Biomarkers of Right Ventricular-Pulmonary Coupling in Chronic Obstructive Pulmonary Disease.
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ABSTRACT:
SUBMITTER: Mehmood M
PROVIDER: S-EPMC6775889 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Publications
Biomarkers of Right Ventricular-Pulmonary Coupling in Chronic Obstructive Pulmonary Disease.
American journal of respiratory and critical care medicine 20190901 6
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Project description:BackgroundPulmonary hypertension (PH) is a complication of chronic obstructive pulmonary disease (COPD). This study examined genetic variations in mediators of vascular remodelling and their association with PH in patients with COPD. In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia.MethodsIn patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia.Results580 COPD patients were recruited, 341 patients had a transthoracic echocardiogram, with RVSP measurable in 278 patients (mean age 69? years, mean FEV1 50% predicted, mean RVSP 44? mmHg, median history of 50 pack-years). Of the 7 tested SNPs, the NOS3-VNTR polymorphism was significantly associated with RVSP in a dose-dependent fashion for the risk allele: mean RVSP for a/a and a/b genotypes were 52.0 and 46.6? mmHg respectively, compared to 43.2 ?mmHg for b/b genotypes (P?=?0.032). No associations were found between RVSP and other polymorphisms. ACE II or ID genotypes were associated with a lower FEV1% predicted than the ACE DD genotype (P?=?0.028). The NOS3-298 TT genotype was associated with lower KCO % predicted than the NOS3-298 GG or GT genotype (P?=?0.031).ConclusionsThe NOS3-VNTR polymorphism was associated with RVSP in patients with COPD, supporting its involvement in the pathogenesis of PH in COPD. ACE and NOS3 genotypes were associated with COPD disease severity, but not with the presence of PH. Further study of these genes could lead to the development of prognostic and screening tools for PH in COPD.
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Project description:Identifying protein biomarkers for chronic obstructive pulmonary disease (COPD) has been challenging. Most previous studies have utilized individual proteins or pre-selected protein panels measured in blood samples. To identify COPD protein biomarkers by applying comprehensive mass spectrometry proteomics in lung tissue samples. We utilized mass spectrometry proteomic approaches to identify protein biomarkers from 152 lung tissue samples representing COPD cases and controls.
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2003-07-16 | GSE475 | GEO
Project description:BackgroundChronic obstructive pulmonary disease (COPD) is associated with structural and mechanical changes in the pulmonary vascular bed that increase right ventricular (RV) afterload and subsequently right heart failure.ObjectivesThe aim of the study was to elucidate RV dysfunction at rest by echocardiography in a cohort of COPD patients and to study its impact on prognosis.Methods84 patients of COPD and 40 matching healthy controls were evaluated at baseline. Evaluation included clinical examination, pulmonary function tests; 6 minutes walk test and echocardiography. Patient with COPD were again evaluated after 6 months.ResultsAll echocardiographic parameters of RV function were significantly impaired in COPD patients as compared to controls. Clinical deterioration in COPD group was much more in patients with baseline abnormal RV function (89%) and patients with RV systolic pressure ≥35 mmHg (P = 0.018). All the six patients who died had three or more abnormal RV systolic function parameters.ConclusionsRV myocardial performance index and basal strain showed largest difference between controls and COPD cases. Clinical deterioration was more common in patients with abnormal RV function parameters and pulmonary hypertension.
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Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients. A five chip study using total RNA recovered from Peripheral Blood Mononuclear Cell of Peripheral Blood.Evaluating the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10 after the hospital admission, to compared with healthy controls or patients with stable COPD. Slides were scanned at 5 μm/pixel resolution using an Axon GenePix 4000B scanner (Molecular Devices Corporation) piloted by GenePix Pro 6.0 software (Axon). Scanned images (TIFF format) were then imported into NimbleScan software (version 2.5) for grid alignment and expression data analysis. Expression data were normalized through quantile normalization and the Robust Multichip Average (RMA) algorithm included in the NimbleScan software. The Probe level (*_norm_RMA.pair) files and Gene level (*_RMA.calls) files were generated after normalization.
