Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials.

TitleSubphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials.
Publication TypeJournal Article
Year of Publication2014
AuthorsCalfee CS, Delucchi K, Parsons PE, B Thompson T, Ware LB, Matthay MA
Corporate AuthorsNHLBI ARDS Network
JournalLancet Respir Med
Volume2
Issue8
Pagination611-20
Date Published2014 Aug
ISSN Number2213-2619
KeywordsAdult, Aged, Apache, Bicarbonates, Biomarkers, Female, Humans, Inflammation, Inflammation Mediators, Male, Middle Aged, Models, Statistical, Phenotype, Respiration, Artificial, Respiratory Distress Syndrome, Adult, Sepsis, Time Factors, Vasoconstrictor Agents
Abstract

<p><b>BACKGROUND: </b>Subphenotypes have been identified within heterogeneous diseases such as asthma and breast cancer, with important therapeutic implications. We assessed whether subphenotypes exist within acute respiratory distress syndrome (ARDS), another heterogeneous disorder.</p><p><b>METHODS: </b>We used data from two ARDS randomised controlled trials (ARMA trial and ALVEOLI trial), sponsored by the National Heart, Lung, and Blood Institute. We applied latent class modelling to identify subphenotypes using clinical and biological data. We modelled data from both studies independently. We then tested the association of subphenotypes with clinical outcomes in both cohorts and with the response to positive end-expiratory pressure (PEEP) in the ALVEOLI cohort.</p><p><b>FINDINGS: </b>We analysed data for 1022 patients: 473 in the ARMA cohort and 549 in the ALVEOLI cohort. Independent latent class models indicated that a two-class (ie, two subphenotype) model was the best fit for both cohorts. In both cohorts, we identified a hyperinflammatory subphenotype (phenotype 2) that was characterised by higher plasma concentrations of inflammatory biomarkers, a higher prevalence of vasopressor use, lower serum bicarbonate concentrations, and a higher prevalence of sepsis than phenotype 1. Participants in phenotype 2 had higher mortality and fewer ventilator-free days and organ failure-free days in both cohorts than did those in phenotype 1 (p<0·007 for all). In the ALVEOLI cohort, the effects of ventilation strategy (high PEEP vs low PEEP) on mortality, ventilator-free days and organ failure-free days differed by phenotype (p=0·049 for mortality, p=0·018 for ventilator-free days, p=0·003 for organ-failure-free days).</p><p><b>INTERPRETATION: </b>We have identified two subphenotypes within ARDS, one of which is categorised by more severe inflammation, shock, and metabolic acidosis and by worse clinical outcomes. Response to treatment in a randomised trial of PEEP strategies differed on the basis of subphenotype. Identification of ARDS subphenotypes might be useful in selecting patients for future clinical trials.</p><p><b>FUNDING: </b>National Institutes of Health.</p>

DOI10.1016/S2213-2600(14)70097-9
Alternate JournalLancet Respir Med
PubMed ID24853585
PubMed Central IDPMC4154544
Grant ListN01-HR 46056 / HR / NHLBI NIH HHS / United States
HL103836 / HL / NHLBI NIH HHS / United States
N01-HR 46058 / HR / NHLBI NIH HHS / United States
N01-HR 46063 / HR / NHLBI NIH HHS / United States
HL090833 / HL / NHLBI NIH HHS / United States
N01-HR 46060 / HR / NHLBI NIH HHS / United States
R01 HL051856 / HL / NHLBI NIH HHS / United States
N01-HR 46057 / HR / NHLBI NIH HHS / United States
HL 51856 / HL / NHLBI NIH HHS / United States
K24 HL103836 / HL / NHLBI NIH HHS / United States
N01-HR 46064 / HR / NHLBI NIH HHS / United States
R37 HL051856 / HL / NHLBI NIH HHS / United States
N01-HR 46061 / HR / NHLBI NIH HHS / United States
N01-HR 46054 / HR / NHLBI NIH HHS / United States
N01-HR 46059 / HR / NHLBI NIH HHS / United States
N01HR46054 / HL / NHLBI NIH HHS / United States
HL112656 / HL / NHLBI NIH HHS / United States
110969 / / PHS HHS / United States
R21 HL112656 / HL / NHLBI NIH HHS / United States
K23 HL090833 / HL / NHLBI NIH HHS / United States
N01-HR 46062 / HR / NHLBI NIH HHS / United States
N01-HR 46055 / HR / NHLBI NIH HHS / United States
R01 HL110969 / HL / NHLBI NIH HHS / United States