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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.)

Background: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs., Methods: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class., Results: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05)., Conclusion: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs., (© 2023 ARS-AAOA, LLC.)

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.)

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., (© 2021 ARS-AAOA, LLC.)

Background: Nasal irrigation is an important component of medical management in chronic rhinosinusitis. Nasal irrigations facilitate topical medication of therapies and lavage of mucin. In this study we aim to compare the influence of increasing surgical sphenoid openings on the distribution, force, and clearance of nasal irrigations., Methods: A study was performed on fresh-frozen adult cadaver heads. The surgical ostium was modified on one side via a simple sphenoidotomy, a sphenoid sinusectomy (type 1), and sphenoid sinusectomy (type 3a). The nasal cavity was irrigated using a 240-mL squeeze bottle with 0.1% fluoroscein. An endoscope passed through the contralateral side through the sphenoid septum recorded the irrigation. Videos were recorded and blindly assessed. The distribution was defined as either no irrigation, less than one third of the sinus, less than or equal to two thirds of the sinus, or the complete sinus. The force was defined as minimal, minor, or major. The clearance was defined as no residual, less than one third of volume, less than or equal to two thirds of volume, and more than two thirds volume. Ordinal correlation scores were assessed using the Kendall tau-B test., Results: Nine specimens (sphenoid sinuses) were assessed (44.4% female; age, 75.0 ± 12.7 years). The use of a sphenoid sinusectomy or larger produced better distribution (percent specimens with more than one third: 100% vs 59%, p < 0.01), more force (percent major: 83% vs 29%, p < 0.01), and better clearance (percent with one third or less remaining: 56% vs 18%, p < 0.01)., Conclusion: Increasing sphenoid ostial size improves nasal irrigation penetration. We propose that greater sphenoid sinusectomy size allows for improved lavage and irrigation penetration. Complete removal of the anterior face appears to mitigate pooling of irrigation., (© 2019 ARS-AAOA, LLC.)

Background: Orbital cavernous hemangiomas (OCH) are the most common adult orbital tumor and represent an ideal index lesion for endonasal orbital tumor surgery. In order to standardize outcomes reporting, an anatomic-based staging system was developed., Methods: An international, multidisciplinary panel of 23 experts in orbital tumor surgery was formed. A modified Delphi method was used to develop the cavernous hemangioma exclusively endonasal resection (CHEER) staging system with a total of 2 rounds being completed., Results: Tumors medial to a plane along the long axis of the optic nerve may be considered amenable for an exclusively endonasal resection. In select cases, tumors may extend inferolaterally if the tumor remains below a plane from the contralateral naris through the long axis of the optic nerve (ie, plane of resectability [POR]). This definition reached consensus with 91.3% of panelists in agreement. Five stages were designed based on increasing technical resection difficulty and potential for morbidity. Stages were based on the relationship of the tumor to the extraocular muscles, the inferomedial muscular trunk of the ophthalmic artery (IMT), and orbital foramina. Staging by anatomic location also reached consensus with 87.0% of panelists in agreement. Size was not included in the staging system due to the lack of agreement on the contribution of size to resection difficulty., Conclusion: Endoscopic orbital tumor surgery is a nascent field with a growing, yet heterogeneous, body of literature. The CHEER staging system is designed to facilitate international, high-quality, standardized studies establishing the safety, efficacy, and outcomes of endonasal resection of OCH., (© 2019 ARS-AAOA, LLC.)

