International Forum of Allergy & Rhinology最新文献

Objective: Neck metastases are a poor prognostic factor in olfactory neuroblastoma (ONB). Pathologic dural invasion (pathDI) may increase the risk of neck metastases due to invasion of dural lymphatics. We aim to evaluate the prognostic value of pathDI in predicting rates of neck metastases and recurrence using a large, multicenter database of ONB patients.

Data sources: Retrospective review of a prospective, multicenter database of electronic health records of all patients who presented with ONB between 2005 and 2021 at nine tertiary academic care centers within North America.

Review methods: Clinicopathologic features including modified Kadish staging systems, margin status, treatment modalities, Hyams grading, follow-up time, and survival.

Results: Of 258 ONB patients, 189 patients met the inclusion criteria. The 10-year neck recurrence-free survival (neck-RFS) rates were 85.7% (75.6‒97.3) and 61.8% (47.9‒79.8) for patients without and with pathDI, respectively (p = 0.018). Time-to-event multivariable regression analysis found pathDI to have an odds ratios of 9.7 (95% confidence interval [CI] 1.2-80.4, p = 0.04) for neck-RFS and 9.5 for RFS at any site (95% CI 1.1-83.3, p = 0.04).

Conclusion: In multivariable analysis, the presence of pathDI appears to be the strongest predictor of neck recurrence and recurrence at any site. Future studies exploring the benefit of elective neck dissection or radiation for patients with pathDI may impact disease management.

Key points: Frailty and aging are associated with a shift toward non-type 2 inflammation in chronic rhinosinusitis (CRS). Frailty-related shifts in sinonasal inflammatory mediators may be linked to biological senescence. Understanding the role of aging and frailty in CRS may have important treatment implications.

Background: Routine prescription of antibiotics to treat chronic rhinosinusitis (CRS) exacerbations may contribute to the propagation of antibiotic resistance. Hops bitter β-acids lupulone and colupulone possess potent antibacterial activities and, as T2R1, T2R14, and/or T2R40 agonists, may improve the impaired mucociliary clearance described in CRS patients. We investigated these molecules as alternative treatments to antibiotics in CRS management based on their antibacterial and T2Rs agonists properties.

Methods: Human nasal primary cells (HNECs) and RPMI2650 cells cultures were used as study models. T2Rs expression in cell culture models and human nasal tissue was assessed using immunofluorescence, quantitative PCR, and Western blot. We performed calcium imaging and cilia beat frequency experiments to investigate T2Rs activation in study models in response to lupulone and colupulone stimulations. Finally, we studied hops β-acids cytotoxicity on cells using CellEvent, crystal violet, lactate dehydrogenase assays, immunofluorescence, and transepithelial electrical resistance assays.

Results: We confirmed lupulone and colupulone potent antibacterial effect on CRS-relevant methicillin-resistant Staphylococcus aureus but found minimal impact on P. aeruginosa. We also report T2R1, T2R14 and T2R40 expression in HNECs and RPMI2650 cell cultures. Lupulone and colupulone induced an increase in cytosolic calcium that appeared dependent on T2Rs signaling. This response was accompanied by mitochondrial membrane depolarization, cellular energy stress, decreased cell proliferation, ciliostasis, and HNECs remodeling after a single exposure to lupulone at micromolar concentrations.

Conclusion: Our data suggest that hops β-acids may not be beneficial as treatments in CRS patients and instead contribute to the disease by impairing cell health and further deteriorating the MCC.

Background: Despite increasing dupilumab use for chronic rhinosinusitis with nasal polyps (CRSwNP), little is known about the factors influencing its use in real-world practice. We aimed to identify factors that may predict dupilumab prescription in CRSwNP patients who have undergone endoscopic sinus surgery (ESS).

Methods: A single-institution, retrospective cohort study of patients who underwent ESS for CRSwNP between 2015 and 2023 was conducted. Demographics, comorbidities, 22-item sinonasal outcome test (SNOT-22) scores, and dupilumab prescription date were extracted from patient records. Intraoperative nasal mucus cytokine levels were measured using a multiplex bead assay. Univariate logistic regression analysis was performed to identify factors associated with dupilumab prescription, and multivariate logistic regression was used to adjust for surgery date.

Results: A total of 299 CRSwNP patients were included, including seventy (23.4%) who were prescribed dupilumab postoperatively. Patients were more likely to be prescribed dupilumab if they had asthma (odds ratio [OR] 2.304), aspirin-exacerbated respiratory disease (AERD, OR 3.375), elevated tissue eosinophils (OR 1.005), and higher 3-month postoperative SNOT-22 scores (OR 1.027). Patients prescribed dupilumab also had greater odds of having elevated mucus interleukin (IL)-5 (OR 1.128) and IL-13 (OR 1.213). When adjusting for surgery date, associated factors included: asthma (OR 2.444), AERD (OR 3.750), allergic rhinitis (OR 1.833), higher tissue eosinophils (OR 1.005), elevated 3-month SNOT-22 scores (OR 1.028), and higher IL-5 (OR 1.123) and IL-13 (OR 1.202) levels.

