{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:00:50Z","timestamp":1775142050201,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Chronic lung allograft dysfunction (CLAD) remains the principal limitation to long-term survival after lung transplantation (LT). Early molecular alterations within the graft may precede clinically overt functional decline, but their biological significance remains incompletely defined. In this single-center exploratory pilot study, 16 bilateral lung transplant recipients underwent bronchoalveolar lavage (BAL) sampling at 7 days, 15 days, and 3 months post-transplantation. BAL-derived microRNA (miRNA) profiles were analyzed longitudinally and correlated with long-term clinical outcomes, including CLAD development and phenotypic classification into bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS), over extended follow-up (mean 98 months). Distinct early miRNA signatures were detectable within the first weeks after transplantation and were associated with divergent long-term clinical trajectories. Specific miRNAs, namely let-7e-5p and miR-30d-3p, were associated with subsequent CLAD, whereas differential expression patterns distinguished trajectories toward BOS or RAS. Enrichment analyses highlighted networks related to innate immune activation, hypoxia, tissue remodeling, and PI3K\u2013mTOR signaling. Notably, the occurrence of acute rejection did not differ significantly between patients who developed CLAD and those who remained stable. These findings, although preliminary, suggest that early BAL-derived miRNA profiles may reflect biologically distinct graft states associated with long-term CLAD phenotypes.<\/jats:p>","DOI":"10.3390\/cells15070611","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:03Z","timestamp":1774878063000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early BAL microRNA Signatures Delineate Biological Trajectories Towards CLAD After Lung Transplantation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3010-3268","authenticated-orcid":false,"given":"Gabriella","family":"Gaudioso","sequence":"first","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Franzi","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery and Lung Transplantation, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-1598","authenticated-orcid":false,"given":"Riccardo","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery and Lung Transplantation, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rosaria De","family":"Filippo","sequence":"additional","affiliation":[{"name":"Laboratory of OMIC Science, Scientific Direction, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4955-3346","authenticated-orcid":false,"given":"Andrea","family":"Terrasi","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra Maria","family":"Storaci","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4444-5052","authenticated-orcid":false,"given":"Nadia","family":"Mansour","sequence":"additional","affiliation":[{"name":"Laboratory of OMIC Science, Scientific Direction, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Digiuni","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9876-171X","authenticated-orcid":false,"given":"Daniele","family":"Marchelli","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-0345","authenticated-orcid":false,"given":"Luca Vittorio Carlo","family":"Valenti","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"},{"name":"Precision Medicine Lab, Biological Resource Centre, Transfusion Medicine, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia De","family":"Turris","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5563-659X","authenticated-orcid":false,"given":"Frederik","family":"von Herz","sequence":"additional","affiliation":[{"name":"Laboratory of OMIC Science, Scientific Direction, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Garulli","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery and Lung Transplantation, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8571-121X","authenticated-orcid":false,"given":"Mario","family":"Nosotti","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery and Lung Transplantation, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Letizia Corinna","family":"Morlacchi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"},{"name":"Respiratory and Cystic Fibrosis Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2285-9970","authenticated-orcid":false,"given":"Francesco","family":"Blasi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"},{"name":"Respiratory and Cystic Fibrosis Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4510-5167","authenticated-orcid":false,"given":"Alessandro","family":"Palleschi","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery and Lung Transplantation, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4416-6216","authenticated-orcid":false,"given":"Valentina","family":"Vaira","sequence":"additional","affiliation":[{"name":"Laboratory of OMIC Science, Scientific Direction, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1600-6143.2012.04313.x","article-title":"MicroRNAs as biomarkers in solid organ transplantation","volume":"13","author":"Mas","year":"2013","journal-title":"Am. 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