Development of obliterative bronchiolitis after allogeneic rat lung transplantation: implication of acute rejection and the time point of treatment

Hirt, Stephan; You, Xiaomang; Möller, Frank; Boeke, Katrin; Starke, M; Spranger, U; Wottge, H.-U.

doi:10.1016/s1053-2498(98)00009-6

Cited by 31 publications

(19 citation statements)

References 18 publications

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“…The first model consists of an orthotopic left single LTx performed in small animals like rats [61] and large animals like pigs [62]. It is mostly used to study acute events, since chronic changes such as BO occur infrequently in this model [62][63][64]. In contrast, the heterotopic airway transplantation model leads to consistent and reproducible airway obliteration and produces a histological lesion, which is very similar to that of human BO.…”

Section: Animal Modelsmentioning

confidence: 99%

Post-transplant bronchiolitis obliterans

Boehler

Estenne²

2003

Eur Respir J

177

105

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Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischaemia/reperfusion injury and infections have made intermediate-term survival after lung transplantation an achievable goal. However, chronic allograft dysfunction in the form of bronchiolitis obliterans remains a major hurdle that threatens both the quality of life and long-term survival of the recipients. It affects up to 50-60% of patients who survive 5 yrs after surgery, and it accounts for w30% of all deaths occurring after the third postoperative year.This article discusses the alloimmune-dependent and -independent risk factors for bronchiolitis obliterans, the current understanding of the pathogenesis of bronchiolitis obliterans based on results of animal and human studies, the clinical staging of the complication, strategies that may contribute to the prevention and/or early detection of bronchiolitis obliterans, and suggestions for future research.

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Section: Animal Modelsmentioning

confidence: 99%

Post-transplant bronchiolitis obliterans

Boehler

Estenne²

2003

Eur Respir J

177

105

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“…An inflammatory cascade directed against allograft bronchiolar epithelial and endothelial cells is initiated by T-lymphocytes, as demonstrated in animals [12][13][14] and human subjects [15,16]. Alloreactive lymphocytes are found in bronchoalveolar lavage fluid, and selective T-cell clones are expanded during bronchiolitis obliterans [17].…”

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confidence: 97%

Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans

et al. 2004

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The majority of patients who develop bronchiolitis obliterans, after lung transplantation, die within 2-3 yrs after onset since treatment with conventional immunosuppression is typically ineffective. A case/control study was conducted in lung transplant recipients with biopsy-documented bronchiolitis obliterans to determine whether aerosol cyclosporin use contributed to increased survival.The cases comprised 39 transplant recipients who received open-label aerosol cyclosporin treatment in addition to conventional immunosuppression. The controls were transplant recipients treated with conventional immunosuppression alone. There were 51 controls from the University of Pittsburgh Medical Center and 100 from a large multicentric database (Novartis Lung Transplant Database).Forced expiratory volume in one second expressed as a percentage of the predicted value was an independent predictor of survival in all patients with bronchiolitis obliterans. Cox proportional-hazards analysis revealed a survival advantage for aerosol cyclosporin cases compared to the Pittsburgh control group. A survival advantage was also seen when comparing study cases to multicentric controls.Aerosol cyclosporin, given with conventional immunosuppression to lung transplant recipients with bronchiolitis obliterans, provides a survival advantage over conventional therapy alone. The 3-yr survival after lung transplantation is 55% [1]. More than half of all lung transplant recipients who survive o1 yr develop chronic allograft rejection that is associated with bronchiolitis obliterans [2][3][4][5]. The development of bronchiolitis obliterans has a negative impact on long-term survival. No immunosuppressive regimen has been shown to prevent this complication or improve survival once it occurs [6][7][8].Bronchiolitis obliterans is thought to be a consequence of immunological lung injury [9][10][11]. An inflammatory cascade directed against allograft bronchiolar epithelial and endothelial cells is initiated by T-lymphocytes, as demonstrated in animals [12][13][14] and human subjects [15,16]. Alloreactive lymphocytes are found in bronchoalveolar lavage fluid, and selective T-cell clones are expanded during bronchiolitis obliterans [17]. Myriad cytokines and lymphocyte gene expression induce small airway inflammation, leading to myofibroblast-like cell proliferation and ingrowth of small airway granulation tissue, and resulting in occlusion of the airway lumen [18][19][20][21]. A cascade of injury and remodelling triggers a fibroproliferative process responsible for bronchiolar scarring and graft failure.Cyclosporin is one of the mainstays of maintenance immunosuppression after transplantation; however, it has a narrow therapeutic index when given systemically [22]. It blocks lymphocyte activation by inhibiting transcription of cytokine genes in a dose-dependent manner [22,23]. Cyclosporin also exerts an antifibrotic effect by inhibiting alveolar macrophage function and suppressing collagen deposition by lung fibroblasts [24,25].Previous inves...

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“…6 Orthotopic transplantation of the left lung in the rat is an established model to study re-implantation responses and acute rejection. The Brown Norway (BN)¡Lewis (LEW) [7][8][9][10][11][12] and the Fischer 344 (F344)¡Wistar Kyoto (WKY) [13][14][15][16][17] rat strain combinations are commonly used to study chronic changes after lung transplantation.…”

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confidence: 99%