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Vascular Endothelial Growth Factor in Human Lung Transplantation^*

^* From the Departments of Medicine (Drs. Meyer, Xiang, and Cornwell, and Mr. Cardoni) and Surgery (Dr. Love), University of Wisconsin Medical School, Madison, WI.

Correspondence to: Keith C. Meyer, MD, FCCP, Department of Medicine, H6/380 Clinical Sciences Center, 600 Highland Ave, Madison, WI 53792; e-mail: kcm{at}medicine.wisc.edu

Study objectives: To determine levels of the vascular endothelial growth factor (VEGF) isoform consisting of 165 amino acids (VEGF₁₆₅) in BAL fluid (BALF) from lung transplant recipients (LTXs).

Design: Bronchoscopy with BAL was performed on LTXs and normal volunteers (NVs).

Setting: University hospital.

Participants: LTXs (n = 57) and NVs (n = 15).

Measurements and result: VEGF₁₆₅ concentrations in BALF were higher (mean ± SEM, 240 ± 32 pg/mL) for NVs (n = 15) vs 133 ± 14 pg/mL for LTXs (n = 37) who were stable without evidence of significant rejection or infection at 6 months after transplantation (p < 0.0001). BALF VEGF concentrations sampled at 24 to 48 h, 2 weeks, 4 weeks, and 6 months after transplantation for 11 LTXs who lacked rejection or infection at any time point were 71 ± 8 pg/mL, 80 ± 20 pg/mL, 82 ± 13 pg/mL, and 167 ± 31 pg/mL, respectively. VEGF concentrations in BALF for LTXs with cytomegalovirus (CMV) pneumonia were 55 ± 12 pg/mL (n = 10), 117 ± 33 pg/mL for grade A3 acute rejection (n = 9), and 82 ± 17 pg/mL (n = 14) for active bronchiolitis obliterans syndrome (BOS). Concentrations of VEGF in BALF at 6 months for the 32 stable recipients with bilateral lung transplantation were significantly higher for those with higher values for FEV₁, and BALF VEGF concentrations were significantly lower in BALF at 6 months for those recipients who subsequently went on to develop BOS (86 ± 19 pg/mL) vs those who did not (158 ± 18 pg/mL; p = 0.03). Serum concentrations of VEGF did not correlate with VEGF concentrations in BALF, but serum VEGF was 291 ± 62 pg/mL at 10 to 14 days after transplantation vs 130 ± 20 pg/mL at 4 weeks for nine LTXs with paired samples (p < 0.02). Serum VEGF concentrations for NVs (n = 15) were 102 ± 15 pg/mL vs 94 ± 17 for stable LTXs (n = 12) at 24 weeks after transplantation and 123 ± 33 pg/mL for LTXs with active BOS (n = 10).

Conclusions: BALF VEGF concentrations are particularly depressed at early time points following lung transplantation, gradually improve in the absence of significant rejection or infection, and are lower with active rejection or CMV pneumonia.

Key Words: BAL • lung transplantation • vascular endothelial growth factor

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