Background: Persistent mucosal inflammation in patients with chronic rhinosinusitis (CRS) often results in ongoing symptoms, recurrence of polypoid mucosa, infective exacerbations, and further systemic medication despite surgical intervention. Debate exists as to the most effective topical therapy in CRS., Methods: The objective was to determine if corticosteroid delivered via a nasal irrigation or via a simple nasal spray would be more effective in controlling the symptoms and signs of CRS. A double-blind placebo-controlled randomized trial over 12 months was performed between 3 tertiary rhinologic clinics. After sinus surgery, all patients performed a nasal irrigation followed by a nasal spray once a day for 12 months. Groups were defined by corticosteroid (2 mg mometasone) delivered by either spray or irrigation. The primary outcomes were patient-reported symptoms: visual analogue score (VAS) and 22-item Sino-Nasal Outcome Test (SNOT-22), a global rating of sinonasal function. Secondary outcomes were also recorded from radiology (Lund-Mackay score [LMS]) and endoscopic (Modified Lund-Kennedy score [mLKS]) assessments., Results: A total of 44 patients were randomized (age 50.3 ± 13.0 years; 40.9% female). Overall, patients improved significantly from either intervention. However, the corticosteroid nasal irrigation group had greater improvement in nasal blockage (-69.91 ± 29.37 vs -36.12 ± 42.94; p = 0.029), a greater improvement on LMS (-12.07 ± 4.43 vs -7.39 ± 6.94; p = 0.031) and less inflammation on mLKS at 12 months (7.33 ± 11.55 vs 21.78 ± 23.37; p = 0.018). One-year posttreatment blockage, drainage, fever, and total VAS scores were all lower in the corticosteroid irrigation group., Conclusion: In the setting of diffuse or patchy CRS disease, the use of corticosteroid delivered by nasal irrigation is superior to simple nasal spray in postsurgical patients., (© 2018 ARS-AAOA, LLC.)

Background: The diagnosis of allergic rhinitis (AR) is based on cutaneous and serological assessment to determine immunoglobulin E (IgE)-mediated disease. However, discrepancies between these tests and nasal provocation exist. Patients diagnosed as non-allergic rhinitis (NAR) but with positive nasal allergen provocation test (NAPT) may represent a local allergic condition or entopy, still suitable to allergy interventions. The objective of this study was to determine the frequency of nasal reactivity toward allergens among AR and NAR patients, and to describe the diagnostic characteristics of NAPT methodologies., Methods: EMBASE (1947-) and Medline (1946-) were searched until December 8, 2015. A search strategy was used to identify studies on AR or NAR patients subjected to diagnostic local nasal provocation. All studies providing original NAPT data among the AR or NAR population were included. Meta-analysis of proportion data was presented as a weighted probability % (95% confidence interval [CI])., Results: The search yielded 4504 studies and 46 were included. The probability of nasal allergen reactivity for the AR population was 86.3% (95% CI, 84.4 to 88.1) and in NAR was 24.7% (95% CI, 22.3 to 27.2). Reactivity was high with pollen for both AR 97.1% (95% CI, 94.2 to 99.2) and NAR 47.5% (95% CI, 34.8 to 60.4), and lowest with dust for both AR 79.1% (95% CI, 76.4 to 81.6) and NAR 12.2% (95% CI, 9.9 to 14.7). NAPT yielded high positivity when defined by subjective end-points: AR 91.0% (95% CI, 86.6 to 94.8) and NAR 30.2% (95% CI, 22.9 to 37.9); and lower with objective end-points: AR 80.8% (95% CI, 76.8 to 84.5) and NAR 14.1% (95% CI, 11.2 to 17.2)., Conclusion: Local allergen reactivity is demonstrated in 26.5% of patients previously considered non-allergic. Similarly, AR, when defined by skin-prick test (SPT) or serum specific IgE (sIgE), may lead to 13.7% of patients with inaccurate allergen sensitization or non-allergic etiologies., (© 2017 ARS-AAOA, LLC.)

Background: Episodic or recurrent sinonasal symptoms are often suspected as "sinus" in origin. With normal sinus radiology between events, the diagnosis of recurrent acute rhinosinusitis (RecARS) is made. However, other conditions can produce episodic symptoms. In this study we analyze acutely performed computed tomography (CT) in a population with suspected or self-diagnosed "sinus" disease., Methods: Patients referred to a tertiary clinic for suspected RecARS were assessed. Sinus changes were defined by CT (initial assessment) and during the acute event, by a semiurgent CT performed during the symptomatic episode. Mucosal thickening, ostiomeatal compromise, and severe septal deformity were recorded. Symptom profile was assessed during both time-points with the 22-item Sino-Nasal Outcome Test (SNOT-22)., Results: Forty-eight patients (49.5 ± 14.7 years of age, 70.8% female) were assessed. At presentation, 75% were resolute in a diagnosis of "sinus." Baseline Lund-Mackay scores were <6 (median 0 [interquartile range 1]). Ostiomeatal compromise was 6.8% left and 4.5% right at baseline. Of the patients who returned for acute CT (n = 27), SNOT-22 and subdomains were similar to baseline. Septal deviation was similar (13.6% vs 15.3%). Acutely, ostiomeatal compromise was 0% left and 7.4% right (n = 2). Of these 2 patients with ostiomeatal compromise, 1 was diagnosed with RecARS (4%) and the other with triptan-responsive migraine, with incidental sinus changes. Final diagnosis was rhinitis (47%), headache/migraine (37%), and facial pain otherwise undefined (12.5%)., Conclusion: Patients with a history of "recurrent acute sinusitis" and normal CT scans between episodes rarely have abnormal CT findings during acute exacerbations of symptoms. Antibiotics and surgical intervention are often inappropriate in this population., (© 2017 ARS-AAOA, LLC.)

