Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment ...Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The 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 syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In 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.展开更多
Thoracic air leak syndrome (TALS) is a rare complication of allogeneic stem cell transplant (Allo-SCT) and is associated with a poor prognosis. We report a case of a 67-year-old male, after 20 months of Allo-SCT for a...Thoracic air leak syndrome (TALS) is a rare complication of allogeneic stem cell transplant (Allo-SCT) and is associated with a poor prognosis. We report a case of a 67-year-old male, after 20 months of Allo-SCT for acute myeloid leukemia, who presented with fever and acute worsening dyspnea on a background of a 4-month history of slowly progressive dyspnea. He was initially diagnosed with parainfluenza pneumonia and later developed TALS as a result of bronchiolitis obliterans (BO) caused by chronic graft-versus-host disease (cGVHD). Herein, we highlight the importance of early recognition and treatment of non-infectious pulmonary complications of Allo-SCT.展开更多
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 ...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.展开更多
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 exposu...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.展开更多
Bronchiolitis obliterans syndrome （BOS） after hematopoietic stem cell transplantation （HSCT） is a major cause of morbidity and mortality with limited treatment options. Lung transplantation （LTX） has been rarely...Bronchiolitis obliterans syndrome （BOS） after hematopoietic stem cell transplantation （HSCT） is a major cause of morbidity and mortality with limited treatment options. Lung transplantation （LTX） has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT （two females, four males） from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years （ranging from 1 to 5 years）. At a median time of 4 years （ranging from 2 to 5 years） after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months （ranging from 12 to 39 months）. At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.展开更多
文摘Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The 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 syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In 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.
文摘Thoracic air leak syndrome (TALS) is a rare complication of allogeneic stem cell transplant (Allo-SCT) and is associated with a poor prognosis. We report a case of a 67-year-old male, after 20 months of Allo-SCT for acute myeloid leukemia, who presented with fever and acute worsening dyspnea on a background of a 4-month history of slowly progressive dyspnea. He was initially diagnosed with parainfluenza pneumonia and later developed TALS as a result of bronchiolitis obliterans (BO) caused by chronic graft-versus-host disease (cGVHD). Herein, we highlight the importance of early recognition and treatment of non-infectious pulmonary complications of Allo-SCT.
基金grants from the National Natural Science Foundation of China，the Natural Science Foundation of Tianjin City
文摘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.
基金This work was partly supported by grants of the National High Technology Research and Development Program of China （Program 863） （No. 2011AA020105）, the National Natural Science Foundation of China （No. 30971292）, and the Key Program of National Natural Science Foundation of China （No. 81230013）.
文摘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.
文摘Bronchiolitis obliterans syndrome （BOS） after hematopoietic stem cell transplantation （HSCT） is a major cause of morbidity and mortality with limited treatment options. Lung transplantation （LTX） has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT （two females, four males） from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years （ranging from 1 to 5 years）. At a median time of 4 years （ranging from 2 to 5 years） after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months （ranging from 12 to 39 months）. At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.
