Biomarkers of inflammation, coagulation and fibrinolysis predict mortality in acute lung injury.
BACKGROUND
Acute lung injury (ALI) is a major cause of acute respiratory failure with high mortality despite lung-protective ventilation. Prior work has shown disordered inflammation and coagulation in ALI, with strong correlations between biomarker abnormalities and worse clinical outcomes. We measured plasma markers of inflammation, coagulation and fibrinolysis simultaneously to assess whether these markers remain predictive in the era of lung-protective ventilation.


METHODS
Plasma samples and ventilator data were prospectively collected from 50 patients with early ALI. Plasma biomarkers of inflammation (IL-6, IL-8, intercellular adhesion molecule 1), of coagulation (thrombomodulin, protein C) and of fibrinolysis (plasminogen activator inhibitor 1) were measured by ELISA. Biomarker levels were compared between survivors (n = 29) and non-survivors (n = 21) using Mann-Whitney analysis.


RESULTS
The tidal volume for the study group was 6.6 +/- 1.1 ml/kg predicted body weight and the plateau pressure was 25 +/- 7 cmH2O (mean +/- standard deviation), consistent with lung-protective ventilation. All markers except IL-6 were significantly different between survivors and nonsurvivors. Nonsurvivors had more abnormal values. Three biomarkers - IL-8, intercellular adhesion molecule 1 and protein C - remained significantly different by multivariate analysis that included age, gender, Simplified Acute Physiology Score II and all biomarkers that were significant on bivariate analysis. Higher levels of IL-8 and intercellular adhesion molecule 1 were independently predictive of worse outcomes (odds ratio = 2.0 and 5.8, respectively; P = 0.04 for both). Lower levels of protein C were independently associated with an increased risk of death (odds ratio = 0.5), a result that nearly reached statistical significance (P = 0.06).


CONCLUSIONS
Despite lung-protective ventilation, abnormalities in plasma levels of markers of inflammation, coagulation and fibrinolysis predict mortality in ALI patients, indicating more severe activation of these biologic pathways in nonsurvivors.
McClintock
Dana
D
Cardiovascular Research Institute, 505 Parnassus Avenue, University of California, San Francisco, San Francisco, CA 94143, USA. mcclintock.dana@gmail.com
Zhuo
Hanjing
H
Wickersham
Nancy
N
Matthay
Michael A
MA
Ware
Lorraine B
LB
D018806:APACHE; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000401:mortality*; D018709:Statistics, Nonparametric; D015996:Survival Rate; D018180:Thrombomodulin / Q000097:blood; D013990:Tidal Volume
D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D018180:Thrombomodulin; D018799:Intercellular Adhesion Molecule-1