Identification of acute respiratory distress syndrome subphenotypes de novo using routine clinical data: a retrospective analysis of ARDS clinical trials.

Pubmed ID: 34992112

Pubmed Central ID: PMC8739395

Journal: BMJ open

Publication Date: Jan. 6, 2022

Affiliation: Department of Clinical Data Science, Endpoint Health, Palo Alto, California, USA.

MeSH Terms: Humans, Adult, Retrospective Studies, Time Factors, Biomarkers, Respiratory Distress Syndrome, Blood Coagulation Tests

Authors: Duggal A, Kast R, Van Ark E, Bulgarelli L, Siuba MT, Osborn J, Rey DA, Zampieri FG, Cavalcanti AB, Maia I, Paisani DM, Laranjeira LN, Serpa Neto A, Deliberato RO

Cite As: Duggal A, Kast R, Van Ark E, Bulgarelli L, Siuba MT, Osborn J, Rey DA, Zampieri FG, Cavalcanti AB, Maia I, Paisani DM, Laranjeira LN, Serpa Neto A, Deliberato RO. Identification of acute respiratory distress syndrome subphenotypes de novo using routine clinical data: a retrospective analysis of ARDS clinical trials. BMJ Open 2022 Jan 6;12(1):e053297.

Studies:

Abstract

OBJECTIVES: The acute respiratory distress syndrome (ARDS) is a heterogeneous condition, and identification of subphenotypes may help in better risk stratification. Our study objective is to identify ARDS subphenotypes using new simpler methodology and readily available clinical variables. SETTING: This is a retrospective Cohort Study of ARDS trials. Data from the US ARDSNet trials and from the international ART trial. PARTICIPANTS: 3763 patients from ARDSNet data sets and 1010 patients from the ART data set. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was 60-day or 28-day mortality, depending on what was reported in the original trial. K-means cluster analysis was performed to identify subgroups. Sets of candidate variables were tested to assess their ability to produce different probabilities for mortality in each cluster. Clusters were compared with biomarker data, allowing identification of subphenotypes. RESULTS: Data from 4773 patients were analysed. Two subphenotypes (A and B) resulted in optimal separation in the final model, which included nine routinely collected clinical variables, namely heart rate, mean arterial pressure, respiratory rate, bilirubin, bicarbonate, creatinine, PaO<sub>2</sub>, arterial pH and FiO<sub>2</sub>. Participants in subphenotype B showed increased levels of proinflammatory markers, had consistently higher mortality, lower number of ventilator-free days at day 28 and longer duration of ventilation compared with patients in the subphenotype A. CONCLUSIONS: Routinely available clinical data can successfully identify two distinct subphenotypes in adult ARDS patients. This work may facilitate implementation of precision therapy in ARDS clinical trials.