慢性阻塞性肺疾病患者痰中TNF-α及其受体水平与气流受限的关系

Change of Induced Sputum TNF-α and Its Receptors Levels in Patients with Acute Exacerbations of COPD

【目的】观察慢性阻塞性肺疾病急性加重期(AECOPD)患者治疗前后气道内炎性介质与抗炎介质水平变化,阐明COPD气道局部炎症与气流受限的关系。【方法】检测48例COPD急性加重期患者入院时(A1组)及治疗1周后(A2组)诱导痰肿瘤坏死因子α(TNF-α)和可溶性肿瘤坏死因子受体55、75(sTNF-R55、sTNF-R75)的水平并进行肺功能测定。以28例健康志愿者(吸烟者,B1组;不吸烟者,B2组)为对照组进行分析治疗前后炎症因子及肺功能变化。【结果】AECOPD治疗前后诱导痰中TNF-α和sTNF-R55、sTNFR75的水平均高于健康组(P<0.01)。治疗后诱导痰中TNF-α浓度较入院时明显下降[A2组(478±266)pg/mLvsA1组(820±343)pg/mL,P<0.001];sTNF-R55浓度明显上升[A2(4.0±1.9)ng/mLvsA1(3.4±1.4)ng/mL,P<0.05),sTNFR75水平亦有所升高。AECOPD患者TNF-α浓度与FEV1、FEV1%pre呈负相关(rTNF-α分别-0.524、-0.490,P<0.01),而sTNF-R55和sTNF-R75水平均与FEV1、FEV1%pre、FEV1/FVC呈正相关(rsTNF-R55分别为0.547、0.312、0.220,P<0.001;rsTNF-R75分别为0.626、0.436、0.273,P<0.01)。对照组吸烟者TNF-α水平高于不吸烟者,且B1、B2组各细胞因子水平与肺功能无明显相关性。【结论】AECOPD患者气道内存在炎性介质与抗炎介质失衡,治疗后sTNF-R55水平上升,TNF-α水平降低,两者重新趋于平衡。抗炎介质水平的增加可能有利于临床肺功能的改善。

[Objective] The objective of this study was to determine the changes in inflammatory and anti-inflammatory mediator levels in patients with acute exacerbations of chronic obstructive pulmonary disease （AECOPD） before and after treatment, and clarify the relationship between local airway inflammation and airway obstruction in COPD. [Methods] Lung functions and tumor necrosis factor-α （TNF-α） and soluble TNF receptor （sTNF-R55 and sTNF-R75） levels of induced sputum were examined in 48 AECOPD patients on admission （group A1） and treatment day 7 （group A2）. Twenty-eight healthy volunteers＇ samples served as controls （smokers as group B1, nonsmokers as group B2）. The relationships between the changes in mediator levels and the AECOPD patients＇ lung functions before and after treatment were analyzed. [Results] Pre-and post-treatment TNF-α, sTNF-R55, and sTNFR75 levels were higher in patients＇ sputum than in controls. TNF-α levels decreased （478 pg/mL ± 266 pg/mL vs 820 pg/mL ± 343 pg/mL in group A1, P〈0.001）; sTNF-R55 levels increased （4.0 pg/mL ± 1.9 ng/mL in group A2 vs 3.4 pg/mL ± 1.4 ng/mL in group A1, P 〈 0.05）, and sTNF-R75 levels tended to increase after treatment. TNF-α levels correlated negatively with FEV1 and FEV1%pre （rTNF-α=-0.524,-0.490 respectively, P 〈 0.01）; sTNF-R55 and sTNF-R75 levels correlated positively with FEV1, FEV1%pre, FEV1/FVC （rsTNF-R55=0.547, 0.312, 0.220 respectively, P 〈 0.001; rsTNF-R75=0.626, 0.436, 0.273, respectively, P 〈 0.01）. Among controls, smokers had higher TNF-α levels than nonsmokers but lung functions and mediator levels were unrelated in controls. [Conclusion] Inflammatory and anti-inflammatory mediators were imbalanced in AECOPD patients＇ airways. After treatment, TNF-α levels decreased, sTNF-R55 levels increased and they tended to balance again. The increase of anti-inflammatory mediators had a possibly beneficial effect with respect to lung function improvement.