Background:The body of knowledge regarding rhinosinusitis (RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods:Evidence-based reviews with recommendations (EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR) was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results:The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS) with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AE-CRS), and pediatric RS. Conclusion:As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too o en the foundation upon which these recommendations are based is comprised of lowerlevel evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed. C 2016 ARS-AAOA, LLC. Key Words:rhinosinusitis; chronic rhinosinusitis; acute rhinosinusitis; recurrent acute rhinosinusitis; evidence-based medicine; systematic review; endoscopic sinus surgery List of Abbreviations Used

I. Executive Summary Background The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS.

Rationale: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. Objectives: The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. Methods: Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. Chronic rhinosinusitis (CRS) is a chronic inflammatory process of the nasal and paranasal sinus mucosa affecting more than 30 million people annually, resulting in significant direct healthcare costs (1). CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively (2, 3), although the cellular and molecular mechanisms driving the Th2-mediated inflammation in CRSwNP are not clearly understood (4, 5). Due largely to a lack of understanding of the pathophysiology of CRS, current treatment options, including high-dose glucocorticosteroids and surgeries, remain noncurative, generic, and largely unchanged over the past decade.IL-33, a member of the IL-1 family of cytokines, is expressed by epithelial cells, endothelial cells, fibroblasts, smooth muscle cells, macrophages, and dendritic cells (6-8). The IL-33 receptor, a heterodimeric complex composed of ST2 and IL-1 receptor accessory protein (IL1RAP), is expressed on numerous immune cells, including Th2 cells, mast cells, basophils, eosinophils, and macrophages (7-9). IL-33 is a chemoattractant for Th2 cells (10) and promotes Th2 polarization of naive CD4 1 T cells, enhancing production of IL-5 and IL-13 independent of IL-4 (11). IL-33 can also induce proinflammatory cytokine and chemokine production by mast cells and enhance degranulation (12), stimulate basophils and eosinophils (13), and enhance IL-13-driven polarization of alternatively activated macrophages (14). More recently, an important role for IL-33 in regulating the development and function of type 2 innate lymphoid cells (ILC) was described (15, 16). The epithelial cell-derived cytokine IL-33 is known to play a key role in the development and regulation of a Th2 immune response, mediated in part by an IL-33-responsive innate lymphoid cell population. However, there is little direct evidence of an important role for these cells in Th2-mediated inflammatory disease in humans. What This Study Adds to the FieldHere we show that the percentage of innate lymphoid cells is significantly elevated in diseased mucosa in chronic rhinosinusitis w...

This study describes frontal pneumatization in patients without a history of conditions that influence frontal pneumatization. The results characterize normal frontal recess/sinus pneumatization patterns.

In this preliminary study, MIER of ASB neoplasia did not differ significantly from tCFR in operative time, estimated blood loss, hospital stay, or complication rate. Survival and recurrence rates were similar also. This early experience suggests that MIER is a viable alternative for the surgical management of ASB lesions in appropriately selected patients.