Dataset Information

Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study.

ABSTRACT: BACKGROUND:It is unknown if the plasma lipidome is a useful tool for improving our understanding of the acute respiratory distress syndrome (ARDS). Therefore, we measured the plasma lipidome of individuals with ARDS at two time-points to determine if changes in the plasma lipidome distinguished survivors from non-survivors. We hypothesized that both the absolute concentration and change in concentration over time of plasma lipids are associated with 28-day mortality in this population. METHODS:Samples for this longitudinal observational cohort study were collected at multiple tertiary-care academic medical centers as part of a previous multicenter clinical trial. A mass spectrometry shot-gun lipidomic assay was used to quantify the lipidome in plasma samples from 30 individuals. Samples from two different days were analyzed for each subject. After removing lipids with a coefficient of variation >?30%, differences between cohorts were identified using repeated measures analysis of variance. The false discovery rate was used to adjust for multiple comparisons. Relationships between significant compounds were explored using hierarchical clustering of the Pearson correlation coefficients and the magnitude of these relationships was described using receiver operating characteristic curves. RESULTS:The mass spectrometry assay reliably measured 359 lipids. After adjusting for multiple comparisons, 90 compounds differed between survivors and non-survivors. Survivors had higher levels for each of these lipids except for five membrane lipids. Glycerolipids, particularly those containing polyunsaturated fatty acid side-chains, represented many of the lipids with higher concentrations in survivors. The change in lipid concentration over time did not differ between survivors and non-survivors. CONCLUSIONS:The concentration of multiple plasma lipids is associated with mortality in this group of critically ill patients with ARDS. Absolute lipid levels provided more information than the change in concentration over time. These findings support future research aimed at integrating lipidomics into critical care medicine.

SUBMITTER: Maile MD

PROVIDER: S-EPMC5894233 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study.

Maile Michael D MD Standiford Theodore J TJ Engoren Milo C MC Stringer Kathleen A KA Jewell Elizabeth S ES Rajendiran Thekkelnaycke M TM Soni Tanu T Burant Charles F CF

Respiratory research 20180410 1

<h4>Background</h4>It is unknown if the plasma lipidome is a useful tool for improving our understanding of the acute respiratory distress syndrome (ARDS). Therefore, we measured the plasma lipidome of individuals with ARDS at two time-points to determine if changes in the plasma lipidome distinguished survivors from non-survivors. We hypothesized that both the absolute concentration and change in concentration over time of plasma lipids are associated with 28-day mortality in this population.<h ...[more]

PMID: 29636049

Similar Datasets

Project description:ObjectivesCirculating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome in adults. However, their role in pediatric acute respiratory distress syndrome is unknown.DesignWe performed a prospective cohort study in children with acute respiratory distress syndrome, with plasma collection within 24 hours of acute respiratory distress syndrome onset. We associated nucleosome levels with severity of acute respiratory distress syndrome and with nonpulmonary organ failures and tested for association of nucleosomes with PICU mortality and ventilator-free days at 28 days in univariate and multivariable analyses. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without acute respiratory distress syndrome in order to identify specific histone proteins elevated in acute respiratory distress syndrome.SettingLarge academic tertiary-care PICU.PatientsIntubated children meeting Berlin criteria for acute respiratory distress syndrome.InterventionsNone.Measurements and main resultsWe enrolled 333 children with acute respiratory distress syndrome, with 69 nonsurvivors (21%). Plasma nucleosomes were correlated with acute respiratory distress syndrome severity and with the number of nonpulmonary organ failures at acute respiratory distress syndrome onset. Nucleosomes were higher (p < 0.001) in nonsurvivors (0.40 [interquartile range, 0.20-0.71] arbitrary units) relative to survivors (0.10 [interquartile range, 0.04-0.25] arbitrary units). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 sd increase; 95% CI, 1.38-2.45; p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio, 0.74; 95% CI, 0.63-0.88; p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with acute respiratory distress syndrome, relative to septic children without acute respiratory distress syndrome.ConclusionsPlasma nucleosomes are associated with acute respiratory distress syndrome severity, nonpulmonary organ failures, and worse outcomes in pediatric acute respiratory distress syndrome.

Project description:The optimal method to assess fluid overload in acute respiratory distress syndrome is not known, and current techniques have limitations. Plasma volume status has emerged as a noninvasive method to assess volume status and is defined as the percentage alteration from ideal plasma volume. We hypothesized that plasma volume status would suggest the presence of significant excess volume and therefore correlate with mortality in acute respiratory distress syndrome.Design and settingThis is a retrospective cohort study of subjects enrolled in four previously completed National Heart Lung and Blood Institute-sponsored acute respiratory distress syndrome trials, using data from the National Institutes of Health Biologic Specimen and Data Repository Information Coordinating Center repository.PatientsStudy subjects included 3,165 patients with acute respiratory distress syndrome previously enrolled in National Heart Lung and Blood Institute-sponsored acute respiratory distress syndrome trials.Measurements and main resultsThe exposure variable of interest was plasma volume status, calculated as the percentage alteration of actual plasma volume calculated on the basis of weight and hematocrit using sex-specific constants. We performed Kaplan-Meier survival analysis and univariable and adjusted Cox proportional hazard models to determine the association of plasma volume status with 60-day mortality. The median age of subjects was 52 years (interquartile range, 40-63 yr). Median plasma volume status was 5.9% (interquartile range, -2.4% to 13.6%), and overall, 68% of subjects had positive plasma volume status suggesting plasma volume higher than ideal plasma volume. In adjusted models, plasma volume status greater than median was associated with 38% greater risk for mortality (hazard ratio, 1.38; 95% CI, 1.20-1.59; p < 0.001). Each interquartile range increase in plasma volume status was associated with greater mortality in adjusted models (hazard ratio, 1.24 per interquartile range increase; 95% CI, 1.13-1.36; p < 0.001). Plasma volume status greater than median was associated with fewer ventilator-free days (18 vs 19 d; p = 0.0026) and ICU-free days (15 vs 17 d; p = 0.0001).ConclusionsPlasma volume status is independently associated with mortality, ICU-free days, and ventilator-free days among subjects with acute respiratory distress syndrome. Plasma volume status could be considered for risk-stratification and to direct therapy, particularly fluid management.

Project description:BackgroundThere is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such "functional metabolites" in ARDS using metabolomics and in vivo experiments in a mouse model.MethodsMetabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for "functional metabolites", which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of "functional metabolites" in the lung injury and mortality caused by the respiratory disorder.ResultsThe metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS.ConclusionIncreased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine.Trial registrationChinese Clinical Trial Registry, ChiCTR1800015930. Registered 29 April 2018, http://www.chictr.org.cn/edit.aspx?pid=25609&htm=4.

Project description:ObjectivesPediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome.DesignLeveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia.SettingThe derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia.PatientsThere were 624 and 640 subjects in the derivation and validation cohorts, respectively.InterventionsNone.Measurements and main resultsThe model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ≥ 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ≥ 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts.ConclusionsWe describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

Dataset Information

Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study.

Publications

Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets