BACKGROUND:Optimizing access to cost-effective care in capacity-constrained health systems is a contemporary imperative. We evaluated whether machine learning (ML) models using patient-reported data could optimize access for patients requiring surgical care in rhinology clinics, without need for CT imaging. The outcome was defined as any rhinologic surgery within 90 days of initial evaluation. METHODS:A de-identified electronic dataset from patients seen at five distinct sites within an integrated healthcare system between 2018 and 2025 was used to train models. Demographic data and 22-item Sinonasal Outcome Test (SNOT-22) responses were studied. Models were trained using stratified 5-fold cross-validation with an 80% development cohort and validated in a 20% held-out validation cohort. Hyperparameters were optimized with Optuna. The primary outcome was performance of any rhinologic surgical intervention within 90 days of initial SNOT-22. RESULTS:Data from 35,170 patients were evaluated. Item-level responses outperformed use of total SNOT-22 score in the models. Among models, XGBoost demonstrated best discrimination with AUC of 0.70 (95% CI, 0.69-0.71), outperforming logistic regression (0.66), random forest (0.63), and TabNet (0.66) (all p < 0.001). At optimal threshold, XGBoost achieved 66% sensitivity, 64% specificity, 28% PPV, and 90% NPV. Top predictors for surgery were age, nasal blockage, facial pain or pressure, and decreased sense of smell or taste. Validation on the held-out cohort remained stable (AUC 0.70), with strong discrimination across sites despite surgical rates ranging from 11.5% to 27.4%. CONCLUSIONS:Demographics and item-level SNOT-22 responses were successful in developing an ML model that demonstrated moderate discrimination and high NPV (90%) for performance of surgery within next 90 days. ML models balanced with human oversight may accelerate triage and optimize surgical yield for rhinology clinics.
BACKGROUND:Biologics and endoscopic sinus surgery (ESS) treat refractory chronic rhinosinusitis with nasal polyposis (CRSwNP), but direct comparisons are lacking. We synthesized efficacy and subgroup data across randomized controlled trials (RCTs) of biologics and ESS. METHODS:PubMed was searched through December 2025 for RCTs and subgroup analyses of biologics or ESS for adult CRSwNP. Included were ten Phase-3 placebo-controlled biologic RCTs, two pragmatic ESS trials, and one head-to-head biologic trial. 22-Item Sino-Nasal Outcome Test (SNOT-22) and nasal polyp score (NPS) effect sizes and subgroup interactions were extracted. RESULTS:A total of 13 trials (n = 3775) from 21 publications were included. By indirect comparison, tezepelumab and dupilumab produced the largest improvements (tezepelumab: SNOT-22: -27.4; NPS: -2.1; dupilumab: SNOT-22: -17 to -21; NPS: -1.7 to -2.1), while mepolizumab and omalizumab showed intermediate effects (SNOT-22: -10.6 to -16.5); benralizumab improved NPS but not SNOT-22, and depemokimab showed improvement below clinically discernible differences. ESS effects varied by trial and follow-up (SNOT-22: -21.9 at 6 months in MACRO vs. -4.9 at 12 months in PolypESS). Predictors of improvement differed across therapies (blood eosinophil count, NSAID-exacerbated respiratory disease, and prior ESS for dupilumab; asthma for benralizumab; baseline severity for ESS), while tezepelumab and omalizumab showed consistent efficacy without effect modification. CONCLUSIONS:ESS and biologics provide clinically meaningful benefit. Among biologics, dupilumab and tezepelumab demonstrated the largest effect sizes, though cross-trial differences in baseline severity, follow-up, and comparators limit indirect comparisons. Head-to-head trials and standardized subgroup analyses are needed to guide treatment selection.
BACKGROUND:Refractory chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS) has traditionally been defined by revision surgery alone. With the emergence of biologic therapies, treatment escalation now includes revision surgery and/or biologic initiation. We sought to identify independent predictors of refractory primary CRS using a composite outcome incorporating surgery and/or biologic initiation. METHODS:Adult patients with primary CRS undergoing FESS after 2015 were identified in the TriNetX Research Network. Patients with secondary CRS, prior biologic therapy, or sinonasal neoplasms were excluded. The primary outcome was refractory CRS, defined as revision FESS or biologic initiation from 3 months to 5 years postoperatively. Preoperative covariates were evaluated using Cox proportional hazards modeling with stepwise selection. RESULTS:Among 24,759 patients, 2866 (11.6%) had refractory CRS after FESS. Of these, 66.6% underwent revision FESS, 42.0% initiated biologic therapy, and 8.7% had revision surgery and initiated a biologic therapy. In multivariable analysis, asthma was the strongest predictor (HR 2.06, p < 0.001), followed by allergy to analgesic agents (e.g., NSAIDs) (HR 1.87, p < 0.001), nasal polyps (HR 1.67, p < 0.001), food allergy (HR 1.37, p = 0.096), COPD (HR 1.27, p = 0.006), eosinophilia (HR 1.27, p < 0.001), and Black or African American race (HR 1.16, p = 0.044). CONCLUSION:Refractory CRS following FESS is strongly associated with type 2 inflammatory comorbidities and select demographic factors. Incorporating biologic therapy into outcome definitions provides a contemporary framework for risk stratification and postoperative counseling.
