Expression Levels of TNF-α，sTNFR-55 and sTNFR-75 in Induced Sputum and Serum of AECOPD Patients and Their Clinical Significance
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摘要:
目的 探讨AECOPD患者诱导痰及血清中TNF-α、sTNFR-55、sTNFR-75表达水平及其临床意义。 方法 2019年1月至2020年12月住院的AECOPD患者40例，比较治疗前（Ⅰ组）和治疗后（Ⅱ组）诱导痰和血清中TNF-α、sTNFR-55、sTNFR-75表达水平及与病情严重程度的相关性分析，同时进行诱导痰和血清中3种炎症介质相关性分析。根据是否戒烟，分为戒烟组（Ⅲ组）和吸烟组（Ⅳ组），比较分析戒烟后TNF-α、sTNFR-55、sTNFR-75水平变化。 结果 （1）治疗后诱导痰和血清TNF-α水平下降（P < 0.05），诱导痰sTNFR-55水平升高（t = 3.044，P = 0.004）；（2）FEV1、FEV1%pred、FEV1/FVC与诱导痰TNF-α水平均呈负相关（r分别为-0.827、-0.865、-0.868，P < 0.001），与诱导痰sTNFR水平均呈正相关（rsTNFR-55分别为0.415、0.330、0.305，P < 0.05；rsTNFR-75分别为0.903、0.969、0.965，P < 0.001）；（3）APACHE-II评分与诱导痰TNF-α水平呈正相关（r = 0.374，P = 0.001），与诱导痰sTNFR-55、sTNFR-75水平均呈负相关（r分别为-0.227、-0.341，P < 0.05）；（4）TNF-α、sTNFR-55、sTNFR-75水平在诱导痰和血清之间未发现相关性，其在血清中的水平与肺功能指标、APACHE-II评分并不相关（P > 0.05）；（5）与吸烟组相关比，戒烟组诱导痰中TNF-α水平偏低（Z = -2.626，P = 0.008），而诱导痰sTNFR-55、sTNFR-75水平偏高（t = 2.716，P = 0.01；Z = -2.696，P = 0.006）。 结论 诱导痰中TNF-α、sTNFR-55、sTNFR-75水平可用于评估AECOPD患者疗效及病情严重程度，AECOPD患者全身及气道炎症未发现相关性，戒烟后气道炎症可能仍在进展。 -
关键词:
- 慢性阻塞性肺疾病 /
- 肿瘤坏死因子α /
- 可溶性肿瘤坏死因子受体 /
- 诱导痰
Abstract:Objective To investigate the different expression levels of TNF-α, sTNFR-55 and sTNFR-75 in the induced sputum and serum of AECOPD patients and their clinical significance. Methods Forty AECOPD patients were enrolled and hospitalized during January 2019 and December 2020. All subjects received the conventional therapy. The expression levels of TNF-α, sTNFR-55 and sTNFR-75 in the induced sputum and serum before the treatment （group Ⅰ） and after the treatment （group Ⅱ） were compared and their correlation with the severity of the disease was analyzed. Meanwhile, the correlation between three inflammatory mediators in the induced sputum and serum was analyzed. According to the smoking history, they were divided into smoking cessation group （group Ⅲ） and smoking group （group Ⅳ）. The changes of TNF-α, sTNFR-55 and sTNFR-75 levels after quitting smoking were also compared and analyzed. Results （1） After the treatment, the levels of TNF-α in sputum and serum decreased significantly （P < 0.05）, while the levels of sTNFR-55 in sputum increased （t = 3.044, P = 0.004）, and the levels of sTNFR-55 and sTNFR-75 in serum showed no significant difference （P > 0.05）. （2） FEV1, FEV1%pred, FEV1/FVC were negatively correlated with the level of TNF-α in sputum （r was -0.827, -0.865, -0.868, respectively, P < 0.001）, and positively correlated with the level of sTNFR in sputum （rsTNFR-55 was 0.415, 0.330 and 0.305, respectively, P < 0.05; rsTNFR-75 was 0.903, 0.969 and 0.965, respectively, P < 0.001）. （3） APACHEIII score was positively correlated with the level of TNF-α in sputum （r = 0.374, P = 0.001）, and negatively correlated with the level of sTNFR level （r was -0.227, -0.341, respectively, P < 0.05）. （4） There was no correlation between TNF-α/sTNFR levels in the induced sputum and serum （P > 0.05）, and its level in serum had no correlation with lung function index and APACHEII score （P > 0.05）. （5） Compared with the smoking group, the TNF-α level in the induced sputum of the smoking cessation group was lower （Z = -2.626, P = 0.008）, while the sTNFR-55 and sTNFR-75 levels in the induced sputum were higher （t = 2.716, P = 0.01; Z = -2.696, P = 0.006）. Conclusion The levels of TNF-α, sTNFR-55 and sTNFR-75 in the induced sputum can be used to evaluate the efficacy and severity of AECOPD patients. No correlation has been found between systemic and airway inflammation in AECOPD patients, and airway inflammation may still progress after smoking cessation. -
