The Role of Inhalant Allergens on the Clinical Manifestations of Atopic Dermatitis.

BACKGROUND: Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD). OBJECTIVE: To review the relationship between inhalant allergens and AD. METHODS: A literature review was conducted using three databases: PubMed/MEDLINE, ClinicalKey, and Web of Science. Search terms, including "atopic dermatitis," "atopic eczema," and "eczema," were used in combination with "inhalant allergen," "inhaled allergen," and "aeroallergen" to identify relevant published manuscripts that highlight the relationship between AD and exposures to inhalant allergens. RESULTS: Fifteen articles were suitable for review. The studies included in the review investigated the effect of inhalant allergens on the clinical manifestations of AD through bronchial provocation, direct skin contact, and allergen sensitization. CONCLUSION: There is a significant relationship between exposures to inhalant allergens and AD. Inhalant allergens may aggravate AD symptoms by either bronchial provocation or direct skin contact. Sensitization of inhalant allergens, mainly house dust mites, follows a specific age-related pattern.

Evaluation and treatment of rhinosinusitis with primary antibody deficiency in adults: Evidence-based review with recommendations.

BACKGROUND: There is clear evidence that the prevalence of primary antibody deficiency (PAD) is higher in patients with recurrent and chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in patients with PAD. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through August 2022. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated. RESULTS: A total of 42 studies were included in this evidence-based review. These studies were evaluated on incidence of PAD in rhinosinusitis patients, incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, PAD can occur in up to 50% of patients with recalcitrant CRS. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher-level studies that compare different treatments in patients with PAD and rhinosinusitis.

Postoperative Polyp Scale (POPS): Development of a New Sinonasal Polyp Grading Scale.

OBJECTIVE: Commonly used endoscopic grading scales, such as the nasal polyp scale, inadequately describe the degree of polyposis found postoperatively in the paranasal sinus cavities. The purpose of this study was to create a novel grading system that more accurately characterizes polyp recurrence in postoperative sinus cavities, the Postoperative Polyp Scale (POPS). METHODS: A modified Delphi method was utilized to establish the POPS using consensus opinion among 13 general otolaryngologists, rhinologists, and allergists. Postoperative endoscopy videos from 50 patients with chronic rhinosinusitis with nasal polyps were reviewed by 7 fellowship-trained rhinologists and scored according to the POPS. Videos were rated again 1 month later by the same reviewers, and scores were assessed for test-retest and inter-rater reliability. RESULTS: Overall inter-rater reliability for the first and second reviews of the 52 videos was Kf = 0.49 (95% CI 0.42-0.57) and Kf = 0.50 (95% CI 0.42-0.57) for the POPS. Intra-rater reliability showed near-perfect test-retest reliability for the POPS with Kf = 0.80 (95% CI 0.76-0.84). CONCLUSION: The POPS is an easy-to-use, reliable, and novel objective endoscopic grading scale that more accurately describes polyp recurrence in the postoperative state which will be useful in the future for measuring the efficacy of various medical and surgical interventions. LEVEL OF EVIDENCE: 5 Laryngoscope, 133:2885-2890, 2023.

Corticosteroid-eluting implants for the management of chronic rhinosinusitis with or without nasal polyps.

INTRODUCTION: Topical corticosteroid therapies are the most popular prescribed medications for patients with chronic rhinosinusitis (CRS). While topical corticosteroids effectively reduce the inflammatory burden associated with CRS, their distribution inside the nasal cavity is limited and primarily dependent on their delivery device. Corticosteroid-eluting implants serve as relatively novel technology, allowing targeted, sustained release of a high concentration of corticosteroids directly onto the sinus mucosa. Three types of corticosteroid-eluting implants can be characterized: 1. intraoperatively inserted corticosteroid-eluting sinus implants, 2. postoperatively inserted, office-based corticosteroid-eluting sinus implants, and 3. office-based corticosteroid-eluting implants for naïve paranasal sinuses. AREAS COVERED: The review summarizes the different steroid-eluting sinus implants, their indications for use in CRS patients, and the existing evidence regarding their clinical efficacy. We also highlight potential areas for improvement and development. EXPERT OPINION: Corticosteroid-eluting sinus implants highlight an evolving field that is constantly investigating and adding new treatment options to the market. Presently, corticosteroid-eluting implants for CRS are most commonly applied intraoperatively and postoperatively with endoscopic sinus surgery, providing significant improvements in mucosal healing and reducing the amount of surgical failures. Future development around corticosteroid-eluting implants should focus on strategies to reduce the amount of crusting around the implants.

