GRAND ROUNDS REVIEW ARTICLE: Rhinitis disease burden and the impact of social determinants of health.

Social determinants of health (SDH) have substantial impact on patient care and outcomes globally, both in low-to-middle income countries and high income countries. In the clinic, lack of availability of diagnostic tools, inequities in access to care, and challenges obtaining and adhering to prescribed treatment plans may further compound these issues. This article addresses a case of rhinitis in the context of SDH and inequities in care that may affect various communities and populations around the world. SDH may include various aspects of one's financial means, education, access to medical care, environment and living situation, and community factors - each of which could play a role in the rhinitis disease manifestations, diagnosis, and management. Allergic and non-allergic rhinitis are considered from this perspective. Rhinitis epidemiology, disease burden, and risk factors are broadly addressed. Patient evaluation, diagnostic tests, and management options are also reviewed, and issues related to SDH are noted. Finally, inequities in care, knowledge gaps, and unmet needs are highlighted. It is critical to consider SDH and care inequities when evaluating and treating patients for rhinitis and other allergic conditions.

Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2).

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays. OBJECTIVE: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps). METHODS: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24. RESULTS: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids. CONCLUSIONS: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status.

Allergy and Asthma Prevalence and Management Across Nasal Polyp Subtypes.

Allergy and asthma prevalence vary across different subsets of chronic rhinosinusitis with nasal polyposis. In this article, the authors investigate the management of allergy and asthma within populations of patients with aspirin-exacerbated respiratory disease, allergic fungal rhinosinusitis, and central compartment atopic disease. Topical steroids, nasal rinses, and endoscopic sinus surgery are frequently employed in the management of nasal polyposis. Further, other causes of upper and lower airway inflammation like allergy and asthma should be considered in the overall treatment plan in order to optimize outcomes.

Inflammatory characteristics of central compartment atopic disease.

BACKGROUND: Central compartment atopic disease (CCAD) is an emerging phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP) characterized by prominent central nasal inflammatory changes. This study compares the inflammatory characteristics of CCAD relative to other phenotypes of CRSwNP. METHODS: A cross-sectional analysis of data from a prospective clinical study was performed on patients with CRSwNP who were undergoing endoscopic sinus surgery (ESS). Patients with CCAD, aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and non-typed CRSwNP (CRSwNP NOS) were included and mucus cytokine levels and demographic data were analyzed for each group. Chi-squared/Mann-Whitney U tests and partial least squares discriminant analysis (PLS-DA) were performed for comparison and classification. RESULTS: A total of 253 patients were analyzed (CRSwNP, n = 137; AFRS, n = 50; AERD, n = 42; CCAD, n = 24). Patients with CCAD were the least likely to have comorbid asthma (p = 0.0004). The incidence of allergic rhinitis in CCAD patients did not vary significantly compared to patients with AFRS and AERD, but was higher compared to patients with CRSwNP NOS (p = 0.04). On univariate analysis, CCAD was characterized by less inflammatory burden, with reduced levels of interleukin 6 (IL-6), IL-8, interferon gamma (IFN-γ), and eotaxin relative to other groups and significantly lower type 2 cytokines (IL-5, IL-13) relative to both AERD and AFRS. These findings were supported by multivariate PLS-DA, which clustered CCAD patients into a relatively homogenous low-inflammatory cytokine profile. CONCLUSIONS: CCAD has unique endotypic features compared to other patients with CRSwNP. The lower inflammatory burden may be reflective of a less severe variant of CRSwNP.

Determinants of physician assessment of chronic rhinosinusitis disease control using EPOS 2020 criteria and the importance of incorporating patient perspectives of disease control.

