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

2016 ◽  
Vol 310 (11) ◽  
pp. L1177-L1184 ◽  
Author(s):  
Nadir Yehya ◽  
Neal J. Thomas ◽  
Susan S. Margulies
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Prospective Observational Study ◽  
Distress Syndrome ◽  
Severity Of Illness ◽  
Enzyme Linked Immunosorbent Assay ◽  
Potential Utility ◽  
Mechanistic Insight ◽  
Organ Failures

Mechanisms underlying pediatric acute respiratory distress syndrome (PARDS) are poorly understood. The recent implication of circulating nucleosomes as pathogenic in sepsis and trauma-associated ARDS in adults led us to investigate the significance of nucleosomes in PARDS. We conducted a prospective, observational study on children with PARDS at the Children's Hospital of Philadelphia between July 2014 and September 2015. Plasma was collected within 48 h of PARDS onset and nucleosomes quantified by enzyme-linked immunosorbent assay. Samples from 76 children with PARDS (11 deaths, 14%) were collected early [median 15 (IQR 7, 21) h] after PARDS onset. Nucleosome levels were higher in nonsurvivors [0.59 AU (IQR 0.46, 0.84)] relative to survivors [0.21 AU (IQR 0.08, 0.33), rank sum P < 0.001]. Nucleosome levels were not associated with either Berlin ( P = 0.845) or PALICC ( P = 0.886) oxygenation categories, nor with etiology of PARDS ( P = 0.527). Nucleosomes were correlated with increasing numbers of nonpulmonary organ failures ( P = 0.009 for trend), and were higher in patients whose PaO2/FiO2 worsened ( P = 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 PaO2/FiO2 (all P < 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.

scholarly journals Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Chiara Robba ◽  
◽  
Lorenzo Ball ◽  
Denise Battaglini ◽  
Danilo Cardim ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Acute Respiratory Distress Syndrome ◽  
Observational Study ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Prospective Observational Study ◽  
Distress Syndrome ◽  
Cerebral Oxygenation ◽  
Arterial Blood ◽  
Early Effects

Abstract Background In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics. Methods This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO2) removal (ECCO2R). Arterial blood gas values (oxygen saturation [SpO2], partial pressure of oxygen [PaO2] and of carbon dioxide [PaCO2]) and cerebral oxygenation (rSO2) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients. Results Forty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57–69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO2 and PaCO2 values, but cerebral oxygenation decreased significantly (52 [51–54]% vs. 49 [47–50]%, p < 0.001). After PP, a significant increase was observed in PaO2 (from 62 [56–71] to 82 [76–87] mmHg, p = 0.005) and rSO2 (from 53 [52–54]% to 60 [59–64]%, p = 0.005). The use of iNO increased PaO2 (from 65 [67–73] to 72 [67–73] mmHg, p = 0.015) and rSO2 (from 53 [51–56]% to 57 [55–59]%, p = 0.007). The use of ECCO2R decreased PaO2 (from 75 [75–79] to 64 [60–70] mmHg, p = 0.009), with reduction of rSO2 values (59 [56–65]% vs. 56 [53–62]%, p = 0.002). In the whole population, a significant relationship was found between SpO2 and rSO2 (R = 0.62, p < 0.001) and between PaO2 and rSO2 (R0 0.54, p < 0.001). Conclusions Rescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs. Registration The study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).

Differentiating septic children with and without acute respiratory distress syndrome using proteomics

2022 ◽  
Author(s):  
Nadir Yehya ◽  
Hossein Fazeliniah ◽  
Deanne M Taylor ◽  
Gladys Gray Lawrence ◽  
Lynn A. Spruce ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Random Forest ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Expression Profiles ◽  
Severity Of Illness ◽  
Source Of Infection ◽  
Galectin 3 ◽  
Definition Of

Both sepsis and acute respiratory distress syndrome (ARDS) rely on imprecise clinical definitions leading to heterogeneity, which has contributed to negative trials. Because circulating protein/DNA complexes have been implicated in sepsis and ARDS, we aimed to develop a proteomic signature of DNA-bound proteins to discriminate between septic children with and without ARDS. We performed a prospective case-control study in twelve septic children with ARDS matched to 12 septic children without ARDS on age, severity of illness score, and source of infection. We performed co-immunoprecipitation and downstream proteomics in plasma collected ≤ 24 hours of intensive care unit admission. Expression profiles were generated, and a random forest classifier was used on differentially expressed proteins to develop a signature which discriminated ARDS. The classifier was tested in six independent blinded samples. Neutrophil and nucleosome proteins were over-represented in ARDS, including two S100A proteins, superoxide dismutase (SOD), and three histones. Random forest produced a 10-protein signature which accurately discriminated between septic children with and without ARDS. This classifier perfectly assigned six independent blinded samples as having ARDS or not. We validated higher expression of the most informative discriminating protein, galectin-3-binding protein, in children with ARDS. Our methodology has applicability to isolation of DNA-bound proteins from plasma. Our results support the premise of a molecular definition of ARDS, and give preliminary insight into why some septic children, but not others, develop ARDS.

