Experimental large-animal model of obliterative bronchiolitis after lung transplantation

Ghannam Al-Dossari, V. R. Kshettry, J. Jessurun, R. M. Bolman, T. M. Egan, T. M. Sundt, H. J. Schaefers, T. E. Oaks

Research output: Contribution to journalArticle

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Abstract

Obliterative bronchiolitis is a major cause of long-term morbidity after lung transplantation. It is characterized by small-airway inflammation and occlusion by fibrous tissue. The pathogenesis is uncertain. To study this disease, we developed a model of posttransplantation obliterative bronchiolitis using genetically defined miniature swine. Group 1 (n = 2) received a left lung autograft; group 2 (n = 7), a left lung allograft. Group 2 recipients were given cyclosporine, prednisone, and azathioprine for 3 months, then immunosuppression was tapered and discontinued over 1 month. The animals were observed for an additional 2 months, then sacrificed. Lung grafts in both groups were monitored with serial bronchoalveolar lavages and transbronchial biopsies for 6 months. After sacrifice, lung grafts underwent histopathologic and immunohistochemical examination. No allograft had histologic evidence of acute rejection or peribronchiolar infiltrate during the first 3 months of immunosuppression. During the tapering period, airway changes characterized by severe peribronchiolar lymphocytic infiltrates were seen. Bronchoalveolar lavages of allografts showed significantly increased lymphocyte counts with CD8+ cells predominating. After the discontinuation of immunosuppression, transbronchial biopsy and autopsy specimens showed progressive fibrous inflammatory occlusion of bronchioles. Immunohistochemical staining demonstrated increased expression of MCH class II antigen on the bronchiolar epithelium and increased dendritic cells and CD4+ lymphocytes. None of these changes were seen in group 1. Our findings suggest obliterative bronchiolitis is an immunologically mediated phenomenon related to chronic graft rejection after lung transplantation. This model will allow systematic study of the pathogenesis of obliterative bronchiolitis and possible therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)34-40
Number of pages7
JournalAnnals of Thoracic Surgery
Volume58
Issue number1
StatePublished - 1994
Externally publishedYes

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Bronchiolitis
Lung Transplantation
Animal Models
Immunosuppression
Allografts
Lung
Bronchoalveolar Lavage
Transplants
Bronchioles
Biopsy
Miniature Swine
Histocompatibility Antigens Class II
Autografts
Azathioprine
Lymphocyte Count
Graft Rejection
Prednisone
Dendritic Cells
Cyclosporine
Autopsy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Al-Dossari, G., Kshettry, V. R., Jessurun, J., Bolman, R. M., Egan, T. M., Sundt, T. M., ... Oaks, T. E. (1994). Experimental large-animal model of obliterative bronchiolitis after lung transplantation. Annals of Thoracic Surgery, 58(1), 34-40.

Experimental large-animal model of obliterative bronchiolitis after lung transplantation. / Al-Dossari, Ghannam; Kshettry, V. R.; Jessurun, J.; Bolman, R. M.; Egan, T. M.; Sundt, T. M.; Schaefers, H. J.; Oaks, T. E.

In: Annals of Thoracic Surgery, Vol. 58, No. 1, 1994, p. 34-40.

Research output: Contribution to journalArticle

Al-Dossari, G, Kshettry, VR, Jessurun, J, Bolman, RM, Egan, TM, Sundt, TM, Schaefers, HJ & Oaks, TE 1994, 'Experimental large-animal model of obliterative bronchiolitis after lung transplantation', Annals of Thoracic Surgery, vol. 58, no. 1, pp. 34-40.
Al-Dossari G, Kshettry VR, Jessurun J, Bolman RM, Egan TM, Sundt TM et al. Experimental large-animal model of obliterative bronchiolitis after lung transplantation. Annals of Thoracic Surgery. 1994;58(1):34-40.
Al-Dossari, Ghannam ; Kshettry, V. R. ; Jessurun, J. ; Bolman, R. M. ; Egan, T. M. ; Sundt, T. M. ; Schaefers, H. J. ; Oaks, T. E. / Experimental large-animal model of obliterative bronchiolitis after lung transplantation. In: Annals of Thoracic Surgery. 1994 ; Vol. 58, No. 1. pp. 34-40.
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