Dataset Information

Multiple biomarkers predict disease severity, progression and mortality in COPD.

ABSTRACT:

Background

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by multiple subtypes and variable disease progression. Blood biomarkers have been variably associated with subtype, severity, and disease progression. Just as combined clinical variables are more highly predictive of outcomes than individual clinical variables, we hypothesized that multiple biomarkers may be more informative than individual biomarkers to predict subtypes, disease severity, disease progression, and mortality.

Methods

Fibrinogen, C-Reactive Protein (CRP), surfactant protein D (SP-D), soluble Receptor for Advanced Glycation Endproducts (sRAGE), and Club Cell Secretory Protein (CC16) were measured in the plasma of 1465 subjects from the COPDGene cohort and 2746 subjects from the ECLIPSE cohort. Regression analysis was performed to determine whether these biomarkers, individually or in combination, were predictive of subtypes, disease severity, disease progression, or mortality, after adjustment for clinical covariates.

Results

In COPDGene, the best combinations of biomarkers were: CC16, sRAGE, fibrinogen, CRP, and SP-D for airflow limitation (p?-4), SP-D, CRP, sRAGE and fibrinogen for emphysema (p?-3), CC16, fibrinogen, and sRAGE for decline in FEV₁ (p?-3), and all five biomarkers together for mortality (p?ConclusionThis comprehensive analysis of two large cohorts revealed that combinations of biomarkers improve predictive value compared with clinical variables and individual biomarkers for relevant cross-sectional and longitudinal COPD outcomes.

SUBMITTER: Zemans RL

PROVIDER: S-EPMC5470282 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Multiple biomarkers predict disease severity, progression and mortality in COPD.

Zemans Rachel L RL Jacobson Sean S Keene Jason J Kechris Katerina K Miller Bruce E BE Tal-Singer Ruth R Bowler Russell P RP

Respiratory research 20170613 1

<h4>Background</h4>Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by multiple subtypes and variable disease progression. Blood biomarkers have been variably associated with subtype, severity, and disease progression. Just as combined clinical variables are more highly predictive of outcomes than individual clinical variables, we hypothesized that multiple biomarkers may be more informative than individual biomarkers to predict subtypes, disease severity, di ...[more]

PMID: 28610627

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Project description:The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls. Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-? and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups. Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV(1), FEV(1)/FVC and DLCO. Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values. To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile. While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV(1) related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-?) formed another cluster associated with both DLCO and FEV(1) related parameters. Associations of Fibrinogen with DLCO and MPO with FEV(1)/FVC were stronger in patients without metabolic syndrome (r ?=? -0.52, p ?=? 0.005 and r ?=? -0.61, p =? 0.023, respectively) compared to patients with coexisting metabolic syndrome (r ?=? -0.25, p ?= ?0.47 and r ?=? -0.15, p ?= ?0.96, respectively), and may be driving overall associations in the general cohort. In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV(1), FEV(1)/FVC and DLCO. These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD.

Project description:Predicting progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) is clinically important. In this study, we propose a dual-model radiomic analysis with multivariate Cox proportional hazards regression models to investigate promising risk factors associated with MCI conversion to AD. T1 structural magnetic resonance imaging (MRI) and 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) data, from the AD Neuroimaging Initiative database, were collected from 131 patients with MCI who converted to AD within 3 years and 132 patients with MCI without conversion within 3 years. These subjects were randomly partition into 70% training dataset and 30% test dataset with multiple times. We fused MRI and PET images by wavelet method. In a subset of subjects, a group comparison was performed using a two-sample t-test to determine regions of interest (ROIs) associated with MCI conversion. 172 radiomic features from ROIs for each individual were established using a published radiomics tool. Finally, L1-penalized Cox model was constructed and Harrell's C index (C-index) was used to evaluate prediction accuracy of the model. To evaluate the efficacy of our proposed method, we used a same analysis framework to evaluate MRI and PET data separately. We constructed prognostic Cox models with: clinical data, MRI images, PET images, fused MRI/PET images, and clinical variables and fused MRI/PET images in combination. The experimental results showed that captured ROIs significantly associated with conversion to AD, such as gray matter atrophy in the bilateral hippocampus and hypometabolism in the temporoparietal cortex. Imaging model (MRI/PET/fused) provided significant enhancement in prediction of conversion compared to clinical models, especially the fused-modality Cox model. Moreover, the combination of fused-modality imaging and clinical variables resulted in the greatest accuracy of prediction. The average C-index for the clinical/MRI/PET/fused/combined model in the test dataset was 0.69, 0.73, 0.73 and 0.75, and 0.78, respectively. These results suggested that a combination of radiomic analysis and Cox model analyses could be used successfully in survival analysis and may be powerful tools for personalized precision medicine patients with potential to undergo conversion from MCI to AD.

Dataset Information

Multiple biomarkers predict disease severity, progression and mortality in COPD.

Background

Methods

Results

Publications

Multiple biomarkers predict disease severity, progression and mortality in COPD.

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