{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:47:12Z","timestamp":1787312832722,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["219718"],"award-info":[{"award-number":["219718"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease often associated with asthma. The global airway hypothesis suggests bidirectional inflammatory interactions between upper and lower airways. Mepolizumab, an anti\u2013IL\u20105 therapy, treats conditions systemically, while functional endoscopic sinus surgery (FESS) primarily addresses sinonasal disease and can improve asthma control. The combined effect on airway outcomes remains unclear. This study evaluated the global airway hypothesis with objective measures and targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the impact of mepolizumab, with or without FESS, on airway inflammation, lung function, and symptom burden in severe CRSwNP with or without asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this RCT, 58 patients received either mepolizumab alone or combined with FESS. Inflammation and symptom outcomes were analyzed in blood, nose, and bronchi at baseline, six, and 12 months. Patients were stratified by baseline inflammatory subgroup.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both groups showed improvements in FEV1% (MepoFESS: +3.4%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.010; Mepo Only: +3.5%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.015), FVC% (MepoFESS: +3.7%,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001; Mepo Only: +2.9%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.009), inflammation markers (FeNO, blood eosinophils, nasal polyp eosinophils), and all patient\u2010reported outcomes. MepoFESS produced greater gains in nasal polyp score, nasal congestion, and overall symptom burden. Lung function and systemic inflammation improved similarly in both groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Mepolizumab improves upper and lower airway outcomes in CRSwNP. FESS adds localized benefits in sinonasal symptom control without further impact on lower airway inflammation. Findings support a comprehensive approach targeting systemic and local type 2 inflammation in global airway disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alr.70073","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:06:09Z","timestamp":1765803969000},"page":"369-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Global Airways in Practice: Long\u2010term Effects of Mepolizumab With or Without FESS on Type 2 Inflammation in Patients With CRSwNP"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6924-1218","authenticated-orcid":false,"given":"Jens","family":"Tidemandsen","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery and Audiology Copenhagen University Hospital  \u00a0 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vibeke","family":"Backer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery and Audiology Copenhagen University Hospital  \u00a0 Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9716-6501","authenticated-orcid":false,"given":"Anne Sophie","family":"Hom\u00f8e","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery and Audiology Copenhagen University Hospital  \u00a0 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H. L.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Pathology Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper","family":"Aan\u00e6s","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery and Audiology Copenhagen University Hospital  \u00a0 Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howraman","family":"Meteran","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Copenhagen University Hospital Hvidovre  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Hostrup","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Physiology Group The August Krogh Section for Human and Molecular Physiology Department of Nutrition Exercise and Sports University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-322X","authenticated-orcid":false,"given":"Lukas","family":"Moesgaard","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Physiology Group The August Krogh Section for Human and Molecular Physiology Department of Nutrition Exercise and Sports University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Haase","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery and Audiology Copenhagen University Hospital  \u00a0 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Gibson","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health The University of Newcastle  New Lambton New South Wales Australia"},{"name":"Department of Respiratory &amp; Sleep Medicine Hunter Medical Research Institute John Hunter Hospital  New Lambton New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.05.009"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/coa.12189"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.05.032"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127228"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.09.063"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.05.011"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2024.06.033"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.03.003"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.23562"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00034805"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00080312"},{"issue":"1","key":"e_1_2_15_13_1","first-page":"39","article-title":"Endoscopic Sinus Surgery in Adult Patients With Chronic Rhinosinusitis With Nasal Polyps (PolypESS): Study Protocol for a Randomised Controlled Trial","volume":"18","author":"Lourijsen E. S.","year":"2017","journal-title":"Curr Control Trials Cardiovasc Med"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202109-2093ST"},{"issue":"2","key":"e_1_2_15_15_1","first-page":"A4235","article-title":"The Sino\u2010Nasal Outcome Test 22 Validated for Danish Patients","volume":"58","author":"Lange B.","year":"2011","journal-title":"Danish Medical Bulletin"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.1999.14d29.x"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.4193\/Rhino15.072"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2005.08.012"},{"issue":"2","key":"e_1_2_15_19_1","first-page":"144","article-title":"The Relationship Between Subjective Assessment Instruments in Chronic Rhinosinusitis","volume":"45","author":"Lim M.","year":"2007","journal-title":"Rhinology"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13223-017-0196-7"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60988-X"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1403290"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/17534666211009398"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00097-7"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.07.056"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808991"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000730"}],"container-title":["International Forum of Allergy &amp; Rhinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.70073","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alr.70073","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.70073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T12:56:25Z","timestamp":1775220985000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/alr.70073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,15]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/alr.70073"],"URL":"https:\/\/doi.org\/10.1002\/alr.70073","archive":["Portico"],"relation":{},"ISSN":["2042-6976","2042-6984"],"issn-type":[{"value":"2042-6976","type":"print"},{"value":"2042-6984","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,15]]},"assertion":[{"value":"2025-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}