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Published ahead of print on April 5, 2007, doi:10.1164/rccm.200610-1485OC

Am. J. Respir. Crit. Care Med., Volume 175, Number 12, June 2007, 1298-1303

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Submitted on October 17, 2006
Accepted on April 5, 2007

Pepsin, a Biomarker of Aspiration in Lung Allografts: A Putative Association with Rejection

Rachel Stovold1, Ian A Forrest2, Paul A Corris2, Desmond M Murphy2, Jaclyn Smith3, Sam Decalmer3, Gail E Johnson2, John H Dark2, Jeffrey P Pearson4, and Chris Ward2*

1 Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Epithelial Research Group, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom, 2 Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom, 3 North West Lung Research Centre, University of Manchester, Manchester, United Kingdom, 4 Epithelial Research Group, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom

* To whom correspondence should be addressed. E-mail: chris.ward{at}ncl.ac.uk.

Rationale: Human lung transplantation is a therapeutic option for selected patients with advanced cardio-pulmonary 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. Objective: 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 BOS. Methods: Levels of Bronchoalveolar lavage pepsin were measured by ELISA in thirty six lung transplant recipients, four normal volunteers and seventeen subjects with unexplained chronic cough. Results: Our primary finding was that compared to controls, BAL pepsin levels were elevated in stable lung transplant recipients, subjects with acute rejection and subjects with BOS. Our secondary finding was that the highest levels were found in recipients with acute vascular rejection grade ≥A2 (median 11.2, range 5.4 - 51.7ng/ml, normal median 1.1, range 0-2.3ng/ml, P= 0.004). Conclusion: 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 ≥A2 acute rejection. This provides further evidence supporting the possible role of aspiration in the development of overall allograft injury.
Key words: Lung allograft, Gastro-esophageal reflux (GER), Pepsin, Rejection




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