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Biomarkers for patients with trauma associated acute respiratory distress syndrome.

ABSTRACT: Trauma is a major factor that contributes to the risk for acute respiratory distress syndrome (ARDS). Biomarkers that predict the risk, diagnosis, treatment response and prognosis of ARDS after trauma have been widely investigated. In addition to their applications in clinical diagnosis and treatment, these biomarkers provide important insights into our understanding of the pathogenesis of ARDS. This review begins with a brief introduction regarding the incidence and pathogenesis of trauma-associated ARDS. Then, we focus on reviewing the clinical trials that have been designed to investigate the value of biomarkers in ARDS after trauma. Biomarkers with a confirmed value in ARDS have been organized on the basis of key pathogenic processes that are central to ARDS and are described in detail. Among these, angiopoietin 2 (Ang-2), L-selectin, Clara cell protein 16 (CC16), soluable receptor for advanced glycation end products (sRAGE), Surfactant protein D (SP-D), histones, mtDNAs and some biomarker panels had a certain association with the diagnosis and prognosis of trauma-related ARDS. Further investigations are needed regarding the design of trials, the best sampling approaches and the optimal combinations of the biomarker panels.

SUBMITTER: Xu W

PROVIDER: S-EPMC5558771 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Biomarkers for patients with trauma associated acute respiratory distress syndrome.

Xu Wujian W Song Yong Y

Military Medical Research 20170816

Trauma is a major factor that contributes to the risk for acute respiratory distress syndrome (ARDS). Biomarkers that predict the risk, diagnosis, treatment response and prognosis of ARDS after trauma have been widely investigated. In addition to their applications in clinical diagnosis and treatment, these biomarkers provide important insights into our understanding of the pathogenesis of ARDS. This review begins with a brief introduction regarding the incidence and pathogenesis of trauma-assoc ...[more]

PMID: 28824814

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Project description:Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known complications of injuries in combat casualties, but there has been no review characterizing them. This scoping review aims to map the combat trauma-related ALI/ARDS literature and characterize these conditions in the military population.Data sourcesPubmed was searched from 1969 to April 2022.Study selectionStudies were included if they examined ALI/ARDS or related entities (blast lung injury [BLI], transfusion-related acute lung injury, and acute respiratory failure) in combat trauma patients in the military (U.S. or allied forces).Data extractionStudy years, design, location, number of patients, target outcomes as related to ALI/ARDS or related entities, and results were collected.Data synthesisThe initial search yielded 442 studies, with 22 ultimately included. Literature on ALI/ARDS comes mostly from retrospective data and case studies, with limited prospective studies. The incidence and prevalence of ALI/ARDS range from 3% to 33%, and mortality 12.8% to 33%. BLI, a known antecedent to ALI/ARDS, has an incidence and mortality ranging from 1.4% to 40% and 11% to 56%, respectively. Risk factors for ALI/ARDS include pulmonary injury, inhalation injury, blunt trauma, pneumonia, higher military injury severity score, higher injury severity score, higher fresh frozen plasma volumes, higher plasma and platelet volumes, the use of warm fresh whole blood, female sex, low blood pressure, and tachycardia. Literature has demonstrated the effectiveness in transportation of these patients and the utility of extracorporeal life support.ConclusionsALI/ARDS incidences and prevalences in modern conflict range from 3% to 33%, with mortality ranging from 12.8% to 33%. ALI/ARDS has been associated with injury severity metrics, injury type, resuscitative fluid amount and type, vital signs, and patient demographics. Studies are limited to mostly retrospective data, and more data are needed to better characterize these conditions.

Project description:ObjectivesAcute respiratory distress syndrome occurring in the setting of direct versus indirect lung injury may reflect different pathobiologies amenable to different treatment strategies. We sought to test whether a panel of plasma biomarkers differed between children with sepsis-associated direct versus indirect acute respiratory distress syndrome. We hypothesized that a biomarker profile indicative of endothelial activation would be associated with indirect acute respiratory distress syndrome.DesignObservational cohort.SettingAcademic PICU.SubjectsPatients less than 18 years old with sepsis-associated direct (pneumonia, n = 52) or indirect (extrapulmonary sepsis, n = 46) acute respiratory distress syndrome.InterventionsNone.Measurements and main resultsOf 58 biomarkers examined, 33 differed by acute respiratory distress syndrome subtype. We used classification and regression tree methodology to examine associations between clinical and biochemical markers and acute respiratory distress syndrome subtype. The classification and regression tree model using only clinical variables (age, sex, race, oncologic comorbidity, and Pediatric Risk of Mortality-III score) performed worse than the classification and regression tree model using five clinical variables and 58 biomarkers. The best classification and regression tree model used only four endothelial biomarkers, including elevated angiopoietin-2/angiopoietin-1 ratio, vascular cell-adhesion molecule, and von Willebrand factor, to identify indirect acute respiratory distress syndrome. Test characteristics were 89% (80-97%) sensitivity, 80% (69-92%) specificity, positive predictive value 84% (74-93%), and negative predictive value 86% (76-96%).ConclusionsIndirect lung injury in children with acute respiratory distress syndrome is characterized by a biomarker profile indicative of endothelial activation, excess inflammation, and worse outcomes. A model using four biomarkers has the potential to be useful for more precisely identifying patients with acute respiratory distress syndrome whose pathobiology may respond to endothelial-targeted therapies in future trials.

Project description:BackgroundIn the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS.MethodsWe conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14.ResultsThe study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range.ConclusionsRosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).

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Biomarkers for patients with trauma associated acute respiratory distress syndrome.

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Biomarkers for patients with trauma associated acute respiratory distress syndrome.

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