SinoNasal Microbiota Transfer to treat recalcitrant chronic rhinosinusitis: A case series.

KEY POINTS: SinoNasal Microbiota Transfer (SNMT) was safe with immediate benefit in all recipients, with sustained improvement in two of three recipients for up to 180 days. The addition of antimicrobial photodynamic therapy worsened chronic rhinosinusitis. These promising SNMT results warrant further study of safety and efficacy.

Olfaction and Quality of Life in Patients with Eosinophilic CRS Undergoing Endoscopic Sinus Surgery.

Introduction Chronic rhinosinusitis (CRS) is a common inflammatory disease. This high prevalence leads to high direct and indirect public health costs, which include medical visits, laboratory tests and imaging, pharmacotherapy, hospitalizations, and surgical treatment. Furthermore, CRS has a substantial impact on patient quality of life, affecting productivity and being a common cause of absence from work CRS-associated olfactory dysfunction is highly prevalent, the actual effectiveness of surgical intervention remains inconsistent. Although there are studies evaluating the postoperative course of patients with eosinophilic Chronic rhinosinusitis (eCRS) treated with high-volume budesonide irrigation, there is little objective information regarding the impact of this intervention on olfactory status and quality of life. Objective To conduct a pre- and postoperative analysis of olfaction and quality of life in patients with eCRS treated with surgical intervention followed by high-volume budesonide nasal irrigation. Methods Prospective, descriptive, uncontrolled study of patients with eCRS. All patients underwent pre- and postoperative nasal endoscopy, SNOT-22 questionnaire, and the University of Pennsylvania Smell Identification Text (UPSIT), always by the same previously trained examiner. The SNOT-22 questionnaire and the UPSIT were readministered to all patients at 3 months, 6 months, and 1 year postoperatively, and scores compared with those obtained preoperatively. Results Twenty patients were included in the study, 13 males and 7 females, between the ages of 23 and 65; 8 patients had comorbid asthma. Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063). There was no significant association between eosinophil concentrations in polypoid tissue and postoperative SNOT-22 and UPSIT results. Patients with tissue eosinophils >50 had a lower preoperative UPSIT score. As early as 3 months postoperatively, a significant improvement in quality of life was already noticeable, as represented by a decrease in SNOT-22 values, which persisted through the 1-year postoperative follow-up evaluation (p = 0.0005). Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063). Conclusion Surgery effectively controlled eCRS in patients who adhered to high-volume budesonide nasal irrigation postoperatively. There were significant improvements in quality of life and olfaction, which persisted at least up to one year postoperatively.

Effect of Body Weight on Response to Nasal Glucocorticoid Treatment in Allergic Rhinitis.

Allergic rhinitis is among the most common chronic diseases in the world. Obesity can lead to a chronic systemic inflammatory process. In this study, we evaluated the effects of body weight on the response to treatment of allergic rhinitis with nasal corticosteroids. Two groups of patients diagnosed with allergic rhinitis were compared: one composed of obese patients and one composed of normal weight patients. Nasal endoscopy, peak nasal inspiratory flow, quality of life, the VAS, SNOT22, and NOSE-5 questionnaires, and the concentration of nasal cytokines (INF-γ, TNF-ᾳ, IL-4, IL-5, IL-6, and IL-10) through nasal brushing were evaluated before and after treatment with 400 mcg/day nasal beclomethasone. No differences were identified between the groups in nasal endoscopy, peak nasal inspiratory flow, the VAS, SNOT22, and NOSE-5 questionnaires, or in the cytokines INF-γ, TNF-ᾳ, IL-4, IL-5, IL-6, and IL-10 prior to nasal corticosteroid treatment. Both groups showed improvement in the VAS, SNOT-22, and NOSE-5 questionnaires and an increase in peak nasal inspiratory volumes after treatment. In the eutrophic group, there was an increase in INF-γ and IL-5 after treatment. When comparing the variation in cytokines before and after treatment between groups, IL-10 was the cytokine that showed altered behavior dependent on weight. Obesity did not seem to impact nasal symptoms and physiology and presented a similar clinical response to treatment with nasal corticosteroids to normal weight patients. However, obese patients had an impaired anti-inflammatory response during treatment with nasal corticosteroids.

Prescribing Practices and Barriers of Biologics for Chronic Rhinosinusitis Amongst Otolaryngologists.

