A Scholarly Review of the Safety and Efficacy of Intranasal Corticosteroids Preparations in the Treatment of Chronic Rhinosinusitis.

OBJECTIVE: The purpose of this scholarly review is to present an update of the efficacy, safety, and distribution of intranasal corticosteroids (INCS) in the context of treatment for chronic rhinosinusitis (CRS). MATERIALS AND METHODS: A literature review from 1999 to 2020 of MEDLINE, PubMed, and EMBASE databases was performed, using a comprehensive search strategy. Studies reporting on efficacy, safety, and distribution of all INCS formulations, both Food and Drug Administration (FDA) and non-FDA approved, were reviewed. RESULTS AND CONCLUSIONS: High-level evidence publications and position papers support the role of INCS in medical treatment for CRS. Significant improvement in disease-specific and general quality of life measures is observed with all formulations of INCS. Overall, the use of both FDA and published non-FDA INCS appears to be safe. Several novel distribution devices might improve penetration to specific areas within the sinuses.

The Microbiome of the Nasolacrimal System and Its Role in Nasolacrimal Duct Obstruction.

PURPOSE: Acquired nasolacrimal duct obstruction (NLDO) is a common problem leading to epiphora, the pathophysiology of which remains unclear. Culture-based studies have found Staphylococcal species to be the most prevalent organisms, reported in 47% to 73% of patients with NLDO. Recently, culture-independent molecular methods of have allowed more comprehensive detailing of local microbiota. This study aims to evaluate the sinonasal and lacrimal microbiome of patients undergoing dacryocystorhinostomy for NLDO using 16S-amplicon sequencing. METHODS: Guarded intraoperative swabs were taken from the middle meatus (MM), inferior meatus, and the opened lacrimal sac of 14 NLDO patients undergoing dacryocystorhinostomy and from the inferior meatus and MM on the contralateral unaffected side. MM swabs from 12 control patients were compared with NLDO patients. RESULTS: Comparing microbiota at lacrimal sac to MM and inferior meatus sites reveals that the lacrimal sac microbiome is dominated by Staphylococci (36.3%) and Corynebacterium (35.8%). No significant genus differential abundance between the 3 sites, and between the ipsilateral and contralateral sinonasal swabs, and no convincing evidence of reduced alpha diversity in all comparisons. There was a statistically significant lower relative abundance of Corynebacterium (37.6% vs. 65.1%; p = 0.035) in the MM of NLDO patients compared with controls. CONCLUSIONS: The lacrimal sac microbiome in acquired NLDO is similar to the sinonasal microbiome. The relative abundance of Corynebacterium was reduced compared with controls. These findings suggest that an altered sinonasal microbiome may be associated with NLDO, either as a consequence or a risk factor, and merits future research.The authors have demonstrated a decreased relative abundance of Corynebacterium at the middle meatus of patients with ipsilateral nasolacrimal duct obstruction (NLDO), compared with controls, and that the lacrimal sac microbiome is similar to the sinonasal microbiome. An altered microbial state may, therefore, be associated with NLDO, either as a consequence or a risk factor, and merits future research.

Extent of maxillary sinus surgery and its effect on instrument access, irrigation penetration, and disease clearance.

BACKGROUND: Middle meatal antrostomy (MMA) provides limited access to the anteromedial and inferior aspect of the maxillary sinus (MS) often resulting in residual disease and inflammatory burden. Newer extended procedures, such as mega-antrostomy (Mega-A) and extended modified mega-antrostomy (EMMA), have been developed to address this limitation. This study assesses the effect of varying extent of MS surgery on irrigation penetration and access of instrumentation. METHODS: The MS of 5 fresh-frozen cadavers were sequentially dissected. Irrigation was evaluated with a squeeze bottle (SB) in different head positions and using different volumes of fluid. Surgical reach and visualization were examined using common sinus instruments and different angled endoscopes. A disease simulation was also performed to check for residual debris after instrumentation and irrigations. RESULTS: Irrigation penetration improved as antrostomy size increased (p < 0.0001), with a significant difference observed between the extended procedures and MMA. The effect of the volume was significant for SB (p < 0.0001) but head positions appeared irrelevant (p = 0.613). Overall visualization improved for Mega-A and EMMA. A similar trend was seen for the reach of the instruments to all sinus wall subsites. EMMA facilitated the most removal of "sinus disease" in the disease simulation model when compared with both MMA and Mega-A, due to its reach of the anteroinferior aspects of the maxillary sinus. CONCLUSIONS: High-volume irrigation using SB achieved good sinus penetration, irrespective of head position. Extended MS procedures appear to further increase irrigation penetration as well as surgical access.

