Identifying PARDS Endotypes

Respiratory Distress Syndrome Clinical Trial

Official title:

Identification of Pediatric Acute Respiratory Distress Syndrome Subtypes by Bronchial and Nasal Epithelial Transcriptomics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03539783
• Other study ID #: CIN_PARDSEndo_001
• Status: Completed
• Start date: April 1, 2018
• Est. completion date: September 5, 2022

Study information

• Verified date: March 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Pediatric acute respiratory distress syndrome (PARDS) is a severe and diffuse lung injury that is a common cause of admission and mortality in the pediatric intensive care unit (PICU). PARDS can be secondary to many different causes, and there are few therapies that have been shown beneficial in PARDS. This study seeks to identify important PARDS subtypes using gene expression profiling of bronchial epithelial cells from control and PARDS subjects.

Description:

Enrolled subjects will have nasal brushings collected at days 1, 3, 7, and 14 of intubation with collection of serum at these same time points. Brushing RNA will be processed by mRNA-Seq for gene expression analysis and compared to previously published serum biomarkers (interleukin-8, advanced glycosylation end-product specific receptor, and angiopoietin-2) to assess correlation and ability to discriminate PARDS endotypes. Changes in gene expression over time will be assessed to define a PARDS recovery gene expression signature, and correlation between bronchial and nasal gene expression will be determined.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: September 5, 2022
• Est. primary completion date: August 11, 2022
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

Inclusion Criteria:

All potential participants must:

1. Be aged zero to 18 years (both control and ARDS, not age matched)

2. Be admitted to the PICU with expected duration of hospitalization 7 days or greater.

ARDS patients must:

1. Have acute changes in chest x-ray (CXR)

2. Have a known or suspected insult within the prior 7 days that is consistent with ARDS

3. Have an oxygenation index (OI) of 4 or greater or and oxygen-sat index (OSI) of 5 or greater

1. OI = mean airway pressure X fraction inspired oxygen (FiO2) / arterial oxygen partial pressure (PaO2)

2. OSI = mean airway pressure X FiO2 / oxyhemoglobin saturation (SpO2) with sat <= 97%.

Exclusion Criteria:

1. Have a baseline oxygen requirement of 2 liters of oxygen or greater at home

2. Have disruption of the nasal passages

3. Have a history of excessive bleeding or known bleeding disorders

4. Be at high risk of bleeding

5. Have a do not resuscitate (DNR) or Limited Resuscitation Order

Related Conditions & MeSH terms

• Acute Lung Injury
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Diagnostic Test:
• Respiratory epithelial cell brushing
At specified time points, nasal brushings will be performed to obtain RNA.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Society of Critical Care Medicine

Country where clinical trial is conducted

United States, 

References & Publications (2)

Williams JG, Jones RL, Yunger TL, Lahni PM, Yehya N, Varisco BM. Comparison of 16 Pediatric Acute Respiratory Distress Syndrome-Associated Plasma Biomarkers With Changing Lung Injury Severity. Pediatr Crit Care Med. 2024 Jan 1;25(1):e31-e40. doi: 10.1097/ — View Citation

Williams JG, Joshi R, Haslam D, Yehya N, Jones RL, Paranjpe A, Pujato M, Roskin KM, Lahni PM, Wong HR, Varisco BM. Multi-omic characterization of pediatric ARDS via nasal brushings. Respir Res. 2022 Jul 9;23(1):181. doi: 10.1186/s12931-022-02098-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of PARDS Endotypes	Use of unbiased cluster analysis of gene expression to identify subtypes in PARDS	6 years
Secondary	Lung Recovery Gene Expression Profile	Determination of pathways and processes that differentiate PARDS recovery from non-recovery as assessed by improvement in oxygenation.	6 years
Secondary	Correlation of Nasal and Bronchial Gene Expression	Similarity analysis of bronchial and nasal gene expression in subjects undergoing bronchoscopy to determine whether nasal can be used as a surrogate for bronchial	6 years
Secondary	Correlation of Endotypes with Lung Cell-specific Biomarkers	Matching PARDS endotypes with published markers of hyperinflammatory, microvascular-injury predominant, and distal lung epithelial cell-predominant injury	6 years