雷帕霉素减轻小鼠气管移植物上皮向间质转化以及阻塞性气道疾病的实验研究
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摘要
第一部分：建立小鼠闭塞性细支气管炎模型
实验背景：近年来众多学者建立了多种动物模型来研究肺移植术后阻塞性细支气管炎(obliterative bronchiolitis,OB)的发病机制。在本研究中,我们在移植术后一段时间内比较几种常见的OB模型的特点。
实验方法：受体小鼠分组后分别接受原位气管移植,大网膜下气管异位移植以及皮下气管异位移植。气管移植物分别在术后14、21以及28天,进行组织学或者免疫组织化学评估。
实验结果：移植术后,来自不同移植部位的同种气管移植物基本保持了正常的组织学结构,而与各移植部位相应的异种移植物的气道出现明显的阻塞,同时在各个实验观测时间点时伴有更多的CD4+/CD8+单个核细胞核肌纤维细胞的浸润,但是新生的上皮细胞核新生血管明显减少(P<0.05)。与两种异位气管异种移植物相比较,原位异种移植物的气管的管腔相对通畅,伴有明显较少的CD4+/CD8+单个核细胞核肌纤维细胞的浸润,但是却有明显更多的新生上皮细胞和新生血管形成(P<0.05)。
实验结论：根据我们的实验结果提示,小鼠原位气管移植可以被用作研究0B发展早期病变的模型,而异位气管移植可以作为OB晚期的研究模型。
第二部分：上皮向间质转化在小鼠气管移植模型中的作用
研究背景：在患有细支气管闭塞综合征(Bronchiolitis Obliterans Syndrome, BOS)的肺移植患者的植肺中,常出现气道正常上皮损伤,而大量纤维疤痕组织增生的气道重构。在本研究中,我们假设小鼠气管原位移植模型中移植气管上皮在出现阻塞性气道疾病时出现上皮向间质转化(epithelial-mesenchymal transition, EMT)。
实验方法：受体小鼠分为同种异体(Balb/C to C57BL/6)以及同种自体(Balb/C to Balb/C)组,分别接受原位气管移植。移植术后受体小鼠均不使用免疫抑制剂治疗。将受体气管移植物分别在术后14、21以及28天进行组织学或者免疫组织化学评估。
实验结果：移植术后,同种自体气管移植物组织学结构基本保持正常,与之相比同种异体气管移植物的管腔较为狭窄(P<0.05)。术后与同种自体气管移植比较,同种异体气管移植物气道上皮内正常上皮标志物E-cadherin表达较低,而间质标志物α-SMA增高,上皮损伤以及EMT标志物MMP-9表达增高(P<0.05)。
实验结论：我们实验结果表明,在小鼠气管移植模型中OAD的发生伴有气道上皮向间质转化的现象。因此提供治疗OB的可能靶点。
第三部分：雷帕霉素抑制小鼠气管移植物中EMT的发生,减少阻塞性气道疾病
实验背景：雷帕霉素(RAPA)作为免疫抑制剂用来治疗多种实体器官免疫排斥反应。雷帕霉素能改善肺移植患者术后肺功能,但是由于诸多不良反应,许多患有BOS的肺移植患者无法耐受雷帕霉素的治疗。在本实验中,我们试图研究小剂量雷帕霉素对同种异体小鼠气管移植物的治疗效果。
实验方法：受体小鼠分组后分别接受原位气管移植,术后根据分组给予不同剂量的雷帕霉素+助溶剂(实验组)或者单独给予助溶剂(载体对照组)。各组受体小鼠的气管移植物分别在移植术后第28天,进行组织病理学、免疫组织化学、Western-Blot以及流式细胞学评估。
实验结果：与各实验组比较,载体照组中同系异体小鼠气管移植物的气道管腔明显狭窄(P<0.05),上皮发生明显的上皮向间质转化：E-Cadherin表达降低(P<0.05),α-SMA以及MMP-9表达升高,移植气管上以及外周血中纤维细胞的表达水平均增高(P<0.05)。中、高剂量RAPA组中治疗效果无统计学差异(P>0.05),切均强于小剂量的RAPA治疗效果(P<0.05)：外周血中纤维细胞的表达水平无统计学差异,但移植气管上纤维细胞表达水平均低于小剂量治疗组。
实验结论：根据我们的实验结果表明,较大剂量的雷帕霉素能够通过抑制EMT发生来减少气道OAD的发生,移植气管上皮中EMT在OAD发生过程中其重要作用。
Part Ⅰ:Establishment of Murine Obliterative Bronchiolitis Model
Background:Couples of animal models have been developed to investigate the mechanisms of obliterative bronchiolitis (OB) post lung transplantation. In this study, we compared three prevalent murine models of obliterative bronchiolitis in terms of several pathologic changes after transplantation.
Methods:Recipient mice received one of the orthotopic, intra-omental and subcutaneous tracheal transplantations in both syngeneic (Balb/C to Balb/C) and allogeneic (Balb/C to C57BL/6) settings. No immunosuppressive drugs were administered. Tracheal grafts were harvested on Day14,21and28post-transplant for histological and immunohistochemical assessment.
Results:Syngeneic tracheal grafts from different transplant sites maintained normal histologic structures, while the corresponding allografts exhibited more occlusion of the airway lumen as well as more infiltration of CD4+/CD8+mononuclear cells and myofibroblasts, but less regenerative epithelium and neovascularized vessels at indicated times (P<0.05). Compared with the two heterotopic allografts, the orthotopic had less occlusion of the tracheal lumen as well as less CD4+/CD8+mononuclear cells and myofibroblasts, but more regenerative epithelium and neovascularized blood vessels (P<0.05).
Conclusions:We presume orthotopic tracheal transplantation in mice can act as a model to study early stages of OB, and heterotopic tracheal transplantation can be a model for late stages of OB.
Part Ⅱ:Epithelial-Mensenchymal Transition in Murine Orthotopic Tracheal Allograft
Background:In graft lungs of patients with BOS, airway remodelling was observed, including epithelium of the airway shedding and fibrosis proliferation. In this study, we hypothesized that epithelial-mesenchymal transition (EMT) occurs with the development of BOS after transplantation.
Methods:Recipient mice received orthotopic tracheal transplantation in both syngeneic (Balb/C to Balb/C) and allogeneic (Balb/C to C57BL/6) setting. No immunosuppressive treatment was administered. Tracheal grafts were harvested on Day14,21and28after transplantation for histological and immunohistochemical analyses.
Results:Syngeneic tracheal graft maintained normal histological structures, while allografts exhibited more occlusion of the airway lumen (P<0.05). Compare with syngeneic tracheal grafts, tracheal allografts exhibited lower expression of epithelium markers E-cadherin, but higher expression of myofibroblasts markers a-SMA as well as marker of epithelial damage and EMT MMP-9(P<0.05).
Conclusions:Our data demonstrates that EMT occurs with the development of Obstructive airway disease in mice tracheal allografts,which suggests that EMT is a potential target in the treatment of OB post lung transplantation.
Part III:Rapamycin Inhibits Epithelial-Mesenchymal Transition and Attenuates Obliterate Airway Disease in Murine Tracheal Allograft
Background:Rapamycin (RAPA) is employed to prevent rejection of transplanted solid organ as an immunosuppressive agent. Rapamycin can improve pulmonary function of lung transplant patients with bronchiolitis obliterans syndrome (BOS), but as a result of severe adverse events, it is sometimes intolerant. In this study, we investigate the outcomes of murine tracheal allografts treated by reduced-dose Rapamycin.
Methods:Recipient mice underwent orthotopic tracheal transplant after been allocated into randomized groups. Recipients were treated with either different doses of Rapamycin (experimental group) or solvent (control group) after transplantation. Tracheal allografts were harvested in the28th day post-transplant for histological, immunohistochemical, Western-Blot and Flow Cytometry analyses.
Results:Compared with tracheal allografts in experimental groups, tracheal allografts in control group exhibited more occlusion of the airway lumen (P<0.05) and underwent epithelium to mesenchymal transition:lower expression of E-Cadherin, but higher expression of myofibroblasts markera-SMA, MMP-9as well as fibrocytes both in peripheral blood and tracheal allografts (P<0.05). The outcomes of mid-dose and high-dose RAPA groups made no differences (P>0.05), which were better than those in low-dose RARA groups:the cell counts of peripheral fibrocytes in all groups were not significantly different (P>0.05), but the cell counts of tissue fibrocytes in mid-dose RAPA groups were both decreased than those in low-dose group (P<0.05).
Conclusions:Our study demonstrated that higer-dose Rapamycin can attenuate obstructive airway disease with inhibiting epithelium-mesenchymal transition in murine tracheal allograft, and EMT plays an import role in development of obstructive airway diseases post tracheal transplantation.
