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Objective: A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial.Design: Retrospective analysis of randomized controlled clinical trial.Setting: Multicenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis.Patients: Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population.Interventions: Random assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge.Measurements and Main Results: We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We tested the association among interleukin-18 level at baseline, rising interleukin-18, and the impact of statin therapy on 60-day mortality, adjusting for severity of illness. Baseline plasma interleukin-18 level greater than or equal to 800 pg/mL was highly associated with 60-day mortality, with a hazard of death of 2.3 (95% CI, 1.7-3.1). Rising plasma interleukin-18 was also associated with increased mortality. For each unit increase in log2 (interleukin-18) at day 3 compared with baseline, the hazard of death increased by 2.3 (95% CI, 1.5-3.5). Subjects randomized to statin were significantly more likely to experience a rise in plasma interleukin-18 levels. Subjects with acute kidney injury, shock, low baseline interleukin-18, and those not receiving systemic corticosteroids were more likely to experience rising interleukin-18. Randomization to statin therapy was associated with rising in interleukin-18 in all of those subsets, however.Conclusions: Elevated baseline plasma interleukin-18 was associated with higher mortality in sepsis-induced acute respiratory distress syndrome. A rise in plasma interleukin-18 was also associated with increased mortality and was more common in subjects randomized to statin therapy in this clinical trial. [ABSTRACT FROM AUTHOR]

The article discusses a study by D. J. Kor and colleagues which examines the accuracy of early warning identification systems, pulmonary vascular permeability index (PVPI) and peak extravascular lung water (EVLWi), in identifying early acute respiratory distress syndrome (ARDS). It says that PVPI and EVLWi were examined as markers of pulmonary edema in patients undergoing high-risk cardiac surgery. It discusses how area under curve (AUC) compare to identification methods for high-risk patients.

Objectives: To identify a novel, generalizable diagnostic for acute respiratory distress syndrome using whole-blood gene expression arrays from multiple acute respiratory distress syndrome cohorts of varying etiologies.Data Sources: We performed a systematic search for human whole-blood gene expression arrays of acute respiratory distress syndrome in National Institutes of Health Gene Expression Omnibus and ArrayExpress. We also included the Glue Grant gene expression cohorts.Study Selection: We included investigator-defined acute respiratory distress syndrome within 48 hours of diagnosis and compared these with relevant critically ill controls.Data Extraction: We used multicohort analysis of gene expression to identify genes significantly associated with acute respiratory distress syndrome, both with and without adjustment for clinical severity score. We performed gene ontology enrichment using Database for Annotation, Visualization and Integrated Discovery and cell type enrichment tests for both immune cells and pneumocyte gene expression. Finally, we selected a gene set optimized for diagnostic power across the datasets and used leave-one-dataset-out cross validation to assess robustness of the model.Data Synthesis: We identified datasets from three adult cohorts with sepsis, one pediatric cohort with acute respiratory failure, and two datasets of adult patients with trauma and burns, for a total of 148 acute respiratory distress syndrome cases and 268 critically ill controls. We identified 30 genes that were significantly associated with acute respiratory distress syndrome (false discovery rate < 20% and effect size >1.3), many of which had been previously associated with sepsis. When metaregression was used to adjust for clinical severity scores, none of these genes remained significant. Cell type enrichment was notable for bands and neutrophils, suggesting that the gene expression signature is one of acute inflammation rather than lung injury per se. Finally, an attempt to develop a generalizable diagnostic gene set for acute respiratory distress syndrome showed a mean area under the receiver-operating characteristic curve of only 0.63 on leave-one-dataset-out cross validation.Conclusions: The whole-blood gene expression signature across a wide clinical spectrum of acute respiratory distress syndrome is likely confounded by systemic inflammation, limiting the utility of whole-blood gene expression studies for uncovering a generalizable diagnostic gene signature. [ABSTRACT FROM AUTHOR]