Andrew R. L. Medford, MD, Sofia I. H. Godinho, PhD, Leigh J. Keen, PhD, Jeffrey L. Bidwell, PhD and Ann B. Millar, MD. CHEST August 2009 vol. 136 no. 2 457-464
Background: Vascular endothelial growth factor (VEGF) is postulated to have a role in ARDS. The functional VEGF + 936 polymorphic T allele is associated with an increased susceptibility to and severity of ARDS. The reasons for this are unclear. We hypothesized that the T allele would be associated with an alteration in the relation between epithelial lining fluid (ELF) and plasma VEGF levels as a potential explanation for its association with susceptibility to and severity of ARDS.
Methods: Plasma and ELF VEGF protein levels were measured by enzyme-linked immunosorbent assay from 10 at-risk patients receiving mechanical ventilation and 16 ARDS patients with the T allele, as well as 18 at-risk patients receiving mechanical ventilation and 26 ARDS patients without the T allele (wild-type CC genotype).
Results: The T allele was associated with a significantly lower mean ELF VEGF level in ARDS patients (2,090 ± 758 pg/mL vs 3,292 ± 865 pg/mL, p < 0.05) and mean ELF/plasma VEGF level ratio (13.7 ± 4.6 pg/mL vs 94.7 ± 51.2 pg/mL, p < 0.01). There was no relation between the T allele and plasma VEGF level, oxygenation, or acute physiology score in at-risk and ARDS patients. ELF VEGF levels were significantly higher than plasma levels in both cohorts except for at-risk patients without the T allele (wild-type CC genotype).
Conclusion: The T allele is associated with a significant decrease in ELF levels and the ELF/plasma ratio in ARDS patients. This may explain the increased susceptibility and physiologic derangement in ARDS patients with the T allele. We speculate VEGF has a protective function in the lung. Further studies are necessary to clarify the underlying mechanisms.
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