{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:38Z","timestamp":1787013998091,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non\u2010steroidal anti\u2010inflammatory drug\u2010exacerbated respiratory disease (N\u2010ERD) is characterised by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells and mediators causing acute symptoms when driving the hypersensitivity reaction to acetylsalicylic acid (ASA) ingestion, remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To investigate the dynamics of nasal mediators during ASA provocation in N\u2010ERD patients before and 24\u2009weeks after therapy with the IL\u20104 receptor alpha\u2010blocking antibody dupilumab (EudraCT (2019\u2010004889\u201018) and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      (NCT04442256)).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Nasal mucosal lining fluids of patients with N\u2010ERD, chronic rhinosinusitis patients with nasal polyp (CRSwNP) and healthy disease controls were collected at selected time points up to 2\u2009h after ASA provocation. Analysis of thirty\u2010three different inflammatory mediators as well as transcriptomic profiling was performed. In N\u2010ERD patients, provocation was repeated after 24\u2009weeks of dupilumab therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixty minutes after provocation with ASA, N\u2010ERD patients showed a significant increase in type 2 associated cytokines (i.e., TSLP, IL\u20105 and eotaxin\u20103) as compared to the other patient groups. This effect was diminished after 24\u2009weeks of dupilumab therapy and was independent of the development of ASA tolerance. Transcriptomics revealed dampened upregulation of type 2 associated pathway genes (i.e.,\n                      <jats:italic>AREG<\/jats:italic>\n                      ) as well as enhanced downregulation of lipid (i.e.,\n                      <jats:italic>ALOX15<\/jats:italic>\n                      ) and peroxisome metabolisms (i.e.,\n                      <jats:italic>NOS2<\/jats:italic>\n                      ) at ASA provocation after dupilumab therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Clinical Relevance<\/jats:title>\n                    <jats:p>Treatment with dupilumab leads to reduced nasal type 2 cytokine secretion and distinct changes in transcriptomic profile during ASA provocation, but changes in type 2 mediators show no association with tolerance development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      EudraCT (2019\u2010004889\u201018) and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      (NCT04442256)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cea.70184","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:44:38Z","timestamp":1764290678000},"page":"227-242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dupilumab Dampens Mucosal Type 2 Response During Acetylsalicylic Acid Challenge in N\u2010ERD 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