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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome; Acute Respiratory Failure
• Intervention / Treatment: Diagnostic test: Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling

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 Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Yingying Yang, MD; Phone Number: +8618800173833; Email: yangyingying2703@outlook.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • PUMC
      • Contact: Hui Xu, MD; Phone Number: 01069156874; Email: pumchkyc@163.com
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Yingying Yang
      • Contact: Yingying Yang; Phone Number: +8618800173833; Email: yangyingying2703@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

ICU patients with the diagnosis of ARDS

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ARDS; Patients who meet the diagnostic criteria of ARDS	Diagnostic test: Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling; Blood samples and BALD samples will be collected for further integrated transcriptomics, metabolomics, lipidomics analysis, and exosome extraction.
Non-ARDS; Patients without ARDS	Diagnostic test: Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling; Blood samples and BALD samples will be collected for further integrated transcriptomics, metabolomics, lipidomics analysis, and exosome extraction.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Director: Yun Long, MD, Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Anticipated): February 15, 2024
• Study Completion (Anticipated): June 15, 2024

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: July 5, 2022
• First Posted (Actual): July 11, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2022
• Last Update Submitted That Met QC Criteria: July 5, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: ARDS, biomarkers, immunometabolism
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: ZS-3391

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No