Angiopoietin-2, permeability oedema, occurrence and severity of ALI/ARDS in septic and non-septic critically ill patients

Melanie van der Heijden ^1*, Geerten P van Nieuw Amerongen ¹, Pieter Koolwijk ¹, Victor WM van Hinsbergh ¹ and AB Johan Groeneveld ¹

¹ VU University Medical Centre, Netherlands

^* To whom correspondence should be addressed. E-mail: m.vanderheijden{at}vumc.nl.

Accepted 7 May 2008

Abstract

Background: Angiopoietin-2 and vascular endothelial growth factor (VEGF) may impair vascular barrier function, while angiopoietin-1 may protect. We hypothesised that circulating angiopoietin-2 is associated with pulmonary permeability oedema and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) during septic or non-septic critical illness.

Methods: In 24 septic and 88 non-septic mechanically ventilated patients, plasma levels of angiopoietin-1 and angiopoietin-2 were measured, together with the pulmonary leak index (PLI) for ⁶⁷Gallium-labelled transferrin and extravascular lung water (EVLW) by transpulmonary thermal-dye dilution as measures of pulmonary permeability and oedema, respectively. ALI/ARDS was characterised by consensus criteria and the lung injury score (LIS). Furthermore, plasma VEGF and von Willebrand factor (VWF) levels were assayed.

Results: Angiopoietin-2, VWF, PLI, EVLW, and LIS were higher in septic than in non-septic patients and higher in patients with ALI/ARDS (n=10/12 in sepsis, n=19/8 in non-sepsis) than without. VEGF was also higher in patients with sepsis than without. Patients with high PLI, regardless of EVLW, had higher angiopoietin-2 levels than patients with normal PLI and EVLW. Angiopoietin-2 correlated to the PLI, LIS, and VWF (minimum r=0.34, P<0.001), but not to EVLW. Angiopoietin-2 and VWF were of predictive value for ARDS in receiver operating characteristic curves (minimum area under the curve=0.69, P=0.006). Angiopoietin-1 and VEGF did not relate to the permeability oedema of ALI/ARDS.

Conclusion: Circulating angiopoietin-2 is associated with pulmonary permeability oedema, occurrence and severity of ALI/ARDS in septic and non-septic patients. The correlation of angiopoietin-2 with VWF suggests activated endothelium as a common source.