&lt;p&gt;Increased von Willebrand Factor Processing in COPD, Reflecting Lung Epithelium Damage, Is Associated with Emphysema, Exacerbations and Elevated Mortality Risk&lt;/p&gt;

Langholm, Lasse; Rønnow, Sarah; Sand, J.M.B.; Leeming, Diana Julie; Tal‐Singer, Ruth; Miller, Bruce E.; Vestbo, Jørgen; Karsdal, Morten A.; Manon‐Jensen, Tina

doi:10.2147/copd.s235673

Cited by 16 publications

(17 citation statements)

References 39 publications

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“…Previously, we showed that VWF-A relates to a more acute state of COPD during exacerbations, whereas VWF-N relates to the more chronic state of COPD emphysema, that VWF could potentially be utilized as a marker for endothelial dysfunction and inflammation [19], which have also previously been suggested [6,31]. In the present study, we demonstrate that the highest hazard ratio was obtained by combining the measurement of PRO-C6 and VWF-N, which could reflect that the patients suffering from a more advanced profibrotic state and emphysema are also the ones at risk for poor outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Competitive ELISAs, utilizing monoclonal antibodies recognizing specific neoepitopes, were used to assess endotrophin/type VI collagen formation (PRO-C6), VWF formation/ endothelial release (VWF-N), and activated VWF (VWF-A) [16,17] (Nordic Bioscience A/S, Herlev, Denmark). Measurements were performed previously in a blinded manner, according to the manufacturer's instructions [18,19].…”

Section: Quantification Of Serological Biomarkersmentioning

confidence: 99%

“…Combining PRO-C6 with VWF-A and VWF-N improves prediction of mortality PRO-C6, VWF-A, and VWF-N have already been shown to be independent predictors of all-cause mortality [18,19]. To investigate if PRO-C6 combined with biomarkers of VWF processing could provide additional prognostic value, we multiplied the biomarkers.…”

Section: Basic Demographicsmentioning

confidence: 99%

“…Kaplan-Meier survival analysis and hazard ratios evaluated the prognostic value of biomarkers alone or in combination for all-cause mortality after 3 years. Previously it was shown that high levels of PRO-C6, VWF-A, and VWF-N were associated with a higher risk of mortality with hazard ratios of 5.6 (95% CI 2.4-13.1), 4.6 (95% CI 2.2-9.6) and 3.7 (95% CI 1.8-7.6), respectively [18,19]. These values were significantly increased when combining PRO-C6 with the VWF processing biomarkers VWF-A 8.8 (2.8-27.7) or VWF-N to hazard ratios of 8.8 (95% CI 2.8-27.7) and 13.3 (95% CI 5.6-32.0), respectively.…”

Section: Basic Demographicsmentioning

confidence: 99%

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Endotrophin, an extracellular hormone, in combination with neoepitope markers of von Willebrand factor improves prediction of mortality in the ECLIPSE COPD cohort

et al. 2020

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Background: Lung epithelial damage, activation of the wound healing cascade, and remodeling of the extracellular matrix (ECM) play a major role in chronic obstructive pulmonary disease (COPD). The pro-peptide of type VI collagen has been identified as the hormone endotrophin. Endotrophin has been shown to promote fibrosis and inflammation, whereas von Willebrand factor (VWF) is a crucial part of wound healing initiation. Here, we assessed the released and activated form of VWF and endotrophin, the pro-peptide of type VI collagen, serologically to investigate their association with mortality in COPD subjects alone or in combination. Methods: One thousand COPD patients with 3 years of clinical follow-up from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort were included. Serum and heparin plasma were collected at 6 months and 1 year, respectively. Competitive ELISA utilizing specific monoclonal antibodies assessed endotrophin/ type VI collagen formation (PRO-C6), VWF release (VWF-N), and activated VWF (VWF-A). Biomarker levels were dichotomized into high and low as defined by receiver operating characteristic (ROC) curves based on mortality data. Kaplan-Meier analysis was used to determine hazard ratios for all-cause mortality for biomarkers alone or in combination. Results: High levels of PRO-C6, VWF-A, and VWF-N have previously been shown to be individually associated with a higher risk of mortality with hazard ratios of 5.6 (95% CI 2.4-13.1), 3.7 (1.8-7.6), and 4.6 (2.2-9.6), respectively. The hazard ratios increased when combining the biomarkers: PRO-C6*VWFA 8.8 (2.8-27.7) and PRO-C6*VWFN 13.3 (5.6-32.0). Notably, PRO-C6*VWF-N increased more than 2-fold.

