• Hilary E Faust, John P Reilly, Brian J Anderson, IttnerCaroline A GCAGPulmonary, Allergy and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Caitlyn M Forker, Peggy Zhang, Benjamin A Weaver, Daniel N Holena, Paul N Lanken, Jason D Christie, Nuala J Meyer, Nilam S Mangalmurti, and ShashatyMichael G SMGSPulmonary, Allergy and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Ph.
• Allergy, Pulmonary and Critical Care Division, University of Wisconsin School of Medicine and Public Health, Madison, WI. Electronic address: hfaust@medicine.wisc.edu.
• Chest. 2020 Jan 1; 157 (1): 677667-76.

BackgroundCritically ill patients who develop ARDS have substantial associated morbidity and mortality. Circulating mitochondrial DNA (mtDNA) released during critical illness causes endothelial dysfunction and lung injury in experimental models. This study hypothesized that elevated plasma mtDNA is associated with ARDS in critically ill patients with trauma and sepsis.MethodsPlasma mtDNA concentrations were measured at ED presentation and approximately 48 h later in separate prospective cohorts of critically ill patients with trauma and sepsis. ARDS was classified according to the Berlin definition. The association of mtDNA with ARDS was tested by using multivariable logistic regression, adjusted for covariates previously shown to contribute to ARDS risk in each population.ResultsARDS developed in 41 of 224 (18%) trauma patients and in 45 of 120 (38%) patients with sepsis. Forty-eight-hour mtDNA levels were significantly associated with ARDS (trauma: OR, 1.58/log copies/μL; 95% CI, 1.14-2.19 [P = .006]; sepsis: OR, 1.52/log copies/μL; 95% CI, 1.12-2.06 [P = .007]). Plasma mtDNA on presentation was not significantly associated with ARDS in either cohort. In patients with sepsis, 48-h mtDNA was more strongly associated with ARDS among those with a nonpulmonary infectious source (OR, 2.20/log copies/μL; 95% CI, 1.36-3.55 [P = .001], n = 69) than those with a pulmonary source (OR, 1.04/log copies/μL; 95% CI, 0.68-1.59 [P = .84], n = 51; P = .014 for interaction).ConclusionsPlasma mtDNA levels were associated with incident ARDS in two critical illness populations. Given supportive preclinical data, our findings suggest a potential link between circulating mtDNA and lung injury and merit further investigation as a potentially targetable mediator of ARDS.Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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