Study identifies two distinct subphenotypes of ARDS

Researchers have identified two new distinct subphenotypes of adults with acute respiratory distress syndrome, according to results published in BMJ Open.

“In current clinical practice, risk stratification for patients with ARDS solely depends on the PaO₂/FiO₂ clinical measure,” Abhijit Duggal, MD, physician in the department of critical care medicine at the Respiratory Institute at Cleveland Clinic, said in a press release issued by Endpoint Health. “The application of this single assessment often results in bedside challenges in evaluating optimal treatment options for patients. It can also lead to challenges in assessing the impact of interventions in clinical trials. While our findings warrant further study before they can be generalized, this analysis demonstrates that it may be possible to enhance risk stratification strategies by using a few additional clinical variables that are collected during routine ARDS care.”

The researchers conducted a retrospective cohort study using data from 3,763 patients from the U.S. ARDSnet trials and 1,010 patients from the international Alveolar Recruitment for ARDS Trial (ART). Using a novel proprietary clustering model (Endpoint Health), the researchers tested 10 different models with varying combinations of proposed clinical variables, according to the press release. The goal was to determine the optimal number of clusters of patients with distinct clinical outcomes, while using the most commonly available clinical variables closest to time of randomization and minimizing the overall number of variables, according to the release. The final model included nine variables: arterial pH, partial pressure of oxygen (PaO₂), bicarbonate, creatinine, bilirubin, heart rate, respiratory rate, mean arterial pressure, and fraction of inspired oxygen (FiO₂).

The primary outcome was 60-day mortality in the U.S. studies or 28-day mortality in the international study.

Sixty-day mortality ranged from 22.7% to 30.1% for the ARDSnet trials and 58.8% for the ART trial.

Researchers identified two subphenotypes (A and B) from the final model.

Subphenotype B was characterized by increased proinflammatory marker levels, consistently higher mortality, a lower number of ventilator-free days at 28 days and longer ventilation duration compared with those with the subphenotype A. Patients with subphenotype B also presented with increased levels of pro-inflammatory markers, according to the release.

“Previous studies in ARDS have relied on models with up to 40 predictor variables, including many that are not commonly available, which makes their translation into clinical practice difficult,” Diego Rey, PhD, chief scientific officer at Endpoint Health, said in the release. “It is encouraging that in this study we narrowed ARDS subphenotyping based on nine commonly available clinical variables, using a novel proprietary clustering approach from Endpoint Health.”

According to the researchers, these data may result in easier ARDS subphenotype identification to help implement precision clinical trial enrollment and the development of targeted therapies without the added burdens of biomarker evaluation.

Reference:

• Endpoint Health presents published results from a retrospective study of adult ARDS patients, identifying an innovative approach to predicting clinical outcomes. Published Jan. 6, 2022. Accessed Jan. 11, 2022.