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Introduction: Hypoxia due to sinus obstruction is a major pathogenic mechanism leading to sinusitis. The objective of the current study is to define the electrophysiologic characteristics of hypoxia in vitro and in vivo., Methods: Cystic fibrosis bronchoepithelial cells expressing wild-type cystic fibrosis transmembrane conductance regulator (CFTR) and human sinonasal epithelial cells were exposed to 1% or atmospheric O 2 for 24 h. Time-dependent production of cytoplasmic free radicals was measured. Cells were subjected to Ussing chamber and patch clamp technique where CFTR currents were recorded in whole-cell and cell-attached mode for single channel studies. Indices of mucociliary transport (MCT) were measured using micro-optical coherence tomography. In a rabbit hypoxic maxillary sinus model, tissue oxygenation, relative mRNA expression of HIF-1α, pH, sinus potential difference (SPD), and MCT were determined., Results: Ussing chamber (p < 0.05), whole-cell (p < 0.001), and single channel patch-clamp (p < 0.0001) showed significant inhibition of Cl - currents in hypoxic cells. Cytoplasmic free radicals showed time-dependent elevation peaking at 4 h (p < 0.0001). Airway surface liquid (p < 0.0001), periciliary liquid (p < 0.001), and MCT (p < 0.01) were diminished. Co-incubation with the free radical scavenger glutathione negated the impact of hypoxia on single channel currents and MCT markers. In sinusitis rabbits, mucosa exhibited low tissue oxygenation (p < 0.0001), increased HIF1α mRNA (p < 0.05), reduced pH (p < 0.01), and decreased MCT (p < 0.001). SPD measurements demonstrated markedly diminished transepithelial Cl - transport (p < 0.0001)., Conclusion: Hypoxia induces severe CFTR dysfunction via free radical production causing reduced MCT in vitro and in vivo. Improved oxygenation is critical to reducing the impact of persistent mucociliary dysfunction., (© 2023 ARS‐AAOA, LLC.)

Objectives: Patients with spontaneous cerebrospinal fluid (CSF) rhinorrhea can experience significant sinonasal symptom burden, leading to poor quality of life (QOL). The objective of this study was to investigate sinonasal outcome test-22 (SNOT-22) scores in patients undergoing endoscopic endonasal surgery for spontaneous CSF rhinorrhea and compare them to patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis without nasal polyps (CRSsNP)., Methods: A multi-institutional retrospective review of patients with spontaneous CSF rhinorrhea and CRSsNP was performed. Pre-surgery and post-surgery SNOT-22 scores and domains were compared within each group. Improvements in SNOT-22 scores after surgery were compared between the groups., Results: Ninety-one patients were in the CSF rhinorrhea group and 105 patients were in the CRSsNP group. Within each group, surgery significantly improved total SNOT-22 scores, domain scores, and most of the individual symptoms. Comparing the 2 groups revealed similar improvements in total SNOT-22 scores ( P  = .244). The CSF rhinorrhea group improved more in runny nose ( P  < .001), postnasal discharge ( P  < .001), wake up at night ( P  = .024), and embarrassed ( P  = .002). The CRSsNP group improved more in sneezing ( P  = .027), nasal blockage ( P  < .001), decreased sense of smell/taste ( P  = .011), thick nasal discharge ( P  < .001), facial pain/pressure ( P  = .008), and the ear/facial domain ( P  = .010)., Conclusions: Patients with spontaneous CSF rhinorrhea experience significant symptom burden. Those who undergo CSF leak repair should experience significant improvement in QOL similar to patients who undergo ESS for CRSsNP as measured by SNOT-22.

