Evolution of multiple omics approaches to define pathophysiology of pediatric acute respiratory distress syndrome

Abstract

Pediatric acute respiratory distress syndrome (PARDS), though both common and deadly in critically ill children, lacks targeted therapies. The development of effective pharmacotherapies has been limited, in part, by lack of clarity about the pathobiology of pediatric ARDS. Epithelial lung injury, vascular endothelial activation, and systemic immune activation are putative drivers of this complex disease process. Prior studies have used either hypothesis-driven (e.g., candidate genes and proteins, in vitro investigations) or unbiased (e.g., genome-wide association, transcriptomic, metabolomic) approaches to predict clinical outcomes and to define subphenotypes. Advances in multiple omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have permitted more comprehensive investigation of PARDS pathobiology. However, omics studies have been limited in children compared to adults, and analyses across multiple tissue types are lacking. Here, we synthesized existing literature on the molecular mechanism of PARDS, summarized our interrogation of publicly available genomic databases to determine the association of candidate genes with PARDS phenotypes across multiple tissues and cell types, and integrated recent studies that used single-cell RNA sequencing (scRNA-seq). We conclude that novel profiling methods such as scRNA-seq, which permits more comprehensive, unbiased evaluation of pathophysiological mechanisms across tissue and cell types, should be employed to investigate the molecular mechanisms of PRDS toward the goal of identifying targeted therapies.

Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications

“…While preclinical studies in animal models of ALI have been conducted for decades, translating these findings into effective treatments or targeted drug therapies for human ARDS remains challenging. However, the advent of single-cell omics technology [246,247] has facilitated the identification of numerous biomarkers for the prognosis of ARDS in humans (Table 1). These biomarkers offer valuable tools for diagnosing the condition and assessing its prognosis, thereby enhancing our ability to manage the disease effectively.…”