BACKGROUND: We identify chronic rhinosinusitis (CRS) manifestations associated with how rhinologists assess CRS control, with a focus on patient perspectives (patient-reported CRS control). METHODS: Fifteen rhinologists were provided with real-world data from 200 CRS patients. Participating rhinologists first classified patients' CRS control as "controlled," "partly controlled," and "uncontrolled" using seven CRS manifestations reflecting European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) CRS control criteria (nasal obstruction, drainage, impaired smell, facial pain/pressure, sleep disturbance, use of systemic antibiotics/corticosteroids in past 6 months, and nasal endoscopy findings) and patient-reported CRS control. They then classified patients' CRS control without knowledge of patient-reported CRS control. Interrater reliability and agreement of rhinologist-assessed CRS control with patient-reported CRS control and EPOS guidelines were determined. RESULTS: CRS control classification with and without knowledge of patient-reported CRS control was highly consistent across rhinologists (κw  = 0.758). Rhinologist-assessed CRS control agreed with patient-reported CRS control significantly better when rhinologists had knowledge of patient-reported CRS control (κw  = 0.736 vs. κw  = 0.554, p < 0.001). Patient-reported CRS control, nasal obstruction, drainage, and endoscopy findings were most strongly associated with rhinologists' assessment of CRS control. Rhinologists' CRS control assessments weakly agreed with EPOS CRS control guidelines with (κw  = 0.529) and without (κw  = 0.538) patient-reported CRS control. Rhinologists classified CRS as more controlled than EPOS guidelines in almost 50% of cases. CONCLUSIONS: This study directly demonstrates the importance of patient-reported CRS control as a dominant influence on rhinologists' CRS control assessment. Knowledge of patient-reported CRS control may better align rhinologists' CRS control assessments and treatment decisions with patients' perspectives.

Trends Following Implementation of an Otolaryngology Hospitalist Model in a Tertiary Care Setting.

OBJECTIVES: The otolaryngology hospitalist (OH) model is an emerging paradigm for inpatient and acute patient care. This study presents encounter volume before and after the implementation of an OH service. Postimplementation trends are evaluated. STUDY DESIGN: Retrospective administrative and clinical database review. SETTING: Tertiary care university hospital. METHODS: This review includes 2 distinct time frames (2008-2012, 2014-2018), representing periods before and after OH implementation. The number of billed patient encounters is compared between these 2 periods using the hospital data warehouse. Additional data is evaluated for the postimplementation period, using a clinical database. Encounter type, the reason for consultation, procedures, and requesting service/location are described. RESULTS: After the OH implementation, there was a 451% increase in evaluation and management encounters submitted for billing. Since the OH model inception, there was an overall increase in encounters (849-910), procedures performed (319-345), and operative cases (46-54) per year. Each inpatient consultation request generates one or more procedures on average. Common reasons for consultation include sinonasal pathology (20.3%), dysphonia/dysphagia (17.5%), and airway evaluation (15%). Critical Care (24%), Emergency Medicine (21%), and Hospital Medicine (21%) requested most of the Otolaryngology consults. Most consults were seen on the inpatient medical/surgical floor (46%), with the ICU (27%) and the Emergency Department (22%) being the next most common locations. CONCLUSIONS: The OH model is an evolving paradigm that is viable and offers timely, specialized care for patients in a hospital or acute care setting.

Single-cell analysis of human nasal mucosal IgE antibody secreting cells reveals a newly minted phenotype.

Immunoglobulin (Ig) E is central to the pathogenesis of allergic conditions, including allergic fungal rhinosinusitis. However, little is known about IgE antibody secreting cells (ASCs). We performed single-cell RNA sequencing from cluster of differentiation (CD)19+ and CD19- ASCs of nasal polyps from patients with allergic fungal rhinosinusitis (n = 3). Nasal polyps were highly enriched in CD19+ ASCs. Class-switched IgG and IgA ASCs were dominant (95.8%), whereas IgE ASCs were rare (2%) and found only in the CD19+ compartment. Through Ig gene repertoire analysis, IgE ASCs shared clones with IgD-CD27- "double-negative" B cells, IgD+CD27+ unswitched memory B cells, and IgD-CD27+ switched memory B cells, suggesting ontogeny from both IgD+ and memory B cells. Transcriptionally, mucosal IgE ASCs upregulate pathways related to antigen presentation, chemotaxis, B cell receptor stimulation, and survival compared with non-IgE ASCs. Additionally, IgE ASCs have a higher expression of genes encoding lysosomal-associated protein transmembrane 5 (LAPTM5) and CD23, as well as upregulation of CD74 (receptor for macrophage inhibitory factor), store-operated Calcium entry-associated regulatory factor (SARAF), and B cell activating factor receptor (BAFFR), which resemble an early minted ASC phenotype. Overall, these findings reinforce the paradigm that human ex vivo mucosal IgE ASCs have a more immature plasma cell phenotype than other class-switched mucosal ASCs and suggest unique functional roles for mucosal IgE ASCs in concert with Ig secretion.

