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Background: Patients with diabetes mellitus (DM) are susceptible to invasive fungal rhinosinusitis (IFRS). The mortality rate of IFRS varies greatly among the patients with DM., Objective: To identify the prognostic factors for the overall survival of patients with DM and IFRS., Methods: A retrospective study was conducted in four tertiary hospitals in Thailand, Malaysia and Myanmar. Patients diagnosed with IFRS and DM from 2008 to 2019 were identified. The outcome was the overall survival. Variables analyzed for risk factors were age, HbA1C level, ketoacidosis, white blood cell count, hyperglycemia, duration of DM, current use of diabetic medications, serum creatinine level, and the extensions of IFRS to the orbit, the cavernous sinus and intracranial cavity., Results: Sixty-five diabetic patients with IFRS (age 57.9 ± 13.4 years, male 60%) were identified. The mortality rate was 21.5%. The extensions of IFRS to the cavernous sinus (hazard ratio 5.1, 95% CI [1.4-18.2], p = 0.01) and intracranial cavity (hazard ratio 3.4, 95% CI [1.1-11.3, p = 0.05) predicted mortality. Current use of diabetic medications decreased the mortality risk (hazard ratio 0.2, 95% CI [0.1-0.9], p = 0.03). The 6-month overall survival of the patients with and without the cavernous sinus extension were 51.4% and 83.6%, (p = 0.001), with and without intracranial extension 53.3% and 88.9%, (p = 0.001), and with and without current diabetic medications 82.3% and 57.5%, respectively (p = 0.045)., Conclusions: The extensions of IFRS to the cavernous sinus and intracranial cavity increased the risk of death in patients with DM. Survival was primarily related to current use of diabetic medications.

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

Background: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone., Objective: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS., Methods: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry., Results: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p  = 0.029), and on histology exhibited a higher degree of tissue inflammation ( τ b  = 0.409, p  = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p  = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm 2 , p  = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p   =  0.015). Other outcomes were similar., Conclusions: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.

Background: Eosinophilic chronic rhinosinusitis is an often treatment-resistant inflammatory disease mediated by type-2 cytokines, including interleukin (IL)-5. Mepolizumab, a monoclonal antibody drug targeting IL-5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study's aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients., Methods: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four-weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24., Results: Twenty patients (47.7 ± 11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64 ± 93.80 vs 41.74 ± 53.76 cells per 0.1 mm 2 ; p = .035), eosinophil degranulation remained unchanged (5.79 ± 2.08 vs 6.07 ± 1.20, p = .662), and type-2 cytokine levels increased in sinonasal tissue for IL-5 (10.84 ± 18.65 vs 63.98 ± 50.66, p = .001), IL-4 (4.48 ± 3.77 vs 9.38 ± 7.56, p = .004), IL-13 (4.02 ± 2.57 vs 6.46 ± 3.99, p = .024) and GM-CSF (1.51 ± 1.74 vs 4.50 ± 2.97, p = .001)., Conclusion: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL-5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type-2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response., (© 2022 John Wiley & Sons Ltd.)

Objective: To determine the range of incidental mucosal changes in a general sinonasally asymptomatic population on radiology., Data Sources: Medline (1996-present) and Embase (1974-present) were searched on March 14, 2020, to identify articles that reported radiological sinus mucosal findings in asymptomatic population groups. Bibliographic search of included studies was conducted to identify additional articles., Review Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane Handbook for Systematic Reviews of Interventions. A comprehensive search strategy was formulated and articles screened to extract data reporting Lund-Mackay (LM) score, presence of mucous retention cysts, and maxillary mucosal thickening. A random-effects model was used in meta-analysis., Results: A total of 950 articles were identified, of which 33 manuscripts met the inclusion criteria. The included studies involved 16,966 sinonasally asymptomatic subjects. The mean LM score was 2.24 (95% CI, 1.61-2.87), and an LM score of ≥4 in 14.71% (95% CI, 6.86-24.82%) was present across all general asymptomatic population groups. Mucous retention cysts were noted in 13% (95% CI, 8.33-18.55%) and maxillary mucosal thickening of ≥2 mm in 17.73% (95% CI, 8.67-29.08%)., Conclusion: The prevalence of incidental mucosal changes in a general asymptomatic population on radiology needs to be considered when making a diagnosis of chronic rhinosinusitis.

Background: Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS., Methods: A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed., Results: 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ 2 (2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τ b  = -8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τ b  = -2.37, p = 0.02)., Conclusion: Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.

