Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials.
Pubmed ID: 24853585
Pubmed Central ID: PMC4154544
Journal: The Lancet. Respiratory medicine
Publication Date: 08/01/2014
Affiliation: Departments of Medicine and Anesthesia, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, San Francisco, CA, USA.
MeSH Terms: Humans, Male, Adult, Female, Aged, Middle Aged, Models, Statistical, Time Factors, Respiration, Artificial, Phenotype, Inflammation Mediators, Inflammation, APACHE, Sepsis, Bicarbonates, Vasoconstrictor Agents, Biomarkers, Respiratory Distress Syndrome
Grants: R37 HL051856, HL 51856, HL103836, K24 HL103836, R21 HL112656, HL112656, 110969, HL090833, K23 HL090833, N01-HR 46054, N01-HR 46055, N01-HR 46056, N01-HR 46057, N01-HR 46058, N01-HR 46059, N01-HR 46060, N01-HR 46061, N01-HR 46062, N01-HR 46063, N01-HR 46064, N01HR46054, R01 HL051856, R01 HL110969
Authors: Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Thompson BT, Hayden D, Parsons PE, Parsons PE, Matthay MA, Matthay MA, Ware LB, Ware LB, Eisner MD, Harabin A, Ringwood N, Molay F, Ancukiewicz M, Wenzlow G, Garcia JG, Lew P, Carter G, Toews GB, Bartlett RH, Watts C, Arnoldi D, Dechert R, Shanholtz C, Corral W, Thompson D, Murray S, Arroliga AC, Abraham E, McIntyre R, Piedalue F, Welsh C, MacIntyre N, Govert J, Bernard G, Christman B, Bozeman S, Finkel B, Hanson CW, Brower RG, Calfee CS, Schoenfeld DA, Kelley J, Leeper K, Waclawiw M, Gottlieb J, Park P, Girod A, Grissom C, Weaver L, Orme J, Clemmer T, Davis R, Lawton C, Hill T, Daniel B, Kallet R, Lanken PN, Delucchi K, Fisher CJ, Komara JJ, Periz-Trepichio P, Fulkerson WJ, Mallatratt L, Sebastian M, Davies J, Van Dyne E, Sevransky J, Fessler HE, Morris AH, Thomas F, Gleich M, D'Hulst J, Peerless JR, Smith C, Luce JM, Yannarell L, Jagusch R, Miller P, Greene KE, Silverman HJ, Anderson H, Barton R, Mone M, Hudson LD, Cooper CL, Hiemstra A, Maier RV, Steinberg KP, Thaut P, Collins L, Swope T, Kazeroonin AS, Gail DB, Spragg RG, Boyett J, Secundy MG, Slutsky A, Emerson SS, Pingleton SK, Shasby MD, Sibbald WJ
Cite As: Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med 2014 Aug;2(8):611-20. Epub 2014 May 19.
BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: National Institutes of Health.