Identifying PARDS Endotypes

Children's Hospital Medical Center, Cincinnati76 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

Conditions

Respiratory Distress Syndrome Respiratory Distress Syndrome, Adult

Interventions

Respiratory epithelial cell brushingDIAGNOSTIC_TEST

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

Eligibility

Sex: ALLMin age: 1 MonthMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Identification of PARDS Endotypes

Use of unbiased cluster analysis of gene expression to identify subtypes in PARDS

Time frame: 6 years

Secondary Outcomes

Lung Recovery Gene Expression Profile

Determination of pathways and processes that differentiate PARDS recovery from non-recovery as assessed by improvement in oxygenation.

Time frame: 6 years

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

Time frame: 6 years

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

Time frame: 6 years

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.