小剂量阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸治疗特发性肺纤维化的临床疗效分析

Analysis of the Clinical Effect of Small Dose Azithromycin Combined with Inhalation of Budesonide and N-acetylcysteine on Idiopathic Pulmonary Fibrosis

目的:观察小剂量阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸对特发性肺纤维化(IPF)患者肺功能及支气管肺泡灌洗液炎症因子表达的影响。方法:随机将56例确诊为IPF的住院患者分为对照组和治疗组,对照组给予常规治疗,吸氧,戒烟,吸入布地奈德及乙酰半胱氨酸;治疗组在常规治疗基础上加服小剂量阿奇霉素片。动态观察两组患者治疗3、6个月的疗效及肺功能的改善情况;完成2个疗程(6个月)治疗后,检测和比较两组支气管肺泡灌洗液相关炎症因子水平的变化。结果:治疗3个月时,两组患者的动脉血氧分压(PO2)、肺活量(VC)、1秒钟用力呼气容积占预计值百分比(FEV1%pred)、最大通气量占预计值百分比(MVV%pred)、单位肺泡容积的一氧化碳弥散量占预计值百分比(DLCO/VA%pred)均较治疗前显著增加(P<0.05);治疗6个月时,治疗组的有效率(20/26,76.9%)明显高于对照组(14/30,46.7%),且PO2、VC、FEV1%pred、MVV%pred及DLCO/VA%pred等肺功能指标均显著高于对照组(P<0.05);对照组支气管肺泡灌洗液TNF-α、IL-8浓度均较治疗前降低(P<0.05),IL-4、IL-10、IFN-γ浓度较治疗前无明显变化;而治疗组支气管肺泡灌洗液TNF-α、IL-8、IL-4、IL-10浓度均较治疗前降低,IFN-γ浓度较治疗前明显增加(P<0.05)。结论:阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸可能通过改变支气管肺泡灌洗液IFN-γ等炎症因子浓度有效改善IPF患者的肺功能。

Objective： To observe the clinical effects of small dose azithromycin combined with inhalation of Budesonide and N-acetylcysteine on cytokines of bronchoalveolar lavage fluid and lung function of patients with idiopathic pulmonary fibrosis （IPF）. Methods： 56 patients with IPF were randomly divided into two groups. The control group was only treated with general treatment, includ- ing oxygen uptaking, quitting smoking and inhaling Budesonide（2 mL/time,Tid） and N-acetylcysteine（3 mL/time, Tid）, while the treatment group was given azithromycin （250 mg, oral, qd） based on general treatment for 60 days. The curative effect and pulmonary function pa- rameters such as PO2, forced vital capacity（VC）, FEVl%pred, MVV% pred and DLCONA% pred of patients in the two groups were dy- namically observed before and 3, 6 months after treatment, the related inflammatory cytokines concentration in bronchoalveolar lavage fluid were deteced and compared before and 6 months after treatment. Results： After three months＇ treatment, the PO2, VC, FEVI% pred, MVV% pred and DLCONA% pred of patients in both groups increased compared to those before treatment （P〈0.05）. 6 months after treatment, the efficiency of treatment group （20/26, 76.9%） was obviously higher than that of the control group （14/30, 46.7%）. The PO2, VC, FEVI% pred, MVV% pred and DLCONA% pred of patients in the treatment group were higher than those in the control group （P〈0.05）. The concentration of TNF-α and IL-8 in bronchoalveoiar lavage fluid of patients in control group were significantly lower （P〈0.05）, but IL-4, IL -10, IFN-γ had no obvious changes compared to those before treatment, respectively. And the concentration of TNF-α, IL -8, IL-4, IL-10 in the treatment group were reduced, the concentration of IFN-γincreased significantly compared to those be- fore treatment （P〈0.05）. Conclusion： Small dose Azithromycin combined with inhalation of Budesonide and N-acetylcysteine could im- prove the lung function of patients with IPF by changing the concentrations of related inflammatory cytokines such as TNF-α, IL -8, IL-4, IL-10 and IFN-γinbronchoalveolar lavage fluid.