Zhi-Qun Huang, Jing Liu, Li-Ying Sun, Qing Luo, Jie-Qing Yu, Li Shen, Yi-Shan Xiong, Ran-Ran Yin, De-Yun Wang, Jing Ye
{"title":"Dupilumab Alleviates IL-13-Induced Nasal Epithelial Barrier Dysfunction by Regulating Claudin-10 Expression.","authors":"Zhi-Qun Huang, Jing Liu, Li-Ying Sun, Qing Luo, Jie-Qing Yu, Li Shen, Yi-Shan Xiong, Ran-Ran Yin, De-Yun Wang, Jing Ye","doi":"10.1002/alr.70179","DOIUrl":"https://doi.org/10.1002/alr.70179","url":null,"abstract":"<p><strong>Backgrounds: </strong>Nasal epithelial barrier impairment is a crucial pathology in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the mechanisms driving tight junctions (TJs) disruption remain unclear. We aimed to elucidate the role of IL-13 in TJs breakdown and epithelial remodeling, and to evaluate whether dupilumab can restore epithelial integrity under Type-2 inflammatory conditions.</p><p><strong>Methods: </strong>Differentially expressed TJs-related genes were identified by integrating the GSE136825 dataset with clinical samples from 23 healthy controls and 73 CRSwNP patients. The effects of IFN-γ, IL-13, IL-17A, and dupilumab on epithelial barrier function and claudin-10 (CLDN10) expression were investigated in seven human nasal epithelial cells using transepithelial electrical resistance (TER), RT-qPCR, WB, and immunofluorescence. Statistical analyses were performed using the chi-square test, one-way ANOVA, Wilcoxon signed-rank test, and Spearman's rank correlation.</p><p><strong>Results: </strong>CLDN10 was identified as the most significantly downregulated TJs in CRSwNP and negatively correlated with eosinophil infiltration (r = -0.4414, p < 0.0001). In vitro, IL-13 markedly reduced CLDN10 and TER levels, and induced epithelial remodeling with fewer club cells and ciliated cells and more goblet cells (all p < 0.05). Additionally, dupilumab effectively mitigated IL-13-induced CLDN10 loss, restored barrier integrity, and normalized epithelial alarmins, including IL-25 and TSLP expression (all p < 0.05).</p><p><strong>Conclusions: </strong>IL-13-driven Type-2 inflammation disrupts nasal epithelial barrier integrity by downregulating CLDN10 and altering epithelial cell differentiation. Dupilumab counteracts these effects by restoring CLDN10 expression and epithelial barrier function, highlighting CLDN10 as a crucial mediator of barrier dysfunction and a potential therapeutic target in CRSwNP.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837512","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}
Aris I Giotakis, Athanasios Ioannidis, Efthymios Kyrodimos, Efthymios Koniaris, Evangelos I Giotakis, Dimitra Riga
{"title":"Distribution of Eosinophils Across Multiple Paranasal Sinuses Within Patients With Chronic Rhinosinusitis With Nasal Polyps.","authors":"Aris I Giotakis, Athanasios Ioannidis, Efthymios Kyrodimos, Efthymios Koniaris, Evangelos I Giotakis, Dimitra Riga","doi":"10.1002/alr.70176","DOIUrl":"https://doi.org/10.1002/alr.70176","url":null,"abstract":"<p><strong>Background: </strong>A single nasal polyp is frequently used for research purposes. We intended to investigate whether a single nasal polyp reflects the total inflammatory load in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).</p><p><strong>Methods: </strong>We intended to prospectively collect polyps from four sites of 30 subjects during surgery for CRSwNP. We collected the most anterior located polyp and polyps of the posterior ethmoidal area on each side. A pathologist, blinded to the sampling sites, quantified the tissue eosinophilic count in the three most dense high-power fields with hematoxylin and eosin staining. We investigated the coefficient of variation within subjects and compared differences across the four sites with the Friedman's test. Moreover, we examined how many subjects had more or less than 10 eosinophils across all four sites and could be characterized as eosinophilic- or non-eosinophilic CRSwNP according to recent guidelines.</p><p><strong>Results: </strong>The mean coefficient of variation was high (82%). The tissue eosinophilic count differed significantly across the four sites when sorted from the lowest to the highest tissue eosinophilic count (Friedman's test; p < 0.001), with significant differences between each rank (Wilcoxon signed-rank test; all p < 0.001). The median tissue eosinophilic counts across the four different sites, when sorted from the lowest to the highest rank, were 7, 27, 52, and 161 eosinophils. Only 14 of 30 subjects had more or fewer than 10 eosinophils across all sites.</p><p><strong>Conclusion: </strong>The distribution of eosinophils may differ substantially across the paranasal sinuses. Investigation of a single nasal polyp may not reflect the total inflammatory load.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837489","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}
Maayan S Kahan, Hoang C B Nguyen, Pallavi Madhusudanan, Margaret B Mitchell, Di Huang, Benjamin S Bleier, Mansoor M Amiji, Alan D Workman
