{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:32:49Z","timestamp":1783366369000,"version":"3.54.6"},"reference-count":37,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Respiratory Investigation"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.resinv.2020.08.002","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T04:21:34Z","timestamp":1599625294000},"page":"90-98","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"title":["Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease"],"prefix":"10.1016","volume":"59","author":[{"given":"Naoki","family":"Nishiyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Masuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Nukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5402-3185","authenticated-orcid":false,"given":"Tomoya","family":"Tateishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Kishino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ukihide","family":"Tateishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Morota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Ohbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9073-9815","authenticated-orcid":false,"given":"Yasunari","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.resinv.2020.08.002_bib1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1513\/pats.200601-005TK","article-title":"Classification and natural history of the idiopathic interstitial pneumonias","volume":"3","author":"Kim","year":"2006","journal-title":"Proc Am Thorac Soc"},{"key":"10.1016\/j.resinv.2020.08.002_bib2","doi-asserted-by":"crossref","DOI":"10.1183\/16000617.0076-2018","article-title":"Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases","volume":"27","author":"Cottin","year":"2018","journal-title":"Eur Respir Rev : Off J Eur Res Soc"},{"key":"10.1016\/j.resinv.2020.08.002_bib3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12931-019-1022-1","article-title":"The natural history of progressive fibrosing interstitial lung diseases","volume":"20","author":"Kolb","year":"2019","journal-title":"Respir Res"},{"key":"10.1016\/j.resinv.2020.08.002_bib4","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1095\/biolreprod45.2.350","article-title":"A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors","volume":"45","author":"Kirchhoff","year":"1991","journal-title":"Biol Reprod"},{"key":"10.1016\/j.resinv.2020.08.002_bib5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1530\/ror.0.0030086","article-title":"Molecular characterization of epididymal proteins","volume":"3","author":"Kirchhoff","year":"1998","journal-title":"Rev Reprod"},{"key":"10.1016\/j.resinv.2020.08.002_bib6","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1038\/sj.onc.1205363","article-title":"The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms","author":"Bingle","year":"2002","journal-title":"Oncogene"},{"key":"10.1016\/j.resinv.2020.08.002_bib7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1465-9921-7-61","article-title":"WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung","volume":"7","author":"Bingle","year":"2006","journal-title":"Respir Res"},{"key":"10.1016\/j.resinv.2020.08.002_bib8","article-title":"Lack of whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (WFDC2) causes neonatal death from respiratory failure in mice","volume":"12","author":"Nakajima","year":"2019","journal-title":"Dis Model Mech"},{"key":"10.1016\/j.resinv.2020.08.002_bib9","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/modpathol.3800612","article-title":"Comprehensive analysis of HE4 expression in normal and malignant human tissues","volume":"19","author":"Galgano","year":"2006","journal-title":"Mod Pathol : Off J United States Canadian Acad Pathol"},{"key":"10.1016\/j.resinv.2020.08.002_bib10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nm.2989","article-title":"Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis","volume":"19","author":"LeBleu","year":"2013","journal-title":"Nat Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib11","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.chest.2018.08.1083","article-title":"Idiopathic pulmonary fibrosis: prospective, case-controlled study of natural history and circulating biomarkers","volume":"154","author":"Raghu","year":"2018","journal-title":"Chest"},{"key":"10.1016\/j.resinv.2020.08.002_bib12","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1164\/rccm.2009-040GL","article-title":"An official ATS\/ERS\/JRS\/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management","volume":"183","author":"Raghu","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib13","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1164\/rccm.201308-1483ST","article-title":"An official American Thoracic Society\/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias","volume":"188","author":"Travis","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib14","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1056\/NEJM197502132920706","article-title":"Polymyositis and dermatomyositis (first of two parts)","volume":"292","author":"Bohan","year":"1975","journal-title":"N Engl J Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib15","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/art.1780230510","article-title":"Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee","volume":"23","year":"1980","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.resinv.2020.08.002_bib16","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1136\/ard.2010.138461","article-title":"2010 rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League against Rheumatism collaborative initiative","volume":"69","author":"Aletaha","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.resinv.2020.08.002_bib17","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1164\/ajrccm\/144.4.765","article-title":"Japanese summer-type hypersensitivity pneumonitis. Geographic distribution, home environment, and clinical characteristics of 621 cases","volume":"144","author":"Ando","year":"1991","journal-title":"Am Rev Respir Dis"},{"key":"10.1016\/j.resinv.2020.08.002_bib18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0091-6749(99)70507-5","article-title":"Chronic hypersensitivity pneumonitis in Japan: a nationwide epidemiologic