TriNetX has quickly become one of the most popular research tools in rhinology. At the 2026 American Rhinologic Society spring meeting, more than one in ten abstracts used the platform, no doubt drawn by its huge sample sizes and built-in statistics. However, our concern is that many of these studies suffer from unrecognized biases and potentially misleading results. In this article, we tell the narrative of our experience using TriNetX, highlighting how easy it can be to produce incorrect results. Common biases that often arise with large databases are presented, as well as examples relevant to rhinology. We argue that researchers need to ensure that their team has expertise in subject matter, study design and potential biases, and the platform's logic and limitations.
BACKGROUND:Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by persistent mucosal inflammation and eosinophilic infiltration. Although epithelial and immune cells have been widely studied, the role of nasal fibroblasts in innate immune activation and eosinophil recruitment remains unclear. METHODS:Public single-cell RNA sequencing data from sinonasal tissues were analyzed to define the cellular distribution of TLR3 and inflammatory mediators. TLR3 expression was validated in patient-derived sinonasal tissues. Primary human nasal fibroblasts were stimulated with polyinosinic-polycytidylic acid (Poly(I:C)), and cytokine and chemokine expression was assessed by real-time PCR and ELISA. Signaling pathways were examined using pharmacologic inhibitors and western blotting. Eosinophil migration toward Poly(I:C)-stimulated fibroblasts was evaluated using a microfluidic chemotaxis platform. RESULTS:TLR3 and inflammatory mediators, including CCL2, IL6, CXCL8, and CCL11, were preferentially enriched in stromal cells. Fibroblast subclustering revealed expansion of activated, remodeling, and inflammatory fibroblast states in CRSwNP, accompanied by increased TLR3 and chemokine expression. Tissue TLR3 expression was increased in CRSwNP and positively correlated with Lund-Mackay CT scores. Poly(I:C) stimulation induced dose-dependent production of IL-6, CXCL8, CCL2, and CCL11 in primary nasal fibroblasts. These responses were mediated through TRIF, p38, JNK, and PI3K/AKT signaling. Functionally, Poly(I:C)-stimulated fibroblasts promoted eosinophil chemotaxis, which was attenuated by inhibition of TRIF, JNK, and PI3K signaling. CONCLUSIONS:Nasal fibroblasts function as active stromal mediators of TLR3-dependent innate immune activation in CRSwNP. Fibroblast-derived inflammatory and eosinophil-recruiting mediators may link viral-like stimulation to eosinophilic inflammation and tissue remodeling in CRSwNP.
BACKGROUND:The proportion of otolaryngology trainees pursuing fellowship has increased alongside rapid expansion in rhinology fellowship programs. Contemporary data evaluating trainee motivations, expectations, and outcomes remain limited. This study assesses contemporary data evaluating trainee motivations, expectations, and outcomes among US rhinology fellows over a 7-year period. METHODS:A combined prospective and retrospective survey study was conducted using questionnaires administered to incoming and outgoing fellows at US rhinology fellowship programs from 2018 to 2025. Surveys evaluated motivations, procedural comfort, research expectations, career plans, and overall satisfaction. Responses were analyzed descriptively. RESULTS:A total of 241 responses were analyzed (124 incoming, 117 outgoing). The primary motivation for fellowship was to enhance surgical skills and clinical decision-making, with fewer respondents citing research or mentorship. Fellows reported high comfort with standard endoscopic sinus procedures but lower confidence with advanced skull base and rhinoplasty techniques. Protected research time was inconsistent, with 16%-45% of graduating fellows reporting none, differing from incoming expectations. Interest in a 2-year fellowship was low (29% incoming vs. 18% outgoing). While 71.8% of incoming fellows anticipated academic careers, 64.1% ultimately entered academic practice. Overall satisfaction was high, with 86.3% reporting that fellowship met expectations. Reported shortcomings included limited skull base exposure, reduced surgical autonomy, inadequate billing/coding training, and insufficient research time. CONCLUSION:Rhinology fellowship trainees primarily pursue subspecialty training to enhance surgical skills and clinical decision-making. Although training is overwhelmingly perceived as meeting expectations, meaningful gaps persist between anticipated and actual experiences, particularly in protected academic time, exposure to advanced procedures, and non-clinical skill development.
