Endothelin-1 is a useful biomarker for early detection of bronchiolitis obliterans in lung transplant recipients

Abstract

Bronchiolitis obliterans (BO) is a severe complication limiting long-term survival after lung transplantation. To date, no cure exists for BO, and the mechanisms leading to BO are not well understood. Endothelin-1 (ET-1) is a potent mitogenic and profibrotic peptide produced by pulmonary vascular endothelial cells that play a role in the pathophysiology of lung allograft dysfunction. Whether ET-1 could predict BO syndrome (BOS) development is unknown. Transbronchial biopsy specimens and serum and bronchoalveolar lavage were obtained from 30 lung transplantation patients with and 30 without BOS at 3 points. The serum and bronchoalveolar lavage ET-1 concentrations were measured by enzyme-linked immunosorbent assay, and the ET-1 mRNA expression in the transbronchial biopsy specimens was examined using real-time polymerase chain reaction. The pretransplant ET-1 serum concentrations were greater in the patients with BOS (P = .02); and ET-1 mRNA was significantly upregulated in the lung grafts of those with versus those without BOS at 3 and 12 months after transplant (P = .01). At 3 and 12 months after transplantation, the ET-1 concentrations were significantly elevated in the serum (P < .01 and P < .0001, respectively) and bronchoalveolar lavage (P < .01 and P = .02, respectively) of patients with compared with those without BOS. On logistic regression analysis, the pretransplant and 3-month post-transplant serum ET-1 level predicted for BOS (odds ratio, 1.01; 95% confidence interval, 1.004-1.025; P < .007; odds ratio, 2.9; 95% confidence interval, 1.01-8.52; P < .001). The serum ET-1 level at 12 months was diagnostic for BOS (odds ratio, 3.9; 95% confidence interval, 1.42-10.80; P = .008). Elevated serum ET-1 concentrations were predictive of BOS, and the assessment of circulating ET-1 might be beneficial in diagnosing and monitoring BO.