诱导痰中白介素-8和白介素-10与高原慢性阻塞性肺疾病急性加重期合并慢性肺心病发病的关系及其干预的研究

Relationship between induced sputum interleukin-8 and interleukin-10 with pathogenesis in patients with acute stage of chronic obstructive pulmonary disease complicated chronic cor pulmonale and the intervention effects of drugs at high altitude

目的探讨诱导痰中白介素-8(IL-8)和IL-10与高原慢性阻塞性肺疾病急性加重期(AECOPD)合并慢性肺心病(CCP)患者发病的关系,评价吸入糖皮质激素(ICS)联合长效β2-激动剂(LABA)对其的干预作用。方法 132例高原AECOPD合并CCP患者随机分为3组,每组44例。3组的常规治疗(抗感染、祛痰、茶碱)相同。治疗2组给予沙美特罗/氟替卡松50μg/250μg,2次/d气道吸入;治疗1组给予布地奈德1mg,2次/d雾化吸入;对照组仅给予常规治疗。治疗前和治疗缓解2周后测定诱导痰中IL-8、IL-10浓度、FEV1%pred、FEV1/FVC、PaO2、PaCO2,观察各组治疗前后IL-8、IL-10浓度变化、肺功能和动脉血气改善程度。结果治疗前各组间诱导痰中IL-8、IL-10、FEV1%pred、FEV1/FVC、PaO2、PaCO2无统计学差异(P>0.05);治疗后各组诱导痰中IL-8、IL-10、FEV1%pred、FEV1/FVC、PaO2、PaCO2与治疗前比较均有非常显著性差异(P<0.01),治疗后各组间比较也有显著性差异(P<0.01或P<0.05)。132例患者治疗前,诱导痰中IL-8与FEV1%pred、FEV1/FVC、PaO2显著负相关(分别r=-0.714、-0.597、-0.682,P<0.001),与PaCO2显著正相关(r=0.662,P<0.001);IL-10与FEV1%pred、FEV1/FVC、PaO2显著正相关(分别r=0.653、0.631、0.656,P<0.001),与PaCO2显著负相关(r=-0.543,P<0.001)。结论 IL-8、IL-10参与了高原AECOPD合并CCP患者的气道炎症过程,ICS可降低气道内IL-8水平、升高IL-10水平,ICS联合LABA治疗高原AECOPD合并CCP的疗效优于单一ICS。

Objective To assess the relationship between induced sputum interleukin-8 （IL-8） and interleukin -10 （IL-10） level with pathogenesis in patients with acute exacerbation of chronic obstructive pulmonary disease （ AECOPD ） complicated chronic eor pulmonale （ CCP ） at high altitude, and to evaluate the intervention effects of inhaled eorticosteroid （ICS） and β2-adrenoceptor agonist in this disease. Methods β2 patients with AECOPD complicated CCP were randomly divided into three groups with 44 cases in each. Three groups received routine treatment （anti-infection, expectorant, aminophylline ）. The treatment 2 group received ICS and LABA 50 μg/250 μg, airway inhalation, two times daily. The treatment 1 group received budesonide 1 rag, spray inhalation, two times daily. The control group received routine treatment. Levels of induced sputum IL-8, IL-10, FEV1% pred, FEV1/FVC, PaO2, and PaCO2 were examined on admission and 2 weeks after treatment stable stage. Induced sputum IL-8, IL-10, FEV1% pred, FEV1/FVC, PaO2, and PaCO2 after treatment in these groups were compared. Results Before treatment, level of induced sputum IL-8, IL-10, FEV1% pred, FEV1/FVC, PaO2, and PaCO2 among three groups were no statistical significance （ all P 〉 0. 05 ）. After treatment, induced sputum IL-8 and PaCO2 decreased significantly, induced sputum IL-10, FEV1% pred, FEV1/FVC, and PaO2 increased significantly in three groups compared to before treatment （ all P 〈 0.01 ）. After treatment, these parameter among three groups were significant difference （P 〈 0.01 or P 〈 0.05 ）. Before treatment, level of induced sputum IL-8 was negatively correlated with FEV1% pred, FEV1/ FVC ,PaO2 （ r = - 0. 714, - 0. 597, - 0. 682, respectively, all P 〈 0. 001 ）, positively correlated with PaCO2 （ r = 0. 662, P 〈 0. 001 ） ; level of induced sputum IL-8 are positively correlated with FEV1%pred, FEV1/FVC, PaO2 （r = 0. 653, 0. 631, 0. 656, respectively, all P 〈 0. 001 ） , negatively correlated with PaCO2 （ r = 0. 543, P 〈 0. 001 ） in β2 cases. Conclusions IL-8 and IL- 10 are involved in the airway inflammation of AECOPD. Treatmen with ICS is a method to decrease the local expression of IL-8 and increase the local expression of IL-10, but combination with ICS and LABA in AECOPD complicated CCP has better effects than single ICS at high altitude.