实验背景：近年来众多学者建立了多种动物模型来研究肺移植术后阻塞性细支气管炎(obliterative bronchiolitis,OB)的发病机制。在本研究中,我们在移植术后一段时间内比较几种常见的OB模型的特点。
实验方法：受体小鼠分组后分别接受原位气管移植,大网膜下气管异位移植以及皮下气管异位移植。气管移植物分别在术后14、21以及28天,进行组织学或者免疫组织化学评估。
实验结果：移植术后,来自不同移植部位的同种气管移植物基本保持了正常的组织学结构,而与各移植部位相应的异种移植物的气道出现明显的阻塞,同时在各个实验观测时间点时伴有更多的CD4+/CD8+单个核细胞核肌纤维细胞的浸润,但是新生的上皮细胞核新生血管明显减少(P<0.05)。与两种异位气管异种移植物相比较,原位异种移植物的气管的管腔相对通畅,伴有明显较少的CD4+/CD8+单个核细胞核肌纤维细胞的浸润,但是却有明显更多的新生上皮细胞和新生血管形成(P<0.05)。
实验结论：根据我们的实验结果提示,小鼠原位气管移植可以被用作研究0B发展早期病变的模型,而异位气管移植可以作为OB晚期的研究模型。
第二部分：上皮向间质转化在小鼠气管移植模型中的作用
研究背景：在患有细支气管闭塞综合征(Bronchiolitis Obliterans Syndrome, BOS)的肺移植患者的植肺中,常出现气道正常上皮损伤,而大量纤维疤痕组织增生的气道重构。在本研究中,我们假设小鼠气管原位移植模型中移植气管上皮在出现阻塞性气道疾病时出现上皮向间质转化(epithelial-mesenchymal transition, EMT)。
实验方法：受体小鼠分为同种异体(Balb/C to C57BL/6)以及同种自体(Balb/C to Balb/C)组,分别接受原位气管移植。移植术后受体小鼠均不使用免疫抑制剂治疗。将受体气管移植物分别在术后14、21以及28天进行组织学或者免疫组织化学评估。
实验结果：移植术后,同种自体气管移植物组织学结构基本保持正常,与之相比同种异体气管移植物的管腔较为狭窄(P<0.05)。术后与同种自体气管移植比较,同种异体气管移植物气道上皮内正常上皮标志物E-cadherin表达较低,而间质标志物α-SMA增高,上皮损伤以及EMT标志物MMP-9表达增高(P<0.05)。
实验结论：我们实验结果表明,在小鼠气管移植模型中OAD的发生伴有气道上皮向间质转化的现象。因此提供治疗OB的可能靶点。
第三部分：雷帕霉素抑制小鼠气管移植物中EMT的发生,减少阻塞性气道疾病
实验背景：雷帕霉素(RAPA)作为免疫抑制剂用来治疗多种实体器官免疫排斥反应。雷帕霉素能改善肺移植患者术后肺功能,但是由于诸多不良反应,许多患有BOS的肺移植患者无法耐受雷帕霉素的治疗。在本实验中,我们试图研究小剂量雷帕霉素对同种异体小鼠气管移植物的治疗效果。
实验方法：受体小鼠分组后分别接受原位气管移植,术后根据分组给予不同剂量的雷帕霉素+助溶剂(实验组)或者单独给予助溶剂(载体对照组)。各组受体小鼠的气管移植物分别在移植术后第28天,进行组织病理学、免疫组织化学、Western-Blot以及流式细胞学评估。
实验结果：与各实验组比较,载体照组中同系异体小鼠气管移植物的气道管腔明显狭窄(P<0.05),上皮发生明显的上皮向间质转化：E-Cadherin表达降低(P<0.05),α-SMA以及MMP-9表达升高,移植气管上以及外周血中纤维细胞的表达水平均增高(P<0.05)。中、高剂量RAPA组中治疗效果无统计学差异(P>0.05),切均强于小剂量的RAPA治疗效果(P<0.05)：外周血中纤维细胞的表达水平无统计学差异,但移植气管上纤维细胞表达水平均低于小剂量治疗组。
实验结论：根据我们的实验结果表明,较大剂量的雷帕霉素能够通过抑制EMT发生来减少气道OAD的发生,移植气管上皮中EMT在OAD发生过程中其重要作用。
Part Ⅰ:Establishment of Murine Obliterative Bronchiolitis Model
Background:Couples of animal models have been developed to investigate the mechanisms of obliterative bronchiolitis (OB) post lung transplantation. In this study, we compared three prevalent murine models of obliterative bronchiolitis in terms of several pathologic changes after transplantation.
Methods:Recipient mice received one of the orthotopic, intra-omental and subcutaneous tracheal transplantations in both syngeneic (Balb/C to Balb/C) and allogeneic (Balb/C to C57BL/6) settings. No immunosuppressive drugs were administered. Tracheal grafts were harvested on Day14,21and28post-transplant for histological and immunohistochemical assessment.
Results:Syngeneic tracheal grafts from different transplant sites maintained normal histologic structures, while the corresponding allografts exhibited more occlusion of the airway lumen as well as more infiltration of CD4+/CD8+mononuclear cells and myofibroblasts, but less regenerative epithelium and neovascularized vessels at indicated times (P<0.05). Compared with the two heterotopic allografts, the orthotopic had less occlusion of the tracheal lumen as well as less CD4+/CD8+mononuclear cells and myofibroblasts, but more regenerative epithelium and neovascularized blood vessels (P<0.05).
Conclusions:We presume orthotopic tracheal transplantation in mice can act as a model to study early stages of OB, and heterotopic tracheal transplantation can be a model for late stages of OB.
Part Ⅱ:Epithelial-Mensenchymal Transition in Murine Orthotopic Tracheal Allograft
Background:In graft lungs of patients with BOS, airway remodelling was observed, including epithelium of the airway shedding and fibrosis proliferation. In this study, we hypothesized that epithelial-mesenchymal transition (EMT) occurs with the development of BOS after transplantation.
Methods:Recipient mice received orthotopic tracheal transplantation in both syngeneic (Balb/C to Balb/C) and allogeneic (Balb/C to C57BL/6) setting. No immunosuppressive treatment was administered. Tracheal grafts were harvested on Day14,21and28after transplantation for histological and immunohistochemical analyses.
Results:Syngeneic tracheal graft maintained normal histological structures, while allografts exhibited more occlusion of the airway lumen (P<0.05). Compare with syngeneic tracheal grafts, tracheal allografts exhibited lower expression of epithelium markers E-cadherin, but higher expression of myofibroblasts markers a-SMA as well as marker of epithelial damage and EMT MMP-9(P<0.05).
Conclusions:Our data demonstrates that EMT occurs with the development of Obstructive airway disease in mice tracheal allografts,which suggests that EMT is a potential target in the treatment of OB post lung transplantation.
Part III:Rapamycin Inhibits Epithelial-Mesenchymal Transition and Attenuates Obliterate Airway Disease in Murine Tracheal Allograft
Background:Rapamycin (RAPA) is employed to prevent rejection of transplanted solid organ as an immunosuppressive agent. Rapamycin can improve pulmonary function of lung transplant patients with bronchiolitis obliterans syndrome (BOS), but as a result of severe adverse events, it is sometimes intolerant. In this study, we investigate the outcomes of murine tracheal allografts treated by reduced-dose Rapamycin.
Methods:Recipient mice underwent orthotopic tracheal transplant after been allocated into randomized groups. Recipients were treated with either different doses of Rapamycin (experimental group) or solvent (control group) after transplantation. Tracheal allografts were harvested in the28th day post-transplant for histological, immunohistochemical, Western-Blot and Flow Cytometry analyses.
Results:Compared with tracheal allografts in experimental groups, tracheal allografts in control group exhibited more occlusion of the airway lumen (P<0.05) and underwent epithelium to mesenchymal transition:lower expression of E-Cadherin, but higher expression of myofibroblasts markera-SMA, MMP-9as well as fibrocytes both in peripheral blood and tracheal allografts (P<0.05). The outcomes of mid-dose and high-dose RAPA groups made no differences (P>0.05), which were better than those in low-dose RARA groups:the cell counts of peripheral fibrocytes in all groups were not significantly different (P>0.05), but the cell counts of tissue fibrocytes in mid-dose RAPA groups were both decreased than those in low-dose group (P<0.05).
Conclusions:Our study demonstrated that higer-dose Rapamycin can attenuate obstructive airway disease with inhibiting epithelium-mesenchymal transition in murine tracheal allograft, and EMT plays an import role in development of obstructive airway diseases post tracheal transplantation.
引文
[1]Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dobbels F, Kirk R, et al. The Registry of the International Society for Heart and Lung Transplantation:Twenty-eighth Adult Lung and Heart-Lung Transplant Report--2011. The Journal of heart and lung transplantation:the official publication of the International Society for Heart Transplantation.2011;30:1104-22.
[2]Sundaresan S, Trulock EP, Mohanakumar T, Cooper JD, Patterson GA. Prevalence and outcome of bronchiolitis obliterans syndrome after lung transplantation. Washington University Lung Transplant Group. The Annals of thoracic surgery.1995;60:1341-6; discussion 6-7.
[3]Dutly AE, Andrade CF, Verkaik R, Kugathasan L, Trogadis J, Liu M, et al. A novel model for post-transplant obliterative airway disease reveals angiogenesis from the pulmonary circulation. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2005;5:248-54.
[4]Jungraithmayr W, Kayser G, Haberstroh J, Weder W, Korom S. An experimental approach toward chronic pulmonary allograft rejection:Orthotopic lung versus heterotopic tracheal segment transplantation in rats. Transplantation proceedings.2010;42:2767-70.
[5]De Vleeschauwer S, Jungraithmayr W, Wauters S, Willems S, Rinaldi M, Vaneylen A, et al. Chronic rejection pathology after orthotopic lung transplantation in mice:the development of a murine BOS model and its drawbacks. PloS one.2012;7:e29802.
[6]Fan L, Benson HL, Vittal R, Mickler EA, Presson R, Fisher AJ, et al. Neutralizing IL-17 prevents obliterative bronchiolitis in murine orthotopic lung transplantation. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.2011;11:911-22.
[7]Hertz MI, Jessurun J, King MB, Savik SK, Murray JJ. Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways. The American journal of pathology.1993;142:1945-51.
[8]Hua X, Deuse T, Tang-Quan KR, Robbins RC, Reichenspurner H, Schrepfer S. Heterotopic and orthotopic tracheal transplantation in mice used as models to study the development of obliterative airway disease. Journal of visualized experiments:JoVE. 2010.
