Early elevations in B‐type natriuretic peptide levels are associated with poor clinical outcomes in pediatric acute lung injury

Reel, Bhupinder; Oishi, Peter; Hsu, Jong Hau; Gildengorin, Ginny; Matthay, Michael A.; Fineman, Jeffrey R.; Flori, Heidi R.

doi:10.1002/ppul.21111

Cited by 14 publications

(12 citation statements)

References 44 publications

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“…There is conflicting data in adult ARDS about the utility of BNP as a marker of RV dysfunction and in predicting mortality (33–36). Contrary to the only report of BNP levels in children with acute lung injury (37), we found that BNP concentration within the first 24 hours of PARDS diagnosis was not associated with patient outcomes and correlated best with LV FS. Despite its wide clinical use, BNP may not accurately reflect RV dysfunction in the setting of acute non-cardiac organ damage and inflammation such as in PARDS.…”

Section: Discussioncontrasting

confidence: 99%

Early Right Ventricular Systolic Dysfunction and Pulmonary Hypertension Are Associated With Worse Outcomes in Pediatric Acute Respiratory Distress Syndrome

Himebauch

Yehya

Wang

et al. 2018

Critical Care Medicine

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Section: Discussioncontrasting

confidence: 99%

Early Right Ventricular Systolic Dysfunction and Pulmonary Hypertension Are Associated With Worse Outcomes in Pediatric Acute Respiratory Distress Syndrome

Himebauch

Yehya

Wang

et al. 2018

Critical Care Medicine

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“…Studies in adults have found that BNP can help discriminate ARDS from cardiogenic pulmonary edema, and higher BNP levels are associated with mortality ( 161 – 163 ). Similarly, in a cohort of children with ALI, elevated BNP levels early in the disease course were associated with worse oxygenation, fewer VFDs, increased need for inotropes, and were significantly elevated among non-survivors ( 52 ). These findings suggest BNP as a possible marker of the altered cardiopulmonary interactions that can occur in the setting of ALI in children.…”

Section: Biomarker Subgroupsmentioning

confidence: 95%

Biomarkers in Pediatric ARDS: Future Directions

Orwoll

Sapru

2016

Front. Pediatr.

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Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

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“…The lower mortality rate of PARDS (relative to adults), which appears to be decreasing over time (39,42), makes the selection of clinically relevant outcomes challenging for biomarker studies. Flori et al have demonstrated the prognostic utility of brain-type natriuretic peptide (27), plasminogen activator inhibitor-1 (30), and soluble intracellular adhesion molecule-1 [sICAM-1, (14)]. Others have validated the association between increased sICAM-1 and nonsurvival in PARDS (3,29).…”

Section: Discussionmentioning

confidence: 99%

Circulating nucleosomes are associated with mortality in pediatric acute respiratory distress syndrome

Yehya

Thomas

Margulies

2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Nucleosome levels were not associated with either Berlin (P ϭ 0.845) or PALICC (P ϭ 0.886) oxygenation categories, nor with etiology of PARDS (P ϭ 0.527). Nucleosomes were correlated with increasing numbers of nonpulmonary organ failures (P ϭ 0.009 for trend), and were higher in patients whose PaO 2 /FiO 2 worsened (P ϭ 0.012) over the first 72 h of PARDS. In regression analysis, nucleosome levels were independently associated with mortality after adjusting for either age, severity of illness score, number of nonpulmonary organ failures, vasopressor score, or Pa O 2 /FiO 2 (all P Ͻ 0.05). In conclusion, plasma nucleosome levels in early PARDS were associated with increased mortality, correlated with number of nonpulmonary organ failures, and preceded worsening oxygenation. The potential utility of this biomarker for prognostication, risk stratification, and mechanistic insight should be investigated further.acute respiratory distress syndrome; ARDS; pediatric acute respiratory distress syndrome; PARDS; nucleosomes MECHANISMS UNDERLYING pediatricacute respiratory distress syndrome (PARDS) remain elusive. While PARDS was historically defined by adult ARDS criteria (6, 25), it possesses a distinct epidemiologic, comorbidity, and outcome profile, prompting the Pediatric Acute Lung Injury Consensus Conference (PALICC) to develop pediatric-specific definitions in 2015 (23). Among other differences, the PALICC definition of PARDS uses oxygenation index (OI), rather than Pa O 2 /Fi O 2 , for risk stratification, despite the inconsistent relationship between oxygenation and outcome (1, 31). Common to both adult (35, 36) and pediatric (13, 39) ARDS is the significance of nonpulmonary organ failures as a predictor of poor outcome. While several investigations have focused on the systemic inflammatory response and the associated neutrophil activation and cytokine release (9, 36), the pathogenic mechanisms invoked remain incomplete for explaining the development of lung injury and multisystem organ failure (MSOF).Recent studies in adult ARDS have implicated circulating nucleosomes, the histone/DNA complexes resulting from nuclear chromatin degradation released after cellular damage, as potentially pathogenic in sepsis (4, 12, 24, 38), aspiration (41), and trauma-related ARDS (2). Normally located within the nucleus, nucleosomes released into the circulation act as damage-associated molecular patterns (DAMP), and have been shown to be toxic to multiple cell types (2,12,24), offering a novel mechanism linking diverse inciting insults with subsequent lung injury and organ failure. However, whether nucleosomes are associated with PARDS development or progression is unknown.Rapid identification of children with PARDS who are most at risk of a poor outcome is essential for accurate risk stratification in clinical trials, as it allows redirection of aggressive interventions toward the sickest cohort. Unlike adult ARDS, few studies address the utility of biomarkers in PARDS. The reduced incidence of PARDS [12.8 per 100,000 person-ye...

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Early elevations in B‐type natriuretic peptide levels are associated with poor clinical outcomes in pediatric acute lung injury

Cited by 14 publications

References 44 publications

Early Right Ventricular Systolic Dysfunction and Pulmonary Hypertension Are Associated With Worse Outcomes in Pediatric Acute Respiratory Distress Syndrome

Early Right Ventricular Systolic Dysfunction and Pulmonary Hypertension Are Associated With Worse Outcomes in Pediatric Acute Respiratory Distress Syndrome

Biomarkers in Pediatric ARDS: Future Directions

Circulating nucleosomes are associated with mortality in pediatric acute respiratory distress syndrome

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