OBJECTIVE(S): Biologics for chronic rhinosinusitis with nasal polyposis (CRSwNP) are an evolving therapeutic option, but there are limited data on physician experiences in prescribing them. The goal of this study was to gain a better understanding of these experiences including prescribing practices, patient factors which guide prescriber decision, and physician and patient-reported issues which might limit cost-effectiveness of these therapies. METHODS: A survey was distributed to attending otolaryngologists using the Canadian Society of Otolaryngology (CSOHNS) email distribution and eSurvey program. Responses were tabulated for the entire cohort and compared between rhinologists and non-rhinologists where appropriate. Frequencies and proportions were expressed as a percentage of total respondents. Fisher's exact test was used for statistical analysis between groups. RESULTS: Seventy-nine total survey responses were recorded representing a response rate of 43%. Significantly more rhinologists reported prescribing biologic medications on their own (100% vs. 50%; p < 0.001) and a higher proportion (1 to 10% vs. <1%) of their patients were on biologics compared with non-rhinologists (p = 0.023). Rhinologists were more likely to consider poor response to medical therapies, need for rescue steroids, and comorbid type 2 conditions in their decision to pursue biologics than non-rhinologists, but they also experienced poorer assistance from patient support programs and less availability to medications. CONCLUSION: Rhinologists are more comfortable with prescribing and managing biologics for CRSwNP compared with non-rhinologist colleagues. Clinicians prescribing biologic medications for CRSwNP should be familiar with guidelines, indications, and potential adverse events. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Comparison between upper and lower airway microbiome profiles in chronic rhinosinusitis patients.

BACKGROUND: Dysregulation of the airway microbiota is thought to contribute to airway inflammation in both chronic rhinosinusitis (CRS) and asthma. However, the relationship between the upper and lower airway microbiome remains unclear. METHODS: Sinus and lung brushes were collected from 29 CRS participants undergoing sinus surgery. DNA was extracted and submitted for 16s rRNA microbiome sequencing. Alpha and beta diversity metrics, taxonomic composition, and differences between individual taxa were compared for paired sinus and bronchial samples. RESULTS: Twenty-three out of 29 participants had sufficient samples for analysis. The mean (standard deviation) age was 51.59 (14.57) years, and 10 (44%) patients were female. Twelve (52%) patients had comorbid asthma. Sinus brushes had significantly higher alpha diversity indexes (Shannon and Faith) compared to bronchial brushes (p < 0.001). Beta diversity metrics were significantly different between the sinus and bronchial samples. Principal coordinate analysis showed no clustering of paired nasal and bronchial samples. Sinus brushes had significantly more Lawsonella, Corynebacterium, and Staphylococcus compared to bronchia brushes, while the latter were enriched in Tropheryma and Sphingomonas, among others (false discovery rate [FDR]-adjusted p < 0.01). Finally, CRS patients with comorbid asthma had significantly higher Pseudomonas and Peptoniphilus in sinus brushes and lower Prevotella in bronchial brushes when compared to non-asthmatics (FDR-adjusted p < 0.01). CONCLUSION: The sinus and bronchial bacterial microbiomes differ in important ways. Our study suggests that migration of bacteria from the sinus into the lower airways is unlikely in patients with CRS.

Real-World Adverse Events After Type 2 Biologic use in Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: To investigate the frequency and nature of adverse events related to type 2 biologic use in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including dupilumab and mepolizumab. METHODS: This is a single-institution retrospective study of real-world patient data. Patients were included if they have a diagnosis of CRSwNP, have undergone at least one endoscopic sinus surgery, and have taken at least two doses of dupilumab or mepolizumab between January 1, 2016, and July 1, 2023. Data collected include clinicodemographic information and past medical/surgical history. The primary outcomes are the incidence and types of adverse events. Adjusted odds ratio was calculated to compare the biologics using logistic regression. Risk factors for developing adverse events were investigated. RESULTS: Eighty-seven patients on dupilumab and 51 patients on mepolizumab were included. Thirty-nine (45%) and 10 (20%) patients respectively encountered adverse events, which differed from phase 3 trial data. The adjusted odds ratio for adverse event rates between these two treatment groups was 3.8 (95% CI, 1.5-10.5). The most common adverse events for dupilumab were arthralgia (16%), rash (14%), and conjunctivitis or xerophthalmia (10%). The main adverse events for mepolizumab were headache (6%) and fatigue (6%). Seven dupilumab and three mepolizumab patients discontinued therapy due to adverse events. The average duration of treatment was 22.5 (range: 1-77) months for mepolizumab and 15.9 (range: 1-35) months for dupilumab. CONCLUSION: Dupilumab and mepolizumab have distinct adverse event profiles. This study contributes to informing clinicians' decisions regarding the use of type 2 biologics in CRSwNP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Non-Type 2 and Mixed Inflammation in Chronic Rhinosinusitis and Lower Airway Disease.

