Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study.

Pubmed ID: 30291376

Pubmed Central ID: PMC6317524

Journal: Intensive care medicine

Publication Date: Nov. 1, 2018

Affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.

MeSH Terms: Humans, Male, Adult, Female, Aged, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cohort Studies, Middle Aged, Survival Rate, Acute Lung Injury, Sepsis, Latent Class Analysis, Rosuvastatin Calcium, Respiratory Distress Syndrome

Grants: 2T32GM008440-21, R35 HL140026, MC_G1002460, HL133390, HL140026, T32 GM008440, HL131621

Authors: Thompson BT, Matthay MA, Calfee CS, Sinha P, Delucchi KL, McAuley DF

Cite As: Sinha P, Delucchi KL, Thompson BT, McAuley DF, Matthay MA, Calfee CS, NHLBI ARDS Network. Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study. Intensive Care Med 2018 Nov;44(11):1859-1869. Epub 2018 Oct 5.

Studies:

Abstract

PURPOSE: Using latent class analysis (LCA), we have consistently identified two distinct subphenotypes in four randomized controlled trial cohorts of ARDS. One subphenotype has hyper-inflammatory characteristics and is associated with worse clinical outcomes. Further, within three negative clinical trials, we observed differential treatment response by subphenotype to randomly assigned interventions. The main purpose of this study was to identify ARDS subphenotypes in a contemporary NHLBI Network trial of infection-associated ARDS (SAILS) using LCA and to test for differential treatment response to rosuvastatin therapy in the subphenotypes. METHODS: LCA models were constructed using a combination of biomarker and clinical data at baseline in the SAILS study (nā€‰=ā€‰745). LCA modeling was then repeated using an expanded set of clinical class-defining variables. Subphenotypes were tested for differential treatment response to rosuvastatin. RESULTS: The two-class LCA model best fit the population. Forty percent of the patients were classified as the "hyper-inflammatory" subphenotype. Including additional clinical variables in the LCA models did not identify new classes. Mortality at day 60 and day 90 was higher in the hyper-inflammatory subphenotype. No differences in outcome were observed between hyper-inflammatory patients randomized to rosuvastatin therapy versus placebo. CONCLUSIONS: LCA using a two-subphenotype model best described the SAILS population. The subphenotypes have features consistent with those previously reported in four other cohorts. Addition of new class-defining variables in the LCA model did not yield additional subphenotypes. No treatment effect was observed with rosuvastatin. These findings further validate the presence of two subphenotypes and demonstrate their utility for patient stratification in ARDS.