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Orlandi et al.

TABLE I-9 Knowledge gaps in RS Category

Research Need

Diagnosis of CRS Treatable Traits

Validation of biosignatures of discreet CRS endotypes

Discovery of biomarkers that directly respond to targeted therapeutics and may predict efficacy Development of formulations specifically designed to optimize mucosal distribution, stability, and absorption Define composition, duration, and response rate to AMT, through well controlled clinical trials Execution of sham-controlled studies using validated PROMS, clinically relevant objective endpoints, cost-benefit analyses SARS-CoV-2 anosmia pathogenesis, rhinologic aerosol generating procedure risk, and how to deliver elective rhinologic care during pandemic conditions.

Topical Therapeutics

Appropriate Medical Therapy

Interventional Strategies

COVID-19

the implications of these findings on viral transmissibil ity, replicativity, and their designation as “aerosol generat ing procedures (AGPs)” remain controversial. 122–127 Both high-speed drill and bipolar electrocautery are consid ered aerosol-generating devices, and are often required in extended surgical approaches for recalcitrant CRS. 123,128 The use of constant suctioning during these procedures may help mitigate particle transmission. 122,125 Notably the microdebrider, with its in-line suction, does not appear to be a significant aerosol producer. 123,128 Other aerosol generating in-office devices include bipolar RF ablation (coblation) and cryotherapy, both used for treatment of rhinitis. 128 The infectious transmission risk of diagnos tic nasal endoscopy remains another area of active inves tigation. Both flexible and rigid nasal endoscopy have been shown to produce airborne aerosols, 127,129 require unmasking, can induce cough/sneeze, and occur within an enclosed space in close proximity to the patient. These features have all been shown to be associated with infectious transmission in community based epi demiologic studies. 130–134 Consequently, comprehensive pre-visit patient screening, environmental safety, and full PPE utilization are recommended as appropriate precautions. 129 I.C.7 Knowledge Gaps The breadth and quality of research into virtually all aspects of RS has advanced considerably in the past decade. The sheer scope of the ICAR-RS document is, itself,

evidence of such progress. However, multiple knowledge gaps remain, particularly within the realm of develop ing better diagnostic and targeted therapeutic strategies to advance personalized treatment of RS (Table I-9). I.D Discussion This executive summary reviews many of the important new topics added to the ICAR-RS document since its first publication in 2016. Furthermore, it highlights the areas in which new evidence has been added to the existing topics, in some cases changing the overall evidence grade. Despite these advances, the knowledge gap section emphasizes the continued need to incorporate next generation research tools in order to gain deeper insights into RS etiopatho genesis and to identify treatable traits against which novel therapies may continue to be developed. While the ICAR-RS-2021 general topic outline with its associated diagnostic and management recommendations largely followed a similar structure to the original ICAR RS document, it is within reason to envision a future con sensus statement which utilizes biosignatures to dissect out RS according to endotype while providing personal ized therapeutic recommendations based on grade A clin ical trial data. The laudable progress we have made since 2016 suggests this future is closer than it may appear. How ever, it is only through the continued aspiration toward and adherence to the type of evidence-based recommendations described in ICAR-RS-2021 that we may collectively make this future a reality.