生物谷报道： 英国研究者报告说，肺脏异基因移植患者支气管肺泡灌洗液中胃蛋白酶水平持续性升高，与肺移植急性排斥有关。
英国泰恩河上游纽卡斯尔大学的Chris Ward博士说，他们认为胃刺激可能与移植肺部的总体损伤有关。意味着非异基因免疫损伤也会导致原来认为仅与异基因免疫有关的病理学改变。”Ward博士及其同事的文章发表在6月15日出版的《美国呼吸和紧急护理医学杂志》上。
研究小组选取36个肺移植患者、17个主诉咳嗽但是肺功能正常的对照、4例健康不吸烟的对照，检测支气管肺泡灌洗液中的胃蛋白酶水平。与对照病例相比，稳定肺移植患者、急性排斥患者、细支气管炎性阻塞综合症患者的胃蛋白酶水平升高。临床明显急性排斥（A2级以上）的肺移植患者中胃蛋白酶水平最高。研究进一步支持，胃食道反流是肺损伤的一个潜在重要因素。
他们还指出，最近研究表明，肺移植之前做手术加强胃和食道之间的瓣膜，有助于延长生存，延迟肺移植患者的阻塞性支气管炎的发病。如果可以证实这种手术有助于预防肺排斥，检测胃蛋白酶可能有助于发现这些手术适应症患者。（引自中国公众科技网）
原始出处:
Published ahead of print on April 5, 2007, doi:10.1164/rccm.200610-1485OC
American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 1298-1303, (2007)
Pepsin, a Biomarker of Gastric Aspiration in Lung Allografts
A Putative Association with Rejection
Rachel Stovold1,2, Ian A. Forrest1, Paul A. Corris1, Desmond M. Murphy1, Jaclyn A. Smith3, Sam Decalmer3, Gail E. Johnson1, John H. Dark1, Jeffrey P. Pearson2 and Chris Ward1
1 Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, and 2 Epithelial Research Group, Institute for Cell and Molecular Biosciences, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, United Kingdom; and 3 North West Lung Research Centre, University of Manchester, Manchester, United Kingdom
Correspondence and requests for reprints should be addressed to Chris Ward, Ph.D., Institute of Cellular Medicine, School of Clinical Medical Sciences, William Leech Building, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK. E-mail: chris.ward@ncl.ac.uk
Rationale: Human lung transplantation is a therapeutic option for selected patients with advanced cardiopulmonary disease, but long-term survival is limited by chronic rejection. Persistent acute rejection and gastric aspiration have been implicated as risk factors but there is little or no evidence to date that they are associated.
Objectives: We have tested the hypothesis that pepsin, a marker of gastric aspiration, is present in lung transplant recipients, and that high levels are associated with biopsy-diagnosed acute rejection and/or bronchiolitis obliterans syndrome.
Methods: Levels of bronchoalveolar lavage (BAL) pepsin were measured by ELISA in 36 lung transplant recipients, 4 normal volunteers, and 17 subjects with unexplained chronic cough.
Measurements and Main Results: Our primary finding was that, compared with control subjects, BAL pepsin levels were elevated in stable lung transplant recipients, subjects with acute rejection, and subjects with bronchiolitis obliterans syndrome. Our secondary finding was that the highest levels were found in recipients with acute vascular rejection grade A2 (median, 11.2; range, 5.4 – 51.7 ng/ml; normal median, 1.1; range, 0–2.3 ng/ml; p = 0.004).
Conclusions: We have shown that elevated levels of pepsin, a biomarker of gastric aspiration, are consistently identified in the BAL of lung allografts. The highest levels were seen in patients with grade A2 acute rejection. This provides further evidence supporting the possible role of aspiration in the development of overall allograft injury.
Key Words: lung allograft • gastroesophageal reflux, GER • pepsin • rejection