OBJECTIVE: The aim was to discuss the role of non-type 2 inflammation in patients diagnosed with chronic rhinosinusitis (CRS) and comorbid lower airway disease. DATA SOURCES: Medline, Embase, National Institute for Health and Care Excellence, TRIP Database, ProQuest, Clinicaltrials.gov, Cochrane Central Registry of Controlled Trials, Web of Science, government and health organizations, and graduate-level theses. REVIEW METHODS: This scoping review followed PRISMA-ScR guidelines. Search strategy was peer-reviewed by medical librarians. Studies were included if they utilized airway sampling, non-type 2 cytokines, and patients with CRS and lower airway disease. RESULTS: Twenty-seven from 7060 articles were included. In patients with CRS and comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and chronic obstructive pulmonary disease (COPD)/bronchiectasis, 60% (n = 12), 33% (n = 2), and 100% (n = 1), respectively, demonstrated mixed or non-type 2 endotypes. Comorbid CRS and asthma produced type 1 (n = 1.5), type 2 (n = 8), type 3 (n = 1), mixed type 1/2 (n = 1), and mixed type 1/2/3 (n = 8.5) endotype shifts. AERD demonstrated type 2 (n = 4), mixed type 2/3 (n = 1), and mixed type 1/2/3 (n = 1) endotype shifts. CRS with COPD or bronchiectasis demonstrated a mixed 1/2 (n = 1) endotype shift. CONCLUSION: Type 2 disease has been extensively reviewed due to advent biologics targeting type 2 inflammation, but outcomes may be suboptimal due to the presence of non-type 2 inflammation. A proportion of patients with CRS and comorbid lower airway disease demonstrated mixed and non-type 2 endotype shifts. This emphasizes that patients with unified airway disease may have forms of inflammation beyond classical type 2 disease which could inform biologic development. Laryngoscope, 134:1005-1013, 2024.

The Serpentine Sign: A Reliable Endoscopic and Radiographic Finding in Empty Nose Syndrome.

OBJECTIVE: Empty nose syndrome (ENS) is a relatively uncommon disease that greatly impacts the quality of life and presents diagnostic challenges. We sought to identify objective clinical findings unique to patients with ENS, and in doing so identified compensatory mucosal hypertrophy in an alternating, undulating swelling on endoscopy and coronal computerized tomography (CT) that we have termed the "Serpentine Sign." Here, we investigated whether this radiographic finding is a reliable manifestation in ENS patients. METHODS: Retrospective review was undertaken to identify ENS patients with past turbinoplasty, an ENS6Q score of at least 11/30, and symptomatic improvement with the cotton placement test. Control patients without complaints of ENS symptoms (ENS6Q < 11) were identified for comparison. ENS and control patients had coronal CT imaging available to evaluate for the Serpentine Sign, as well as ENS6Q scores, and histologic analysis of nasal tissue. RESULTS: 34 ENS and 74 control patients were evaluated for the presence of the Serpentine Sign. Of the 34 patients with ENS, 18 exhibited this radiographic finding on CT imaging (52.9%) compared to 0 of the 74 control patients (p < 0.0001). Further analysis demonstrated that ENS patients with the Serpentine Sign had lower median scores on ENS6Q than ENS patients without (17.5 vs. 22, p = 0.033). Histology revealed disorganized subepithelium rich in seromucinous glands similar to the nasal septum swell body. CONCLUSION: The "Serpentine Sign" is a unique presentation of hypertrophic change to the nasal septum soft tissue that is specific to ENS patients and may serve as a reliable radiographic and endoscopic finding in diagnosis. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1089-1095, 2024.

Quantifying surgical completeness in patients with aspirin exacerbated respiratory disease.

