{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:07:46Z","timestamp":1789186066404,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"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":["Allergy"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Longer asthma duration predicts non\u2010remission in Type\u20102 (T2) biologic\u2010treated severe asthma, but underlying mechanisms remain unclear. We investigated associations between asthma duration and inflammatory biomarkers that may explain differential biologic response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed cross\u2010sectional data from adults with severe asthma in U\u2010BIOPRED. Asthma duration was defined as years from diagnosis to study entry. T2 and non\u2010T2 biomarkers were measured in blood and sputum. Identical assays were performed in PRISM, a validation cohort of biologic\u2010initiators. Multivariable regression models adjusted for age, sex, ethnicity, BMI, smoking and oral corticosteroid dose. Associations between duration\u2010related biomarkers and 12\u2010month biologic remission were explored in PRISM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In U\u2010BIOPRED (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009411), median asthma duration was 23\u2009years (IQR 12\u201338). Longer duration was associated with higher non\u2010T2 biomarkers including sputum CXCL9 (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.024, 95% CI 0.011\u20130.038), sputum IL\u20106 (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.024, 95% CI 0.011\u20130.037) and sputum neutrophils (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.009, 95% CI 0.001\u20130.017), but lower T2 biomarkers including plasma periostin (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.006, 95% CI \u22120.009 to \u22120.003), eosinophils (blood:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.002, 95% CI \u22120.003 to \u22120.001; sputum:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.023, 95% CI \u22120.035 to \u22120.011), sputum EDN (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.032, 95% CI \u22120.049 to \u22120.014) and FeNO (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.006, 95% CI \u22120.010 to \u22120.001). PRISM (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009474) confirmed these associations. Higher sputum CXCL9 was associated with reduced remission in anti\u2010IL\u20104R\u03b1\u2010treated patients with asthma duration \u2265\u200920\u2009years (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22121.73, 95% CI \u22123.180 to \u22120.276).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Longer asthma duration was associated with elevated airway non\u2010T2 inflammation and reduced systemic and airway T2 inflammation. This highlights the importance of airway biomarker sampling and suggests combined T2 and non\u2010T2 therapeutic strategies may be needed to achieve remission in long\u2010standing asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT05164939\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70436","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:07:08Z","timestamp":1783598828000},"page":"3286-3299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Longer Asthma Duration Is Associated With Elevated Non\u2010\n                    <scp>T2<\/scp>\n                    Sputum Biomarkers and Reduced\n                    <scp>T2<\/scp>\n                    Inflammation in Severe Asthma"],"prefix":"10.1111","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2858-1559","authenticated-orcid":false,"given":"Freda","family":"Yang","sequence":"first","affiliation":[{"name":"National Heart &amp; Lung Institute, Imperial College London  London UK"},{"name":"Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0111-5048","authenticated-orcid":false,"given":"Sujin","family":"Seo","sequence":"additional","affiliation":[{"name":"Institute of Health and Environment, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-4942","authenticated-orcid":false,"given":"Takehiro","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Sysmex R&amp;D Center Europe GmbH  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-7602","authenticated-orcid":false,"given":"Chloe I.","family":"Bloom","sequence":"additional","affiliation":[{"name":"National Heart &amp; Lung Institute, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-3861","authenticated-orcid":false,"given":"Nazanin","family":"Zounemat\u2010Kermani","sequence":"additional","affiliation":[{"name":"National Heart &amp; Lung Institute, Imperial College London  London UK"},{"name":"Data Science Institute, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3511-756X","authenticated-orcid":false,"given":"Pankaj K.","family":"Bhavsar","sequence":"additional","affiliation":[{"name":"National Heart &amp; Lung Institute, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3417-1003","authenticated-orcid":false,"given":"Katie","family":"Raby","sequence":"additional","affiliation":[{"name":"National Heart &amp; Lung Institute, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-8843","authenticated-orcid":false,"given":"Ian M.","family":"Adcock","sequence":"additional","affiliation":[{"name":"National Heart &amp; Lung Institute, Imperial College London  London UK"},{"name":"Data Science Institute, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-5089","authenticated-orcid":false,"given":"Sungho","family":"Won","sequence":"additional","affiliation":[{"name":"Institute of Health and Environment, Seoul National University  Seoul Republic of Korea"},{"name":"Department of Public Health Sciences Graduate School of Public Health, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-0640","authenticated-orcid":false,"given":"Tae\u2010Bum","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology Asan Medical Center, University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-1426","authenticated-orcid":false,"given":"Kian 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