[9]Genden EM, Boros P, Liu J, Bromberg JS, Mayer L. Orthotopic tracheal transplantation in the murine model. Transplantation.2002;73:1420-5.
[10]Genden EM, Iskander AJ, Bromberg JS, Mayer L. Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium. Archives of otolaryngology--head & neck surgery.2003;129:118-23.
[11]Chen C, Zhang YZ, Zheng H, Xu BB, Gao W. Suppression of the obliteration process by ventilation in a mouse orthotopic tracheal transplantation model. Transplantation. 2009;87:1762-8.
[12]Minamoto K, Pinsky DJ. Recipient iNOS but not eNOS deficiency reduces luminal narrowing in tracheal allografts. The Journal of experimental medicine.2002; 196:1321-33.
[13]Rock JR, Randell SH, Hogan BL. Airway basal stem cells:a perspective on their roles in epithelial homeostasis and remodeling. Disease models & mechanisms.2010;3:545-56.
[14]Hele DJ, Yacoub MH, Belvisi MG. The heterotopic tracheal allograft as an animal model of obliterative bronchiolitis. Respiratory research.2001;2:169-83.
[15]Sato M, Keshavjee S, Liu M. Translational research:animal models of obliterative bronchiolitis after lung transplantation. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.2009;9:1981-7.
[16]Adams BF, Brazelton T, Berry GJ, Morris RE. The role of respiratory epithelium in a rat model of obliterative airway disease. Transplantation.2000;69:661-4.
[17]Neuringer IP, Aris RM, Burns KA, Bartolotta TL, Chalermskulrat W, Randell SH. Epithelial kinetics in mouse heterotopic tracheal allografts. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.2002;2:410-9.
[18]Chalermskulrat W, Neuringer IP, Brickey WJ, Felix NJ, Randell SH, Ting JP, et al. Hierarchical contributions of allorecognition pathways in chronic lung rejection. American journal of respiratory and critical care medicine.2003;167:999-1007.
[19]Babu AN, Murakawa T, Thurman JM, Miller EJ, Henson PM, Zamora MR, et al. Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis. The Journal of clinical investigation.2007; 117:3774-85.
[20]Jiang X, Khan MA, Tian W, Beilke J, Natarajan R, Kosek J, et al. Adenovirus-mediated HIF-1alpha gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection. The Journal of clinical investigation. 2011;121:2336-49.
[21]Ramirez AM, Shen Z, Ritzenthaler JD, Roman J. Myofibroblast transdifferentiation in obliterative bronchiolitis:tgf-beta signaling through smad3-dependent and -independent pathways. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.2006;6:2080-8.
[22]Hayes D, Jr. A review of bronchiolitis obliterans syndrome and therapeutic strategies. Journal of cardiothoracic surgery.2011;6:92.
[23]Yousem SA, Duncan SR, Griffith BP. Interstitial and airspace granulation tissue reactions in lung transplant recipients. The American journal of surgical pathology. 1992;16:877-84.
[24]Luckraz H, Goddard M, McNeil K, Atkinson C, Sharples LD, Wallwork J. Is obliterative bronchiolitis in lung transplantation associated with microvascular damage to small airways? The Annals of thoracic surgery.2006;82:1212-8.
[25]Luckraz H, Goddard M, McNeil K, Atkinson C, Charman SC, Stewart S, et al. Microvascular changes in small airways predispose to obliterative bronchiolitis after lung transplantation. The Journal of heart and lung transplantation:the official publication of the International Society for Heart Transplantation.2004;23:527-31.
[1]Christie, J.D., et al., The Registry of the International Society for Heart and Lung Transplantation:Twenty-eighth Adult Lung and Heart-Lung Transplant Report--2011. J Heart Lung Transplant,2011.30(10):p.1104-22.
[2]Fixman, E.D., A. Stewart, and J.G. Martin, Basic mechanisms of development of airway structural changes in asthma. Eur Respir J,2007.29(2):p.379-89.
[3]Knight, D.A. and S.T. Holgate, The airway epithelium:structural and functional properties in health and disease. Respirology,2003.8(4):p.432-46.
[4]Olman, M.A., Epithelial cell modulation of airway fibrosis in asthma. Am J Respir Cell Mol Biol,2003.28(2):p.125-8.
[5]Hackett, T.L. and D.A. Knight, The role of epithelial injury and repair in the origins of asthma. Curr Opin Allergy Clin Immunol,2007.7(1):p.63-8.
[6]Davies, D.E., et al., Airway remodeling in asthma:new insights. J Allergy Clin Immunol,2003.111(2):p.215-25; quiz 226.
[7]Xu, J., et al., Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts. Clin Exp Allergy,2002.32(6):p.881-8.
[8]Ward, C., et al., Reticular basement membrane thickening in airways of lung transplant recipients is not affected by inhaled corticosteroids. Clin Exp Allergy, 2004.34(12):p.1905-9.
[9]Ward, C., et al., Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell transition in clinically stable lung transplant recipients. Thorax, 2005.60(10):p.865-71.
[10]Estenne, M. and M.I. Hertz, Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med,2002.166(4):p.440-4.
[11]Boehler, A. and M. Estenne, Post-transplant bronchiolitis obliterans. Eur Respir J, 2003.22(6):p.1007-18.
[12]Zheng, L., et al., Scar collagen deposition in the airways of allografts of lung transplant recipients. Am J Respir Crit Care Med,1997.155(6):p.2072-7.
[13]Parks, W.C., C.L. Wilson, and Y.S. Lopez-Boado, Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol,2004.4(8):p. 617-29.
[14]Parks, W.C. and S.D. Shapiro, Matrix metalloproteinases in lung biology. Respir Res, 2001.2(1):p.10-9.
[15]Nagase, H. and J.F. Woessner, Jr., Matrix metalloproteinases. J Biol Chem,1999. 274(31):p.21491-4.
[16]Lambert, E., et al., TIMPs as multifacial proteins. Crit Rev Oncol Hematol,2004. 49(3):p.187-98.
[17]Beeh, K.M., et al., Sputum levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, and their ratio correlate with airway obstruction in lung transplant recipients:relation to tumor necrosis factor-alpha and interleukin-10. J Heart Lung Transplant,2001.20(11):p.1144-51.
[18]Taghavi, S., et al., Broncho-alveolar lavage matrix metalloproteases as a sensitive measure of bronchiolitis obliterans. Am J Transplant,2005.5(6):p.1548-52.
[19]Eerola, L.M., et al., Matrix metalloproteinase induction in post-transplant obliterative bronchiolitis. J Heart Lung Transplant,2005.24(4):p.426-32.
[20]Trello, C.A., et al., Increased gelatinolytic activity in bronchoalveolar lavage fluid in stable lung transplant recipients. Am J Respir Crit Care Med,1997.156(6):p. 1978-86.
[21]Hubner, R.H., et al., Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation. Eur Respir J,2005.25(3):p.494-501.
[22]Boehler, A., et al., Bronchiolitis obliterans after lung transplantation:a review. Chest, 1998.114(5):p.1411-26.
[23]Brazelton, T.R., et al., Chronic rejection:the result of uncontrolled remodelling of graft tissue by recipient mesenchymal cells? Data from two rodent models and the effects of immunosuppressive therapies. Inflamm Res,1999.48 SuppI 2:p. S134-5.
[24]Hinz, B., et al., Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell,2001.12(9):p.2730-41.
[25]Genden, E.M., et al., Orthotopic tracheal transplantation in the murine model. Transplantation,2002.73(9):p.1420-5.
[26]Genden, E.M., et al., Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium. Arch Otolaryngol Head Neck Surg,2003.129(1):p. 118-23.
[27]Ward, C., et al., Hypothesis:epithelial-to-mesenchymal transition is a common cause of chronic allograft failure. Transplant Proc,2005.37(2):p.977-80.
[28]Kalluri, R. and E.G. Neilson, Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest,2003.112(12):p.1776-84.
[1]Khoury, N., et al., Posttransplant diabetes mellitus in kidney transplant recipients under tacrolimus immunosuppression. Transplant Proc,2000.32(8):p.2763-4.
[2]Paul, E. and E. Thiele, Efficacy of sirolimus in treating tuberous sclerosis and lymphangioleiomyomatosis. N Engl J Med,2008.358(2):p.190-2.
[3]Inoki, K., et al., TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol,2002.4(9):p.648-57.
[4]Martin, M., et al., Role of the phosphatidylinositol 3 kinase-Akt pathway in the regulation of IL-10 and IL-12 by Porphyromonas gingivalis lipopolysaccharide. J Immunol, 2003.171(2):p.717-25.
[5]Fukao, T., et al., PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat Immunol,2002.3(9):p.875-81.
[6]Hay, N. and N. Sonenberg, Upstream and downstream of mTOR. Genes Dev,2004. 18(16):p.1926-45.
[7]Huang, S., M.A. Bjornsti, and PJ. Houghton, Rapamycins:mechanism of action and cellular resistance. Cancer Biol Ther,2003.2(3):p.222-32.
[8]Dittrich, E., et al., Rapamycin-associated post-transplantation glomerulonephritis and its remission after reintroduction of calcineurin-inhibitor therapy. Transpl Int,2004.17(4):p. 215-20.
[9]Izzedine, H., I. Brocheriou, and C. Frances, Post-transplantation proteinuria and sirolimus. N Engl J Med,2005.353(19):p.2088-9.
[10]Singer, S.J., R. Tiernan, and E.J. Sullivan, Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. N Engl J Med,2000.343(24):p.1815-6.
[11]Thaunat, O., et al., Anemia after late introduction of sirolimus may correlate with biochemical evidence of a chronic inflammatory state. Transplantation,2005.80(9):p. 1212-9.
