Association discussion of TWEAK expression in induced sputum and asthma severity

doi:10.3877/cma.j.issn.1674-6902.2025.03.006

Abstract

Abstract:

Objective

To investigate the expression of tumor necrosis factor-like cell weak apoptosis factor （TWEAK） in induced sputum and its association with asthma severity.

Methods

A total of 50 asthma patients were recruited from March 2022 to September 2022，and induced TWEAK in sputum were determined using enzyme-linked immunosorbent assay. According to the TWEAK value，asthma patients were divided into TWEAK high expression group （≥0.70 ng/ml） and TWEAK low expression group （＜0.70 ng/ml），with 25 cases in each group. Spearman was used to analyze the correlation between TWEAK and lung function indexes，inflammation markers and M1 macrophages.

Results

The interferon （IFN）-γ in the TWEAK high expression group were significantly lower than those in the low expression group （P ＜0.05），and the percentages of interleukin （IL）-17A，CD45⁺/CD68⁺ macrophages%，M1 type （CD11c⁺/CD86⁺） macrophages % in the TWEAK high expression group were significantly higher than those in the low expression group （P＜0.05）.According to Spearman analysis，induced sputum TWEAK was significantly negatively correlated with the percentage of forced expiratory volume （FEV₁） in 1 second （r_s=-0.476），FEV₁/forced vital capacity （r_s=-0.394），and induced sputum IFN-γ （r_s=-0.346）（P＜0.05）. The induced sputum TWEAK was significantly positively correlated with tumor cell necrosis factor-α （r_s=0.315），IL-6 （r_s=0.286），IL-17A （r_s=0.320），M1 type （CD11c⁺/CD86⁺） macrophage % （r_s =0.470），neutrophil % （r_s =0.293） and peripheral blood neutrophil % （r_s=0.351）（P＜0.05）. The expression of induced sputum TWEAK in patients with a family history of allergies was significantly lower than that in patients without a family history of allergies（P＜0.05）.

Conclusion

There was a significant correlation between induced sputum TWEAK overexpression and inflammation progression and disease flare-up in asthma patients，and induced TWEAK in sputum may be a marker of asthma severity.

Key words: Tumor necrosis factor-like cell weak apoptotic factor, Bronchial asthma, Induce sputum, Asthma severity, Inflammatory cytokines

Yidan Guo, Jun Wang, Xiang Zhu, Ze Ji, Beijuan Wang. Association discussion of TWEAK expression in induced sputum and asthma severity[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(03): 375-379.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhfbjbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-6902.2025.03.006

