The overall goal of the study is to risk stratify pediatric Acute Respiratory Distress Syndrome (ARDS) patients and to identify sub-phenotypes with shared biology in order to appropriately target therapies in future trials. This is a prospective, multicenter study of 500 intubated children with ARDS, with planned blood collection within 24 hours of ARDS onset and subsequent measurement of plasma protein biomarkers and peripheral blood gene expression.

Investigators will measure pre-determined biomarkers with known or suspected association with ARDS severity or outcome. Simultaneously, investigators will measure gene expression of peripheral blood. Both plasma biomarkers and gene expression profiles will be analyzed using various machine learning techniques, including classification and regression tree, latent class analysis, and hierarchical clustering with the goal of identifying sub-phenotypes of ARDS. These sub-phenotypes will be examined for association with outcome (primary is 28-day mortality), and explicitly tested for variation in response to exogenous treatments (e.g., corticosteroids).

Inclusion Criteria:

1. acute (≤ 7 days of risk factor) respiratory failure requiring invasive mechanical ventilation
2. age > 44 weeks corrected gestational age and < 17.5 years
3. invasive mechanical ventilation via endotracheal tube
4. bilateral infiltrates on chest radiograph
5. oxygenation index (OI) ≥ 4; or oxygen saturation index (OSI) ≥ 5 on 2 consecutive measurements at least 4 hours apart but < 24 hours apart
6. invasively ventilated ≤ 7 days before meeting above radiographic and oxygenation criteria

Exclusion Criteria:

1. weight < 3 kilograms
2. cyanotic congenital heart disease (other than Patent Foramen Ovale (PFO) or Patent Ductus Arteriosus (PDA))
3. tracheostomy at time of screening
4. invasively ventilated for > 7 days when meet ARDS criteria above
5. cardiac failure as predominant cause of respiratory failure
6. primary obstructive airway disease (asthma, bronchiolitis) by judgement of clinician as the primary cause of respiratory failure
7. alternative known chronic lung disease as cause of respiratory failure (cystic fibrosis, eosinophilic pneumonia, interstitial pneumonitis, pulmonary hemosiderosis, cryptogenic organizing pneumonia)
8. severe neurologic morbidity not expected to survive > 72 hours
9. any limitations of care at time of screening
10. previous enrollment in this study

Infants to adolescents between the ages of 44 weeks and 17.5 years, who are admitted to PICU for acute respiratory failure requiring invasive mechanical ventilation.

Specific consent will be obtained to store blood and use data for future research. We will share data with the research community using the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) program at NHLBI, and we will follow suggested guidelines for de-identifying the data (coding of site IDs, conversion of dates to study days).

Pursuant to the NIH policy, all data obtained from this proposal will be made available for research by qualified individuals within the scientific community after publication of the proposed studies. Gene expression data from Aims 2 and 3 will be made available simultaneous with publication of the results of these aims by uploading to the Gene Expression Omnibus. For dissemination of plasma biomarker results and the associated clinical dataset, we will use BioLINCC program at NHLBI, with release of a de-identified dataset with untraceable identifiers within 2 years of publication of the main manuscript.

Gene expression data will be released to Gene Expression Omnibus simultaneously with the publication of the data. Biomarker data will be released within 2 years of publication of the main manuscript.

We will follow NHLBI's guidelines for accessing BioLINCC data.