Objectives: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)-22 could suggest a diagnosis of spontaneous CSF rhinorrhea versus chronic rhinosinusitis without nasal polyps (CRSsNP)., Methods: A multi-institutional retrospective chart review of patients with spontaneous CSF rhinorrhea and a control group of CRSsNP patients was performed. Individual SNOT-22 scores and domain scores were compared., Results: One hundred fifteen patients were included in both cohorts. Of the patients in the CSF rhinorrhea group, 48% were misdiagnosed as chronic rhinosinusitis (CRS) prior to the correct identification of a CSF leak. On bivariate analysis, the CSF rhinorrhea group scored significantly higher on the SNOT-22 for runny nose ( P  < .001) and was more likely to designate this symptom as most important ( P  < .001). The CRSsNP group scored significantly higher in nasal blockage ( P  < .001), thick nasal discharge ( P  < .001), facial pain/pressure ( P  < .001), and in the ear/facial ( P  < .001) and rhinologic ( P  = .003) domains. Multivariable logistic regression revealed that runny nose ( P  < .001) was most predictive of spontaneous CSF rhinorrhea while nasal blockage ( P  < .001), thick nasal discharge ( P  < .001), and facial pain/pressure ( P  = .001) were predictive of CRSsNP after adjusting for relevant confounders. No significant difference was observed in total SNOT-22 scores between groups ( P  = .676)., Conclusions: Spontaneous CSF rhinorrhea is commonly misdiagnosed as other sinonasal pathologies. However, individual SNOT-22 items can help aid in suggesting a CSF leak. Spontaneous CSF rhinorrhea should be suspected in patients who have high SNOT-22 scores for runny nose and report this symptom as most important, but have lower scores related to the other cardinal symptoms of CRS.

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.)

Background: Abnormal chloride (Cl - ) transport dehydrates airway surface liquid (ASL) in sinonasal epithelium leading to mucus stasis and chronic rhinosinusitis. As an experimental epithelium, rabbit tissue provides an excellent representation of human sinus disease, and the rabbit sinusitis model is both established and well suited for therapeutic interventions in vivo. Our objective in this study was to evaluate whether ivacaftor reverses the consequences of Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction., Methods: Rabbit nasal cavities were assessed for responsiveness to ivacaftor in vivo (by nasal potential difference [NPD] assay). Rabbit nasal epithelial (RNE) cultures were incubated with an ultrafiltrate of P aeruginosa (PAO1 strain) for 4 hours and tested for acquired CFTR dysfunction. Markers of mucociliary function, including airway surface liquid depth (ASL), periciliary liquid depth (PCL), ciliary beat frequency (CBF), and mucociliary transport (MCT), were measured by micro-optical coherence tomography (μOCT) after PAO1 and/or ivacaftor incubation., Results: Ivacaftor resulted in a significant mean NPD polarization of 21.8 ± 2.1 mV, which was significantly greater than that seen in the low Cl - control (12.9 ± 1.3; p = 0.01). PAO1 exposure induced a state of acquired CFTR dysfunction in rabbit nasal epithelium as measured by forskolin-stimulated short-circuit current (I SC ) (control, 37.0 ± 1.1 μA/cm 2 ; PAO1, 24.4 ± 1.1 μA/cm 2 ; p < 0.001). RNE cultures exposed to PAO1 had inhibited mucociliary function, whereas coincubation with ivacaftor restored mucociliary clearance, as measured by μOCT., Conclusion: In rabbit nasal epithelium, ivacaftor robustly stimulates CFTR-mediated Cl - secretion and normalizes ASL and CBF in PAO1-induced acquired CFTR dysfunction. Preclinical testing of CFTR potentiators as therapy for P aeruginosa rabbit sinusitis is planned., (© 2021 ARS-AAOA, LLC.)