Conclusion: Asthma, AERD, allergic rhinitis, and elevated tissue eosinophil, IL-5, and IL-13 levels are predictive of dupilumab prescription in CRSwNP patients. These may serve as clinical and inflammatory biomarkers and can aid in counseling patients about expected disease trajectory.

Background: Chronic rhinosinusitis (CRS) is a persistent inflammatory condition of the sinus mucosa. While Staphylococcus aureus has been shown to play a significant role in mucosal barrier disruption in CRS patients, coagulase-negative staphylococci (CoNS) such as Staphylococcus epidermidis and Staphylococcus lugdunensis are also implicated in CRS pathophysiology. This study investigates the effects of exoproteins secreted by planktonic and biofilm forms of clinical isolates of S. epidermidis and S. lugdunensis on the nasal epithelial barrier.

Methods: Thirty-one clinical isolates of CoNS were grown in planktonic and biofilm forms, and their exoproteins were concentrated. The epithelial barrier structure was assessed by measuring transepithelial electrical resistance (TEER) and the permeability of fluorescein isothiocyanate-dextran. Toxicity and inflammatory response were also studied.

Results: Our findings demonstrate that exoproteins from all planktonic forms of S. lugdunensis disrupted the mucosal barrier, whereas only nine of 16 biofilm-derived exoproteins had similar effects. Conversely, 11 of 15 exoproteins from planktonic S. epidermidis significantly disrupted barrier integrity; however, biofilm exoproteins did not. The study also showed that some exoproteins from planktonic S. epidermidis significantly reduced cell viability, while exoproteins from planktonic and biofilm forms of S. lugdunensis and biofilm S. epidermidis did not induce any statistically significant change in cell viability. Notably, four of 16 biofilm exoproteins from S. lugdunensis induced higher interleukin-6 (IL-6) secretion, whereas none of the S. epidermidis isolates showed a significant increase in IL-6 secretion.

Conclusion: Our results suggest that CoNS exoproteins may contribute to CRS etiopathogenesis.

Key points: Decreased overall dietary consumption of micronutrients may be linked to an increased risk of olfactory dysfunction (OD) including subjective report of OD, subjective report of phantosmia, and objective OD. Interactions were identified between these micronutrients, suggesting that outcomes may vary depending on the mixture of micronutrients taken.

Background: Emerging evidence has underscored the harmful effects of air pollution on the upper airway. We investigated the relationship between ambient particulate matter (PM) level and the frequency of outpatient visits for chronic rhinosinusitis (CRS).

Methods: We conducted an ecological cohort study of US adults enrolled in The Merative MarketScan outpatient database from 2007 to 2020. For each geographical subunit (core-based statistical area [CBSA]), we calculated the annual rate of CRS-related outpatient visits per 1000 well-patient checkup visits (CRS-OV). Using data from the Environmental Protection Agency's Air Quality System, we mapped the rolling statistical average of daily PM_2.5 and PM₁₀ over the preceding year onto each CBSA × year combination. We employed multivariable negative binomial regression modeling to estimate the association between PM levels and subsequent CRS-OV.

Results: Across 3933 observations (CBSA × year combinations), encompassing ∼4 billion visits, the median CRS-OV was 164 (interquartile range 110-267). The mean PM_2.5 level was 8.9 µg/m³ (SD 2.6) and the mean PM₁₀ level was 20.2 µg/m³ (SD 7.2). Adjusting for patient demographics and respiratory comorbidities, a compounded rise in subsequent CRS-OV was observed with increasing PM levels. Each µg/m³ rise in PM_2.5 independently predicted a 10% increase in CRS-OV (adjusted incidence rate ratio [aIRR]) 1.10, 95% confidence interval [CI] 1.08-1.13) and each µg/m³ rise in PM₁₀ independently predicted a 3% increase in CRS-OV (aIRR 1.03, 95% CI 1.02-1.04).

Conclusion: Elevated ambient PM_2.5 and PM₁₀ levels are associated with a subsequent compounded increase in the frequency of CRS-OV, with PM_2.5 predicting a more pronounced rise compared to PM₁₀.

Key points: Viral infections lead to a greater than twofold increased risk of developing chronic rhinosinusitis within 1 year. Viral infections lead to a greater than twofold increased risk of developing chronic rhinosinusitis within 1 year. Recurrent viral infections pose a greater risk of chronic rhinosinusitis than single episodes.