A Synopsis of Guidance for Allergic Rhinitis Diagnosis and Management From ICAR 2023.

An updated edition of the International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) has recently been published. This consensus document, which included the participation of 87 primary authors and 40 additional consultant authors, who critically appraised evidence on 144 individual topics concerning allergic rhinitis, provides guidance for health care providers using the evidence-based review with recommendations (EBRR) methodology. This synopsis highlights topical areas including pathophysiology, epidemiology, disease burden, risk and protective factors, evaluation and diagnosis, aeroallergen avoidance and environmental controls, single and combination pharmacotherapy options, allergen immunotherapy (subcutaneous, sublingual, rush, cluster), pediatric considerations, alternative and emerging therapies, and unmet needs. Based on the EBRR methodology, ICAR:AR includes strong recommendations for the treatment of allergic rhinitis: (1) for the use of newer generation antihistamines compared with first-generation alternatives, intranasal corticosteroid, intranasal saline, combination therapy with intranasal corticosteroid plus intranasal antihistamine for patients not responding to monotherapy, and subcutaneous immunotherapy and sublingual tablet immunotherapy in properly selected patients; (2) against the use of oral decongestant monotherapy and routine use of oral corticosteroids.

International consensus statement on allergy and rhinology: Allergic rhinitis - 2023.

BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Hemostasis in endoscopic sinus and skull base surgery.

PURPOSE OF REVIEW: Bleeding during endoscopic endonasal procedures can quickly obscure critical anatomic landmarks. This increases both the difficulty of the surgical procedure and the risk of complications faced by the patient. As the indications for surgical management of sinonasal pathology grow, it is important to review techniques to minimize bleeding and facilitate safe surgery. RECENT FINDINGS: Evidence continues to accumulate for best practices in the surgical management of sinonasal disease. Recently, international guidelines have attempted to summarize this body of evidence, lending further support to several interventions which have been advocated as methods to decrease bleeding during endoscopic endonasal surgery. Additional studies have specifically investigated the safety of certain commonly employed techniques. The utility of preoperative corticosteroid therapy and the use of total intravenous anesthetic techniques in increasingly validated. Further evidence supports the safety of reverse Trendelenburg positioning for surgical management of inflammatory disease. SUMMARY: Recent wide scale systematic review of the literature regarding perioperative and intraoperative management of hemostasis has reinforced the utility of certain interventions, while others remain ambiguous.

Diagnosis, Prognosticators, and Management of Acute Invasive Fungal Rhinosinusitis: Multidisciplinary Consensus Statement and Evidence-Based Review with Recommendations.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated. RESULTS: A review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms.

Unified Airway Disease: Examining Prevalence and Treatment of Upper Airway Eosinophilic Disease with Comorbid Asthma.

The "unified airway" describes the concept that inflammation affects upper and lower airways by similar mechanisms; this often manifests as rhinitis, rhinosinusitis, and/or nasal polyposis in the upper airway with associated asthma or bronchial inflammation in the lower airways. The relationships between eosinophilic diseases of the upper and lower airways are highlighted by examining their prevalence and treatment regimens along with the synergistic effects of treatment on upper and lower airway symptoms. It is important to recognize the interrelatedness of upper and lower airway eosinophilic disease to assess and manage patients accurately and holistically.

Management paradigms for chronic rhinosinusitis in individuals with asthma: An evidence-based review with recommendations.

BACKGROUND: Despite the significant morbidity associated with chronic rhinosinusitis (CRS) in individuals with asthma (CRSwA), there is a paucity of codified, evidence-based management strategies for CRS in this population. METHODS: Using PubMed, Embase, and Cochrane Review Databases, a systematic review was performed covering management strategies for CRSwA. A total of 5903 articles were screened, and 70 were included for full-text analysis. After application of exclusion criteria, 53 articles comprised the qualitative synthesis. The level of evidence was graded and benefit-harm assessments, as well as value judgment and recommendations, were provided RESULTS: Strong evidence confirms the benefit of oral and topical medications on sinonasal-specific outcomes in individuals with CRSwA; there is low-grade evidence demonstrating that these agents improve lung function and/or asthma control. Moderate to strong evidence suggests that endoscopic sinus surgery (ESS) improves both sinonasal- and asthma-specific quality of life. Although there is insufficient to low evidence to indicate that ESS improves pulmonary function in this population, data indicate a positive impact of this intervention on asthma control. Biologic medications strongly improve both subjective and objective sinonasal- and asthma-specific outcomes. CONCLUSION: Evidence supports managing CRS in individuals with CRSwA in a stepwise fashion, starting with traditional nonbiologic oral and topical medication, and escalating to second-line treatments, such as ESS and biologics. Optimal treatment of individuals who have CRSwA often requires concurrent, directed management of asthma, as not all CRS interventions impact asthma status.