BACKGROUND: Aspirin exacerbated respiratory disease (AERD) in patients who have had sinus surgery remains a management challenge. Aspirin desensitization and biologics are additional treatment options. It remains unclear if patients require a more comprehensive surgery prior to implementing such additional therapies. The purpose of this study was to quantify prior surgery completeness in AERD patients at a tertiary rhinology practice. METHODS: Paranasal sinus CT scans were reviewed by four academic rhinologists to assess surgery completeness. Using a published CT grading system, each sinus was graded on the completeness of surgery and middle turbinate reduction. A score out of 14 was calculated for each patient (7 per side). RESULTS: Sixty-one patients with AERD out of 141 available were included. Mean inter-rater agreement across all sinuses was moderate (k = 0.42). The mean completeness score was 6.7/14. The following procedures were rated as complete (means): uncinectomy (L: 84%, R: 82%, k = 0.44), maxillary (L: 83%, R: 77%, k = 0.32), middle turbinate reduction (L: 45%, R: 46%, k = 0.31), anterior ethmoid (L: 35%, R: 39%, k = 0.51), sphenoid (L: 36%, R: 35%, k = 0.4), posterior ethmoid (L: 30%, R: 30%, k = 0.48), frontal (L: 22%, R: 21%, k = 0.46). CONCLUSION: Prior surgery in AERD patients were mostly deemed incomplete. Uncinectomy and maxillary antrostomy are the most common procedures previously performed. It remains toe seen whether this would be considered 'adequate' surgery or more 'complete' surgery is required to achieve greater disease control.

Cost-effectiveness analysis of biologics for the treatment of chronic rhinosinusitis with nasal polyps in Canada.

BACKGROUND: Dupilumab, omalizumab, and mepolizumab are the three biologics currently approved for use in CRSwNP in Canada. Despite evidence of efficacy, their cost-effectiveness, which is a key factor influencing prescribing patterns, has not yet been compared to each other. METHODS: A cost-effectiveness model using quality-adjusted life years (QALYs) was constructed using a Decision Tree Markov analysis. A third-party healthcare payer perspective and a 10-year time horizon was used. A willingness-to-pay (WTP) threshold of 50,000 Canadian dollars (CAD) per QALY was used to determine cost-effectiveness. Dupilumab, omalizumab, and mepolizumab were each compared to each other. RESULTS: Omalizumab was the most cost-effective biologic using current estimates of cost and efficacy in CRSwNP. Using omalizumab as a baseline, dupilumab had an ICER of $235,305/QALY. Mepolizumab was dominated by omalizumab and dupilumab at the current drug prices and estimates of efficacy. Sensitivity analyses determined that when increasing the WTP threshold to $150,000/QALY, dupilumab became cost-effective compared to omalizumab in 22.5% of simulation scenarios. Additionally, altering dosing frequency had a significant effect on cost-effectiveness. CONCLUSION: When comparing the relative cost-effectiveness of biologics in recalcitrant CRSwNP, omalizumab currently appears to be the most cost-effective option. Future reductions in drug prices, adjustments to currently approved dosing regimens, better patient selection, and improvements in sinus surgery outcomes will challenge the current cost-effectiveness models and necessitate reassessment as treatments for CRSwNP continue to evolve.

Cost-effectiveness Analysis of Inferior Turbinate Reduction and Immunotherapy in Allergic Rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common condition that is frequently associated with atopic inferior turbinate hypertrophy (ITH) resulting in nasal obstruction. Current guidelines support the use of subcutaneous allergen immunotherapy (SCIT) when patients fail pharmacologic management. However, there is a lack of consensus regarding the role of inferior turbinate reduction (ITR), a treatment that we hypothesize is cost-effective compared with other available treatments. METHODS: We conducted a cost-effectiveness analysis comparing the following treatment combinations over a 5-year time horizon for AR patients presenting with atopic nasal obstruction who fail initial pharmacotherapy: (1) continued pharmacotherapy alone, (2) allergy testing and SCIT, (3) allergy testing and SCIT and then ITR for SCIT nonresponders, and (4) ITR and then allergy testing and SCIT for ITR nonresponders. Results were reported as incremental cost-effectiveness ratios (ICERs). RESULTS: For patients who fail initial pharmacotherapy, prioritizing ITR, either by microdebrider-assisting submucous resection or radiofrequency ablation, before SCIT was the most cost-effective strategy. Probabilistic sensitivity analysis demonstrated that prioritizing ITR before SCIT was the most cost-effective option in 95.4% of scenarios. ITR remained cost-effective even with the addition of concurrent septoplasty. CONCLUSION: For many AR patients who present with nasal obstruction secondary to atopic inferior turbinate hypertrophy that is persistent despite pharmacotherapy, ITR is a cost-effective treatment that should be considered prior to immunotherapy. LEVEL OF EVIDENCE: N/A - Laryngoscope, 2023 Laryngoscope, 2023.