Importance: Eosinophilic chronic rhinosinusitis (eCRS), contemporarily classified as diffuse type 2 dominant chronic rhinosinusitis (CRS), is characterized by eosinophil-dominant mucosal inflammation. Contemporary management of eCRS as an inflammatory airway condition is multimodal with corticosteroid irrigations after the surgical creation of a neosinus cavity., Objectives: To assess long-term treatment outcomes in patients with primary diffuse type 2 CRS or eCRS receiving multimodal treatment., Design, Setting, and Participants: A prospective cohort study of patients seen in a tertiary rhinology practice recruited from May 2010 to November 2018 was conducted. Follow-up duration was 12 months or more following endoscopic sinus surgery (ESS) with a neosinus cavity formed. Data analysis was performed from August to November 2020. Consecutive adult (≥18 years) patients diagnosed with primary diffuse type 2 dominant CRS or eCRS based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria were included. Type 2 inflammation was defined as more than 10 eosinophils per high-power field obtained from sinus mucosal biopsy and managed with neosinus cavity ESS and ongoing corticosteroid irrigations. Exclusion criteria were less than 12 months of follow-up and secondary CRS., Interventions: Endoscopic sinus surgery with complete removal of intersinus bony partitions to create a neosinus cavity. Nasal irrigation (240 mL) with betamethasone, 1 mg, or budesonide, 1 mg, daily for 3 to 6 months after ESS and tapered to an as-needed basis (minimum, 2-3 per week)., Main Outcomes and Measures: Poor control was defined as polyp recurrence (polyp growth in >1 sinus area on a single side), use of long-term systemic therapy (biologic therapy or ≥3 consecutive months of oral corticosteroids), and revision surgery involving polypectomy. The disease in patients with no poor control criteria was defined as well controlled, and the disease in those with 1 or more criteria was considered poorly controlled. Maintenance medical therapy use and patient-reported outcomes based on the 22-item Sinonasal Outcomes Test for preoperative and last follow-up were collected., Results: Of the 222 participants recruited with primary diffuse type 2 dominant CRS or eCRS and minimum of year of follow-up, 126 were men (56.8%). Mean (SD) age was 54.8 (13.6) years, and median (SD) follow-up was 2.2 (2.2) years. Of the 222 patients, 195 (87.8%) had well-controlled disease, 16 (7.2%) had polyp recurrence, 7 (3.2%) continued to receive long-term oral corticosteroid therapy, 5 (2.3%) received biologic therapy, and 8 (3.6%) underwent a revision polypectomy. Clinically meaningful change on the 22-item Sinonasal Outcomes Test and the nasal subdomain score was maintained at the last follow-up in 134 patients (67.0%). Poor disease control was not associated with poor adherence to irrigation use., Conclusions and Relevance: The findings of this cohort study suggest that long-term disease control and reduction in symptom burden in patients with primary diffuse type 2 CRS or eCRS might be achieved when managed as an inflammatory disorder. Maintenance corticosteroid irrigations in the population examined appeared to be successfully self-tapered to disease activity.

Objectives: Oral corticosteroid (OCS) as a part of appropriate medical therapy (AMT) (formerly maximal medical therapy) in chronic rhinosinusitis remains controversial. While the risks of OCS are well known, the benefit remains unclear due the absence of a standardized prescribing regimen. Consequently, it is difficult to characterize whether the risks of OCS and its ability to avert endoscopic sinus surgery (ESS) are helpful in AMT. When OCS is highly effective at averting surgery, the lesser risks of OCS would be justified because it can avoid the greater risks of ESS. When OCS is poorly effective at averting ESS, the risks of OCS would not be justified because many patients will be exposed to both risks. This study seeks to identify the threshold effectiveness of OCS at averting ESS that would minimize risk exposure to patients., Methods: A probabilistic risks-based decision analysis was constructed from literature reported incidences and impacts of adverse events of OCS and ESS. Monte Carlo analysis was performed to identify the minimum effectiveness required to avoid further intervention (MERAFI) for chronic sinusitis without nasal polyp (CRSsNP) and chronic sinusitis with nasal polyp (CRSwNP)., Results: The analysis showed MERAFI results of 20.8% (95% CI 20.7-20.9%) for CRSsNP and 16.8% (95% CI 16.7-16.9%) for CRSwNP., Conclusions: Given reported OCS effectiveness in the range of 34-71% in CRSsNP and 46-63% in CRSwNP, this analysis suggests that the inclusion of OCS in AMT may be the lower risk strategy., Level of Evidence: N/A Laryngoscope, 131:473-481, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Kimura's disease is a rare, benign, chronic inflammatory disorder characterised by its eosinophilic infiltrate. Patients often present with one or more progressively enlarging subcutaneous lymph nodes in the head and neck region or enlarging salivary glands. We describe the case of a 26-year-old man presenting with severe peripheral eosinophilia and upper airway inflammatory symptoms, who later developed cervical lymphadenopathy and formally diagnosed with Kimura's disease. Based on our English-language MEDLINE literature search, to our knowledge this is the first case report describing treatment of Kimura's disease with mepolizumab., Competing Interests: Competing interests: RJH is a consultant with Medtronic, Olympus and NeilMed pharmaceuticals. He has also been on the speakers’ bureau for Glaxo-Smith-Kline, Seqiris and Astra-Zeneca. JH is supported by an Australian Government Research Training Program (RTP) Scholarship. All other authors have no financial disclosures or conflicts of interest., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Chronic rhinosinusitis (CRS) is a broadly defined process that has previously been used to describe many different sinonasal pathologic conditions from odontogenic sinusitis and allergic fungal sinusitis to the more contemporary definition of broad inflammatory airway conditions. Previous classification systems have dichotomized these conditions into CRS with nasal polyps and CRS without nasal polyps. However, clinicians are learning more about the inflammatory subtypes of CRS, which can lead to improved delivery and effectiveness of treatment., Observations: In clinical practice, treatment decisions are often based on observable findings, clinical history, presumed disease, and molecular pathophysiologic characteristics. A proposed classification system is simple and practical. It proposes that the functional anatomical compartments involved create the first level of separation into local and diffuse CRS, which are usually unilateral or bilateral in distribution. Diffuse does not imply "pansinusitis" but simply that the disease is not confined to a known functional anatomical unit. This classification takes into account whether local anatomical factors are associated with pathogenesis. Then the inflammatory endotype dominance is separated into a type 2 skewed inflammation, as this has both causal and treatment implications. The non-type 2 CRS encompasses everything else that is not yet known about inflammation and may change over time. The phenotypes or clinical examples are CRS entities that have been described and how they align with this system., Conclusions and Relevance: Although research continues to further define the subtypes of CRS into phenotypes and endotypes, the proposed classification system of primary CRS by anatomical distribution and endotype dominance allows for a pathway forward.

