{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:17:42Z","timestamp":1788452262701,"version":"build-2803163510"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Platelet activation is elevated in chronic obstructive pulmonary disease (COPD) and associated with self-reported respiratory symptoms. Observational studies link the antiplatelet drug aspirin to lower exacerbation rates and fewer symptoms. However, it is unknown if platelet activation predicts incident respiratory exacerbations or mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Is systemic platelet activation prospectively associated with respiratory exacerbations and mortality among ever-smokers with or at risk for COPD?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured two systemic platelet activation biomarkers, urinary 11-dehydro-thromboxane B2 (11dTxB2) and plasma soluble CD40 ligand (sCD40L), at baseline in self-reported aspirin non-users in the longitudinal SPIROMICS cohort. Adjusted generalized negative binomial and linear mixed-effects models assessed associations between these biomarkers and prospective rates of total and severe exacerbations, plus cross-sectional and longitudinal respiratory health (St. George\u2019s Respiratory Questionnaire, COPD Assessment Test, modified Medical Research Council questionnaire, and six minute walk distance). Cox proportional hazard and competing risk models evaluated associations between platelet activation biomarkers and all-cause and cause-specific mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 2,711 participants, 1,572 (58.0%) reported aspirin non-use; of these, 1,433 and 1,437 had 11dTxB2 and sCD40L measured, respectively. Over a median 6.6 years, a two-fold higher baseline 11dTxB2 was associated with increased rates of total (8.8%; 95%CI: 0.4-17.8%) and severe (18.1%; 95%CI: 5.1-32.6%) exacerbations. Although there were no significant interactions, there was a trend toward higher severe exacerbation rates among current cigarettes smokers and those with COPD. There were no significant results for sCD40L. Among aspirin non-users, higher 11dTxB2, but not sCD40L, was associated with worse cross-sectional respiratory health and modestly increased all-cause mortality over a median 8.2 years (adjusted hazard ratio 1.11; 95%CI: 1.00-1.24). After covariate adjustment, there were no associations with longitudinal respiratory health or cause-specific mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Systemic platelet activation, measured by urinary 11dTxB2, is a statistically significant but modest predictor of respiratory exacerbations and all-cause mortality in individuals with or at risk for COPD, suggesting its potential utility as a prognostic and predictive biomarker for antiplatelet therapy trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>NCT 01969344<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/annalsats\/aaoag246","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:34:47Z","timestamp":1788449687000},"source":"Crossref","is-referenced-by-count":0,"title":["Systemic Platelet Activation and Respiratory Exacerbations, Pulmonary Symptoms, and Mortality among Current and Former Smokers in SPIROMICS"],"prefix":"10.1093","author":[{"given":"Ashraf","family":"Fawzy","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine Division of Pulmonary and Critical Care Medicine, , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia N","family":"Hansel","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Division of Pulmonary and Critical Care Medicine, , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirupama","family":"Putcha","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Division of Pulmonary and Critical Care Medicine, , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Division of Pulmonary and Critical Care Medicine, , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L","family":"Curtis","sequence":"additional","affiliation":[{"name":"University of Michigan Division of Pulmonary and Critical Care Medicine, , Ann Arbor, MI"},{"name":"VA Ann Arbor Healthcare System Medical Service, , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wassim W","family":"Labaki","sequence":"additional","affiliation":[{"name":"University of Michigan Division of Pulmonary and Critical Care Medicine, , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"O\u2019Neal","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill Division of Pulmonary Diseases and Critical Care Medicine, , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J","family":"Martinez","sequence":"additional","affiliation":[{"name":"University of Massachusetts Division of Pulmonary Medicine, , Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Robert","family":"Paine","sequence":"additional","affiliation":[{"name":"University of Utah School of Medicine Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, , Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vickram","family":"Tejwani","sequence":"additional","affiliation":[{"name":"Integrated Hospital Care Institute, Cleveland Clinic Department of Pulmonary Medicine, , Cleveland, OH"},{"name":"Cleveland Clinic Department of Genome Sciences and Systems Biology, Lerner Research, , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Michael","family":"Wells","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham Division of Pulmonary, Allergy, and Critical Care Medicine, , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prescott","family":"Woodruff","sequence":"additional","affiliation":[{"name":"University of California Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, , San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Graham","family":"Barr","sequence":"additional","affiliation":[{"name":"Columbia University Department of Medicine, , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie L","family":"Pistenmaa","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,3]]},"container-title":["Annals of the American Thoracic 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