Identifying PARDS Endotypes

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Respiratory Distress Syndrome, Respiratory Distress Syndrome, Adult

Intervention / Treatment
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* Diagnostic Test: Respiratory epithelial cell brushing


Participation Criteria
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Eligibility Criteria
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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%. Exclusion Criteria: Have a baseline oxygen requirement of 2 liters of oxygen or greater at home Have disruption of the nasal passages Have a history of excessive bleeding or known bleeding disorders Be at high risk of bleeding Have a do not resuscitate (DNR) or Limited Resuscitation Order

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PARDS<br>Children <18 years of age with PARDS and expected duration of hospitalization seven days or greater. | Diagnostic Test: Respiratory epithelial cell brushing<br>* At specified time points, nasal brushings will be performed to obtain RNA.<br>|
| Control<br>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<br>* At specified time points, nasal brushings will be performed to obtain RNA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of PARDS Endotypes | Use of unbiased cluster analysis of gene expression to identify subtypes in PARDS | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endotype, Pediatric Acute Respiratory Distress Syndrome, Gene Expression, Transcriptomics