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Plasma Surfactant Protein-D, Matrix Metalloproteinase-7, and Osteopontin Index Distinguishes Idiopathic Pulmonary Fibrosis from Other Idiopathic Interstitial Pneumonias
Open accessAbstract
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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“Another study showed that a panel including MMP7, surfactant protein D (SP-D) and osteopontin (OPN) enhanced diagnostic accuracy in IPF versus alternative idiopathic ILDs when plasma levels of at least one analyte in the panel exceeded a threshold (White et al., 2016).”
From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as White et al., 2016
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“SASP factors that had been associated with frailty (IL6, MCP-1, activin A, apelin) [27–30] or had been reported to have prognostic or diagnostic potential in IPF (MMP1, MMP7, osteopontin) [31,32] were further validated by single target enzyme-linked immunosorbent assays (ELISA).”
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Self-citation
Metadata
- 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
- 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
- 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
- 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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