International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis

Background: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). Methods: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. Results: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. Conclusion: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding

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

Disparities in access to health care: A survey-based, pilot investigation of sinonasal complaints in the community care setting

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175776/1/alr23055.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175776/2/alr23055_am.pd

Development of a Clinically Relevant Endoscopic Grading System for Chronic Rhinosinusitis Using Canonical Correlation Analysis

Background Diagnostic nasal endoscopy is a routine measure of sinonasal inflammation in patients with chronic rhinosinusitis (CRS). Although multiple staging systems have been proposed and evaluated, evidence of association between concurrent symptoms and endoscopic findings remains discordant. The goal of this study is to identify the relevant endoscopic attributes associated with symptom burden, and to systematically derive a weighted endoscopic scale that optimizes prediction of concurrent symptoms. Methods Reported baseline symptom (22-item Sino-Nasal Outcome Test [SNOT-22]) and endoscopic evaluation scores (Lund-Kennedy [LK]) were obtained from patients with CRS enrolled in a prospective cohort study. Canonical correlation analysis of the SNOT-22 subdomains and LK variables was completed. Results A total of 629 patients were included in analysis including 343 with prior endoscopic sinus surgery. Significant canonical correlations outperformed aggregate correlations in explaining variance of the data (33% vs 3%, respectively). The first canonical correlation was dominated by the rhinologic symptom domain and the endoscopic polyp score (r = 0.54; p \u3c 0.05) whereas additional significant canonical correlation was found between the extra-rhinologic symptom subdomain and the edema score in patients without prior ESS (r = 0.21; p \u3c 0.05), and discharge in patients with prior ESS (r = 0.22; p \u3c 0.05). All other domains and endoscopic variables did not significantly contribute to the canonical correlation. Conclusion Although aggregate symptoms and endoscopic scores demonstrate minimal correlation, a weighted combination of symptom domains and endoscopic attributes greatly improves this correlation. A simple approximation of the weights of each of the endoscopic variables of polyps, edema, discharge, scarring, and crusting, is an approximate ratio of 4:2:1:0:0, respectively

Defining the Minimal Clinically Important Difference for Olfactory Outcomes in the Surgical Treatment of Chronic Rhinosinusitis

Background Olfactory dysfunction is a common and defining symptom of chronic rhinosinusitis (CRS). Many measures of olfactory dysfunction in CRS are limited by scoring criteria defined within general populations with interpretations of statistical significance to infer clinically meaningful improvement. In this investigation we define a minimal clinically important difference (MCID) for the Brief Smell Identification Test (BSIT) in CRS patients electing endoscopic sinus surgery (ESS). Methods: A multicenter cohort of 290 adult patients electing ESS for medically recalcitrant CRS were prospectively enrolled between March 2011 and June 2015 and completed BSIT evaluations before and after ESS. Distribution and anchor-based analytic approaches were utilized to define MCID values of the BSIT across patient cofactors. Results: A total of 92 (∽32%) patients were found to have preoperative olfactory dysfunction (BSIT \u3c 9), significantly associated with nasal polyposis (χ(2) = 35.0; p \u3c 0.001). The effect-size distribution-based approach identified 1.0 as a MCID criterion value between small and medium effect (range, 0.61-1.52) overall. Significant mean postoperative change (ΔM) was reported for patients with olfactory dysfunction (ΔM = 2.28; p \u3c 0.001), both with (n = 54; ΔM = 2.52; p \u3c 0.001) and without (n = 38; ΔM = 1.95; p \u3c 0.001) nasal polyposis, significantly exceeding the MCID criterion. Anchor-based approaches with regression modeling confirmed associations between MCID values and postoperative changes to olfactory-specific survey responses (p \u3c 0.001). Conclusion: Clinically meaningful change in BSIT scores may be defined as an absolute value difference of at least 1.0 unit for heterogeneous patients electing ESS for CRS. Significantly exceeding this criterion may be restricted to CRS patients with baseline olfactory dysfunction, regardless of nasal polyposis. PMID: 28556611 [PubMed - as supplied by publisher

Diagnosis of cerebrospinal fluid rhinorrhea : an evidence-based review with recommendations

Background: Diagnostic strategies employed for cases of cerebrospinal fluid (CSF) rhinorrhea vary widely due to limited evidence-based guidance. Methods: A systematic review of the literature was performed using PubMed, EMBASE, and Cochrane databases from January 1990 through September 2014, to examine 9 diagnostic and localization modalities for CSF rhinorrhea. Benefit-harm assessments, value judgments and recommendations were made based on the available evidence. Study exclusion criteria were language other than English, pre-1990 studies, case reports, and nonrhinologic leak. All authors agreed on recommendations through an iterative process. Results: We reviewed 68 studies examining 9 practices pertinent to the diagnosis of CSF rhinorrhea, with a highest aggregate grade of evidence of C. The literature does not support the use of the ring sign, glucose testing, radionuclide cisternography (RNC), or computed tomography cisternography (CTC) for identification of CSF leak. Beta-2 transferrin is the most reliable confirmatory test for CSF leak. High-resolution CT (HRCT) is then recommended as the first-line study for localization. Magnetic resonance cisternography (MRC) should be used for CSF leak identification as a second line for each of these if beta-2 transferrin is not available or if HRCT is ambiguous. Intrathecal fluorescein (IF) may also be of benefit in certain clinical scenarios. Conclusion: Despite relatively low levels of evidence, recommendations for the diagnosis and management of CSF rhinorrhea can be made based on the current literature. Higher-level studies are needed to better determine optimal diagnostic and clinical management approaches.9 page(s

