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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.

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.

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.

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.