Efficacy of povidone-iodine nasal rinse and mouth wash in COVID-19 management: a prospective, randomized pilot clinical trial (povidone-iodine in COVID-19 management).

OBJECTIVES/HYPOTHESIS: To assess the efficacy of 0.23% povidone-iodine (PVP-I) nasal rinses and mouth washes on detectability of the coronavirus disease 2019 (COVID-19) virus and cycle threshold (Ct) values in nasopharyngeal swabs. STUDY DESIGN: This was an open-label, prospective, randomized, placebo-controlled clinical trial. SETTING: The study was conducted in King Saud University Medical City, Riyadh, Saudi Arabia, from August 2021 to July 2022. METHODS: Participants diagnosed with SARS-CoV-2 were randomly assigned to one of three groups, with participants receiving either 0.23% PVP-I, 0.9% normal saline (NS) nasal rinses and mouth washes, or no intervention (control group). Nasopharyngeal swabs were taken 4, 8, 12, and 18 days after the first swab to measure the detectability of the virus and the Ct. RESULTS: A total of 19 participants were involved in this study. The mean viral survival was 9.8, 12, and 12.6 days for the PVP-I, NS, and control groups, respectively, with a statistically significant difference (p = 0.046). The Ct mean values were 23 ± 3.4, 23.5 ± 6.3, and 26.3 ± 5.9 at the time of recruitment and 25.2 ± 3.5, 15 ± 11.7, and 26.9 ± 6.4 after 4 days for the PVP-I, NS, and control groups, respectively. CONCLUSIONS: When used continuously at a concentration of 0.23%, PVP-I showed promising results in terms of decreasing the pandemic burden by reducing the period of infectiousness and viral load. However, the use of PVP-I did not result in significantly different changes in the quality-of-life parameters in recently vaccinated and mild COVID-19 patients.

The prevalence of CFTR mutations in patients with chronic rhinosinusitis: A systematic review and meta-analysis.

OBJECTIVES: Undetected cystic fibrosis transmembrane regulator (CFTR) mutations may predispose individuals to develop CRS independent of formal CF diagnosis. The objective of this study was to determine the prevalence of CFTR mutations among individuals with CRS. DESIGN: A systematic search following PRISMA guidelines was performed. A meta-analysis was performed to calculate pooled estimates for the prevalence of any CFTR mutation and for the DF508 mutation. SETTING AND PARTICIPANTS: The systematic search included all studies identifying adults diagnosed with CRS, with no limitation to region or publication date. Studies had to identify a sample of patients previously diagnosed with CRS but not with CF and reporting testing for the prevalence of CF or the CFTR gene mutation. MAIN OUTCOME MEASURES: Prevalence of CFTR mutations among the general CRS population, with subgroup analysis of individuals with the dF508 mutation. RESULTS AND CONCLUSIONS: The 6 included studies represented five countries: the United States, the UK, France, Poland and Finland. The pooled prevalence of CFTR mutations of any kind in CRS subjects without CF was 5.65% (RE 95% CI 2.99 - 10.41). The overall prevalence for the dF508 mutation was 4.22% (RE 95% CI 1.71 - 10.07). These estimates were significantly higher than the baseline estimated prevalence of CFTR carrier status of 3%-4% in the general population. However, the clinical relevance of the presence of CFTR mutations in CRS patients who have not been diagnosed with CF is currently unclear. Future studies should include sweat chloride testing as a measure of CFTR function.

Effect of endoscopic sinus surgery on clinical outcomes in DeltaF508 cystic fibrosis patients.

