mucus data were collected and the SNOT-22 and CRS-PRO were administered to 123 patients (71 CRS without nasal polyps [CRSsNP], 52 CRS with nasal polyps [CRSwNP]) with CRS before and 6 to 12 months after undergoing ESS. Interleukin (IL)-4, IL-5, IL-13, and eosinophilic cationic protein (ECP) were measured using a multiplexed bead assay and enzyme-linked immunoassay. Pre- and post-ESS SNOT-22 and CRS-PRO were compared with T2 biomarkers.Before ESS neither PROM correlated with any biomarker. After ESS, CRS-PRO showed a correlation with 2 mediators (IL-5 and IL-13: p = 0.012 and 0.003, respectively) compared with none for the SNOT-22. For CRSwNP patients, pre-ESS CRS-PRO and SNOT-22 correlated with IL-4 (p = 0.04 for both). However, after ESS, CRS-PRO correlated with 3 biomarkers (IL-5, IL-13, and ECP: p = 0.02, 0.024, and 0.04, respectively) and SNOT-22 with 2 biomarkers (IL-5 and IL-13: p = 0.038 and 0.02, respectively). There were no significant relationships between any of the T2 biomarkers pre- or post-ESS among patients with CRSsNP. Exploratory analyses of the subdomains showed the SNOT-22 rhinologic and CRS-PRO rhinopsychologic subdomains correlated better with the T2 biomarkers. On individual item analysis, IL-13 correlated significantly post-ESS with 8 of 12 items on the CRS-PRO vs 6 of 22 items on the SNOT-22.The CRS-PRO total score showed a significant correlation with T2 biomarkers especially when assessed post-ESS and among CRSwNP patients.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is well characterized by type 2 (T2) inflammation characterized by eosinophilia in Western countries. However, the presence and the roles of neutrophils in T2 CRSwNP are poorly understood. OBJECTIVE: To clarify accumulation and inflammatory roles of neutrophils in Western CRSwNP. METHODS: Sinonasal tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS, and neutrophil markers were determined by ELISA. The presence of neutrophils in tissue was determined by flow cytometry. The gene expression profiles in neutrophils were determined by RNA-Sequencing. RESULTS: A neutrophil marker elastase was selectively elevated in nasal polyp (NP) tissue whereas eosinophilic cationic protein (an eosinophil marker) was elevated in both uncinate and NP tissues of CRSwNP patients. NLF myeloperoxidase (another neutrophil marker) was also significantly elevated in CRSwNP compared to control patients. Neutrophil markers were more greatly elevated in CRSwNP patients with recurrent disease. Flow cytometric analysis confirmed that neutrophil numbers were significantly elevated in NPs compared to control tissues. RNA-Sequencing analysis found that 344 genes were >3-fold and significantly elevated in NP neutrophils compared to peripheral blood neutrophils. Gene ontology analysis suggested that elevated genes in NP neutrophils were significantly associated with activation. Results suggest that neutrophils are accumulated in T2 NP tissues and that accumulated neutrophils are highly activated and contribute to inflammation in NPs. CONCLUSIONS: Neutrophils may play a heretofore unrecognized meaningful role in the pathogenesis of CRSwNP in western countries and may be considered to be a potentially important therapeutic target in T2 CRSwNP.

Patients with aspirin-exacerbated respiratory disease (AERD) regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells.This study sought to determine whether endogenous retinoids are involved in NP pathophysiology and disease severity in patients with CRSwNP and AERD.NP tissue was collected from patients with AERD or CRSwNP, and concentrations of retinoids and fibrinolysis markers were measured using ELISA. Normal human bronchial epithelial cells were stimulated alone or in combination with RA and IL-13 for 24 hours.This study observed lower retinoid levels in nasal polyps of patients with AERD than those with CRSwNP or healthy controls (P lt; .01). Levels of the fibrin-breakdown product d-dimer were the lowest in AERD polyps (P lt; .01), which is consistent with lower tPA expression (P lt; .01). In vitro, all-trans RA upregulated tPA levels in normal human bronchial epithelial cells by 15-fold and reversed the IL-13-induced attenuation of tPA expression in cultured cells (P lt; .01).RA, a potent inducer of epithelial tPA in vitro, is reduced in tissue from patients with AERD, a finding that may potentially contribute to decreased levels of tPA and fibrinolysis in AERD. RA can induce tPA in epithelial cells and can reverse IL-13-induced tPA suppression in vitro, suggesting the potential utility of RA in treating patients with CRSwNP and/or AERD.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including TH2 cells in NPs. The co-culture of NP-derived ILC2s and TH2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.

