Clinical trial NCT03539783: Identifying PARDS Endotypes
Official title: Identification of Pediatric Acute Respiratory Distress Syndrome Subtypes by Bronchial and Nasal Epithelial Transcriptomics
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Distress Syndrome
Respiratory Distress Syndrome, Adult
Keywords: Endotype
Pediatric Acute Respiratory Distress Syndrome
Gene Expression
Transcriptomics
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Society of Critical Care Medicine
First posted: 2018-05-29
Enrollment: 76
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of PARDS Endotypes
timeFrame: 6 years
Secondary outcomes:
measure: Lung Recovery Gene Expression Profile
timeFrame: 6 years
measure: Correlation of Nasal and Bronchial Gene Expression
timeFrame: 6 years
measure: Correlation of Endotypes with Lung Cell-specific Biomarkers
timeFrame: 6 years
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Stephen M Standage, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.