Abstract
Background: 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.
Methods: Standardised 3x60 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.
Results: 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.
Conclusion: 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.
Full Text
The Full Text of this article is available as a PDF (62.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Davis R. Duane, Jr, Lau Christine L., Eubanks Steve, Messier Robert H., Hadjiliadis Denis, Steele Mark P., Palmer Scott M. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. J Thorac Cardiovasc Surg. 2003 Mar;125(3):533–542. doi: 10.1067/mtc.2003.166. [DOI] [PubMed] [Google Scholar]
- Estenne Marc, Hertz Marshall I. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med. 2002 Aug 15;166(4):440–444. doi: 10.1164/rccm.200201-003pp. [DOI] [PubMed] [Google Scholar]
- Gourishankar Sita, Halloran Philip F. Late deterioration of organ transplants: a problem in injury and homeostasis. Curr Opin Immunol. 2002 Oct;14(5):576–583. doi: 10.1016/s0952-7915(02)00386-2. [DOI] [PubMed] [Google Scholar]
- Maes B. D., Vanwalleghem J., Kuypers D., Ghoos Y., Rutgeerts P. J., Vanrenterghem Y. F. Differences in gastric motor activity in renal transplant recipients treated with FK-506 versus cyclosporine. Transplantation. 1999 Nov 27;68(10):1482–1485. doi: 10.1097/00007890-199911270-00009. [DOI] [PubMed] [Google Scholar]
- Moloney Edward D., Mumby Sharon E., Gajdocsi Reka, Cranshaw Julius H., Kharitonov Sergei A., Quinlan Gregory J., Griffiths Mark J. Exhaled breath condensate detects markers of pulmonary inflammation after cardiothoracic surgery. Am J Respir Crit Care Med. 2003 Oct 9;169(1):64–69. doi: 10.1164/rccm.200307-1005OC. [DOI] [PubMed] [Google Scholar]
- Reid K. R., McKenzie F. N., Menkis A. H., Novick R. J., Pflugfelder P. W., Kostuk W. J., Ahmad D. Importance of chronic aspiration in recipients of heart-lung transplants. Lancet. 1990 Jul 28;336(8709):206–208. doi: 10.1016/0140-6736(90)91734-r. [DOI] [PubMed] [Google Scholar]
- Tasker Andrea, Dettmar Peter W., Panetti Marguerite, Koufman James A., Birchall John P., Pearson Jeffery P. Reflux of gastric juice and glue ear in children. Lancet. 2002 Feb 9;359(9305):493–493. doi: 10.1016/S0140-6736(02)07665-1. [DOI] [PubMed] [Google Scholar]
- Tasker Andrea, Dettmar Peter W., Panetti Marguerite, Koufman James A., P Birchall John, Pearson Jeffrey P. Is gastric reflux a cause of otitis media with effusion in children? Laryngoscope. 2002 Nov;112(11):1930–1934. doi: 10.1097/00005537-200211000-00004. [DOI] [PubMed] [Google Scholar]
- Veale D., Glasper P. N., Gascoigne A., Dark J. H., Gibson G. J., Corris P. A. Ciliary beat frequency in transplanted lungs. Thorax. 1993 Jun;48(6):629–631. doi: 10.1136/thx.48.6.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Verleden G. M., Dupont L. J., Van Raemdonck D. E. Is it bronchiolitis obliterans syndrome or is it chronic rejection: a reappraisal? Eur Respir J. 2005 Feb;25(2):221–224. doi: 10.1183/09031936.05.00057404. [DOI] [PubMed] [Google Scholar]
- Ward C., Snell G. I., Zheng L., Orsida B., Whitford H., Williams T. J., Walters E. H. Endobronchial biopsy and bronchoalveolar lavage in stable lung transplant recipients and chronic rejection. Am J Respir Crit Care Med. 1998 Jul;158(1):84–91. doi: 10.1164/ajrccm.158.1.9707117. [DOI] [PubMed] [Google Scholar]
- Ward C., Thien F., Secombe J., Gollant S., Walters E. H. Bronchoalveolar lavage fluid urea as a measure of pulmonary permeability in healthy smokers. Eur Respir J. 2000 Feb;15(2):285–290. doi: 10.1034/j.1399-3003.2000.15b11.x. [DOI] [PubMed] [Google Scholar]
- Ward C., Walters E. H., Zheng L., Whitford H., Williams T. J., Snell G. I. Increased soluble CD14 in bronchoalveolar lavage fluid of stable lung transplant recipients. Eur Respir J. 2002 Mar;19(3):472–478. doi: 10.1183/09031936.02.00225502. [DOI] [PubMed] [Google Scholar]
- Widdicombe Jonathan H. Volume of airway surface liquid in health and disease. Am J Respir Crit Care Med. 2002 Jun 1;165(11):1566–1566. doi: 10.1164/ajrccm.165.11.165111. [DOI] [PubMed] [Google Scholar]
- Yousem S. A., Berry G. J., Cagle P. T., Chamberlain D., Husain A. N., Hruban R. H., Marchevsky A., Ohori N. P., Ritter J., Stewart S. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group. J Heart Lung Transplant. 1996 Jan;15(1 Pt 1):1–15. [PubMed] [Google Scholar]