Reply to Liufu et al. and to Palanidurai et al.

From the Authors:

We thank Liufu and colleagues for their comments regarding our article on the new global definition of acute respiratory distress syndrome (ARDS) (1). The authors express concern that defining a clinical syndrome on the basis of response to a therapeutic intervention is not correct. We agree that it would be preferable to define ARDS on the basis of clinical or laboratory tests that are specific for the underlying pathophysiology, as in the use of troponin to define acute myocardial infarction; however, such measurements of underlying pathophysiology are not currently available for clinical use in defining ARDS, so the current definitions (Berlin and the new global definition) rely on imaging and physiological measurements. The value of the new global definition is that it broadens the criteria for respiratory support to include spontaneously breathing patients treated with high-flow supplemental oxygen or noninvasive ventilation, and it incorporates methods to allow patients in resource-limited settings to be included in the definition of ARDS, regardless of the availability of supportive therapies. These changes allow more patients with the underlying pathophysiology of acute lung injury to meet the definition of ARDS. This has important implications for clinical care and research studies. The authors’ concluding recommendation to include measurement of pulmonary vascular permeability, lung weight, and aeration of lung tissue in the diagnostic criteria for ARDS is an excellent aspirational suggestion to improve precision, but it is currently impractical, even for research studies.

We also thank Palanidurai and colleagues for their comments. The authors point out the limitations of using the Pa_O2/Fi_O2 (P/F) ratio to define the severity of ARDS and refer to their prior study of a new oxygenation ratio that incorporates positive end-expiratory pressure (PEEP) in the denominator (P/FP) to improve categorization of patients with ARDS into mild, moderate, and severe categories. We agree that the P/F ratio can change over short periods of time, particularly in some patients with recruitable areas of the lung, resulting in an apparent change in the severity of lung injury. Because the P/F ratio is dependent on Fi_O2, changes in Fi_O2 may also result in apparent changes in severity (2). To minimize these effects, research studies have required that patients be observed on standardized ventilator settings for some period of time (e.g., 12–24 h or longer) before meeting eligibility criteria for inclusion in a trial, although such an approach is impractical for interventions targeting the earliest phases of ARDS (3). Although imperfect, the ARDS severity categories based on P/F ratio do correlate with mortality (4). We agree that the P/FP ratio is a promising method to incorporate PEEP, but the major limitation is that this applies only to intubated patients, in whom PEEP can be measured accurately. The value of the new global definition of ARDS is that it applies to nonintubated patients who require high levels of oxygen support and to those in resource-limited settings, in whom the P/FP cannot be measured (5). We believe that further prospective studies comparing the P/F versus P/PF, as well as the oxygen saturation as measured by pulse oximetry/Fi_O2 (S/F) versus S/FP ratios, will be valuable.