Explore Potential Plasma and BALF Immunometabolic and Lipidomic Biomarkers for Identifying ARDS Endotypes

Study Overview
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Brief Summary
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Acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes high mortality (41% to 58%). Previous studies have reported that biomarkers can facilitate phenotypic diagnosis of ARDS, enabling precision treatment of ARDS. Although there were many studies that found some potential therapeutic targets for ARDS, no pharmacotherapies have been validated to treat ARDS. The development of biomarkers to predict the prognosis and monitor the response to treatment would be of interest for selecting patients for specific therapeutic trials. Many recent studies have shown that immune metabolic changes are involved in the pathogenesis of ARDS and may become a new therapeutic target for them. We aimed to identify a panel of immunometabolic and lipidomic biomarkers derived from blood and bronchoalveolar lavage fluid (BALF) which may help differentiate the ARDS endotypes.

Detailed Description
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PROTOCOL OUTLINE: This is an observational study. The blood and BALF samples will be collected from patients with ARDS for exosome extraction and transcriptome and metabolomic analysis. Exosome characterization and differential genes and metabolites will be identified.

Official Title
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Explore Potential Plasma and BALF Immunometabolic and Lipidomic Biomarkers for Identifying the Endotypes in Patients With ARDS

Conditions
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Acute Respiratory Distress Syndrome, Acute Respiratory Failure

Intervention / Treatment
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* Diagnostic Test: Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged >18 years old; Meet the diagnostic criteria of ARDS according to the Berlin Criteria. Exclusion Criteria: Aged≤18 years old; Pregnancy; No informed consent;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ARDS<br>Patients who meet the diagnostic criteria of ARDS | Diagnostic Test: Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling<br>* Blood samples and BALD samples will be collected for further integrated transcriptomics, metabolomics, lipidomics analysis, and exosome extraction.<br>|
| Non-ARDS<br>Patients without ARDS | Diagnostic Test: Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling<br>* Blood samples and BALD samples will be collected for further integrated transcriptomics, metabolomics, lipidomics analysis, and exosome extraction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of ARDS Endotypes | Blood samples will be collected on day 1, 3, 5,7 since ARDS diagnosis is made (day 0) and BALF samples will be collected on day 1 and day 7. Blood samples are used to extract PBMC and BALF samples are used to extract alveolar macrophage. Afterwards, PBMC and alveolar macrophage are saved for further transcriptomic and metabomic analysis. At the same time, clinical and biological date are collected to identify subgroups of patients that might share mortality risk, clinical course, and/or treatment responsiveness. At last, the relationship between transcriptomic and metabomic signature of PBMC and alveolar macrophage and the clinical phenotypes are analyzed to determine ARDS endotypes. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the PBMC and alveolar macrophage derived exosome levels between patients with ARDS and without ARDS | Plasma and BLAF supernatant are used for exosome extraction | 2 years | 
| Correlation of Endotypes with published ARDS specific Biomarkers | Correlate the endotypes with published markers of hyperinflammatory, microvascular-injury predominant, and distal lung epithelial cell-predominant injury in ARDS | 2 years | 
| Correlation of Endotypes with Intensive care unit-free days | Intensive care unit-free days are calculated by the number of days in the first 28 days following ICU admission that a patient is alive and not in the intensive care unit. | Until 28 days following ICU admission | 
| Correlation of Endotypes with Ventilator-free days | Ventilator-free days are calculated by the number of days in the first 28 days following ICU admissionthat a patient is alive and not on a ventilator. | Until 28 days following ICU admission | 
| Correlation of Endotypes with All-cause mortality |  | Until death or hospital discharge, assessed up to 28 days following ICU admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, biomarkers, immunometabolism