ARDS Definition Gets a Global Makeover to Reach the 87 Percent

Acute respiratory distress syndrome, or ARDS, is one of the most feared conditions in intensive care, and the way doctors define it is now being rethought for the entire world. In a new editorial published in Intensive Care Medicine, researchers Elisabeth D. Riviello, Lorraine B. Ware and Michael A. Matthay argue that the definition of ARDS must simultaneously become more global and more personal. Writing in the second part of a two-part editorial, they explain that the current Global Definition of ARDS is a major step forward because it can be applied even in resource-constrained settings, yet it remains a syndromic and clinical description with no clear connection to the underlying biology of the disease. Their central claim is that the next era of ARDS care depends on using this accessible definition to bring patients everywhere into research, while also refining the syndrome into treatable traits that can be targeted by specific therapies.

The stakes are enormous. ARDS is common, carries high mortality and often leaves survivors with long-term deficits. The LUNG SAFE study, which spanned 50 countries on 5 continents, found that 10 percent of all intensive care unit patients had ARDS, that 23 percent of all ventilated patients had the syndrome, and that hospital mortality reached 40 percent. Notably, LUNG SAFE included no low-income countries. The Kigali ARDS study in Rwanda helps fill that gap: in a single center, 4 percent of all adult hospital admissions, not just intensive care admissions, had ARDS, 70 percent of these patients were cared for entirely outside the intensive care unit, and hospital mortality was 50 percent. Those who survive ARDS can be left with long-term and sometimes severe deficits, the editorial notes.

Why does a definition matter so much in clinical practice? The authors give three reasons: ARDS is a common and morbid condition, the definition is required for diagnosis and treatment, and the definition is necessary for research that includes diverse populations and explores treatable traits. Diagnosis is the gateway to proven interventions supported by guidelines. Low tidal volume ventilation, tested in the ARMA trial; conservative fluid management, tested in the FACTT trial; and prone positioning for severe ARDS, tested in the PROSEVA trial, have all been shown to improve outcomes for ARDS patients. Crucially, the editorial points out that these interventions are always feasible in resource-constrained settings in the case of conservative fluids, and often feasible in the case of proning and low tidal volume ventilation. An accessible definition, followed by proven treatment, is what current ARDS patients need.

The second reason the definition matters is research equity. Study inclusion criteria are built from definitions, so the way a syndrome is defined determines which populations get studied and, ultimately, which populations benefit from discoveries. The authors warn that future studies should not be done exclusively in the 13 percent of the world’s population living in high-income countries and then generalized to the other 87 percent, given differences in prevalent infectious disease pathogens, co-morbidities, time to presentation, resources including critical care and other organ support, and potential genetic variations.

Sepsis resuscitation offers a striking example of why this matters. Liberal fluid resuscitation in sepsis was initially thought to be advantageous compared with conservative resuscitation in high-income countries, then was definitively found to be neutral in those settings, but was found to be definitively harmful in resource-constrained settings. The lesson is that a treatment strategy validated in wealthy hospitals cannot simply be exported to the rest of the world without testing it there. Another example is ongoing research on advanced noninvasive respiratory support in resource-constrained settings: the ARISE-AFRICA and BREATHE trials are operating under the hypothesis that less-resource-intensive interventions such as high flow oxygen or continuous positive airway pressure could have even greater positive benefits in settings where safe invasive ventilation is less available than they do in resource-rich settings, though also potentially higher risks.

The editorial also describes how an accessible definition opens the door for resource-constrained settings to participate in the cutting edge of ARDS research, including subphenotyping along several different axes to target specific pathways. Subphenotypes and treatable traits can be based on the severity of hypoxemia, the presence or absence of shock, protein biomarkers, and biomarkers that are common laboratory values and vital signs. Physiologic traits can also define subgroups, including recruitability, chest wall and pleural pressures, right ventricular dysfunction, dead space fraction, and spontaneous effort. Interventions being examined for different subphenotypes include options that are feasible in resource-constrained settings, such as corticosteroids, statins, furosemide, and noninvasive respiratory support. Defining ARDS in a way that researchers and populations globally can access allows future interventional studies to be done in the very populations to which they will apply.

So what comes next? The authors believe the most critical advances in defining ARDS currently lie in going broader and also more specific: accelerating equity in ARDS treatment and research by ensuring that ARDS patients in all settings globally can be identified, and moving toward treatable traits and personalization within global ARDS populations, so that the mechanisms underlying ARDS in different patients can be targeted directly by relevant therapies. In other words, the same definition must serve a farmer in a rural district hospital and a patient in a high-tech academic intensive care unit, yet it must also become precise enough to route each of them toward the therapy that matches their disease mechanism.

The Global Definition of ARDS provides an actionable definition and is applicable globally, even in resource-constrained settings, but the editorial is candid about its limits. It remains a syndromic and clinical definition, without a clear connection to underlying biology and treatable traits. The preponderance of negative trials in ARDS suggests the need for a paradigm shift toward definitions that include personalized mechanistic targets. In addition, the reliability and necessity of the bilateral opacity requirement in the ARDS definition requires further study, the authors write, pointing to evidence gaps that remain even in the newest framework.

Much has changed since ARDS was first described in 1967. Definitional changes have been critical for progress, enabling both research and treatment to advance. The editorial closes with a call to use the tools the Global Definition of ARDS has given the field to ensure that patients across the world, regardless of resources, are included in research and care. With that entire global population enrolled, the authors argue, the definition can be refined over time, leveraging the science around subphenotypes and treatable traits to develop effective personalized interventions that target the pathophysiologic pathways of ARDS for patients everywhere. The time has come, they conclude, for the combined globalization and personalization of ARDS.

For clinicians, researchers and policymakers, the message is clear. A definition is not an academic formality; it decides who is counted, who is treated with proven therapies, and who is represented in the trials that shape tomorrow’s standards of care. By pairing a globally accessible case definition with a research agenda built on treatable traits, the authors sketch a future in which a diagnosis of ARDS carries the same meaning in Kigali as in Boston, and in which the next generation of therapies is tested in, and designed for, the full diversity of the patients it is meant to save.

Subject of Research: Redefining the definition of acute respiratory distress syndrome to enable global diagnosis, equitable research participation and personalized treatment based on treatable traits

Article Title: Defining ARDS: globalization and personalization to better serve the world—part 2

Article References: Riviello, E. D., Ware, L. B., & Matthay, M. A. (2026). Defining ARDS: globalization and personalization to better serve the world—part 2. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08652-7

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08652-7

Keywords: ARDS, acute respiratory distress syndrome, global definition, LUNG SAFE, treatable traits, subphenotypes, low tidal volume ventilation, prone positioning, resource-constrained settings, critical care, research equity, personalized medicine