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Eosinophilic chronic rhinosinusitis (eCRS) is an inflammatory endotype of CRS. Contemporary treatment includes creation of a "neo-sinus" cavity and postoperative corticosteroid irrigations. Not all patients gain control with local therapy. This study aims to determine, in patients with polyp recurrence, the most common sinuses involved., Methods: A prospective case-series was conducted on consecutive adult (≥18 years) post-FESS eCRS patients followed for a minimum of 12 months. All patients had a neo-sinus cavity created surgically and used corticosteroid irrigations daily for 3-6 months, then tapered to disease control. Sinus cavities were assessed by endoscopy on last follow-up. Polyp recurrence was defined as a score of 5 or 6 in the MLMES in ≥3 sinus cavities. Patient-reported outcomes based on SNOT22 and NSS, frequency of corticosteroid irrigations, and courses of systemic antibiotics and corticosteroid were collected. The pattern of sinus involvement was analyzed., Result: A total of 342 sinus cavities were assessed (mean ± standard deviation, 54.9 ± 13.4 years, 43.2% female). Polyp recurrence occurred in 4.3% (6.4% of patients, n = 7 unilateral) of sinus cavities. Frontal and ethmoid sinus cavities were most affected in those with polyp recurrence, compared to the maxilla and sphenoid (100% vs 100% vs 53% vs 53%, p < 0.01). Although those patients with polyp recurrence utilized more systemic corticosteroids courses per year (0.4 ± 0.4 vs 0.1 ± 0.3, p < 0.01), the use of corticosteroid irrigations was similar (% >4/week; 66.7% vs 48.9%, p = 0.13). Prior surgery was more common in patients with polyp recurrence (86.7% vs 53.5%, p = 0.01)., Conclusion: The frontal and ethmoid sinuses were most affected in those patients with polyp recurrence. Whether the disease is more active in this location or topical therapy has limited access requires further evaluation., (© 2020 ARS-AAOA, LLC.)

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal "microbiotypes" or "states": the first is Corynebacterium -dominated, the second is Staphylococcus -dominated, and the third dominated by the other core genera of the sinonasal microbiome ( Streptococcus, Haemophilus, Moraxella , and Pseudomonas ). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus , suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future., (Copyright © 2020 Bassiouni, Paramasivan, Shiffer, Dillon, Cope, Cooksley, Ramezanpour, Moraitis, Ali, Bleier, Callejas, Cornet, Douglas, Dutra, Georgalas, Harvey, Hwang, Luong, Schlosser, Tantilipikorn, Tewfik, Vreugde, Wormald, Caporaso and Psaltis.)

Purpose of Review: The current understanding of eosinophilic chronic rhinosinusitis (CRS) has developed rapidly over the past decades. Classification of CRS based on the inflammatory endotype more accurately reflects the underlying pathophysiology and better directs treatment. Corticosteroids and more recently biologic agents, target the eosinophil inflammatory that drives this subtype of CRS. Tissue sampling is not always accessible or available and surrogate markers are sought to define this endotype of CRS. The purpose of this review is to assess current systemic predictors of eosinophilic CRS (eCRS) diagnosis., Recent Findings: Blood eosinophils are a moderate surrogate predictor of eCRS. A blood eosinophil count of more than 0.24 × 10/l predicts eCRS with tissue eosinophilia of more than 10 eosinophils per high-power field. It has been further shown that a blood eosinophil count more than 0.45 × 10/l is associated with need for long-term systemic therapy following endoscopic sinus surgery. Other biomarkers reviewed include IgE, eosinophilic cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, IL-5, periostin, eotaxin-3 and IL-16., Summary: There remains limited data surrounding the prognostic use of biomarkers in eCRS. However, peripheral eosinophilia best predicts the eosinophilic density that best predicts the eCRS phenotype. In addition, it is also prognostic of need for more intensive therapy. Simple haematoxylin and eosin stained sinus mucosa still remains the most reliable tissue for assessment and is more accessible than bronchial biopsies.

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.)