Climate change, the environment, and rhinologic disease.

BACKGROUND: The escalating negative impact of climate change on our environment has the potential to result in significant morbidity of rhinologic diseases. METHODS: Evidence based review of examples of rhinologic diseases including allergic and nonallergic rhinitis, chronic rhinosinusitis, and allergic fungal rhinosinusitis was performed. RESULTS: The lower socioeconomic population, including historically oppressed groups, will be disproportionately affected. CONCLUSIONS: We need a systematic approach to improve healthcare database infrastructure and funding to promote diverse scientific collaboration to address these healthcare needs.

Nasal Nitric Oxide as a Biomarker in the Diagnosis and Treatment of Sinonasal Inflammatory Diseases: A Review of the Literature.

OBJECTIVE: To critically review the literature on nasal nitric oxide (nNO) and its current clinical and research applicability in the diagnosis and treatment of different sinonasal inflammatory diseases, including acute bacterial rhinosinusitis (ABRS), allergic rhinitis (AR), and chronic rhinosinusitis (CRS). METHODS: A search of the PubMed database was conducted to include articles on nNO and sinonasal diseases from January 2003 to January 2020. All article titles and abstracts were reviewed to assess their relevance to nNO and ABRS, AR, or CRS. After selection of the manuscripts, full-text reviews were performed to synthesize current understandings of nNO and its applications to the various sinonasal inflammatory diseases. RESULTS: A total of 79 relevant studies from an initial 559 articles were identified using our focused search and review criteria. nNO has been consistently shown to be decreased in ABRS and CRS, especially in cases with nasal polyps. While AR is associated with elevations in nNO, nNO levels have also been found to be lower in AR cases with higher symptom severity. The obstruction of the paranasal sinuses is speculated to be an important variable in the relationship between nNO and the sinonasal diseases. Treatment of these diseases appears to affect nNO through the reduction of inflammatory disease burden and also mitigation of sinus obstruction. CONCLUSION: nNO has been of increasing interest to researchers and clinicians over the last decade. The most compelling data for nNO as a clinical tool involve CRS. nNO can be used as a marker of ostiomeatal complex patency. Variations in measurement techniques and technology continue to impede standardized interpretation and implementation of nNO as a biomarker for sinonasal inflammatory diseases.

Predictive value of pituitary tumor morphology on outcomes and complications in endoscopic transsphenoidal surgery.

Purpose: Endoscopic transsphenoidal surgery (ETSS) is an increasingly utilized approach for resection of pituitary tumors. Prior studies have evaluated preoperative tumor size, location, and extent as prognostic factors for surgical resection. There is little data on the relationship between preoperative pituitary tumor radiographic morphology and surgical outcomes. Study Design: Retrospective longitudinal study. Setting: Single tertiary care institution. Subjects and Methods: Preoperative magnetic resonance imaging and computed tomography scans from patients undergoing ETSS for pituitary tumor resections from 2007 to 2017 were retrospectively evaluated. A neuroradiologist classified these pituitary tumors into six morphologic groups, each defined by volume, dimensions, extension, and shape. Surgical difficulty, rates of incomplete resection, and postoperative complications were then stratified in relation to the morphologic groups. Results: Pituitary tumors from 131 patients were classified from preoperative imaging into six characteristic morphologies: (1) microtumor, (2) round, (3) transverse oblong, (4) superior-inferior oblong, (5) bilobed, and (6) large lobulated. Tumors that were characterized with the large lobulated, bilobed, and transverse oblong morphologies correlated with higher rates of postoperative evidence of residual tumor (70%, 36%, and 47%, respectively, all P < 0.002). Likewise, large lobulated, bilobed, and transverse oblong morphologies were also associated with intraoperative cerebrospinal fluid leaks (70%, 31%, and 35%, respectively, all P < 0.05). Conclusions: We describe a novel descriptive system for the morphology of pituitary tumors that can be determined from preoperative imaging. Different tumor morphologic groups are associated with varying degrees of gross tumor resection, complications, and surgical difficulty. Utilizing pituitary tumor morphology may aid surgeons in planning the extent of resection, need for complex closure, and patient counseling.

Management of complicated acute sinusitis in the setting of concurrent COVID-19.