BACKGROUND: Chronic rhinosinusitis (CRS) is associated with bronchiectasis; however, this relationship has not been well studied in the United States (US) population. In this work we aimed to determine the prevalence of CRS among patients with bronchiectasis affiliated with a US tertiary medical center and identify which comorbid diseases are associated with the presence of CRS in patients with bronchiectasis. METHODS: This was a retrospective cohort study in which data were obtained from a large database warehouse at a tertiary care center. Patients with bronchiectasis were identified from 2007 to 2017 using diagnosis codes from the the ninth and tenth revisions of the International Classification of Diseases (ICD-9/10) and confirmed by radiographic evidence of bronchiectasis on chest computed tomography (CT) scans. Patients were divided into cohorts based on presence or absence of concomitant CRS. Characteristics analyzed included demographics, comorbidities, peripheral eosinophil counts, and pulmonary function testing. RESULTS: CRS was present in 45% (408 of 900) of patients with bronchiectasis. Females represented a majority of bronchiectasis patients, both with and without CRS (69% and 64%, respectively, p = 0.09). After controlling for demographic factors, asthma (p < 0.01), allergic rhinitis (p

Objectives To explore the degree to which patients undergoing unilateral endoscopic sinus surgery (ESS) experience post-operative contralateral sinonasal symptoms and determine risk factors for contralateral symptomatology following unilateral ESS. Methods Patients who underwent unilateral surgery for chronic rhinosinusitis (CRS) were contacted and asked if they felt symptomatic on the contralateral side at that point in time. Nasal Obstruction Symptom Evaluation (NOSE) scores were obtained based on contralateral symptomatology they recalled at the following time points: pre-ESS, 1 month post-ESS, and 3 months post-ESS. Demographics, contralateral symptomatology, and NOSE scores were compared between those with 2 or fewer sinusotomies versus 3 or more sinusotomies. Results Of the 97 patients included in this study, 24% of patients reported contralateral congestion, a median of 24 months post-ESS, and more than 10% of patients reported other contralateral symptoms including swelling, rhinorrhea, difficulty breathing, and hyposmia post-ESS. Those with 2 or fewer sinusotomies were more likely to feel that they had developed worsened sensation of contralateral sinus swelling ( P = .008). The median amount of time from the participants’ index surgery until the time they were interviewed was 24 months. There were no differences in long-term contralateral symptomatology between those who did and did not have septoplasty (27%). Conclusion Patients who have unilateral ESS for CRS may experience long-term contralateral symptoms. Having a septoplasty did not affect contralateral symptoms.

A 55-year-old woman presented with a 5–6 month history of focal right frontal pressure that was partially relieved with over-the-counter (OTC) analgesics. She had mild issues with nasal congestion and obstruction; however, she denied discolored nasal discharge or significant problems with her sense of smell. She was evaluated for migraines by a neurologist who ordered an MRI, and this MRI revealed a right frontal sinus osseous lesion that was associated with post-obstructive secretions. She had been treated with antibiotics and steroids by her primary care doctor as well as two otolaryngologists. Each otolaryngologist recommended surgery, but recommended a rhinologist perform the procedure.

Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP.We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS.Samples were collected from 135 subjects with CRSwNP, 80 subjects with chronic CRS without nasal polyps (NP), and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex, tissue factor (TF), and TF pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, immunohistochemistry, or immunofluorescence. Heteromeric complexes of TF with activated factor VII (FVII) and TF with activated FVII and FXa were assessed by coimmunoprecipitation and Western blotting.Increased levels of FXa, F1+2, and thrombin-antithrombin complex were detected in NP tissue compared to uncinate tissue from CRS and control subjects. Although free TF protein levels were not increased in NP, immunoprecipitation of TF in NP tissue revealed increased complexes of TF with FVII. Local expression of FVII was detected in sinonasal mucosa, and the ratio of TFPI to FXa was lower in NP tissue.The coagulation cascade is associated with NP compared to control and uncinate tissue from CRS patients, and TF and FVII are produced locally in sinonasal mucosa in patients. TF and FVII can activate the extrinsic coagulation pathway, suggesting that this pathway may activate fibrin deposition in CRSwNP. Reduced formation of the complex of FXa and TFPI in NP may reduce natural suppression of the extrinsic coagulation pathway in CRSwNP.

