Advancing precision medicine for acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome. Understanding of the complex pathways involved in lung injury pathogenesis, resolution, and repair has grown considerably in recent decades. Nevertheless, to date, only therapies targeting ventilation-induced lung injury have consistently proven beneficial, and despite these gains, ARDS morbidity and mortality remain high. Many candidate therapies with promise in preclinical studies have been ineffective in human trials, probably at least in part due to clinical and biological heterogeneity that modifies treatment responsiveness in human ARDS. A precision medicine approach to ARDS seeks to better account for this heterogeneity by matching therapies to subgroups of patients that are anticipated to be most likely to benefit, which initially might be identified in part by assessing for heterogeneity of treatment effect in clinical trials. In October 2019, the US National Heart, Lung, and Blood Institute convened a workshop of multidisciplinary experts to explore research opportunities and challenges for accelerating precision medicine in ARDS. Topics of discussion included the rationale and challenges for a precision medicine approach in ARDS, the roles of preclinical ARDS models in precision medicine, essential features of cohort studies to advance precision medicine, and novel approaches to clinical trials to support development and validation of a precision medicine strategy. In this Position Paper, we summarise workshop discussions, recommendations, and unresolved questions for advancing precision medicine in ARDS. Although the workshop took place before the COVID-19 pandemic began, the pandemic has highlighted the urgent need for precision therapies for ARDS as the global scientific community grapples with many of the key concepts, innovations, and challenges discussed at this workshop.

An online nomogram of acute respiratory distress syndrome originating from pulmonary disease

“…The primary aetiology of ARDS is diverse, and the pathophysiological mechanism is complex; moreover, the response to treatment varies greatly among patients. The high heterogeneity was one of the principal reasons for the inconsistent results of many clinical trials 7 ; hence, there was an urgent need for precision medicine 35 …”

“…The high heterogeneity was one of the principal reasons for the inconsistent results of many clinical trials 7 ; hence, there was an urgent need for precision medicine. 35 The nomogram focused on ARDSp, with robust validations both internally and externally; thus, the strict inclusion criteria might largely reduce the defects caused by the insufficient sample size to some extent.…”

Obacunone alleviates ferroptosis during lipopolysaccharide-induced acute lung injury by upregulating Nrf2-dependent antioxidant responses

“…The pathogenesis of ALI has not been clearly elucidated. Currently, its clinical treatment mainly includes protective mechanical ventilation, with no effective drug for its treatment [ 5 , 6 ]. Therefore, it is important to elucidate the detailed pathogenesis and pathophysiological mechanisms of ALI and develop effective drugs for its treatment.…”

Distinct respiratory tract biological pathways characterizing ARDS molecular phenotypes

“…While some pharmacologic treatments have decreased mortality in mechanically ventilated patients with COVID-19 2,3 , no drug has consistently reduced mortality in more typical heterogeneous cohorts of patients with ARDS. There is a growing recognition that biological heterogeneity within the syndrome is a significant barrier to identifying effective treatments 4 .…”