OBJECTIVES: Chronic rhinosinusitis (CRS) is prevalent in the Cystic Fibrosis (CF) population. CRS exacerbations in CF are thought to contribute to pulmonary exacerbations. Literature regarding the impact of endoscopic sinus surgery (ESS) is inconclusive. This study examines rates of lung function decline and pulmonary exacerbation in CF patients who have undergone ESS. DESIGN: Retrospective review of medical records. SETTING: Academic Hospital. PARTICIPANTS: 40 adult CF patients. MAIN OUTCOME MEASURES: Rate of lung function decline (% predicted Forced Expiratory Volume in 1 second [ppFEV1 ]), number of pulmonary exacerbations (IV/oral antibiotic therapy ± hospital admission) and total number days hospitalised 2-year postoperatively was collected. CRS patients undergoing ESS were matched to those without ESS by gender, age, and F508del genotype. RESULTS: Forty patients (mean age 37.4, 60% male) were reviewed. No significant difference was found between the surgical group and controls in baseline ppFEV1 (72.5% vs. 72.7%, P = .98), 2-year preoperative number of pulmonary exacerbations (3.05 vs. 1.65, P = .10), or Lund-Mackay scores (12.25 vs. 11.55, P = .71). No significant difference was found in 1-year (70.5% vs. 72.8%, P = .84) or 2-year (70.4% vs. 72.6% P = .80) postoperative ppFEV1 and 2-year postoperative pulmonary exacerbations (1.7 vs. 1.45, P = .87). A significant increase was identified in total number days hospitalised postoperatively (4.85, P = .02). In the surgical group, no significant difference was identified between preoperative and postoperative ppFEV1 , 1 year (-2.51%, P = .32) and 2 years after ESS (-3.10%, P = .51), postoperative rate of pulmonary exacerbations (-1.28, P = .11), or in total number days hospitalised (3.74, P = .14). CONCLUSIONS: In this study, ESS does not appear to significantly improve ppFEV1 or decrease the number of pulmonary exacerbations postoperatively.

Optimization of the Surgical Field in Endoscopic Sinus Surgery: an Evidence-Based Approach.

PURPOSE OF REVIEW: The advent of endoscopic sinus surgery (ESS) has enabled the development of minimally invasive surgical procedures in Rhinology. However, proficiency with ESS techniques can still be hampered by poorly controlled bleeding limiting visibility of the surgical field (VSF). This can lead to increased operating time and, more importantly, increased risk of major and minor complications. To optimize the VSF and mitigate the risk of complications, many strategies have been explored. RECENT FINDINGS: This is a narrative review of the relative risks and benefits of pre- and intra-operative interventions aimed at optimizing intraoperative conditions during ESS. The value of these interventions is determined based on their impact on intraoperative blood loss, time of surgery, and the VSF, and weighed against their adverse event profile. This review provides a comprehensive overview of the evidence relating to the safety and efficacy of interventions used to improve intraoperative conditions during ESS.

The efficacy of diluted topical povidone-iodine rinses in the management of recalcitrant chronic rhinosinusitis: a prospective cohort study.

PURPOSE: Recalcitrant chronic rhinosinusitis is a persistent inflammatory condition of the sinonasal mucosa despite adequate medical therapy and sinus surgery. This study aimed to demonstrate the effectiveness and safety of dilute povidone-iodine (PVP-I) sinonasal rinses as an adjunctive therapy. METHODS: Prospective cohort study. Twenty-nine recalcitrant CRS patients with endoscopic evidence of ongoing inflammation and purulent discharge were prescribed 0.08% diluted PVP-I rinses. Changes to endoscopic modified Lund-Kennedy (MLK) scores at 7 weeks post-PVP-I rinsing served as the primary outcome measure. RESULTS: The median MLK-discharge score significantly decreased in all patients by 1.50 points post-PVP-I rinsing (p value < 0.01). The total MLK score significantly decreased in all patients by 1.50 points (p value = 0.01). Up to a 17% reduction in serum inflammatory markers was measured post-PVP-I rinsing. Sinonasal culture revealed a shift from moderate-heavy growth to lighter bacterial growth overall. Subjective SNOT-22 scores significantly improved overall by ≥ 1 minimal clinically important difference (MCID > 12; baseline median = 33; follow-up median = 20; p value < 0.01; n = 22). TSH levels increased non-significantly within normal ranges (baseline median = 1.59 mU/L; follow-up median = 1.92 mU/L; p = 0.10; n = 15). Mucociliary clearance time increased non-significantly within normal ranges (baseline median = 9 min; follow-up median = 10 min; p value = 0.53; n = 17). Olfactory Sniffin'16 scores non-significantly decreased within age-related normal ranges (baseline median = 14; follow-up median = 13; p value = 0.72; n = 18). CONCLUSION: A dilute 0.08% PVP-I sinonasal rinse as an ancillary therapy in recalcitrant CRS significantly reduces signs of infection alongside notable symptom improvement, without affecting thyroid function, mucociliary clearance or olfaction.