https://zhfbjbzz.cma-cmc.com.cn/EN/Y2025/V18/I03/375

Figures/Tables 3

References 22

1	Schoettler N，Strek ME. Recent advances in severe asthma：from phenotypes to personalized Medicine［J］. Chest，2020，157（3）：516-528.
2	Gupta RK，Gracias DT，Figueroa DS，et al.TWEAK functions with TNF and IL-17 on keratinocytes and is a potential target for psoriasis therapy［J］. Sci Immunol，2021，6（65）：eabi8823.
3	陈鹿鹿，廖成成，刘建国，等. TWEAK/Fn14 信号通路在肿瘤发生发展及治疗中的作用研究进展［J］. 现代肿瘤医学，2023，31（16）：3105-3110.
4	史卫群，吕剑平，王骞，等. 哮喘患儿血浆TWEAK 浓度和外周血单个核细胞中NF-κB 活性变化及意义［J］. 江苏大学学报（医学版），2019，29（1）：82-83，86.
5	王婷，李海舰，廖明，等. 基于TWEAK/Fn14 信号通路探讨大黄酚对OVA 诱导哮喘小鼠的保护作用［J］. 天津中医药大学学报，2022，41（5）：644-648.
6	Dwyer BJ，Jarman EJ，Gogoi-Tiwari J，et al. TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression［J］. J Hepatol，2021，74（4）：860-872.
7	Wang M，Xie Z，Xu J，et al. TWEAK/Fn14 axis in respiratory diseases［J］. Clin Chim Acta，2020，509：139-148.
8	Brandsma J，Schofield JPR，Yang X，et al. Stratification of asthma by lipidomic profiling of induced sputum supernatant［J］. J Allergy Clin Immunol，2023，152（1）：117-125.
9	Chen S，Chen Z，Deng Y，et al. Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma［J］. Allergol Int，2022，71（1）：73-82.
10	Jackson DJ，Bacharier LB，Calatroni A，et al. Serum IL-6：A biomarker in childhood asthma？［J］. J Allergy Clin Immunol，2020，145（6）：1701-1704.e3.
11	Golikova EA，Lopatnikova JA，Kovalevskaya-Kucheryavenko TV，et al. Levels of TNF，TNF autoantibodies and soluble TNF receptors in patients with bronchial asthma［J］. J Asthma，2013，50（7）：705-711.
12	Niessen NM，Gibson PG，Baines KJ，et al. Sputum TNF markers are increased in neutrophilic and severe asthma and are reduced by azithromycin treatment［J］. Allergy，2021，76（7）：2090-2101.
13	Paplinska-Goryca M，Misiukiewicz-Stepien P，Proboszcz M，et al.The expressions of TSLP，IL-33，and IL-17A in monocyte derived dendritic cells from asthma and COPD patients are related to epithelial-macrophage Interactions［J］. Cells，2020，9（9）：1944.
14	刘汶睿，高丽娜，于书娴，等. 支气管哮喘患者血清IL-27 与IFN-γ 及肺功能相关性分析［J/CD］. 中华肺部疾病杂志（电子版），2023，16（2）：224-226.
15	管馨馨，张建华，雷小勇. TWEAK 及其受体Fn14 信号通路与肺部疾病的研究进展［J］. 中国医师杂志，2018，20（4）：635-638.
16	Xu H，Okamoto A，Ichikawa J，et al. TWEAK/Fn14 interaction stimulates human bronchial epithelial cells to produce IL-8 and GMCSF［J］. Biochem Biophys Res Commun，2004，318（2）：422-427.
17	Lechner A，Henkel FDR，Hartung F，et al. Macrophages acquire a TNF-dependent inflammatory memory in allergic asthma ［J］. J Allergy Clin Immunol，2022，149（6）：2078-2090.
18	苏柳杭，陈炳秀，李兆恺，等. CD163/TWEAK 通路对动脉粥样硬化的作用［J］. 中国病理生理杂志，2019，35（4）：679-685.
19	Chen F，Yu M，Zhong Y，et al. The role of neutrophils in asthma［J］. Zhejiang Da Xue Xue Bao Medical Science，2021，50（1）：123-130.
20	Nabe T. Steroid-resistant asthma and neutrophils［J］. Biol Pharm Bull，2020，43（1）：31-35.
21	Kim SY，Kim JD，Sol IS，et al. Sputum TWEAK expression correlates with severity and degree of control in non-eosinophilic childhood asthma［J］. Pediatr Allergy Immunol，2018，29（1）：42-49.
22	Wang Y，Gu LF，Zhao X，et al.TFR1 expression in induced sputum is associated with asthma severity［J］. PeerJ，2022，10：e13474.

临床资料	高表达组 (n=25 例)	低表达组 (n=25 例)	t/Z/χ²	P 值
白细胞计数 [×10⁹/L,(x̄ ± s)]	6.66±1.84	6.36±1.72	0.583	0.563
中性粒细胞 [%,(x̄ ± s)]	50.17±17.15	51.38±11.92	-0.283	0.779
嗜酸性粒细胞 [%,M₅₀(P₂₅,P>₇₅]	3.80 (1.80,7.0)	3.50 (1.83,5.90)	-0.341	0.733
诱导痰分类计数
中性粒细胞 [%,(x̄ ± s)]	60.93±21.59	64.35±20.78	-0.502	0.618
嗜酸性粒细胞 [%,M₅₀(P₂₅,P>₇₅]	5.63 (2.88,15.30)	3.75 (2.80,10.87)	-0.689	0.491
肺功能指数
FEV1% pred [%,(x̄ ± s)]	91.84 (82.50, 103.83)	103.69 (97.12, 108.84)	-1.310	0.190
FEV1% pred [%,(x̄ ± s)]	78.31 (67.69, 101.33)	97.76 (91.90, 103.83)	-1.892	0.059
FEV₁/FVC [%,(x̄ ± s)]	80.84 (70.52, 87.95)	84.16 (80.02, 88.71)	-1.581	0.114
INOS[pg/ml, M₅₀(P₂₅,P>₇₅]	0.22 (0.05,1.00)	0.19 (0.02,0.47)	-0.878	0.380
TNF-α[pg/ml, M₅₀(P₂₅,P>₇₅]	3.03 (1.27,18.53)	1.87 (0.76,3.69)	-1.746	0.081
IL-6[pg/ml, M₅₀(P₂₅,P>₇₅]	3.19 (1.66,14.78)	3.18 (1.22,9.10)	-0.611	0.541
IFN-γ[pg/ml, M₅₀(P₂₅,P>₇₅]	0.80 (0.24,2.07)	3.07 (0.61,17.31)	-2.445	0.014
IL-17A[pg/ml, M₅₀(P₂₅,P>₇₅]	0.35 (0.07,1.22)	0.11 (0.03,0.23)	-2.726	0.006
IL-1β[pg/ml, M₅₀(P₂₅,P>₇₅]	3.19 (1.53,9.86)	2.28 (0.78,7.40)	-1.116	0.265
CD45⁺/CD68⁺ 巨噬细胞 [%,M₅₀(P₂₅,P>₇₅]	5.98 (3.36,8.02)	3.03 (1.60,5.75)	-2.280	0.023
M1 型(CD11c⁺/CD86⁺)巨噬细胞 [%,M₅₀(P₂₅,P>₇₅]	5.44 (1.59,8.44)	2.45 (1.52,4.47)	-2.493	0.013

