Introduction: Tissue eosinophil count (TEC) is recommended for defining Type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). TEC is usually assessed by a one-time polyp biopsy. Because TEC may change over time, its reliability for diagnosing type 2 CRSwNP has not been previously assessed. This study aims to explore whether TEC fluctuates across different time points.
Methods: Adult patients with CRSwNP were prospectively recruited at Rajavithi Hospital, Thailand. Participants who had used any form of steroids within 4 weeks were excluded. Polyps were taken for TEC evaluation upon recruitment and repeated at 3 and 6 months. Participants were assessed using the 22-items Sinonasal Outcome Test (SNOT-22), Lund-Kennedy endoscopic score (LKES), blood eosinophil count, and its percentage at each time point.
Results: Thirty-seven participants were enrolled. The medians (Quartiles 1-3) of TEC were 17 (4-53.5), 19 (5-47.5), and 21 (4.5-51) cells/high-powered field at 0, 3, and 6 months, respectively. Friedman's two-way analysis of variance showed no statistical differences across the three time points for TEC (p = 0.53), blood eosinophil counts (p = 0.61), blood eosinophil percentages (p = 0.23), SNOT-22 (p = 0.21), or LKES (p = 0.23). TEC significantly correlated with blood eosinophil counts at 0 and 3 months and with blood eosinophil percentages at 0, 3, and 6 months (all p < 0.05).
Conclusion: The study showed that TEC did not significantly fluctuate over time, aligning with blood eosinophil levels, SNOT-22, and LKES. This stability within the 6-month period supports the reliability of TEC from a single biopsy for clinical use in managing CRSwNP.
{"title":"Fluctuation of tissue eosinophils in chronic rhinosinusitis with nasal polyp.","authors":"Kunjira Sombutpiboonphon, Kornkiat Snidvongs, Saranath Lawpoolsri, Nutpacha Chotikawichean, Patlada Kowatanamongkon, Kittichai Mongkolkul, Wirach Chitsuthipakorn","doi":"10.1002/alr.23494","DOIUrl":"https://doi.org/10.1002/alr.23494","url":null,"abstract":"<p><strong>Introduction: </strong>Tissue eosinophil count (TEC) is recommended for defining Type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). TEC is usually assessed by a one-time polyp biopsy. Because TEC may change over time, its reliability for diagnosing type 2 CRSwNP has not been previously assessed. This study aims to explore whether TEC fluctuates across different time points.</p><p><strong>Methods: </strong>Adult patients with CRSwNP were prospectively recruited at Rajavithi Hospital, Thailand. Participants who had used any form of steroids within 4 weeks were excluded. Polyps were taken for TEC evaluation upon recruitment and repeated at 3 and 6 months. Participants were assessed using the 22-items Sinonasal Outcome Test (SNOT-22), Lund-Kennedy endoscopic score (LKES), blood eosinophil count, and its percentage at each time point.</p><p><strong>Results: </strong>Thirty-seven participants were enrolled. The medians (Quartiles 1-3) of TEC were 17 (4-53.5), 19 (5-47.5), and 21 (4.5-51) cells/high-powered field at 0, 3, and 6 months, respectively. Friedman's two-way analysis of variance showed no statistical differences across the three time points for TEC (p = 0.53), blood eosinophil counts (p = 0.61), blood eosinophil percentages (p = 0.23), SNOT-22 (p = 0.21), or LKES (p = 0.23). TEC significantly correlated with blood eosinophil counts at 0 and 3 months and with blood eosinophil percentages at 0, 3, and 6 months (all p < 0.05).</p><p><strong>Conclusion: </strong>The study showed that TEC did not significantly fluctuate over time, aligning with blood eosinophil levels, SNOT-22, and LKES. This stability within the 6-month period supports the reliability of TEC from a single biopsy for clinical use in managing CRSwNP.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amber Cradeur, Mark Knackstedt, Mackenzie Latour, Michael Yim
Key points: Simulation models have utility in rehearsal of endoscopic skull base repair with a nasoseptal flap. Trainee confidence, technical skill, and repair quality saw significant improvement in this study.