Objective: The role of the microbiome in the etiology of chronic rhinosinusitis (CRS) is still in debate. Reductions in richness and diversity have been implicated in CRS; however, limited knowledge exists regarding the impact of the severity of disease on the microbiome. The associations between constituents of the microbiome and the degree of mucosal inflammation and tissue eosinophilia are described., Methods: A cross-sectional study of CRS and non-CRS patients who underwent endoscopic sinus surgery was performed. Sinus mucosal biopsies were assessed for the degree of inflammation and tissue eosinophilia. Middle-meatal swabs were subjected to 16S rRNA gene sequencing, which quantified the prevalence, mean relative abundance, richness, and diversity. Comparisons between the microbiome at the genus level and degree of inflammation (absent, mild, moderate, severe) and tissue eosinophilia (absent, < 10, 10-100, > 100 per high-powered field) were performed., Results: Eight-nine patients (52.8 ± 14.21 years, 64.0% male) were assessed. Of those, 52 had CRS and 37 were controls. Corynebacterium and Staphylococcus were the most abundant genera in both the CRS (29% and 16%) and non-CRS groups (40% and 20%). Richness decreased in more severely inflamed patients (23.2 ± 13.9 vs. 18.1 ± 16.1 vs. 16.8 ± 12.3 vs. 14.7 ± 10.9; P < 0.01), as did diversity (1.4 ± 0.7 vs. 1.2 ± 1.0 vs. 1.2 ± 0.8 vs. 0.9 ± 0.7; P = 0.05). Richness was associated with higher tissue eosinophilia (23.2 ± 13.9 vs. 19.3 ± 17.2 vs. 15.9 ± 11.6 vs. 13.4 ± 6.6; P < 0.01)., Conclusion: The loss of richness and diversity seen in the CRS microbiome appears to be a product of severity of inflammation and tissue eosinophilia. Whether this dysbiosis is causative or a result of the disease with impaired epithelial integrity requires ongoing research., Level of Evidence: 4 Laryngoscope, 129:1265-1273, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Chronic rhinosinusitis (CRS) is a complex disease that incorporates many different conditions. Currently, primary CRS is considered a disease of broad airway inflammation, however, the previous classification of CRS with and without nasal polyposis fails to adequately classify patients based upon their etiology of illness. Our aim with this review is discuss the clinical presentation, radiology, endoscopy, histopathology, and treatment algorithm of three different phenotypes of primary CRS: central compartment atopic disease, eosinophilic CRS, and non-eosinophilic CRS., Methods: A narrative review of a tertiary rhinology center's research themes and how they are applied to clinical protocols and practice was assessed., Discussion: Diagnosis and treatment of upper and lower airway conditions become increasingly important as phenotypes and endotypes are being described. There are well-described therapies to treat the different phenotypes of CRS, based upon the presumed underlying cause of the inflammatory process. Research continues to shed more light on different endotypes and phenotypes of airway inflammation, however, clinical differentiation of CRS can be applied in clinic practice with three simple phenotypes of CRS. Understanding these different phenotypes and their etiologies allows for further management beyond the 'maximum medical therapy and then surgery' approach that has often been used in the management of CRS.

Background: Chronic rhinosinusitis (CRS) has previously been thought to occur secondary to infectious or obstructive etiologies. However, in recent years, primary CRS has been more discretely defined as diffuse airway inflammation, similar to asthma. Adequate medical and surgical therapy are needed to control the inflammation. Our purpose in this study was to evaluate the efficacy and safety of topical corticosteroid treatment., Methods: A focused literature review was conducted and we identified 11 original articles from the years 2013-2018 evaluating safety or efficacy of topical corticosteroid irrigations., Results: Eleven articles were identified. One study found significant benefit between corticosteroid irrigations versus corticosteroid sprays. Two studies found significant benefit between corticosteroid irrigations compared to saline irrigations while two did not. One study found significant improvement in certain patient populations when using corticosteroid irrigations compared to no irrigation. Five studies found no significant increase in risk of adverse side effects with the use of topical corticosteroids., Conclusion: Many factors are associated with efficacious and adequate treatment of primary CRS. The pathology must be correctly diagnosed and be inflammatory in nature. The treatment paradigm should include wide and complete endoscopic sinus surgery for the adequate delivery of topical therapy. Topical therapy should be delivered in large-volume, low-pressure devices with adequate dosing. Although there is some systemic absorption, multiple studies have demonstrated that long-term, daily use of topical corticosteroids does not increase intraocular pressure, suppress the hypothalamic-pituitary-adrenal axis, or increase the risk of subcapsular cataracts. Therefore, topical corticosteroid irrigations should be considered a part of first-line medical treatment in postsurgical CRS patients., (© 2019 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS), in particular with nasal polyps (CRSwNP), has been linked with skewed T-helper 2 and immunoglobulin E (IgE)-mediated allergic responses. The role of atopy in CRS, however, remains unclear. Correlations between immunological allergic markers and patient-reported outcomes measures (PROMs) were investigated., Methods: A cross-sectional study of adult patients with CRS undergoing endoscopic sinus surgery was conducted. Immunological allergic markers included automated immunoassay testing for serum-specific IgE to common allergens (house dust mite, grass, mold, animal epithelia) and total IgE. PROMs were assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22). Patients were defined as atopic based on either a positive specific IgE or elevated total IgE (>160 kU/L)., Results: A total of 446 patients (45.7% female, age 49.05 ± 14.96 years) were recruited, of which 42.8% had asthma, 51.6% had CRSwNP, and 63.0% had eosinophilic CRS. Positive allergen sensitization was detected in 52.9% patients. Total IgE levels were elevated in 28.0% with mean IgE level of 161 ± 269 kU/L. Atopy was associated with younger age at the time of surgery, CRSwNP, asthma, and eosinophilic CRS (eCRS). Atopy was also associated with increased severity in nasal symptom score (13.1 ± 6.4 vs 11.9 ± 6.0, p = 0.04), as well as worse scores in the loss of smell/taste (χ 2 (1) = 5.97, p = 0.02) and need to blow nose (χ 2 (1) = 4.26, p = 0.04) questions in the CRS population. In the CRSwNP population, there was no significant association between atopy and PROMs., Conclusion: Comorbid atopy in CRS is associated with additional symptom burden, reflected mainly within the nasal symptom quality of life markers. Atopy assessment in CRS is important to ensure appropriate and successful treatment of the disease., (© 2018 ARS-AAOA, LLC.)