表 1 各组一般情况比较（
$ \bar x \pm s $ ）Table 1. The general situation of each group is compared （
$ \bar x \pm s $ ）组别 n 年龄（岁） BMI（kg/m2） 吸烟指数 FEV1（L） FEV1%pred FEV1/
FVC（%）PaO2
（mmHg）PaCO2
（mmHg）APACHE-II
评分Ⅰ组 40 72.43 ± 8.51 20.29 ± 2.04 563.00 ± 308.85 0.98 ± 0.32 42.83 ± 11.94 44.68 ± 8.69 56.75 ± 3.07 39.00 ± 2.86 34.00 ± 6.03 Ⅱ组 40 72.43 ± 8.51 20.29 ± 2.04 563.00 ± 308.85 1.00 ± 0.30 44.22 ± 11.57 46.26 ± 8.31 61.28 ± 3.16 38.85 ± 3.65 31.45 ± 6.05 t − − − 2.713 2.997 3.166 11.785 0.256 7.727 P − − − 0.010* 0.005* 0.003* < 0.001* 0.799 < 0.001* Ⅲ组 25 72.72 ± 9.12 20.11 ± 1.95 560.80 ± 320.91 1.09 ± 0.27 46.62 ± 10.62 47.35 ± 7.45 56.40 ± 3.16 39.08 ± 2.81 34.24 ± 6.69 Ⅳ组 15 71.93 ± 7.68 20.20 ± 2.76 566.67 ± 298.61 0.79 ± 0.32 36.50 ± 11.64 40.23 ± 9.02 57.33 ± 2.92 38.87 ± 3.02 33.60 ± 4.93 t 0.280 −0.121 −0.057 3.078 2.816 2.706 −0.929 0.226 0.321 P 0.781 0.904 0.955 0.004* 0.008* 0.010* 0.359 0.822 0.750 *P < 0.05。 
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表 2 治疗后TNF-α、sTNFR-55、sTNFR-75水平的变化[（
$ \bar x \pm s $ ），pg/mL]Table 2. Changes of TNF-α，sTNFR-55 and sTNFR-75 levels after treatment [（
$ \bar x \pm s $ ），pg/mL]组别 血清 诱导痰 TNF-α sTNFR-55 sTNFR-75 TNF-α sTNFR-55 sTNFR-75 Ⅰ组 72.47 ± 8.57 1088.89 ± 240.54 1531.50 ± 323.48 75.86 ± 14.99 873.00 ± 183.96 1581.67 ± 351.72 Ⅱ组 71.07 ± 9.31 1097.99 ± 250.55 1540.07 ± 325.04 73.00 ± 14.95 932.00 ± 204.02 1591.17 ± 348.28 t 2.348 1.859 1.762 2.191 3.044 1.920 P 0.024* 0.071 0.086 0.035* 0.004* 0.062 *P < 0.05。
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表 3 戒烟后诱导痰和血清中TNF-α、sTNFR-55、sTNFR-75的变化[
$ \bar x \pm s $ /M（P25，P75）]Table 3. The changes of TNF-α，sTNFR-55 and sTNFR-75 in sputum and serum were induced after smoking cessation [
$ \bar x \pm s $ /M（P25，P75）]分组 AECOPD Z/t P Ⅲ戒烟组（n = 25） Ⅳ目前吸烟组（n = 15） 痰上清 TNF-α（pg/mL） 77.60（59.48，80.77） 85.99（76.95，95.47） −2.626 0.008* STNFR-55（pg/mL） 929.73 ± 181.12 778.47 ± 150.71 2.716 0.010* sTNFR-75（pg/mL） 1679.56（1476.90，2000.26） 1283.44（1021.31，1675.90） −2.696 0.006* 血清 TNF-α（pg/mL） 72.32 ± 9.06 72.73 ± 8.00 −0.145 0.885 sTNFR-55（pg/mL） 1046.38 ± 243.01 1159.74 ± 226.59 −1.464 0.151 sTNFR-75（pg/mL） 1531.13 ± 296.11 1532.11 ± 375.74 −0.009 0.993 *P < 0.05。
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表 4 TNF-α、sTNFR-55、sTNFR-75水平与肺功能、APACHE-II评分的相关性分析（r/rs）
Table 4. Correlation analysis of TNF-α，sTNFR-55，sTNFR-75 levels with lung function and APACHE-II score （r/rS）
指标 诱导痰 血清 TNF-α sTNFR-55 sTNFR-75 TNF-α sTNFR-55 sTNFR-75 FEV1 −0.827* 0.415* 0.903* 0.166 0.086 −0.016 FEV1%pred −0.865* 0.330* 0.969* 0.149 0.092 −0.059 FEV1%FVC −0.868* 0.305* 0.965* 0.162 0.101 −0.069 APACHE-II评分 0.374* −0.227* −0.341* −0.160 −0.082 −0.083 *P < 0.05。
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表 5 诱导痰与血清中TNF-α、sTNFR-55、sTNFR-75水平相关性分析