[12]Miller, J.L., Sirolimus approved with renal transplant indication. Am J Health Syst Pharm,1999.56(21):p.2177-8.
[13]Halloran, P.F., Immunosuppressive drugs for kidney transplantation. N Engl J Med, 2004.351(26):p.2715-29.
[14]Ahya, V.N., et al., Increased risk of venous thromboembolism with a sirolimus-based immunosuppression regimen in lung transplantation. J Heart Lung Transplant,2011.30(2):p. 175-81.
[15]Bucala, R., et al., Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med,1994.1(1):p.71-81.
[16]Shook, D. and R. Keller, Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev,2003.120(11):p. 1351-83..
[17]Frid, M.G., V.A. Kale, and K.R. Stenmark, Mature vascular endothelium can give rise to smooth muscle cells via endothelial-mesenchymal transdifferentiation:in vitro analysis. Circ Res,2002.90(11):p.1189-96
[18]Abe, R., et al., Peripheral blood fibrocytes:differentiation pathway and migration to wound sites. J Immunol,2001.166(12):p.7556-62..
[19]Strieter, R.M., B.N. Gomperts, and M.P. Keane, The role of CXC chemokines in pulmonary fibrosis. J Clin Invest,2007.117(3):p.549-56..
[20]Mehrad, B., M.D. Burdick, and R.M. Strieter, Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis. Int J Biochem Cell Biol,2009.41(8-9):p.1708-18.
[21]Metz, C.N., Fibrocytes:a unique cell population implicated in wound healing. Cell Mol Life Sci,2003.60(7):p.1342-50.
[22]Strieter, R.M., et al., The role of circulating mesenchymal progenitor cells, fibrocytes, in promoting pulmonary fibrosis. Trans Am Clin Climatol Assoc,2009.120:p.49-59.
[1]Arcasoy, S.M. and R.M. Kotloff, Lung transplantation. N Engl J Med,1999.340(14):p. 1081-91.
[2]Hopkins, P.M., et al., Prospective analysis of 1,235 transbronchial lung biopsies in lung transplant recipients. J Heart Lung Transplant,2002.21(10):p.1062-7.
[3]Christie, J.D., et al., The Registry of the International Society for Heart and Lung Transplantation:twenty-seventh official adult lung and heart-lung transplant report--2010. J Heart Lung Transplant,2010.29(10):p.1104-18.
[4]Verleden, G.M., Chronic allograft rejection (obliterative bronchiolitis). Semin Respir Crit Care Med,2001.22(5):p.551-8.
[5]Estenne, M. and M.I. Hertz, Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med,2002.166(4):p.440-4.
[6]Estenne, M., et al., Bronchiolitis obliterans syndrome 2001:an update of the diagnostic criteria. J Heart Lung Transplant,2002.21(3):p.297-310.
[7]Stewart, S., et al., Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant,2007. 26(12):p.1229-42.
[8]Yousem, S.A., et al., Revision of the 1990 working formulation for the classification of pulmonary allograft rejection:Lung Rejection Study Group. J Heart Lung Transplant,1996.15(1 Pt 1):p.1-15.
[9]Verleden, G.M., L.J. Dupont, and D.E. Van Raemdonck, Is it bronchiolitis obliterans syndrome or is it chronic rejection:a reappraisal? Eur Respir J,2005.25(2):p. 221-4.
[10]Heng, D., et al., Bronchiolitis obliterans syndrome:incidence, natural history, prognosis, and risk factors. J Heart Lung Transplant,1998.17(12):p.1255-63.
[11]Burton, C.M., et al., Long-term survival after lung transplantation depends on development and severity of bronchiolitis obliterans syndrome. J Heart Lung Transplant,2007.26(7):p.681-6.
[12]Yousem, S.A., S.R. Duncan, and B.P. Griffith, Interstitial and airspace granulation tissue reactions in lung transplant recipients. Am J Surg Pathol,1992.16(9):p. 877-84.
[13]Cooper, J.D., et al., A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. International Society for Heart and Lung Transplantation. J Heart Lung Transplant,1993.12(5): p.713-6.
[14]Knoop, C. and M. Estenne, Acute and chronic rejection after lung transplantation. Semin Respir Crit Care Med,2006.27(5):p.521-33.
[15]Jackson, C.H., et al., Acute and chronic onset of bronchiolitis obliterans syndrome (BOS):are they different entities? J Heart Lung Transplant,2002.21(6):p.658-66.
[16]Lama, V.N., et al., Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients. Am J Respir Crit Care Med,2007.175(11):p.1192-8.
[17]de Jong, P.A., et al., Bronchiolitis obliterans following lung transplantation:early detection using computed tomographic scanning. Thorax,2006.61(9):p.799-804.
[18]Bankier, A.A., et al., Bronchiolitis obliterans syndrome in heart-lung transplant recipients:diagnosis with expiratory CT. Radiology,2001.218(2):p.533-9.
19] Boehler, A., et al., Bronchiolitis obliterans after lung transplantation:a review. Chest, 1998.114(5):p.1411-26.
[20]Hadjiliadis, D., et al., Impact of lung transplant operation on bronchiolitis obliterans syndrome in patients with chronic obstructive pulmonary disease. Am J Transplant, 2006.6(1):p.183-9.
[21]Burton, C.M., et al., Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1. J Heart Lung Transplant, 2009.28(9):p.888-93.
[22]Corris, P.A., Lung transplantation. Bronchiolitis obliterans syndrome. Chest Surg Clin N Am,2003.13(3):p.543-57.
[23]Sharples, L.D., et al., Risk factors for bronchiolitis obliterans:a systematic review of recent publications. J Heart Lung Transplant,2002.21(2):p.271-81.
[24]Husain, A.N., et al., Analysis of risk factors for the development of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,1999.159(3):p.829-33.
25] Girgis, R.E., et al., Risk factors for the development of obliterative bronchiolitis after lung transplantation. J Heart Lung Transplant,1996.15(12):p.1200-8.
[26]Kroshus, T.J., et al., Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation. J Thorac Cardiovasc Surg,1997.114(2):p. 195-202.
[27]Hachem, R.R., et al., The significance of a single episode of minimal acute rejection after lung transplantation. Transplantation,2005.80(10):p.1406-13.
[28]Daud, S.A., et al., Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,2007.175(5):p. 507-13.
[29]Whitson, B.A., et al., Primary graft dysfunction and long-term pulmonary function after lung transplantation. J Heart Lung Transplant,2007.26(10):p.1004-11.
[30]Fiser, S.M., et al., Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome. Ann Thorac Surg,2002.73(4):p.1041-7; discussion 1047-8.
[31]Blondeau, K., et al., Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection. Eur Respir J,2008.31(4):p. 707-13.
[32]D'Ovidio, F., et al., Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation. J Thorac Cardiovasc Surg,2005.129(5):p.1144-52.
[33]Cantu, E.,3rd, et al., J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease. Ann Thorac Surg,2004.78(4):p.1142-51; discussion 1142-51.
[34]Davis, R.D., Jr., et al., Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. J Thorac Cardiovasc Surg,2003.125(3):p.533-42.
[35]Verleden, GM., et al., Effect of switching from cyclosporine to tacrolimus on exhaled nitric oxide and pulmonary function in patients with chronic rejection after lung transplantation. J Heart Lung Transplant,2003.22(8):p.908-13.
[36]Kotsimbos, T.C., et al., Chlamydia pneumoniae serology in donors and recipients and the risk of bronchiolitis obliterans syndrome after lung transplantation. Transplantation,2005.79(3):p.269-75.
[37]Weigt, S.S., et al., Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome. Am J Transplant,2009.9(8):p.1903-11.
[38]McManus, T.E., et al., Exudative bronchiolitis after lung transplantation. J Heart Lung Transplant,2008.27(3):p.276-81.
[39]Neurohr, C., et al., Human herpesvirus 6 in bronchalveolar lavage fluid after lung transplantation:a risk factor for bronchiolitis obliterans syndrome? Am J Transplant, 2005.5(12):p.2982-91.
[40]Khalifah, A.P., et al., Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death. Am J Respir Crit Care Med,2004.170(2):p.181-7.
[41]Kumar, D., et al., Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Am J Transplant,2005.5(8):p. 2031-6.
[42]Vilchez, R.A., et al., Parainfluenza virus infection in adult lung transplant recipients: an emergent clinical syndrome with implications on allograft function. Am J Transplant,2003.3(2):p.116-20.
[43]Glanville, A.R., et al., Intravenous ribavirin is a safe and cost-effective treatment for respiratory syncytial virus infection after lung transplantation. J Heart Lung Transplant,2005.24(12):p.2114-9.
[44]Smith, M.A., et al., Effect of development of antibodies to HLA and cytomegalovirus mismatch on lung transplantation survival and development of bronchiolitis obliterans syndrome. J Thorac Cardiovasc Surg,1998.116(5):p.812-20.
[45]Keenan, R.J., et al., Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation. Transplantation,1991.51(2):p.433-8.
[46]Tamm, M., et al., Treated cytomegalovirus pneumonia is not associated with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,2004.170(10):p. 1120-3.
[47]Engelmann, I., et al., Detection of Epstein-Barr virus DNA in peripheral blood is associated with the development of bronchiolitis obliterans syndrome after lung transplantation. J Clin Virol,2009.45(1):p.47-53.
[48]Girnita, A.L., et al., HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction. Am J Transplant,2005.5(1):p. 131-8.
[49]Palmer, S.M., et al., Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome. Transplantation,2002.74(6):p.799-804.