Key Points Balloon sinuplasty in AERD is linked to higher lifetime sinus surgical burden. History of balloon sinuplasty in AERD patients is tied to worse current sinonasal symptoms. Balloon procedure AERD patients resided in more socioeconomically disadvantaged areas.
BACKGROUND:To systematically evaluate the local biomarkers correlated with olfactory dysfunction (OD) in chronic rhinosinusitis (CRS). METHODS:A systematic review was conducted in CINAHL, Cochrane Library, PubMed, and Scopus from inception to July 2025. Studies on CRS patients who underwent olfactory testing and measurement of biomarkers within olfactory mucus were included. Collected variables included CRS phenotype, olfactory test, mucus protein levels, quantification method, and reported correlation coefficients. Meta-analysis of outcome measures in 351 participants included continuous measures (mean), proportions (%), and correlations (r) with 95% confidence intervals (CIs). RESULTS:Seven prospective studies met criteria, with 4 studies comprising 201 patients with CRS with nasal polyps (CRSwNP) and 150 with CRS without nasal polyps (CRSsNP) for meta-analysis. The CRSwNP and CRSsNP cohorts were 53.08% and 58.09% male, respectively, with a mean age of 49.09 (1.36) and 46.84 (0.4), respectively. In participants with CRSwNP, IL-5, IL-6, IL-10, IL-13, IgE, CCL2, and CCL3 were inversely correlated with olfactory function scores (r = -0.223 to -0.333; all p ≤ 0.016). CXCL5 and VEGF-A were positively correlated in CRSwNP (r = 0.240-0.247, both p < 0.01). Other Type 2 cytokines, including IL-4, IL-23, and IL-33, did not show any significant correlations. In CRSsNP, IL-8 was negatively correlated (r = -0.182, p = 0.028) and CXCL5 was positively correlated with olfactory function scores (r = 0.274, p = 0.01). CONCLUSION:OD in CRSwNP is moderately or mildly associated with specific Type 2 cytokines and other biomarkers. OD in CRSsNP is weakly correlated with IL8 and CXCL5, but not Type 2 cytokines. Further prospective studies are needed to elucidate causal relationships and prognostic utility between local biomarkers and OD.
KEY POINTS:The IOQ measures the value patients place on olfaction, a construct distinct from disease burden. The IOQ is most precise across the central trait range typical of routine ENT patients. Association items carry most measurement information, enabling a brief affective screen.
BACKGROUND:Cognitive dysfunction is increasingly recognized as an extra-nasal manifestation of chronic rhinosinusitis (CRS). This scoping review characterizes the primary evidence on cognition in adult CRS, covering measures, treatment response, and incident dementia. METHODS:We searched EMBASE, PubMed/MEDLINE, Web of Science, the Cochrane Library, CINAHL, and Global Index Medicus through May 2026 using a MeSH and free-text strategy. Inclusion criteria include primary studies of adult CRS with a formal clinical diagnosis (AAO-HNS, EPOS or ICD-coded) reporting at least one validated cognitive measure or recognized cognitive impairment. Two reviewers screened independently. Animal studies, reviews, conference abstracts, and non-CRS populations were excluded. PRISMA-ScR reporting was performed; heterogeneity precluded meta-analysis. RESULTS:Twenty-four primary studies met inclusion criteria. Adults with CRS perform worse than controls on subjective (Cognitive Failures Questionnaire [CFQ], Neuro-QoL) and objective (Montreal Cognitive Assessment [MoCA], Automated Neuropsychological Assessment Metrics [ANAM], eye movement assessment, P300) cognitive instruments. Deficits correlate with disease-specific QoL severity (SNOT-22, Rhinosinusitis Disability Index [RSDI]). Cognitive measures improve after medical therapy or endoscopic sinus surgery. Two resting-state fMRI analyses identified altered orbitofrontal-precuneus connectivity scaling with sinonasal inflammation. Dementia results are mixed: a UK Biobank analysis (7176 CRS cases among 364,945 participants) reported increased Alzheimer disease risk (HR 1.33), while two Korean cohorts and a 2025 meta-analysis found no association. CONCLUSION:Adults with CRS show measurable cognitive dysfunction that may improve with treatment, with a plausible neuroinflammatory pathophysiology. Whether this translates to incident dementia is contested. Outcome heterogeneity limits synthesis; therefore, development of a CRS-specific cognitive measurement set is recommended.