Table 5. Correlation analysis between induced sputum and serum levels of TNF-α，sTNFR-55 and sTNFR-75
诱导痰与血清 AECOPD rs P TNF-α −0.160 0.156 sTNFR-55 −0.004 0.972 sTNFR-75 −0.080 0.480
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[1] 中华医学会呼吸病学分会慢性阻塞性肺疾病学组,中国医师协会呼吸医师分会慢性阻塞性肺疾病工作委员会. 慢性阻塞性肺疾病诊治指南(2021年修订版)[J]. 中华结核和呼吸杂志,2021,44(3):170-205. doi: 10.3760/cma.j.cn112147-20210109-00031 [2] 蔡柏蔷,陈荣昌. 慢性阻塞性肺疾病急性加重(AECOPD)诊治中国专家共识(2017年更新版)[J]. 国际呼吸杂志,2017,37(14):1041-1057. doi: 10.3760/cma.j.issn.1673-436X.2017.14.001 [3] 中华医学会呼吸病学分会哮喘学组. 咳嗽的诊断与治疗指南(2021)[J]. 中华结核和呼吸杂志,2022,45(1):13-46. doi: 10.3760/cma.j.cn112147-20211101-00759 [4] Dragonieri S,Lacedonia D,Scioscia G,et al. Assessment of induced sputum cellularity in COPD patients belonging to two different classes of air pollution exposure[J]. Arch Bronconeumol (Engl Ed),2020,56(4):214-217. [5] Ditz B,Kistemaker L E M,Van den Berge M,et al. Responsivity and reproducibility of sputum inflammatory biomarkers during COPD exacerbation and stable phases - A pilot study[J]. Int J Chron Obstruct Pulmon Dis,2021,10(16):3055-3064. [6] Dentener M A,Creutzberg E C,Schols A M,et al. Systemic anti-inflammatory mediators in COPD: Increase in soluble interleukin 1 receptor II during treatment of exacerbations[J]. Thorax,2001,56(9):721-726. doi: 10.1136/thx.56.9.721 [7] Lage V K S,Lacerda A C R,Neves C D C,et al. Acute effects of whole-body vibration on inflammatory markers in people with chronic obstructive pulmonary disease: A pilot study[J]. Rehabilitation Research and Practice,2018,7(2):.5480214. [8] Zeng M,Wen Y,Liu LY,et al. Role of TNF-α,sTNF-R55 and sTNF-R75 in inflammation of acute exacerbations of chronic obstructive pulmonary disease[J]. Respiration,2009,78(4):399-403. doi: 10.1159/000210263 [9] Vernooy J H,Küçükaycan M,Jacobs J A,et al. Local and systemic inflammation in patients with chronic obstructive pulmonary disease: Soluble tumor necrosis factor receptors are increased in sputum[J]. Am J Respir Crit Care Med,2002,166(9):1218-1224. doi: 10.1164/rccm.2202023 [10] 李现东,韩纪昌,李磊,等. 肿瘤坏死因子-α和可溶性肿瘤坏死因子受体在慢性阻塞性肺病患者肺功能变化中的表达及意义[J]. 中国老年学杂志,2014,34(2):357-358. doi: 10.3969/j.issn.1005-9202.2014.02.035 [11] Sapey E,Ahmad A,Bayley D,et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. Journal of Clinical Immunology,2009,29(4):508-516. doi: 10.1007/s10875-009-9286-8 [12] Eklund C M. Proinflammatory cytokines in CRP baseline regulation[J]. Advances in Clinical Chemistry,2009,48(9):111-136. [13] 蒋雪莲,胡旭,钟萍,等. 慢性阻塞性肺疾病患者持续性系统性炎症的前瞻性研究[J]. 中国呼吸与危重监护杂志,2020,19(6):536-542. [14] Willemse B W,Ten H N,Rutgers B,et al. Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers[J]. European Respiratory Journal,2005,26(5):835-845. doi: 10.1183/09031936.05.00108904 [15] De Cunto G,Bartalesi B,Cavarra E,et al. Ongoing lung inflammation and disease progression in mice after smoking cessation:Beneficial effects of formyl-peptide receptor blockade[J]. The American Journal of Pathology,2018,188(10):2195-2206. doi: 10.1016/j.ajpath.2018.06.010 [16] Yoon Y J,Lee M S,Jang K W,et al. Association between smoking cessation and obstructive spirometry pattern among Korean adults aged 40–79 years[J]. Scientific Reports,2021,11(1):1-8. doi: 10.1038/s41598-020-79139-8 -
