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ObjectivesTo address concerns related to the safety profile of both Food and Drug Administration (FDA)–approved and non–FDA‐approved intranasal corticosteroid (INCS) use in the adult population.Data SourceSystematic review of MEDLINE, PubMed, and EMBASE databases using a comprehensive search strategy including all INCS formulations and adverse events. The study design was developed using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Additional sources were identified from study references of relevant articles.Review MethodsA structured literature search was conducted. Each study was graded for level of evidence using the Oxford Centre for Evidence‐Based Medicine. Extracted data included population size, study design, drug (dosage, route, and frequency), presence of hypothalamus pituitary axis suppression, ocular symptoms, and treatment‐related adverse events.ResultsA total of 60 studies met inclusion criteria. The studies included use of INCS as metered nasal sprays, drops, injections, aerosols, and irrigations. There were no persistent abnormalities in cortisol level or intraocular pressure change. Meta‐analysis of epistaxis showed a significantly increased risk in the FDA‐approved treatment group in comparison with control (risk ratio 1.56; 95% confidence interval, 1.13‐2.14; P =. 007).ConclusionsOverall, it appears that the use of both FDA and published non‐FDA application of INCS are safe in the adult population. Meta‐analysis demonstrated an increased risk of epistaxis in patients using INCS compared with placebo. Otherwise, there was no significant difference between in adults in the treatment group and placebo group. As an important caveat, the interpretation of safety of nonstandard INCS is restricted to delivery methods and dosages published in the literature.

As rhinologists return to practice amid SARS‐CoV‐2, special considerations are warranted given the unique features of their subspecialty. Rhinologist manipulation of nasal tissue, proximity, and frequent aerosol‐generating procedures (AGPs) create high risk for infection transmission. There are 4 areas of special consideration to mitigate risk: (1) previsit planning for risk stratification/mitigation, (2) appropriate personal protective equipment, (3) preprocedural testing, and (4) environmental controls. During previsit planning, risk factors of the patient and procedures are considered. High‐risk AGPs are identified by duration, proximity, manipulation of high–viral load tissue, and use of powered instrumentation. Appropriate personal protective equipment includes selection of respiratory and eye protection. COVID‐19 testing can screen for asymptomatic carriers prior to high‐risk procedures; however, alternative testing methods are required in rhinologic patients not eligible for nasopharyngeal testing due to nasal obstruction or skull base defects. Last, AGPs in rhinologic practices require considerations of room air handling and environmental controls.

BackgroundSubtyping chronic rhinosinusitis (CRS) by tissue eosinophilia has prognostic and therapeutic implications, and is difficult to predict using peripheral eosinophil counts or polyp status alone. The objective of this study was to test machine learning for prediction of eosinophilic CRS (eCRS).MethodsInput variables were defined as peripheral eosinophil count, urinary leukotriene E4 (uLTE4) level, and polyp status. The output was diagnosis of eCRS, defined as tissue eosinophil count >10 per high‐power field. Patients undergoing surgery for CRS were retrospectively reviewed for complete datasets. Univariate analysis was performed for each input as a predictor of eCRS. Logistic regression and artificial neural network (ANN) machine learning models were developed using random and surgeon‐specific training/test datasets.ResultsA total of 80 patients met inclusion criteria. In univariate analysis, area under the receiver operator characteristic curve (AUC) for peripheral eosinophil count and uLTE4 were 0.738 (95% confidence interval [CI], 0.616 to 0.840) and 0.728 (95% CI, 0.605 to 0.822), respectively. Presence of polyps was 94.1% sensitive, but 51.7% specific. Logistic regression models using random and surgeon specific datasets resulted in AUC of 0.882 (95% CI, 0.665 to 0.970) and 0.945 (95% CI, 0.755 to 0.995), respectively. ANN models resulted in AUC of 0.918 (95% CI, 0.756 to 0.975) and 0.956 (95% CI, 0.828 to 0.999) using random and surgeon‐specific datasets, respectively. Model comparison of logistic regression and ANN was not statistically different. All machine learning models had AUC greater than univariate analyses (all p < 0.003).ConclusionMachine learning of 3 clinical inputs has the potential to predict eCRS with high sensitivity and specificity in this patient population. Prospective investigation using larger and more diverse populations is warranted.

