Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: No single clinical or biologic marker reliably predicts clinical outcomes in acute lung injury (ALI)/ARDS. We hypothesized that a combination of biologic and clinical markers would be superior to either biomarkers or clinical factors alone in predicting ALI/ARDS mortality and would provide insight into the pathogenesis of clinical ALI/ARDS. METHODS: Eight biologic markers that reflect endothelial and epithelial injury, inflammation, and coagulation (von Willebrand factor antigen, surfactant protein D [SP-D]), tumor necrosis factor receptor-1, interleukin [IL]-6, IL-8, intercellular adhesion molecule-1, protein C, plasminogen activator inhibitor-1) were measured in baseline plasma from 549 patients in the ARDSNet trial of low vs high positive end-expiratory pressure. Mortality was modeled with multivariable logistic regression. Predictors were selected using backward elimination. Comparisons between candidate models were based on the receiver operating characteristics (ROC) and tests of integrated discrimination improvement. RESULTS: Clinical predictors (Acute Physiology And Chronic Health Evaluation III [APACHE III], organ failures, age, underlying cause, alveolar-arterial oxygen gradient, plateau pressure) predicted mortality with an area under the ROC curve (AUC) of 0.82; a combination of eight biomarkers and the clinical predictors had an AUC of 0.85. The best performing biomarkers were the neutrophil chemotactic factor, IL-8, and SP-D, a product of alveolar type 2 cells, supporting the concept that acute inflammation and alveolar epithelial injury are important pathogenetic pathways in human ALI/ARDS. CONCLUSIONS: A combination of biomarkers and clinical predictors is superior to clinical predictors or biomarkers alone for predicting mortality in ALI/ARDS and may be useful for stratifying patients in clinical trials. From a pathogenesis perspective, the degree of acute inflammation and alveolar epithelial injury are highly associated with the outcome of human ALI/ARDS.

Full Text

Duke Authors

Cited Authors

  • Ware, LB; Koyama, T; Billheimer, DD; Wu, W; Bernard, GR; Thompson, BT; Brower, RG; Standiford, TJ; Martin, TR; Matthay, MA; NHLBI ARDS Clinical Trials Network,

Published Date

  • February 2010

Published In

Volume / Issue

  • 137 / 2

Start / End Page

  • 288 - 296

PubMed ID

  • 19858233

Pubmed Central ID

  • PMC2816641

Electronic International Standard Serial Number (EISSN)

  • 1931-3543

Digital Object Identifier (DOI)

  • 10.1378/chest.09-1484


  • eng

Conference Location

  • United States