Safety and Tolerability of Bacteriophage Therapy for Chronic Rhinosinusitis Due to Staphylococcus aureus.

IMPORTANCE: Staphylococcus aureus infections are associated with recalcitrant chronic rhinosinusitis (CRS). The emerging threat of multidrug-resistant S aureus infections has revived interest in bacteriophage (phage) therapy. OBJECTIVE: To investigate the safety, tolerability, and preliminary efficacy of ascending multiple intranasal doses of investigational phage cocktail AB-SA01 in patients with recalcitrant CRS due to S aureus. DESIGN, SETTING, AND PARTICIPANTS: This phase 1, first-in-humans, open-label clinical trial of multiple ascending doses was conducted at a single tertiary referral center from December 1, 2015, through September 30, 2016, with follow-up completed on December 31, 2016. Patients with recalcitrant CRS (aged 18-70 years) in whom surgical and medical treatment had failed and who had positive S aureus cultures sensitive to AB-SA01 were recruited. Findings were analyzed from February 2 through August 31, 2017. INTERVENTIONS: Three patient cohorts (3 patients/cohort) received serial doses of twice-daily intranasal irrigations with AB-SA01 at a concentration of 3 × 108 plaque-forming units (PFU) for 7 days (cohort 1), 3 × 108 PFU for 14 days (cohort 2), and 3 × 109 PFU for 14 days (cohort 3). MAIN OUTCOMES AND MEASURES: The primary study outcome was the safety and tolerability of intranasal AB-SA01. Safety observations included vital signs, physical examinations, clinical laboratory test results, and adverse events. The secondary outcome was preliminary efficacy assessed by comparing pretreatment and posttreatment microbiology results, disease-relevant endoscopic Lund-Kennedy Scores, and symptom scores using a visual analog scale and Sino-Nasal Outcome Test-22. RESULTS: All 9 participants (4 men and 5 women; median age, 45 years [interquartile range, 41.0-71.5 years]) completed the trial. Intranasal phage treatment was well tolerated, with no serious adverse events or deaths reported in any of the 3 cohorts. No change in vital signs occurred before and 0.5 and 2.0 hours after administration of AB-SA01 and at the exit visit. No changes in biochemistry were found except for 1 participant in cohort 3 who showed a decrease in blood bicarbonate levels on exit visit, with normal results of physical examination and vital signs. All biochemistry values were normalized 8 days later. No changes in temperature were recorded before, during, or after treatment. Six adverse effects were reported in 6 participants; all were classified as mild treatment-emergent adverse effects and resolved by the end of the study. Preliminary efficacy results indicated favorable outcomes across all cohorts, with 2 of 9 patients showing clinical and microbiological evidence of eradication of infection. CONCLUSIONS AND RELEVANCE: Intranasal irrigation with AB-SA01 of doses to 3 × 109 PFU for 14 days was safe and well tolerated, with promising preliminary efficacy observations. Phage therapy could be an alternative to antibiotics for patients with CRS. TRIAL REGISTRATION: http://anzctr.org.au identifier: ACTRN12616000002482.

International assessment of inter- and intrarater reliability of the International Frontal Sinus Anatomy Classification system.

