Systems Biology ARDS Research with a Focus on Metabolomics

Metwaly, Sayed; Winston, Brent W.

doi:10.3390/metabo10050207

Cited by 17 publications

(17 citation statements)

References 65 publications

(98 reference statements)

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“…We have found specific metabolic differences between ARDS patients induced by COVID-19 or IAP. Most of these metabolic alterations have been previously reported as biomarkers of ARDS or ARDS severity [ 8 – 10 ]. For example, a similar serum metabolic profile including proline, glutamate, phenylalanine, and valine was reported as a sensitive biomarker of ARDS severity (mild, moderate, and severe) [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Alteration in amino acidic metabolism has been reported as one of the key features of ARDS development [ 8 , 9 ], and it has also been found significantly up-regulated in COVID-19 patients [ 34 , 39 , 46 , 47 ]. However, when we compared the metabolic profile of patients with ARDS due to COVID-19 or to IAP, we found that the amino acidic metabolism was decreased in COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, Magnetic Resonance Spectroscopy (MRS) emerges as a highly potential tool for studying metabolic disorders in respiratory diseases [ 7 ]. Several studies have proved the potential of MRS-based metabolomics to monitor patients with ARDS induced by respiratory infections [ 8 – 10 ]. A previous study compared the specific metabolic fingerprint of ARDS patients with either influenza A pneumonia (IAP) caused by the H1N1-2009 influenza virus or pneumonia caused by Streptococcus pneumoniae [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic diferences between COVID-19 and H1N1 influenza induced ARDS

Lorente

Nín²,

Villa

et al. 2021

Crit Care

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Background Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by lung inflammation and pulmonary edema. Coronavirus disease 2019 (COVID-19) is associated with ARDS in the more severe cases. This study aimed to compare the specificity of the metabolic alterations induced by COVID-19 or Influenza A pneumonia (IAP) in ARDS. Methods Eighteen patients with ARDS due to COVID-19 and twenty patients with ARDS due to IAP, admitted to the intensive care unit. ARDS was defined as in the American-European Consensus Conference. As compared with patients with COVID-19, patients with IAP were younger and received more often noradrenaline to maintain a mean arterial pressure > 65 mm Hg. Serum samples were analyzed by Nuclear Magnetic Resonance Spectroscopy. Multivariate Statistical Analyses were used to identify metabolic differences between groups. Metabolic pathway analysis was performed to identify the most relevant pathways involved in ARDS development. Results ARDS due to COVID-19 or to IAP induces a different regulation of amino acids metabolism, lipid metabolism, glycolysis, and anaplerotic metabolism. COVID‐19 causes a significant energy supply deficit that induces supplementary energy-generating pathways. In contrast, IAP patients suffer more marked inflammatory and oxidative stress responses. The classificatory model discriminated against the cause of pneumonia with a success rate of 100%. Conclusions Our findings support the concept that ARDS is associated with a characteristic metabolomic profile that may discriminate patients with ARDS of different etiologies, being a potential biomarker for the diagnosis, prognosis, and management of this condition. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolomic diferences between COVID-19 and H1N1 influenza induced ARDS

Lorente

Nín²,

Villa

et al. 2021

Crit Care

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“…To our knowledge metabolomics have not been used to study PARDS. Previous studies of adult ARDS ( Supplementary file 1 ) used targeted metabolomics platforms with relatively limited chemical space coverage ( Metwaly and Winston, 2020 ). Recently, Rogers et al used an untargeted metabolomics platform to compare the profile of pulmonary edema fluid collected at the time of endotracheal intubation for 16 adults with ARDS compared to 13 with cardiogenic pulmonary edema.…”

Section: Summary Of Research To Datementioning

confidence: 99%

Evolution of multiple omics approaches to define pathophysiology of pediatric acute respiratory distress syndrome

Whitney

Lee

et al. 2022

eLife

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Pediatric acute respiratory distress syndrome (PARDS), though both common and deadly in critically ill children, lacks targeted therapies. The development of effective pharmacotherapies has been limited, in part, by lack of clarity about the pathobiology of pediatric ARDS. Epithelial lung injury, vascular endothelial activation, and systemic immune activation are putative drivers of this complex disease process. Prior studies have used either hypothesis-driven (e.g., candidate genes and proteins, in vitro investigations) or unbiased (e.g., genome-wide association, transcriptomic, metabolomic) approaches to predict clinical outcomes and to define subphenotypes. Advances in multiple omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have permitted more comprehensive investigation of PARDS pathobiology. However, omics studies have been limited in children compared to adults, and analyses across multiple tissue types are lacking. Here, we synthesized existing literature on the molecular mechanism of PARDS, summarized our interrogation of publicly available genomic databases to determine the association of candidate genes with PARDS phenotypes across multiple tissues and cell types, and integrated recent studies that used single-cell RNA sequencing (scRNA-seq). We conclude that novel profiling methods such as scRNA-seq, which permits more comprehensive, unbiased evaluation of pathophysiological mechanisms across tissue and cell types, should be employed to investigate the molecular mechanisms of PRDS toward the goal of identifying targeted therapies.

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“…Previously, ARDS groups have been studied in comparison to non-ARDS reference groups, such as healthy controls or hospitalized patients without ARDS [5][6][7][8][9][14][15][16]. Here, we present the first detailed comparative multi-omic analysis between COVID-19 ARDS (n=43) and bacterial sepsisinduced (non-COVID-19) ARDS (n=24).…”

Section: Introductionmentioning

confidence: 99%

Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS

Batra

Whalen

Alvarez-Mulett

et al. 2022

Preprint

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BackgroundAcute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions.Methods and FindingsIn this study, we compared COVID-19 ARDS (n=43) and bacterial sepsis-induced (non-COVID-19) ARDS (n=24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within-ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation.ConclusionWe present a first comprehensive molecular characterization of differences between two ARDS etiologies – COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions.

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Systems Biology ARDS Research with a Focus on Metabolomics

Cited by 17 publications

References 65 publications

Metabolomic diferences between COVID-19 and H1N1 influenza induced ARDS

Metabolomic diferences between COVID-19 and H1N1 influenza induced ARDS

Evolution of multiple omics approaches to define pathophysiology of pediatric acute respiratory distress syndrome

Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS

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