scholarly journals High Burden of Acquired Morbidity in Survivors of Pediatric Acute Respiratory Distress Syndrome

2021 ◽  
Author(s):  
Sin Wee Loh ◽  
Ming Ying Gan ◽  
Judith Ju-Ming Wong ◽  
Chengsi Ong ◽  
Yee Hui Mok ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Hospital Discharge ◽  
Functional Outcomes ◽  
Distress Syndrome ◽  
Severity Of Illness ◽  
Bivariate Analysis ◽  
Clinical Records

Introduction: With improving mortality rates in pediatric acute respiratory distress syndrome (PARDS), functional outcomes in survivors are increasingly important. We aim to describe the change in functional status score (FSS) from baseline to discharge and to identify risk factors associated with poor functional outcomes. Methods: We examined clinical records of patients with PARDS admitted to our pediatric intensive care unit (PICU) from 2009 to 2016. Our primary outcome was acquired morbidity at PICU and hospital discharge (defined by an increase in FSS ≥3 points above baseline). We included severity of illness scores and severity of PARDS in our bivariate analysis for risk factors for acquired morbidity. Results: There were 181 patients with PARDS, of which 90 (49.7%) survived. Median pediatric index of mortality 2 score was 4.05 (1.22, 8.70) and 21 (26.6%) patients had severe PARDS. 59 (65.6%) and 14 (15.6%) patients had acquired morbidity at PICU and hospital discharge, respectively. Median baseline FSS was 6.00 (6.00, 6.25), which increased to 11.00 (8.75, 12.00) at PICU discharge before decreasing to 7.50 (6.00, 9.25) at hospital discharge. All patients had significantly higher median FSS score at both PICU and hospital discharge compared to baseline. Feeding and respiratory were the most affected domains. After adjusting for severity of illness, severity categories of PARDS was not a risk factor for acquired morbidity. Conclusion: Acquired morbidity in respiratory and feeding domains was common in PARDS survivors. Specific attention should be given to these two domains of functional outcomes in these children.

scholarly journals Pretreatment of ferulic acid attenuates inflammation and oxidative stress in a rat model of lipopolysaccharide-induced acute respiratory distress syndrome

2018 ◽  
Vol 31 ◽  
pp. 039463201775051 ◽  
Author(s):  
Sheng Zhang ◽  
Pengyu Wang ◽  
Pengxin Zhao ◽  
Dong Wang ◽  
Yanwei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Ferulic Acid ◽  
Rat Model ◽  
Distress Syndrome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Histological Changes ◽  
Anti Oxidant

Acute respiratory distress syndrome (ARDS) is a fatal clinical condition that can be caused by pulmonary and non-pulmonary diseases. Oxidative stress and inflammation play key roles in the development of ARDS. In this study, we investigated whether ferulic acid (FA), an anti-oxidant, was beneficial for prophylaxis of ARDS. We established an ARDS rat model using lipopolysaccharide (LPS) administration. Lung injury was assessed by lung wet/dry ratio and broncho-alveolar lavage fluid (BALF) analysis. Hematoxylin and eosin staining was performed to evaluate the histological changes of the lungs. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting were performed to detect proteins in BALF and lung tissue, respectively. Pulmonary function was determined by testing the oxygen level in BALF. FA pretreatment significantly alleviated LPS-induced pulmonary histological changes. FA reversed LPS-induced changes of lung wet/dry ratio, total protein in BALF, P(A-a)O2, and PaO2/FiO2. In addition, LPS dramatically up-regulated the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10 in BALF ( P < 0.01). However, pretreatment of FA significantly improved LPS-induced inflammation. We found that FA indeed reduced oxidative stress in the lungs by testing malondialdehyde level, myeloperoxidase level, and total anti-oxidant capacity. We also proved that FA inactivated multiple mitogen-activated protein kinase signaling pathways in the lungs. In conclusion, FA alleviated LPS-induced ARDS through its anti-inflammatory and anti-oxidant activities.

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