Pepsin, a biomarker of gastric aspiration in lung allografts: a putative association with rejection.
BACKGROUND
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.


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 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.


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 > or = 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 > or = grade A2 acute rejection. This provides further evidence supporting the possible role of aspiration in the development of overall allograft injury.
Stovold
Rachel
R
Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, United Kingdom.
Forrest
Ian A
IA
Corris
Paul A
PA
Murphy
Desmond M
DM
Smith
Jaclyn A
JA
Decalmer
Sam
S
Johnson
Gail E
GE
Dark
John H
JH
Pearson
Jeffrey P
JP
Ward
Chris
C
D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology*; D006801:Humans; D008168:Lung / Q000737:chemistry*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010434:Pepsin A / Q000032:analysis*; D011446:Prospective Studies; D053120:Respiratory Aspiration / Q000453:epidemiology*; D014184:Transplantation, Homologous
D010434:Pepsin A