Ratio of angiopoietin-2 to angiopoietin-1 as a predictor of mortality in acute lung injury patients.
OBJECTIVE
To test the hypothesis that the concentration of angiopoietin-2 relative to angiopoietin-1 may be a useful biological marker of mortality in acute lung injury patients. We also tested the association of concentration of angiopoietin-2 relative to angiopoietin-1 with physiologic and biological markers of activated endothelium.


METHODS
Prospective, observational cohort study.


METHODS
Intensive care units in a tertiary care university hospital and a university-affiliated city hospital.


METHODS
Fifty-six mechanically ventilated patients with acute lung injury.


METHODS
Baseline plasma samples and pulmonary dead-space fraction measurements were collected within 48 hrs of acute lung injury diagnosis.


RESULTS
Plasma levels of angiopoietin-1 and angiopoietin-2 and of biomarkers of endothelial activation were measured by enzyme-linked immunosorbent assay. Baseline concentration of angiopoietin-2 relative to angiopoietin-1 was significantly higher in patients who died (median, 58 [interquartile range, 17-117] vs. 14 [interquartile range, 6-35]; p = .01). In a multivariable analysis stratified by dead-space fraction, concentration of angiopoietin-2 relative to angiopoietin-1 was an independent predictor of death, with an adjusted odds ratio of 4.3 (95% confidence interval, 1.3-13.5; p = .01) in those with an elevated pulmonary dead-space fraction (p = .03 for interaction between pulmonary dead-space fraction and concentration of angiopoietin-2 relative to angiopoietin-1). Moderate to weak correlation was found with biological markers of endothelial activation.


CONCLUSIONS
The ratio of concentration of angiopoietin-2 relative to angiopoietin-1 may be a prognostic biomarker of endothelial activation in acute lung injury patients and, along with pulmonary dead-space fraction, may be useful for risk stratification of acute lung injury patients, particularly in identifying subgroups for future research and therapeutic trials.
Ong
Thida
T
Division of Pulmonary Medicine, Department of Pediatrics, University of California, San Francisco, California, USA.
McClintock
Dana E
DE
Kallet
Richard H
RH
Ware
Lorraine B
LB
Matthay
Michael A
MA
Liu
Kathleen D
KD
D055371:Acute Lung Injury / Q000097:blood / Q000401:mortality*; D000328:Adult; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers