Plasma surfactant protein-D, matrix metalloproteinase-7, and osteopontin index distinguishes idiopathic pulmonary fibrosis from other idiopathic interstitial …

ES White, M Xia, S Murray, R Dyal… - American journal of …, 2016 - atsjournals.org
ES White, M Xia, S Murray, R Dyal, CM Flaherty, KR Flaherty, BB Moore, L Cheng, TJ Doyle…
American journal of respiratory and critical care medicine, 2016atsjournals.org
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 …
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.
ATS Journals
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