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

Chest. 2010 Feb;137(2):288-96. doi: 10.1378/chest.09-1484. Epub 2009 Oct 26.

Abstract

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Lung Injury / diagnosis
  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / mortality
  • Adult
  • Aged
  • Biomarkers / metabolism*
  • Blood Coagulation Factors / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-8 / blood
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Pulmonary Surfactant-Associated Protein D / metabolism
  • Survival Rate
  • United States / epidemiology

Substances

  • Biomarkers
  • Blood Coagulation Factors
  • Interleukin-8
  • Pulmonary Surfactant-Associated Protein D