Chronic rhinosinusitis with nasal polyps is frequently managed with endoscopic sinus surgery (ESS). Prior studies describe individual clinical variables and eosinophil density measures as prognostic for polyp recurrence (PR). However, the relative prognostic significance of these have not been extensively investigated.We sought to evaluate the impact of PR on measures of disease severity post-ESS and quantify the prognostic value of various clinical variables and biomarkers.Ninety-four patients with chronic rhinosinusitis with nasal polyps and prospectively biobanked polyp homogenates at the time of ESS were recruited 2 to 5 years post-ESS. Patients were evaluated with patient-reported outcome measures and endoscopic and radiographic scoring pre- and post-ESS. Biomarkers in polyp homogenates were measured with ELISA and Luminex. Relaxed least absolute shrinkage and selection operator regression optimized predictive clinical, biomarker, and combined models. Model performance was assessed using receiver-operating characteristic curve and random forest analysis.PR was found in 39.4% of patients, despite significant improvements in modified Lund-Mackay (MLM) radiographic and 22-item Sinonasal Outcomes Test scores (both P .0001). PR was significantly associated with worse post-ESS MLM, modified Lund-Kennedy, and 22-item Sinonasal Outcomes Test scores. Relaxed least absolute shrinkage and selection operator identified 2 clinical predictors (area under the curve = 0.79) and 3 biomarkers (area under the curve = 0.78) that were prognostic for PR. When combined, the model incorporating these pre-ESS factors: MLM, asthma, eosinophil cationic protein, anti-double-stranded DNA IgG, and IL-5 improved PR predictive accuracy to area under the curve of 0.89. Random forest analysis identified and validated each of the 5 variables as the strongest predictors of PR.PR had strong associations with patient-reported outcome measures, endoscopic and radiographic severity. A combined model comprised of eosinophil cationic protein, IL-5, pre-ESS MLM, asthma, and anti-double-stranded DNA IgG could accurately predict PR.

Objectives: Corticosteroids represent one of the mainstays of medical management of chronic rhinosinusitis (CRS) in both locally acting topical and systemic derivations. The application of topical corticosteroids is limited by a variety of factors including patient compliance, positioning, and nasal anatomy. Systemic corticosteroids confer a risk of medical complication that restricts their ability to be used repeatedly. The objective of this publication is to review the evolution of the in-office intranasal placement of corticosteroids in the management of CRS. The efficacy, outcomes, and safety of a variety of corticosteroid-containing devices meant to be placed in an office setting are reviewed. Methods: Pertinent literature was reviewed and summarized beginning with the earliest reports of direct intralesional injection of corticosteroids up through manufactured modern-day bioresorbable implants that contain corticosteroids. Results: The utilization of in-office placement of corticosteroid-containing material and implants has rapidly evolved since the concept was introduced, particularly in the last decade. Modern-day corticosteroid-eluting implants are reliably placed in the office, yield results across a range of objective and subjective outcomes, may decrease the need for revision endoscopic sinus surgery, and have a favorable safety profile. Conclusions: In-office placement of corticosteroid-containing stents are a viable treatment option for select patients, particularly those wishing to avoid revision surgery, and should be considered an important adjunct for treatment of refractory CRS in an otolaryngologist’s armamentarium.

Background Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) is a common disease that is characterized by multiple inflammatory endotypes. However, the molecular mechanisms in CRSsNP are poorly understood compared with those of polypoid CRS. Objective Our aim was to identify mechanisms and biomarkers associated with inflammatory endotypes underpinning CRSsNP. Methods Ethmoid tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS. The gene expression profiles were determined by microarray analysis and quantitative RT-PCR, and expression of proteins was measured by ELISA and Luminex analysis. Results Microarray found that compared with their levels of expression in control tissue, the levels of expression of 126, 241, and 545 genes were more than 3-fold and significantly elevated in CRSsNP with type 1 (T1) endotype, type 2 (T2) endotype, and type 3 (T3) endotype, respectively. Selected identified genes were confirmed by RT-PCR. Gene set enrichment analysis suggested that T1 CRSsNP was associated with IFN-γ signaling and antiviral immunity controlled by T cells (TH1 and CD8+), natural killer cells, and antigen-presenting cells; T2 CRSsNP was associated with STAT6 signaling and IgE-mediated activation controlled by eosinophils, mast cells, TH2 cells, group 2 innate lymphoid cells, and antigen-presenting cells; and T3 CRSsNP was associated with IL-17 signaling, acute inflammatory response, complement-mediated inflammation, and infection controlled by neutrophils, TH17 cells, B cells, and antigen-presenting cells. The results suggest that T1 (CXCL9 and CXCL10), T2 (eosinophilic proteins and CCL26), and T3 (CSF3) endotypic biomarkers in NLF may be able to distinguish tissue endotypes in CRSsNP. Conclusions Inflammatory endotypes in CRSsNP were controlled by different molecular mechanisms. NLF biomarker assays may allow for more precise and personalized medical treatments in CRS.

