[Source: PLOS One, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials
Elizabeth Sanchez , David R. Price , Kuei-Pin Chung, Clara Oromendia, Augustine M. K. Choi, Edward J. Schenck, Ilias I. Siempos
Published: January 27, 2020 / DOI: https://doi.org/10.1371/journal.pone.0227346
Acute respiratory distress syndrome (ARDS) is heterogeneous. As an indication of the heterogeneity of ARDS, there are patients whose syndrome improves rapidly (i.e., within 24 hours), others whose hypoxemia improves gradually and still others whose severe hypoxemia persists for several days. The latter group of patients with persistent severe ARDS poses challenges to clinicians. We attempted to assess the baseline characteristics and outcomes of persistent severe ARDS and to identify which variables are useful to predict it.
A secondary analysis of patient-level data from the ALTA, EDEN and SAILS ARDSNet clinical trials was conducted. We defined persistent severe ARDS as a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) of equal to or less than 100 mmHg on the second study day following enrollment. Regularized logistic regression with an L1 penalty [Least Absolute Shrinkage and Selection Operator (LASSO)] techniques were used to identify predictive variables of persistent severe ARDS.
Of the 1531 individuals with ARDS alive on the second study day after enrollment, 232 (15%) had persistent severe ARDS. Of the latter, 100 (43%) individuals had mild or moderate hypoxemia at baseline. Usage of vasopressors was greater [144/232 (62%) versus 623/1299 (48%); p<0.001] and baseline severity of illness was higher in patients with versus without persistent severe ARDS. Mortality at 60 days [95/232 (41%) versus 233/1299 (18%); p<0.001] was higher, and ventilator-free (p<0.001), intensive care unit-free [0 (0–14) versus 19 (7–23); p<0.001] and non-pulmonary organ failure-free [3 (0–21) versus 20 (1–26); p<0.001] days were fewer in patients with versus without persistent severe ARDS. PaO2:FiO2, FiO2, hepatic failure and positive end-expiratory pressure at enrollment were useful predictive variables.
Patients with persistent severe ARDS have distinct baseline characteristics and poor prognosis. Identifying such patients at enrollment may be useful for the prognostic enrichment of trials.
Citation: Sanchez E, Price DR, Chung K-P, Oromendia C, Choi AMK, Schenck EJ, et al. (2020) Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials. PLoS ONE 15(1): e0227346. https://doi.org/10.1371/journal.pone.0227346
Editor: Christophe Leroyer, Universite de Bretagne Occidentale, FRANCE
Received: July 31, 2019; Accepted: December 15, 2019; Published: January 27, 2020
Copyright: © 2020 Sanchez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Patient-level data from randomized controlled trials for this secondary analysis were obtained through the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) of National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) (relevant reference: Coady SA, Mensah GA, Wagner EL, Goldfarb ME, Hitchcock DM, Giffen CA: Use of the National Heart, Lung, and Blood Institute Data Repository. N Engl J Med 2017; 376:1849-58; https://biolincc.nhlbi.nih.gov/home). Others would be able to access these data in the same manner as the authors; i.e., after submission of a protocol to the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) of National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) and institution review board (IRB) approval from their institution. Details on how others can assess the datasets are provided both in website https://biolincc.nhlbi.nih.gov/home and the article Coady SA, Mensah GA, Wagner EL, Goldfarb ME, Hitchcock DM, Giffen CA: Use of the National Heart, Lung, and Blood Institute Data Repository. N Engl J Med 2017; 376:1849-58. The authors confirm that they did not have any special access privileges that others would not have.
Funding: This work was supported by National Institutes of Health grants UL1 TR000457-06 (to DRP), KL2 TR000458-10 (to EJS), R01 HL055330 (to AMKC) and P01 HL108801 (to AMKC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The corresponding author has read the journal’s policy and the authors of this manuscript have the following competing interests: AMC is a co-founder of Proterris and serving as a consultant for an advisory board meeting of Teva Pharmaceutical Industries, July 2018. None declared (ES, DRP, KPC, CO, EJS, IIS). This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.