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

Lorraine B. Ware, Tatsuki Koyama, David D Billheimer, William Wu, Gordon R. Bernard, B. Taylor Thompson, Roy G. Brower, Theodore J. Standiford, Thomas R. Martin, Michael A. Matthay, G. R. Bernard

Research output: Contribution to journalArticle

178 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)288-296
Number of pages9
JournalChest
Volume137
Issue number2
DOIs
StatePublished - Feb 1 2010

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Acute Lung Injury
Biomarkers
Interleukin-8
Pulmonary Surfactant-Associated Protein D
ROC Curve
Mortality
Inflammation
Wounds and Injuries
Alveolar Epithelial Cells
APACHE
Positive-Pressure Respiration
Tumor Necrosis Factor Receptors
Plasminogen Activator Inhibitor 1
von Willebrand Factor
Intercellular Adhesion Molecule-1
Protein C
Area Under Curve
Interleukin-6
Logistic Models
Clinical Trials

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury. / Ware, Lorraine B.; Koyama, Tatsuki; Billheimer, David D; Wu, William; Bernard, Gordon R.; Thompson, B. Taylor; Brower, Roy G.; Standiford, Theodore J.; Martin, Thomas R.; Matthay, Michael A.; Bernard, G. R.

In: Chest, Vol. 137, No. 2, 01.02.2010, p. 288-296.

Research output: Contribution to journalArticle

Ware, LB, Koyama, T, Billheimer, DD, Wu, W, Bernard, GR, Thompson, BT, Brower, RG, Standiford, TJ, Martin, TR, Matthay, MA & Bernard, GR 2010, 'Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury', Chest, vol. 137, no. 2, pp. 288-296. https://doi.org/10.1378/chest.09-1484
Ware, Lorraine B. ; Koyama, Tatsuki ; Billheimer, David D ; Wu, William ; Bernard, Gordon R. ; Thompson, B. Taylor ; Brower, Roy G. ; Standiford, Theodore J. ; Martin, Thomas R. ; Matthay, Michael A. ; Bernard, G. R. / Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury. In: Chest. 2010 ; Vol. 137, No. 2. pp. 288-296.
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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.",
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AU - Ware, Lorraine B.

AU - Koyama, Tatsuki

AU - Billheimer, David D

AU - Wu, William

AU - Bernard, Gordon R.

AU - Thompson, B. Taylor

AU - Brower, Roy G.

AU - Standiford, Theodore J.

AU - Martin, Thomas R.

AU - Matthay, Michael A.

AU - Bernard, G. R.

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N2 - 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.

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