BACKGROUND Whether for research or quality improvement, assessment of postoperative quality of life outcomes faces a challenge in reliable data collection. Typical coordinator-led studies cite response rates from 35% to 70%. This study evaluates the utility of a digital patient engagement platform to track patient-reported outcome measures (PROMs) following septoplasty and functional endoscopic sinus surgery (FESS). METHODS A prospective cohort was recruited at a tertiary care center from January 2017 to March 2018. A mobile phone application relayed PROMs, including pain (assessed on a 0 to 10 visual analogue scale [VAS] every other day for 2 weeks, as well as the patient-reported outcome measure information system [PROMIS] pain interference short form 4a at baseline, 2 weeks, and 3 months) and timing of return to work. RESULTS Of 288 patients enrolled, 249 (86.5%) provided clinical data, including 208 who underwent septoplasty or FESS. Granular VAS scores, submitted by 195 patients, demonstrated 80% of these patients achieved minimal pain by postoperative day 8. A nonsignificant trend of increased days to pain relief by procedure emerged: septoplasty (mean ± standard deviation [SD], 3.60 ± 2.44), FESS (3.96 ± 3.25), FESS with septoplasty (4.40 ± 3.04), and FESS with drilling (4.86 ± 3.68). Across procedures, PROMIS pain interference increased at 2 weeks (9.17 ± 4.15) and decreased at 3 months (5.32 ± 2.61) compared with baseline (7.09 ± 4.63), with greater improvement noted in the FESS subgroup at 3 months. Patients returned to work at mean 7.1 days regardless of procedure. CONCLUSIONS With its high response rate, mobile digital patient engagement platforms may effectively track postoperative outcomes with the potential for reduced sample bias.

Introduction: Chronic rhinosinusitis (CRS) is a broad heterogeneous inflammatory disorder of the nose and paranasal sinuses, resulting from the dysfunctional interplay between host immunity, defective epithelial barrier, and environmental factors. CRS with nasal polyps (CRSwNP) is considered a more severe clinical phenotype with greater burden of symptoms and higher relapse rate, especially with comorbid asthma or aspirin sensitivity. Available treatment options after endoscopic sinus surgery (ESS) - systemic corticosteroids or revision surgery - have significant risks and limitations. Areas covered: Bioabsorbable, steroid-eluting implants have been studied extensively for the ability to dilate and re-establish sinus patency by the localized, controlled delivery of topical corticosteroids to diseased sinonasal lining and nasal polyps. This review provides a comprehensive, up to date analysis of the literature regarding a novel, office-based, mometasone furoate (MF) sinus implant that may treat patients with recurrent CRSwNP after ESS. Expert commentary: Clinical evidence has demonstrated the safety and efficacy of steroid-eluting implant in the reduction of polyp size, symptom burden, and the need for revision sinus surgery. MF sinus implants may play an important role in the management of patients with recurrent polyposis after sinus surgery.

Background Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down-regulation of tissue plasminogen activator (t-PA) in NPs. As t-PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t-PA would be a potential new strategy for the treatment of NPs. Objective The objective of this study was to determine whether short-chain fatty acids (SCFAs) can induce t-PA in airway epithelial cells via their known receptors GPR41 and GPR43. Methods We performed immunohistochemistry (IHC) to determine whether receptors for SCFAs, known as G protein-coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE) cells were stimulated with different concentrations of SCFAs to test induction of t-PA, which was analysed by expression of mRNA and protein. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA. Results Immunohistochemistry study revealed that airway epithelial cells expressed GPR41 and GPR43. Acetic acid, propionic acid, butyric acid and valeric acid significantly induced t-PA expression from two- to tenfolds. The strongest inducer of t-PA from NHBE cells was propionic acid; cells stimulated with propionic acid released t-PA into the supernatant in its active form. Gene silencing of GPR41 and GPR43 revealed that induction of t-PA by SCFAs was dependent upon both GPR41 and GPR43. Conclusions and clinical relevance Short-chain fatty acids were shown to induce airway epithelial cell expression of t-PA via GPR41 and GPR43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.

