{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:23:26Z","timestamp":1791509006294,"version":"4.3.4"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL085083, R01 HL109118, RC2 HL101740, K23 HL119558, P01HL114501, R01HL130974, HL115618"],"award-info":[{"award-number":["R01 HL085083, R01 HL109118, RC2 HL101740, K23 HL119558, P01HL114501, R01HL130974, HL115618"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease (ILD) characterized by abnormal extracellular matrix (ECM) remodeling. We hypothesized that ECM remodeling might result in a plasma profile of proteins specific for IPF that could distinguish patients with IPF from other idiopathic ILDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To identify biomarkers that might assist in distinguishing IPF from non-IPF ILD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a panel of 35 ECM, ECM-related, and lung-specific analytes measured in plasma from 86 patients with IPF (derivation cohort) and in 63 patients with IPF (validation cohort). Comparison groups included patients with rheumatoid arthritis\u2013associated ILD (RA-ILD; n\u2009=\u200933), patients with alternative idiopathic ILDs (a-ILD; n\u2009=\u200941), and healthy control subjects (n\u2009=\u2009127). Univariable and multivariable logistic regression models identified biomarkers that differentiated patients with IPF from those with a-ILD. Both continuous and diagnostic threshold versions of biomarkers were considered; thresholds were chosen to maximize summed diagnostic sensitivity and specificity in univariate receiver-operating characteristic curve analysis. A diagnostic score was created from the most promising analytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Plasma surfactant protein (SP)-D\u2009&amp;gt;\u200931 ng\/ml, matrix metalloproteinase (MMP)-7\u2009&amp;gt;\u20091.75 ng\/ml, and osteopontin\u2009&amp;gt;\u20096 ng\/ml each significantly distinguished patients with IPF from patients with a-ILD, both individually and in a combined index. The odds ratio for IPF when at least one analyte in the index exceeded the threshold was 4.4 (95% confidence interval, 2.0\u20139.7; P\u2009=\u20090.0003). When at least two analytes were elevated, the odds ratio for IPF increased to 5.0 (95% confidence interval, 2.2\u201311.5; P\u2009=\u20090.0002).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A biomarker index of SP-D, MMP-7, and osteopontin enhanced diagnostic accuracy in patients with IPF compared with those with non-IPF ILD. Our data suggest that this biomarker index may improve diagnostic confidence in IPF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201505-0862oc","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T17:04:30Z","timestamp":1462467870000},"page":"1242-1251","source":"Crossref","is-referenced-by-count":166,"title":["Plasma Surfactant Protein-D, Matrix Metalloproteinase-7, and Osteopontin Index Distinguishes Idiopathic Pulmonary Fibrosis from Other Idiopathic Interstitial Pneumonias"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-8443","authenticated-orcid":false,"given":"Eric S.","family":"White","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Dyal","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace M.","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin R.","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany B.","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Cheng","sequence":"additional","affiliation":[{"name":"Center for International Health Research, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy J.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Villalba","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Dellaripa","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women\u2019s Hospital, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan O.","family":"Rosas","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Kurtis","sequence":"additional","affiliation":[{"name":"Center for International Health Research, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Joan and Sanford Weill Department of Internal Medicine, Weill Cornell Medical College New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,11,15]]},"reference":[{"key":"2026032023574305800_bib1","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":"2026032023574305800_bib2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1164\/rccm.201411-2044ED","article-title":"Nintedanib and pirfenidone. 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