{"title":"Modeling nasal septal flap repair of an anterior skull base defect: A pilot simulation study.","authors":"Amber Cradeur, Mark Knackstedt, Mackenzie Latour, Michael Yim","doi":"10.1002/alr.23500","DOIUrl":"https://doi.org/10.1002/alr.23500","url":null,"abstract":"<p><strong>Key points: </strong>Simulation models have utility in rehearsal of endoscopic skull base repair with a nasoseptal flap. Trainee confidence, technical skill, and repair quality saw significant improvement in this study.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junhao Tu, Fan Jiang, Jing Liu, Hsiao Hui Ong, Zhiqun Huang, Keshuang Wang, Qing Luo, Li Shi, Jing Ye, Deyun Wang
Key points: Sinonasal inverted papilloma (SNIP) is a benign epithelial proliferative disease with a high recurrence rate. The role of epithelial-mesenchymal transition (EMT) in the pathogenesis of SNIP remains unclear. EMT marker expression is elevated in SNIP tissues and is associated with its recurrence.
{"title":"Increased expression of epithelial-mesenchymal transition markers associated with recurrence of sinonasal inverted papilloma.","authors":"Junhao Tu, Fan Jiang, Jing Liu, Hsiao Hui Ong, Zhiqun Huang, Keshuang Wang, Qing Luo, Li Shi, Jing Ye, Deyun Wang","doi":"10.1002/alr.23501","DOIUrl":"https://doi.org/10.1002/alr.23501","url":null,"abstract":"<p><strong>Key points: </strong>Sinonasal inverted papilloma (SNIP) is a benign epithelial proliferative disease with a high recurrence rate. The role of epithelial-mesenchymal transition (EMT) in the pathogenesis of SNIP remains unclear. EMT marker expression is elevated in SNIP tissues and is associated with its recurrence.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rory J Lubner, Christina Dorismond, Mason Krysinski, Ping Li, Rakesh K Chandra, Justin H Turner, Dawn C Newcomb, Katherine N Cahill, Naweed I Chowdhury
Key points: CRS patients with asthma show differential nasal mucus cytokine signatures based on endotype. IL-7 concentration is positively associated with higher %FEV1 and %FVC in CRS patients with asthma.
{"title":"Nasal Mucus Cytokines Are Correlated with Spirometry Measures in CRS Patients with Comorbid Asthma.","authors":"Rory J Lubner, Christina Dorismond, Mason Krysinski, Ping Li, Rakesh K Chandra, Justin H Turner, Dawn C Newcomb, Katherine N Cahill, Naweed I Chowdhury","doi":"10.1002/alr.23492","DOIUrl":"https://doi.org/10.1002/alr.23492","url":null,"abstract":"<p><strong>Key points: </strong>CRS patients with asthma show differential nasal mucus cytokine signatures based on endotype. IL-7 concentration is positively associated with higher %FEV1 and %FVC in CRS patients with asthma.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saawan D Patel, Isha K Thapar, Alan D Workman, Dana F Lopez, Benjamin F Bitner, Hannah B Bukzin, David K Lerner, Jadyn Wilensky, Jennifer E Douglas, James N Palmer, Nithin D Adappa, Charles C L Tong, Edward C Kuan, Michael A Kohanski
Background: Recurrence of sinonasal squamous cell carcinoma (SNSCC) follows an aggressive course, and early detection is paramount. This study identifies the parameters of different surveillance modalities.
Methods: We conducted a retrospective study of 105 SNSCC patients at three academic institutions from November 2009 to July 2024. Patient records were reviewed for demographics, tumor characteristics, endoscopy, CT, PET/CT, and MRI findings. Multivariable analyses were performed in RStudio.