BACKGROUND: Inconsistencies in the nomenclature of structures of the frontal sinus have impeded the development of a validated "reference standard" classification system that surgeons can reliably agree upon. The International Frontal Sinus Anatomy Classification (IFAC) system was developed as a consensus document, based on expert opinion, attempting to address this issue. The purposes of this study are to: establish the reliability of the IFAC as a tool for classifying cells in the frontal recess among an international group of rhinologists; and improve communication and teaching of frontal endoscopic sinus surgery (ESS). METHODS: Forty-two computed tomography (CT) scans, each with a marked frontal cell, were reviewed by 15 international fellowship-trained rhinologists. Each marked cell was classified into 1 of 7 categories described in the IFAC, on 2 occasions separated by 2 weeks. Inter- and intrarater reliability were evaluated using Light's kappa (κ), the interclass correlation coefficient (ICC), and simple proportion of agreement. RESULTS: Interrater reliability showed pairwise κ values ranging from 0.7248 to 1.0, with a mean of 0.9162 (SD, 0.0537). The ICC was 0.98. Intrarater reliability showed κ values ranging from 0.8613 to 1.0, with a mean of 0.9407 (SD, 0.0376). The within-rater ICC was 0.98. CONCLUSION: Among a diverse sample of rhinologists (raters), there was substantial to almost perfect agreement between raters, and among individual raters at different timepoints. The IFAC is a reliable tool for classification of cells in the frontal sinus. Further outcome studies are still needed to determine the validity of the IFAC.

Evaluation of sheep sinonasal endoscopic anatomy as a model for rhinologic research.

OBJECTIVES: Despite many publications describing sheep models for functional endoscopic sinus surgery (FESS) procedures, accurate endoscopic anatomical studies are lacking. There are no publications correlating computed tomography (CT) and 3D models with endoscopic anatomical descriptions. This study evaluates and describes the endoscopic anatomy of a sheep model. METHODS: Ten live sheep (20-sides) were included. Two cadaveric specimens, imaged using thin slice CT for 3D reconstruction correlation were also included. Using endoscopy, anatomical structures were measured and described. Measurement of the same structures was carried out using the 3D imaging model. RESULTS: Three sets of turbinates were identified at 2.3, 5.1 and 8.5 cm from the anterior nasal sill. Frontal recess and uncinate process were identified at 12.7 cm. The septum has a bony and cartilaginous component and measures 10.5 cm. The sphenopalatine foramen was measured at 12.1 cm. All anatomical measurements were correlated with the measurements on the CT scan 3D volume-rendering model, thereby allowing for an accurate description of the sheep sinonasal anatomy. CONCLUSION: This study describes the endoscopic sinonasal anatomical measurements of the adult sheep. It is the first study to evaluate the sheep CT and endoscopic anatomy in order to determine its feasibility as an animal model for research in FESS.

Topical Colloidal Silver for the Treatment of Recalcitrant Chronic Rhinosinusitis.

Background: The management of recalcitrant chronic rhinosinusitis (CRS) is challenged by difficult-to-treat polymicrobial biofilms and multidrug resistant bacteria. This has led to the search for broad-spectrum non-antibiotic antimicrobial therapies. Colloidal silver (CS) has significant antibiofilm activity in vitro and in vivo against S. aureus, MRSA, and P. aeruginosa. However, due to the lack of scientific efficacy, it is only currently used as an alternative medicine. This is the first study looking at the safety and efficacy of CS in recalcitrant CRS. Methods: Patients were included when they had previously undergone endoscopic sinus surgery and presented with signs and symptoms of sinus infection with positive bacterial cultures. Twenty-two patients completed the study. Patients were allocated to 10-14 days of culture directed oral antibiotics with twice daily saline rinses (n = 11) or 10 days of twice daily 0.015 mg/mL CS rinses (n = 11). Safety observations included pre- and post-treatment serum silver levels, University of Pennsylvania Smell Identification Test (UPSIT) and adverse event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund Kennedy Scores (LKS) and symptom scores using Visual Analog Scale (VAS) and Sino-Nasal Outcome Test (SNOT-22). Results: CS demonstrated good safety profile with no major adverse events, no changes in UPSIT and transient serum silver level changes in 4 patients. CS patients had 1/11 (9.09%) negative cultures, compared to 2/11 (18.18%) in the control group upon completion of the study. Whilst not statistically significant, both groups showed similar improvement in symptoms and endoscopic scores. Conclusion: This study concludes that twice daily CS (0.015 mg/mL) sinonasal rinses for 10 days is safe but not superior to culture-directed oral antibiotics. Further studies including more patients and looking at longer treatment or improving the tonicity of the solution for better tolerability should be explored.