BACKGROUND Chronic rhinosinusitis (CRS) is strongly associated with comorbid asthma. This study compares early-onset and late-onset asthma in a CRS population using patient-reported and clinical characteristics. METHODS At enrollment into a clinical registry, CRS patients completed the 22-item Sino-Nasal Outcome Test (SNOT-22), Asthma Control Test (ACT), mini-Asthma Quality of Life Questionnaire (miniAQLQ), the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29), and medication use questionnaires. Patients also reported comorbid asthma and age at first asthma diagnosis. Early-onset ( 18 years) asthma groups were defined. Analysis of variance (ANOVA), chi-square, and Kruskal-Wallis tests were used to compare patient responses. RESULTS A total of 199 non-asthmatic (56.1%), 71 early-onset asthmatic (20.0%), and 85 late-onset asthmatic (23.9%) CRS patients completed the survey. Body mass index (BMI) was significantly higher in late-onset asthmatic (p = 0.046) while age, gender, race, and smoking history did not differ with time of asthma onset. SNOT-22, ACT, and miniAQLQ were not different between asthma groups, but late-onset asthmatics had significantly lower physical function than non-asthmatics (p = 0.008). Compared to non-asthmatics, late-onset asthmatics showed increased rates of nasal polyps (p < 0.001), higher Lund-Mackay scores (p = 0.005), and had received more oral steroid courses (p < 0.001) and endoscopic surgeries (p = 0.008) for CRS management. Late-onset asthmatics compared to early-onset asthmatics showed increased nasal polyposis (p = 0.011) and oral steroid courses for CRS (p = 0.003). CONCLUSION While CRS-specific and asthma-specific patient-reported outcome measures (PROMs) were not significantly different among groups, CRS patients with late-onset asthma had poorer physical function, more frequent nasal polyposis, and required increased treatment for CRS. Late-onset asthma may predict more severe disease in CRS.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high propensity for recurrence. Studies suggest that eosinophilia influences disease severity and surgical outcomes, but the selection of sinonasal site for measuring eosinophilia has not been examined. The aim of this study was to investigate how region-specific tissue eosinophilia affects radiographic severity, comorbidity prevalence, and polyp recurrence risk following sinus surgery. Methods Eosinophil cationic protein (ECP) levels in uncinate tissue (UT) and nasal polyp (NP) homogenates from 116 CRSwNP patients were measured using enzyme-linked immunosorbent assay (ELISA). Clinical history, radiographic severity, and time to polyp recurrence were obtained from electronic health records. The correlations between baseline Lund-Mackay scores and comorbidities were compared between UT and NP ECP levels. Cox regression and Kaplan-Meier analysis were then performed to assess whether UT or NP ECP better predicted recurrence. Censoring occurred at 4 years or at last follow-up if there was no endoscopic diagnosis of recurrent polyps. Results Lund-Mackay scores were significantly correlated with UT and NP ECP (r = 0.46 and 0.26 respectively, p < 0.05). UT but not NP ECP was significantly higher in patients with asthma (p < 0.01) and aspirin-exacerbated respiratory disease (AERD) (p < 0.05). Polyp recurrence risk was only significantly higher for patients with eosinophilic UT tissue (hazard ratio [HR] = 2.84, p = 0.025). When measured in NP, eosinophilia did not predict recurrence. Conclusion Although ECP in NP was higher than in UT tissue, eosinophilia in UT tissue was a more clinically coherent biomarker of baseline radiographic severity, comorbid asthma and AERD, and prospective polyp recurrence risk than NP eosinophilia.

Background Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines. However, the presence of various types of ILC in CRS is poorly understood. Objective The objective of this study was to fully characterize the presence of all ILC subsets in CRS and to identify phenotypical differences of group 2 ILC (ILC2) in CRSwNP compared to ILC2 from non-type 2 inflamed areas. Methods We investigated the presence of ILC subsets in peripheral blood mononuclear cells (PBMC) from healthy subjects, tonsil tissue, ethmoid tissue from control subjects and patients with non-polypoid CRS (CRSsNP) and CRSwNP, as well as nasal polyp (NP) tissue from CRSwNP by flow cytometry. Sorted ILC2 were cultured in the presence and absence of IL-33 and production of IL-5 and IL-13 was assessed by Luminex. Results We found that all ILC subsets were present in NP but ILC2 were dominant and significantly elevated compared to PBMC, tonsil, CRSsNP, and normal sinus tissue. We also found that inducible T-cell co-stimulator (ICOS) and side scatter were increased and CD127 was down-regulated in ILC2 from NP compared to blood or tonsil ILC2. Thymic stromal lymphopoietin, IL-7, and IL-33 were able to down-regulate expression of CD127 and increase side scatter in blood ILC2. Furthermore, sorted NP ILC2 but not blood ILC2 spontaneously released type 2 cytokines including IL-5 and IL-13. Conclusions and Clinical Relevance These results suggest that ILC2 are not only elevated but also activated in CRSwNP in vivo and that ILC2 may play important roles in the type 2 inflammation in CRSwNP.