Remission: does it already exist in chronic rhinosinusitis with nasal polyposis?

BACKGROUND: Remission, defined as absence of symptoms and objective markers of disease, is emerging as the penultimate goal in the management of several chronic diseases. The concept of remission, well-established in Rheumatology as well as Gastroenterology, is currently emerging in Respiratory Medicine for asthma. It is interesting to consider whether the disease remission concept might successfully be applied to Otolaryngology-Head and Neck Surgery in the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). OBJECTIVE: The purpose of this letter is to explore the evidence supporting the concept of remission under continued medical therapy in chronic rhinosinusitis with nasal polyposis. METHODS: The authors reviewed the literature and summarized studies in chronic rhinosinusitis with nasal polyposis evaluating for evidence of clinical, biochemical, and endoscopic remission. RESULTS: Findings of the studies revealed that endoscopic sinus surgery with continued medical therapy achieved remission in approximately 50% of all patients. CRSwNP patients after primary endoscopic sinus surgery were able to achieve remission in 72% of instances, however this drops to 42% for patients having revision sinus surgery. For CRSwNP patients with co-morbidities such as asthma and aspirin exacerbated respiratory disease, remission rate drops to 23% and 23.5%, respectively compared to non-asthmatic CRSwNP patients who present a remission rate under continued medical therapy of 60%. CONCLUSION: Remission of symptoms and evidence of disease under medical therapy is indeed a concept achievable in patients with CRSwNP, as demonstrated by studies in the literature. Various co-morbidities, notably asthma, apparently influence rate of remission. Better defining this outcome through consensus-based definitions will allow for the development of strategies in CRSwNP care that can help affected patients attain complete relief from clinical, biochemical, and endoscopic markers of CRS with judicious use of medication and surgery. Future efforts will attempt to improve on these outcomes by achieving symptomatic and endoscopic control of disease following cessation of therapy, potentially paving the way towards clinical remission or a 'cure' in CRS.

Engineered dry powders for the nose-to-brain delivery of transforming growth factor-beta.

Nose-to-brain delivery is increasing in popularity as an alternative to other invasive delivery routes. However, targeting the drugs and bypassing the central nervous system are challenging. We aim to develop dry powders composed of nanoparticles-in-microparticles for high efficiency of nose-to-brain delivery. The size of microparticles (between 250 and 350 µm), is desired for reaching the olfactory area, located below the nose-to-brain barrier. Moreover, nanoparticles with a diameter between 150 and 200 nm are desired for traveling through the nose-to-brain barrier. The materials of PLGA or lecithin were used in this study for nanoencapsulation. Both types of capsules showed no toxicology on nasal (RPMI 2650) cells and a similar permeability coefficient (Papp) of Flu-Na, which was about 3.69 ± 0.47 × 10-6 and 3.88 ± 0.43 × 10-6 cm/s for TGF-ß-Lecithin and PLGA, respectively. The main difference was related to the location of deposition; the TGF-ß-PLGA showed a higher drug deposition in the nasopharynx (49.89 ± 25.90 %), but the TGF-ß-Lecithin formulation mostly placed in the nostril (41.71 ± 13.35 %).

Spatial analysis of transnasal olfactory cleft access: a computed tomography study.

Objective: To our knowledge, the spatial access of naris to olfactory cleft has not been quantified. We aimed to study the relationship and space of middle turbinate, septum, anterior nasal spine and cribriform plate to improve topical medication delivery and drug applicators. Methods: One hundred CT scans of patients (50 males, 50 females) over the age of 18 were included. Subjects with radiographic sinonasal pathology, previous surgery, or specific variant nasal anatomy were excluded. Scans were independently reviewed and bilateral measurements on bony landmarks were taken by two blinded authors. Inter-rater reliability was analysed with intraclass correlation. Results: The average age was 46.26 years (σ = 14.0). Average distance from the anterior nasal spine to olfactory cleft was 52.3 mm (σ = 4.2 mm), and the average length of cribriform plate was 18.8 mm (σ = 3.8) with an angle relative to hard palate averaging -8.8 degrees below parallel (σ = 5.5 degree). The widths of the olfactory cleft at anterior and posterior edges of cribriform plate were 2.3 mm (σ = 0.7 mm) and 2.0 mm (σ = 0.7 mm). Conclusions: The findings suggest a 52.3 mm distance from the naris to the anterior border of cribriform plate. The average width along this path was 3.2 mm, suggesting devices narrower than this could potentiate direct drug delivery access.