[50]Schulman, L.L., et al., Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation. Am J Respir Crit Care Med,1998.157(6 Pt1):p.1833-7.
[51]Quantz, M.A., et al., Does human leukocyte antigen matching influence the outcome of lung transplantation? An analysis of 3,549 lung transplantations. J Heart Lung Transplant,2000.19(5):p.473-9.
[52]Sumpter, T.L. and D.S. Wilkes, Role of autoimmunity in organ allograft rejection:a focus on immunity to type Ⅴ collagen in the pathogenesis of lung transplant rejection. Am J Physiol Lung Cell Mol Physiol,2004.286(6):p. L1129-39.
53] Valentine, V.G., et al., Effect of etiology and timing of respiratory tract infections on development of bronchiolitis obliterans syndrome. J Heart Lung Transplant,2009. 28(2):p.163-9.
[54]Revell, M.P., et al., Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation. J Heart Lung Transplant,2000.19(12):p.1219-23.
[55]Hachem, R.R., et al., A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation. J Heart Lung Transplant,2007.26(10):p.1012-8.
[56]Whyte, R.I., et al., Mycophenolate mofetil for obliterative bronchiolitis syndrome after lung transplantation. Ann Thorac Surg,1997.64(4):p.945-8.
[57]Cairn, J., et al., Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome. J Heart Lung Transplant,2003. 22(1):p.50-7.
[58]Iacono, A.T., et al., Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. Eur Respir J,2004.23(3):p.384-90.
[59]Groves, S., et al., Inhaled cyclosporine and pulmonary function in lung transplant recipients. J Aerosol Med Pulm Drug Deliv,2010.23(1):p.31-9.
[60]Iacono, A.T., et al., A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med,2006.354(2):p.141-50.
[61]Hayes, D., Jr., J.B. Zwischenberger, and H.M. Mansour, Aerosolized tacrolimus:a case report in a lung transplant recipient. Transplant Proc,2010.42(9):p.3876-9.
[62]Reams, B.D., et al., Alemtuzumab in the treatment of refractory acute rejection and bronchiolitis obliterans syndrome after human lung transplantation. Am J Transplant,2007.7(12):p.2802-8.
[63]Johnson, B.A., et al., Statin use is associated with improved function and survival of lung allografts. Am J Respir Crit Care Med,2003.167(9):p.1271-8.
[64]Yates, B., et al., Azithromycin reverses airflow obstruction in established bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,2005.172(6):p.772-5.
[65]Verleden, G.M. and L.J. Dupont, Azithromycin therapy for patients with bronchiolitis obliterans syndrome after lung transplantation. Transplantation,2004.77(9):p. 1465-7.
[66]Gerhardt, S.G., et al., Maintenance azithromycin therapy for bronchiolitis obliterans syndrome:results of a pilot study. Am J Respir Crit Care Med,2003.168(1):p. 121-5.
[67]Gottlieb, J., et al., Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation,2008.85(1):p.36-41.
[68]Neurohr, C., et al., Prognostic value of bronchoalveolar lavage neutrophilia in stable lung transplant recipients. J Heart Lung Transplant,2009.28(5):p.468-74.
[69]Mamessier, E., et al., T regulatory cells in stable posttransplant bronchiolitis obliterans syndrome. Transplantation,2007.84(7):p.908-16.
[70]Yong, Z., et al., Role and mechanisms of CD4+CD25+ regulatory T cells in the induction and maintenance of transplantation tolerance. Transpl Immunol,2007. 17(2):p.120-9.
[71]O'Hagan, A.R., et al., Photopheresis in the treatment of refractory bronchiolitis obliterans complicating lung transplantation. Chest,1999.115(5):p.1459-62.
[72]Salerno, C.T., et al., Adjuvant treatment of refractory lung transplant rejection with extracorporeal photopheresis. J Thorac Cardiovasc Surg,1999.117(6):p.1063-9.
[73]Meloni, F., et al., Peripheral CD4(+)CD25(+) TREG cell counts and the response to extracorporeal photopheresis in lung transplant recipients. Transplant Proc,2007. 39(1):p.213-7.
[74]George, J.F., et al., Role for CD4(+)CD25(+) T cells in inhibition of graft rejection by extracorporeal photopheresis. J Heart Lung Transplant,2008.27(6):p.616-22.
[75]Benden, C., et al., Extracorporeal photopheresis after lung transplantation:a 10-year single-center experience. Transplantation,2008.86(11):p.1625-7.
[76]Morrell, M.R., et al., The efficacy of photopheresis for bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant,2010.29(4):p. 424-31.
[77]Diamond, D.A., et al., Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation. Int J Radiat Oncol Biol Phys, 1998.41(4):p.795-800.
[78]Tsuchida, M., et al., Electroporation-mediated transfer of plasmid DNA encoding IL-10 attenuates orthotopic tracheal allograft stenosis in rats. Transpl Immunol, 2008.19(3-4):p.173-7.
[79]Fukuyama, S., et al., Blockage of the macrophage migration inhibitory factor expression by short interference RNA inhibited the rejection of an allogeneic tracheal graft. Transpl Int,2005.18(10):p.1203-9.
[80]English, K., A. French, and K.J. Wood, Mesenchymal stromal cells:facilitators of successful transplantation? Cell Stem Cell,2010.7(4):p.431-42.
[81]Lee, J.C., J.D. Christie, and S. Keshavjee, Primary graft dysfunction:definition, risk factors, short- and long-term outcomes. Semin Respir Crit Care Med,2010.31(2):p. 161-71.
[82]Jain, R., et al., Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome. J Heart Lung Transplant,2010. 29(5):p.531-7.
[83]Siegel, M.J., et al., Post-lung transplantation bronchiolitis obliterans syndrome: usefulness of expiratory thin-section CT for diagnosis. Radiology,2001.220(2):p. 455-62.
[84]Konen, E., et al., Bronchiolitis obliterans syndrome in lung transplant recipients:can thin-section CT findings predict disease before its clinical appearance? Radiology, 2004.231(2):p.467-73.
[85]Miller, W.T., Jr., et al., Utility of high resolution computed tomography in predicting bronchiolitis obliterans syndrome following lung transplantation:preliminary findings. J Thorac Imaging,2001.16(2):p.76-80.
[86]Choi, Y.W., et al., Bronchiolitis obliterans syndrome in lung transplant recipients: correlation of computed tomography findings with bronchiolitis obliterans syndrome stage. J Thorac Imaging,2003.18(2):p.72-9.
[87]Vos, R., et al., Airway colonization and gastric aspiration after lung transplantation:do birds of a feather flock together? J Heart Lung Transplant,2008.27(8):p.843-9.
[88]Verleden, G.M, et al., Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,2006. 174(5):p.566-70.
[89]Botha, P., et al., Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation, 2008.85(5):p.771-4.
[90]Vos, R., et al., Pseudomonal airway colonisation:risk factor for bronchiolitis obliterans syndrome after lung transplantation? Eur Respir J,2008.31(5):p. 1037-45.
[91]Novick, R.J., et al., Seventy-two pulmonary retransplantations for obliterative bronchiolitis:predictors of survival. Ann Thorac Surg,1995.60(1):p.111-6.
[92]Novick, R.J., et al., Pulmonary retransplantation:predictors of graft function and survival in 230 patients. Pulmonary Retransplant Registry. Ann Thorac Surg,1998. 65(1):p.227-34.
[93]Novick, R.J., et al., Recurrence of obliterative bronchiolitis and determinants of outcome in 139 pulmonary retransplant recipients. J Thorac Cardiovasc Surg,1995. 110(5):p.1402-13; discussion 1413-4.
[94]Osaki, S., et al., Redo lung transplantation for acute and chronic lung allograft failure: long-term follow-up in a single center. Eur J Cardiothorac Surg,2008.34(6):p. 1191-7.
[95]Aigner, C., et al., Pulmonary retransplantation:is it worth the effort? A long-term analysis of 46 cases. J Heart Lung Transplant,2008.27(1):p.60-5.
[96]Strueber, M., et al., Long-term outcome after pulmonary retransplantation. J Thorac Cardiovasc Surg,2006.132(2):p.407-12.
[97]Martinu, T., et al., Pathologic correlates of bronchiolitis obliterans syndrome in pulmonary retransplant recipients. Chest,2006.129(4):p.1016-23.
[98]Brugiere, O., et al., Lung retransplantation for bronchiolitis obliterans syndrome: long-term follow-up in a series of 15 recipients. Chest,2003.123(6):p.1832-7.
[99]Kawut, S.M., et al., Outcomes after lung retransplantation in the modern era. Am J Respir Crit Care Med,2008.177(1):p.114-20.
[100]Emaminia, A., et al., Bronchiolitis obliterans syndrome occurs earlier in the post-lung allocation score era. J Thorac Cardiovasc Surg,2011.141(5):p.1278-82.
[2]Sundaresan S, Trulock EP, Mohanakumar T, Cooper JD, Patterson GA. Prevalence and outcome of bronchiolitis obliterans syndrome after lung transplantation. Washington University Lung Transplant Group. The Annals of thoracic surgery.1995;60:1341-6; discussion 6-7.
[3]Dutly AE, Andrade CF, Verkaik R, Kugathasan L, Trogadis J, Liu M, et al. A novel model for post-transplant obliterative airway disease reveals angiogenesis from the pulmonary circulation. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2005;5:248-54.
[4]Jungraithmayr W, Kayser G, Haberstroh J, Weder W, Korom S. An experimental approach toward chronic pulmonary allograft rejection:Orthotopic lung versus heterotopic tracheal segment transplantation in rats. Transplantation proceedings.2010;42:2767-70.