Background: Vitamin D deficiency is associated with many inflammatory respiratory disease states. However, serum vitamin D concentrations may not reflect tissue-specific availability. In this study we sought to assess the local expression of genes essential in vitamin D regulation in chronic rhinosinusitis (CRS)., Methods: A cross-sectional study of adult patients undergoing endoscopic sinus surgery was performed. Patients were defined as having CRS with polyps (CRSwNP) or without polyps (CRSsNP), or normal sinus mucosa. Sinus mucosal biopsies were assessed using quantitative polymerase chain reaction to determine expression of genes encoding the vitamin D receptor (VDR), 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1). Expression levels correlated with serum 25(OH)D [sum 25(OH)D 2  and 25(OH)D 3 ], the 22-item Sinonasal Outcome Test (SNOT-22), and Nasal Symptom Score (NSS). Separate analyses were performed for patients grouped by tissue eosinophilia., Results: Thirty-one patients were assessed (age 49.47 ± 18.14 years, 48.4% female), including 8 CRSsNP, 10 CRSwNP, and 13 controls. CRSsNP and CRSwNP mucosa exhibited decreased CYP27B1 compared with controls (0.0437 [Interquartile range (IQR) 0.0999] vs 0.3260 [IQR 2.9384] vs 0.6557 [IQR 1.1005], p = 0.039), whereas CYP24A1 was upregulated (0.8522 [IQR 1.3170] vs 1.2239 [IQR 4.4197] vs 0.1076 [IQR 0.1791], p = 0.025). CYP24A1 was upregulated in both non-eosinophilic CRS and eosinophilic CRS (1.1337 [IQR 2.3790] vs 0.9555 [IQR 3.2811] vs 0.1076 [IQR 0.1791], p = 0.033). Significant correlations were observed between NSS and CYP2R1 (r = -0.432, p = 0.022), CYP24A1 (r = 0.420, P = 0.026), and VDR (r = 0.425, p = 0.024), although no correlations with serum 25(OH)D were observed., Conclusions: The local regulation of vitamin D in sinonasal tissue during CRS may be independent of serum 25(OH)D levels. Vitamin D may be dysregulated at multiple levels, with decreased transcription of the metabolic gene CYP27B1 and increased transcription of the catabolic gene CYP24A1 observed., (© 2016 ARS-AAOA, LLC.)

