Martinu Tereza, Howell David N, Davis R Duane, Steele Mark P, Palmer Scott M
Duke University Medical Center, Box 3876, Durham, NC 27710, USA.
Chest. 2006 Apr;129(4):1016-23. doi: 10.1378/chest.129.4.1016.
The main hindrance to long-term success of lung transplantation is bronchiolitis obliterans syndrome (BOS), generally thought to be a manifestation of chronic allograft rejection. BOS is associated histologically with epithelial injury, bronchocentric mononuclear inflammation, and fibrosis of small airways known as bronchiolitis obliterans (BO). Few studies have directly compared clinical, radiographic, and histologic findings of BOS and BO, particularly in the era of improved immunosuppression and infection prophylaxis. Patients undergoing pulmonary retransplantation for BOS provide a unique opportunity to investigate these relationships.
All patients who underwent pulmonary retransplantation for BOS from 1992 to 2004 at Duke University Medical Center were reviewed. Pathology findings in explanted lung allografts were compared with clinical, radiographic, and transbronchial biopsy data.
Over the 12-year study period, 12 patients underwent pulmonary retransplantation for BOS. The median time to BOS was 517 days (intraquartile range, 396 to 819.8 days). BOS scores prior to retransplantation were 2 in 2 patients and 3 in 10 patients. We developed a semiquantitative scoring system for epithelial, inflammatory, and fibrotic changes in affected airways to permit better comparison between BO and BOS. Somewhat surprisingly, only 50% (6 of 12 patients) had severe fibrotic changes, although all had some degree of epithelial injury, fibrosis, or inflammation centered around the bronchi and bronchioles. Furthermore, pathology findings other than BO were present in most explanted allografts and included cholesterol clefts (n = 4), focal invasive aspergillosis (n = 1), interstitial fibrosis (n = 2), and chronic vascular rejection (n = 1).
In this series of patients with advanced BOS undergoing retransplantation, at least some degree of BO was present in all explanted allografts. However, the degree of epithelial changes, fibrosis, and inflammation present among affected bronchi varied considerably. Furthermore, a wide range of pathologic processes of potential clinical significance were evident in half of the patients. We conclude that significant histologic heterogeneity exists among patients undergoing retransplantation for BOS, potentially contributing to the variability of patient responses to treatment.
肺移植长期成功的主要障碍是闭塞性细支气管炎综合征（BOS），一般认为它是慢性移植物排斥反应的一种表现。BOS在组织学上与上皮损伤、支气管周围单核细胞炎症以及称为闭塞性细支气管炎（BO）的小气道纤维化有关。很少有研究直接比较BOS和BO的临床、影像学和组织学表现，特别是在免疫抑制和感染预防得到改善的时代。因BOS接受肺再次移植的患者提供了一个研究这些关系的独特机会。
回顾了1992年至2004年在杜克大学医学中心因BOS接受肺再次移植的所有患者。将移植肺同种异体移植物的病理结果与临床、影像学和经支气管活检数据进行比较。
在12年的研究期间，12例患者因BOS接受了肺再次移植。发生BOS的中位时间为517天（四分位间距，396至819.8天）。再次移植前BOS评分为2分的患者有2例，评分为3分的患者有10例。我们开发了一种半定量评分系统，用于评估受影响气道的上皮、炎症和纤维化变化，以便更好地比较BO和BOS。有点令人惊讶的是，只有50%（12例患者中的6例）有严重的纤维化变化，尽管所有患者都有一定程度的上皮损伤、纤维化或围绕支气管和细支气管的炎症。此外，大多数移植的同种异体移植物中存在除BO以外的病理结果，包括胆固醇裂隙（n = 4）、局灶性侵袭性曲霉病（n = 1）、间质纤维化（n = 2）和慢性血管排斥反应（n = 1）。
在这组接受再次移植的晚期BOS患者中，所有移植的同种异体移植物中至少存在一定程度的BO。然而，受影响支气管中上皮变化、纤维化和炎症的程度差异很大。此外，在一半的患者中明显存在一系列具有潜在临床意义的病理过程。我们得出结论，因BOS接受再次移植的患者中存在显著的组织学异质性，这可能导致患者对治疗反应的变异性。