Background: Hypoxia due to closure at the ostiomeatal complex is widely considered one of the major pathogenic mechanisms leading to chronic inflammation in chronic rhinosinusitis (CRS). The objective of this study was to develop and characterize an oxygen-generating biomaterial (OGB) as an innovative treatment strategy for CRS., Methods: An OGB was fabricated by coating hydrophobic beeswax (BW, 15mg or 30mg) on the surface of calcium peroxide - catalase complex (CPO-CA, 30mg) and characterized using scanning electron microscopy (SEM). In vitro releases of both oxygen and hydrogen peroxide (H 2 O 2 ) were spectrophotometrically quantified, and cytotoxicity in human sinonasal epithelial cells (HSNECs) was evaluated. The influence of OGB on transepithelial Cl - secretion was also determined by pharmacologically manipulating HSNECs, cultured under hypoxic conditions, in Ussing chambers., Results: Three groups of OGBs: (1) CPO only; (2) CPO coated with CA and BW (1:1 ratio, CPO-CA(1)-BW(1)); and (3) CPO coated with CA and BW (1:0.5 ratio, CPO-CA(1)-BW(0.5) were analyzed for accumulated oxygen release over 7 days: highest release (mmol/mg) was observed in CPO-CA(1)-BW(1) = 0.11 ± 0.003, followed by CPO-CA(1)-BW(0.5) = 0.08 ± 0.010, and CPO = 0.05 ± 0.004 (p < 0.0001). H 2 O 2 production (mM) was significantly higher in CPO (1.87 ± 0.50) compared to CPO-CA (1)-BW(1) (0.00 ± 0.00) (p < 0.001) after 24 h. CPO-CA(1)-BW(1) showed significantly reduced cytotoxicity and increased Cl - transport compared to the CPO group., Conclusion: A novel OGB (CPO-CA-BW complex) exhibited sustained oxygen release over 7 days without significant cytotoxicity after 24 h in vitro. Preclinical studies evaluating the efficacy of OGB in CRS are warranted, especially for potential therapy in an obstruction-based CRS model., (© 2021 ARS-AAOA, LLC.)

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.

Background: Eosinophilic chronic rhinosinusitis (eCRS) is contemporarily managed by surgical creation of a 'neo-sinus' cavity and corticosteroid irrigations. While most patients gain control of their disease with this approach, similar to preventive inhaler therapy in asthma, some patients need systemic therapies. This study aimed to define those patients needing ongoing systemic therapy for eCRS., Methods: Consecutive adult patients (&gt;18 years) who were seen at a tertiary referral clinic, diagnosed as eCRS and underwent endoscopic sinus surgery were included. Patients were followed up for a minimum of 12 months. All patients had a simple neo- sinus cavity surgically created and used initially a once daily topical corticosteroid irrigation maintenance therapy. Patients who re- quired long term systemic oral corticosteroids and/or biologic therapy were compared to those who remained on topical control., Results: 222 patients with eCRS were assessed (follow-up 2.76 years). Long term systemic therapy was required in 5.4% of pa- tients. Receiver operating curve analysis predicted local treatment failure at an eosinophil count cut-off level 0.455x109/L. Asthma, atopy and aspirin sensitivity also predicted long term systemic therapy. There were no associations with nasal polyposis or revi- sion surgery. Multivariate logistic regression showed elevated blood eosinophil count &gt;0.455 x109/L was 9.27 times more likely to require for systemic medication., Conclusion: Pre-operative blood eosinophil count &gt;0.45 x109/L was associated with failure of local therapy following contem- porary management of eCRS. The quantitative value of serum eosinophilia may be a useful predictor of disease progression and those patients in need of systemic therapies, such as biologic agents.