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Section: Discussionmentioning

confidence: 99%

Section: Quantification Of Serological Biomarkersmentioning

confidence: 99%

Section: Basic Demographicsmentioning

confidence: 99%

Section: Basic Demographicsmentioning

confidence: 99%

See 2 more Smart Citations

Endotrophin, an extracellular hormone, in combination with neoepitope markers of von Willebrand factor improves prediction of mortality in the ECLIPSE COPD cohort

et al. 2020

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“…Фактор Виллебранда -белок системы гемостаза и маркер дисфункции эндотелия. У больных ХОБЛ фактор Виллебранда ассоциирован с тяжестью симптомов, эмфиземы, обострениями и смертностью [30].…”

Section: резюме основного результата исследованияunclassified

Molecular Markers in Occupational Chronic Obstructive Pulmonary Disease Comorbid with Heart Failure

et al. 2020

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Background.Comorbid heart failure (HF) is common in chronic obstructive pulmonary disease (COPD). Comorbid condition features are studied well in COPD due to tobacco smoke. There is a lack of data about mechanisms, clinical and functional specificity of occupational COPD and HF comorbidity. As occupational COPD and HF share common symptoms and sometimes lung function disorders, there is an unmet need in new markers of HF in occupational COPD.Aims to establish molecular markers associated with occupational COPD with HF comorbidity.Methods.Subjects with occupational COPD were enrolled in a single-center prospective cohort observational study. Comparison group COPD due to tobacco smoke. Then groups were stratified according to HF so the following subgroups were compared: occupational COPD with HF (n=63), occupational COPD without HF (n=52), COPD due to tobacco smoke with HF (n=41), COPD due to tobacco smoke without HF (n=74). Control group healthy people (n=115). Groups were matched by demographics, duration of COPD and HF. CODP was diagnosed according to GOLD 20112020 criteria, HF according to Russian Federal clinical guidelines. Occupational etiological factors were silica dust, organic solvents, metal fumes. Clinical and functional characteristics of CODP and HF were obtained. Serum levels of pulmonary and activation-regulated chemokine (PARC/CCL-18), protein S100, troponin, N terminal pro brain natriuretic peptide (NT-pro-BNP), von Willebrand factor, C-reactive protein were measured by enzyme linked immunosorbent assay, fibrinogen were measured by Clauss method, lactate dehydrogenase, creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase were measured by standard biochemical method. Data are presented as median and interquartile range. Linear regression were used to explore relationships.Results.The molecular specificity of occupational COPD comorbid with HF were the largest increase in serum concentration of PARC-CCL18, NT-pro-BNP, protein S100, troponin, von Willebrand factor and fibrinogen. This factors were associated with length of service. For PARC-CCL18 В=1.1; for NT-pro-BNP В=0.9; for protein S100 В=1.3; for troponin В=0.8, for von Willebrand factor В=1.5 and for fibrinogen В=1.1. Molecular factors also were related to phenotype characteristics of COPD and HF. In multiply regression model the best predictors of comorbidity of CODP and HF were PARC-CCL18 (В=1.1; р=0.002), NT-pro-BNP (В=1.5; р=0.001), protein S100 (В=1.2; р=0.002), troponin (В=0.9; р=0.003). The model was adjusted for gender, age, duration of CODP and HF, FEV1.Conclusions.Occupational CODP comorbid with heart failure is the distinct phenotype. The perspective molecular markers of this phenotype are serum levels of PARC-CCL18, NT-pro-BNP, protein S100, troponin.

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Regional and disease specific human lung extracellular matrix composition

et al. 2023

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<p>Increased von Willebrand Factor Processing in COPD, Reflecting Lung Epithelium Damage, Is Associated with Emphysema, Exacerbations and Elevated Mortality Risk</p>

Cited by 16 publications

References 39 publications

Endotrophin, an extracellular hormone, in combination with neoepitope markers of von Willebrand factor improves prediction of mortality in the ECLIPSE COPD cohort

Endotrophin, an extracellular hormone, in combination with neoepitope markers of von Willebrand factor improves prediction of mortality in the ECLIPSE COPD cohort

Molecular Markers in Occupational Chronic Obstructive Pulmonary Disease Comorbid with Heart Failure

Regional and disease specific human lung extracellular matrix composition

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