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.
KEY POINTS:Bevacizumab reduced epistaxis-related ablation frequency by 55.6% in HHT patients. Over half of HHT patients (57.7%) required no ablation intervention after bevacizumab initiation. Maintenance bevacizumab dosing remains highly variable, underscoring the need for standardization.
KEY POINTS:Self-controlled analysis: mean episodes reduced from 2.72 to 1.18 per year; 56.6% reduction. Treatment effect consistent across subgroups, from patients using intranasal corticosteroids (ICS) to those with concurrent chronicc rhinosinusitis (CRS). Findings support prospective randomized controlled trial evaluation of azelastine for recurrent acute rhinosinusitis (RARS).
BACKGROUND:Platelet-rich plasma (PRP) has emerged as a promising therapy for post-viral olfactory dysfunction (PVOD) though its biological mechanisms remain unclear. This study evaluated clinical outcomes and targeted proteomic changes following PRP for refractory PVOD. METHODS:Adults with PVOD ≥ 6 months refractory to standard therapies underwent a single bilateral PRP injection into the olfactory clefts. Demographics, subjective olfactory ratings, and psychophysical assessment using the University of Pennsylvania Smell Identification Test (UPSIT) were obtained at baseline and follow-up. Paired olfactory cleft mucus samples were analyzed using the Olink Target 48 immune panel, and baseline cytokine profiles were compared with normosmic controls. RESULTS:Nineteen subjects were enrolled; 17 completed follow-ups. The mean baseline UPSIT was 19 with a median PVOD duration of 27 months. At a mean follow-up of 45 days, 47% reported subjective improvement and 53% achieved minimal clinically important difference. Mean UPSIT improved by +3.1 points (SD 6.0). Compared with controls, PVOD was associated with increased IL-18 and CCL13 expression. Following PRP, paired comparisons demonstrated increased CSF2 and IL-1β, and decreased IL-6 and IL-33. Pathway enrichment showed increased immune cell recruitment and tissue remodeling. Responders demonstrated increased oncostatin M (OSM) and a greater reduction in IL-17F, with concurrent within-subject increases in VEGFA and decreases in IL-6 and IL-33. CONCLUSION:PRP for refractory PVOD was associated with modest clinical improvement. Responder-specific analyses suggest PRP may promote coordinated immune remodeling characterized by reduction of inflammatory and epithelial stress signaling and activation of reparative pathways. These findings support biological plausibility and warrant further investigation.
BACKGROUND:Chronic rhinosinusitis (CRS) is highly prevalent in patients with cystic fibrosis (CF) and has traditionally been considered a predominantly neutrophilic condition. Emerging evidence, however, suggests that type-2 inflammatory pathways may contribute to disease heterogeneity. Data linking local inflammatory mediators with objective sinonasal disease severity and olfactory dysfunction in CF-associated CRS remain limited. METHODS:In this cross-sectional study, 42 adults with CF-associated CRS (22 with nasal polyps and 20 without) underwent assessment of disease severity using the nasal polyp score (Meltzer classification) (NPS-MS), modified Lund-Kennedy score (mLKS), and Lund-Mackay score (LMS), together with olfactory testing (Sniffin' Sticks Identification Test) and quality-of-life evaluation (22-item Sinonasal Outcome Test [SNOT-22]). Nasal lavage concentrations of IL-4, IL-13, and IL-8 were quantified by ELISA. RESULTS:IL-4 and IL-13 were significantly associated with objective measures of sinonasal disease severity, including NPS-MS and LMS (all p < 0.05), whereas IL-8 did not show consistent associations with disease severity. In multivariable models, IL-4 remained independently associated with mLKS (p = 0.025), LMS (p = 0.047), and olfactory dysfunction (p = 0.002). IL-13 was primarily associated with NPS-MS (p = 0.007) and LMS (p = 0.005). Lung transplantation modified cytokine-severity relationships. Exploratory analyses showed lower IL-4 levels in elexacaftor/tezacaftor/ivacaftor-treated patients (p = 0.036), with no significant effects for IL-8 or IL-13. CONCLUSIONS:CF-associated CRS exhibits a heterogeneous inflammatory profile in which type-2 cytokines, particularly IL-4 and IL-13, are linked to disease severity and olfactory dysfunction. Nasal lavage cytokines may represent promising compartment-specific biomarkers to support inflammatory endotyping and targeted therapeutic strategies.
