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However, this is challenging in practice as repeated spirometry measurements from childhood are rarely available. We investigated potential blood biomarkers associated with pre\u2010COPD trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The Tasmanian Longitudinal Health Study has unique lung function data from 7 to 53\u2009years, from which lifetime FEV\n                      <jats:sub>1<\/jats:sub>\n                      \/FVC trajectories were modelled (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092442). Serum levels of CC16, sRAGE, CRP, ECP, SPD, fibrinogen and a range of cytokines were quantified at 53\u2009years of age. These were related to respective FEV\n                      <jats:sub>1<\/jats:sub>\n                      \/FVC trajectories. Classification And Regression Tree (CART) analysis was used to investigate biomarker combinations in relation to the distribution of pre\u2010COPD FEV\n                      <jats:sub>1<\/jats:sub>\n                      \/FVC trajectories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among six FEV\n                      <jats:sub>1<\/jats:sub>\n                      \/FVC trajectories, three trajectories at increased risk of COPD (pre\u2010COPD trajectories) were \u2018Early Low\u2010Rapid Decline\u2019, \u2018Early Normal\u2010Rapid Decline\u2019 and \u2018Early Low\u2010Normal Decline\u2019. CC16, sRAGE, SPD, IL\u201017A, IL\u20105 and IL\u201010 differed significantly between these three pre\u2010COPD and the normal trajectory. Notably, within the pre\u2010COPD trajectories, these biomarkers also differentiated two rapid decline trajectories from the relatively stable one. CART analysis identified different combinations of biomarkers that distinguish different pre\u2010COPD trajectories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first study to show that established COPD biomarkers are already active during the pre\u2010COPD phase and could distinguish pre\u2010COPD lung function trajectories. Biomarkers, particularly together with clinical history, may have the potential to identify those at risk and optimise management of both Pre\u2010COPD and COPD.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/resp70279-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/resp.70279","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T23:12:06Z","timestamp":1783984326000},"page":"993-1002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biomarkers of Pre\u2010\n                    <scp>COPD<\/scp>\n                    Lung Function Trajectories in Middle Age: A Prospective Study From 1st to 6th Decade"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4388-784X","authenticated-orcid":false,"given":"Dinh S.","family":"Bui","sequence":"first","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Vicendese","sequence":"additional","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Pham","sequence":"additional","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7079-3670","authenticated-orcid":false,"given":"Nur Sabrina","family":"Idrose","sequence":"additional","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Lowe","sequence":"additional","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Lodge","sequence":"additional","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raisa","family":"Cassim","sequence":"additional","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamara","family":"Senaratna","sequence":"additional","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayan","family":"Bowatte","sequence":"additional","affiliation":[{"name":"Allergy and Lung Health Unit, School of Population and Global Health The University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garun","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Lung, Sleep, Allergy &amp; 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