Cited by 180Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisOccupational and environmental lung diseasesSystemic Sclerosis and Related Diseases

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Plasma Surfactant Protein-D, Matrix Metalloproteinase-7, and Osteopontin Index Distinguishes Idiopathic Pulmonary Fibrosis from Other Idiopathic Interstitial Pneumonias

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White, Eric S., Xia, Meng, Murray, Susan, Dyal, Rachel, Flaherty, Candace M., Flaherty, Kevin R., Moore, Bethany B., Cheng, Ling, Doyle, Tracy J., Villalba, Julian, Dellaripa, Paul F., Rosas, Ivan O., Kurtis, Jonathan D., Martinez, Fernando J.·2016·American Journal of Respiratory and Critical Care Medicine

DOI 10.1164/rccm.201505-0862ocPMC PMC5114439

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Abstract

Rationale: 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. Objectives: To identify biomarkers that might assist in distinguishing IPF from non-IPF ILD. Methods: 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–associated ILD (RA-ILD; n = 33), patients with alternative idiopathic ILDs (a-ILD; n = 41), and healthy control subjects (n = 127). 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. Measurements and Main Results: Plasma surfactant protein (SP)-D > 31 ng/ml, matrix metalloproteinase (MMP)-7 > 1.75 ng/ml, and osteopontin > 6 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, 2.0–9.7; P = 0.0003). When at least two analytes were elevated, the odds ratio for IPF increased to 5.0 (95% confidence interval, 2.2–11.5; P = 0.0002). Conclusions: 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.

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Additional file 3 of Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan
Ikeda, K., Chiba, H., Nishikiori, H., Azuma, A., Kondoh, Y., Ogura, T., Taguchi, Y., Ebina, M., Sakaguchi, H., Miyazawa, S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13311127
Additional file 2 of Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan
Ikeda, K., Chiba, H., Nishikiori, H., Azuma, A., Kondoh, Y., Ogura, T., Taguchi, Y., Ebina, M., Sakaguchi, H., Miyazawa, S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13311124
Additional file 1 of Biomarkers of cellular senescence in idiopathic pulmonary fibrosis
Aversa, Z., Atkinson, E. J., Carmona, E. M., White, T. A., Heeren, A. A., Jachim, S. K., Zhang, X., Cummings, S. R., Chiarella, S. E., LIMPER, A. H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22624408
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Waich, A., Ochsner, S. A., Villalba, J. A., Rose, J. A., Cala-García, J., Zuluaga, J. D., McKenna, N. J., Echartea, M. E. R., He, C., Celada, L. J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.28.727955
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Authors: White, E. S., Xia, M., Murray, S., Dyal, R., Flaherty, C. M., Flaherty, K. R., Moore, B. B., Cheng, L., Doyle, T. J., Villalba, J., Dellaripa, P. F., Rosas, I. O., Kurtis, J. D., & Martinez, F. J.
Affiliations: University of Michigan (US)
Brown University (US)
Division of Pulmonary and Critical Care and
Brigham and Women's Hospital (US)
Joan and Sanford Weill Department of Internal Medicine, Weill Cornell Medical College New York, New York
Corresponding author: White, Eric S.
ORCID: White, Eric S.
Xia, Meng
Murray, Susan
Flaherty, Kevin R.
Moore, Bethany B.
Cheng, Ling
Doyle, Tracy J.
Villalba, Julian
Dellaripa, Paul F.
Kurtis, Jonathan D.
Venue: American Journal of Respiratory and Critical Care Medicine
Publisher: Oxford University Press (OUP)
Published: 2016-11
Volume: 194
Issue: 10
Pages: 1242-1251
ISSN: 1073-449X (ISSN-L)
1535-4970
DOI: 10.1164/rccm.201505-0862oc
PMC: PMC5114439
OpenAlex: W2346999058
Cited by: 180
References: 39
Citations by year: 2026: 9 · 2025: 18 · 2024: 15 · 2023: 17 · 2022: 9 · 2021: 23 · 2020: 18 · 2019: 17 · 2018: 19 · 2017: 28 · 2016: 7
FWCI: 21.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: American Journal of Respiratory and Critical Care Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (R01 HL085083, R01 HL109118, RC2 HL101740, K23 HL119558, P01HL114501, R01HL130974, HL115618)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
Keywords: idiopathic pulmonary fibrosis, idiopathic interstitial lung disease, plasma biomarkers, surfactant protein D, matrix metalloproteinase-7, osteopontin, extracellular matrix remodeling, rheumatoid arthritis-associated interstitial lung disease
MeSH terms: Diagnosis, Differential, Female, Humans, Male, Middle Aged, ROC Curve, Sensitivity and Specificity, Cohort Studies, Biomarkers, Matrix Metalloproteinase 7, Pulmonary Surfactant-Associated Protein D, Osteopontin, Idiopathic Interstitial Pneumonias, Idiopathic Pulmonary Fibrosis

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Plasma Surfactant Protein-D, Matrix Metalloproteinase-7, and Osteopontin Index Distinguishes Idiopathic Pulmonary Fibrosis from Other Idiopathic Interstitial Pneumonias

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