학술논문

Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis
Document Type
article
Author
Maddali, Manoj VChurpek, MatthewPham, TaiRezoagli, EmanueleZhuo, HanjingZhao, WendiHe, JuneDelucchi, Kevin LWang, ChunxueWickersham, NancyMcNeil, J BrennanJauregui, AlejandraKe, SerenaVessel, KathrynGomez, AntonioHendrickson, Carolyn MKangelaris, Kirsten NSarma, AartikLeligdowicz, AleksandraLiu, Kathleen DMatthay, Michael AWare, Lorraine BLaffey, John GBellani, GiacomoCalfee, Carolyn SSinha, PratikRios, FernandoVan Haren, FrankSottiaux, TLora, Fredy SAzevedo, Luciano CDepuydt, PFan, EddyBugedo, GuillermoQiu, HaiboGonzalez, MarcosSilesky, JuanCerny, VladimirNielsen, JonasJibaja, ManuelPham, TàiWrigge, HermannMatamis, DimitriosRanero, Jorge LuisHashemian, SMAmin, PravinClarkson, KevinKurahashi, KiyoyasuVillagomez, AsiscloZeggwagh, Amine AliHeunks, Leo MLaake, Jon HenrikPalo, Jose Emmanueldo Vale Fernandes, AnteroSandesc, DorelArabi, YaasenBumbasierevic, VesnaNin, NicolasLorente, Jose ALarsson, AndersPiquilloud, LiseAbroug, FekriMcAuley, Daniel FMcNamee, LiaHurtado, JavierBajwa, EdDémpaire, GabrielFrancois, Guy MSula, HektorNunci, LordianCani, AlmaZazu, AlanDellera, ChristianInsaurralde, Carolina SAlejandro, Risso VDaldin, JulioVinzio, MauricioFernandez, Ruben OCardonnet, Luis PBettini, Lisandro RBisso, Mariano CarboniOsman, Emilio MSetten, Mariano GLovazzano, PabloAlvarez, JavierVillar, VeronicaMilstein, CesarPozo, Norberto CGrubissich, NicolasPlotnikow, Gustavo AVasquez, Daniela NIlutovich, SantiagoTiribelli, NorbertoChena, ArielPellegrini, Carlos ASaenz, María GEstenssoro, ElisaBrizuela, MatiasGianinetto, Hernan
Source
The Lancet Respiratory Medicine. 10(4)
Subject
Lung
Clinical Research
Acute Respiratory Distress Syndrome
Rare Diseases
Respiratory
Good Health and Well Being
Acute Lung Injury
Humans
Machine Learning
Positive-Pressure Respiration
Respiratory Distress Syndrome
Retrospective Studies
LUNG SAFE Investigators and the ESICM Trials Group
Clinical Sciences
Public Health and Health Services
Other Medical and Health Sciences
Language
Abstract
BackgroundTwo acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS.MethodsIn this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable.FindingsThe primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90-0·95) in EARLI and 0·88 (0·84-0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81-0·94] vs 0·92 [0·88-0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p