Locally Destructive Skull Base Lesion: IgG4-related Sclerosing Disease

A unique case of IgG4 + sclerosing disease was diagnosed in the sphenoid sinus, a previously unreported location, and was treated in a novel manner. This study describes the clinical presentation and management of IgG4 sclerosing disease in the paranasal sinuses. A retrospective case review and review of the medical literature were performed. A 38-year-old woman with a 2-year history of constant frontal headaches presented to our clinic. Imaging showed bony destruction of the sphenoid sinus and sellar floor. The patient underwent a right-sided sphenoidotomy with debridement and biopsy. Pathological evaluation showed a dense plasmacytic infiltrate with >150 IgG4 + cells/high-power field. She was subsequently started on a nasal corticosteroid with improved patency of the sphenoid antrostomy. We report an unusual case of a middle-aged woman who presented with IgG4-sclerosing disease (IGSD) isolated to the sphenoid sinus. Although our knowledge concerning treatment in extrapancreatic organs is lacking, there is evidence that glucocorticoid treatment improves nasal sinus opacification on CT findings (Sato Y, Ohshima K, Ichimura K, et al., Ocular adnexal IgG4-related disease has uniform clinicopathology, Pathol Int 58:465–470, 2008). This case study and literature review adds to the growing literature describing IGSD in the head and neck and more specifically isolated to the sphenoid sinus with preliminary data concerning local control with topical steroids

In cells committed to terminal cell death, caspase-1 and -8 activity is increased with LL-37 treatment and reduced with GM-0111.

<p><b>A</b>. The percentage of total HNEpCs and J774.2 cells with active caspase-1 and 7-AAD (late cell death marker) is significantly increased with LL-37 treatment, and this is dose-dependently reversed with GM-0111 treatment. <b>B</b>. The percentage of total HNEpCs and J774.2 cells with active caspase-8 and 7-AAD is significantly increased with LL-37 treatment and dose-dependently decreased with GM-0111. ****P ≤ 0.0001, *P ≤ 0.05, ns (not significant) P > 0.05. The data represent the means ± SD (n = 2–5). Note the differences in y-axis scale (panel B y-axis maximum only 1.5%), adjusted to allow visual resolution but heights of bars are not comparable between panels. <b>C</b>. There is a statistically significant though minimal (<1%) increase in caspase-3 or -7 activity in HNEpCs also positive for 7-AAD after LL-37 treatment, and the effect is reversed with GM-0111. There is no significant change in caspase-3 or -7 activity with LL-37 or GM-0111 in J774.2 cells.</p

Patient‐centered decision making: the role of the baseline SNOT‐22 in predicting outcomes for medical management of chronic rhinosinusitis

BackgroundFor patients with chronic rhinosinusitis (CRS), the decision to elect continued medical management vs surgery is complex and involves tradeoffs between benefits, risks, and overall effectiveness of each therapy. The purpose of this study is to investigate whether baseline disease-specific quality of life (QOL) can assist in predicting outcomes in patients with refractory CRS who elect continued medical management.MethodsCRS patients electing medical management were enrolled in a prospective, multi-institutional cohort study. Patients were stratified into pretreatment 22-item Sino-Nasal Outcome Test (SNOT-22) subgroups based on 10-point score increments (eg, 10 to 19, 20 to 29, 30 to 39, etc.) to capture potential outcome differences by baseline SNOT-22 disease burden. The proportion of patients achieving minimal clinically important difference (MCID≥9 points) and relative improvement (%) for each score category were calculated.ResultsSeventy-five CRS patients with a mean ± standard deviation pretreatment SNOT-22 score of 45.2 ± 16.6 were followed for a mean of 14.9 months. The majority of participants electing medical therapy failed to improve 1 MCID (57%) with a mean relative score improvement of 16%. Overall, 37% of patients maintained baseline SNOT-22 QOL status, whereas 20% of patients deteriorated &gt;1 MCID. When treatment crossover patients (to endoscopic sinus surgery [ESS]) were included (n = 117), approximately 1 in 4 (27%) patients achieved an MCID.ConclusionResults from this study suggest that the majority of CRS patients electing ongoing medical management with low baseline disease-specific QOL impairment maintain stable QOL with continued medical management. Furthermore, of CRS patients electing ongoing medical therapy, approximately 1 in 4 patients achieved MCID, whereas 1 in 5 experienced deterioration by &gt;1 MCID

Diagram of the proposed mechanism of LL-37-induced cell death and protection from GM-0111.

<p>Nasal epithelial cells subjected to LL-37 demonstrate a pro-inflammatory response, characterized by increased ATP, IL-6, and -8 production and pyroptosis and/or necrosis via caspase-1 and -8 but not caspase-3 or -7 activation. These changes are prevented by GM-0111 treatment. IL-6 and -8 promote an inflammatory response <i>in vivo</i> through the recruitment of neutrophils and further inflammatory signaling in a positive feedback loop. The process of pro-inflammatory cell death is propagated to nearby cells due to these changes in the local environment, resulting in an unchecked cytotoxic response initiated by LL-37.</p