Identifying PARDS Endotypes

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Adult
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

• Study Contact: Name: Rhonda Jones, RN; Phone Number: 513-636-9749; Email: rhonda.jones@cchmc.org
• Study Contact Backup: Name: Toni Yunger; Phone Number: 513-636-5572; Email: toni.yunger@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Control subjects will be patients admitted to the PICU for non-lung injury related conditions.

PARDS subjects will be intubated patients with PARDS in the PICU.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Society of Critical Care Medicine
• Investigators: Principal Investigator: Stephen M Standage, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• Williams JG, Joshi R, Haslam D, Yehya N, Jones RL, Paranjpe A, Pujato M, Roskin KM, Lahni PM, Wong HR, Varisco BM. Multi-omic characterization of pediatric ARDS via nasal brushings. Respir Res. 2022 Jul 9;23(1):181. doi: 10.1186/s12931-022-02098-3.
• Williams JG, Jones RL, Yunger TL, Lahni PM, Yehya N, Varisco BM. Comparison of 16 Pediatric Acute Respiratory Distress Syndrome-Associated Plasma Biomarkers With Changing Lung Injury Severity. Pediatr Crit Care Med. 2024 Jan 1;25(1):e31-e40. doi: 10.1097/PCC.0000000000003311. Epub 2023 Jun 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): August 11, 2022
• Study Completion (Actual): September 5, 2022

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Gene Expression; Transcriptomics; Endotype; Pediatric Acute Respiratory Distress Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: CIN_PARDSEndo_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Study info will be shared with interested investigators on a case by case basis. Microarray data will be posted on an archive such as GeoDatasets but we are unclear how correlative clinical and serum biomarker data would be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No