儿童造血干细胞移植后发生重度非感染性肺部并发症影响因素的病例对照研究OA

Background Non-infectious pulmonary complications(NIPC)after hematopoietic stem cell transplantation(HSCT)in children have an insidious onset,and are usually difficult to diagnose in the early stage.Also,these disorders are prone to progressing into a severe condition with poor therapeutic effect.Objective To explore the risk factors for severe NIPC after HSCT in children,providing a reference for the clinical diagnosis and management of pediatric NIPC.Design Case-control study.Methods Children who developed NIPC after HSCT at the children's medical center of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 1,2020,to December 31,2023,aged under 16 years,underwent bronchoalveolar lavage fluid(BALF)immunological examination were enrolled.Exclude cases with NIPC caused by drugs or other factors as well as substandard quality of pulmonary function testing.Based on the degree of ventilatory dysfunction at the time of NIPC diagnosis,the children were divided into a mild-to-moderate group and a severe group.Clinical data of the children such as the general information,transplantation-related data,and BALF immunological indicators were collected via the hospital electronic medical record system.Influencing factors for severe NIPC outcomes in children undergoing HSCT were analyzed through univariate and multivariate analysis.Main Outcome Measures Influencing factors for severe NIPC outcomes in children undergoing HSCT.Results A total of 25 children with NIPC after HSCT were finally included in this study,with 14(56.0%)assigned to the mild-to-moderate group and 11(44.0%)to the severe group.Among them,22 cases(88.0%)manifested with bronchiolitis obliterans syndrome(BOS),3 cases(12.0%)presented with pulmonary fibrosis,and 4 cases(16.0%)were complicated by pneumothorax,pneumomediastinum,or subcutaneous emphysema.The univariate analysis showed that interleukin(IL)-8,IL-17A and CD8+T lymphocyte levels in the BALF of the mild-to-moderate group were significantly lower than that in the severe group(P<0.05),while CD4+T lymphocyte/CD8+T lymphocyte ratio in the BALF of the severe group was significantly lower than those in the mild-to-moderate group group(P<0.05).No statistically significant difference was observed in terms of pre-transplant pulmonary function,chest high resolution computed tomography findings,and transplantation methods between the two groups(all P>0.05).Also,the multivariable analysis indicated that the development of moderate-to-severe chronic graft-versus-host disease(cGVHD)(OR=14.302,95%CI:1.103-185.435)was related to the progression into severe NIPC after HSCT in children,and up-regulation of CD8+T lymphocyte in BALF(OR=1.107,95%CI:1.107-1.204)was identified as independent risk factor for severe NIPC following pediatric HSCT(P<0.05).Conclusion The development of moderate-to-severe cGVHD is related to the progression into severe NIPC after HSCT in children,and up-regulation of CD8+T lymphocyte in BALF is an independent risk factor for progressing into a severe condition in children with NIPC following HSCT.Great attention should be paid to these pediatric patients and early intervention is recommended to improve prognosis.