Background: We recently developed a ciprofloxacin and azithromycin sinus stent (CASS) to target recalcitrant infections in chronic rhinosinusitis (CRS). The objective of this study was to evaluate the anti-inflammatory activity of azithromycin released from the CASS and assess the impact on the integrity and function of primary human sinonasal epithelial cells (HSNECs)., Methods: Pseudomonas aeruginosa lipopolysaccharide (LPS)-stimulated HSNECs were treated with azithromycin and/or ciprofloxacin at concentrations attainable from CASS release. Interleukin-8 (IL-8) secretion was quantified by enzyme-linked immunosorbent assay (ELISA). Epithelial integrity (transepithelial resistance [TEER], paracellular permeability [fluorescein isothiocyanate-labeled dextran], lactate dehydrogenase [LDH] assays) and function (ciliary beat frequency [CBF]) were also evaluated., Results: Azithromycin significantly reduced secreted IL-8 from P. aeruginosa LPS-stimulated HSNECs at all concentrations tested (mean ± standard deviation; control = 5.77 ± 0.39 ng/mL, azithromycin [6 μg/mL] = 4.58 ± 0.40 ng/mL, azithromycin [60 µg/mL] = 4.31 ± 0.06, azithromycin [180 µg/mL] = 4.27 ± 0.26 ng/mL, p < 0.05). Co-incubation with azithromycin (6 µg/mL) and ciprofloxacin (2.4 µg/mL) in LPS-stimulated HSNECs also displayed a significant reduction in secreted IL-8 when compared to P. aeruginosa LPS alone (co-treatment = 4.61 ± 0.29 ng/mL, P. aeruginosa LPS = 7.35 ± 0.89 ng/mL, p < 0.01). The drugs did not negatively impact TEER, paracellular permeability, LDH release, or CBF, indicating retention of cell integrity and function., Conclusion: Azithromycin decreased P. aeruginosa LPS IL-8 production in HSNECs at drug concentrations attainable with sustained release of azithromycin from the CASS. In addition to antibacterial activity, anti-inflammatory properties of the CASS should provide further benefit for patients with recalcitrant CRS., (© 2020 ARS-AAOA, LLC.)

Purpose of Review: Chronic rhinosinusitis (CRS) is a broad classification of airway inflammation that affects a significant portion of the population. The current model of delineating patients suffering from CRS is dated and is no longer as simple as the presence of polyps or no polyps. Continued advances in the endotype descriptions of CRS have allowed for new phenotypic descriptions that aid in driving management and research efforts., Recent Findings: Geographic differences exist between patient presentations, which require a molecular evaluation of the driving forces. Increased understanding of these differences allows for patient-specific treatment decisions., Summary: New descriptions of CRS phenotypes allow for more targeted therapy for patients, particularly to those with difficult to control disease. The previously broad classification of CRS with or without nasal polyps is no longer sufficient at driving these treatment decisions., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: Chronic rhinosinusitis (CRS) is characterized by complex bacterial infections with persistent inflammation. Based on our rabbit model of sinusitis, blockage of sinus ostia generated a shift in microbiota to a predominance of mucin degrading microbes (MDM) with acute inflammation at 2 weeks. This was followed by conversion to chronic sinus inflammation at 3 months with a robust increase in pathogenic bacteria (e.g., Pseudomonas ). MDMs are known to produce acid metabolites [short chain fatty acids (SCFA)] that have the potential to stimulate pathogen growth by offering a carbon source to non-fermenting sinus pathogens (e.g., Pseudomonas ). The objective of this study is to evaluate the concentrations of SCFA within the mucus and its contribution to the growth of P. aeruginosa . Methods: Healthy and sinusitis mucus from the rabbit model were collected and co-cultured with the PAO1 strain of P. aeruginosa for 72 h and colony forming units (CFUs) were determined with the targeted quantification of three SCFAs (acetate, propionate, butyrate). Quantification of SCFAs in healthy and sinusitis mucus from patients with P. aeruginosa was also performed via high performance liquid chromatography. Results: To provide evidence of fermentative activity, SCFAs were quantified within the mucus samples from rabbits with and without sinusitis. Acetate concentrations were significantly greater in sinusitis mucus compared to controls (4.13 ± 0.53 vs. 1.94 ± 0.44 mM, p < 0.01). After 72 h of co-culturing mucus samples with PAO1 in the presence of mucin medium, the blue-green pigment characteristic of Pseudomonas was observed throughout tubes containing sinusitis mucus. CFUs were higher in cultures containing mucus samples from sinusitis (8.4 × 10 9 ± 4.8 × 10 7 ) compared to control (1.4 × 10 9 ± 2.0 × 10 7 ) or no mucus (1.5 × 10 9 ± 2.1 × 10 7 ) ( p < 0.0001). To provide evidence of fermentative activity in human CRS with P. aeruginosa , the presence of SCFAs in human mucus was analyzed and all SCFAs were significantly higher in CRS with P. aeruginosa compared to controls ( p < 0.05). Conclusion: Given that SCFAs are solely derived from bacterial fermentation, our evidence suggests a critical role for mucin-degrading bacteria in generating carbon-source nutrients for pathogens. MDM may contribute to the development of recalcitrant CRS by degrading mucins, thus providing nutrients for potential pathogens like P. aeruginosa ., (Copyright © 2020 Cho, Skinner, Hunter, Weeks, Lim, Thompson, Walz, Zhang, Grayson, Swords, Rowe and Woodworth.)