BACKGROUND:Long-term management strategies for severe chronic rhinosinusitis with nasal polyps (CRSwNP) increasingly include biologic therapy targeting Type 2 inflammation. However, data on outcomes after complete discontinuation of dupilumab following sustained disease control are scarce. METHODS:In this single-center, retrospective real-world study, adult CRSwNP patients who discontinued dupilumab after ≥ 2 years of treatment and sustained good-to-excellent disease control were included. Disease control at cessation was defined according to EPOS/EUFOREA-aligned criteria (bilateral nasal polyp score [NPS] ≤ 2; SNOT-22 < 20). Patients were followed for up to 12 months. Outcomes included SNOT-22, visual analog scale (VAS), NPS, olfactory function (SSIT-12), relapse timing, and reinitiation of therapy. RESULTS:A total of 46 patients were included (median treatment duration 189.7 weeks). At discontinuation, disease control was excellent (mean SNOT-22 10.1 ± 6.1; NPS 0.2 ± 0.5). Within 3 months, a marked and statistically significant deterioration occurred across all major outcomes (SNOT-22 36.4 ± 20.0; VAS 5.0 ± 2.7; NPS 1.5 ± 1.9; all p < 0.001). Median time to first symptom worsening was 7.6 weeks. Most The majority of patients (87.0%) reinitiated dupilumab within 12 months, primarily due to nasal symptom recurrence. Retreatment led to rapid and significant clinical improvement. Six patients remained off therapy, but demonstrated progressive objective and/or subjective worsening over time. CONCLUSIONS:Complete discontinuation of dupilumab after long-term disease control appears feasible in only a minority of patients and is associated with early relapse in most cases. These findings support the concept of dupilumab as a disease-controlling rather than disease-modifying or curative therapy and favor individualized dose tapering over full cessation in severe Type 2-driven CRSwNP.
INTRODUCTION:Traditional management of traumatic skull base dural injury has often favored observation and conservative therapy, despite the risk of delayed intracranial complications. This paradigm originated when operative intervention required craniotomy and carried significant morbidity. The objectives of this study were to evaluate outcomes of early endoscopic repair for traumatic skull base dural injury and to assess whether radiographic evidence of dural violation, including pneumocephalus, may support consideration of early intervention. METHODS:A retrospective review was performed of 385 patients with traumatic skull base injury and evidence of dural disruption. Patients with congenital, spontaneous, or neoplastic etiologies were excluded. Endoscopic repair was performed in all patients with clinical or radiographic evidence of dural violation, including pneumocephalus, regardless of the presence of overt cerebrospinal fluid (CSF) leak. Outcomes, prior management, and complications were analyzed. RESULTS:Among 385 patients, 219 (56.9%) presented with CSF leak and 254 (66.0%) with pneumocephalus. The ethmoid (244), frontal (212), and sphenoid (157) sinuses were most involved. Primary endoscopic repair success was achieved in 97.4% (375/385), increasing to 99.0% (381/385) following endoscopic revision. One hundred and two patients had prior conservative management, with 34 (33.3%) developing meningitis or intracerebral infection. Patients requiring multiple interventions were predominantly those with penetrating trauma. CONCLUSION:Early endoscopic repair was highly effective for traumatic skull base dural violation. Pneumocephalus should be recognized as an important marker of dural disruption, even without overt CSF leak, and may justify early definitive repair in selected patients. Morbidity after conservative management supports reconsideration of observation-based algorithms.