PURPOSE: Intraorbital and intracranial complications of acute bacterial rhinosinusitis require timely medical and surgical treatment to prevent the development of long-term neurologic sequelae. The era of Coronavirus Disease-2019 (COVID-19) has complicated the management of complicated acute rhinosinusitis, especially when patients have concurrent acute sinusitis and COVID-19 infection. This case series aims to highlight the clinical course of pediatric patients at a single tertiary pediatric hospital with concurrent complicated bacterial rhinosinusitis and COVID-19. MATERIALS AND METHODS: A search of pediatric patients treated for COVID-19 and complications from acute sinusitis was performed using billing records for the year 2020-2021 at a single pediatric tertiary hospital. Data regarding presentation, management, microbiology, and hospital course was collected for review. RESULTS: A total of 6 patients with complicated bacterial sinusitis in the setting of COVID-19 infection were included. All patients were initially managed with medical therapy, consisting of systemic antibiotics, but 3 of these patients ultimately required surgical intervention. Cultures from the cohort grew Staphylococcus aureus, streptococcus intermedius, streptococcus constellatus or Prevotella species. All patients experienced clinical improvements and were eventually discharged home with oral antibiotics. CONCLUSION: COVID-19 continues to be an unusual disease especially for the pediatric population. Concurrent complicated acute rhinosinusitis and COVID-19 appear to have higher rates of surgical requirement in the pediatric population. COVID-19 safety precautions have influenced management practices for patients with severe bacterial rhinologic infections. While there may be an association between complicated bacterial rhinosinusitis and COVID-19 infection, further research is necessary to determine a true correlation.

A review of phase III clinical trials of US FDA-approved biologic therapies for chronic rhinosinusitis with nasal polyposis.

Chronic rhinosinusitis with nasal polyposis is a heterogenous disease with complex underlying pathophysiologic mechanisms. Biologics have been proven to be an effective add-on therapeutic option in severe and/or refractory cases. Currently, dupilumab, omalizumab and mepolizumab have phase III data to support their use in these patients and have received approval from the United States Food and Drug Administration specifically for the treatment of nasal polyposis. Each of these biologics has shown its ability to reduce nasal polyp size and improve nasal congestion/obstruction and sense of smell, but additional research is needed to directly compare the efficacy and safety of the different biologic agents for different nasal polyposis endotypes.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a complex disease that has many different causes. Biological therapies have been proven to be effective when added on to standard treatment in severe and/or cases that are not responsive to initial treatment. Currently, dupilumab, omalizumab and mepolizumab have data supporting their use in such patients and have received approval by the United States Food and Drug Administration for the treatment of CRSwNP. Each of these biologics has shown its ability to reduce nasal polyp size and improve nasal congestion/obstruction and sense of smell, but additional research is needed to directly compare the efficacy and safety of the different biologic agents for different CRSwNP subtypes.

ACR Appropriateness Criteria® Sinonasal Disease: 2021 Update.

This article presents guidelines for initial imaging utilization in patients presenting with sinonasal disease, including acute rhinosinusitis without and with suspected orbital and intracranial complications, chronic rhinosinusitis, suspected invasive fungal sinusitis, suspected sinonasal mass, and suspected cerebrospinal fluid leak. CT and MRI are the primary imaging modalities used to evaluate patients with sinonasal disease. Given its detailed depiction of bony anatomy, CT can accurately demonstrate the presence of sinonasal disease, bony erosions, and anatomic variants, and is essential for surgical planning. Given its superior soft tissue contrast, MRI can accurately identify clinically suspected intracranial and intraorbital complications, delineate soft tissue extension of tumor and distinguish mass from obstructed secretions.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The role of omalizumab in the treatment of chronic rhinosinusitis with nasal polyposis.

Introduction: Chronic rhinosinusitis with nasal polyposis (CRSwNP) poses a significant healthcare challenge, with diminished quality of life for patients and high costs and resource utilization for disease management. The understanding of CRSwNP pathophysiology has progressed with identification of various inflammatory biomarkers and subsequent development of monoclonal antibodies that target the underlying mechanisms of inflammation.Areas covered: Omalizumab is a biologic agent for CRSwNP treatment that targets immunoglobulin (Ig)-E. The US FDA has approved the use of omalizumab as an add-on biologic therapy for nasal polyposis in December 2020. Two Phase III clinical trials, POLYP 1 and POLYP 2, have shown that omalizumab improves both subjective patient-reported outcomes and objective physician-evaluated metrics for CRSwNP. Ongoing studies are still exploring the efficacy, safety, and cost-effectiveness of biologics for CRSwNP.Expert opinion: Biologics will continue develop as a viable management option for CRSwNP. Omalizumab is regarded as a promising addition to current treatment strategies for refractory disease.

