Reichenspurner H, Girgis R E, Robbins R C, Conte J V, Nair R V, Valentine V, Berry G J, Morris R E, Theodore J, Reitz B A
Department of Cardiothoracic Surgery, Stanford University School of Medicine, California 94305-5247, USA.
Ann Thorac Surg. 1995 Dec;60(6):1845-53. doi: 10.1016/0003-4975(95)00776-8.
Obliterative bronchiolitis (OB) has emerged as the main cause of morbidity and mortality in the long-term follow-up after lung and heart-lung transplantation. The pathogenesis of OB is multifactorial, with acute rejection and cytomegalovirus infection being the main risk factors for the development of OB. The final common pathway of all inciting events seems to be an alloimmune injury, with subsequent release of immunologic mediators and production of growth factors leading to luminal obliteration and fibrous scarring of the small airways. Analyzing the 14 years of experience in 163 patients at Stanford University, we found a current incidence of bronchiolitis obliterans syndrome or histologically proven OB within the first 3 years after lung and heart-lung transplantation of 36.3%, with an overall prevalence of 58.1% after heart-lung and 51.4% after lung transplantation. Both pulmonary function indices (forced expiratory flow between 25% and 75% of forced vital capacity and forced expiratory volume in 1 second) and transbronchial biopsies have proven helpful in diagnosing bronchiolitis obliterans syndrome or OB at an early stage. Early diagnosis of OB and improved management have achieved survival rates in patients with OB after 1, 3, 5, and 10 years of 83%, 66%, 46%, and 22%, compared with 86%, 83%, 67%, and 67% in patients without OB. Recently, different experimental models have been developed to investigate the cellular and molecular events leading to OB and to evaluate new treatment strategies for this complication, which currently limits the long-term success of heart-lung and lung transplantation.
闭塞性细支气管炎(OB)已成为肺移植和心肺移植长期随访中发病和死亡的主要原因。OB的发病机制是多因素的,急性排斥反应和巨细胞病毒感染是OB发生的主要危险因素。所有诱发事件的最终共同途径似乎是同种免疫损伤,随后免疫介质的释放和生长因子的产生导致小气道管腔闭塞和纤维瘢痕形成。通过分析斯坦福大学163例患者14年的经验,我们发现肺移植和心肺移植后3年内闭塞性细支气管炎综合征或经组织学证实的OB的当前发病率为36.3%,心肺移植后的总体患病率为58.1%,肺移植后为51.4%。肺功能指标(用力肺活量25%至75%之间的用力呼气流量和1秒用力呼气量)和经支气管活检已被证明有助于早期诊断闭塞性细支气管炎综合征或OB。OB的早期诊断和改进的管理使OB患者1年、3年、5年和10年的生存率分别达到83%、66%、46%和22%,而无OB患者的生存率分别为86%、83%、67%和67%。最近,已经开发了不同的实验模型来研究导致OB的细胞和分子事件,并评估针对这种并发症的新治疗策略,这种并发症目前限制了心肺移植和肺移植的长期成功率。