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      Latent class analysis to predict intensive care outcomes in Acute Respiratory Distress Syndrome: a proposal of two pulmonary phenotypes

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          Abstract

          Background

          Acute respiratory distress syndrome remains a heterogeneous syndrome for clinicians and researchers difficulting successful tailoring of interventions and trials. To this moment, phenotyping of this syndrome has been approached by means of inflammatory laboratory panels. Nevertheless, the systemic and inflammatory expression of acute respiratory distress syndrome might not reflect its respiratory mechanics and gas exchange.

          Methods

          Retrospective analysis of a prospective cohort of two hundred thirty-eight patients consecutively admitted patients under mechanical ventilation presenting with acute respiratory distress syndrome. All patients received standardized monitoring of clinical variables, respiratory mechanics and computed tomography scans at predefined PEEP levels. Employing latent class analysis, an unsupervised structural equation modelling method, on respiratory mechanics, gas-exchange and computed tomography-derived gas- and tissue-volumes at a PEEP level of 5cmH 2O, distinct pulmonary phenotypes of acute respiratory distress syndrome were identified.

          Results

          Latent class analysis was applied to 54 respiratory mechanics, gas-exchange and CT-derived gas- and tissue-volume variables, and a two-class model identified as best fitting. Phenotype 1 ( non-recruitable) presented lower respiratory system elastance, alveolar dead space and amount of potentially recruitable lung volume than phenotype 2 ( recruitable). Phenotype 2 ( recruitable) responded with an increase in ventilated lung tissue, compliance and PaO 2/FiO 2 ratio ( p < 0.001), in addition to a decrease in alveolar dead space ( p < 0.001), to a standardized recruitment manoeuvre. Patients belonging to phenotype 2 ( recruitable) presented a higher intensive care mortality (hazard ratio 2.9, 95% confidence interval 1.7–2.7, p = 0.001).

          Conclusions

          The present study identifies two ARDS phenotypes based on respiratory mechanics, gas-exchange and computed tomography-derived gas- and tissue-volumes. These phenotypes are characterized by distinctly diverse responses to a standardized recruitment manoeuvre and by a diverging mortality. Given multicentre validation, the simple and rapid identification of these pulmonary phenotypes could facilitate enrichment of future prospective clinical trials addressing mechanical ventilation strategies in ARDS.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13054-021-03578-6.

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          Most cited references51

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          Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

          Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
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            Acute respiratory distress syndrome: the Berlin Definition.

            The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.
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              A Proportional Hazards Model for the Subdistribution of a Competing Risk

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                Author and article information

                Contributors
                davide.chiumello@unimi.it
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                22 April 2021
                22 April 2021
                2021
                : 25
                : 154
                Affiliations
                [1 ]GRID grid.412004.3, ISNI 0000 0004 0478 9977, Institute of Intensive Care Medicine, , University Hospital of Zurich, ; Zurich, Switzerland
                [2 ]GRID grid.415093.a, Department of Anesthesia and Intensive Care, ASST Santi Paolo E Carlo, , San Paolo University Hospital, ; Via Di Rudinì, Milan, Italy
                [3 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Health Sciences, , University of Milan, ; Milan, Italy
                [4 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Coordinated Research Center on Respiratory Failure, , University of Milan, ; Milan, Italy
                Author information
                http://orcid.org/0000-0001-9260-3930
                Article
                3578
                10.1186/s13054-021-03578-6
                8060783
                33888134
                efce2ebe-3a53-4e37-88b2-9eb187390ded
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 31 December 2020
                : 13 April 2021
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Emergency medicine & Trauma
                ards,latent class analysis,phenotypes,mechanical ventilation,respiratory mechanics,radiological data,recruitment,enrichment

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