While writing this editorial, we learned that Professor Luciano Gattinoni—a giant in our field—had passed away. “Giant” seems an inadequate descriptor for a physician-scientist whose profound insights have fundamentally reshaped our understanding of critical care in general, and of acute respiratory distress syndrome (ARDS) in particular. His enduring legacy will continue to impact researchers, clinicians, and—most importantly—patients worldwide. It is our privilege to offer comment on some of his final contributions to the field of ARDS.

Since Ashbaugh and colleagues’ first description of ARDS in 1967 [1], efforts have been made to classify ARDS by disease severity to guide prognosis and treatment [2,3,4,5]. Oxygenation impairment, as defined by PaO₂:FiO₂ (P:F) or SaO₂:FiO₂ (S:F) ratios, is the primary basis for classifying severity in the Berlin Definition [4] and in the new Global Definition of ARDS [5]. However, other approaches for stratifying ARDS are emerging based on observations of differential risk and differential treatment response, including biological subphenotyping [6] and respiratory mechanics [7].

In this issue of Intensive Care Medicine, Catozzi et al. report the results of a study in which they suggest that hypoxemia may not be the most relevant parameter to guide lung-protective ventilation strategies in ARDS. They conducted a retrospective analysis of computed tomography scans, respiratory mechanics, and gas exchange in 228 ARDS patients with P:F ratio < 200 mmHg. They found no association between hypoxemia and driving pressure (ΔP) or mechanical power and concluded that respiratory mechanics and ventilatory ratio (a surrogate for dead space), rather than severity of hypoxemia, may be more relevant markers of risk for ventilator-induced lung injury. On this basis, they suggested that intensification of therapies for ARDS based on the severity of hypoxemia may be misguided.