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

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). This executive summary consolidates the findings of the ICAR:RS document.Methods: ICAR:RS presents over 140 topics in the forms of evidence-based reviews with recommendations (EBRRs) and evidence-based reviews (EBR). The structured recommendations of the EBRR sections are summarized in this executive summary.Results: This summary compiles the EBRRs regarding medical and surgical management of acute RS (ARS) and chronic RS with and without nasal polyps (CRSwNP and CRSsNP). Conclusion:This ICAR:RS Executive Summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS. C 2016 ARS-AAOA, LLC.

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.

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.

The incidence of major complications associated with ESS appears to have decreased since early reports over 10 years ago. There may be different complication rates in the pediatric population. Study design limitations did not allow for comprehensive assessment of IGS in the development of these complications. These data help to educate otolaryngologists and patients about complication rates in ESS in a modern context.

Most patients do not have classic CT findings of bone erosion or extrasinus extension in the early course of IFS. We found that severe unilateral thickening of the nasal cavity mucosa was the most consistent finding on CT suggestive of underlying IFS, occurring much more frequently in immunocompromised patients with IFS than without IFS. Even though severe nasal cavity soft tissue thickening is much more common in IFS, this is a nonspecific finding that can be seen, to a lesser degree, in all forms of rhinosinusitis. Therefore, the clinician cannot rely solely on CT imaging and must maintain a high index of suspicion when evaluating immunocompromised patients to establish a prompt diagnosis. Early nasal endoscopy with biopsy and initiation of appropriate therapy are necessary to improve prognosis.

In sinus or nasal surgery, topical vasoconstrictors should be used in a manner that minimizes the risk of cardiovascular morbidity.

Background Solitary chemosensory cells (SCCs) are specialized cells in the respiratory epithelium that respond to noxious chemicals including bacterial signaling molecules. SCCs express components of bitter taste transduction including the TAS2R bitter taste receptors and downstream signaling effectors: α-Gustducin, PLCβ2, and TRPM5. When activated, SCCs evoke neurogenic reflexes, resulting in local inflammation. The purpose of this study was to test for the presence SCCs in human sinonasal epithelium, and to test for a correlation with inflammatory disease processes such as allergic rhinitis and chronic rhinosinusitis. Methods Patient demographics and biopsies of human sinonasal mucosa were obtained from control patients (n=7) and those with allergic rhinitis and/or chronic rhinosinusitis (n=15). RT-PCR, qPCR and immunohistochemistry were used to determine whether expression of signaling effectors was altered in diseased patients. Results RT-PCR demonstrated that bitter taste receptors TAS2R4, TAS2R14 and TAS2R46 and downstream signaling effectors α-Gustducin, PLCβ2, and TRPM5 are expressed in the inferior turbinate, middle turbinate, septum and uncinate of both control and diseased patients. PLCβ2/TRPM5-immunoreactive SCCs were identified in the sinonasal mucosa of both control and diseased patients. qPCR showed similar expression of α-Gustducin and TRPM5 in the uncinate process of control and diseased groups, and there was no correlation between level of expression and SNOT-22 or pain scores. Conclusion SCCs are present in human sinonasal mucosa in functionally relevant areas. Expression level of signaling effectors was similar in control and diseased patients and did not correlate with measures of pain and inflammation. Further study into these pathways may provide insight into nasal inflammatory diseases and may offer potential therapeutic targets.