Observational studyThorax2022
Latent class analysis-derived subphenotypes are generalisable to observational cohorts of acute respiratory distress syndrome: a prospective study.
Observational study in Thorax, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07511582 (Efficacy, Safety, and Tolerability of Methylprednisolone in Critically Ill Patients With the Hyperinflammatory Phenotype), which is not on this map. Cited by 73 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy, Safety, and Tolerability of Methylprednisolone in Critically Ill Patients With the Hyperinflammatory Phenotype: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Trial
Who cites it
73 citing papers in PubMed, 126 citations in OpenAlex.
- Early differential protein expression in blood and bronchoalveolar fluid among ARDS phenotypes.Scientific reports · 2026Trial
- Longitudinal multiomic signatures of ARDS and sepsis inflammatory phenotypes identify pathways associated with mortality.The Journal of clinical investigation · 2026Trial
- Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.The Journal of clinical investigation · 2024Trial
- Novel subtypes of severe COVID-19 respiratory failure based on biological heterogeneity: a secondary analysis of a randomized controlled trial.Critical care (London, England) · 2024Trial
- Identifying clinical subtypes in acute dyspnoea patients admitted to the emergency department: a secondary model-based clustering of prospective cohorts.ESC heart failure · 2026Article
- Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS.Critical care (London, England) · 2026Observational
- Integrative bioinformatics and machine learning reveal an association of LTF and MMP8 with systemic inflammation and lung injury.Respiratory research · 2026Article
- Data-driven subphenotyping of severe ARDS patients requiring VV-ECMO.Frontiers in digital health · 2026Article
- Nursing interventions and multidomain physiological trajectories in ARDS: a retrospective cohort study.Frontiers in medicine · 2026Article
- Parsimonious Subphenotyping Algorithms Perform Differently in Patients With Sepsis and Hematologic Malignancy.Critical care medicine · 2025Article
- The utility of angiopoietin-2 and blood cell-derived biomarker indices in differentiating rapidly improving acute respiratory distress syndrome (RIARDS) phenotype from persistent-ARDS: a prospective observational study.Annals of medicine · 2025Observational
- Acute Respiratory Distress Syndrome Molecular Phenotypes Have Distinct Lower Respiratory Tract Transcriptomes.American journal of respiratory and critical care medicine · 2025Article
- Prognostic Relevance of Inflammatory Subphenotypes in Immunocompromised Patients With Sepsis.Critical care medicine · 2025Observational
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- Clinical Phenotyping in Acute Respiratory Distress Syndrome: Steps Towards Personalized Medicine.Journal of clinical medicine · 2025Article
- Prediction of Hyperinflammatory Phenotypes in Critically Ill Patients via Routine Clinical Data and IL-6: Towards Personalized Anti-Inflammatory Therapy.International journal of molecular sciences · 2025Article
- Longitudinal multi-omic signatures of ARDS and sepsis inflammatory phenotypes identify key pathways associated with mortality.medRxiv : the preprint server for health sciences · 2025Article
- A Computable Electronic Health Record ARDS Classifier and the Association Between theCHEST critical care · 2025Article
- Acute Respiratory Distress Syndrome Phenotypes After Stem Cell Transplantation: A Latent Class Analysis.Critical care explorations · 2025Article
- Heterogeneity in association of myocardial injury and mortality in sepsis or acute respiratory distress syndrome by subphenotype: a retrospective study.Critical care (London, England) · 2025Observational
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- AssociatedDataset
Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
Abstract
rationaleUsing latent class analysis (LCA), two subphenotypes of acute respiratory distress syndrome (ARDS) have consistently been identified in five randomised controlled trials (RCTs), with distinct biological characteristics, divergent outcomes and differential treatment responses to randomised interventions. Their existence in unselected populations of ARDS remains unknown. We sought to identify subphenotypes in observational cohorts of ARDS using LCA.
methodsLCA was independently applied to patients with ARDS from two prospective observational cohorts of patients admitted to the intensive care unit, derived from the Validating Acute Lung Injury markers for Diagnosis (VALID) (n=624) and Early Assessment of Renal and Lung Injury (EARLI) (n=335) studies. Clinical and biological data were used as class-defining variables. To test for concordance with prior ARDS subphenotypes, the performance metrics of parsimonious classifier models (interleukin 8, bicarbonate, protein C and vasopressor-use), previously developed in RCTs, were evaluated in EARLI and VALID with LCA-derived subphenotypes as the gold-standard.
resultsA 2-class model best fit the population in VALID (p=0.0010) and in EARLI (p<0.0001). Class 2 comprised 27% and 37% of the populations in VALID and EARLI, respectively. Consistent with the previously described 'hyperinflammatory' subphenotype, Class 2 was characterised by higher proinflammatory biomarkers, acidosis and increased shock and worse clinical outcomes. The similarities between these and prior RCT-derived subphenotypes were further substantiated by the performance of the parsimonious classifier models in both cohorts (area under the curves 0.92-0.94). The hyperinflammatory subphenotype was associated with increased prevalence of chronic liver disease and neutropenia and reduced incidence of chronic obstructive pulmonary disease. Measurement of novel biomarkers showed significantly higher levels of matrix metalloproteinase-8 and markers of endothelial injury in the hyperinflammatory subphenotype, whereas, matrix metalloproteinase-9 was significantly lower.
conclusionPreviously described subphenotypes are generalisable to unselected populations of non-trauma ARDS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.