ArticleCritical care (London, England)2013
Biomarkers of lung epithelial injury and inflammation distinguish severe sepsis patients with acute respiratory distress syndrome.
Article in Critical care (London, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
134 citing papers in PubMed, 3 syntheses or guidelines pooled it, 227 citations in OpenAlex.
- Incidence and predictors of acute respiratory distress syndrome in sepsis: a systematic review and meta-analysis.Frontiers in medicine · 2026Pooled it
- Predictive Modeling of Acute Respiratory Distress Syndrome Using Machine Learning: Systematic Review and Meta-Analysis.Journal of medical Internet research · 2025Pooled it
- Circulating Pulmonary-Originated Epithelial Biomarkers for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2023Pooled it
- Anesthetics to Prevent Lung Injury in Cardiac Surgery: A Randomized Controlled Trial.Journal of cardiothoracic and vascular anesthesia · 2022Trial
- RAGE has potential pathogenetic and prognostic value in nonintubated hospitalized patients with COVID-19.JCI insight · 2022Trial
- Predictive model for acute respiratory distress syndrome events in ICU patients in China using machine learning algorithms: a secondary analysis of a cohort study.Journal of translational medicine · 2019Trial
- The beta agonist lung injury trial prevention. A randomized controlled trial.American journal of respiratory and critical care medicine · 2014Trial
- Research trends and cellular targets of NF-κB pathway in acute lung injury [2005-2024]: a combined bibliometric analysis and systematic review.Journal of thoracic disease · 2026Article
- Ferroptosis-Senescence Crosstalk in Sepsis-Associated Acute Lung Injury: Mechanisms and Therapeutic Opportunities.Biomedicines · 2026Review
- Unraveling mortality risk in pediatric acute respiratory distress syndrome: key biomarkers and pathophysiological insights.Pediatric research · 2026Review
- Surfactant protein D expression and clinical value of hypobaric hypoxia-induced acute lung injury and acute respiratory distress syndrome patients.Annals of medicine and surgery (2012) · 2026Article
- Source-renewing ectopic ApoB-TRL lipolysis in non-resolving ARDS: a testable spatial hypothesis.Frontiers in immunology · 2026Article
- Circulating and Respiratory Biomarkers in Sepsis-Induced ARDS: Diagnostic and Prognostic Insights - A Narrative Review.Journal of inflammation research · 2026Review
- Role of Lipidomics in Respiratory Tract Infections: A Systematic Review of Emerging Evidence.Microorganisms · 2025Review
- 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
- Immunobiological effects of tocilizumab across respiratory subphenotypes in COVID-19 ARDS.Intensive care medicine experimental · 2025Article
- Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.Pediatric research · 2025Review
- Oxidized Cell-Free Hemoglobin Induces Mitochondrial Dysfunction by Activation of the Mitochondrial Permeability Transition Pore in the Pulmonary Microvasculature.Microcirculation (New York, N.Y. : 1994) · 2025Article
- Expert consensus on cancer treatment-related lung injury.Journal of thoracic disease · 2025Review
- ICU 'Magic Numbers': The Role of Biomarkers in Supporting Clinical Decision-Making.Diagnostics (Basel, Switzerland) · 2025Review
74 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
introductionDespite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.
methodsThis was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.
resultsUsing the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.
conclusionsAbnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.
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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.