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Risk factors for bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplantation

Chinese Medical Journal 2013年第13期126卷 2489-2494页

作者： MO Xiao-dong XU Lan-ping LIU Dai-hong ZHANG Xiao-hui CHEN Huan CHEN Yu-hong HAN Wei WANG Yu WANG Feng-rong WANG Jing-zhi LIU Kai-yan HUANG Xiao-jun Peking University People's Hospital & Institute of Hematology Beijing Key laboratory of Hematopoitic Stem Cell Transplantation Beijing 100044 China

Background The occurrence of bronchiolitis obliterans syndrome （BOS） after allogeneic hematopoietic stem cell transplantation （alIo-HSCT） is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after alIo-HSCT. Methods A nested case-control study was designed. Cases with BOS and controls matched for the year of alIo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent alIo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia. Results Thirty-six patients suffered from BOS; the mean age at the time of presentation was （32.7±2.4） years, and the mean time to presentation was （474±350） days post-HSCT. A pre-HSCT cyclophosphamide dose of 〉3.2 g/m2 （OR=8.74, P=0.025）, chronic graft-versus-host disease （moderate to severe）（OR=12.02, P=0.000）, and conditioning regimens without antithymocyte globulin （OR=2.79, P=0.031） were independently associated with BOS. Conclusions We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after alIo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.

关键词： bronchiolitis obliterans syndrome allogeneic hematopoietic stem cell transplantation graft-versus-host disease,"antithymoeyte globulin

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3aired Capacity of Fibroblasts to Support Airway Epithelial Progenitors in bronchiolitis obliterans syndrome

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Chinese Medical Journal 2016年第17期129卷 2040-2044页

作者： Su-Bei Zhang Xin Sun Qi Wu Jun-Ping Wu Huai-Yong Chen Haihe Clinical College of Tianjin Medical University Tianjin 300070 China Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine Tianjin Institute of Respiratory Diseases Tianjin Haihe Hospital Tianjin 300350 China Tianjin Institute of Respiratory Diseases Tianjin Haihe Hospital Tianjin 300350 China Department of Respiratory Tianjin Haihe Hospital Tianjin 300350 China Department of Basic Medicine Tianjin Haihe Hospital Tianjin 300350 China

Background： bronchiolitis obliterans syndrome （BOS） often develops in transplant patients and results in injury to the respiratory and terminal airway epithelium. Owing to its rising incidence, the pathogenesis of BOS is currently an area of intensive research. Studies have shown that injury to the respiratory epithelium results in dysregulation of epithelial repair. Airway epithelial regeneration is supported by stromal cells, including fibroblasts. This study aimed to investigate whether the supportive role of lung fibroblasts is altered in BOS. Methods： Suspensions of lung cells were prepared by enzyme digestion. Lung progenitor cells （LPCs） were separated by fluorescence-activated cell sorting. Lung fibroblasts from patients with BOS or healthy controls were mixed with sorted mouse LPCs to compare the colony-forming efficiency of LPCs by counting the number of colonies with a diameter of_〉50/.tln in each culture. Statistical analyses were pertbrmed using the SPSS 17.0 software （SPSS Inc., USA）. The paired Student＇s t-test was used to test tbr statistical significance. Results： LPCs were isolated with the surface phenotype ofCD31-CD34-CD45- EpCAMtSca- I . The colony-lbrming efficiency of LPCs was significantly reduced when co-cultured with fibroblasts isolated from patients with BOS. The addition ofSB431542 increased the colony-forming efficiency of LPCs to 1.8%; however, it was still significantly less than that in co-culture with healthy control fibroblasts （P 〈 0.05）. Conclusion： The epithelial-supportive capacity offibroblasts is impaired in the development of BOS and suggest that inefficient repair of airway epithelium could contribute to persistent airway inflammation in BOS.

关键词： bronchiolitis obliterans syndrome Fibroblasts Lung Progenitor Cells Proliferation

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Chronic lung allograft dysfunction post-lung transplantation:The era of bronchiolitis obliterans syndrome and restrictive allograft syndrome

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World Journal of Transplantation 2020年第5期10卷 104-116页

作者： Nobuyuki Yoshiyasu Masaaki Sato Department of Thoracic Surgery The University of Tokyo HospitalTokyo 113-8655Japan

Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival *** main reason for this is a lack of knowledge regarding the pathological condition and the establishment of *** consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes:bronchiolitis obliterans syndrome and restrictive allograft *** with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are *** this review,we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome,which have been elucidated from clinicopathological observations and animal experiments worldwide.

关键词： Lung transplantation Chronic lung allograft dysfunction bronchiolitis obliterans syndrome Restrictive allograft syndrome Interaction of immune cells Anatomical changes in transplanted lungs

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