1. Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data
- Author
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Tommaso Mauri, Bruno Pereira, Antonio Pesenti, Ognjen Gajic, Raiko Blondonnet, Michael A. Matthay, Carolyn S. Calfee, Florian Uhle, Andrea Coppadoro, Helena Brodska, Jean-Michel Constantin, Ségolène Mrozek, Christoph Lichtenstern, Vincent Sapin, Rogier M. Determann, Rolf D. Hubmayr, Tomas Drabek, Marcus J. Schultz, Marco Ranieri, Rodrigo Cartin-Ceba, Matthieu Jabaudon, CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Department of Anaesthesiology, Heidelberg University Hospital [Heidelberg], Mayo Clinic [Rochester], Jabaudon, M., Blondonnet, R., Pereira, B., Cartin-Ceba, R., Lichtenstern, C., Mauri, T., Determann, R.M., Drabek, T., Hubmayr, R.D., Gajic, O., Uhle, F., Coppadoro, A., Pesenti, A., Schultz, M.J., Ranieri, M.V., Brodska, H., Mrozek, S., Sapin, V., Matthay, M.A., Constantin, J.-M., Calfee, C.S., Intensive Care Medicine, AII - Inflammatory diseases, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,ARDS ,Receptor for Advanced Glycation End Products ,clinical outcome ,Critical Care and Intensive Care Medicine ,MESH: Tidal Volume ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,0302 clinical medicine ,MESH: Risk Factors ,Risk Factors ,Medicine ,MESH: APACHE ,randomized controlled trial (topic) ,Tidal volume ,APACHE ,Randomized Controlled Trials as Topic ,Work of Breathing ,Respiratory Distress Syndrome ,MESH: Middle Aged ,Acute respiratory distress syndrome ,adult respiratory distress syndrome ,respiratory system ,Middle Aged ,lung alveolus epithelium ,Prognosis ,3. Good health ,Observational Studies as Topic ,medicine.anatomical_structure ,MESH: Work of Breathing ,Meta-analysis ,Cardiology ,multicenter study (topic) ,Biomarker (medicine) ,Female ,medicine.medical_specialty ,Prognosi ,advanced glycation end product receptor, adult ,MESH: Observational Studies as Topic ,Lung injury ,Article ,lung epithelium ,03 medical and health sciences ,Internal medicine ,Tidal Volume ,Humans ,human ,lung injury ,Lung ,Lung epithelial injury ,MESH: Humans ,business.industry ,MESH: Receptor for Advanced Glycation End Products ,030208 emergency & critical care medicine ,Odds ratio ,Biomarker ,medicine.disease ,major clinical study ,mortality ,Confidence interval ,MESH: Male ,Receptor for advanced glycation end-products ,MESH: Randomized Controlled Trials as Topic ,030228 respiratory system ,protein blood level ,MESH: Biomarkers ,MESH: Respiratory Distress Syndrome, Adult ,observational study ,business ,MESH: Female ,Biomarkers - Abstract
Purpose: The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. Methods: We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Results: Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT. Conclusions: Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241). © 2018, The Author(s).
- Published
- 2018