Respiratory Distress Syndrome, Respiratory Distress Syndrome, Adult
Conditions
Keywords
Endotype, Pediatric Acute Respiratory Distress Syndrome, Gene Expression, Transcriptomics
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.
Interventions
DIAGNOSTIC_TESTRespiratory epithelial cell brushing
At specified time points, nasal brushings will be performed to obtain RNA.
Sponsors
Society of Critical Care Medicine
Children's Hospital Medical Center, Cincinnati
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of PARDS Endotypes | 6 years | Use of unbiased cluster analysis of gene expression to identify subtypes in PARDS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
Countries
United States
Outcome results
None listed