Purpose of Review: Chronic rhinosinusitis (CRS) is a heterogenous disease process affecting a significant proportion of the population and impacting quality of life and productivity. Historically, CRS has been classified broadly into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Increased understanding regarding unique presentations of CRS subsets and their underlying inflammatory profiles has led to a new system for classifying CRS phenotypes., Recent Findings: Consideration of CRS phenotypes has traditionally been a key factor in determining treatment paradigms. Under a new phenotype classification system, physical findings will continue to drive treatment decisions, but with more precision. Recent rapidly accumulated knowledge indicates that the broad categorization of CRSwNP or CRSsNP is no longer clinically useful. Reorganization of CRS phenotypes and their underlying endotypes will lead to more targeted and efficacious therapy.

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.)

Background: Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivacaftor-releasing biodegradable sinus stent (CISS)-a drug-delivery system that administers ciprofloxacin and the mucociliary activator (ivacaftor) at high local concentrations with prolonged mucosal contact time and sustained delivery. The objective of this study is to evaluate the efficacy of the CISS in a rabbit model of P aeruginosa (PAO1 strain) sinusitis., Methods: Ciprofloxacin/ivacaftor (double layer) was coated on biodegradable poly-D/L-lactic acid (PLLA). A total of 10 sinus stents (5 bare PLLA stent controls, 5 CISSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing infection for 1 week with PAO1. Animals were assessed 3 weeks after stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in-vivo sinus potential difference (SPD) assay., Results: Rabbits treated with CISS had significant reductions in computed tomography (∆ Kerschner scale: control, 0.55 ± 0.92; CISS, -5.92 ± 1.69; p = 0.024) and endoscopy (control, 4.0 ± 0.0; CISS, 1.875 ± 0.74; p = 0.003) scores. A 2-log reduction of PAO1 was observed (control, -2.14 ± 0.77; CISS, 1.84 ± 1.52; p = 0.047). SPD revealed significantly increased Cl - transport in the CISS group compared with the control group (Cl - -free + forskolin ΔPD: control, -4.23 ± 1.04 mV; CISS, -18.36 ± 6.31 mV; p = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals., Conclusion: The CISS had robust clinical efficacy in treating P aeruginosa rabbit sinusitis. The innovative design of double-layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for P aeruginosa sinusitis., (© 2019 ARS-AAOA, LLC.)

Purpose of Review: To assess the most recent evidence for macrolide therapy in chronic rhinosinusitis (CRS)., Recent Findings: Macrolides play a significant role in a select group of patients with CRS. Low-serum and tissue eosinophilia in patients who do not respond to corticosteroid therapy appeared to be an effective predictor of a CRS phenotype suitable for a trial of long-term macrolide therapy. Therapies using half a dose for longer than 12 weeks have noted good outcomes., Summary: The anti-inflammatory and immunomodulatory effects of macrolides have been demonstrated in several studies. Macrolides have shown an important role in patients who are nonresponsive to corticosteroid therapies, therefore patient selection is key. Previous inconsistencies in results may be due to poor patient selection.

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: 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.)