[5]De Vleeschauwer S, Jungraithmayr W, Wauters S, Willems S, Rinaldi M, Vaneylen A, et al. Chronic rejection pathology after orthotopic lung transplantation in mice:the development of a murine BOS model and its drawbacks. PloS one.2012;7:e29802.
[6]Fan L, Benson HL, Vittal R, Mickler EA, Presson R, Fisher AJ, et al. Neutralizing IL-17 prevents obliterative bronchiolitis in murine orthotopic lung transplantation. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.2011;11:911-22.
[7]Hertz MI, Jessurun J, King MB, Savik SK, Murray JJ. Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways. The American journal of pathology.1993;142:1945-51.
[8]Hua X, Deuse T, Tang-Quan KR, Robbins RC, Reichenspurner H, Schrepfer S. Heterotopic and orthotopic tracheal transplantation in mice used as models to study the development of obliterative airway disease. Journal of visualized experiments:JoVE. 2010.
[9]Genden EM, Boros P, Liu J, Bromberg JS, Mayer L. Orthotopic tracheal transplantation in the murine model. Transplantation.2002;73:1420-5.
[10]Genden EM, Iskander AJ, Bromberg JS, Mayer L. Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium. Archives of otolaryngology--head & neck surgery.2003;129:118-23.
[11]Chen C, Zhang YZ, Zheng H, Xu BB, Gao W. Suppression of the obliteration process by ventilation in a mouse orthotopic tracheal transplantation model. Transplantation. 2009;87:1762-8.
[12]Minamoto K, Pinsky DJ. Recipient iNOS but not eNOS deficiency reduces luminal narrowing in tracheal allografts. The Journal of experimental medicine.2002; 196:1321-33.
[13]Rock JR, Randell SH, Hogan BL. Airway basal stem cells:a perspective on their roles in epithelial homeostasis and remodeling. Disease models & mechanisms.2010;3:545-56.
[14]Hele DJ, Yacoub MH, Belvisi MG. The heterotopic tracheal allograft as an animal model of obliterative bronchiolitis. Respiratory research.2001;2:169-83.
[15]Sato M, Keshavjee S, Liu M. Translational research:animal models of obliterative bronchiolitis after lung transplantation. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.2009;9:1981-7.
[16]Adams BF, Brazelton T, Berry GJ, Morris RE. The role of respiratory epithelium in a rat model of obliterative airway disease. Transplantation.2000;69:661-4.
[17]Neuringer IP, Aris RM, Burns KA, Bartolotta TL, Chalermskulrat W, Randell SH. Epithelial kinetics in mouse heterotopic tracheal allografts. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.2002;2:410-9.
[18]Chalermskulrat W, Neuringer IP, Brickey WJ, Felix NJ, Randell SH, Ting JP, et al. Hierarchical contributions of allorecognition pathways in chronic lung rejection. American journal of respiratory and critical care medicine.2003;167:999-1007.
[19]Babu AN, Murakawa T, Thurman JM, Miller EJ, Henson PM, Zamora MR, et al. Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis. The Journal of clinical investigation.2007; 117:3774-85.
[20]Jiang X, Khan MA, Tian W, Beilke J, Natarajan R, Kosek J, et al. Adenovirus-mediated HIF-1alpha gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection. The Journal of clinical investigation. 2011;121:2336-49.
[21]Ramirez AM, Shen Z, Ritzenthaler JD, Roman J. Myofibroblast transdifferentiation in obliterative bronchiolitis:tgf-beta signaling through smad3-dependent and -independent pathways. American journal of transplantation:official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.2006;6:2080-8.
[22]Hayes D, Jr. A review of bronchiolitis obliterans syndrome and therapeutic strategies. Journal of cardiothoracic surgery.2011;6:92.
[23]Yousem SA, Duncan SR, Griffith BP. Interstitial and airspace granulation tissue reactions in lung transplant recipients. The American journal of surgical pathology. 1992;16:877-84.
[24]Luckraz H, Goddard M, McNeil K, Atkinson C, Sharples LD, Wallwork J. Is obliterative bronchiolitis in lung transplantation associated with microvascular damage to small airways? The Annals of thoracic surgery.2006;82:1212-8.
[25]Luckraz H, Goddard M, McNeil K, Atkinson C, Charman SC, Stewart S, et al. Microvascular changes in small airways predispose to obliterative bronchiolitis after lung transplantation. The Journal of heart and lung transplantation:the official publication of the International Society for Heart Transplantation.2004;23:527-31.
[1]Christie, J.D., et al., The Registry of the International Society for Heart and Lung Transplantation:Twenty-eighth Adult Lung and Heart-Lung Transplant Report--2011. J Heart Lung Transplant,2011.30(10):p.1104-22.
[2]Fixman, E.D., A. Stewart, and J.G. Martin, Basic mechanisms of development of airway structural changes in asthma. Eur Respir J,2007.29(2):p.379-89.
[3]Knight, D.A. and S.T. Holgate, The airway epithelium:structural and functional properties in health and disease. Respirology,2003.8(4):p.432-46.
[4]Olman, M.A., Epithelial cell modulation of airway fibrosis in asthma. Am J Respir Cell Mol Biol,2003.28(2):p.125-8.
[5]Hackett, T.L. and D.A. Knight, The role of epithelial injury and repair in the origins of asthma. Curr Opin Allergy Clin Immunol,2007.7(1):p.63-8.
[6]Davies, D.E., et al., Airway remodeling in asthma:new insights. J Allergy Clin Immunol,2003.111(2):p.215-25; quiz 226.
[7]Xu, J., et al., Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts. Clin Exp Allergy,2002.32(6):p.881-8.
[8]Ward, C., et al., Reticular basement membrane thickening in airways of lung transplant recipients is not affected by inhaled corticosteroids. Clin Exp Allergy, 2004.34(12):p.1905-9.
[9]Ward, C., et al., Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell transition in clinically stable lung transplant recipients. Thorax, 2005.60(10):p.865-71.
[10]Estenne, M. and M.I. Hertz, Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med,2002.166(4):p.440-4.
[11]Boehler, A. and M. Estenne, Post-transplant bronchiolitis obliterans. Eur Respir J, 2003.22(6):p.1007-18.
[12]Zheng, L., et al., Scar collagen deposition in the airways of allografts of lung transplant recipients. Am J Respir Crit Care Med,1997.155(6):p.2072-7.
[13]Parks, W.C., C.L. Wilson, and Y.S. Lopez-Boado, Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol,2004.4(8):p. 617-29.
[14]Parks, W.C. and S.D. Shapiro, Matrix metalloproteinases in lung biology. Respir Res, 2001.2(1):p.10-9.
[15]Nagase, H. and J.F. Woessner, Jr., Matrix metalloproteinases. J Biol Chem,1999. 274(31):p.21491-4.
[16]Lambert, E., et al., TIMPs as multifacial proteins. Crit Rev Oncol Hematol,2004. 49(3):p.187-98.
[17]Beeh, K.M., et al., Sputum levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, and their ratio correlate with airway obstruction in lung transplant recipients:relation to tumor necrosis factor-alpha and interleukin-10. J Heart Lung Transplant,2001.20(11):p.1144-51.
[18]Taghavi, S., et al., Broncho-alveolar lavage matrix metalloproteases as a sensitive measure of bronchiolitis obliterans. Am J Transplant,2005.5(6):p.1548-52.
[19]Eerola, L.M., et al., Matrix metalloproteinase induction in post-transplant obliterative bronchiolitis. J Heart Lung Transplant,2005.24(4):p.426-32.
[20]Trello, C.A., et al., Increased gelatinolytic activity in bronchoalveolar lavage fluid in stable lung transplant recipients. Am J Respir Crit Care Med,1997.156(6):p. 1978-86.
[21]Hubner, R.H., et al., Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation. Eur Respir J,2005.25(3):p.494-501.
[22]Boehler, A., et al., Bronchiolitis obliterans after lung transplantation:a review. Chest, 1998.114(5):p.1411-26.
[23]Brazelton, T.R., et al., Chronic rejection:the result of uncontrolled remodelling of graft tissue by recipient mesenchymal cells? Data from two rodent models and the effects of immunosuppressive therapies. Inflamm Res,1999.48 SuppI 2:p. S134-5.
[24]Hinz, B., et al., Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell,2001.12(9):p.2730-41.
[25]Genden, E.M., et al., Orthotopic tracheal transplantation in the murine model. Transplantation,2002.73(9):p.1420-5.
[26]Genden, E.M., et al., Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium. Arch Otolaryngol Head Neck Surg,2003.129(1):p. 118-23.
[27]Ward, C., et al., Hypothesis:epithelial-to-mesenchymal transition is a common cause of chronic allograft failure. Transplant Proc,2005.37(2):p.977-80.
[28]Kalluri, R. and E.G. Neilson, Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest,2003.112(12):p.1776-84.
[1]Khoury, N., et al., Posttransplant diabetes mellitus in kidney transplant recipients under tacrolimus immunosuppression. Transplant Proc,2000.32(8):p.2763-4.
[2]Paul, E. and E. Thiele, Efficacy of sirolimus in treating tuberous sclerosis and lymphangioleiomyomatosis. N Engl J Med,2008.358(2):p.190-2.
[3]Inoki, K., et al., TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol,2002.4(9):p.648-57.
[4]Martin, M., et al., Role of the phosphatidylinositol 3 kinase-Akt pathway in the regulation of IL-10 and IL-12 by Porphyromonas gingivalis lipopolysaccharide. J Immunol, 2003.171(2):p.717-25.
[5]Fukao, T., et al., PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat Immunol,2002.3(9):p.875-81.
[6]Hay, N. and N. Sonenberg, Upstream and downstream of mTOR. Genes Dev,2004. 18(16):p.1926-45.