Purpose of Review: Osteitis is recognized as a common factor in recalcitrant chronic rhinosinusitis (CRS). There is evidence for the association of osteitis with revision surgeries and CRS severity, in terms of higher Lund-Mackay scores. This is a narrative review on the osteitis in CRS patients., Recent Findings: Evidence to date is inconclusive with regard to the etiology and pathogenesis of this bony thickening. Histopathology of osteitis in primary CRS is likely a process of neo-osteogenesis and bone remodeling. For better understanding, various associating factors have been studied including an inflammatory pattern of rhinosinusitis. Recent studies have associated osteitis with nasal polyps and tissue eosinophilia with the increase in periostin expression and P-glycoprotein mucosal expression. There is no association of osteitis to symptoms or quality of life. Osteitis is an outcome of neo-osteogenesis rather than inflammatory processes in CRS patients without a prior history of surgery. While CT has become a staple in osteitis assessment, the standards for grading osteitic severity remain in an experimental stage. There is no association between the presence or severity of osteitis at the time of surgery and clinical outcomes at 1 year after surgery. This review provides a comprehensive overview of the pathogenesis, epidemiology, and correlation with clinical and biological factors of osteitis in CRS patients.

Objectives: The Draf III frontal sinusotomy is an established surgical procedure with an important role in the surgical management of recalcitrant chronic rhinosinusitis (CRS). In 2012, the outside-in approach to the Draf III was described as a safe and efficient procedure. Smell recovery in inflammatory CRS is challenging, and to date there is limited evidence suggesting that Draf III improves patient-reported olfactory dysfunction from CRS., Methods: A consecutive series of patients who underwent an outside-in Draf III for inflammatory CRS by a single, tertiary rhinologist were reviewed. Patients were excluded if the Draf III was performed for noninflammatory conditions. Postoperatively, patients were maintained on long-term corticosteroid irrigations, and adherence was assessed. Prospectively collected data included patient demographics, a visual analogue scale for smell, overall Sinonasal Outcome Test Score (SNOT-22), global nasal function score, and a clinician-graded clinical outcome score., Results: One hundred and four patients (41.1% female) aged 54 ± 12 years underwent an outside-in Draf III. The median follow-up time was 30.6 months (range 12.2-72.1). The majority of patients rated their smell loss as moderate or worse preoperatively; however, this was significantly improved at postoperative review (71.2% vs. 27.6%; Kendall tau-b, P < 0.01). The SNOT-22 score improved after surgery (2.32 ± 1.09 vs. 0.78 ± 0.69, P < 0.0001). Medication adherence was significantly associated with improved clinical outcome score (Kendall tau-b, P < 0.004). Aspirin exacerbated respiratory disease was found to be a significant risk factor predicting poor clinical outcome on univariate analysis (Odds Ratio = 4.69 (1.03-21.2), P = 0.04)., Conclusion: The outside-in Draf III appears to facilitate sustained, meaningful improvement in several self-reported outcomes, including smell. However, further study and comparison to less aggressive surgery will be required to confirm its true benefit., Level of Evidence: Level 4 Laryngoscope, 129:25-30, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Since fungi were postulated as a potential cause of CRS in the late 1990s, there has been increasing controversy about the use of both topical and systemic antifungal agents in its management. Although interaction between the immune system and fungus has been demonstrated in CRS, this does not necessarily imply that fungi are the cause of CRS or that antifungals will be effective its management., Objectives: To assess the effectiveness of topical or systemic antifungal therapy in the treatment of CRS., Search Methods: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 8 March 2011., Selection Criteria: All randomised, placebo-controlled trials considering the use of topical or systemic antifungal therapy in the treatment of CRS and allergic fungal sinusitis (AFS). CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) or American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria., Data Collection and Analysis: We reviewed the titles and abstracts of all studies obtained from the searches and selected trials that met the eligibility criteria. We extracted data using a pre-determined data extraction form. There was significant heterogeneity of outcome data reporting with reports containing both parametric and non-parametric representations of data for the same outcomes. Means and standard deviations for change data were unavailable for a number of trials. Due to the limited reported data, we contacted authors and used original data for data analysis., Main Results: Six studies were included (380 participants). Five studies investigated topical antifungals and one study investigated systemic antifungals. The risk of bias in all included studies was low, with all trials being double-blinded and randomised. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo for any outcome. Symptom scores in fact statistically favoured the placebo group. Adverse event reporting was statistically significantly higher in the antifungal group., Authors' Conclusions: On the basis of this meta-analysis, there is no evidence to support the use of either topical or systemic antifungal treatment in the management of CRS.

