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Biological Phenotyping in Sepsis and Acute Respiratory Distress Syndrome.

ABSTRACT: Heterogeneity in sepsis and acute respiratory distress syndrome (ARDS) is increasingly being recognized as one of the principal barriers to finding efficacious targeted therapies. The advent of multiple high-throughput biological data ("omics"), coupled with the widespread access to increased computational power, has led to the emergence of phenotyping in critical care. Phenotyping aims to use a multitude of data to identify homogenous subgroups within an otherwise heterogenous population. Increasingly, phenotyping schemas are being applied to sepsis and ARDS to increase understanding of these clinical conditions and identify potential therapies. Here we present a selective review of the biological phenotyping schemas applied to sepsis and ARDS. Further, we outline some of the challenges involved in translating these conceptual findings to bedside clinical decision-making tools.

SUBMITTER: Sinha P

PROVIDER: S-EPMC10617629 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Biological Phenotyping in Sepsis and Acute Respiratory Distress Syndrome.

Sinha Pratik P Meyer Nuala J NJ Calfee Carolyn S CS

Annual review of medicine 20221205

Heterogeneity in sepsis and acute respiratory distress syndrome (ARDS) is increasingly being recognized as one of the principal barriers to finding efficacious targeted therapies. The advent of multiple high-throughput biological data ("omics"), coupled with the widespread access to increased computational power, has led to the emergence of phenotyping in critical care. Phenotyping aims to use a multitude of data to identify homogenous subgroups within an otherwise heterogenous population. Incre ...[more]

PMID: 36469902

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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.).

Project description:Background: Acute respiratory distress syndrome (ARDS) is an unresolved challenge in the field of respiratory and critical care, and the changes in the lung microbiome during the development of ARDS and their clinical diagnostic value remain unclear. This study aimed to explore the role of the lung microbiome in disease progression in patients with sepsis-induced ARDS and potential therapeutic targets. Methods: Patients with ARDS were divided into two groups according to the initial site of infection, intrapulmonary infection (ARDSp, 111 cases) and extrapulmonary infection (ARDSexp, 45 cases), and a total of 28 patients with mild pulmonary infections were enrolled as the control group. In this study, we sequenced the DNA in the bronchoalveolar lavage fluid collected from patients using metagenomic next-generation sequencing (mNGS) to analyze the changes in the lung microbiome in patients with different infectious site and prognosis and before and after antibiotic treatment. Results: The Shannon-Wiener index indicated a statistically significant reduction in microbial diversity in the ARDSp group compared with the ARDSexp and control groups. The ARDSp group was characterized by a reduction in microbiome diversity, mainly in the normal microbes of the lung, whereas the ARDSexp group was characterized by an increase in microbiome diversity, mainly in conditionally pathogenic bacteria and intestinal microbes. Further analysis showed that an increase in Bilophila is a potential risk factor for death in ARDSexp. An increase in Escherichia coli, Staphylococcus aureus, Candida albicans, enteric microbes, or conditional pathogens may be risk factors for death in ARDSp. In contrast, Hydrobacter may be a protective factor in ARDSp. Conclusion: Different initial sites of infection and prognoses are likely to affect the composition and diversity of the pulmonary microbiome in patients with septic ARDS. This study provides insights into disease development and exploration of potential therapeutic targets.

Dataset Information

Biological Phenotyping in Sepsis and Acute Respiratory Distress Syndrome.

Publications

Biological Phenotyping in Sepsis and Acute Respiratory Distress Syndrome.

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