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Therapeutic targeting of metabolic alterations in acute respiratory distress syndrome.

ABSTRACT: Acute respiratory distress syndrome (ARDS) remains a significant source of mortality in critically ill patients. Characterised by acute, widespread alveolar inflammation and pulmonary oedema, its pathophysiological heterogeneity has meant that targeted treatments have remained elusive. Metabolomic analysis has made initial steps in characterising the underlying metabolic derangements of ARDS as an indicator of phenotypical class and has identified mitochondrial dysfunction as a potential therapeutic target. Mesenchymal stem cells and their derived extracellular vesicles have shown significant promise as potential therapies in delivering mitochondria in order to redivert metabolism onto physiological pathways.

SUBMITTER: Robinson MJ

PROVIDER: S-EPMC9488567 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Therapeutic targeting of metabolic alterations in acute respiratory distress syndrome.

Robinson Matthew John MJ Krasnodembskaya Anna D AD

European respiratory review : an official journal of the European Respiratory Society 20200601 156

Acute respiratory distress syndrome (ARDS) remains a significant source of mortality in critically ill patients. Characterised by acute, widespread alveolar inflammation and pulmonary oedema, its pathophysiological heterogeneity has meant that targeted treatments have remained elusive. Metabolomic analysis has made initial steps in characterising the underlying metabolic derangements of ARDS as an indicator of phenotypical class and has identified mitochondrial dysfunction as a potential therape ...[more]

PMID: 32620587

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Project description:ImportanceObesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome.ObjectiveTo determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19.Design, setting, and participantsThis multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021.ExposuresExposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia.Main outcomes and measuresThe primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS).ResultsAmong 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P < .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P < .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P < .001; 3 criteria: 817 patients with ARDS [19.3%]; P < .001; 4 criteria: 203 patients with ARDS [24.3%]; P < .001).Conclusions and relevanceThese findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present.

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Therapeutic targeting of metabolic alterations in acute respiratory distress syndrome.

Publications

Therapeutic targeting of metabolic alterations in acute respiratory distress syndrome.

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