Objectives/hypothesis: Polypoid edema of the middle turbinate is a marker of inhalant allergy. Extensive edematous changes may result in limited central nasal and sinus disease, which has been called central compartment atopic disease (CCAD). Radiologically, this is seen as soft tissue thickening in the central portion of the sinonasal cavity with or without paranasal sinus involvement. When the sinuses are involved, the soft tissue thickening spares the sinus roof or lateral wall (centrally limited). This centrally limited radiological pattern was assessed among chronic rhinosinusitis (CRS) patients and compared to allergy status., Study Design: Diagnostic cross-sectional study., Methods: This study included consecutive CRS patients without prior sinus surgery. Computed tomography (CT) scans of the paranasal sinuses were blindly assessed and allergy status was confirmed by serum or skin testing. Individual sinus cavities were defined as either centrally limited or diffuse disease. The radiological pattern that may predict allergy was determined, and its diagnostic accuracy was calculated., Results: One hundred twelve patients diagnosed to have CRS, representing 224 sides, were assessed (age 46.31 ± 13.57 years, 38.39% female, 41.07% asthma, Lund-Mackay CT score 15.88 ± 4.35, 56.25% atopic). The radiological pattern defined by centrally limited changes in all of the paranasal sinuses was associated with allergy status (73.53% vs. 53.16%, P = .03). This predicted atopy with 90.82% specificity, 73.53% positive predictive value, likelihood positive ratios of 2.16, and diagnostic odds ratio of 4.59., Conclusions: A central radiological pattern of mucosal disease is associated with inhalant allergen sensitization. This group may represent a CCAD subgroup of patients with mainly allergic etiology., Level of Evidence: 3b Laryngoscope, 128:2015-2021, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Background Eosinophilic chronic rhinosinusitis (eCRS) is linked with skewed T-helper 2 or immunoglobulin E (IgE)-mediated allergic responses, with differing diagnosis, prognosis, and management to non-eCRS. Objective The association between biomarkers and eCRS was investigated to assess the predictors of eCRS. Methods A cross-sectional study of adult patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery was conducted. eCRS was defined by histopathological assessment showing >10 eosinophils/high-power field on sinus mucosal biopsy. Blood tests were performed preoperatively and assessed for a full blood count including eosinophils and a white cell count (WCC) as well as biochemical markers of inflammation and atopy including Immunoglobulin E (IgE), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ImmunoCAP testing for serum-specific IgE. Comparisons between eCRS and non-eCRS patients were performed. Results 345 patients (48.1% female, age 48.72 ± 15.06 years) were recruited, with 206 (59.7%) identified as eCRS, 41% with asthma and 47% CRS with nasal polyps. eCRS patients were more likely to have asthma ( P < .01) and nasal polyps ( P < .01). Blood eosinophils were significantly elevated in eCRS (0.42±0.34 vs 0.17±0.13 × 10 9 /L, P < .01) as were eosinophils as a ratio of WCC (6.21 ± 4.48 vs 2.55 ± 1.84, P < .01). ESR was decreased when compared with non-eCRS (8.1±7.87 vs 10.65±11.91, P = .03). Receiver operating characteristic curve analysis predicted high tissue eosinophilia at blood eosinophil levels above 0.24 × 10 9 /L (sensitivity 70.9%, specificity 78.4%, area under the curve [AUC]: 0.792, P < .01). eCRS was predicted at eosinophil above 4.27% of total WCC (sensitivity 64.1%, specificity 88.5%, AUC 0.797; P < .01; positive predictive value 89.2%, negative predictive value 62.4%, positive likelihood ratio 5.57, and diagnostic odds ratio 13.71). There was no significant association among WCC, CRP, IgE, or ImmunoCAP testing. Conclusion eCRS is associated with elevated blood eosinophils (>0.24 × 10 9 /L), eosinophil ratio (>4.27% of total WCC), and lower ESR when compared with non-eCRS.

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.)

Purpose of Review: Chronic rhinosinusitis (CRS) is a multidimensional inflammatory disorder of the nose and paranasal sinuses. We reviewed the recent literature to identify improved methods to assess, control, and manage these difficult to control patients., Recent Findings: The role of endotyping in CRS has offered a better understanding of the underlying pathophysiology and allows for more targeted treatment. The understanding of systemic disorders and their role in CRS and the importance of topical treatment reaching the sinuses has also allowed for better control of these patients. We have provided some of the commonly identified causes for uncontrolled CRS and a sensible approach to assessing these patients. We have also focused on common areas of pitfalls in the surgery and choice of patients and the role for ongoing systemic treatment. The future of managing this difficult condition includes endotyping using inflammatory markers and individualizing the treatment to the patient by using specific monoclonal antibodies.

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: Isolated polypoid changes of the middle turbinate were recently reported as having a high association with inhalant allergy. A more advanced manifestation of this association may present as polypoid changes of the entire central sinonasal compartment (i.e., the middle and superior turbinates, and the posterosuperior nasal septum), while the lateral sinus mucosa remains relatively normal., Objective: To introduce and describe this newly recognized variant of chronic rhinosinusitis (CRS), termed central compartment atopic disease (CCAD)., Methods: A case series of 15 patients from two institutions who presented with sinonasal symptoms and demonstrated central compartment polypoid mucosal changes on computed tomography (CT). The endoscopic appearance of central compartment edema was assessed. Allergy status was determined by skin or serum in vitro testing., Results: The mean ± standard deviation patient age was 42.4 ± 14.8 years, and 47% of the patients were women. All 15 patients had a diagnosis of allergic rhinitis symptomatically, and those who underwent allergy assessment (14/15) tested positive. All the patients had central compartment polypoid edema on endoscopy and central nasal soft-tissue thickening with peripheral clearing on CT. Even with more severe sinus disease, a central focus of inflammatory change existed., Conclusion: CCAD may represent a local inhalant allergy process that affects the central nasal structures of ethmoid origin. Although inhalant allergy changes mainly appear within the nasal cavity, medial-to-lateral progression to involve the sinuses can occur as a simple obstructive phenomenon. This is a pattern of CRS distinct from the more diffuse sinonasal inflammatory disease and likely requires allergy management as a core component.

