Identifying PARDS Endotypes

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Recruiting

CT.gov ID

NCT03539783

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome Respiratory Distress Syndrome, Adult	Diagnostic Test: Respiratory epithelial cell brushing

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 Design

Study Type:

Observational

Anticipated Enrollment :

60 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Apr 1, 2018

Anticipated Primary Completion Date :

Mar 31, 2024

Anticipated Study Completion Date :

Mar 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
PARDS Children <18 years of age with PARDS and expected duration of hospitalization seven days or greater.	Diagnostic Test: Respiratory epithelial cell brushing At specified time points, nasal brushings will be performed to obtain RNA.
Control Children <18 years of age without PARDS or other lung disease and expected duration of hospitalization 7 days or greater.	Diagnostic Test: Respiratory epithelial cell brushing At specified time points, nasal brushings will be performed to obtain RNA.

Arm

Intervention/Treatment

PARDS

Children <18 years of age with PARDS and expected duration of hospitalization seven days or greater.

Diagnostic Test: Respiratory epithelial cell brushing

At specified time points, nasal brushings will be performed to obtain RNA.

Control

Children <18 years of age without PARDS or other lung disease and expected duration of hospitalization 7 days or greater.

Diagnostic Test: Respiratory epithelial cell brushing

At specified time points, nasal brushings will be performed to obtain RNA.

Outcome Measures

Primary Outcome Measures

Identification of PARDS Endotypes [6 years]
Use of unbiased cluster analysis of gene expression to identify subtypes in PARDS

Secondary Outcome Measures

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 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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 18 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

All potential participants must:

Be aged zero to 18 years (both control and ARDS, not age matched)
Be admitted to the PICU with expected duration of hospitalization 7 days or greater.

ARDS patients must:

Have acute changes in chest x-ray (CXR)
Have a known or suspected insult within the prior 7 days that is consistent with ARDS
Have an oxygenation index (OI) of 4 or greater or and oxygen-sat index (OSI) of 5 or greater
OI = mean airway pressure X fraction inspired oxygen (FiO2) / arterial oxygen partial pressure (PaO2)
OSI = mean airway pressure X FiO2 / oxyhemoglobin saturation (SpO2) with sat <= 97%.