孟鲁司特联合噻托溴铵对慢性阻塞性肺疾病患者肺功能、免疫功能及炎性因子的影响研究

Influence of Montelukast Combined with Tiotropium Bromide on Pulmonary Function, Immune Function and Inflammatory Cytokines of Patients with Chronic Obstructive Pulmonary Disease

目的探讨孟鲁司特联合噻托溴铵对慢性阻塞性肺疾病(COPD)患者肺功能、免疫功能及炎性因子的影响。方法选取广西壮族自治区南溪山医院2012年5月—2015年5月收治的COPD患者160例,采用随机数字表法分为对照组、A组、B组和C组,每组40例。对照组患者给予常规治疗,A组患者在常规治疗基础上给予孟鲁司特片口服,B组患者在常规治疗基础上给予噻托溴铵雾化吸入,C组患者在常规治疗基础上给予孟鲁司特片口服联合噻托溴铵雾化吸入;4组患者均连续治疗3个月。比较4组患者治疗前后肺功能指标〔第1秒用力呼气容积占预计值百分比(FEV_1%)、第1秒用力呼气容积与用力肺活量比值(FEV_1/FVC)〕、6分钟步行距离、伯格呼吸困难量表(Borg)评分、T淋巴细胞亚群(CD_3^+细胞分数、CD_4^+细胞分数、CD_8^+细胞分数、CD_4^+/CD_8^+细胞比值)及血清炎性因子〔白介素6(IL-6)、C反应蛋白(CRP)、脂联素(APN)〕水平,观察4组患者治疗期间不良反应发生情况。结果治疗前4组患者FEV_1%和FEV_1/FVC比较,差异无统计学意义(P>0.05);治疗后A、B、C组患者FEV_1%和FEV_1/FVC高于对照组、治疗前,C组患者FEV_1%和FEV_1/FVC高于A、B组(P<0.05);对照组患者治疗前后FEV_1%和FEV_1/FVC比较,差异无统计学意义(P>0.05)。治疗前4组患者6分钟步行距离和Borg评分比较,差异无统计学意义(P>0.05);治疗后A、B、C组患者6分钟步行距离长于对照组、治疗前,Borg评分低于对照组、治疗前,C组患者6分钟步行距离长于A、B组,Borg评分低于A、B组(P<0.05);对照组患者治疗前后6分钟步行距离和Borg评分比较,差异无统计学意义(P>0.05)。治疗前4组患者CD_3^+细胞分数、CD_4^+细胞分数、CD_8^+细胞分数及CD_4^+/CD_8^+细胞比值比较,差异无统计学意义(P>0.05);治疗后A、B、C组患者CD_3^+细胞分数、CD_4^+细胞分数、CD_8^+细胞分数及CD_4^+/CD_8^+细胞比值高于对照组、治疗前,C组患者CD_3^+细胞分数、CD_4^+细胞分数、CD_8^+细胞分数及CD_4^+/CD_8^+细胞比值高于A组、B组(P<0.05);对照组患者治疗前后CD_3^+细胞分数、CD_4^+细胞分数、CD_8^+细胞分数及CD_4^+/CD_8^+细胞比值比较,差异无统计学意义(P>0.05)。治疗前4组患者血清IL-6、CRP及APN水平比较,差异无统计学意义(P>0.05);治疗后A、B、C组患者血清IL-6、CRP、APN水平低于对照组、治疗前,C组患者血清IL-6、CRP、APN水平低于A、B组,对照组患者血清IL-6、CRP、APN水平低于治疗前(P<0.05)。治疗期间4组患者均未出现严重不良反应。结论孟鲁司特联合噻托溴铵可有效改善COPD患者肺功能和免疫功能,减轻患者炎性反应,且安全性较高,有利于促进患者康复。

Objective To explore the influence of montelukast combined with tiotropium bromide on pulmonary function,immune function and inflammatory cytokines of patients with chronic obstructive pulmonary disease( COPD).Methods A total of 160 patients with COPD were selected in Nanxi Mountain Hospital of Guangxi Zhuang Autonomous Region from May 2012 to May 2015, and they were divided into control group, A group, B group and C group, each of 40 cases. Patients of control group received conventional treatment,patients of A group received oral montelukast tablets,patients of B group received aerosol inhalation of tiotropium bromide,while patients of C group received oral montelukast tablets combined with aerosol inhalation of tiotropium bromide;all of the four groups continuously treated for 3 months. Index of pulmonary function( including FEV1% and FEV1/ FVC),6-minute walking distance,Borg score,T-lymphocyte subsets( CD3+cell percentage,CD4^+cell percentage,CD8^+cell percentage and CD4^+/ CD8^+cell ratio) and serum inflammatory cytokines( including IL-6,CRP and APN) levels before and after treatment were compared among the four groups,incidence of adverse reactions during the treatment was observed. Results No statistically significant differences of FEV1% or FEV1/ FVC was found among the four groups before treatment( P > 0. 05);after treatment, FEV1% and FEV1/ FVC of A group, B group and C group were statistically significantly higher than those of control group and those before treatment,FEV1% and FEV1/ FVC of C group were statistically significantly higher than those of A group and B group( P < 0. 05),while no statistically significant differences of FEV1% or FEV1/ FVC of control group was found compared with those before treatment( P > 0. 05). No statistically significant differences of 6-minute walking distance or Borg score was found among the four groups before treatment( P > 0. 05);after treatment,6-minute walking distance of A group,B group and C group was statistically significantly longer than that of control group and that before treatment,Borg score of A group,B group and C group was statistically significantly lower than that of control group and that before treatment,6-minute walking distance of C group was statistically significantly longer than that of A group and B group,respectively,Borg score of C group was statistically significantly lower than that of A group and B group,respectively( P < 0. 05),while no statistically significant differences of 6-minute walking distance or Borg score of control group was found compared with those before treatment( P > 0. 05). No statistically significant differences of CD3+cell percentage,CD4^+cell percentage,CD8^+cell percentage or CD4^+/ CD8^+cell ratio was found among the four groups before treatment( P > 0. 05);after treatment,CD3+cell percentage,CD4^+cell percentage,CD8^+cell percentage and CD4^+/ CD8^+cell ratio of A group,B group and C group were statistically significantly higher than those of control group and those before treatment,CD3+cell percentage,CD4^+cell percentage,CD8^+cell percentage and CD4^+/ CD8^+cell ratio of C group were statistically significantly higher than those of A group and B group( P < 0. 05),while no statistically significant differences of CD3+cell percentage,CD4^+cell percentage,CD8^+cell percentage or CD4^+/ CD8^+cell ratio of control group was found compared with those before treatment( P> 0. 05). No statistically significant differences of serum level of IL-6,CRP or APN was found among the four groups before treatment( P > 0. 05);after treatment,serum levels of IL-6,CRP and APN of A group,B group and C group were statistically significantly lower than those of control group and those before treatment,serum levels of IL-6,CRP and APN of C group were statistically significantly lower than those of A group and B group,serum levels of IL-6,CRP and APN of control group were statistically significantly higher than those before treatment( P < 0. 05). No one of the four groups occurred any serious adverse reactions during the treatment. Conclusion Montelukast combined with tiotropium bromide can effectively improve the pulmonary function and immune function,relive the inflammatory reaction of patients with COPD,is safe and helpful to promote the recovery.