{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:46:07Z","timestamp":1792856767448,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"E-RARE project, JRC 2011 IPF-AE","award":["DLR 01GM1210A"],"award-info":[{"award-number":["DLR 01GM1210A"]}]},{"name":"KFO311"},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["UH3HL 123886"],"award-info":[{"award-number":["UH3HL 123886"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["RO1 HL 127349"],"award-info":[{"award-number":["RO1 HL 127349"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a variable and unpredictable course.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether BAL cell gene expression is predictive of survival in IPF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study analyzed the BAL transcriptome of three independent IPF cohorts: Freiburg (Germany), Siena (Italy), and Leuven (Belgium) including 212 patients. BAL cells from 20 healthy volunteers, 26 patients with sarcoidosis stage III and IV, and 29 patients with chronic obstructive pulmonary disease were used as control subjects. Survival analysis was performed by Cox models and component-wise boosting. Presence of airway basal cells was tested by immunohistochemistry and flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A total of 1,582 genes were predictive of mortality in the IPF derivation cohort in univariate analyses adjusted for age and sex at false discovery rate less than 0.05. A nine-gene signature, derived from the discovery cohort (Freiburg), performed well in both replication cohorts, Siena (P\u2009&amp;lt;\u20090.0032) and Leuven (P\u2009=\u20090.0033). nCounter expression analysis confirmed the array results (P\u2009&amp;lt;\u20090.0001). The genes associated with mortality in BAL cells were significantly enriched for genes expressed in airway basal cells. Further analyses by gene expression, flow cytometry, and immunohistochemistry showed an increase in airway basal cells in BAL and tissues of IPF compared with control subjects, but not in chronic obstructive pulmonary disease or sarcoidosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results identify and validate a BAL signature that predicts mortality in IPF and improves the accuracy of outcome prediction based on clinical parameters. The BAL signature associated with mortality unmasks a potential role for airway basal cells in IPF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201712-2551oc","type":"journal-article","created":{"date-parts":[[2018,8,24]],"date-time":"2018-08-24T16:38:21Z","timestamp":1535128701000},"page":"622-630","source":"Crossref","is-referenced-by-count":198,"title":["BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis"],"prefix":"10.1093","volume":"199","author":[{"given":"Antje","family":"Prasse","sequence":"first","affiliation":[{"name":"Department of Pulmonology, Hannover Medical School, Hannover, Germany"},{"name":"Department of Pneumology and"},{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany"},{"name":"German Center for Lung Research, BREATH, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Binder","sequence":"additional","affiliation":[{"name":"Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas C.","family":"Schupp","sequence":"additional","affiliation":[{"name":"Department of Pneumology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian","family":"Kayser","sequence":"additional","affiliation":[{"name":"Institute of Surgical Pathology, University Medical Center, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bargagli","sequence":"additional","affiliation":[{"name":"Respiratory Diseases and Lung Transplantation Unit, AOUS and Siena University, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Jaeger","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany"},{"name":"German Center for Lung Research, BREATH, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Hess","sequence":"additional","affiliation":[{"name":"Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Rittinghausen","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Vuga","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Simmons Center, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Lynn","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelia","family":"Violette","sequence":"additional","affiliation":[{"name":"Biogen Idec Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Jung","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. 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KG Research, Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Vanaudenaerde","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens M.","family":"Hohlfeld","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany"},{"name":"German Center for Lung Research, BREATH, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Krug","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany"},{"name":"German Center for Lung Research, BREATH, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose D.","family":"Herazo-Maya","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rottoli","sequence":"additional","affiliation":[{"name":"Respiratory Diseases and Lung Transplantation Unit, AOUS and Siena University, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim A.","family":"Wuyts","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium; 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