survey","volume":"103","author":"Yoshizawa","year":"1999","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.resinv.2020.08.002_bib19","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1164\/rccm.201604-0801CI","article-title":"Acute exacerbation of idiopathic pulmonary fibrosis","volume":"194","author":"Collard","year":"2016","journal-title":"Int Work Group Rep Am J Res Critical Care Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib20","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1007\/s00330-011-2098-2","article-title":"Fibrotic idiopathic interstitial pneumonias: HRCT findings that predict mortality","volume":"21","author":"Edey","year":"2011","journal-title":"Eur Radiol"},{"key":"10.1016\/j.resinv.2020.08.002_bib21","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software 'EZR' for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant"},{"key":"10.1016\/j.resinv.2020.08.002_bib22","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1080\/03007995.2019.1647040","article-title":"Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management","volume":"35","author":"Wijsenbeek","year":"2019","journal-title":"Curr Med Res Opin"},{"key":"10.1016\/j.resinv.2020.08.002_bib23","doi-asserted-by":"crossref","DOI":"10.1183\/16000617.0100-2018","article-title":"Fibrosing interstitial lung diseases: knowns and unknowns","volume":"28","author":"Cottin","year":"2019","journal-title":"Eur Respir Rev : Off J Eur Res Soc"},{"key":"10.1016\/j.resinv.2020.08.002_bib24","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01592-2016","article-title":"Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry","volume":"49","author":"Jo","year":"2017","journal-title":"Eur Respir J"},{"key":"10.1016\/j.resinv.2020.08.002_bib25","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1164\/ajrccm.158.5.9803115","article-title":"Circulating KL-6 predicts the outcome of rapidly progressive idiopathic pulmonary fibrosis","volume":"158","author":"Yokoyama","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib26","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1440-1843.2006.00834.x","article-title":"Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis","volume":"11","author":"Yokoyama","year":"2006","journal-title":"Respirology"},{"key":"10.1016\/j.resinv.2020.08.002_bib27","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.rmed.2015.10.005","article-title":"The usefulness of KL-6 and SP-D for the diagnosis and management of chronic hypersensitivity pneumonitis","volume":"109","author":"Okamoto","year":"2015","journal-title":"Respir Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib28","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3343\/alm.2017.37.6.526","article-title":"Clinical usefulness of human epididymis protein 4 in lung cancer","volume":"37","author":"Choi","year":"2017","journal-title":"Ann Lab Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib29","first-page":"3695","article-title":"The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma","volume":"63","author":"Hellstr\u00f6m","year":"2003","journal-title":"Canc Res"},{"key":"10.1016\/j.resinv.2020.08.002_bib30","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1258\/acb.2011.011258","article-title":"Elevated human epididymis protein 4 concentrations in chronic kidney disease","volume":"49","author":"Nagy","year":"2012","journal-title":"Ann Clin Biochem"},{"key":"10.1016\/j.resinv.2020.08.002_bib31","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s13277-011-0256-4","article-title":"Human epididymis protein 4 reference limits and natural variation in a Nordic reference population","volume":"33","author":"Bolstad","year":"2012","journal-title":"Tumour Biol : J Int Soc Oncodevelop Biol Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib32","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.it.2008.07.001","article-title":"Novel innate immune functions of the whey acidic protein family","volume":"29","author":"Bingle","year":"2008","journal-title":"Trends Immunol"},{"key":"10.1016\/j.resinv.2020.08.002_bib33","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.matbio.2018.03.021","article-title":"Idiopathic pulmonary fibrosis: epithelial-mesenchymal interactions and emerging therapeutic targets","volume":"71\u201372","author":"Hewlett","year":"2018","journal-title":"Matrix Biol : J Int Soc Matrix Biol"},{"key":"10.1016\/j.resinv.2020.08.002_bib34","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1164\/rccm.201807-1255ST","article-title":"Diagnosis of idiopathic pulmonary fibrosis. An official ATS\/ERS\/JRS\/ALAT clinical practice guideline","volume":"198","author":"Raghu","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.resinv.2020.08.002_bib35","doi-asserted-by":"crossref","DOI":"10.1378\/chest.128.5_suppl_1.526S","article-title":"Pathogenesis and natural history of usual interstitial pneumonia: the whole story or the last chapter of a long novel","volume":"128","author":"Strieter","year":"2005","journal-title":"Chest"},{"key":"10.1016\/j.resinv.2020.08.002_bib36","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1183\/09031936.00092309","article-title":"Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease","volume":"35","author":"Kim","year":"2010","journal-title":"Eur Respir J"},{"key":"10.1016\/j.resinv.2020.08.002_bib37","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.rmed.2017.08.025","article-title":"Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients","volume":"131","author":"Salisbury","year":"2017","journal-title":"Respir Med"}],"container-title":["Respiratory Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212534520301180?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212534520301180?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T22:31:42Z","timestamp":1761949902000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212534520301180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["S2212534520301180"],"URL":"https:\/\/doi.org\/10.1016\/j.resinv.2020.08.002","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-18084\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-18084\/v1","asserted-by":"object"}]},"ISSN":["2212-5345"],"issn-type":[{"value":"2212-5345","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease","name":"articletitle","label":"Article Title"},{"value":"Respiratory Investigation","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.resinv.2020.08.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}