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慢性阻塞性肺疾病肺气肿表型的气道炎症观察

摘要

目的 探讨慢性阻塞性肺疾病(COPD)肺气肿表型的气道炎症特征.方法 研究对象为我院呼吸科门诊52例COPD稳定期患者.全部患者均接受肺功能及支气管舒张试验、胸部HRCT及诱导痰检查.根据肺功能成像肺气肿指数分为2组:肺气肿组(n =29)和无肺气肿组(n=23).对两组患者临床资料、肺功能、痰炎症细胞计数以及上清液白介素6(IL-6)、IL-8、肿瘤坏死因子α(TNF-α)、血管内皮生长因子(VEGF)、基质金属蛋白酶9(MMP-9)和基质金属蛋白酶组织抑制剂1(TIMP-1)等细胞因子和炎症介质水平进行组间对比分析.对肺气肿程度与气道炎症细胞和细胞因子水平进行相关分析.结果 两组间性别、年龄、体质量指数、咳喘病史、吸烟史差异均无统计学意义(P>0.05).肺气肿组FEV1%pred、DLCO% pred、DLCO/VA% pred较无肺气肿组明显降低[(48.21±13.44)%与(57.04±12.61)%,P=0.019;(48.57±16.76)%与(65.64±12.48)%,P=0.001;(59.52±15.33)%与(82.99±16.31)%,P<0.001],而RV/TLC及RV% pred较无肺气肿组明显增高[(53.86±10.9)%与(44.93±6.72)%,P=0.003;(129.95±18.88)%与(118.77±13.16)%,P=0.037].肺气肿组痰嗜酸粒细胞计数及百分比较无肺气肿组升高[0.05(0.00,0.13)×109/L与0.00(0.00,0.01)×109/L,P =0.032;0.50(0.00,2.00)%与0.00(0.00,0.25)%,P=0.033];且痰嗜酸粒细胞百分比与肺气肿指数呈正相关(B=1.248,P=0.007).两组间痰中性粒细胞、淋巴细胞、巨噬细胞计数及百分比差异均无统计学意义(P>0.05).肺气肿组TNF-α浓度较无肺气肿组有增高趋势[221.72(100.00,351.57) ng/L与144.85(54.51,269.16) ng/L,P=0.063].两组间IL-8、IL-6、VEGF、MMP-9、TIMP-1水平及MMP-9/TIMP 1比值差异均无统计学意义(P>0.05).结论 本组COPD病例中肺气肿表型诱导痰嗜酸粒细胞及TNF-α水平有增高趋势,嗜酸粒细胞与肺气肿指数存在相关性,提示COPD肺气肿表型的气道炎症可能存在其特征性,值得进一步研究证实.%Objective To evaluate the characteristics of airway inflammation in patients with the emphysema phenotype of chronic obstructive pulmonary disease (COPD).Methods Fifty-two outpatients with stable COPD were examined.For each subject,the clinical data were collected,and HRCT scanning and lung function tests were performed.Sputum cells were counted and the supernants were processed for measurement of IL-6,IL-8,TNF-α,VEGF,MMP-9 and TIMP-1.The subjects were divided into 2 groups:an emphysema group (n =29) and a non-emphysema group (n =23) based on the HRCT emphysema index (EI).Results There was no difference between the 2 groups in sex,age,body mass index,time course of cough and wheeze,and smoking (all P >0.05).FEV1 %pred,DLCO%pred,and DLCO/VA% pred were significantly decreased in the emphysema group as compared to the nonemphysema group [(48.21± 13.44)% vs (57.04± 12.61)%,P =0.019; (48.57± 16.76)% vs (65.64±12.48)%,P=0.001;(59.52±15.33)% vs (82.99±16.31) %,P<0.001],but RV/TLC and RV%pred were significantly increased in the emphysema group [(53.86± 10.98)% vs (44.93 ±6.72)%,P =0.003;(129.95±18.88)% vs (118.77±13.16)%,P =0.037].The number and the percentage of sputum eosinophils were higher in the emphysema group [0.05 (0.00,0.13) × 109/L vs 0.00(0.00,0.01) × 109/L,P =0.032;0.50(0.00,2.00)% vs 0.00(0.00,0.25)%,P =0.033].Moreover,the percentage of sputum eosinophils was positively correlated with emphysema index (B =1.248,P =0.007).However,there was no difference between the 2 groups in the number or percentage of sputum neutrophils,lymphocytes and macrophages.The sputum level of TNF-αtended to be higher in the emphysema group as compared to the non emphysema group [221.72(100.00,351.57) ng/L vs 144.85(54.51,269.16) ng/L,P =0.063],but the levels of IL-8,IL-6,VEGF,MMP-9,TIMP-1 and the ratio of MMP 9/TIMP-1 were not different between groups.Conclusions Patients with the emphysema phenotype of COPD in this study tended to have higher airway eosinophils and TNF-α,suggesting a differenct inflammatory profile which needed to be further explored.

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