Table 3:

Studies of PARDS-related phenotypes and endotypes

	Studytype	Participants	Sample type	Variables	Analysis	Key findings
Dahmer and colleagues (2022)47	Secondary analysis of data from the RESTORE trial29 and BALI ancillary study48	304 patients (≥2 weeks and <18 years) with PARDS	Plasma	Demographic and clinical variables and protein biomarkers	Latent class analysis to identify PARDS phenotypes and association with clinically relevant outcomes	Two phenotypes, hyperinflammatory and hypoinflammatory, identified with characteristics similar to those in adults; hyperinflammatory phenotype associated with worse outcomes
Grunwell and colleagues (2021)49	Prospective observational cohort study	74 patients (2 days to 18 years) recruited within 72 h of intubation for acute hypoxaemic respiratory failure (41 [55%] with PARDS)	Tracheal aspirate	Targeted metabolites	Clustering and partial least squares-discriminant analysis to explore clusters of metabolites and association with acute hypoxaemia severity and ventilator-free days	Three clusters of amino acid metabolites important to acute hypoxaemia severity correlated with ventilator-free days
Yehya and colleagues (2020)50	Prospective observational cohort study	96 patients (>1 month and <18 years) with PARDS*	mRNA from whole blood	Genome-wide transcripts	K-means clustering of expression profiles to identify subphenotypes and association with PICU mortality and ventilator-free days	Three subphenotypes identified with different clinical characteristics and prognoses
Yehya and colleagues (2019)51	Secondary analysis of a microarray-based study of paediatric sepsis52	67 patients (≤10 years) with sepsis-associated acute hypoxaemic respiratory failure (PaO2/FiO2 ratio ≤200 mm Hg)	mRNA from whole blood	Expression of 100 genes	Analysis of visual gene-expression patterns to test whether endotypes identified in paediatric sepsis are applicable to paediatric acute hypoxaemic respiratory failure†	Endotypes of paediatric acute hypoxaemic respiratory failure secondary to sepsis identified with differential risk for poor outcomes
Yehya and Wong (2018)53	Prospective observational cohort study	122 mechanically ventilated patients (>1 month and <18 years) with PARDS*	Plasma	Protein biomarkers	Classification and regression tree analysis to derive a risk prediction model for PARDS	Biomarker-based risk-stratification tool designed and validated for paediatric sepsis adapted for use in PARDS

BALI=Genetic Variation and Biomarkers in Children with Acute Lung Injury. FiO₂=fraction of inspired oxygen. PaO₂=partial pressure of arterial oxygen. PARDS=paediatric acuterespiratory distress syndrome. RESTORE=Randomised Evaluation of Sedation Titration for Respiratory Failure.

^*Defined using the Berlin criteria.⁹

^†Using the Gene Expression Dynamics Inspector software.