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Project description:Rationale: Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes.Objectives: To explore the relationship between computed tomography measures of emphysema and distal pulmonary arterial morphology with RV volume, and their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study.Methods: Epicardial (myocardium and chamber) RV volume (RVEV), distal pulmonary arterial blood vessel volume (arterial BV5: vessels <5 mm2 in cross-section), and objective measures of emphysema were extracted from 3,506 COPDGene computed tomography scans. Multivariable linear and Cox regression models and the log-rank test were used to explore the association between emphysema, arterial BV5, and RVEV with exercise capacity (6-min-walk distance) and all-cause mortality.Measurements and Main Results: The RVEV was approximately 10% smaller in Global Initiative for Chronic Obstructive Lung Disease stage 4 versus stage 1 COPD (P < 0.0001). In multivariable modeling, a 10-ml decrease in arterial BV5 (pruning) was associated with a 1-ml increase in RVEV. For a given amount of emphysema, relative preservation of the arterial BV5 was associated with a smaller RVEV. An increased RVEV was associated with reduced 6-minute-walk distance and in those with arterial pruning an increased mortality.Conclusions: Pulmonary arterial pruning is associated with clinically significant increases in RV volume in smokers with COPD and is related to exercise capacity and mortality in COPD.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).
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Project description:Chronic obstructive pulmonary disease causes significant morbidity and concomitant pulmonary vascular disease and cardiac dysfunction are associated with poor prognosis. Computed tomography-detected relative pulmonary artery (PA) enlargement defined as a PA to ascending aorta diameter ratio >1 (PA:A>1) is a marker for pulmonary hypertension and predicts chronic obstructive pulmonary disease exacerbations. However, little is known about the relationship between the PA:A ratio, pulmonary blood volume, and cardiac function. A single-center prospective cohort study of patients with chronic obstructive pulmonary disease was conducted. Clinical characteristics and computed tomography metrics, including the PA:A and pulmonary blood vessel volume, were measured. Ventricular functions, volumes, and dimensions were measured by cine cardiac MRI with 3-dimensional analysis. Linear regression examined the relationships between clinical characteristics, computed tomography and cardiac MRI metrics, and 6-minute walk distance. Twenty-four patients were evaluated and those with PA:A>1 had higher right ventricular (RV) end-diastolic and end-systolic volume indices accompanied by lower RV ejection fraction (52±7% versus 60±9%; P=0.04). The PA:A correlated inversely with total intraparenchymal pulmonary blood vessel volume and the volume of distal vessels with a cross-sectional area of <5 mm(2). Lower forced expiratory volume, PA:A>1, and hyperinflation correlated with reduced RV ejection fraction. Both PA diameter and reduced RV ejection fraction were independently associated with reduced 6-minute walk distance. The loss of blood volume in distal pulmonary vessels is associated with PA enlargement on computed tomography. Cardiac MRI detects early RV dysfunction and remodeling in nonsevere chronic obstructive pulmonary disease patients with a PA:A>1. Both RV dysfunction and PA enlargement are independently associated with reduced walk distance. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00608764.
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Project description:Identifying protein biomarkers for chronic obstructive pulmonary disease (COPD) has been challenging. Most previous studies have used individual proteins or preselected protein panels measured in blood samples. Mass spectrometry proteomic studies of lung tissue have been based on small sample sizes. We used mass spectrometry proteomic approaches to discover protein biomarkers from 150 lung tissue samples representing COPD cases and controls. Top COPD-associated proteins were identified based on multiple linear regression analysis with false discovery rate (FDR) < 0.05. Correlations between pairs of COPD-associated proteins were examined. Machine learning models were also evaluated to identify potential combinations of protein biomarkers related to COPD. We identified 4,407 proteins passing quality controls. Twenty-five proteins were significantly associated with COPD at FDR < 0.05, including interleukin 33, ferritin (light chain and heavy chain), and two proteins related to caveolae (CAV1 and CAVIN1). Multiple previously reported plasma protein biomarkers for COPD were not significantly associated with proteomic analysis of COPD in lung tissue, although RAGE was borderline significant. Eleven pairs of top significant proteins were highly correlated (r > 0.8), including several strongly correlated with RAGE (EHD2 and CAVIN1). Machine learning models using Random Forests with the top 5% of protein biomarkers demonstrated reasonable accuracy (0.707) and area under the curve (0.714) for COPD prediction. Mass spectrometry-based proteomic analysis of lung tissue is a promising approach for the identification of biomarkers for COPD.
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