{"title":"Inflammatory Effects of Microplastics and Nanoplastics on Nasal Airway Epithelial Cells.","authors":"Maayan S Kahan, Hoang C B Nguyen, Pallavi Madhusudanan, Margaret B Mitchell, Di Huang, Benjamin S Bleier, Mansoor M Amiji, Alan D Workman","doi":"10.1002/alr.70086","DOIUrl":"10.1002/alr.70086","url":null,"abstract":"<p><strong>Background: </strong>Microplastics and nanoplastics (MNPs) have emerged as ubiquitous environmental contaminants; these particles have been detected in mucus and irrigation fluids, and at greater concentrations in patients with sinusitis and allergic rhinitis. Emerging evidence at other mucosal surfaces, including the gut and lung, suggests that MNPs exacerbate epithelial barrier dysfunction and induce inflammatory responses. Despite their relevance, the impact of inhaled plastics on the nasal epithelium, the initial point of contact for airborne plastics, remains underexplored.</p><p><strong>Methods: </strong>Submerged RPMI 2650 nasal epithelial cultures and air-liquid interface (ALI) cultures of primary human nasal epithelial cells were dosed with polystyrene (PS) MNPs, with a focus on the effects of 100 nm nanoplastics and surface charge alterations. Analyses of secreted cytokines, transcriptomic changes, epithelial integrity, and histologic appearance were performed.</p><p><strong>Results: </strong>Note that 100 nm PS nanoplastics caused transcriptomic inflammatory and oxidative stress pathway activation in RMPI 2650 submerged cultures, with conserved inflammatory gene signatures in the ALI exposure model as well. Dose-dependent elevations in IL-8 and TNFα were observed after ALI exposure to 1 µm PS microplastics, and 100 nm PS nanoplastics elicited early elevations in IL-6, IL-8, and TNF, with more pronounced effects from amine-modified particles, while no cytotoxicity, barrier disruption, or type-2 alarmin induction was observed. Scanning electron microscopy revealed ciliary disruption and particle adherence.</p><p><strong>Conclusions: </strong>PS MNPs cause inflammatory cytokine responses in nasal epithelial cells over even a short timeframe, in addition to ciliary blunting and transcriptional evidence of significant inflammation and stress response. This sinonasal model can help answer critical questions about the pathogenicity of plastic exposures.</p>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":"467-476"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793511","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}
Jens Tidemandsen, Vibeke Backer, Howraman Meteran, Peter G Gibson
{"title":"Response to the Letter to the Editor by Pirola and Hopkins Regarding \"The Global Airways in Practice: Long-Term Effects of Mepolizumab with or without FESS on Type 2 Inflammation in Patients with CRSwNP\".","authors":"Jens Tidemandsen, Vibeke Backer, Howraman Meteran, Peter G Gibson","doi":"10.1002/alr.70159","DOIUrl":"10.1002/alr.70159","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":"530-531"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608744","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}
{"title":"Enhancing Operative Documentation in Rhinology: Surgical Navigation as a Practical Adjunct.","authors":"Daniel B Spielman","doi":"10.1002/alr.70150","DOIUrl":"10.1002/alr.70150","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":"441-442"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503833","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}
Alexandria L Irace, Isha Thapar, John V Bosso, Jennifer E Douglas
{"title":"Efficacy and Safety of a Three-Step Aspirin Challenge Protocol for Diagnosis of Aspirin-Exacerbated Respiratory Disease in a Monitored Clinic Setting.","authors":"Alexandria L Irace, Isha Thapar, John V Bosso, Jennifer E Douglas","doi":"10.1002/alr.70137","DOIUrl":"10.1002/alr.70137","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":"495-497"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503836","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}
Mishek Thapa, Missael Vasquez, Kyohei Itamura, Arthur W Wu, Christopher Roxbury, Dennis M Tang
{"title":"Trends in Olfaction and Sexual Activity: A National Health and Nutrition Examination Survey (NHANES) Database Study.","authors":"Mishek Thapa, Missael Vasquez, Kyohei Itamura, Arthur W Wu, Christopher Roxbury, Dennis M Tang","doi":"10.1002/alr.70143","DOIUrl":"10.1002/alr.70143","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":"498-501"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511825","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}
{"title":"Appropriate Medical Therapy and Selective Modulation of Inflammatory Endotypes in Chronic Rhinosinusitis.","authors":"Sushma Narsing Katkuri, Varshini Vadhithala, Sachin Kumar, Sushma Verma, Jeffrin Reneus Paul","doi":"10.1002/alr.70153","DOIUrl":"10.1002/alr.70153","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":"518-519"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511788","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}
Daniel Xiao, Martin J Citardi, William C Yao, Amber U Luong
{"title":"Response to \"Probabilistic Sensitivity and Net Benefit Reporting in the Cost-Utility Comparison of EDS-Fluticasone Versus Budesonide Irrigation for Postoperative CRSwNP \".","authors":"Daniel Xiao, Martin J Citardi, William C Yao, Amber U Luong","doi":"10.1002/alr.70155","DOIUrl":"10.1002/alr.70155","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":" ","pages":"532-533"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623024","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}