Background: Middle turbinate edema could be a characteristic feature of aeroallergen sensitization. In this study we sought to determine the diagnostic characteristics of middle turbinate edema as a marker of inhalant allergy., Methods: A cross-sectional diagnostic study was performed on patients who had undergone nasal endoscopy and allergy testing. Allergy status was determined by positive serology or epicutaneous testing. Endoscopy was reviewed by blinded assessors for middle turbinate head edema. Appearance was graded as either normal, focal, multifocal, diffuse, or polypoid edema. Receiver-operator (ROC) analysis, likelihood ratio (LR), sensitivity, specificity, and positive predictive value (PPV) were determined., Results: One hundred eighty-seven patients representing 304 nasal cavities were assessed (42% female, age 39.74 ± 14.7 years, 57% allergic). Diffuse edema (PPV 91.7%/LR = 8) and polypoid edema (PPV 88.9%/LR = 6.2) demonstrated the strongest association with inhalant allergy. Multifocal edema was used as a cut-off to represent inhalant allergy from ROC analysis, which demonstrated 94.7% specificity and 23.4% sensitivity. The PPV for multifocal was 85.1% and LR = 4.4., Conclusion: Middle turbinate edema is a useful nasal endoscopic feature to predict presence of inhalant allergy and, although not sensitive, has excellent PPV., (© 2016 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: Effective mucus lavage and delivery of topical pharmaceuticals are central to successful management of chronic rhinosinusitis (CRS). The frontal sinus remains difficult to penetrate with topical therapies. This study evaluates the benefit of Draf III frontal dissection compared to traditional Draf IIa for distribution of topical therapies., Methods: Fresh human cadaver heads were dissected sequentially with Draf IIa frontal sinusotomy and then Draf III procedures. Each cavity was irrigated with pediatric (120 mL) and adult (240 mL) irrigation bottles with 1/1000 10% fluorescein-labeled free water in 2 fixed positions (vertex and Frankfort horizontal). An endoscope at a fixed position within the frontal sinus recorded frontal sinus and frontal recess penetration. The images then underwent blinded evaluation of fluid distribution scored as 0 to 4 (nasal cavity only, frontal recess, medial one-half, lateral one-half, and lavage). Ordinal distribution score was analyzed with Kendall's tau-b., Results: Eight specimens (age 76 ± 11.2 years; 50% female) were assessed. Draf III was superior to Draf IIa in ability to achieve frontal sinus distribution of irrigation (90.6% vs 50.1%, p < 0.001). Vertex head position improved distribution (90.6% vs 50.1%, p < 0.001), was synergistic with Draf III (100% with 87.5% lavage, p < 0.001), but was unable to overcome Draf IIa (81.2% with 25% lavage, p < 0.001). Irrigation volume trended toward improved distribution with larger volume irrigations., Conclusion: Successful treatment of sinonasal disease may require postoperative delivery of topical therapies. Draf III frontal sinusotomy achieves superior topical access, and access to the frontal sinus with Draf IIa appears limited, despite large volumes and positioning., (© 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: Techniques for inferior turbinate reduction vary from complete turbinectomy to limited cauterization. Surgical methods differ on the degree of tissue reduction and reliance on surgical tissue removal vs tissue ablation. The outcome and morbidity from 3 different turbinate techniques are compared., Methods: A randomized double-blinded study was performed. Patient nasal cavities were randomized to different interventions on each side within the same patient. One group had a combination of submucosal powered turbinate reduction (designated "submucosal") and submucosal electrocautery (designated "electrocautery"); and the second group had a combination of submucosal powered turbinate reduction (designated "submucosal") and medial flap turbinoplasty (designated "turbinoplasty"). Patient-scored nasal obstruction and rhinorrhoea (1 to 5) along with blindly assessed nasal airway patency ratings (1 to 4) was done at 12 and 60 months postoperatively. Pain requiring additional analgesia, crusting, bleeding (needing review), and revision were documented., Results: A total of 100 patients were recruited (age 32.79 ± 13.58 years; 39% female). This represented 200 nasal airway surgeries with 100 submucosal procedures, 50 electrocautery and 50 medial flap turbinoplasties. No patients complained of worsening of their obstruction. At 60 months patients in the turbinoplasty group had greater outcomes, with 90.2% having occasional or no decongestant use (Kendall's tau B p < 0.001) compared to electrocautery (15.8%) and submucosal (37.8%). Fewer turbinoplasty patients had a revision procedure (12%, χ(2) = 20.08, p < 0.001) compared to electrocautery (54%) and submucosal (40%). Crusting was more common in the electrocautery group (58% vs submucosal 2% and turbinoplasty 0%; χ(2) = 92.04; p < 0.001)., Conclusion: The medial flap turbinoplasty provided consistent, robust results. Long-term relief of obstructive symptoms without additional risk of complication was observed in the turbinoplasty group., (© 2015 ARS-AAOA, LLC.)

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., (© 2015 ARS-AAOA, LLC.)

