Chronic aspiration of gastric fluid induces the development of obliterative bronchiolitis in rat lung transplants

B. Li, M. G. Hartwig, J. Z. Appel, E. L. Bush, K. R. Balsara, Z. E. Holzknecht, B. H. Collins, D. N. Howell, W. Parker, S. S. Lin, R. D. Davis

Research output: Contribution to journalArticlepeer-review

Abstract

Long-term survival of a pulmonary allograft is currently hampered by obliterative bronchiolitis (OB), a form of chronic rejection that is unique to lung transplantation. While tracheobronchial aspiration from gastroesophageal reflux disease (GERD) has clinically been associated with OB, no experimental model exists to investigate this problem. Using a WKY-to-F344 rat orthotopic left lung transplant model, the effects of chronic aspiration on pulmonary allograft were evaluated. Recipients received cyclosporine with or without 8 weekly aspirations of gastric fluid into the allograft. Six (66.7%) of 9 allografts with aspiration demonstrated bronchioles with surrounding monocytic infiltrates, fibrosis and loss of normal lumen anatomy, consistent with the development of OB. In contrast, none of the allografts without aspiration (n = 10) demonstrated these findings (p = 0.002). Of the grafts examined grossly, 83% of the allografts with chronic aspiration but only 20% without aspiration appeared consolidated (p = 0.013). Aspiration was associated with increased levels of IL-1α, IL-1β, IL-6, IL-10, TNF-α and TGF-β in BAL and of IL-1α, IL-4 and GM-CSF in serum. This study provides experimental evidence linking chronic aspiration to the development of OB and suggests that strategies aimed at preventing aspiration-related injuries might improve outcomes in clinical lung transplantation.

Original languageEnglish (US)
Pages (from-to)1614-1621
Number of pages8
JournalAmerican Journal of Transplantation
Volume8
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

Keywords

  • Bronchiolitis obliterans
  • Chronic aspiration
  • Gastroesophageal reflux
  • Pulmonary allografts

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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