Acute lung injury in patients with traumatic injuries: utility of a panel of biomarkers for diagnosis and pathogenesis.
BACKGROUND
The diagnosis of acute lung injury (ALI) is based on a consensus clinical definition. Despite the simplicity of this definition, ALI remains underdiagnosed and undertreated. Severe trauma is a well-described cause of ALI that represents a relatively homogeneous subset of patients with ALI. The aims of this study were to develop a panel of plasma biomarkers to facilitate diagnosis of trauma-induced ALI and to enhance our understanding of the pathogenesis of human ALI.


METHODS
A retrospective nested case control of 192 patients admitted to the trauma intensive care unit at a university hospital between 2002 and 2006. We compared 107 patients with ALI to 85 patients without ALI. Plasma was collected within 72 hours of intensive care unit admission. Twenty-one plasma biomarkers were measured in duplicate in each plasma sample.


RESULTS
Patients with ALI had higher severity of illness scores, more days of mechanical ventilation, longer hospital stays, and higher mortality versus controls. Seven biomarkers (receptor for advanced glycation end products, procollagen peptide III, brain natriuretic peptide, angiopoietin-2, interleukin-10, tumor necrosis factor alpha, and interleukin-8) had a high diagnostic accuracy as reflected by the area under the receiver operating characteristic curve of 0.86 (95% confidence interval, 0.82-0.92) in differentiating ALI from controls.


CONCLUSIONS
A model using seven plasma biomarkers had a high diagnostic accuracy in differentiating patients with trauma-induced ALI from trauma patients without ALI. In addition, use of a panel of biomarkers provides insight into the likely importance of alveolar epithelial injury in the pathogenesis of early ALI.
Fremont
Richard D
RD
Division of Allergy, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650, USA.
Koyama
Tatsuki
T
Calfee
Carolyn S
CS
Wu
William
W
Dossett
Lesly A
LA
Bossert
Fred R
FR
Mitchell
Daphne
D
Wickersham
Nancy
N
Bernard
Gordon R
GR
Matthay
Michael A
MA
May
Addison K
AK
Ware
Lorraine B
LB
D055371:Acute Lung Injury / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D000328:Adult; D042702:Angiopoietin-2 / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D015984:Causality; D024061:Collagen Type III / Q000097:blood; D016002:Discriminant Analysis; D005260:Female; D006785:Hospitals, University; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007902:Length of Stay / Q000706:statistics & numerical data; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011237:Predictive Value of Tests; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014947:Wounds and Injuries / Q000150:complications*
D042702:Angiopoietin-2; D015415:Biomarkers; D024061:Collagen Type III; D016209:Interleukin-8; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D016753:Interleukin-10