Potential risk factors associated with the development of synechiae following functional endoscopic sinus surgery.

PURPOSE: Synechiae formation in the middle meatus is the most common complication of functional endoscopic sinus surgery (FESS). Our objectives were to determine the incidence of synechiae occurring in a cohort of patients that have undergone FESS and identify characteristics associated with the development of synechiae postoperatively. METHODS: A retrospective chart review was conducted of CRS patients, with or without nasal polyposis, that had undergone bilateral FESS in the past. All patients had received non-absorbable spacers intraoperatively that were left in situ for 6 days. Demographic and preoperative variables were analyzed to identify synechiae risk factors. A multivariable logistic regression model was constructed to estimate the probability of developing synechiae, given demographic and preoperative variables. RESULTS: Two hundred cases of bilateral FESS were retrospectively reviewed. Thirty-eight (19.0%, 95% CI 13.6-24.4%) patients developed synechiae. Individuals receiving primary FESS and nasal septal reconstruction (NSR) were strongly associated with the development of synechiae (OR 3.5, 95% CI 1.5-8.5; OR 3.0, 95% CI 1.3-6.9). A multivariable logistic regression model adjusting for NSR, recurrent FESS, concha bullosa, requirement of anterior and posterior ethmoidectomy, Lund-Mackay CT score and gender, identified the likelihood of developing synechiae with a sensitivity of 68%, specificity of 73%, positive predictive value of 38% and likelihood ratio of 2.5. CONCLUSION: Patients undergoing primary FESS and NSR are at greatest odds of developing postoperative synechiae. Methods of assessing risk factors and preventing synechiae formation in this population should be evaluated in future prospective investigations.

Omalizumab therapy for refractory allergic fungal rhinosinusitis patients with moderate or severe asthma.

PURPOSE: 1. To assess the efficacy of omalizumab therapy in improving sinonasal outcomes in refractory allergic fungal rhinosinusitis (AFRS) patients with moderate or severe asthma. 2. To determine if omalizumab therapy reduces the usage of corticosteroids or antifungal therapy in AFRS patients DESIGN: The clinical charts of patients with AFRS with moderate or severe asthma who received at least three subcutaneous injections of omalizumab therapy between 1st January 2012 and 1st May 2014 were retrospectively reviewed. These patients had undergone bilateral functional endoscopic sinus surgery (FESS) and failed adjunct medical treatments (oral or topical corticosteroids and/or antifungal therapy) prior to omalizumab therapy. RESULTS: Seven patients met the inclusion criteria and were included in this study. The mean age of the patients was 48.14. The average number of subcutaneous omalizumab injections was 7.57 (range 6-11) with a mean dosage of 287mg (range 225-375mg). The mean pre-omalizumab treatment Sino-Nasal Outcome Test-22 (SNOT-22) score was 52.14 while the mean post-omalizumab treatment SNOT-22 score was 35.86 (31% improvement). The mean pre-omalizumab therapy Phillpott-Javer endoscopic score (over the last one year before omalizumab therapy) was 36 while the mean post-omalizumab therapy endoscopic score (from the last clinic visit) was 14 (61% improvement). Omalizumab therapy reduced the dependence of AFRS patients on corticosteroid and antifungal treatments. CONCLUSION: Omalizumab therapy can be considered as a potential adjunct for the treatment for patients with refractory AFRS with moderate or severe asthma. However, larger prospective studies to confirm the findings of this study will be required.

Short Cilia, Immunodeficiency, and Cystic Fibrosis in a Mother-Daughter Pair.