Biologics for chronic rhinosinusitis with nasal polyps: Economics and ethics.

Biologics have recently been approved for use in chronic rhinosinusitis with nasal polyps patients. While effective in controlling disease on subjective and objective short-term outcome measures, limited data suggest that biologics have the potential to be used long term. The current wholesale acquisition costs for biologics are quite high. Widespread, prolonged use of these medications may create a large burden to our healthcare system. Cost-effectiveness analyses, particularly for specific patient cohorts, are needed to determine appropriate use of these medications. The ethics of patient preference of various treatment options, counseling regarding side effect profiles, and healthcare economics also need to be addressed.

Revisiting the controversy: The role of fungi in chronic rhinosinusitis.

In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial. Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have focused on the bacterial community, mainly highlighting the loss of diversity associated with sinus inflammation. Within the various CRS with nasal polyps (CRSwNP) phenotypes, allergic fungal rhinosinusitis presents an opportunity to investigate the role of fungi in chronic type 2 immune responses as well as the antifungal immune pathways designed to prevent invasive fungal diseases. In this review, we examine the spectrum of fungi-associated sinus diseases highlighting the interaction between fungal species and host immune status on disease presentation. With a focus on fungi and type 2 immune response, we highlight the current knowledge and its limitations of the sinus mycobiota along with cellular interactions and activated molecular pathways linked to fungi.

Variations in utilization and clinical outcomes for endoscopic sphenopalatine artery ligation and endovascular arterial embolization in a single multi-hospital network.

PURPOSE: Endoscopic sphenopalatine artery ligation (ESPAL) and endovascular arterial embolization (EAE) are increasingly common treatment options for patients with refractory epistaxis. The objective of this study was to compare the utilization pattern and clinical outcomes between these interventions within our single multi-hospital network. MATERIALS AND METHODS: A retrospective study of all patients undergoing ESPAL and/or EAE within any of the hospitals in a single healthcare network between 2008 and 2017 was conducted. We compared differences in procedure utilization with various hospital characteristics. Secondarily, we evaluated clinical outcomes and costs associated with each procedure. RESULTS: Forty-three ESPAL and 33 EAE procedures were performed across 7 hospitals, with the majority of procedures being performed at teaching institutions (65% and 91%, p = .013). The majority of both interventions were performed in larger hospitals and EAE patients were more likely to undergo inter-hospital transfer compared to ESPAL patients (48.5% and 16.3%, p = .02). Success rates for ESPAL and EAE were comparable (95% and 93%); however, the median direct cost of treatment for EAE was significantly higher than the cost for ESPAL ($12984.89 and $5002.02, p < .0001). CONCLUSIONS: The majority of both ESPAL and EAE interventions were performed at teaching and larger hospitals. Transfers occurring prior to EAE may have been due to the limited availability of interventional radiology services, and likely contributed to the increased cost of treatment. ESPAL is a known cost-effective management strategy and should be considered early in treatment algorithms of refractory epistaxis.

Cryosurgical Ablation for Treatment of Rhinitis: Two-Year Results of a Prospective Multicenter Study.

OBJECTIVES/HYPOTHESIS: To assess the long-term (12-24 months) safety and effectiveness of cryoablation of the posterior nasal nerve as treatment for chronic rhinitis. STUDY DESIGN: A multicenter, prospective, single-arm clinical study. METHODS: The study was conducted from February 2017 to April 2020. Study endpoints included change from baseline in the reflective Total Nasal Symptom Score (rTNSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), physician assessment of improvement using the Clinical Global Impression-Improvement (CGI-I), and the incidence of treatment-related adverse events. RESULTS: Ninety-one participants completed the study through the initial 12-month study period. Sixty-two participants consented to the long-term follow-up with 57 completing the 24-month follow-up. Significant improvements in the total rTNSS were reflected in a median change from baseline of -3.0 or -4.0 at all timepoints (P < .001). Greater than 80.0% of participants achieved the minimum clinically important difference (MCID) of improvement by ≥1 point on the rTNSS at all follow-ups. Total RQLQ scores indicated significant improvement (P < .0001) in quality of life. Over 77% of participants achieved the MCID (≥0.5 points) for the total RQLQ score. According to the CGI-I, ≥83.0% experienced improvement at all but the 12-month visit (61.9%). One participant experienced two treatment-related serious adverse events (epistaxis and retained pledget). A total of 29 nonserious treatment-related AEs were reported in 23 participants; most events were transient and resolved with little to no intervention. CONCLUSIONS: Cryotherapy significantly and clinically improves rhinitis symptoms and quality of life with outcomes that are durable through 24 months after treatment. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1952-1957, 2021.