Treatment strategies for postviral olfactory dysfunction: A systematic review.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been associated with a dramatic increase in postviral olfactory dysfunction (PVOD) among patients who are infected. A contemporary evidence-based review of current treatment options for PVOD is both timely and relevant to improve patient care. Objective: This review seeks to impact patient care by qualitatively reviewing available evidence in support of medical and procedural treatment options for PVOD. Systematic evaluation of data quality and of the level of evidence was completed to generate current treatment recommendations. Methods: A systematic review was conducted to identify primary studies that evaluated treatment outcomes for PVOD. A number of medical literature data bases were queried from January 1998 to May 2020, with completion of subsequent reference searches of retrieved articles to identify all relevant studies. Validated tools for the assessment of bias among both interventional and observational studies were used to complete quality assessment. The summary level of evidence and associated outcomes were used to generate treatment recommendations. Results: Twenty-two publications were identified for qualitative review. Outcomes of alpha-lipoic acid, intranasal and systemic corticosteroids, minocycline, zinc sulfate, vitamin A, sodium citrate, caroverine, intranasal insulin, theophylline, and Gingko biloba are reported. In addition, outcomes of traditional Chinese acupuncture and olfactory training are reviewed. Conclusion: Several medical and procedural treatments may expedite the return of olfactory function after PVOD. Current evidence supports olfactory training as a first-line intervention. Additional study is required to define specific treatment recommendations and expected outcomes for PVOD in the setting of COVID-19.

A Prospective Analysis of Systemic and Local Aeroallergen Sensitivity in Central Compartment Atopic Disease.

OBJECTIVE: To compare systemic allergen sensitivity and local allergen sensitivity in the sinonasal tissue of patients with a recently identified subtype of chronic rhinosinusitis strongly associated with allergy: central compartment atopic disease (CCAD). STUDY DESIGN: Prospective cohort study. SETTING: Academic tertiary care rhinology clinic. METHODS: Fifteen participants with endoscopic and radiographic evidence of CCAD underwent systemic allergy testing with skin testing and measurement of serum specific immunoglobulin E (sIgE) to 15 regionally common aeroallergens. Local allergen sensitivity was determined by measuring sIgE to these same 15 allergens in their sinonasal tissue. sIgE testing was performed by ImmunoCAP assay. RESULTS: Of the 15 participants, 14 were sensitive to at least 1 allergen locally in the central compartment and systemically on skin or serum testing. Among all participants, 4 were sensitive to allergens on central compartment sIgE testing that they were not sensitive to on skin and serum sIgE testing (range, 1-8 discordant allergens). Comparisons between local and systemic aeroallergen sensitivity results showed statistically significant correlations (P < .05) ranging from weak to strong. CONCLUSION: Systemic allergy testing is recommended in the initial workup for CCAD. Local allergen sensitivities may be present in a subset of patients with CCAD. Further study of the clinical significance of these sensitivities should be undertaken in CCAD, with evaluation of the role of medical therapies and allergen immunotherapy in the treatment of CCAD.

Pituitary Gland Surgical Emergencies: The Role of Endoscopic Intervention.

True pituitary surgical emergencies are rare. These events can occur throughout the perioperative period and are broadly categorized by the timing of occurrence. Acute indications for emergent pituitary surgery include pituitary apoplexy, vision loss, and severe Cushing presentation. Emergencies may also occur intraoperatively, secondary to bleeding. Postoperative emergencies include epistaxis, pneumocephalus, and intracranial bleeding. Cerebrospinal fluid (CSF) leak occurs in about 37.4% of transsphenoidal sellar surgery, yet postoperative CSF leaks are less frequent at approximately 2.6%. As they occur often during pituitary surgery, CSF leaks alone are generally not considered a true surgical emergency unless associated with symptomatic tension pneumocephalus.