Background Chronic rhinosinusitis (CRS) is complicated by frequent acute exacerbations leading to significant health care burden and impaired quality of life. Objective The objective of this study was to identify clinical factors associated with frequent acute exacerbation of CRS (AECRS). Methods This is a retrospective cohort study of patients with CRS from January 1, 2014, to May 31, 2016. Frequent AECRS was defined as at least 4 episodes over a 12-month period in which an antibiotic was prescribed for worsening sinus symptoms, and infrequent AECRS was defined as 0 to 3 episodes. Clinical factors, including asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease, were evaluated for associations between the 2 groups. Results Of the 3109 patients with CRS who were identified, 600 (19.3%) were classified as having frequent exacerbation. Asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease were associated with frequent AECRS with statistically significant adjusted odds ratios (aORs) after controlling for age, race, and sex in multivariate analysis (asthma aOR = 2.61 [95% CI = 2.14-3.18]; allergic rhinitis aOR = 1.96 [95% CI = 1.58-2.42]; eosinophil count of at least 150 cells per microliter aOR = 1.54 [95% CI = 1.21-1.97]; and autoimmune disease aOR = 1.68 [95% CI = 1.36-2.07]). Antibody deficiency, antibiotic allergy, lower FEV1, radiographic sinus disease severity, nasal polyposis, and systemic corticosteroid use were also associated with frequent AECRS. Conclusion Patients with frequent episodes of AECRS were characterized by a higher prevalence of asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, autoimmune disease, and other allergic and immunologic diseases. These findings identify a high-risk phenotype of patients with CRS for preventive interventions to reduce exacerbation frequency.

Chronic rhinosinusitis (CRS) is a common comorbidity in patients with asthma, and they share similar pathophysiologic mechanisms. The concomitant conditions of CRS and asthma can significantly exacerbate each other. The medical and/or surgical treatment of CRS may significantly improve asthma control.

Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD.Our aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD.Single-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence.The gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P .05) or controls (P .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LOEpithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.

TNF receptor II is expressed on ILC2s and TNF is able to induce production of type 2 cytokines in human ILC2s. TNF may play a role in causing or amplifying type 2 immunity contributing to health and disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type 2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear. OBJECTIVE: We sought to characterize the systemic and local basophil responses in patients with AERD compared with patients with CRSwNP. METHODS: Sinonasal tissues including inferior turbinate and/or nasal polyps (NPs) and peripheral blood were collected from controls, patients with AERD, and patients with CRSwNP. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63), and intracellular (2D7) markers associated with basophils was characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained. RESULTS: The mean number of basophils (CD45(+)CD203c(+)FcεRI(+)CD117(−)) detected in AERD NPs (147 ± 28 cells/mg tissue) was significantly elevated compared with that detected in CRSwNP NPs (69 ± 20 cells/mg tissue; P = .01). The number of circulating basophils was significantly elevated in patients with AERD (P = .04). Basophils in NPs had significantly higher CD203c and CD63 mean fluorescence intensity compared with blood in both conditions (P < .01). Basophils from AERD NPs had lower expression of the granule content marker 2D7 compared with those from matched blood (P < .01) or NPs of patients with CRSwNP (P = .06), suggesting ongoing degranulation. Basophil 2D7 mean fluorescence intensity significantly correlated with pulmonary function (r = 0.62; P = .02) and inversely correlated with sinonasal inflammation (r = −0.56; P = .004). CONCLUSIONS: Increased basophil numbers and extent of ongoing degranulation in NPs of patients with AERD compared with patients with CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.

Whereas chronic rhinosinusitis (CRS) is associated with asthma, and vice versa, the association between CRS and other lower respiratory conditions is not well-established. Bronchiectasis is characterized by permanent damage of the airways, and as many as 45% of bronchiectasis patients have CRS, but the prevalence of bronchiectasis among CRS patients is not known.To determine the prevalence of bronchiectasis among CRS patients and to characterize demographic and clinical features of patients with bronchiectasis and CRS.Electronic medical records of patients with rhinosinusitis were searched by computer algorithm supplemented with manual chart review to identify patients with CRS, asthma, and/or bronchiectasis. Demographic and clinical features and antibiotic courses for sinopulmonary infections 2 years before and after sinus surgery were obtained by manual chart review.The prevalence of bronchiectasis as determined by International Classification of Diseases, Ninth Revision code was significantly higher in CRS patients than in asthmatic patients (2.3% vs 1.7%; P.003). Similarly, based on a text word search of "bronchiectasis" in the chest computed tomography (CT) scan reports, patients with CRS who had chest CT scans had a higher prevalence of bronchiectasis than did asthmatic patients with chest CT scans (24.3% vs 19.5%; P = .005). Patients with CRS and concurrent bronchiectasis did not have a reduction in the frequency of sinopulmonary infections after sinus surgery compared with patients with CRS without bronchiectasis (P .05).Bronchiectasis is an important comorbidity in patients with CRS and may identify a severe phenotype of chronic sinonasal disease.

