吡非尼酮联合乙酰半胱氨酸对特发性肺纤维化的临床疗效

Clinical efficacy of pirfenidone combined with acetylcysteine in patients with idiopathic pulmonary fibrosis

目的探讨吡非尼酮联合乙酰半胱氨酸治疗特发性肺纤维化(IPF)的疗效及其对涎液化糖链抗原-6(KL-6)和炎症因子水平的影响。方法选取2020年7月至2022年7月在该院就诊的67例IPF患者作为研究对象,采用随机数字表法将其分为对照组(33例)和研究组(34例)。对照组在呼吸内科常规治疗基础上采用口服吡非尼酮胶囊治疗,研究组在对照组治疗的基础上采用口服乙酰半胱氨酸颗粒治疗,两组均连续治疗4个月。检测两组患者治疗前、后的肺功能相关指标[一氧化碳弥散量(DLCO)、功能残气量(FRC)、第1秒用力呼气容积(FEV1)和用力肺活量(FVC)];收集IPF患者治疗前、后空腹静脉血和支气管肺泡灌洗液(BALF)标本,并采用酶联免疫吸附试验检测两组标本中KL-6水平及炎症因子指标[乳酸脱氢酶(LDH)、C反应蛋白(CRP)、红细胞沉降率(ESR)、单核细胞趋化蛋白-1(MCP-1)、白细胞介素-6(IL-6)以及肿瘤坏死因子-α(TNF-α)]水平。结果治疗前,两组FEV1、FVC、FRC及DLCO比较,差异均无统计学意义(P>0.05);治疗后,两组FEV1、FVC、FRC及DLCO高于治疗前,且研究组FEV1、FVC、FRC及DLCO高于对照组,差异均有统计学意义(P<0.05)。治疗前,两组血清和BALF中KL-6水平比较,差异均无统计学意义(P>0.05);治疗后,两组血清和BALF中KL-6水平低于治疗前,且研究组血清和BALF中KL-6水平低于对照组,差异均有统计学意义(P<0.05)。治疗前,两组血清WBC、LDH、CRP、ESR、MCP-1、IL-6、TNF-α水平及BALF中MCP-1、IL-6、TNF-α水平比较,差异均无统计学意义(P>0.05);治疗后,两组血清WBC、LDH、CRP、ESR、MCP-1、IL-6、TNF-α水平及BALF中MCP-1、IL-6、TNF-α水平低于治疗前,且研究组血清WBC、LDH、CRP、ESR、MCP-1、IL-6、TNF-α水平及BALF中MCP-1、IL-6、TNF-α水平低于对照组,差异均有统计学意义(P<0.05)。Pearson相关性分析结果显示,血清KL-6水平与FVC、DLCO呈负相关(r=—0.387、—0.406,P<0.05),而与FEV1呈正相关(r=0.375,P<0.05)。结论吡非尼酮联合乙酰半胱氨酸治疗IPF的疗效较好,能降低KL-6及炎症因子水平,改善肺功能,具有一定的临床推广价值。

Objective To explore the therapeutic effect of pirfenidone combined with acetylcysteine on idiopathic pulmonary fibrosis(IPF)and its impact on Krebs Von den Lungen-6(KL-6)and inflammatory cytokine levels.Methods Totally 67 IPF patients who attended the hospital from July 2020 to July 2022 were selected and randomly divided into control group(33 cases)and study group(34 cases)by numerical table method.The control group was treated with oral pirfenidone capsule therapy on the basis of routine conventional treatment in the respiratory department,the study group was treated with oral acetylcysteine granules on the basis of the treatment in the control group,and both groups were treated continuously for 4 months.Lung function-related indexes[carbon monoxide diffusion capacity(DLCO),functional residual capacity(FRC),exertional expiratory volume in the first second(FEV 1)and exertional lung capacity(FVC)]were examined in the two groups before and after treatment;fasting venous blood and bronchoalveolar lavage(BALF)specimens of the IPF patients were collected before and after treatment,and KL-6 levels and inflammatory factor indexes[lactate dehydrogenase(LDH),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),monocyte chemotactic protein-1(MCP-1),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)]levels in fasting venous blood and BALF in both groups were detected by enzyme linked immunosorbent assay.Results Before treatment,the FEV 1,FVC,FRC and DLCO between the two groups were not statistically significant(P>0.05);after treatment,the FEV 1,FVC,FRC and DLCO were higher than those before treatment in the two groups,and the FEV 1,FVC,FRC and DLCO in the study group were higher than those in the control group,with statistically significant differences(P<0.05).Before treatment,the levels of KL-6 in serum and BALF between the two groups showed no statistically significant differences(P>0.05);after treatment,the levels of KL-6 in serum and BALF of the two groups were lower than those before treatment,and the levels of KL-6 in serum and BALF of the study group were lower than those of the control group,with statistically significant differences(P<0.05).Before treatment,the serum WBC,LDH,CRP,ESR,MCP-1,IL-6 and TNF-αlevels,as well as the levels of MCP-1,IL-6 and TNF-αin BALF between the two groups had no statistically significant differences(P>0.05);after treatment,the serum WBC,LDH,CRP,ESR,MCP-1,IL-6 and TNF-αlevels,as well as the levels of MCP-1,IL-6 and TNF-αin BALF in the two groups were lower than those before treatment,and serum WBC,LDH,CRP,ESR,MCP-1,IL-6 and TNF-αlevels in the study group,as well as the levels of MCP-1,IL-6,and TNF-αin BALF,were lower than those in the control group,with statistically significant differences(P<0.05).Pearson′s correlation analysis results showed that serum KL-6 level was negatively correlated with FVC and DLCO(r=—0.387,—0.406,P<0.05),while positively correlated with FEV 1(r=0.375,P<0.05).Conclusion Pirfenidone combined with acetylcysteine has better efficacy in the treatment of IPF,which can reduce the levels of KL-6 and inflammatory factors,and improve lung function,with certain clinical promotion value.