Comparing the efficacy of Silastic and gloved-Merocel middle meatal spacers for functional endoscopic sinus surgery: a randomized controlled trial.

BACKGROUND: Spacers are inserted into the middle meatal space (MMS) following functional endoscopic sinus surgery (FESS) to prevent lateralization of the middle turbinate, scarring, and synechiae. Our objective was to determine if the incidence of postoperative synechiae, facial pain/discomfort, pain during spacer removal, scarring, and discharge differed between nasal cavities receiving Silastic or gloved-Merocel (GM) spacers following FESS. METHODS: A double-blind, randomized controlled trial (RCT) was conducted in adults requiring bilateral FESS for chronic rhinosinusitis (CRS) ± nasal polyposis. Participants served as their own controls, with each subject receiving both a Silastic and GM spacer. Spacers were inserted into the MMS during FESS and left in situ for 6 days. Participants were reviewed at 6 days, 5 weeks, and 12 weeks postoperatively. The presence of synechiae and scarring were evaluated endoscopically. Inflammation, discharge, and pain during spacer removal were assessed using a visual analogue scale (VAS). RESULTS: Forty-eight participants (96 nasal cavities) were recruited. Preoperatively, Lund-Mackay computed tomography (CT) scores were similar between Silastic-treated and GM-treated cavities (6.38 ± 2.35 vs 6.18 ± 2.17). The incidence of synechiae and scarring did not differ significantly between spacers up to 12 weeks postoperatively. Pain during spacer removal was significantly greater for Silastic than GM spacers (2.13 ± 1.34 vs 1.51 ± 1.23, p = 0.020). Facial pain prior to removal and extent of discharge did not differ significantly between spacers. CONCLUSION: Following FESS, patients report less pain during removal of GM than Silastic spacers. However, the likelihood of synechiae and scarring did not differ between either of the spacers.

Safety of long-term intranasal budesonide delivered via the mucosal atomization device for chronic rhinosinusitis.

BACKGROUND: Although short-term use (≤2 months) of atomized topical nasal steroids has been shown to be safe and effective, the long-term safety has yet to be demonstrated. The aim of this study was to determine the impact of long-term topical budesonide treatment via the mucosal atomization device (MAD) on the hypothalamic-pituitary-adrenal axis (HPAA) and intraocular pressure (IOP). METHODS: A cross-sectional study of patients with chronic rhinosinusitis (CRS), with or without nasal polyposis, managed with daily nasal budesonide via MAD was conducted at a tertiary rhinology center. Patients using systemic steroids within 3 months of assessment were excluded. HPAA impact was assessed using the cosyntropin stimulation test for adrenal function and a survey of relevant symptomatology. Patients also underwent tonometry to assess for elevated IOP potentially related to corticosteroid use. RESULTS: A total of 100 CRS patients were recruited with a mean budesonide treatment duration of 23.5 months (range, 6-37 months). Stimulated cortisol response was diminished in 3 patients (3%). No patients with adrenal suppression had relevant symptomatology. IOP was elevated in 6 patients (6%). CONCLUSION: These findings suggest that there is a risk of adrenal suppression and raised IOP associated with the long-term use of topical nasal budesonide via MAD. Otolaryngologists should consider periodic surveillance for these adverse events in this patient cohort.

Rapid hemostasis in a sheep model using particles that propel thrombin and tranexamic acid.

