Bedside Identification of ARDS Subphenotypes May Predict Mortality

Researchers from the U.K. and Ireland believe bedside subphenotyping of patients with the acute respiratory distress syndrome (ARDS) can predict which patients are most likely to die from the condition — and possibly open the door to precision medicine approaches aimed at better treating these patients as well.

The study, published in The Lancet Respiratory Medicine, combined test results for three key factors — plasma interleukin-6 (IL-6), soluble TNF receptor-1 (TNFR1), and plasma bicarbonate — to prospectively classify 486 patients into two subphenotypes identified in previous research.

A near-patient benchtop immunoanalyser was used to test for IL-6 and TNFR1, and plasma bicarbonate was measured from an arterial blood sample.

Based on these tests, 398 patients were classified as hypoinflammatory and 88 as hyperinflammatory. All were receiving either invasive or noninvasive mechanical ventilation or high-flow nasal oxygen. Men made up 60% of the group, and the mean age was 57. Eighty-seven percent were white, 4% were black, and 3% were Asian.

The researchers then compared 60-day mortality rates between the two groups, finding a significantly higher rate in the hyperinflammatory group (51%) than in the hypoinflammatory group (28%). Other findings showed:

• The 28-day mortality rate was 44% in the hyperinflammatory group and 23% in the hypoinflammatory group.
• At day 28, patients in the hypoinflammatory group had a median of 14 ventilator-free days vs. zero ventilator-free days in the hyperinflammatory group.
• Re-intubation rates, duration of days with ventilation, length of ICU stay, and length of hospital stay did not differ between the two groups overall, but when the researchers looked at duration of days with ventilation, length of ICU stay, and length of hospital stay between survivors and non-survivors, significant differences were noted between the two phenotypes.

“Rapid identification of ARDS inflammatory subphenotypes using a near-patient assay was feasible and associated with many clinical characteristics and outcomes consistent with those described in earlier retrospective studies, including mortality, prevalence of sepsis, and incidence of metabolic acidosis,” wrote the authors. “These findings support the implementation of precision medicine approaches in ARDS and the urgent need for prospective, subphenotype-stratified interventional trials.” 

Highlighted in RC Buzz April 13, 2026