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

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.

3aired Capacity of Fibroblasts to Support Airway Epithelial Progenitors in Bronchiolitis Obliterans Syndrome

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.

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

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.

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

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.

Cryptogenic organizing pneumonia associated with pregnancy:A case report

BACKGROUND Cryptogenic organizing pneumonia(COP),formerly known as bronchiolitis obliterans organizing pneumonia,is an extremely rare disease in pregnancy.In this case,we report on COP diagnosed in recurrent pneumonia that does not respond to antibiotics in pregnant woman.CASE SUMMARY A 35-year-old woman with no prior lung disease presented with concerns of chest pain with cough,sputum,dyspnea,and mild fever at 11 wk’gestation.She was diagnosed with community-acquired pneumonia and treated with antibiotics;her symptoms improved temporarily.Four weeks after discharge,she was readmitted with aggravated symptoms.Chest computed tomography demonstrated multifocal patchy airspace consolidation and ground-glass opacities at the basal segments of the right lower lobe,at the lateral basal segment of the lower lobe,and at the lingular segment of the left upper lobe.Bronchoalveolar lavage revealed an increased lymphocyte count and a decreased CD4/CD8 ratio.Prednisolone(0.5 mg/kg/d)was administered for 10 d after the second admission.Dyspnea improved after 3 d of steroid treatment and other symptoms improved on the 5th day of steroid administration.Post-delivery transbronchial lung biopsy further revealed the presence of granulation tissue with fibroblasts in smallbronchiole lumens.CONCLUSION This case suggests that it is important to differentiate COP from atypical pneumonia in the deteriorated condition despite antibiotic treatment.