Patients with chronic rhinosinusitis (CRS) that is refractory to maximal medical and surgical therapy should be evaluated for other primary conditions. Cystic fibrosis (CF), primary immunodeficiency (PID), and primary ciliary dyskinesia (PCD) are potential risk factors for refractory CRS. These conditions present with variable disease severity and diagnosis may be delayed into adulthood. We report a case of a mother-daughter pair with CRS refractory to maximal medical management. The patients were further evaluated and found to have features consistent with CF, PID, and PCD. All 3 are rare disorders and thought to cause CRS in isolation. Patients with refractory CRS should be further evaluated to identify alternative diagnoses and ensure proper management. Refractory CRS may be multifactorial, with different risk factors simultaneously contributing to its persistence.

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, 134:3054-3059, 2024.

Successful use of a patient specific 3D-printed biomodel as surgical guide for excision of juvenile nasopharyngeal angiofibroma extending to skull base: A case report.

Background: 3-Dimensional (3D) printing has proven its role in various fields. Recently, 3D printing has also been introduced in the otolaryngology domain. The nasopharynx, paranasal sinuses, and the anterior skull base have a complex anatomy. Critical structures must be delicately protected and preserved during a surgical procedure. It is, therefore, very important for the surgeon to have an excellent spatial understanding of the complex surgical field that is being traversed. Case Description: Our case is of a 19-year-old male with a 2-month history of recurrent epistaxis, nasal blockage, and headache. Based on the computed tomography scan and the clinical presentation, the patient was diagnosed with juvenile nasopharyngeal angiofibroma. The patient underwent angioembolization of the tumor followed by endoscopic surgical resection. The patient remained stable postoperatively and demonstrated a good recovery in the follow-up visit with no signs of cranial deficits. This case report highlights the use of a patient-specific 3D-printed biomodel to visualize this rare tumor of the nasopharynx. The benefits of using the model in surgical planning, patient education, and resident training are reported. We found that the ability to visualize the tumor on a tangible model, viewing its actual size in relation to the adjacent anatomy and all the structures associated with it, greatly enhances the surgeon's capacity to tackle such a difficult tumor endoscopically. Conclusion: Incorporating 3D-printed biomodels in surgical practice should result in improved outcomes for the patients.

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.

Switching biologics in chronic rhinosinusitis with nasal polyps: A multicenter Canadian experience.

BACKGROUND: Type 2 biologics have been used increasingly for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). However, patterns of biologic switching are understudied, and established guidelines for sequential or simultaneous use do not yet exist. METHODS: This is a Canadian multicenter retrospective study of real-world patient data. Patients were included if they had recurrent CRSwNP despite maximal medical and surgical management, and received at least one dose of a type 2 biologic. Patients who remained on their initial biologic comprised the continuous group. Patients with sequential or simultaneous use of more than one biologic comprised the switched group. We compared the characteristics of patients who continued and switched biologics. RESULTS: Note that 225 consecutive patients were included. Thirty-six (16%) switched biologics at least once, and six (3%) switched twice. The most common switch was from mepolizumab to dupilumab, with poor control of CRSwNP symptoms being the leading cause for this switch. Lack of efficacy was the main reason for switching off mepolizumab and omalizumab, while adverse events were the leading cause for switching off dupilumab. Additionally, mepolizumab patients were more likely to switch biologics late in their treatment, while dupilumab patients rarely switched after 12 months of therapy (p-value < 0.001). CONCLUSIONS: Switching biologics for CRSwNP is frequent in Canadian rhinology practices, with 16% of patients switching at least once. The most common switch is from mepolizumab to dupilumab with inadequate CRSwNP control driving this switch. This study may help guide sequential or simultaneous use of biologics in CRSwNP patients.

Assessment of chronic rhinosinusitis with nasal polyps: Development of the Nasal Polyp Patient Assessment Scoring Sheet tool.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with a wide range of validated subjective and objective assessment tools to assess disease severity. However, a comprehensive and easy-to-use tool that integrates these measures for determining disease severity and response to treatment is still obscure. The objective of this study was to develop a standardized assessment tool that facilitates diagnosis, uniform patient monitoring, and comparison of treatment outcomes between different centers both in routine clinical practice and in research. Methods: To develop this tool, published literature on assessment tools was searched on various databases. A panel of 12 steering committee members conducted an advisory board meeting to review the findings. Specific outcome measures to be included in a comprehensive assessment tool and follow-up sheet were then collated following consensus approval from the panel. The tool was further validated for content and revised with expert recommendations to arrive at the finalized Nasal Polyp Patient Assessment Scoring Sheet (N-PASS) tool. Results: The N-PASS tool was developed by integrating the subjective and objective measures for CRS assessment. Based on expert opinions, N-PASS was revised to be used as an easy-to-use guidance tool that captures patient-reported and physician-assessed components for comprehensively assessing disease status and response to treatment. Conclusion: The N-PASS tool can be used to aid in the diagnosis and management of CRS cases with nasal polyps. The tool would also aid in improved monitoring of patients and pave the way for an international disease registry. Level of evidence: Oxford Level 3.