Intraoperative Applications of Topical Corticosteroid Therapy for Chronic Rhinosinusitis.

OBJECTIVES: To provide an overview of recent techniques and technologies for the application of topical corticosteroid therapy immediately following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). METHODS: A comprehensive search in the PubMed and Google Scholar databases was conducted to identify publications between January 2000 and December 2019 detailing clinical trials that have evaluated the efficacy and safety of intraoperative applications of topical corticosteroids for CRS. RESULTS: A total of 21 articles, all of which highlight a variety of corticosteroid-infused products, including Propel corticosteroid-eluting stents, NasoPore, Merocel, SinuBand, calcium alginate, and bioresorbable gel-type products, are included for review. Propel stents are the only devices that have achieved level 1A evidence in terms of efficacy and have data to support their safety. The remaining products have shown mixed results in terms of efficacy and safety. CONCLUSION: A wide range of techniques and technologies have been introduced to enhance the topical delivery of corticosteroids into the neosinuses after ESS for CRS. Regarding efficacy, there is level 1A evidence to support the use of Propel stents. Most of the remaining strategies show some degree of efficacy. Direct comparisons across the different strategies are limited owing to the varied uses of delivery vectors, corticosteroid choices, and doses of corticosteroids. Propel stents and SinuBand have sufficient data to support systemic and ocular safety, whereas the remaining products have limited data to support their safety.

Dupilumab in the treatment of chronic rhinosinusitis with nasal polyposis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) imparts a significant healthcare challenge, resulting in diminished quality of life for patients and high costs with resource utilization for disease management. Understanding of CRSwNP pathophysiology has progressively evolved and the identification of various inflammatory biomarkers has led to the development of monoclonal antibodies that target the underlying mechanisms of inflammation. Dupilumab, which targets IL-4 and IL-13 signaling, serves as a novel agent for CRSwNP treatment. Three clinical trials, NCT01920893, SINUS-24 and SINUS-52, have shown that dupilumab improves both subjective patient-reported outcomes and objective physician-evaluated metrics for CRSwNP. The favorable findings have resulted in approval by the US FDA in June 2019 as the first biologic therapy for CRSwNP.

Establishing Urinary Leukotriene E4 as a Diagnostic Biomarker for Chronic Rhinosinusitis with Comorbid Asthma and Atopy.

OBJECTIVE: While urinary leukotriene E4 (uLTE4) is a validated biomarker for the cysteinyl leukotriene pathway, which is central to the pathophysiology of asthma, atopy, and chronic rhinosinusitis (CRS), the contributions of comorbid asthma and atopy to uLTE4 levels in various CRS subtypes have not been previously characterized. We sought to (1) identify reference values for uLTE4 in subjects with and without CRS and (2) determine how the presence of comorbid atopy and asthma affects uLTE4 levels in CRS. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: A prospective case-control study was conducted to compare uLTE4 levels between patients with CRS and healthy controls. Urinary LTE4 levels were measured by enzyme immunoassay and were adjusted for urinary creatinine concentrations (pg/mg Cr). Patients with CRS were stratified by the clinical comorbidities to determine normative uLTE4 values for patients with CRS with and without comorbid asthma or atopy. RESULTS: A total of 153 patients (mean age, 47.3; 47.1% female) were included in the study. Patients with CRS demonstrated significantly higher concentrations of uLTE4 than healthy controls (1652 vs 1065 pg/mg Cr, P = .032). Within the group of patients with CRS, comorbid asthma also individually correlated with elevated uLTE4 levels (1597 pg/mg Cr, P = .0098). Patients with CRS who did not have comorbid allergy and asthma, in contrast, did not have statistically higher uLTE4 levels than healthy controls (1142 pg/mg Cr, P = .61). CONCLUSION: Urinary LTE4 serves as a noninvasive measure of the inflammatory state in CRS. Comorbid asthma and atopy contribute to elevated uLTE4 levels in CRS.