Precision medicine in acute respiratory distress syndrome: workshop report and recommendations for future research

Abstract

Acute respiratory distress syndrome (ARDS) is a devastating critical illness that can be triggered by a wide range of insults and remains associated with a high mortality of around 40%. The search for targeted treatment for ARDS has been disappointing, possibly due to the enormous heterogeneity within the syndrome. In this perspective from the European Respiratory Society research seminar on "Precision medicine in ARDS", we will summarise the current evidence for heterogeneity, explore the evidence in favour of precision medicine and provide a roadmap for further research in ARDS. There is evident variation in the presentation of ARDS on three distinct levels: 1) aetiological; 2) physiological and 3) biological, which leads us to the conclusion that there is no typical ARDS. The lack of a common presentation implies that intervention studies in patients with ARDS need to be phenotype aware and apply a precision medicine approach in order to avoid the lack of success in therapeutic trials that we faced in recent decades. Deeper phenotyping and integrative analysis of the sources of variation might result in identification of additional treatable traits that represent specific pathobiological mechanisms, or so-called endotypes.

FIGURE 1

ARDS can be phenotyped based on information in three domains: aetiology, physiology and biology. Multiple phenotypes can coexist between and within a domain (within domain coexistence not shown). We recognise that there is a complex interaction between phenotypes and that true endotypes might capture phenotypic presentations within multiple domains. Traits are potentially treatable based on phenotypic recognition and subsequent empirical evidence for effectivity of intervention or on deep understanding of the critical causal pathways. ARDS: acute respiratory distress syndrome; PEEP: positive end-expiratory pressure.