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Extracellular vesicle-enriched microRNAs (EV-miRNAs) may represent reliable markers of early lung injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Evaluate associations of plasma EV-miRNAs with lung function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The prospective NAS (Normative Aging Study) collected plasma EV-miRNA measurements from 1996\u20132015 and spirometry every 3\u20135 years through 2019. Associations of EV-miRNAs with baseline lung function were modeled using linear regression. To complement the individual miRNA approach, unsupervised machine learning was used to identify clusters of participants with distinct EV-miRNA profiles. Associations of EV-miRNA profiles with multivariate latent longitudinal lung function trajectories were modeled using log binomial regression. Biological functions of significant EV-miRNAs were explored using pathway analyses. Results were replicated in an independent sample of NAS participants and in the HEALS (Health Effects of Arsenic Longitudinal Study).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In the main cohort of 656 participants, 51 plasma EV-miRNAs were associated with baseline lung function (false discovery rate-adjusted P value\u2009&amp;lt;\u20090.05), 28 of which were replicated in the independent NAS sample and\/or in the HEALS cohort. A subset of participants with distinct EV-miRNA expression patterns had increased risk of declining lung function over time, which was replicated in the independent NAS sample. Significant EV-miRNAs were shown in pathway analyses to target biological pathways that regulate respiratory cellular immunity, the lung inflammatory response, and airway structural integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Plasma EV-miRNAs may represent a robust biomarker of subclinical lung injury and may facilitate early identification and treatment of patients at risk of developing overt lung disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202109-2208oc","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T09:50:27Z","timestamp":1660038627000},"page":"50-59","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":36,"title":["Extracellular Vesicle-Encapsulated microRNAs as Novel Biomarkers of Lung Health"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-926X","authenticated-orcid":false,"given":"Christina M.","family":"Eckhardt","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Irving Medical Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Gambazza","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi di Milano, Milan, Italy"},{"name":"Healthcare Professions Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa R.","family":"Bloomquist","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"De Hoff","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Vuppala","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantel S.","family":"Vokonas","sequence":"additional","affiliation":[{"name":"Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Boston, Massachusetts"},{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto A.","family":"Litonjua","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Rochester Medical Center, Rochester, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sparrow","sequence":"additional","affiliation":[{"name":"Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Boston, Massachusetts"},{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faruque","family":"Parvez","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise C.","family":"Laurent","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. 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