AECOPD患者诱导痰和血清中TNF-α、sTNFR-55、sTNFR-75表达水平及其临床意义

马青松; 赵芝焕; 马丽容; 李玮璟; 刘凌

doi:10.12259/j.issn.2095-610X.S20230112

AECOPD患者诱导痰和血清中TNF-α、sTNFR-55、sTNFR-75表达水平及其临床意义

doi: 10.12259/j.issn.2095-610X.S20230112

昆明医科大学第一附属医院呼吸与危重医学二科，云南昆明　650032

基金项目: 云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目[2019FE001（-198）]

详细信息

作者简介:
马青松（1995～），女，云南曲靖人，医学硕士，住院医师，主要从事呼吸系统疾病研究工作

通讯作者:
刘凌，E-mail：liuling7744@126.com

中图分类号: R563.9
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出版历程
- 收稿日期: 2022-11-14
- 网络出版日期: 2022-12-23
- 刊出日期: 2023-01-18

Expression Levels of TNF-α，sTNFR-55 and sTNFR-75 in Induced Sputum and Serum of AECOPD Patients and Their Clinical Significance

Dept. of Respiratory Critical Care Medicine，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

摘要

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（r_sTNFR-55分别为0.415、0.330、0.305，P < 0.05；r_sTNFR-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。
- 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 （r_sTNFR-55 was 0.415, 0.330 and 0.305, respectively, P < 0.05; r_sTNFR-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.
- Chronic obstructive pulmonary disease /
- Tumor necrosis factor-α /
- Soluble tumor necrosis factor receptor /
- Induced sputum

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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
组别	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
分组	Ⅲ戒烟组（n = 25）	Ⅳ目前吸烟组（n = 15）	Z/t	P
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/r_s）

Table 4. Correlation analysis of TNF-α，sTNFR-55，sTNFR-75 levels with lung function and APACHE-II score （r/r_S）

指标	诱导痰			血清
指标	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
诱导痰与血清	r_s	P
TNF-α	−0.160	0.156
sTNFR-55	−0.004	0.972
sTNFR-75	−0.080	0.480

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