Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury.
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.
DivisionAllergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA. lorraine.ware@vanderbilt.edu
Lorraine B
LB
Ware
Tatsuki
T
Koyama
D Dean
DD
Billheimer
William
W
Wu
Gordon R
GR
Bernard
B Taylor
BT
Thompson
Roy G
RG
Brower
Theodore J
TJ
Standiford
Thomas R
TR
Martin
Michael A
MA
Matthay
D055371:Acute Lung Injury / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D001779:Blood Coagulation Factors; D016209:Interleukin-8; D037663:Pulmonary Surfactant-Associated Protein D