Identifying PARDS Endotypes

Completed

• Conditions: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Adult
• Interventions: Diagnostic Test: Respiratory epithelial cell brushing

• Registration Number: NCT03539783
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2018-04-01
• Study First Submitted: 2018-05-16
• Study First Submitted QC: 2018-05-16
• Study First Posted: 2018-05-29
• Primary Completion: 2022-08-11
• Study Completion: 2022-09-05
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-15
• Last Update Posted: 2024-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 76

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PARDS	Respiratory epithelial cell brushing	Children \<18 years of age with PARDS and expected duration of hospitalization seven days or greater.
Control	Respiratory epithelial cell brushing	Children \<18 years of age without PARDS or other lung disease and expected duration of hospitalization 7 days or greater.

Primary Outcome Measures

Name	Time	Method
Identification of PARDS Endotypes	6 years	Use of unbiased cluster analysis of gene expression to identify subtypes in PARDS

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States