临床资料	高表达组 (n=25 例)	低表达组 (n=25 例)	t/Z/χ²	P 值
白细胞计数 [×10⁹/L,(x̄ ± s)]	6.66±1.84	6.36±1.72	0.583	0.563
中性粒细胞 [%,(x̄ ± s)]	50.17±17.15	51.38±11.92	-0.283	0.779
嗜酸性粒细胞 [%,M₅₀(P₂₅,P>₇₅]	3.80 (1.80,7.0)	3.50 (1.83,5.90)	-0.341	0.733
诱导痰分类计数
中性粒细胞 [%,(x̄ ± s)]	60.93±21.59	64.35±20.78	-0.502	0.618
嗜酸性粒细胞 [%,M₅₀(P₂₅,P>₇₅]	5.63 (2.88,15.30)	3.75 (2.80,10.87)	-0.689	0.491
肺功能指数
FEV1% pred [%,(x̄ ± s)]	91.84 (82.50, 103.83)	103.69 (97.12, 108.84)	-1.310	0.190
FEV1% pred [%,(x̄ ± s)]	78.31 (67.69, 101.33)	97.76 (91.90, 103.83)	-1.892	0.059
FEV₁/FVC [%,(x̄ ± s)]	80.84 (70.52, 87.95)	84.16 (80.02, 88.71)	-1.581	0.114
INOS[pg/ml, M₅₀(P₂₅,P>₇₅]	0.22 (0.05,1.00)	0.19 (0.02,0.47)	-0.878	0.380
TNF-α[pg/ml, M₅₀(P₂₅,P>₇₅]	3.03 (1.27,18.53)	1.87 (0.76,3.69)	-1.746	0.081
IL-6[pg/ml, M₅₀(P₂₅,P>₇₅]	3.19 (1.66,14.78)	3.18 (1.22,9.10)	-0.611	0.541
IFN-γ[pg/ml, M₅₀(P₂₅,P>₇₅]	0.80 (0.24,2.07)	3.07 (0.61,17.31)	-2.445	0.014
IL-17A[pg/ml, M₅₀(P₂₅,P>₇₅]	0.35 (0.07,1.22)	0.11 (0.03,0.23)	-2.726	0.006
IL-1β[pg/ml, M₅₀(P₂₅,P>₇₅]	3.19 (1.53,9.86)	2.28 (0.78,7.40)	-1.116	0.265
CD45⁺/CD68⁺ 巨噬细胞 [%,M₅₀(P₂₅,P>₇₅]	5.98 (3.36,8.02)	3.03 (1.60,5.75)	-2.280	0.023
M1 型(CD11c⁺/CD86⁺)巨噬细胞 [%,M₅₀(P₂₅,P>₇₅]	5.44 (1.59,8.44)	2.45 (1.52,4.47)	-2.493	0.013

变量		例数	诱导痰 TWEAK 表达	Z/H	P 值
性别	男	21	0.76(0.49,2.91)	-0.796	0.426
	女	29	0.69(0.38,1.68)	-0.796	0.426
幼儿哮喘病史	是	14	0.56(0.18,1.67)	-1.394	0.163
	否	36	0.73(0.46,2.56)	-1.394	0.163
过敏性鼻炎	是	20	0.77(0.43,3.00)	-0.931	0.352
	否	30	0.69(0.36,1.67)	-0.931	0.352
过敏史	是	20	0.31(0.13,0.60)	-1.426	0.154
	否	30	0.47(0.17,0.84)	-1.426	0.154
过敏家族史	是	17	0.38(0.15,0.87)	-2.898	0.004
	否	33	0.92(0.51,2.91)	-2.898	0.004
吸烟史	是	21	0.68(0.33,1.84)	-0.049	0.961
	否	29	0.70(0.42,1.75)	-0.049	0.961
ACT 评分	25 分	3	0.61(1.84,2.45)	1.118	0.572
	20~24 分	7	0.76(0.17,3.71)
	<20 分	40	0.69(0.38,1.20)

