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- Maddali, Manoj V., et al.
(author)
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Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data : an observational, multicohort, retrospective analysis
- 2022
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In: The Lancet Respiratory Medicine. - 2213-2600. ; 10:4, s. 367-377
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Journal article (peer-reviewed)abstract
- Background: Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. Methods: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. Findings: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90–0·95) in EARLI and 0·88 (0·84–0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81–0·94] vs 0·92 [0·88–0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Interpretation: Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. Funding: US National Institutes of Health and European Society of Intensive Care Medicine.
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- Pham, Tai, et al.
(author)
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Outcome of acute hypoxaemic respiratory failure : insights from the LUNG SAFE Study
- 2021
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In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 57:6
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Journal article (peer-reviewed)abstract
- Background: Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). Methods: An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio <= 300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of >= 5 cmH(2)O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared. Findings: 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved. Interpretation: More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
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- Retamal, Jaime, et al.
(author)
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High PEEP levels are associated with overdistension and tidal recruitment/derecruitment in ARDS patients
- 2015
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 59:9, s. 1161-1169
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Journal article (peer-reviewed)abstract
- BackgroundPositive end-expiratory pressure (PEEP) improves gas exchange and respiratory mechanics, and it may decrease tissue injury and inflammation. The mechanisms of this protective effect are not fully elucidated. Our aim was to determine the intrinsic effects of moderate and higher levels of PEEP on tidal recruitment/derecruitment, hyperinflation, and lung mechanics, in patients with acute respiratory distress syndrome (ARDS). MethodsNine patients with ARDS of mainly pulmonary origin were ventilated sequential and randomly using two levels of PEEP: 9 and 15cmH(2)O, and studied with dynamic computed tomography at a fix transversal lung region. Tidal recruitment/derecruitment and hyperinflation were determined as non-aerated tissue and hyperinflated tissue variation between inspiration and expiration, expressed as percentage of total weight. We also assessed the maximal amount of non-aerated and hyperinflated tissue weight. ResultsPEEP 15cmH(2)O was associated with decrease in non-aerated tissue in all the patients (P<0.01). However, PEEP 15cmH(2)O did not decrease tidal recruitment/derecruitment compared to PEEP 9cmH(2)O (P=1). In addition, PEEP 15cmH(2)O markedly increased maximal hyperinflation (P<0.01) and tidal hyperinflation (P<0.05). Lung compliance decreased with PEEP 15cmH(2)O (P<0.001). ConclusionIn this series of patients with ARDS of mainly pulmonary origin, application of high levels of PEEP did not decrease tidal recruitment/derecruitment, but instead consistently increased tidal and maximal hyperinflation.
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