OBJECTIVES/HYPOTHESIS: Bleeding during endoscopic sinus surgery and open surgeries can easily obstruct the surgeons' field of view and increase morbidity and risk of intraoperative complications. Intraoperative bleeding could potentially be addressed by a hemostatic agent that safely disperses itself through the escaping blood. We tested the safety and efficacy of a self-propelling formulation of thrombin and tranexamic acid (SPTT) in stopping bleeding in a paranasal sinus injury and in an open surgical carotid injury sheep model. STUDY DESIGN: Interventional animal study. METHODS: SPTT was tested in the sinonasal space following endoscopic injury to the inferior turbinate of six sheep, and to the common carotid artery following open surgical injury in eight sheep. In the nasal cavity, bleeding time and local inflammation were measured and compared to plain gauze. Following carotid arteriotomy, successful hemostasis and markers of thrombosis and coagulopathy were compared to Floseal. RESULTS: SPTT significantly decreased bleeding times in the sinonasal space compared to plain gauze (mean difference = 3.8 minutes, P = .002). All of the carotid bleeds (100%) were successfully controlled with SPTT after 10 minutes of application under pressure, compared to 25% with Floseal. No adverse events were noted, and there was no evidence of thromboembolism. CONCLUSIONS: SPTT significantly reduced bleeding time in a sheep model of surgical sinus bleeding and successfully stopped bleeding following catastrophic carotid artery injury, with no adverse events observed. LEVEL OF EVIDENCE: NA Laryngoscope, 127:787-793, 2017.

[Anatomic variations and references of the sphenopalatine foramen in cadaveric specimens: a Mexican study]. / Variantes y referencias anatómicas del foramen esfenopalatino en especímenes cadavéricos: un estudio en población mexicana.

BACKGROUND: The sphenopalatine foramen is located on the lateral nasal wall and has multiple variants and anatomic landmarks that are important to know to optimize RESULTS in the surgical management of posterior epistaxis. OBJECTIVE: This study describes the endoscopic anatomy of the sphenopalatine foramen, related structures and anatomic variations in a Mexican population. METHODS: We performed a prospective, observational, and experimental study. Five cadaveric specimens were included. Dissections were performed to identify the anatomy of the sphenopalatine foramen and anatomic variants. Measurements were obtained from different anatomic references to the columella. RESULTS: Of a total of ten dissections, in 100% of cases ethmoid crests were identified anterior to the sphenopalatine foramen. Localization of the sphenopalatine foramen in the lateral nasal wall in 60% cases was in the transition from middle meatus with superior meatus. The vidian nerve in 90% of cases was located superior and posterior to the sphenopalatine foramen. For the measurements, no significant differences between the two sides of each specimen were noticed. CONCLUSIONS: The sphenopalatine foramen presents multiple anatomic variants and numerous landmarks, which are important to comprehend in order to perform a successful and safe endoscopic sinus surgery.

ANTECEDENTES: el foramen esfenopalatino se localiza en la pared nasal, con múltiples variantes y referencias anatómicas que es importante conocer para optimizar los RESULTADOS del tratamiento quirúrgico y la epistaxis posterior. OBJETIVO: describir la anatomía endoscópica del foramen esfenopalatino, las estructuras relacionadas, y las variantes anatómicas en población mexicana. MATERIAL Y MÉTODOS: estudio prospectivo, observacional y experimental. Se incluyeron 5 especímenes cadavéricos, se realizaron las disecciones para identificar la anatomía del foramen esfenopalatino y sus variantes anatómicas, se midieron diferentes referencias anatómicas a la columela. RESULTADOS: de 10 disecciones realizadas, en 100% de los casos se identificó la cresta etmoidal anterior al foramen esfenopalatino, la localización en la pared nasal en 60% de los casos fue en la transición del meato medio con el meato superior, el nervio Vidiano en 90% de los casos se localizó posterosuperior al foramen esfenopalatino. En relación con las mediciones no se encontraron diferencias significativas entre ambos lados de cada fosa nasal. CONCLUSIONES: las variantes anatómicas del foramen esfenopalatino son múltiples, por lo que contar con referencias anatómicas es de suma importancia para poder localizarlo durante la cirugía endoscópica nasal. Palabras clave: foramen esfenopalatino, arteria esfenopalatina, nervio vidiano, epistaxis posterior, cresta etmoidal, pared nasal.