Purpose of Review: We assess the literature on the pharmacokinetics, indications, important considerations, and effectiveness of long-term, low-dose macrolide antibiotics in chronic rhinosinusitis (CRS)., Recent Findings: The key to effective implementation of macrolide therapy in CRS is appropriate patient selection. Macrolides have demonstrated the most benefit in Th1-mediated non-eosinophilic CRS when used for durations of at least 3 months. Macrolide antibiotics have demonstrated great benefit when used for their anti-inflammatory or immunomodulatory properties, which include the blockage of pro-inflammatory cytokines, such as interleukin (IL)-8 and tumor necrosis factor-α (TNF-α). They have been used in CRS patients not responding to traditional corticosteroid-based treatment regimens, but appear to be most effective specifically in Th1-mediated non-eosinophilic CRS in long durations and low doses. Further research is needed to better identify characteristics known to correlate with macrolide response so early directed therapy can be implemented.

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: Chronic rhinosinusitis (CRS) has a multifactorial etiology, with a debate about the role of inhalant allergy in the pathogenesis of CRS., Objective: This study assessed the impact of allergy status on externalized paranasal sinuses after tumor resection to determine if a predisposition to inhalant allergy brought about additional inflammation after sinus surgery., Methodology: A case-control study was performed on patients who had no history of CRS who underwent paranasal sinus tumor resection. Allergic sensitization was defined by a positive serum ImmunoCAP test result. Outcomes were measured at least 6 months after surgery by using the modified Lund-MacKay endoscopic score and the 22-item Sino-Nasal Outcome test, with rhinitis, sleep, psychological, ear and/or facial, and sinus subscores to assess the impact of allergy status on mucosal inflammation., Results: A total of 103 patients (53.44 ± 17.46 years; 46% women) were assessed. Of these, 61.17% were allergically sensitized at the time of surgery. Postsurgery endoscopic assessment was similar [the modified Lund-Mackay endoscopic score allergic sensitized 0.5 (1.7) versus nonallergic sensitized 0.0 (0.9); p = 0.15]. Sinonasal symptoms were also similar between the groups' 22-item Sino-Nasal Outcome test scores, allergic sensitized versus allergic nonsensitized, (allergic 28.9 ± 20.8 versus nonallergic 33.5 ± 19.7; p = 0.31), rhinitis score (5.9 ± 5.5 versus 6.4 ± 4.7; p = 0.66), sleep score (6.9 ± 5.9 versus 7.7 ± 4.8; p = 0.50), ear and/or facial symptom score (3.4 ± 3.6 versus 4.3 ± 3.3; p = 0.22), psychological score (6.9 ± 6.0 versus 8.3 ± 6.7; p = 0.29), and of nasal symptom score (6.4 ± 5.2 versus 7.0 ± 5.3; p = 0.61)., Conclusions: Externalization of the sinuses in patients with inhalant allergy did not bring about significant additional inflammation in patients after tumor surgery.

Background: Retromaxillary air cells (RMC) are posterior ethmoid cells that separate the maxillary and ethmoid sinuses. The clinical significance of these cells in contributing to revision functional endoscopic sinus surgery (FESS) is unknown., Objectives: To investigate the prevalence, anatomic dimensions, and radiographic characteristics of RMC in patients with recalcitrant chronic rhinosinusitis after previous FESS., Methods: A retrospective review of patients who underwent revision FESS at a tertiary medical center between January 1, 2012, and December 31, 2014. Computed tomographies of patients who underwent revision FESS, including posterior ethmoidectomies, were reviewed. Each side of the scan was assessed for residual RMCs. The radiographic dimensions and Lund-Mackay (LM) scores of these cells were recorded., Results: Sixty-nine patients who underwent revision FESS were identified. The median age of the patient population was 51 years (range, 21-79 years). Forty-two percent of the patients had nasal polyps. The mean number of previous FESS was 2 (range, 1-10). Incompletely dissected RMCs were identified in 101 of 138 analyzed sides (73%), despite documented previous posterior ethmoidectomies. Sixty-five percent of RMCs had an LM score of ≥1; RMCs of patients with polyps were more likely to have an LM score of 2 (p = 0.049). There was a significant correlation between the number of previous FESS procedures and whether the RMCs had been dissected (p = 0.010). There also was a significant correlation between RMC height and the number of previous FESS procedures (p = 0.015)., Conclusion: RMCs seemed to often be undissected during primary FESS and, thus, were commonly encountered in revision FESS. The majority of analyzed cells in this cohort demonstrated an LM score of ≥1, which indicated that these cells frequently harbor residual diseased mucosa that may contribute to the need for revision surgery.