AbstractObjectiveTo determine whether the complaint of cough in chronic rhinosinusitis (CRS) patients is associated with asthma and if there is a potential predictive value for asthma diagnosis.MethodConsecutive patients presenting for initial evaluation at a tertiary rhinology clinic who were diagnosed with CRS were considered for inclusion in a cross‐sectional study. The presence and severity of cough was determined using the 22‐item Sinonasal Outcome Test (SNOT‐22). Subgroup analysis included asthma diagnosis confirmed by pulmonary function testing (PFT) in our institution, and for chronic rhinosinusitis patients with (CRSwNP) and without nasal polyps (CRSsNP).ResultsThe total study population included 297 patients with a diagnosis of CRS, with 63.9% of patients reporting cough. Physician‐confirmed diagnosis of asthma was made in 38.7% of patients, and confirmed in 69.6% by PFT. Cough was more frequently reported by CRS patients diagnosed with asthma (relative risk [RR] = 1.60, 95% confidence interval [CI], 1.13‐2.25), with sensitivity of 73.9% (95% CI, 65.0%‐81.1%). This remained significant in the CRSsNP subgroup (RR = 2.65, 95% CI, 1.32‐5.30), with sensitivity of 83.3% (95% CI, 70.4%‐91.3%) and specificity of 41.2% (95% CI, 33.2%‐49.8%). Cough was not associated with asthma in CRSwNP patients (RR = 1.26, 95% CI, 0.89‐1.79). Cough severity had poor predication for asthma diagnosis (AUC = 0.60, 95% CI, 0.54‐0.65).ConclusionsComplaint of cough is associated with diagnosis of asthma in CRS patients. In CRSsNP, complaint of cough was sensitive for asthma diagnosis, although specificity was low. Cough in CRS patients can be multifactorial and asthma may be an important diagnostic consideration.Level of evidence4.

AbstractObjectiveThe histopathological characteristics of primary vs recurrent nasal polyps in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have not been studied comprehensively. Identification of these features may be helpful for prognostication, postoperative management, and consideration of novel eosinophil‐targeting biologic therapy. This study investigates the histopathological differences in primary vs recurrent CRSwNP tissue.MethodsPatients undergoing endoscopic sinus surgery for CRSwNP were included if all 13 histopathological and mucin characteristics on a standardized report were available. Histopathology parameters were compared in surgical tissue and mucin from primary vs recurrent CRSwNP.ResultsComplete structured histopathology reports were available for 96 patients (39 primary polyps and 57 recurrent polyps). Compared to primary polyp tissue, recurrent CRSwNP mucin was significantly more likely to feature eosinophil aggregates (57.9% vs 35.9%; P = .047). Tissue eosinophilia (using a threshold >10 per high power field [HPF]) was not significantly different in primary and recurrent CRSwNP tissue. Other histopathologic parameters and clinical characteristics were similar.ConclusionEosinophil aggregates on histopathology are significantly more likely to be present in recurrent CRSwNP. In the limited series, tissue eosinophilia (>10 per HPF) was not significantly different in primary and recurrent CRSwNP. Therefore, in addition to the study of tissue eosinophilia levels, Rhinologic surgeons should also direct attention to CRSwNP mucin. Mucin eosinophilic aggregates are an independent marker of severe inflammation that is associated more likely with recurrent vs primary polyposis. Further study of this marker may help determine its role of choice of postoperative medical therapies, including anti‐eosinophilic biologics.Level of Evidence4

AbstractObjectivesThere is interest in identifying chronic rhinosinusitis (CRS) endotypes that align pathophysiology with clinical observation and outcomes. CRS with polyps (CRSwNP) has classically been studied with reference to tissue eosinophilia, but the role of other cellular infiltrates remains uncharacterized. No particular tissue prognosticators have been described for CRS without nasal polyps (CRSsNP). Predominance of leukocytes seen in surgical tissue may be useful for differentiating CRS subtypes, severity of inflammation, and outcomes.MethodsStructured histopathology reports were examined for 277 patients undergoing endoscopic sinus surgery for CRSwNP (n = 115), CRSsNP (n = 141), and recurrent acute rhinosinusitis (RARS, n = 21). Inflammatory predominance was examined for associations with nasal polyposis, asthma, allergic rhinitis, aspirin exacerbated respiratory disease (AERD), immune deficiency, preoperative Lund‐Mackay score, and outcome (SNOT‐22 score change).ResultsIn order of frequency, the prevalence of predominant inflammatory patterns accounting for 93.5% of CRS patients were: lymphoplasmocytic (n = 111), lymphocytic (n = 74), eosinophilic (n = 50), and lymphoplasmocytic with eosinophilic (n = 24). Eosinophilic predominance was 97.4% specific for nasal polyps (95% confidence interval [CI], 93.4%‐99.3%), although sensitivity was 43.4% (95% CI, 33.8%‐53.4%). The absence of eosinophilic predominance was 100% sensitive for RARS (95% CI, 82.4%‐100%), however specificity was 30.8% (95% CI 25.1%‐37.1%). There were no significant differences in preoperative SNOT‐22 scores or change postoperatively.ConclusionsEosinophilic inflammatory predominance was predictive for nasal polyps and against RARS. Nevertheless, the majority of CRSwNP patients had a different inflammatory predominance, demonstrating heterogeneity in CRS, even among patients with nasal polyps. Symptomatic outcomes were not associated with inflammatory predominance through 12 months follow up.Level of Evidence4.