Differential Angiogenic Induction Impacts Nasal Polyp Tissue Growth.

In chronic rhinosinusitis with nasal polyps, inflammatory edema drives tissue remodeling favoring anomalous growth of the nasal mucosa, but a proangiogenic contribution of nasal polyp in support of tissue growth is still controversial. The chorioallantoic membrane of chicken embryo model was employed to address the potentiality of nasal tissue fragments to modulate angiogenesis. Fifty-seven fertilized eggs were implanted with polyp or healthy nasal mucosa tissue or were kept as non-implanted controls. The embryos' size, length, and development stage, and chorioallantoic membrane vasculature morphology were evaluated after 48 h. Quantitative computer vision techniques applied to digital chorioallantoic membrane images automatically calculated the branching index as the ratio between the areas of the convex polygon surrounding the vascular tree and the vessels' area. Ethics approval and consent to participate: the study was approved by the Human Research Ethics Committee of the Federal University of São Paulo (CAAE number: 80763117.1.0000.5505) and by the Animal Research Ethics Committee of University of São Paulo (nº CEUA 602-2019). Mucosal, but not polyp tissue implants, hampered embryo development and induced underdeveloped chorioallantoic membranes with anastomosed, interrupted, and regressive vessels. Vessels' areas and branching indexes were higher among the chorioallantoic membranes with polyp implants and controls than among those with healthy mucosa implants. Nasal polyp presents differential angiogenic induction that impacts tissue growth.

Canadian multidisciplinary expert consensus on the use of biologics in upper airways: a Delphi study.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1-9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures-kappa coefficient ([Formula: see text]) value > 0.61. RESULTS: After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

Population-based Long-term Outcomes for Squamous Cell Carcinoma of the Nasal Cavity.

BACKGROUND: This study evaluates population-based outcomes of patients with squamous cell carcinoma (SCC) of the nasal cavity treated in British Columbia. METHODS: A retrospective review of nasal cavity SCC treated from 1984 to 2014 was performed (n = 159). Locoregional recurrence (LRR) and overall survival (OS) were evaluated. RESULTS: The 3-year OS was 74.2% for radiation alone, 75.8% for surgery alone, and 78.4% for surgery and radiation ( P = 0.16). The 3-year LRR was 28.4% for radiation alone, 28.2% for surgery alone, and 22.6% for surgery and radiation ( P = 0.21). On multivariable analysis, surgery and postoperative radiation relative to surgery alone was associated with a lower risk of LRR (hazard ratio: 0.36, P = 0.03). Poor Eastern Cooperative Oncology Group status, node-positive, orbital invasion, smoking, and advanced age were associated with worse OS (all P <0.05). CONCLUSION: In this population-based analysis, multimodality treatment with surgery and adjuvant radiation were associated with improved locoregional control for SCC of the nasal cavity.

Impact of Chronic Rhinosinusitis with Nasal Polyposis on IL-12 and IL-8.

Introduction: The pathophysiology of Chronic Rhinosinusitis is coordinated by distinct inflammatory reactions in different individuals. Inflammatory environments with a predominance of Th2 lymphocytes tend also to be rich in eosinophils. These environments are common during the formation of nasal polyps associated with aspirin intolerance, which is also marked by an increase in inflammatory mediators, especially IL-4, IL-5, and IL-13. Despite the significance of these inflammatory mediators, the relevance of IL-12 subunits' presence within eosinophilic nasal polyps, however, has been less studied. The current study aims to evaluate the presence of IL-12 subunits, IL-12p40 and IL-12p70, in eosinophilic nasal polyps and their correlations with IL-8 presence. Materials and Methods: We compared the concentrations of IL-8, IL12p40, and IL12p70 among samples of eosinophilic nasal polypoid tissue, eosinophilic nasal polypoid tissue associated with aspirin intolerance, and healthy nasal mucosa, using an indirect immunoassay (ELISA) kit. Results: When compared to healthy nasal mucosa, there was a lower concentration of IL-8 in Chronic Rhinosinusitis with Nasal Polyp (CRSwNP) tissue. Aspirin Intolerant polypoid tissue also presented a lower concentration of IL-12 subunits compared to healthy nasal mucosa. There was no significant correlation between IL-8 and IL-12 in the eosinophilic polypoid conditions. Conclusion: In CRSwNP, there is a reduction in IL-8 and IL-12 subunits compared to control, with a lack of correlation between IL-12 and IL-8. The lack of correlation can be justified by a type two inflammatory storm environment.