Background B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NP), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways. Objective We sought to determine the mechanisms that drive B cell activation and antibody production during chronic airway inflammation. Methods We analyzed B cells from NP or tonsil, or after ILC2 co-culture, by flow cytometry. Antibody production from tissue was measured using Luminex assays, and the frequency of antibody-secreting cells by ELISpot. Formation of B cell clusters was assessed using immunohistochemistry. Expression of genes associated with B cell activation and class switch recombination was measured by qRT-PCR. Results NP contained significantly elevated frequencies of plasmablasts, especially those that expressed the extra follicular marker Epstein-Barr virus-induced protein 2 (EBI2), but significantly fewer germinal center (GC) B cells compared to tonsil. Antibody production and the frequency of antibody-secreting cells were significantly elevated in NP, and there was evidence for local class switch recombination in NP. Finally, ILC2s directly induced EBI2 expression on B cells in vitro. Conclusions and Clinical Relevance Our data suggest there is a unique B cell activation environment within NP that is distinct from classic GC-mediated mechanisms. We show for the first time that ILC2s directly induce EBI2 expression on B cells, indicating that ILC2s may play an important role in B cell responses. B cell-targeted therapies may provide new treatment options for CRSwNP. This article is protected by copyright. All rights reserved.

Background Responsiveness, or sensitivity to clinical change, is important when selecting patient-reported outcome measures (PROMs) for research and clinical applications. This study compares responsiveness of PROMs used in chronic rhinosinusitis (CRS) to inform the future development of a highly responsive instrument that accurately portrays CRS patients’ symptom experiences. Methods Adult CRS patients initiating medical therapy (MT; n = 143) or undergoing endoscopic sinus surgery after failing MT (ESS; n = 123) completed the 22-item Sino-Nasal Outcome Test (SNOT-22), European Position Statement on Rhinosinusitis (EPOS) visual analog scale (VAS), and 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) at baseline and 3 months after treatment. Cohen's d and paired t statistics were used to evaluate the responsiveness of each measure. Results Fifty-two (36.4%) subjects and 42 (34.1%) subjects in the MT and ESS groups, respectively, completed baseline and 3-month questionnaires. Subjects with and without 3-month data were similar with respect to baseline demographics, VAS scores, and SNOT-22 scores (p > 0.05). In MT patients, CRS-specific measures, like VAS (d = −0.58, p 0.05) and SNOT-22 (d = −0.70, p 0.05 for Cohen's d). In ESS patients, VAS (d = −1.97; t = −9.63, both p < 0.01) and SNOT-22 (d = −1.56; t = −9.99, both p < 0.01) scores were similarly more responsive, although changes in PROMIS-29 domains of Fatigue (d = −0.82, p = 0.01; t = −4.63, p < 0.01), Sleep Disturbance (d = −0.83; t = −3.77, both p < 0.01), and Pain Intensity (d = −1.0; t = −5.67, both p < 0.01) were significant. All 22 individual SNOT-22 items differed significantly after surgery, whereas only 8 items were consistently responsive after MT. Conclusions For both MT and ESS patients, CRS-specific PROMs are more responsive to posttreatment clinical changes than general health measures. Still, the SNOT-22 contains items that likely decrease its overall responsiveness. Our findings also indicate that existing PROMs had a greater response to ESS than MT.

An elderly African American woman presented to our clinic following 9 months of right-sided unilateral headache, otorrhoea and progressive hearing loss. Despite treatment with topical and oral antibiotics, her clinical condition worsened, and imaging showed mastoid coalescence with an associated subgaleal abscess. She underwent right mastoidectomy and was discharged 3 days later on broad-spectrum intravenous antibiotics despite negative operative cultures. Six weeks later, she was hospitalised with diplopia secondary to a right lateral rectus palsy. Imaging showed abscess resolution but progressive bony remodelling and enhancement of the lateral extending into anterior skull base. Chest CT demonstrated upper lobe predominant pulmonary micronodules, and mastoid biopsy on revision surgery was notable for non-caseating granulomas. Further extensive work-up could not identify an alternative cause, and a presumptive diagnosis of neurosarcoidosis was made. The patient was initiated on intravenous steroids, experienced symptomatic improvement and was thereafter transitioned to oral steroid taper on discharge.

