Fabio S. Ryser, Tina Mauthe, Catrin Brühlmann, Michael B. Soyka, Urs C. Steiner
{"title":"Improvement of Mixed Inflammatory Environment in Nasal Secretions of Diffuse Type 2 Chronic Rhinosinusitis With Nasal Polyps Under Dupilumab","authors":"Fabio S. Ryser, Tina Mauthe, Catrin Brühlmann, Michael B. Soyka, Urs C. Steiner","doi":"10.1002/clt2.70180","DOIUrl":"10.1002/clt2.70180","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In Western countries, Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is predominantly associated with a type 2 inflammatory endotype. While nasal secretion analysis shows promise for disease endotyping, current biomarkers remain limited for accurate stratification, disease monitoring, and prediction of treatment response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate the inflammatory patterns in nasal secretions of patients with type 2 Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) undergoing treatment with dupilumab, an anti-IL4Rα antibody. A second objective was to evaluate markers for therapy response and monitoring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nasal secretions and blood samples were collected at four time points from 23 patients with histological type 2 CRSwNP undergoing dupilumab treatment and compared with 10 healthy controls. Samples were analysed using proximity extension assay method by Olink.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Proteomic analysis of nasal secretions revealed 50 differentially expressed proteins in type 2 CRSwNP compared to healthy controls. Nasal secretions of most patients revealed a mixed inflammatory endotype. Under dupilumab treatment, cytokines of all different endotypes decreased. The cytokines with the highest mean change (MCP-4, CCL23, GDNF and CCL11) showed good associations with clinical variables and were effective predictors of dupilumab response and disease control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The inflammatory environment of the nasal mucosa in histological type 2 CRSwNP is most often characterized by a mixed type 1, 2, and 3 inflammatory endotype. Targeting type 2 inflammation with dupilumab reduces inflammation markers of all three types of inflammation. GDNF has emerged as a valuable marker for stratifying therapy and monitoring success in type 2 CRSwNP under dupilumab treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 6","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Programmed Cell Death in Chronic Rhinosinusitis","authors":"Xingchen Liu, Junying Hu, Weigang Gan, Qi Wu, Bing Zhong, Feng Liu","doi":"10.1002/clt2.70175","DOIUrl":"10.1002/clt2.70175","url":null,"abstract":"<p>Chronic rhinosinusitis (CRS) is a prevalent upper respiratory condition characterized by a multifaceted etiology involving various cellular and molecular processes. In recent years, researchers have increasingly recognized the significance of different forms of programmed cell death (PCD), such as apoptosis and pyroptosis, in the pathological mechanisms underlying CRS. Studies suggest that these PCD pathways not only influence the disease's progression but may also serve as novel therapeutic targets. Thus, gaining a thorough understanding of how PCD contributes to CRS is crucial for elucidating its pathogenesis and developing new treatment strategies. This article aims to investigate the mechanisms of PCD in CRS, examining its effects on disease progression and potential implications for treatment. We will begin by discussing the background of CRS and its underlying processes, followed by an exploration of the roles played by various types of PCD in CRS, and conclude with a discussion on future research directions and their practical applications.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 6","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deniz Göcebe, Hannah Nürnberg, Alexander Enk, Elham Khatamzas, Knut Schäkel
{"title":"Performance of PEN-FAST and CEPH-FAST for Cephalosporin Allergy Delabeling.","authors":"Deniz Göcebe, Hannah Nürnberg, Alexander Enk, Elham Khatamzas, Knut Schäkel","doi":"10.1002/clt2.70178","DOIUrl":"10.1002/clt2.70178","url":null,"abstract":"<p><strong>Background: </strong>Unverified antibiotic allergy labels lead to suboptimal antimicrobial prescribing and increased antibiotic resistance. Cephalosporins are among the most frequently administered antibiotics and cephalosporin allergy labels increasingly limit optimal therapy. Clinical decision rules that enable delabeling of low-risk patients by non-allergists are emerging as important tools. The PEN-FAST score is a validated rule for identifying low-risk penicillin allergy labels suitable for direct drug challenge. CEPH-FAST is a recently proposed adaptation for cephalosporin allergy. We evaluated the diagnostic performance of PEN-FAST and CEPH-FAST for cephalosporin allergy.</p><p><strong>Methods: </strong>In this single-center retrospective cohort study, 100 adults with reported cephalosporin allergy labels underwent allergy assessment including skin testing and drug provocation testing at a tertiary allergy clinic in Heidelberg, Germany. Logistic regression was used to identify predictors of confirmed allergy. Diagnostic performance of PEN-FAST and CEPH-FAST scores was assessed using sensitivity, specificity, predictive values, and area under the receiver operating curve (AU-ROC).</p><p><strong>Results: </strong>Cephalosporin allergy was confirmed in 48 of 100 patients. PEN-FAST categorized 20 patients at low risk, of whom one had a positive skin test (NPV 95.0%, sensitivity 97.9%, AU-ROC 0.769). CEPH-FAST classified 42 patients low-risk, but 12 had confirmed allergies (NPV 71.4%, sensitivity 75.0%, AU-ROC 0.667). Higher PEN-FAST and CEPH-FAST scores were significantly associated with confirmed allergy.</p><p><strong>Conclusion: </strong>PEN-FAST demonstrated high sensitivity and negative predictive value for identifying low-risk cephalosporin allergy and may support safe delabeling strategies. In contrast, CEPH-FAST showed reduced diagnostic performance in this cohort, highlighting the need for further validation before routine clinical implementation.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 6","pages":"e70178"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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