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

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 140; no. 6; pp. 1422 - 1427
• Main Authors: Salama, Mohamed, MD, Jaksch, Peter, MD, Andrukhova, Olena, PhD, Taghavi, Shahrokh, MD, Klepetko, Walter, MD, Aharinejad, Seyedhossein, MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.12.2010; Elsevier
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biomarkers - analysis; Biopsy; Bronchiolitis Obliterans - diagnosis; Bronchiolitis Obliterans - etiology; Bronchiolitis Obliterans - physiopathology; Bronchiolitis Obliterans - therapy; Bronchoalveolar Lavage; Cardiology. Vascular system; Cardiothoracic Surgery; Chronic obstructive pulmonary disease, asthma; Endothelin-1 - analysis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunosuppressive Agents - therapeutic use; Logistic Models; Lung Transplantation - adverse effects; Male; Medical sciences; Middle Aged; Pneumology; Predictive Value of Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; transbronchial biopsy; OR; bronchiolitis obliterans syndrome; CI; BOS; bronchiolitis obliterans; odds ratio; BAL; BO; CMV; ET-1; FEV 1; cytomegalovirus; TBB; confidence interval; forced expiratory volume in 1 second; endothelin-1; bronchoalveolar lavage; PCR; polymerase chain reaction; Respiratory disease; Lung; Biological marker; Early stage; Transplantation; Endothelin 1; Homotransplantation; Treatment; Surgery; Graft; Bronchus disease; Anesthesia; Bronchiolitis obliterans; Circulatory system; Cardiology
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/j.jtcvs.2010.08.046

Objectives 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. Methods 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. Results 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). Conclusions Elevated serum ET-1 concentrations were predictive of BOS, and the assessment of circulating ET-1 might be beneficial in diagnosing and monitoring BO.