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ACUTE LUNG INJURY |
1 Intensive Care Unit, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, UK
2 Lung Research Group, University of Bristol Medical School Unit, Southmead Hospital, Bristol, UK
3 Lung Injury Fibrosis Treatment Programme, University of Birmingham, Lung Investigation Unit, Nuffield House, Queen Elizabeth Hospital, Birmingham, UK
Correspondence to:
Correspondence to:
Dr D Thickett
Lung Injury Fibrosis Treatment Programme, University of Birmingham, Lung Investigation Unit, Nuffield House, Queen Elizabeth Hospital, Birmingham B15 2TT, UK; d.thickett{at}bham.ac.uk
ABSTRACT
Background: Reduced bioactive vascular endothelial growth factor (VEGF) has been demonstrated in several inflammatory lung conditions including the acute respiratory distress syndrome (ARDS). sVEGFR-1, a soluble form of VEGF-1 receptor, is a potent natural inhibitor of VEGF. We hypothesised that sVEGFR-1 plays an important role in the regulation of the bioactivity of VEGF within the lung in patients with ARDS.
Methods: Forty one patients with ARDS, 12 at risk of developing ARDS, and 16 normal controls were studied. Bioactive VEGF, total VEGF, and sVEGFR-1 were measured by ELISA in plasma and bronchoalveolar lavage (BAL) fluid. Reverse transcriptase polymerase chain reaction for sVEGFR-1 was performed on BAL cells.
Results: sVEGFR-1 was detectable in the BAL fluid of 48% (20/41) of patients with early ARDS (1.4–54.8 ng/ml epithelial lining fluid (ELF)) compared with 8% (1/12) at risk patients (p = 0.017) and none of the normal controls (p = 0.002). By day 4 sVEGFR-1 was detectable in only 2/18 ARDS patients (p = 0.008). Patients with detectable sVEGFR-1 had lower ELF median (IQR) levels of bioactive VEGF than those without detectable sVEGFR-1 (1415.2 (474.9–3192) pg/ml v 4761 (1349–7596.6) pg/ml, median difference 3346 pg/ml (95% CI 305.1 to 14711.9), p = 0.016), but there was no difference in total VEGF levels. BAL cells expressed mRNA for sVEGFR-1 and produced sVEGFR-1 protein which increased following incubation with tumour necrosis factor 
.
Conclusion: This study shows for the first time the presence of sVEGFR-1 in the BAL fluid of patients with ARDS. This may explain the presence of reduced bioactive VEGF in patients early in the course of ARDS.
Abbreviations: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ELF, epithelial lining fluid; LIS, lung injury score; TNF, tumour necrosis factor ; VEGF, vascular endothelial growth factor
Keywords: acute lung injury; vascular endothelial growth factor; acute respiratory distress syndrome
This article has been cited by other articles:
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  A R L Medford and A B Millar Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm? Thorax, July 1, 2006; 61(7): 621 - 626. [Abstract] [Full Text] [PDF]
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A G Richter, E O Maughan, G D Perkins, N Nathani, and D R Thickett VEGF levels in pulmonary fibrosis Thorax, February 1, 2005; 60(2): 171 - 171. [Full Text] [PDF]
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