[7]Huang, S., M.A. Bjornsti, and PJ. Houghton, Rapamycins:mechanism of action and cellular resistance. Cancer Biol Ther,2003.2(3):p.222-32.
[8]Dittrich, E., et al., Rapamycin-associated post-transplantation glomerulonephritis and its remission after reintroduction of calcineurin-inhibitor therapy. Transpl Int,2004.17(4):p. 215-20.
[9]Izzedine, H., I. Brocheriou, and C. Frances, Post-transplantation proteinuria and sirolimus. N Engl J Med,2005.353(19):p.2088-9.
[10]Singer, S.J., R. Tiernan, and E.J. Sullivan, Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. N Engl J Med,2000.343(24):p.1815-6.
[11]Thaunat, O., et al., Anemia after late introduction of sirolimus may correlate with biochemical evidence of a chronic inflammatory state. Transplantation,2005.80(9):p. 1212-9.
[12]Miller, J.L., Sirolimus approved with renal transplant indication. Am J Health Syst Pharm,1999.56(21):p.2177-8.
[13]Halloran, P.F., Immunosuppressive drugs for kidney transplantation. N Engl J Med, 2004.351(26):p.2715-29.
[14]Ahya, V.N., et al., Increased risk of venous thromboembolism with a sirolimus-based immunosuppression regimen in lung transplantation. J Heart Lung Transplant,2011.30(2):p. 175-81.
[15]Bucala, R., et al., Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med,1994.1(1):p.71-81.
[16]Shook, D. and R. Keller, Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev,2003.120(11):p. 1351-83..
[17]Frid, M.G., V.A. Kale, and K.R. Stenmark, Mature vascular endothelium can give rise to smooth muscle cells via endothelial-mesenchymal transdifferentiation:in vitro analysis. Circ Res,2002.90(11):p.1189-96
[18]Abe, R., et al., Peripheral blood fibrocytes:differentiation pathway and migration to wound sites. J Immunol,2001.166(12):p.7556-62..
[19]Strieter, R.M., B.N. Gomperts, and M.P. Keane, The role of CXC chemokines in pulmonary fibrosis. J Clin Invest,2007.117(3):p.549-56..
[20]Mehrad, B., M.D. Burdick, and R.M. Strieter, Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis. Int J Biochem Cell Biol,2009.41(8-9):p.1708-18.
[21]Metz, C.N., Fibrocytes:a unique cell population implicated in wound healing. Cell Mol Life Sci,2003.60(7):p.1342-50.
[22]Strieter, R.M., et al., The role of circulating mesenchymal progenitor cells, fibrocytes, in promoting pulmonary fibrosis. Trans Am Clin Climatol Assoc,2009.120:p.49-59.
[1]Arcasoy, S.M. and R.M. Kotloff, Lung transplantation. N Engl J Med,1999.340(14):p. 1081-91.
[2]Hopkins, P.M., et al., Prospective analysis of 1,235 transbronchial lung biopsies in lung transplant recipients. J Heart Lung Transplant,2002.21(10):p.1062-7.
[3]Christie, J.D., et al., The Registry of the International Society for Heart and Lung Transplantation:twenty-seventh official adult lung and heart-lung transplant report--2010. J Heart Lung Transplant,2010.29(10):p.1104-18.
[4]Verleden, G.M., Chronic allograft rejection (obliterative bronchiolitis). Semin Respir Crit Care Med,2001.22(5):p.551-8.
[5]Estenne, M. and M.I. Hertz, Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med,2002.166(4):p.440-4.
[6]Estenne, M., et al., Bronchiolitis obliterans syndrome 2001:an update of the diagnostic criteria. J Heart Lung Transplant,2002.21(3):p.297-310.
[7]Stewart, S., et al., Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant,2007. 26(12):p.1229-42.
[8]Yousem, S.A., et al., Revision of the 1990 working formulation for the classification of pulmonary allograft rejection:Lung Rejection Study Group. J Heart Lung Transplant,1996.15(1 Pt 1):p.1-15.
[9]Verleden, G.M., L.J. Dupont, and D.E. Van Raemdonck, Is it bronchiolitis obliterans syndrome or is it chronic rejection:a reappraisal? Eur Respir J,2005.25(2):p. 221-4.
[10]Heng, D., et al., Bronchiolitis obliterans syndrome:incidence, natural history, prognosis, and risk factors. J Heart Lung Transplant,1998.17(12):p.1255-63.
[11]Burton, C.M., et al., Long-term survival after lung transplantation depends on development and severity of bronchiolitis obliterans syndrome. J Heart Lung Transplant,2007.26(7):p.681-6.
[12]Yousem, S.A., S.R. Duncan, and B.P. Griffith, Interstitial and airspace granulation tissue reactions in lung transplant recipients. Am J Surg Pathol,1992.16(9):p. 877-84.
[13]Cooper, J.D., et al., A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. International Society for Heart and Lung Transplantation. J Heart Lung Transplant,1993.12(5): p.713-6.
[14]Knoop, C. and M. Estenne, Acute and chronic rejection after lung transplantation. Semin Respir Crit Care Med,2006.27(5):p.521-33.
[15]Jackson, C.H., et al., Acute and chronic onset of bronchiolitis obliterans syndrome (BOS):are they different entities? J Heart Lung Transplant,2002.21(6):p.658-66.
[16]Lama, V.N., et al., Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients. Am J Respir Crit Care Med,2007.175(11):p.1192-8.
[17]de Jong, P.A., et al., Bronchiolitis obliterans following lung transplantation:early detection using computed tomographic scanning. Thorax,2006.61(9):p.799-804.
[18]Bankier, A.A., et al., Bronchiolitis obliterans syndrome in heart-lung transplant recipients:diagnosis with expiratory CT. Radiology,2001.218(2):p.533-9.
19] Boehler, A., et al., Bronchiolitis obliterans after lung transplantation:a review. Chest, 1998.114(5):p.1411-26.
[20]Hadjiliadis, D., et al., Impact of lung transplant operation on bronchiolitis obliterans syndrome in patients with chronic obstructive pulmonary disease. Am J Transplant, 2006.6(1):p.183-9.
[21]Burton, C.M., et al., Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1. J Heart Lung Transplant, 2009.28(9):p.888-93.
[22]Corris, P.A., Lung transplantation. Bronchiolitis obliterans syndrome. Chest Surg Clin N Am,2003.13(3):p.543-57.
[23]Sharples, L.D., et al., Risk factors for bronchiolitis obliterans:a systematic review of recent publications. J Heart Lung Transplant,2002.21(2):p.271-81.
[24]Husain, A.N., et al., Analysis of risk factors for the development of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,1999.159(3):p.829-33.
25] Girgis, R.E., et al., Risk factors for the development of obliterative bronchiolitis after lung transplantation. J Heart Lung Transplant,1996.15(12):p.1200-8.
[26]Kroshus, T.J., et al., Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation. J Thorac Cardiovasc Surg,1997.114(2):p. 195-202.
[27]Hachem, R.R., et al., The significance of a single episode of minimal acute rejection after lung transplantation. Transplantation,2005.80(10):p.1406-13.
[28]Daud, S.A., et al., Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,2007.175(5):p. 507-13.
[29]Whitson, B.A., et al., Primary graft dysfunction and long-term pulmonary function after lung transplantation. J Heart Lung Transplant,2007.26(10):p.1004-11.
[30]Fiser, S.M., et al., Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome. Ann Thorac Surg,2002.73(4):p.1041-7; discussion 1047-8.
[31]Blondeau, K., et al., Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection. Eur Respir J,2008.31(4):p. 707-13.
[32]D'Ovidio, F., et al., Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation. J Thorac Cardiovasc Surg,2005.129(5):p.1144-52.
[33]Cantu, E.,3rd, et al., J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease. Ann Thorac Surg,2004.78(4):p.1142-51; discussion 1142-51.
[34]Davis, R.D., Jr., et al., Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. J Thorac Cardiovasc Surg,2003.125(3):p.533-42.
[35]Verleden, GM., et al., Effect of switching from cyclosporine to tacrolimus on exhaled nitric oxide and pulmonary function in patients with chronic rejection after lung transplantation. J Heart Lung Transplant,2003.22(8):p.908-13.
[36]Kotsimbos, T.C., et al., Chlamydia pneumoniae serology in donors and recipients and the risk of bronchiolitis obliterans syndrome after lung transplantation. Transplantation,2005.79(3):p.269-75.
[37]Weigt, S.S., et al., Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome. Am J Transplant,2009.9(8):p.1903-11.
[38]McManus, T.E., et al., Exudative bronchiolitis after lung transplantation. J Heart Lung Transplant,2008.27(3):p.276-81.
[39]Neurohr, C., et al., Human herpesvirus 6 in bronchalveolar lavage fluid after lung transplantation:a risk factor for bronchiolitis obliterans syndrome? Am J Transplant, 2005.5(12):p.2982-91.
[40]Khalifah, A.P., et al., Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death. Am J Respir Crit Care Med,2004.170(2):p.181-7.
[41]Kumar, D., et al., Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Am J Transplant,2005.5(8):p. 2031-6.
[42]Vilchez, R.A., et al., Parainfluenza virus infection in adult lung transplant recipients: an emergent clinical syndrome with implications on allograft function. Am J Transplant,2003.3(2):p.116-20.
[43]Glanville, A.R., et al., Intravenous ribavirin is a safe and cost-effective treatment for respiratory syncytial virus infection after lung transplantation. J Heart Lung Transplant,2005.24(12):p.2114-9.