变量		例数	诱导痰 TWEAK 表达	Z/H	P 值
性别	男	21	0.76(0.49,2.91)	-0.796	0.426
	女	29	0.69(0.38,1.68)	-0.796	0.426
幼儿哮喘病史	是	14	0.56(0.18,1.67)	-1.394	0.163
	否	36	0.73(0.46,2.56)	-1.394	0.163
过敏性鼻炎	是	20	0.77(0.43,3.00)	-0.931	0.352
	否	30	0.69(0.36,1.67)	-0.931	0.352
过敏史	是	20	0.31(0.13,0.60)	-1.426	0.154
	否	30	0.47(0.17,0.84)	-1.426	0.154
过敏家族史	是	17	0.38(0.15,0.87)	-2.898	0.004
	否	33	0.92(0.51,2.91)	-2.898	0.004
吸烟史	是	21	0.68(0.33,1.84)	-0.049	0.961
	否	29	0.70(0.42,1.75)	-0.049	0.961
ACT 评分	25 分	3	0.61(1.84,2.45)	1.118	0.572
	20~24 分	7	0.76(0.17,3.71)
	<20 分	40	0.69(0.38,1.20)

[1]	Yuanyuan Han, Sabeiti Reziya, Zhijie Mao, Aierken Mufunayi, Chen Lu, Xiaohong Sang, Mulati Aerman, Li Zhang. Effect of combined blood purification on serum inflammatory cytokines levels and clinical prognosis in patients with sepsis [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(04): 272-278.
[2]	Ying Liu, Qun Li, Wenjing Chang, Yunhui Zheng, Xuefeng Zang. Clinical analysis of pathogenic bacteria distribution characteristics and changes of cardiac function and inflammatory factors in elderly patients with severe septic shock [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2021, 16(01): 59-63.
[3]	Wei Fan, Yufu Wang, Xinlong Zhang. Effects of low-dose sevoflurane and oxycodone on anesthesia in laparoscopic inguinal hernia repair [J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2022, 16(04): 443-446.
[4]	Jing Bao, Xia Wu, Yaping Tian, Gang Yin. Effects of vitamin D₃ combined with Montelukast sodium on serum VEGF, TGF-β1 and lung function in patients with bronchial asthma [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(01): 63-67.
[5]	Lingfang Tan, Kebing Zhou. Identification of biomarkers associated with diagnosis of bronchial asthma based on integrated bioinformatics analysis [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(03): 329-334.
[6]	Chao Zhang, Xiaozhe Yue. Association of eosinophils, total IgE with severity and lung function in children with asthma [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(02): 183-186.
[7]	Mengqing Shen, Ting Wu, Fei Wang. Effects of budesonide combined with specific immunotherapy on the levels of 1, 25-dihydroxyvitamin D3, IL-6 and IL-10 in children with bronchial asthma [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2021, 14(01): 43-47.
[8]	Cui Zhai, Yang Song, Xiaofan Su, Qingting Wang, Wenhua Shi, Manxiang Li. Determinants of treatment compliance for inhaled glucocorticoids in asthma patients [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(03): 302-306.
[9]	Yueyan Lou, Yu Zheng, Liyan Zhang, Feng Zhu, Xueling Wu. Clinical significance of fractional exhaled nitric oxide in asthma patients [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(03): 297-301.
[10]	Chunxiao Shang, Naqi Li. Research progress on the role of interleukin-11 in chronic kidney disease [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2022, 11(03): 156-160.
[11]	Ke Shang, Yikui Wang, Bei Liu, Wei Liu. Mini-plate internal fixation for treatment of Lisfranc joint injury: Efficacy and postoperative joint function recovery [J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(12): 989-994.
[12]	Yisireyili Maimaiti, Qiang Yin, Hailong Yin, Zhijian Li, Yuwei Dong, Yongkang Wang, Abudureyimu Kelimu, Aisa Ajiaikebaier. The mechanism of Luo Le Wei Mi Gao inhibited acid induced esophageal epithelial cell inflammation [J]. Chinese Journal of Gastroesophageal Reflux Disease(Electronic Edition), 2024, 11(03): 137-142.
[13]	Shuqin Hu, Hongyan Xu, Dan Cao, Yayan Ding. Effect of quality control circle and interactive health education on FeNO and disease control in children with severe bronchial asthma [J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2025, 11(01): 10-15.
[14]	Hang Men, Zhou Li, Shuai Han. Advances in obesity and type 2 diabetes mellitus research [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 62-69.
[15]	Zekai Zhou, Baoyin Liu, Yuntao Nie, Hua Meng. Research progress in the effects of obesity on lung function [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2024, 10(01): 58-65.

Please choose a citation manager

Content to export