Prevalence and Associated Factors of Medication Non-Adherence in CRS Patients following Endoscopic Sinus Surgery.

This study aimed to evaluate factors that may predispose patients to not adhere to prescribed medication after endoscopic sinus surgery (ESS) and to compare SNOT-22 scores at 0-12 months post-operatively between adherent and non-adherent patients. CRS patients who underwent ESS between 2012 and 2016 were recruited to this retrospective cohort study. Adherence was assessed through a questionnaire and review of medical notes. Ninety-four participants were included (61% male, mean age 60). Of those, 66% did not adhere to their prescribed post-operative CRS medication timing or dosage. The most common reason for non-adherence was improvement of symptoms (17%), followed by deterioration of symptoms (11%) and side effects (10%). Post-operative SNOT-22 scores were lowest for non-intentionally non-adherent (NINA) participants with a mean of 10.5 [95% CI: 7.47-13.5], compared to 25.0 for intentionally non-adherent (INA) [95% CI: 17.6-32.4] and 17.7 for adherent patients [95% CI: 13.7-21.7], p = 0.01. This study identifies that almost two-thirds of patients are not compliant with CRS medications after ESS. NINA participants reported lower post-operative SNOT-22 scores compared to INA and adherent participants. Future studies should focus on educating patients to continue with medications post-operatively despite an initial improvement in symptoms.

Syndrome of Inappropriate Antidiuretic Hormone Release Secondary to Ectopic Olfactory Neuroblastoma: Case Report and Review of Literature.

Ectopic olfactory neuroblastoma (ONB) is a rare neuroendocrine sinonasal malignancy which arises from sinonasal regions where olfactory neuroepithelium does not exist. Presentation of syndrome of inappropriate antidiuretic hormone release (SIADH) in patients with ectopic ONB is extremely rare. We report a case of a 22-year-old patient with ectopic ONB and paraneoplastic SIADH that was managed at our center. The ONB was arising from the left lamina papyracea and extending into the maxillary and ethmoid sinuses and filling the nasal cavity. Correction of sodium levels occurred within 24 hours of endoscopic resection via a combined trans-nasal transorbital approach. To avoid negative sequela secondary to rapid sodium correction, the patient was managed by desmopressin to obtain gradual sodium correction, which was achieved on the fourth postoperative day. Ectopic presentation of ONB with paraneoplastic SIADH is extremely rare with only 7 cases reported in the literature to date. Management via surgical resection and/or radiotherapy for these patients requires the managing clinician to be vigilant of serum sodium levels. A multidisciplinary approach is essential for optimal outcomes.

The Effects of Nasal Surgery on Pulmonary Function: A Systematic Review and Meta-Analysis.

