Ward C, Forrest I A, Brownlee I A, Johnson G E, Murphy D M, Pearson J P, Dark J H, Corris P A
Applied Immunobiology and Transplantation Research Group, Freeman Hospital and University of Newcastle upon Tyne, Newcastle upon Tyne NE7 7DN, UK.
Thorax. 2005 Oct;60(10):872-4. doi: 10.1136/thx.2004.036426. Epub 2005 Jul 29.
A biologically plausible link between gastro-oesophageal reflux (GOR), aspiration, and lung allograft dysfunction has been suggested, but there is no systematic evidence indicating the presence of gastric contents in the lung. We have tested the hypothesis that pepsin, as a marker of aspiration, is detectable in bronchoalveolar lavage (BAL) fluid of allograft recipients who had not reported symptoms of GOR.
Standardised 3 x 60 ml surveillance BAL fluid samples from 13 chronologically sequential stable lung allograft recipients without chronic rejection (10 patients treated with a prophylactic proton pump inhibitor) were studied. Lavage supernatants were assayed by an ELISA based on a monospecific goat antibody for pepsin/pepsinogen. Pepsin levels were compared with those from four normal volunteer controls.
Pepsin levels were measurable in all allograft recipients, in keeping with gastric aspiration (median 109 ng/ml (range 35-1375)). In the control group the pepsin levels were below the limit of detection. Treatment with a proton pump inhibitor was not correlated with pepsin levels. There was no correlation between BAL fluid neutrophils and pepsin levels.
These data demonstrate lung epithelial lining fluid concentrations of pepsin in lung allograft recipients which are much higher than blood reference levels, with no detectable pepsin in controls. This provides direct evidence of gastric aspiration, which is potentially injurious to the allograft.
胃食管反流(GOR)、误吸与肺移植功能障碍之间存在生物学上合理的联系,但尚无系统证据表明肺内存在胃内容物。我们检验了这样一个假设:在未报告GOR症状的移植受者的支气管肺泡灌洗(BAL)液中可检测到作为误吸标志物的胃蛋白酶。
对13例按时间顺序依次入选的无慢性排斥反应的稳定肺移植受者(10例接受预防性质子泵抑制剂治疗)的标准化3×60 ml监测BAL液样本进行研究。用基于单特异性山羊抗胃蛋白酶/胃蛋白酶原抗体的ELISA法检测灌洗上清液。将胃蛋白酶水平与4名正常志愿者对照的水平进行比较。
所有移植受者的胃蛋白酶水平均可测,符合胃内容物误吸情况(中位数为109 ng/ml(范围35 - 1375))。对照组胃蛋白酶水平低于检测限。质子泵抑制剂治疗与胃蛋白酶水平无关。BAL液中性粒细胞与胃蛋白酶水平之间无相关性。
这些数据表明,肺移植受者肺上皮衬液中的胃蛋白酶浓度远高于血液参考水平,而对照组中未检测到胃蛋白酶。这为胃内容物误吸提供了直接证据,胃内容物误吸可能对移植肺造成损害。