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.)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition with heterogeneous pathophysiology. A cornerstone of the management of this condition is the use of anti-inflammatory agents. Corticosteroids are very effective and the most commonly used, but other drugs with immunodulatory activity such as anti-IL5, doxycycline (Th2), and macrolides (anti-neutrophilic/IL8) have been shown to have efficacy. Although systemic corticosteroids have shown benefit in managing this condition, the frequency of use often required in this condition is associated with significant adverse effects. Topical corticosteroids, particularly when utilized after endoscopic sinus surgery and delivered in a high volume, high pressure manner, provide the desired anti-inflammatory effects with nearly negligible systemic absorption. Studies assessing the long-term use of second generation topical corticosteroids have demonstrated no significant effects on cortisol levels, growth rate, intraocular pressures or lens opacification, or local mucosal atrophy. Patients who often respond most favorably to corticosteroid treatment are those with a Th2-mediated, highly eosinophilic CRSwNP. However, there is a subset of patients who are steroid resistant. In the case of a predominantly neutrophilic CRSwNP, it is important to be aware that patients may respond well to the use of macrolide therapy. Additionally, the use of verapamil has shown promise in increasing steroid responsiveness in a difficult to treat group of patients with steroid resistance. Topical corticosteroids play a key role in the long term management of this complicated inflammatory condition by providing the much needed pharmacologic local control with minimal systemic adverse effects., (© 2016 S. Karger AG, Basel.)

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: The initiating mediators of T-helper 2 inflammation, often seen in eosinophillic chronic rhinosinusitis (CRS), remains poorly understood. Interleukin (IL) 25, IL-33, and thymic stromal lymphopoietin (TSLP) are epithelial-derived cytokines implicated in the initiation of T-helper 2 inflammation and eosinophilia in other diseases. The expression of these cytokines was compared with phenotypic and histopathologic markers to investigate the factors that may drive eosinophilic inflammation in CRS., Method: Sinus mucosal samples from patients with CRS who were undergoing sinus surgery as part of their management were analyzed for IL-25, IL-33, and TSLP messenger RNA (mRNA) expression by quantitative polymerase chain reaction. Patients with tumor and who were undergoing surgery via an endonasal approach with normal sinus mucosa were controls. The mRNA expression was compared with CRS phenotype and histopathologic measures of eosinophilic inflammation. Immunohistochemical staining was used to confirm mRNA expression., Results: Thirty-nine patients (mean ± standard deviation age; 48.2 ± 15.0 years, 38% women), 12 patients with CRS with nasal polyps, 20 patients with CRS without nasal polyps, and 7 controls were recruited. Higher IL-25 (p = 0.005) and IL-33 (p = 0.003) mRNA and protein expression was observed in patients with >10 eosinophil/hpf. TSLP showed no significant associations (p = 0.39). Similar overexpression was seen in eosinophilic dominated inflammation (IL-25, p = 0.01; IL-33, p = 0.02) and patients with greater inflammatory severity., Conclusion: IL-25 and IL-33 overexpression was observed in eosinophilic CRS, The release of these cytokines by dysfunctional endothelium may perpetuate the eosinophillic inflammation in CRS.

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.)

Chronic rhinosinusitis (CRS) has a significant impact not only on individuals who are afflicted but also on society as a whole. An increasing emphasis is being placed on incorporating the best available evidence into the care of patients, in association with an individual clinician's expertise and the patient's values. Recent evidence-based reviews with recommendations (EBRRs) have distilled our knowledge of CRS treatment options and have also pointed out continued gaps in this knowledge. This review synthesizes the findings of 8 EBRRs regarding CRS published in the International Forum of Allergy and Rhinology between 2011 and 2014. The recommendations in this review are based on the best available evidence and are meant to be incorporated into each patient's individual care, along with the practitioner's expertise and the individual patient's values and expectations. It is hoped that the EBRRs, and the process that spawned them, can provide the foundation for future guidelines in the diagnosis and management of CRS., (© 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.)

Objectives: To develop a chronic rhinosinusitis (CRS) disease control staging system that predicts patient and physician opinion. This involved exploring the predictive capacity of the proposed European Position Paper on Rhinosinusitis (EPOS) 2012 staging system and other potential scoring systems based on patient symptoms and objective criteria., Study Design: Prospective study., Setting: Tertiary hospitals., Subjects and Methods: Adults CRS patients undergoing sinus surgery were prospectively enrolled from a tertiary clinic. The Sino-Nasal Outcome Test 22, endoscopy score, and systemic medication were recorded at 6 and 12 months. A physician and patient report of their condition as either "controlled,""partly controlled," or "uncontrolled" was also recorded. Ordinal regression was used for modeling a staging system. The EPOS criteria and various combinations were assessed. Kappa agreements between the staging systems and patient/physician reports were analyzed., Results: One hundred six patients were assessed. Nasal obstruction (P = .02), endoscopic mucosal inflammation (P < .001), and thick and/or purulent discharge (P = .01) associated with progress reports. A modified staging system of Nasal Obstruction, Systemic medication used, and Endoscopic inflammation (NOSE) was selected on predictive strengths. The EPOS and NOSE had significant agreement with physician's (k = 0.29, P < .01, and k = 0.45, P < .01) and patient's report (k = 0.18, P = .01, and k = 0.32, P < .01)., Conclusions: The disease control assessment by EPOS has slight agreement with patients and a physician. A simpler NOSE system using nasal obstruction, mucosa, and discharge is proposed.

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.)