Patient-reported outcome (PRO) measures developed and validated on patients with the currently defined phenotypes of chronic rhinosinusitis (CRS) are needed to support clinical trials in CRS.This study developed and examined the initial reliability and validity of the CRS-PRO, a new PRO measure of CRS.Instrument development was performed through structured interviews and focus groups with clinical experts and 45 patients with CRS meeting current definitions of disease, 21 patients with CRS without nasal polyps (CRSsNP), and 24 patients with CRS with nasal polyps (CRSwNP) to identify items important to patients. Then another 50 patients (32 with CRSsNP and 18 with CRSwNP) with stable CRS symptoms were enrolled to evaluate the reliability of the instrument. Each patient completed the CRS-PRO, Sinonasal Outcome Test-22 (SNOT-22), and 4 Patient-Reported Outcome Measurement Information System short forms at the baseline visit and then at least 7 days later.After the development process, 21 items were identified from the conceptual domains of physical symptoms, sensory impairment, psychosocial effects, and life impact. Using the responses of the 50 patients with CRS, 21 draft items were further refined to 12 items by eliminating conceptually similar or highly correlated items or those with low mean symptom severity. The 12-item questionnaire was shown to have excellent internal consistency (Cronbach α, 0.86) and test-retest reliability with a high intraclass correlation coefficient (0.89) and Pearson's correlation (r = 0.82, P.0001). The 12-item CRS-PRO correlated highly with the longer SNOT-22 (r = 0.83, P.0001) demonstrating its concurrent validity. We also demonstrated validity and reliability in a separate analysis for patients with CRSsNP and CRSwNP.The CRS-PRO is a concise, valid, and reliable measure that was developed with extensive input from patients with CRS with current disease definitions.

Background The CRS-PRO is a new patient-reported outcome measure (PROM) for chronic rhinosinusitis (CRS) that was developed using extensive patient input per Food and Drug Administration guidance on PROMs acceptable for use as end points in clinical trials. Objective To assess the responsiveness and convergent validity of the CRS-PRO following standard-of-care medical therapy. Methods This was a prospective study of 51 patients (21 with nasal polyps and 30 without) with newly diagnosed CRS or having an acute CRS exacerbation who were initiated on appropriate medical therapy. At the baseline visit each patient completed the CRS-PRO questionnaire, the 22-item Sino-Nasal Outcome Test, the EuroQol 5-dimensional questionnaire, and 4 Patient-Reported Outcome Measure Information System short forms along with objective testing including endoscopic and radiographic scores, smell discrimination, and nasal inspiratory flow testing. This same battery of questionnaires and testing was administered at a follow-up visit 4 to 8 weeks later. Results We verified that shortening the 21-item CRS-PRO to 12 items as previously described maintains its psychometric properties. The 12-item CRS-PRO was responsive with a large effect size (Cohen's d, 0.94) comparable to the longer 22-item Sino-Nasal Outcome Test (Cohen's d, 0.93). The instrument was slightly more responsive to medically treated patients with CRS without nasal polyps compared with patients with CRS with nasal polyps (Cohen's d, 1.1 vs 0.89, respectively). The change in 12-item CRS-PRO total score has moderate correlation with change in Lund-Mackay computed tomography scores. Conclusions The CRS-PRO is a 12-item rigorously developed, responsive, and valid PROM that was developed using extensive input from patients with current definitions of CRS, including its 2 major phenotypes.

Although minimally invasive endoscopic frontal sinus surgery has become the mainstay of managing both chronic and in many cases neoplastic disease of the frontal sinus, open approaches to the frontal sinus remain viable options for managing many diseases in the frontal sinus. Once considered the gold standard for managing frontal sinusitis, the osteoplastic flap with and without obliteration is a useful approach and surgical treatment of recalcitrant chronic frontal rhinosinusitis that has failed—or is not amenable—to endoscopic management as well as many benign or malignant frontal sinus tumors and frontal sinus trauma. Because it has fallen out of the mainstay of surgical management, performing an osteoplastic flap with or without obliteration requires a considerable knowledge of the anatomy of the scalp, its neurovascular architecture, and osteology of the frontal bone. Once fully understood, the osteoplastic approach can remain in the armamentarium of the otolaryngologist for the successful treatment of a wide array of ailments affecting the frontal sinus.

Cerebrospinal fluid (CSF) leaks from the nose, and sinuses are infrequent problems that require skilled techniques to manage. Whether iatrogenic or spontaneous, CSF leaks occurring in the cribriform area of the ethmoid sinuses are aptly suited for minimally invasive and endoscopic repair. While CSF leaks were in the past solely within the purview of the neurosurgeon, these defects can be approached via a transnasal endoscopic route and typically repaired using a variety of reconstructive techniques––many of them including grafts harvested from within the nasal cavity or sinuses––by an otolaryngologist. Today, endoscopic repair of cribriform CSF leaks is the mainstay of surgical repair, and this technique enjoys a very high success rate with few complications, recurrence rates, and morbidity.