激素联合环磷酰胺治疗结缔组织病相关性间质性肺疾病的疗效及其影响因素分析

苏菁 杨雅婷 贾聚娟 项保利 钱海红 支学军 李琛 赵建清

摘 要 目的：探討激素联合环磷酰胺治疗结缔组织病相关性间质性肺疾病（CTD-ILD）的疗效，并分析其影响因素。方法：将2018年1月-2019年1月于我院确诊CTD-ILD的患者100例根据随机数字表法分为观察组和对照组各50例。对照组患者给予复方环磷酰胺片治疗，每次50 mg，每天3～4次;观察组患者在对照组基础上加用醋酸泼尼松片，每次10 mg，每天3～4次;两组患者的疗程均为6个月。比较两组患者的临床疗效、不良反应发生情况和治疗前后的肺功能，外周血白细胞介素6（IL-6）、C反应蛋白（CRP）、降钙素原（PCT）水平以及生活质量[圣乔治呼吸问卷（SGRQ）评分]。根据疗效结果，将所有患者分为治疗有效组和治疗无效组，采用单因素及多因素Logistic回归分析法分析影响CTD-ILD临床疗效的相关因素。结果：治疗后，观察组患者的总有效率、用力肺活量、第1 秒用力呼气容积和一氧化碳弥散量均显著高于对照组，SGRQ评分和外周血IL-6、CRP、PCT水平均显著低于对照组（P<0.05）。两组患者的不良反应总发生率比较，差异无统计学意义（P>0.05）。单因素分析结果显示，治疗有效组患者的性别、年龄、既往病史和CTD类型与治疗无效组比较，差异均无统计学意义（P>0.05）; 但两组患者在不同外周血IL-6、CRP和PCT水平中的分布比较，差异均有统计学意义（P<0.05）。多因素Logistic回归分析结果显示，IL-6是影响该联合用药方案疗效的独立危险因素[比值比为4.537，95%置信区间为（3.668，10.352），P=0.002]。结论：激素联合环磷酰胺可以显著提高CTD-ILD患者的疗效，改善其肺功能和生活质量，降低其炎性因子表达水平;IL-6水平是影响该方案疗效的独立危险因素，在治疗过程中应密切关注该指标水平变化。

关键词 结缔组织病相关性间质性肺疾病;激素;环磷酰胺;临床疗效;白细胞介素6;影响因素

ABSTRACT   OBJECTIVE： To investigate the efficacy of hormone combined with cyclophosphamide in the treatment of connective tissue disease-associated interstitial lung disease （CTD-ILD） and to analyze its influential factors. METHODS： 100 patients diagnosed as CTD-ILD in our hospital from Jan. 2018 to Jan. 2019 were randomly divided into observation group and control group， with 50 cases in each group. Control group was treated with Compound cyclophosphamide tablets， 50 mg each time， 3-4 times each day. Observation group was additionally treated with Prednisone acetate tablets， 10 mg each time， 3-4 times each day， on the basis of control group. Treatment courses of 2 groups lasted for 6 months. The clinical efficacy， the occurrence of ADR， lung function before and after treatment， the levels of peripheral IL-6， CRP and PCT and quality of life （SGRQ score） were compared between 2 groups. According to the therapeutic efficacy， all patients were divided into effective group and ineffective group. The related factors influencing the clinical efficacy of CTD-ILD were analyzed by univariate and multivariate Logistic regression analysis. RESULTS： After treatment， total response rate， FVC， FEV1 and DLCO of observation group were significantly higher than those of control group， while SGRQ score， levels of IL-6， CRP and PCT in peripheral blood were significantly lower than control group （P<0.05）. There was no significant difference in the total incidence of ADR between 2 groups （P>0.05）. Univariate analysis showed that there were no significant differences in gender， age， past medical history and CTD type between effective group and ineffective group （P>0.05）. However， there were statistical significancant differences in the distribution of different levels of IL-6， CRP and PCT in peripheral blood between 2 groups （P<0.05）. Multivariate Logistic regression analysis showed that IL-6 was an independent risk factor for therapeutic efficacy of combined therapy [OR（95%CI）=4.537（3.668，10.352），P=0.002]. CONCLUSIONS： Hormone combined with cyclophosphamide can significantly improve the therapeutic efficacy of CTD-ILD patients， improve their lung function and quality of life， and reduce the expression level of inflammatory factors. The level of IL-6 is an independent risk factor affecting the efficacy of the treatment， and its changes should be paid close attention to during the treatment.

KEYWORDS   Connective tissue disease-associated interstitial lung disease; Hormone; Cyclophosphamide; Clinical efficacy; IL-6; Influencing factor

结缔组织病（CTD）是一种自身免疫性疾病，包括系统性红斑狼疮、类风湿关节炎、干燥综合征和系统性硬化等一系列病变，以全身血管和结缔组织的持续性炎症反应及病理改变为主要特点[1-2]。其病……