生物谷報(bào)道: 英國研究者報(bào)告說,,肺臟異基因移植患者支氣管肺泡灌洗液中胃蛋白酶水平持續(xù)性升高,與肺移植急性排斥有關(guān),。
英國泰恩河上游紐卡斯?fàn)柎髮W(xué)的Chris Ward博士說,,他們認(rèn)為胃刺激可能與移植肺部的總體損傷有關(guān)。意味著非異基因免疫損傷也會(huì)導(dǎo)致原來認(rèn)為僅與異基因免疫有關(guān)的病理學(xué)改變,。”Ward博士及其同事的文章發(fā)表在6月15日出版的《美國呼吸和緊急護(hù)理醫(yī)學(xué)雜志》上,。
研究小組選取36個(gè)肺移植患者、17個(gè)主訴咳嗽但是肺功能正常的對照,、4例健康不吸煙的對照,,檢測支氣管肺泡灌洗液中的胃蛋白酶水平。與對照病例相比,,穩(wěn)定肺移植患者,、急性排斥患者、細(xì)支氣管炎性阻塞綜合癥患者的胃蛋白酶水平升高,。臨床明顯急性排斥(A2級以上)的肺移植患者中胃蛋白酶水平最高,。研究進(jìn)一步支持,胃食道反流是肺損傷的一個(gè)潛在重要因素,。
他們還指出,,最近研究表明,肺移植之前做手術(shù)加強(qiáng)胃和食道之間的瓣膜,有助于延長生存,,延遲肺移植患者的阻塞性支氣管炎的發(fā)病,。如果可以證實(shí)這種手術(shù)有助于預(yù)防肺排斥,檢測胃蛋白酶可能有助于發(fā)現(xiàn)這些手術(shù)適應(yīng)癥患者,。(引自中國公眾科技網(wǎng))
原始出處:
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: [email protected]
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