Plasma levels of the three endothelial-specific proteins von Willebrand factor, tissue factor pathway inhibitor, and thrombomodulin do not predict the development of acute respiratory distress syndrome

Bajaj, Monika; Tricomi, Sally M.

doi:10.1007/s001340051054

Cited by 47 publications

(18 citation statements)

References 24 publications

(39 reference statements)

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“…Four studies looked at its correlation with ALI/ARDS, with two studies showing its ability to differentiate those with ALI/ARDS from those without [45,96], and two studies showing that it is not predictive of ALI/ARDS [97,98]. …”

Section: Resultsmentioning

confidence: 99%

Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review

et al. 2012

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IntroductionA strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis.MethodsThe objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded.ResultsSixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis.ConclusionsMultiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.

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Section: Resultsmentioning

confidence: 99%

Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review

et al. 2012

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“…The von Willebrand factor (vWF) and ICAM-1 have been proposed as predictive markers of endothelial injury but with mixed results [25], [26], [27]. Surfactant proteins SP-A and SP-D expressed by type II pneumocytes, the receptor for advance glycation end-product (RAGE), and KL-6 have been associated with pulmonary epithelial cell damage [28], [29], [30], [31].…”

Section: Discussionmentioning

confidence: 99%

Cytochrome b5 and Cytokeratin 17 Are Biomarkers in Bronchoalveolar Fluid Signifying Onset of Acute Lung Injury

2012

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Acute lung injury (ALI) is characterized by pulmonary edema and acute inflammation leading to pulmonary dysfunction and potentially death. Early medical intervention may ameliorate the severity of ALI, but unfortunately, there are no reliable biomarkers for early diagnosis. We screened for biomarkers in a mouse model of ALI. In this model, inhalation of S. aureus enterotoxin A causes increased capillary permeability, cell damage, and increase protein and cytokine concentration in the lungs. We set out to find predictive biomarkers of ALI in bronchoalveolar lavage (BAL) fluid before the onset of clinical manifestations. A cutting edge proteomic approach was used to compare BAL fluid harvested 16 h post S. aureus enterotoxin A inhalation versus BAL fluid from vehicle alone treated mice. The proteomic PF 2D platform permitted comparative analysis of proteomic maps and mass spectrometry identified cytochrome b5 and cytokeratin 17 in BAL fluid of mice challenged with S. aureus enterotoxin A. Validation of cytochrome b5 showed tropic expression in epithelial cells of the bronchioles. Importantly, S. aureus enterotoxin A inhalation significantly decreased cytochrome b5 during the onset of lung injury. Validation of cytokeratin 17 showed ubiquitous expression in lung tissue and increased presence in BAL fluid after S. aureus enterotoxin A inhalation. Therefore, these new biomarkers may be predictive of ALI onset in patients and could provide insight regarding the basis of lung injury and inflammation.

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“…In a prospective study of 45 patients with non-pulmonary sepsis Rubins and colleagues found elevations in vWF to be predictive of developing ALI with a sensitivity of 87% and specificity of 77% (65). However, these findings were not confirmed in subsequent trials, including one by Bajaj and coworkers where vWF along with other endothelial markers, tissue factor pathway inhibitor and thrombomodulin, were not found to be predictive of developing ARDS (66). This study was limited due to its small size; where only eight of the 15 patients at risk actually developed ARDS.…”

Section: Biomarkers Of Ards/ali Stagesmentioning

confidence: 87%

Biomarkers in acute lung injury

Bhargava

Wendt

2012

Translational Research

129

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Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) result in high permeability pulmonary edema causing hypoxic respiratory failure with high morbidity and mortality. As the population ages, the incidence of ALI is expected to rise. Over the last decade, several studies have identified biomarkers in plasma and bronchoalveolar lavage fluid providing important insights into the mechanisms involved in the pathophysiology of ALI. Several biomarkers have been validated in subjects from the large, multicenter ARDS clinical trials network. Despite these studies, no single or group of biomarkers has made it into routine clinical practice. New high throughput ‘omics’ techniques promise improved understanding of the biologic processes in the pathogenesis in ALI and possibly new biomarkers that predict disease and outcomes. In this article we review the current knowledge on biomarkers in ALI.

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Plasma levels of the three endothelial-specific proteins von Willebrand factor, tissue factor pathway inhibitor, and thrombomodulin do not predict the development of acute respiratory distress syndrome

Abstract: Plasma levels of vWF, TFPI and TM did not appear to serve as useful markers for predicting ARDS in patients at risk.

Cited by 47 publications

References 24 publications

Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review

Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review

Cytochrome b5 and Cytokeratin 17 Are Biomarkers in Bronchoalveolar Fluid Signifying Onset of Acute Lung Injury

Biomarkers in acute lung injury

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