Background: Inadvertent injury to the internal carotid artery (ICA), if poorly managed, not only presents a risk of exsanguination but can also result in significant long-term morbidity. Through the implementation of a novel animal model of endoscopic carotid artery injury (CAI), effective techniques to manage this scenario have been developed. The Vascular Injuries Workshop has trained over 110 surgeons in these techniques. This study reviews events of major arterial hemorrhage managed by surgeons who completed this vascular injury workshop training., Methods: We report a retrospective multicenter case series of patients who required endoscopic management of intranasal major arterial hemorrhage. Delegates who had attended the course were contacted by e-mail and surveyed with regard to instances of major arterial bleeding and the management undertaken. Patient demographics, tumor type, factors influencing injury, management technique, and outcomes were reviewed., Results: The cases reported herein are characterized as follows: 9 cases are reported in total, 3 male, 6 female; age range 37 to 82 years; 1 basilar artery, and 8 ICA injuries. Each case was successfully managed endoscopically with intraoperative muscle patch application. There were no deaths, 1 case of pseudoaneurysm with successful endovascular treatment, 2 cases of impaired carotid flow, and 1 carotid dissection was conservatively managed. There were no permanent neurological sequelae or other permanent morbidity., Conclusion: The Vascular Injuries Workshop arms surgeons with a structured approach to managing the surgical field and provides effective hemostatic techniques in the face of impending catastrophe. In comparison to the existing literature on ICA rupture, our results show trained surgeons are well equipped to achieve safe outcomes for their patients., (© 2014 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: 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., (© 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: The influence of the microbial community on inflammatory subtype in chronic rhinosinusitis (CRS) has been proposed. Superantigen mechanisms potentially create a T helper 2 (Th-2)/eosinophilic dominated inflammation as a product of local flora rather than an intrinsic mucosal process. The associations between culturable bacteria and the histopathology and clinical features of CRS patients are described., Methods: A cross-sectional study involving patients with CRS undergoing surgery was undertaken. Middle meatal swabs were performed at surgery for microbiological evaluation. Mucosal biopsies were taken and a blinded histopathological profile was performed. Disease specific quality of life and nasal symptom scores were recorded. The presence of culturable organisms and particular pathogens were compared with histopathology and clinical outcomes., Results: A total of 95 patients were assessed (48.4% female, mean age 45.6 ± 14.0 years), of which 47.3% had a culturable organism. Tissue eosinophilia (>10/high-power field [HPF]) was found in 46.1% of these patients and 30.3% had neutrophilic infiltrate, with the presence of neither Gram-positive organisms, Gram-negative organisms, nor species correlating to pathology subtype. A culturable pathogen was a predictor of subepithelial fibrosis (χ(2) = 6.36, p = 0.04) and Gram-negative bacteria had the strongest association (χ(2) = 18.82, p < 0.01). There were no other significant associations with other clinical outcomes., Conclusion: The culturable bacterial community has little impact on histopathology in CRS. While more sensitive tests may detect bacteria in the sinuses, the impact of the simple "culturable" bacteria on the underlying pathologic process is limited. Changes, such as subepithelial fibrosis, suggest colonization may lead to undesirable local mucosal damage and remodeling., (© 2013 ARS-AAOA, LLC.)

Background: Osteitic bone is a feature of chronic rhinosinusitis (CRS), potentially playing a role in pathogenesis. Although seen after previous endoscopic sinus surgery (ESS), it is also a de novo feature in patients without prior interventions. In these patients, osteitis is associated with high tissue and serum eosinophilia. However, the impact of osteitis on prognosis is unclear. This study investigates the clinical and endoscopic outcomes between patients with and without osteitis after primary ESS., Methods: A prospective study of a cohort of previously unoperated patients with CRS undergoing ESS was performed. The sinuses were scored radiologically for osteitis using the Global Osteitis Score (GOS) and Kennedy Osteitis Score (KOS) preoperatively and were also scored dichotomously for the presence or absence of osteitis. Disease-specific quality of life (22-item Sino-Nasal Outcomes Test [SNOT-22]), nasal symptom score (NSS), endoscopic score (Lund-Kennedy), and clinical outcomes-including oral steroid use, frequency of nasal steroid irrigation, and infective exacerbations-were collected at baseline and 1 year postsurgery. The presence and extent of osteitis was assessed relative to clinical outcome., Results: Fifty-three patients were included (41.5% female, age 47.4 ± 13.8 years), 42.9% of which had radiologic osteitis. There was no significant association between the presence or severity of osteitis at the time of surgery and SNOT-22, NSS, or endoscopy scores at 12 months postsurgery. However, the presence of osteitis was associated with the need for a course of oral steroid postsurgery (odds ratio [OR]=4.17; p = 0.026). High tissue eosinophilia could not predict this alone (p = 0.55). There was no significant relationship between osteitis and the frequency of steroid irrigations or infective exacerbations., Conclusion: Osteitis in CRS is associated with the degree of eosinophilia and as a independent process it was associated with the need for a course of systemic corticosteroid over a 12-month period, but did it not affect overall disease control., (© 2013 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals, Inc., on behalf of ARS-AAOA, LLC.)

