Nucleotide Polymorphism in ARDS Outcome

Nucleotide Polymorphism in ARDS Outcome: a Whole Exome Sequencing Association Study

Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary vascular permeability and reduced aerated lung tissue. With an extremely high hospital mortality among 35 - 46%, current therapeutic strategies to increase ARDS survival are still limited. Advances in etiology and pathology of ARDS are urging. Numerous genetic variants were identified associated with ARDS outcome. By whole-exome sequencing association study, our goal was to explore the associations between genetic variants and ARDS outcome.

Study Overview

• Status: Completed
• Conditions: ARDS
• Intervention / Treatment: Other: Baseline-recorded data recorded

Detailed Description

Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary vascular permeability and reduced aerated lung tissue. With an extremely high hospital mortality among 35 - 46%, current therapeutic strategies to increase ARDS survival are still limited. Advances in etiology and pathology of ARDS are urging. Numerous genetic variants were identified associated with ARDS outcome. Then a few genetic risk factors have been discovered by large-scale genotyping approaches, from in vivo or in vitro models of lung injury, which highlight the importance of identifying genetic biomarkers of ARDS outcome to further improve stratification. The mutational landscape and variability at single nucleotide polymorphisms (SNP) with ARDS outcome in Chinese is unknown, not to mention their associations. By whole-exome sequencing association study, our goal was to explore the associations between genetic variants and ARDS outcome.

• Study Type: Observational
• Enrollment (Actual): 105

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Southeast university

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

ARDS adult patients

Description

Inclusion Criteria:

Adult ARDS (according to Berlin definition) patients were enrolled in the trial.

The diagnostic criteria included

1. within one week of a known clinical insult or new or worsening respiratory symptoms;
2. chest imaging showing that bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules;
3. respiratory failure not fully explained by cardiac failure or fluid overload;
4. arterial partial pressure of oxygen / fraction of inspiration oxygen (PaO2/FiO2 ratio, P/F ratio) less than or equal to 300 mmHg.

Exclusion criteria:

Patients refused to participate in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

ARDS patients; Adult ARDS (according to Berlin definition) patients were enrolled in the trial. The diagnostic criteria included (a) within one week of a known clinical insult or new or worsening respiratory symptoms; (b) chest imaging showing that bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules; (c) respiratory failure not fully explained by cardiac failure or fluid overload; and (d) arterial partial pressure of oxygen / fraction of inspiration oxygen (PaO2/FiO2 ratio, P/F ratio) less than or equal to 300 mmHg.

Other: Baseline-recorded data recorded; Baseline-recorded data recorded. Peripheral blood samples were drawn.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of survived participants	Survivors and non-survivors in ICU	through study completion, an average of 28 day

Collaborators and Investigators

• Sponsor: Southeast University, China
• Investigators: Principal Investigator: Jingyuan Xu, M.D., Southeast university

Publications and helpful links

General Publications

• Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS; ARDS Network. Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy. Am J Respir Crit Care Med. 2017 Feb 1;195(3):331-338. doi: 10.1164/rccm.201603-0645OC. Erratum In: Am J Respir Crit Care Med. 2018 Dec 15;198(12):1590. Am J Respir Crit Care Med. 2019 Sep 1;200(5):649.
• Calfee CS, Janz DR, Bernard GR, May AK, Kangelaris KN, Matthay MA, Ware LB. Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies. Chest. 2015 Jun;147(6):1539-1548. doi: 10.1378/chest.14-2454.
• Shankar-Hari M, McAuley DF. Acute Respiratory Distress Syndrome Phenotypes and Identifying Treatable Traits. The Dawn of Personalized Medicine for ARDS. Am J Respir Crit Care Med. 2017 Feb 1;195(3):280-281. doi: 10.1164/rccm.201608-1729ED. No abstract available.
• Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014 Aug;2(8):611-20. doi: 10.1016/S2213-2600(14)70097-9. Epub 2014 May 19.
• Xu JY, Liu AR, Wu ZS, Xie JF, Qu XX, Li CH, Meng SS, Liu SQ, Yang CS, Liu L, Huang YZ, Guo FM, Yang Y, Qiu HB. Nucleotide polymorphism in ARDS outcome: a whole exome sequencing association study. Ann Transl Med. 2021 May;9(9):780. doi: 10.21037/atm-20-5728.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: April 20, 2015
• First Submitted That Met QC Criteria: December 31, 2015
• First Posted (Estimate): January 1, 2016

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: ARDS; Nucleotide polymorphism
• Other Study ID Numbers: 2015ZDSYLL014.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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