A narrative review on the future of ARDS: evolving definitions, pathophysiology, and tailored management

Abstract

Acute respiratory distress syndrome (ARDS) is a severe complication of critical illness, characterized by bilateral lung infiltrates and hypoxemia. Its clinical and pathophysiological heterogeneity poses challenges for both diagnosis and treatment. This review outlines the evolution of ARDS definitions, discusses the underlying pathophysiology of ARDS, and examines the clinical implications of its heterogeneity. Traditional ARDS definitions required invasive mechanical ventilation and relied on arterial blood gas measurements to calculate the PaO₂/FiO₂ ratio. Recent updates have expanded these criteria to include patients receiving noninvasive respiratory support, such as high-flow nasal oxygen, and the adoption of the SpO₂/FiO₂ ratio as an alternative to the PaO₂/FiO₂ ratio. While these changes broaden the diagnostic criteria, they also introduce additional complexity. ARDS heterogeneity-driven by varying etiologies, clinical subphenotypes, and underlying biological mechanisms-highlights the limitations of a uniform management approach. Emerging evidence highlights the presence of distinct ARDS subphenotypes, each defined by unique molecular and clinical characteristics, offering a pathway to more precise therapeutic targeting. Advances in omics technologies-encompassing genomics, proteomics, and metabolomics-are paving the way for precision-medicine approaches with the potential to revolutionize ARDS management by tailoring interventions to individual patient profiles. This paradigm shift from broad diagnostic categories to precise, subphenotype-driven care holds promise for redefining the landscape of treatment for ARDS and, ultimately, improving outcomes in this complex, multifaceted syndrome.

Keywords: Acute respiratory distress syndrome; Heterogeneity; Omics; Pathophysiology; Personalized medicine; Subphenotype.

Fig. 1

Historical development of the definition of ARDS. Many investigators and organizations have made efforts towards the accurate description and identification of ARDS, beginning with Ashbaugh’s description of the syndrome in 1967 and leading to the “Berlin definition” in 2012. Two new guidelines (ESICM guidelines in ARDS, 2023 and A New global definition of ARDS, 2024) have been published recently. ARDS, Acute respiratory distress syndrome; PEEP, Positive end-expiratory pressure; PaO₂, Arterial oxygen pressure; FiO₂, Fraction of inspired oxygen; AECC, American–European Consensus Conference, HFNO, High-Flow Nasal Oxygen; SpO₂; Peripheral oxygen saturation

Fig. 2

Summary of PEEP (Positive End-Expiratory Pressure) Strategies in ARDS Subphenotypes A and B