[44]Smith, M.A., et al., Effect of development of antibodies to HLA and cytomegalovirus mismatch on lung transplantation survival and development of bronchiolitis obliterans syndrome. J Thorac Cardiovasc Surg,1998.116(5):p.812-20.
[45]Keenan, R.J., et al., Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation. Transplantation,1991.51(2):p.433-8.
[46]Tamm, M., et al., Treated cytomegalovirus pneumonia is not associated with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,2004.170(10):p. 1120-3.
[47]Engelmann, I., et al., Detection of Epstein-Barr virus DNA in peripheral blood is associated with the development of bronchiolitis obliterans syndrome after lung transplantation. J Clin Virol,2009.45(1):p.47-53.
[48]Girnita, A.L., et al., HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction. Am J Transplant,2005.5(1):p. 131-8.
[49]Palmer, S.M., et al., Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome. Transplantation,2002.74(6):p.799-804.
[50]Schulman, L.L., et al., Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation. Am J Respir Crit Care Med,1998.157(6 Pt1):p.1833-7.
[51]Quantz, M.A., et al., Does human leukocyte antigen matching influence the outcome of lung transplantation? An analysis of 3,549 lung transplantations. J Heart Lung Transplant,2000.19(5):p.473-9.
[52]Sumpter, T.L. and D.S. Wilkes, Role of autoimmunity in organ allograft rejection:a focus on immunity to type Ⅴ collagen in the pathogenesis of lung transplant rejection. Am J Physiol Lung Cell Mol Physiol,2004.286(6):p. L1129-39.
53] Valentine, V.G., et al., Effect of etiology and timing of respiratory tract infections on development of bronchiolitis obliterans syndrome. J Heart Lung Transplant,2009. 28(2):p.163-9.
[54]Revell, M.P., et al., Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation. J Heart Lung Transplant,2000.19(12):p.1219-23.
[55]Hachem, R.R., et al., A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation. J Heart Lung Transplant,2007.26(10):p.1012-8.
[56]Whyte, R.I., et al., Mycophenolate mofetil for obliterative bronchiolitis syndrome after lung transplantation. Ann Thorac Surg,1997.64(4):p.945-8.
[57]Cairn, J., et al., Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome. J Heart Lung Transplant,2003. 22(1):p.50-7.
[58]Iacono, A.T., et al., Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. Eur Respir J,2004.23(3):p.384-90.
[59]Groves, S., et al., Inhaled cyclosporine and pulmonary function in lung transplant recipients. J Aerosol Med Pulm Drug Deliv,2010.23(1):p.31-9.
[60]Iacono, A.T., et al., A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med,2006.354(2):p.141-50.
[61]Hayes, D., Jr., J.B. Zwischenberger, and H.M. Mansour, Aerosolized tacrolimus:a case report in a lung transplant recipient. Transplant Proc,2010.42(9):p.3876-9.
[62]Reams, B.D., et al., Alemtuzumab in the treatment of refractory acute rejection and bronchiolitis obliterans syndrome after human lung transplantation. Am J Transplant,2007.7(12):p.2802-8.
[63]Johnson, B.A., et al., Statin use is associated with improved function and survival of lung allografts. Am J Respir Crit Care Med,2003.167(9):p.1271-8.
[64]Yates, B., et al., Azithromycin reverses airflow obstruction in established bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,2005.172(6):p.772-5.
[65]Verleden, G.M. and L.J. Dupont, Azithromycin therapy for patients with bronchiolitis obliterans syndrome after lung transplantation. Transplantation,2004.77(9):p. 1465-7.
[66]Gerhardt, S.G., et al., Maintenance azithromycin therapy for bronchiolitis obliterans syndrome:results of a pilot study. Am J Respir Crit Care Med,2003.168(1):p. 121-5.
[67]Gottlieb, J., et al., Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation,2008.85(1):p.36-41.
[68]Neurohr, C., et al., Prognostic value of bronchoalveolar lavage neutrophilia in stable lung transplant recipients. J Heart Lung Transplant,2009.28(5):p.468-74.
[69]Mamessier, E., et al., T regulatory cells in stable posttransplant bronchiolitis obliterans syndrome. Transplantation,2007.84(7):p.908-16.
[70]Yong, Z., et al., Role and mechanisms of CD4+CD25+ regulatory T cells in the induction and maintenance of transplantation tolerance. Transpl Immunol,2007. 17(2):p.120-9.
[71]O'Hagan, A.R., et al., Photopheresis in the treatment of refractory bronchiolitis obliterans complicating lung transplantation. Chest,1999.115(5):p.1459-62.
[72]Salerno, C.T., et al., Adjuvant treatment of refractory lung transplant rejection with extracorporeal photopheresis. J Thorac Cardiovasc Surg,1999.117(6):p.1063-9.
[73]Meloni, F., et al., Peripheral CD4(+)CD25(+) TREG cell counts and the response to extracorporeal photopheresis in lung transplant recipients. Transplant Proc,2007. 39(1):p.213-7.
[74]George, J.F., et al., Role for CD4(+)CD25(+) T cells in inhibition of graft rejection by extracorporeal photopheresis. J Heart Lung Transplant,2008.27(6):p.616-22.
[75]Benden, C., et al., Extracorporeal photopheresis after lung transplantation:a 10-year single-center experience. Transplantation,2008.86(11):p.1625-7.
[76]Morrell, M.R., et al., The efficacy of photopheresis for bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant,2010.29(4):p. 424-31.
[77]Diamond, D.A., et al., Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation. Int J Radiat Oncol Biol Phys, 1998.41(4):p.795-800.
[78]Tsuchida, M., et al., Electroporation-mediated transfer of plasmid DNA encoding IL-10 attenuates orthotopic tracheal allograft stenosis in rats. Transpl Immunol, 2008.19(3-4):p.173-7.
[79]Fukuyama, S., et al., Blockage of the macrophage migration inhibitory factor expression by short interference RNA inhibited the rejection of an allogeneic tracheal graft. Transpl Int,2005.18(10):p.1203-9.
[80]English, K., A. French, and K.J. Wood, Mesenchymal stromal cells:facilitators of successful transplantation? Cell Stem Cell,2010.7(4):p.431-42.
[81]Lee, J.C., J.D. Christie, and S. Keshavjee, Primary graft dysfunction:definition, risk factors, short- and long-term outcomes. Semin Respir Crit Care Med,2010.31(2):p. 161-71.
[82]Jain, R., et al., Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome. J Heart Lung Transplant,2010. 29(5):p.531-7.
[83]Siegel, M.J., et al., Post-lung transplantation bronchiolitis obliterans syndrome: usefulness of expiratory thin-section CT for diagnosis. Radiology,2001.220(2):p. 455-62.
[84]Konen, E., et al., Bronchiolitis obliterans syndrome in lung transplant recipients:can thin-section CT findings predict disease before its clinical appearance? Radiology, 2004.231(2):p.467-73.
[85]Miller, W.T., Jr., et al., Utility of high resolution computed tomography in predicting bronchiolitis obliterans syndrome following lung transplantation:preliminary findings. J Thorac Imaging,2001.16(2):p.76-80.
[86]Choi, Y.W., et al., Bronchiolitis obliterans syndrome in lung transplant recipients: correlation of computed tomography findings with bronchiolitis obliterans syndrome stage. J Thorac Imaging,2003.18(2):p.72-9.
[87]Vos, R., et al., Airway colonization and gastric aspiration after lung transplantation:do birds of a feather flock together? J Heart Lung Transplant,2008.27(8):p.843-9.
[88]Verleden, G.M, et al., Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med,2006. 174(5):p.566-70.
[89]Botha, P., et al., Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation, 2008.85(5):p.771-4.
[90]Vos, R., et al., Pseudomonal airway colonisation:risk factor for bronchiolitis obliterans syndrome after lung transplantation? Eur Respir J,2008.31(5):p. 1037-45.
[91]Novick, R.J., et al., Seventy-two pulmonary retransplantations for obliterative bronchiolitis:predictors of survival. Ann Thorac Surg,1995.60(1):p.111-6.
[92]Novick, R.J., et al., Pulmonary retransplantation:predictors of graft function and survival in 230 patients. Pulmonary Retransplant Registry. Ann Thorac Surg,1998. 65(1):p.227-34.
[93]Novick, R.J., et al., Recurrence of obliterative bronchiolitis and determinants of outcome in 139 pulmonary retransplant recipients. J Thorac Cardiovasc Surg,1995. 110(5):p.1402-13; discussion 1413-4.
[94]Osaki, S., et al., Redo lung transplantation for acute and chronic lung allograft failure: long-term follow-up in a single center. Eur J Cardiothorac Surg,2008.34(6):p. 1191-7.
[95]Aigner, C., et al., Pulmonary retransplantation:is it worth the effort? A long-term analysis of 46 cases. J Heart Lung Transplant,2008.27(1):p.60-5.
[96]Strueber, M., et al., Long-term outcome after pulmonary retransplantation. J Thorac Cardiovasc Surg,2006.132(2):p.407-12.
[97]Martinu, T., et al., Pathologic correlates of bronchiolitis obliterans syndrome in pulmonary retransplant recipients. Chest,2006.129(4):p.1016-23.
[98]Brugiere, O., et al., Lung retransplantation for bronchiolitis obliterans syndrome: long-term follow-up in a series of 15 recipients. Chest,2003.123(6):p.1832-7.
[99]Kawut, S.M., et al., Outcomes after lung retransplantation in the modern era. Am J Respir Crit Care Med,2008.177(1):p.114-20.
[100]Emaminia, A., et al., Bronchiolitis obliterans syndrome occurs earlier in the post-lung allocation score era. J Thorac Cardiovasc Surg,2011.141(5):p.1278-82.
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