Results: Mean time to recurrence was 12.1 months (SD 13.9 months). Patients with higher Charlson Comorbidity Index (p = 0.041), endoscopic surgical approach (p = 0.015), and suspicious surveillance findings (p = 0.029) had higher rates of recurrence. Endoscopy showed a sensitivity of 18.5% and specificity of 99.2%, with a positive predictive value (PPV) of 45.5% and negative predictive value (NPV) of 97.0%. CT had a sensitivity of 75.0% and specificity of 100.0%, with a PPV of 100.0% and NPV of 97.6%. PET/CT demonstrated a sensitivity of 95.2% and specificity of 90.8%, with a PPV of 64.5% and NPV of 97.6%. MRI showed a sensitivity of 72.4% and specificity of 97.1%, with a PPV of 65.6% and NPV of 97.9%. The median time from the last normal surveillance to recurrence was 2.07 months for endoscopy, 8.61 months for CT, 8.15 months for PET/CT, and 6.49 months for MRI.
Conclusions: The high specificity and NPV of endoscopy, alongside the high sensitivity of PET/CT, support a multimodal approach for surveillance. Given the mean onset of SNSCC recurrence at 12.1 months, surveillance beyond the National Comprehensive Cancer Network's asymptomatic 6-month guideline is warranted, and follow-up should be tailored to patient-specific risk factors.
{"title":"Comparison of surveillance modalities in the surveillance of sinonasal squamous cell carcinoma recurrence: A multi-institutional study.","authors":"Saawan D Patel, Isha K Thapar, Alan D Workman, Dana F Lopez, Benjamin F Bitner, Hannah B Bukzin, David K Lerner, Jadyn Wilensky, Jennifer E Douglas, James N Palmer, Nithin D Adappa, Charles C L Tong, Edward C Kuan, Michael A Kohanski","doi":"10.1002/alr.23495","DOIUrl":"https://doi.org/10.1002/alr.23495","url":null,"abstract":"<p><strong>Background: </strong>Recurrence of sinonasal squamous cell carcinoma (SNSCC) follows an aggressive course, and early detection is paramount. This study identifies the parameters of different surveillance modalities.</p><p><strong>Methods: </strong>We conducted a retrospective study of 105 SNSCC patients at three academic institutions from November 2009 to July 2024. Patient records were reviewed for demographics, tumor characteristics, endoscopy, CT, PET/CT, and MRI findings. Multivariable analyses were performed in RStudio.</p><p><strong>Results: </strong>Mean time to recurrence was 12.1 months (SD 13.9 months). Patients with higher Charlson Comorbidity Index (p = 0.041), endoscopic surgical approach (p = 0.015), and suspicious surveillance findings (p = 0.029) had higher rates of recurrence. Endoscopy showed a sensitivity of 18.5% and specificity of 99.2%, with a positive predictive value (PPV) of 45.5% and negative predictive value (NPV) of 97.0%. CT had a sensitivity of 75.0% and specificity of 100.0%, with a PPV of 100.0% and NPV of 97.6%. PET/CT demonstrated a sensitivity of 95.2% and specificity of 90.8%, with a PPV of 64.5% and NPV of 97.6%. MRI showed a sensitivity of 72.4% and specificity of 97.1%, with a PPV of 65.6% and NPV of 97.9%. The median time from the last normal surveillance to recurrence was 2.07 months for endoscopy, 8.61 months for CT, 8.15 months for PET/CT, and 6.49 months for MRI.</p><p><strong>Conclusions: </strong>The high specificity and NPV of endoscopy, alongside the high sensitivity of PET/CT, support a multimodal approach for surveillance. Given the mean onset of SNSCC recurrence at 12.1 months, surveillance beyond the National Comprehensive Cancer Network's asymptomatic 6-month guideline is warranted, and follow-up should be tailored to patient-specific risk factors.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anthony Tang, Suchet Taori, Nicholas Fung, Joao Paulo Almeida, Pierre-Olivier Champagne, Juan C Fernandez-Miranda, Paul Gardner, Peter H Hwang, Jayakar V Nayak, Chirag Patel, Zara M Patel, Maria Peris Celda, Carlos Pinheiro-Neto, Olabisi Sanusi, Carl Snyderman, Brian D Thorp, Jamie J Van Gompel, Georgios A Zenonos, Nathan T Zwagerman, Eric W Wang, Mathew Geltzeiler, Garret Choby
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.