OBJECTIVE: A deviated nasal septum (DNS) can result in an anatomical obstruction and impact lung function through prolonged suboptimal inspiration. Given the improvements in respiration reported by patients following septoplasty or septorhinoplasty (with or without inferior turbinate reduction), our study investigated the effect of these procedures on pulmonary function through a systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Databases, Web of Science, and Google Scholar. REVIEW METHODS: The review was registered with PROSPERO [CRD42022316309]. The study population was composed of adult patients (18-65) who were symptomatic with confirmed DNS. Extracted outcomes (pre-operative versus postoperative) included the six-minute walk test (6MWT) and pulmonary function tests (FEV1, FVC, FEV1/FVC, FEF25-75, PEF). Meta-analyses were performed using a random-effects model. RESULTS: Three studies included measures of the 6MWT in meters and all three found a statistically significant increase in the distance walked after surgery with a mean difference of 62.40 m (95% CI 24.79-100.00). Statistically significant improvements in PFT outcomes were observed with a standard mean difference of 0.72 for FEV1 (95% CI 0.31-1.13), 0.63 for FVC (95% CI 0.26-1.00), and 0.64 for PEF (95% CI 0.47-0.82). Of the twelve studies which measured PFT outcomes, six showed statistically significant improvements, three studies showed mixed results, and three studies found no difference in PFT outcomes between pre-and post-surgery testing. CONCLUSIONS: The present study suggests that pulmonary function does improve after nasal surgery for DNS, but the high heterogeneity observed in the meta-analyses indicates that the evidence supporting this conclusion is low. Laryngoscope, 133:2837-2845, 2023.

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.

Allergic Fungal Rhinosinusitis: The Role and Expectations of Biologics.

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS.

Multiple spontaneous cerebrospinal fluid leaks: a rare case report and review of literature.

While a spontaneous cerebrospinal fluid leak (sCSFL) is a rare phenomenon, patients who present with multiple cerebrospinal fluid leaks (mCSFLs) are an even rarer entity. There have been documented cases reported over the last decades, but many with only limited descriptions of each patient. We present a mCSFL patient as a case report and demonstrate the need for future prospective studies to improve further understanding and management of the condition. This is explored through summarizing the literature on mCSFLs to the present time. A 45-year-old obese female presented with a 5-week history of bilateral clear nasal discharge with no previous surgery or trauma. Initially misdiagnosed as allergic rhinitis, nasal discharge was later confirmed positive for beta-2-transferrin and a CT scan revealed multiple bony areas of skull base erosion. The patient underwent image guided endoscopic sinus surgery with multilayer skull base defect repair of three active CSFLs. Three months post-operatively the patient had no evidence of a recurrence. As mCSFL tend to be sporadic and asymptomatic in nature, it is likely they are underreported. Future prospective studies in the area of mCSFLs that take into consideration demographic and geographical information are needed for more accurate interpretation and better recruitment. Additionally, studies need to ensure longer follow-up time due to the underlying chronicity of increased intracranial pressure (ICP) and investigate whether or not a non-active leak site should be repaired or left alone.

Canadian clinical practice guidelines for acute and chronic rhinosinusitis.

This document provides healthcare practitioners with information regarding the management of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) to enable them to better meet the needs of this patient population. These guidelines describe controversies in the management of acute bacterial rhinosinusitis (ABRS) and include recommendations that take into account changes in the bacteriologic landscape. Recent guidelines in ABRS have been released by American and European groups as recently as 2007, but these are either limited in their coverage of the subject of CRS, do not follow an evidence-based strategy, or omit relevant stakeholders in guidelines development, and do not address the particulars of the Canadian healthcare environment.Advances in understanding the pathophysiology of CRS, along with the development of appropriate therapeutic strategies, have improved outcomes for patients with CRS. CRS now affects large numbers of patients globally and primary care practitioners are confronted by this disease on a daily basis. Although initially considered a chronic bacterial infection, CRS is now recognized as having multiple distinct components (eg, infection, inflammation), which have led to changes in therapeutic approaches (eg, increased use of corticosteroids). The role of bacteria in the persistence of chronic infections, and the roles of surgical and medical management are evolving. Although evidence is limited, guidance for managing patients with CRS would help practitioners less experienced in this area offer rational care. It is no longer reasonable to manage CRS as a prolonged version of ARS, but rather, specific therapeutic strategies adapted to pathogenesis must be developed and diffused.Guidelines must take into account all available evidence and incorporate these in an unbiased fashion into management recommendations based on the quality of evidence, therapeutic benefit, and risks incurred. This document is focused on readability rather than completeness, yet covers relevant information, offers summaries of areas where considerable evidence exists, and provides recommendations with an assessment of strength of the evidence base and degree of endorsement by the multidisciplinary expert group preparing the document.These guidelines have been copublished in both Allergy, Asthma & Clinical Immunology and the Journal of Otolaryngology-Head and Neck Surgery.