xRead - Nasal Obstruction (September 2024) Full Articles

20426984, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.22741 by Stanford University, Wiley Online Library on [01/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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International consensus statement on rhinosinusitis

approaches 56 validate the treatable trait concept in CRS. However, the disease phenotype appears to recur after withdrawal of agents targeting the inflammatory cytokine cascade suggesting these traits are secondary to the incit ing event or events. The application of poly-omic and bioinformatic approaches to patients with CRS 2447–2450 has revealed a host of potential upstream novel targets whose role in disease development remains unknown. Further more, these targets may exist within previously unrecog nized populations of epithelial progenitor cells. 2451 The mechanistic investigation of these targets and identifica tion of potential etiopathological treatable traits remains a significant research opportunity. ICAR-RS provides evidence for the primary pharmacologic management of RS within multiple disease subtypes as well as in the pre- and post-operative period. Indeed, some of the highest quality grade data within the entire docu ment exist around the effective use of INCS for the treat ment of adult ARS, pediatric ARS, CRSsNP, and CRSwNP. These results are generally consistent with the promise of topical treatments for sinonasal disease in the context of providing high local concentrations directly to the end tar get organ while avoiding systemic exposure and off-target toxicity. In contradistinction, the data for topical antibi otic use consistently fail to demonstrate clear benefit. This finding appears paradoxical, particularly in light of grade A evidence for the benefit of systemic antibiotics. There are likely multiple factors contributing to this result how ever, 1 generalizable concept is that the majority of off-label agents have not been specifically studied or formulated for a topical sinonasal application. As such local mucosal fac tors including mucosal residence time, proteolytic degra dation, mucus penetration, cellular uptake and metabo lization may play unforeseen roles in limiting clinical effi cacy. Consequently, continued research into systems to both model local sinonasal drug delivery and develop for mulations and/or carriers specifically designed to optimize topical delivery represent a significant need. The risks and benefits of pharmacologic management of CRS, particularly within the context of antibiotic adminis tration, are germane to the concept of “appropriate (max imal) medical therapy” or AMT. It has become increas ingly clear that inappropriate systemic antibiotic use is associated with significant risks including allergic reac tion, resistance, and microbiome disruption. 2452 Further more, nascent evidence has emerged that a delay in surgical therapy may, in some cases, result in reduced QoL, increased absenteeism, 2453 and reduced surgical XV.C Pharmacologic Management and the Topical Paradox

benefit. 1917 As described in ICAR-RS, there remains a sig nificant gap in the literature regarding how to define the composition, length, and response rate to AMT. As the con cept of AMT continues to be widely employed as a relative prerequisite for interventional strategies with their own pros and cons, it is incumbent upon the field to continue to develop high grade evidence-based algorithms to help guide the application of AMT. XV.D Interventional Strategies in Upper Airway Disease The general growth of rhinology as an interventional field has ushered in an array of technical innovations in devices and implants aimed toward improving patient outcomes with less invasive techniques. Examples of these include balloon dilation, cryoablation, and biodegradable steroid eluting implants. These technologies each offer an oppor tunity to provide enhanced care to patients provided they are used in an evidence-based manner. While the poten tial benefits are apparent, these must further be weighed against risk, effect size, and alternatives. This information is best attained through well-designed, sham-controlled studies, using validated patient reported outcome mea sures and clinically relevant objective endpoints. Even in the context of established efficacy, new pharmacolog ical and interventional strategies require further scrutiny using shared decision modeling, cost-effectiveness, cost minimization, and cost-benefit analyses to establish both relative value and where they should fit into overall treat ment algorithms. The application of rigorous trial designs addressing each of these variables, therefore, remains an important research opportunity for both existing and future interventional technologies. XV.E Next Generation Research Tools Rhinology is a unique field in which complex inflamma tory pathways involving multiple cell and tissue types exert their effects in an area easily amenable to epithelial and mucus sampling as well as direct application of therapeu tics. In many ways these features have facilitated signif icant research progress despite the conspicuous paucity of animal models and disease specific immortalized cell lines. Consequently, the rhinology research endeavor is well positioned to take advantage of many of the aston ishing recent advances in biomedical research tools. These include CRISPR-Cas9, single cell RNA sequencing, 3D printing, artificial intelligence/machine learning, pharma cogenomics, and many others. The upper airway also pro vides for the ability to model other immunologic and