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Am J Respir Crit Care Med. 2016 Nov 15;194(10):1242-1251.

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

Author information

1
1 Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
2
2 Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan.
3
3 Center for International Health Research, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island.
4
4 Division of Pulmonary and Critical Care and.
5
5 Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts; and.
6
6 Joan and Sanford Weill Department of Internal Medicine, Weill Cornell Medical College New York, New York.

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.

KEYWORDS:

biomarker; fibrosis; plasma

PMID:
27149370
PMCID:
PMC5114439
DOI:
10.1164/rccm.201505-0862OC
[Indexed for MEDLINE]
Free PMC Article

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