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 × 10(9) /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., (© 2013 ARS-AAOA, LLC.)

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.)

Background: Inflammatory dysfunction is considered an important part of chronic rhinosinusitis (CRS). Corticosteroid therapy has been widely used in CRS. Effective topical delivery has been previously problematic. The post-endoscopic sinus surgery (ESS) corridor is essential for adequate topical drug access. Devices delivering large volume with positive pressure allow better distribution to sinus mucosa. The objective of this study is to evaluate the efficacy of postoperative topical sinonasal steroid irrigations for CRS., Methods: Patients with CRS undergoing ESS after failing previous medical therapy were recruited. Structured histopathology including markers of eosinophilia was performed. After surgery, patients received either budesonide 1 mg or betamethasone 1 mg delivered in a 240-mL squeeze bottle daily. Outcomes of the symptom score, Sino-Nasal Outcome Test 22 (SNOT-22) score, and endoscopy score were recorded., Results: A total of 111 patients (mean 50.1 ± 13.5 standard deviation [SD] years, 40.5% female) were included. Mean follow-up was 55.5 ± 33.9 weeks. Baseline and posttreatment symptom scores (2.6 ± 1.1 vs 1.2 ± 1.0), SNOT-22 scores (2.2 ± 1.1 vs 1.0 ± 0.8), and endoscopy scores (6.7 ± 3.0 vs 2.5 ± 2.0) revealed significant improvement (all, p < 0.001). Contrary to previous publications, patients with high tissue eosinophilia (>10/high power field [HPF]) had significantly more improvement on symptom score (1.9 ± 1.4 vs 1.1 ± 1.0, p = 0.04), SNOT-22 score (1.6 ± 1.3 vs 1.0 ± 0.8, p = 0.03), and endoscopy score (5.12 ± 3.4 vs 3.06 ± 3.0, p = 0.01) than those without., Conclusion: The philosophical approach to ESS in CRS is evolving. Topical therapies, when used appropriately, are highly effective for the most challenging eosinophilic patients. Although corticosteroid is a nonspecific therapy, it is effective when appropriately delivered., (Copyright © 2012 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.)

Background: The modified endoscopic Lothrop (MELP) or Draf III procedure can provide extended endoscopic access to the frontal sinus. The ability to access the entire frontal sinus entirely endoscopically is often debated and there is little published data to predict access based on tumor location., Methods: MELP was performed in 10 cadaver heads. Access was defined as the ability to contact the bone under vision with the head of a 70-degree diamond burr. Access was assessed in 3 areas: the orbital roof and the anterior and posterior walls of the frontal sinus. Endpoints were defined in millimeters from medial orbit and lateral quartile zones., Results: Complete lateral access was excellent anterior and posterior in 95% of sinuses (mean 15.5 ± 7.8 mm and 15.4 ± 7.7 mm, respectively). Access to the orbital roof was limited (10.3 ± 4.6 mm; p = 0.01 comparing anterior and posterior). For sinuses pneumatized beyond the midorbital point, only 10% of lateral orbital roofs were contacted. Orbital roof access correlated with the anteroposterior (AP) distance between the olfactory fossa and outer periosteum of the frontal beak (r = 0.6, p < 0.01)., Conclusion: Lateral endoscopic access to the walls of the frontal sinus is excellent except for the sinus floor. Access to the orbital roof is reliable in the medial quarter only and minimal lateral to the midorbital point. The ability to predict the areas accessible by the endoscopic approach and those areas that might require ancillary approaches is important for both surgical planning and patient expectations., (Copyright © 2011 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.)