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

• Conditions: Acute Respiratory Failure; Acute Respiratory Distress Syndrome
• Interventions: Diagnostic Test: Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling

• Registration Number: NCT05451342
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2022-02-15
• Status Verified: 2022-06
• Study First Submitted: 2022-06-27
• Study First Submitted QC: 2022-07-05
• Last Update Submitted: 2022-07-05
• Study First Posted: 2022-07-11
• Last Update Posted: 2022-07-11
• Primary Completion: 2024-02-15
• Study Completion: 2024-06-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Aged >18 years old;
2. Meet the diagnostic criteria of ARDS according to the Berlin Criteria.

Exclusion Criteria

1. Aged≤18 years old;
2. Pregnancy;
3. No informed consent;

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
ARDS	Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling	Patients who meet the diagnostic criteria of ARDS
Non-ARDS	Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling	Patients without ARDS

Primary Outcome Measures

Name	Time	Method
Identification of ARDS Endotypes	2 years	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.

Secondary Outcome Measures

Name	Time	Method
Correlation of Endotypes with published ARDS specific Biomarkers	2 years	Correlate the endotypes with published markers of hyperinflammatory, microvascular-injury predominant, and distal lung epithelial cell-predominant injury in ARDS
Correlation of Endotypes with Intensive care unit-free days	Until 28 days following ICU admission	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.
Correlation of Endotypes with Ventilator-free days	Until 28 days following ICU admission	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.
Correlation of Endotypes with All-cause mortality	Until death or hospital discharge, assessed up to 28 days following ICU admission
Compare the PBMC and alveolar macrophage derived exosome levels between patients with ARDS and without ARDS	2 years	Plasma and BLAF supernatant are used for exosome extraction

Trial Locations

Locations (2)

PUMC; 🇨🇳 Beijing, Beijing, China

Yingying Yang; 🇨🇳 Beijing, Beijing, China