沙利度胺联合布地奈德雾化吸入治疗特发性肺纤维化的效果观察

Efficacy of thalidomide combined with budesonide aerosol inhalation on idiopathic pulmonary fibrosis

目的探讨沙利度胺联合布地奈德雾化吸入治疗特发性肺纤维化的效果及对患者肺功能、T淋巴细胞亚群的影响。方法2020年6月—2022年6月郑州大学附属郑州中心医院诊治特发性肺纤维化患者102例,随机分为观察组和对照组各51例,2组均采用抗感染、支气管扩张、抗纤维化等常规治疗,对照组在常规治疗基础上加用布地奈德雾化吸入治疗,观察组在对照组基础上加用沙利度胺口服治疗,2组持续治疗12周后评价疗效,比较2组治疗总有效率及治疗期间腹泻、眩晕、恶心、皮疹等不良反应发生情况。2组分别于治疗前、后应用肺功能检测仪检测肺功能[第1 s用力呼气量(FEV_(1))、用力肺活量(FVC)、一氧化碳弥散量(DLCO)],应用流式细胞仪检测外周血CD4^(+)、CD8^(+)T淋巴细胞比率及辅助性T细胞1(Th1)、辅助性T细胞2(Th2)比率,计算CD4^(+)/CD8^(+)、Th1/Th2。结果观察组治疗总有效率(96.08%)高于对照组(74.51%)(χ^(2)=9.457,P=0.002)。2组治疗前FEV_(1)、FVC、DLCO、CD4^(+)T淋巴细胞比率、CD8^(+)T淋巴细胞比率、CD4^(+)/CD8^(+)、Th1比率、Th2比率、Th1/Th2比较差异均无统计学意义(P>0.05);2组治疗后FEV_(1)、FVC、DLCO、CD4^(+)T淋巴细胞比率、CD8^(+)T淋巴细胞比率、Th1比率、Th2比率、Th1/Th2均高于治疗前(P<0.05),CD4^(+)/CD8^(+)均低于治疗前(P<0.05);观察组治疗后FEV_(1)[(2.16±0.25)L]、FVC[(2.05±0.31)L]、DLCO[(17.96±1.24)mL/(min·mmHg)]、CD4^(+)T淋巴细胞比率[(31.82±3.03)%]、CD8^(+)T淋巴细胞比率[(29.63±2.35)%]、Th1比率[(25.79±3.12)%]、Th2比率[(2.44±0.71)%]、Th1/Th2(11.37±3.06)均高于对照组[(1.58±0.28)L、(1.79±0.29)L、(14.28±1.15)mL/(min·mmHg)、(27.98±2.85)%、(24.89±1.86)%、(20.31±3.22)%、(2.17±0.65)%、10.03±2.59](P<0.05),CD4^(+)/CD8^(+)(1.07±0.08)低于对照组(1.12±0.09)(t=2.919,P=0.004)。治疗期间观察组发生腹泻2例,眩晕1例,恶心2例,皮疹1例;对照组发生腹泻1例,恶心1例,皮疹1例;观察组不良反应发生率(11.76%)与对照组(5.88%)比较差异无统计学意义(χ^(2)=1.097,P=0.295)。结论沙利度胺联合布地奈德雾化吸入治疗特发性肺纤维化效果良好,可改善患者肺功能,调节免疫功能及CD4^(+)/CD8^(+)、Th1/Th2失衡,不良反应较少。

Objective To investigate the efficacy of thalidomide combined with budesonide aerosol inhalation on idiopathic pulmonary fibrosis,and the influence on pulmonary function and T cell subsets.Methods Totally 102 patients with idiopathic pulmonary fibrosis diagnosed and treated in Zhengzhou Central Hospital Affiliated to Zhengzhou University from June 2020 to June 2022 were randomly and equally divided into observation group and control group.In addition to the conventional treatment as anti-infection,bronchodilatation and anti-fibrosis,control group received budesonide aerosol inhalation,and observation group received oral administration of thalidomide plus budesonide aerosol inhalation.The efficacy was evaluated after 12 weeks of treatment,and the total effective rate and the occurrence of adverse reactions such as diarrhea,vertigo,nausea and skin rash during treatment were compared between two groups.The forced expiratory volume in one second(FEV_(1)),forced vital capacity(FVC)and carbon monoxide diffusion capacity(DLCO)were detected by lung function detector,and the percentages of CD4^(+)and CD8^(+)T cells as well as T helper-1(Th1)and T helper-2(Th2)cells were measured by flow cytometry.The ratios of CD4^(+)/CD8^(+)and Thl/Th2 were calculated,Results The total effective rate was higher in observation group(96.08%)than that in control group(74.51%)(χ^(2)=9.457,P=0.002).There were no significant differences in FEV_(1),FCV,DLCO,percentages of CD4^(+)and CD8^(+)T cells,CD4^(+)/CD8^(+)ratio,percentages of Th1 and Th2 cells,and Th1/Th2 ratio before treatment between two groups(P>0.05).FEV_(1),FCV,DLCO,percentages of CD4^(+)and CD8^(+)T cells as well as Th1 and Th2 cells,and Thl/Th2 ratio were higher after treatment than those before treatment in two groups(P<0.05),and the ratio of CD4^(+)/CD8^(+)was lower than that before treatment(P<0.05).After treatment,FEV_(1),FCV,DLCO,percentages of CD4^(+)and CD8^(+)T cells as well as Th1 and Th2 cells,and Th1/Th2 ratio were higher in observation group[(2.16±0.25)L,(2.05±0.31)L,(17.96±1.24)mL/(min·mmHg),(31.82±3.03)%,(29.63±2.35]%,(25.79±3.12)%,(2.44±0.71)%,11.37±3.06]than those in control group[(1.58±0.28)L,(1.79±0.29)L,(14.28±1.15)mL/(min·mmHg),(27.98±2.85)%,(24.89±1.86)%,(20.31±3.22)%,(2.17±0.65)%,10.03±2.59](P<0.05),and the ratio of CD4^(+)/CD8^(+)was lower in observation group(1.07+0.08.)than that in control group(1.12±0.09)(t=2.919,P=0.004),During treatment,the adverse reactions occurred as diarrhea in 2 patients,vertigo in 1,nausea in 2,and rash in 1 in observation group,and diarrhea in 1 patient,nausea in 1,and rash in 1 in control group.The incidence of adverse reactions showed no significant difference between observation group(11.76%)and control group(5.88%)(χ^(2)=1.097,P=0.295).Conclusion The combination of thalidomide and budesonide aerosol inhalation has a good efficacy on idiopathic pulmonary fibrosis,and it can improve the pulmonary function,regulate the immune level,and correct the imbalance of CD4^(+)/CD8^(+)and Thl/Th2,with less adverse reactions.