BACKGROUND:Chronic rhinosinusitis is common in people with cystic fibrosis (PwCF). Highly effective modulator therapy (HEMT) has been shown to improve sinonasal outcomes. However, prior studies failed to show improvement in objective olfaction with HEMT, and the impact of HEMT on olfactory-specific quality of life has yet to be studied. Furthermore, the underlying changes in gene expression within the olfactory epithelium (OE) of PwCF remains poorly understood. METHODS:Single-center cross-sectional cohort study of PwCF. Patients with no history of cystic fibrosis (CF) or comorbid sinus disease were used as controls. Olfactory-specific quality-of-life (QOD-NS) and objective olfactory testing (Sniffin' Sticks comprehensive test) were collected. Cytology brushings from the OE were obtained to isolate RNA for olfactory-specific gene expression (OMP, TUJ1, KRT5, SOX2, OR9K2, and OR5AN1). RESULTS:Fifty PwCF were enrolled (HEMT n = 32, non-HEMT n = 18, and control n = 17). A significant difference was found for QOD-NS (p = 0.041) but not for objective olfaction (p = 0.72) by HEMT status. There was a significant difference between HEMT and non-HEMT cohorts for SOX2 gene expression (p = 0.016); there were no significant differences observed in other markers. Comparing PwCF to controls, significant differences were found in gene expression across all markers. CONCLUSION:HEMT is associated with QOD-NS but not objective olfaction in PwCF. HEMT may impact gene expression of support cells in the OE but does not appear to affect olfactory neuronal gene expression. This suggests PwCF have early and irreversible damage to the OE. Further studies are necessary to better understand CF-induced changes to the OE.
INTRODUCTION:Immunomodulatory therapies, including tumor necrosis factor alpha (TNF-α) inhibitors and anti-CD20 agents, are often used for autoimmune, inflammatory, and neoplastic disorders. While infection risk is well recognized, their association with rhinosinusitis remains poorly characterized. GOAL:To map the existing literature on TNF-α and anti-CD20 agents and rhinosinusitis and to identify emerging clinical patterns. METHODS:A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search of PubMed, Scopus, Web of Science, and Cochrane databases was performed. Studies that reported sinonasal outcomes in patients receiving TNF-α inhibitors or anti-CD20 agents were included. RESULTS:A total of 33 studies were included. The literature was limited and predominantly comprised of case reports and retrospective cohorts. Distinct patterns emerged between drug classes. TNF-α inhibitors were primarily associated with new-onset or severe rhinosinusitis, including opportunistic and invasive fungal infections, often without documented hypogammaglobulinemia. In contrast, anti-CD20 therapy was consistently linked to recurrent bacterial rhinosinusitis within a broader sinopulmonary infection phenotype, frequently accompanied by secondary hypogammaglobulinemia. Several studies reported improvement in infection burden following immunoglobulin replacement therapy. Definitions of rhinosinusitis and outcome reporting were highly heterogeneous across studies. CONCLUSION:Immunomodulator-associated rhinosinusitis appears to manifest as two distinct phenotypes: a TNF-α inhibitor related opportunistic infection pattern and an anti-CD20 associated antibody-deficiency phenotype. Prospective studies are needed to define incidence, risk stratification, and optimal screening and management strategies for sinonasal disease in this patient population.
Key Points Comprehensive CFTR sequencing detects intronic and exonic variants missed by standard CF panels. The intronic 5T allele was the most common CFTR variant in refractory CRSwNP patients.
INTRODUCTION:Chronic rhinosinusitis (CRS) has been consistently associated with reduced quality of life, including limitations in mobility and daily activities. Wearable technology has demonstrated utility in tracking physical activity after surgical interventions, with limited studies on activity levels after sinus surgery. METHODS:We performed a retrospective review of Apple Health data from participants diagnosed with CRS who underwent sinus surgery at two tertiary academic centers. Daily activity metrics were aggregated over 12 months preoperatively and 2-13 months postoperatively following a 1-month washout period. Metrics analyzed included average daily steps, and other ambulatory activity elements. Pre- and post-surgical values were compared using Wilcoxon signed-rank tests. RESULTS:Among 51 CRS patients (mean age 37.7 ± 11.2 years), average daily step count significantly increased following surgery, from 7501.4 ± 4119.9 to 8843.5 ± 5107.3 per day (p = 0.003). Daily active energy burned rose from 335.5 ± 210.7 to 383.4 ± 244.8 kilocalories (p = 0.025), and daily distance walking or running increased (3.25 ± 1.88 to 3.80 ± 2.29 miles, p = 0.006). Daily exercise minutes and flights climbed also improved (p = 0.014 and p = 0.022, respectively). SNOT-22 scores demonstrated significant postoperative reductions, decreasing from 43.46 ± 24.18 to 21.15 ± 18.83, p < 0.001. CONCLUSION:We observed CRS patients post-sinus surgery to have significant increases in activity metrics as measured by wearable technology. This pilot study suggests that postoperative recovery may extend beyond symptom relief to measurable changes in daily physical activity.
