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Pepsin, a Biomarker of Gastric Aspiration in Lung Allografts

A Putative Association with Rejection

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{at}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

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject There is strong clinical suspicion regarding the potential role of gastric aspiration in the dysfunction of lung allografts; however, there is a lack of appropriate translational research. What This Study Adds to the Field Levels of pepsin, a marker of gastric aspiration, are elevated in bronchoalveolar lavage fluid in lung transplant recipients. Elevated bronchoalveolar lavage fluid pepsin levels are associated with acute rejection and may contribute to overall allograft injury.

 

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