{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:33:15Z","timestamp":1793298795430,"version":"4.5.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["AGBORE20QI0"],"award-info":[{"award-number":["AGBORE20QI0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Distinguished Scholar Program"},{"name":"National Heart, Lung, and Blood Institute Division of Intramural Research"},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["AGBORE20QI0"],"award-info":[{"award-number":["AGBORE20QI0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Distinguished Scholar Program"},{"DOI":"10.13039\/100000897","name":"National Heart, Lung, and Blood Institute Division of Intramural Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The association of acute cellular rejection (ACR) with chronic lung allograft dysfunction (CLAD) in lung transplant recipients has primarily been described before consensus recommendations incorporating restrictive phenotypes. Furthermore, the association of the degree of molecular allograft injury during ACR with CLAD or death remains undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the association of ACR with the risk of CLAD or death and to further investigate if this risk depends on the degree of molecular allograft injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter, prospective cohort study included 188 lung transplant recipients. Subjects underwent serial plasma collections for donor-derived cell-free DNA (dd-cfDNA) at prespecified time points and bronchoscopy. Multivariable Cox proportional-hazards analysis was conducted to analyze the association of ACR with subsequent CLAD or death as well as the association of dd-cfDNA during ACR with risk of CLAD or death. Additional outcomes analyses were performed with episodes of ACR categorized as \u201chigh risk\u201d (dd-cfDNA\u2009\u2265\u20091%) and \u201clow risk\u201d (dd-cfDNA\u2009&amp;lt;\u20091%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In multivariable analysis, ACR was associated with the composite outcome of CLAD or death (hazard ratio [HR], 2.07 [95% confidence interval (CI), 1.05\u20134.10]; P\u2009=\u20090.036). Elevated dd-cfDNA\u2009\u2265\u20091% at ACR diagnosis was independently associated with increased risk of CLAD or death (HR, 3.32; 95% CI, 1.31\u20138.40; P\u2009=\u20090.012). Patients with high-risk ACR were at increased risk of CLAD or death (HR, 3.13; 95% CI, 1.41\u20136.93; P\u2009=\u20090.005), whereas patients with low\u2013risk status ACR were not.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with ACR are at higher risk of CLAD or death, but this may depend on the degree of underlying allograft injury at the molecular level.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 02423070).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202305-0798oc","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T16:54:55Z","timestamp":1704732895000},"page":"1238-1245","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":32,"title":["Higher Molecular Injury at Diagnosis of Acute Cellular Rejection Increases the Risk of Lung Allograft Failure: A Clinical Trial"],"prefix":"10.1093","volume":"209","author":[{"given":"Michael B.","family":"Keller","sequence":"first","affiliation":[{"name":"Genomic Research Alliance for Transplantation, Bethesda, Maryland"},{"name":"Laboratory of Applied Precision Omics and"},{"name":"Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tian","sequence":"additional","affiliation":[{"name":"Office of Biostatistics Research, NHLBI, NIH, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon Kyoo","family":"Jang","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation, Bethesda, Maryland"},{"name":"Laboratory of Applied Precision Omics 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New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyesik","family":"Kong","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation, Bethesda, Maryland"},{"name":"Laboratory of Applied Precision Omics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana L.","family":"Ponor","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shambhu","family":"Aryal","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation, Bethesda, Maryland"},{"name":"Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Fairfax, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Orens","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation, 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