{"title":"Pathologic dural invasion is associated with regional recurrence in olfactory neuroblastoma: A multi-institutional study.","authors":"Anthony Tang, Suchet Taori, Nicholas Fung, Joao Paulo Almeida, Pierre-Olivier Champagne, Juan C Fernandez-Miranda, Paul Gardner, Peter H Hwang, Jayakar V Nayak, Chirag Patel, Zara M Patel, Maria Peris Celda, Carlos Pinheiro-Neto, Olabisi Sanusi, Carl Snyderman, Brian D Thorp, Jamie J Van Gompel, Georgios A Zenonos, Nathan T Zwagerman, Eric W Wang, Mathew Geltzeiler, Garret Choby","doi":"10.1002/alr.23489","DOIUrl":"https://doi.org/10.1002/alr.23489","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Data sources: </strong>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.</p><p><strong>Review methods: </strong>Clinicopathologic features including modified Kadish staging systems, margin status, treatment modalities, Hyams grading, follow-up time, and survival.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mason R Krysinski, Christina Dorismond, Yash Trivedi, Rory Lubner, Andrea A Lopez, Kolin Rubel, Rakesh K Chandra, Naweed I Chowdhury, Justin H Turner
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.
{"title":"Aging and frailty are associated with inflammatory endotypic shifts in patients with chronic rhinosinusitis.","authors":"Mason R Krysinski, Christina Dorismond, Yash Trivedi, Rory Lubner, Andrea A Lopez, Kolin Rubel, Rakesh K Chandra, Naweed I Chowdhury, Justin H Turner","doi":"10.1002/alr.23484","DOIUrl":"https://doi.org/10.1002/alr.23484","url":null,"abstract":"<p><strong>Key points: </strong>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.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yobouet Ines Kouakou, Joel C Thompson, Li Hui Tan, Zoey A Miller, Ray Z Ma, Nithin D Adappa, James N Palmer, Noam A Cohen, Robert J Lee
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.
{"title":"Hops bitter β-acids have antibacterial effects against sinonasal Staphylococcus aureus but also induce sinonasal cilia and mitochondrial dysfunction.","authors":"Yobouet Ines Kouakou, Joel C Thompson, Li Hui Tan, Zoey A Miller, Ray Z Ma, Nithin D Adappa, James N Palmer, Noam A Cohen, Robert J Lee","doi":"10.1002/alr.23487","DOIUrl":"https://doi.org/10.1002/alr.23487","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina Dorismond, Mason R Krysinski, Yash Trivedi, Rory J Lubner, Rakesh K Chandra, Naweed I Chowdhury, Justin H Turner
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.
{"title":"Real-world predictors of dupilumab prescription in patients with chronic rhinosinusitis with nasal polyps.","authors":"Christina Dorismond, Mason R Krysinski, Yash Trivedi, Rory J Lubner, Rakesh K Chandra, Naweed I Chowdhury, Justin H Turner","doi":"10.1002/alr.23483","DOIUrl":"https://doi.org/10.1002/alr.23483","url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahnaz Ramezanpour, Sholeh Feizi, Hashan Dilendra Paththini Arachchige, George Bouras, Clare Cooksley, Gohar Shaghayegh, Peter-John Wormald, Alkis James Psaltis, Sarah Vreugde
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.
{"title":"Evaluation of mucosal barrier disruption due to Staphylococcus lugdunensis and Staphylococcus epidermidis exoproteins in patients with chronic rhinosinusitis.","authors":"Mahnaz Ramezanpour, Sholeh Feizi, Hashan Dilendra Paththini Arachchige, George Bouras, Clare Cooksley, Gohar Shaghayegh, Peter-John Wormald, Alkis James Psaltis, Sarah Vreugde","doi":"10.1002/alr.23481","DOIUrl":"https://doi.org/10.1002/alr.23481","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Our results suggest that CoNS exoproteins may contribute to CRS etiopathogenesis.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}