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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis
The Lancet Respiratory Medicine, Volume 10, No. 4, Year 2022
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Description
Background: Two 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. Methods: In 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. Findings: The 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<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Interpretation: Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. Funding: US National Institutes of Health and European Society of Intensive Care Medicine. © 2022 Elsevier Ltd
Authors & Co-Authors
Rezoagli, Emanuele
Italy, Milan
Università Degli Studi Di Milano-bicocca
Hendrickson, Carolyn M.
United States, San Francisco
University of California, San Francisco
United States, San Francisco
San Francisco General Hospital and Trauma Center
Leligdowicz, Aleksandra
United States, San Francisco
University of California, San Francisco
Canada, Toronto
University of Toronto
Matthay, Michael Anthony
United States, San Francisco
University of California, San Francisco
Ware, Lorraine B.
United States, Nashville
Vanderbilt University Medical Center
Laffey, John
Ireland, Galway
University of Galway
Ireland, Galway
University Hospital Galway
Bellani, Giacomo
Italy, Milan
Università Degli Studi Di Milano-bicocca
Italy, Monza
Azienda Ospedaliera San Gerardo Monza
Calfee, Carolyn S.
United States, San Francisco
University of California, San Francisco
Sinha, Pratik
United States, St. Louis
Washington University School of Medicine in St. Louis
United States, St. Louis
Washington University in St. Louis
Ríos, Fernando Gonçalves
Unknown Affiliation
van Haren, Frank M.P.
Unknown Affiliation
Sottiaux, Thierry M.
Unknown Affiliation
Lora, Fredy S.
Unknown Affiliation
Azevedo, Luciano César Pontes
Unknown Affiliation
Fan, Eddy
Unknown Affiliation
Bugedo, Guillermo
Unknown Affiliation
Qiu, Haibo
Unknown Affiliation
González, Marco A.
Unknown Affiliation
Silesky, Juan
Unknown Affiliation
Nielsen, Jonas Bille
Unknown Affiliation
Jibaja, Manuel
Unknown Affiliation
Pham, Tài I.
Unknown Affiliation
Wrigge, Hermann
Unknown Affiliation
Matamis, Dimitrios
Unknown Affiliation
Ranero, Jorge Luis M.
Unknown Affiliation
Hashemian, Seyed Mohammad Reza
Unknown Affiliation
Amin, Pravin R.
Unknown Affiliation
Clarkson, Kevin P.
Unknown Affiliation
Kurahashi, Kiyoyasu
Unknown Affiliation
Villagómez, Asisclo Jesús
Unknown Affiliation
Zeggwagh, Amine Ali
Unknown Affiliation
Heunks, Leo M.A.
Unknown Affiliation
Laake, Jon Henrik
Unknown Affiliation
Palo, Jose Emmanuel M.
Unknown Affiliation
do Vale Fernandes, Antero
Unknown Affiliation
Sǎndesc, Dorel
Unknown Affiliation
Arabi, Yaseen M.
Unknown Affiliation
Bumbasierevic, Vesna
Unknown Affiliation
Nín, Nicholas
Unknown Affiliation
Lorente, José Ángel A.
Unknown Affiliation
Larsson, Anders Sune
Unknown Affiliation
Piquilloud, Lise
Unknown Affiliation
McAuley, Daniel F.
Unknown Affiliation
McNamee, Lia
Unknown Affiliation
Hurtado, Javier L.
Unknown Affiliation
Bajwa, Ed
Unknown Affiliation
d’Empaire, Gabriel
Unknown Affiliation
François, Guy M.
Unknown Affiliation
Sula, Hektor H.
Unknown Affiliation
Nunci, Lordian
Unknown Affiliation
Cani, Alma
Unknown Affiliation
Zazu, Alan
Unknown Affiliation
Dellera, Christian
Unknown Affiliation
Insaurralde, Carolina S.
Unknown Affiliation
Alejandro, Risso V.
Unknown Affiliation
Daldin, Julio
Unknown Affiliation
Vinzio, Mauricio
Unknown Affiliation
Fernández, Rubén Oscar
Unknown Affiliation
Cardonnet, Luis Pablo
Unknown Affiliation
Bettini, Lisandro Roberto
Unknown Affiliation
Bisso, Mariano Carboni
Unknown Affiliation
Osman, Emilio M.
Unknown Affiliation
Setten, Mariano G.
Unknown Affiliation
Lovazzano, Pablo
Unknown Affiliation
Álvarez, Javier Abades Vila
Unknown Affiliation
Villar, Veronica
Unknown Affiliation
Pozo, Norberto Christian
Unknown Affiliation
Grubissich, Nicolas
Unknown Affiliation
Plotnikow, Gustavo Adrián
Unknown Affiliation
Vásquez, Daniela Noris
Unknown Affiliation
Ilutovich, Santiago
Unknown Affiliation
Tiribelli, Norberto
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Chena, Ariel
Unknown Affiliation
Pellegrini, Carlos Anibal
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Saenz, María Gabriela
Unknown Affiliation
Estenssoro, Elisa
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Brizuela, Matías
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Gianinetto, Hernan
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Gómez, Pablo Edgardo
Unknown Affiliation
Cerrato, Valeria I.
Unknown Affiliation
Bezzi, Marco Guillermo
Unknown Affiliation
Borello, Silvina A.
Unknown Affiliation
Loiacono, Flavia A.
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Fernandez, Adriana M.
Unknown Affiliation
Knowles, Serena
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Reynolds, Claire
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Inskip, Deborah M.
