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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is usually treated with corticosteroids, given their anti-inflammatory effects. Unlike the nasal administration, the oral and ocular use of tretinoin, an immunoregulatory drug, is well established. Therefore, tretinoin was thought to act on nasal polyps, and possible adverse and/or therapeutic effects were investigated., Methods: A first-in-human open-label trial was conducted enrolling patients with CRSwNP randomized into: a control group (CTR, n = 15), treated with budesonide for 24 weeks; and an intervention group (TRT, n = 15), who received budesonide and 0.1% tretinoin in the last 12 weeks. Primary endpoint included histopathological analysis and tissue immunoassay (Multiplex) for tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-4, IL-5, IL-13, and matrix metalloproteinase 9 (MMP-9) at 12 and 24 weeks. Secondary endpoints were: adverse events report, endoscopy (modified Lund-Kennedy scoring system [LKS]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), and olfactory test (Connecticut Chemosensory Clinical Research Center) at baseline, at 12 weeks, and at 24 weeks, in addition to serum biochemistry and tomographic findings (Lund-Mackay computed tomography [CT] staging system [LMS]) at baseline and 24 weeks., Results: TRT showed less microscopic edema (2/13 [15.4%] vs 8/13 [61.5%]; p = 0.044) as well as no increase in cytokines levels. All adverse events were categorized as "grade 1" (asymptomatic; mild). The most interesting part of this study was the improvement in smell between baseline (T0) and week 24 (T2) in TRT only (p = 0.041)., Conclusion: Transnasal tretinoin associated with budesonide was safe and well tolerated, and it should be investigated as a treatment option for some CRSwNP endotypes. ©2021 ARSAAOA, LLC., (© 2021 ARS-AAOA, LLC.)

Background: Chronic Rhinosinusitis is currently classified into eosinophilic and non-eosinophilic, according to the histologic quantification of the number of eosinophils in nasal mucosa biopsy. There is a lack of unanimous histopathologic criteria and methodology for this classification and no consensus regarding a cut-off point for Eosinophils per High power field., Methodology: A systematic electronic search was performed on BVS, PUBMED, PUBMED PMC, SCOPUS, WEB OF SCIENCE, EMBASE, COCHRANE and PROQUEST databases looking for studies that reported a cut point for classification of Eosinophilic Chronic Rhinosinusitis (eCRS), and data concerning methodology of classification was extracted., Results: We identified 142 studies that reported 29 different cut-off values for classification of eCRS, and different methods of histologic analysis. Out of these studies 13 reported their own methodology to establish the cut-off point, and used different reference standards as polyp recurrence, asthma and allergy, immunocytochemistry, quality of life index, standard deviation of the control population and cluster analysis., Conclusions: Further studies are needed to determine a precise cut-off point, especially international multicentered cluster analysis. Moreover, methodologic standardization of biopsy and analysis is needed to certify comparable results. Multiple biopsy sites, densest cellular infiltration area examination and oral steroids restriction at least four weeks before sampling are advisable.