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Miller, Jennene J.
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Kong, Jing
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Whitehead, Christina
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Bihari, Shailesh
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Seven, Aylin
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Krstevski, Amanda
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Rodgers, Helen J.
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Millar, Rebecca T.
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McKenna, Toni E.
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Bailey, Irene M.
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Åneman, Erik Anders
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Staudinger, Thomas
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Wittebole, Xavier
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Bulpa, Pierre A.
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Depuydt, Pieter O.
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Piras, Cláudio
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Beloncle, François Michel
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Cirone, Rob
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Goligher, Ewan C.
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Rittayamai, Nuttapol
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Ferguson, Niall D.
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Mehta, Sangeeta K.
Unknown Affiliation
Bruhn, Alejandro R.
Unknown Affiliation
An, Youzhong
Unknown Affiliation
Qin, Bingyu
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Zhou, Suming
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Silesky-Jiménez, Juan Ignacio
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Maca, Jan
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Sklienka, Peter
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Gjedsted, Jakob
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Burtin, Philippe
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Beuret, Pascal
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Mercat, Alain
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Carteaux, Guillaume
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de Prost, Nicolas
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Chiche, Jean Daniel
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Daviaud, Fabrice
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Fartoukh, Muriel Sarah
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Dellamonica, Jean
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Arnal, Jean Michel
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Papazian, Laurent
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Messika, Jonathan
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Combes, Alain
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Béduneau, Gaëtan
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Zogheib, Élie H.
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Dupont, Hervé
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Besset, Sébastien L.
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Danin, Pierre Éric
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Badie, Julio C.
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Schneider, Francis
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Rigaud, Jean Philippe
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Duranteau, Jacques
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Chabanne, Russell
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Richecoeur, Jack R.
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Robine, Adrien
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Dres, Martin
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Demoule, Alexandre
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Baboi, Loredana
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Guérin, Claude
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Krassler, Jens
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Zacharowski, Kai D.
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Meybohm, Patrick
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Simon, Philipp
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Mouloudi, Eleni K.
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Jog, Sameer Arvind
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Shah, Bhagyesh Ashwinkumar
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Gurjar, Mohan
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Baronia, Arvind Kumar
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Ramakrishnan, N.
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Nichol, Alistair D.
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Spadaro, S.
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Protti, Alessandro
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Cortegiani, Andrea
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Antonelli, Massimo M.
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Montini, Luca Maria
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Beck, Eduardo J.
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Cinnella, Gilda
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Fossali, Tommaso
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Colombo, Riccardo
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Mojoli, Francesco
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Foti, Giuseppe
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Brazzi, Luca
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Iotti, Giorgio Antonio
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Ñamendys-Silva, Silvio A.
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Sanchez-Hurtado, Luis A.
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del Carmen Marín, María
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Dendane, Tarek
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Balkhi, Hicham
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Elkhayari, Mina
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Samkaoui, Nacer
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Ezzouine, Hanane
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Benslama, Abdellatif
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Amor, Mourad
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Maazouzi, Wajdi
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Schouten, Jeroen A.
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Schultz, Marcus Josephus
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Navarra, Leanlove
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Hunt, Anna L.
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Newby, Lynette
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McArthur, Colin J.
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Andersen, Finn Husøy
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Barratt-Due, Andreas
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Söreide, Eldar
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Andruszkiewicz, Pawel
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Berger-Estilita, Joana M.
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Tomescu, Dana Rodica
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Pǎpuricǎ, Marius
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Gritsan, Alexey I.
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Almekhlafi, Ghaleb A.
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Maghrabi, Khalid A.
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Salahuddin, Nawal
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Aisa, Tharwat Mahmoud
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Al-Dorzi, Hasan M.
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Tabhan, Edgardo E.
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Bolon, Stefan
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Smith, Oliver I.
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Mancebo, Jordi B.Y.J.
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Aguirre-Bermeo, Hernán
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Rialp, Gemma
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Forteza, Catalina
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Artigas, Antonio A.
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Roche-Campo, Ferrán
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Peñuelas, Óscar
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Broman, Lars Mikael
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Oscarsson, Anna
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ElAtrous, Souheil
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Bouchoucha, Slaheddine
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Chouchene, Imed
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Ouanes, Islem
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Demirkiran, Oktay
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Özçelik, Menekşe
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Meço, Başak Ceyda Orbey
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Kakar, Vivek
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Humphreys, Sally K.
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Ferguson, Andrew J.
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Raj, Ashok Sundai
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Kannan, Santhanagopalan G.
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Camsooksai, Julie
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Dempsey, Ged A.
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McKechnie, Stuart R.
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Hutton, Paula J.
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Di Tomasso, Nora
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Williams, Alexandra J.
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Boyd, Owen F.
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de Gordoa, Laura Ortiz Ruiz
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Szakmany, Tamas
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Welters, Ingeborg Dorothea M.
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Careless, Jon P.
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Wise, Matt P.
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Cole, Jade M.
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Banner-Goodspeed, Valerie M.
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Beitler, Jeremy R.
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Bauer, Philippe R.
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Batra, Hitesh
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Kheir, Fayez M.
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Baron, Rebecca M.
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Bumbaširević, Vesna D.
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Jovanović, Bojan M.
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Statistics
Citations: 55
Authors: 246
Affiliations: 14
Identifiers
Doi:
10.1016/S2213-2600(21)00461-6
ISSN:
22132600
Research Areas
Health System And Policy
Violence And Injury
Study Design
Randomised Control Trial
Cohort Study