肺癌合并肺栓塞危险因素的Meta分析

doi:10.3969/j.issn.1004-583X.2021.12.001

摘要/Abstract

摘要：

目的系统评价肺癌合并肺栓塞的相关危险因素。方法计算机检索PubMed、Embase、中国知网、万方等数据库,收集有关肺癌合并肺栓塞危险因素的文献,检索时限均为建库至2021年1月。由2名研究人员独立进行文献筛选、资料提取以及文献质量评价,并采用RevMan5.4软件和Stata16.0软件对纳入的数据进行Meta分析。结果共纳入25项研究,共3 480例。Meta分析研究结果显示,肺癌患者发生肺栓塞的危险因素包括腺癌(OR =2.06, 95% CI:1.75~2.44, P <0.01)、肿瘤分期(Ⅲ~Ⅳ期)( OR =2.67, 95% CI:2.19~3.26, P <0.01)、化疗(OR =2.69, 95% CI:2.08~3.47, P <0.01)、深静脉置管(OR =2.66, 95% CI:1.68~4.19, P <0.01)、白蛋白<30 g/L(OR =6.65, 95% CI:2.91~15.18, P <0.01)、D二聚体>500 mg/L(OR =5.87, 95% CI:2.12~16.27, P <0.01)、白细胞>11×10⁹/L(OR =8.26, 95% CI:4.50~15.13, P <0.01)及慢性阻塞性肺疾病(OR =1.51, 95% CI:1.16~1.95, P <0.01)。结论本研究显示腺癌、肿瘤分期(Ⅲ~Ⅳ期)、化疗、深静脉置管、白蛋白<30 g/L、D二聚体>500 mg/L、白细胞>11×10⁹/L及慢性阻塞性肺疾病是肺癌患者发生肺栓塞的危险因素。受纳入研究数量及质量的限制,需更多高质量文章进一步加以验证。

关键词: 肺肿瘤, 肺栓塞, 危险因素, Meta分析

Abstract:

Objective To evaluate the risk factors of lung cancer with pulmonary embolism systematically. Methods By January 2021, pertinent literature on risk factors of lung cancer with pulmonary embolism were included form PubMed, Embase, CNKI, Wanfang database and others. Two researchers independently completed the literature screening, data extraction and quality evaluation of the included literature. RevMan5.4 software and Stata16.0 software were used to conduct meta-analysis. Results A total of 25 studies involving 3480 patients were included. Meta-analysis results show that the risk factors of pulmonary embolism in patients with lung cancer include adenocarcinoma (OR =2.06, 95% CI [1.75, 2.44], P <0.01), tumor stage (stage Ⅲ-Ⅳ)( OR =2.67, 95% CI [2.19, 3.26], P <0.01), chemotherapy (OR =2.69, 95% CI [2.08, 3.47], P <0.01), deep vein catheterization (OR =2.66, 95% CI [1.68, 4.19], P<0.01), albumin<30 g/L(OR=6.65, 95% CI [2.91, 15.18], P<0.01), D dimer>500 g/L (OR =5.87, 95% CI [2.12, 16.27], P <0.01), white blood cells >11×10⁹/L(OR =8.26, 95% CI [4.50, 15.13], P <0.01) and chronic obstructive pulmonary disease(OR =1.51, 95% CI [1.16, 1.95], P <0.01). Conclusion The risk factors for pulmonary embolism with lung cancer are adenocarcinoma, tumor staging (stage Ⅲ-Ⅳ), chemotherapy, deep venous catheterization, albumin <30 g/L, D-dimer >500 ng/mL, white blood cell >11×10⁹/L and chronic obstructive pulmonary disease(COPD). Due to limited quality and quantity of the included studies, more high-quality articles are needed to verify the conclusions.

Key words: lung neoplasms, pulmonary embolism, risk factors, meta-analysis

中图分类号:

R734.2

黄平, 刘汉芸, 李玉红. 肺癌合并肺栓塞危险因素的Meta分析[J]. 临床荟萃, 2021, 36(12): 1061-1066.

Huang Ping, Liu Hanyun, Li Yuhong. Risk factors of lung cancer with pulmonary embolism:a meta-analysis[J]. Clinical Focus, 2021, 36(12): 1061-1066.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2021.12.001

https://huicui.hebmu.edu.cn/CN/Y2021/V36/I12/1061

图/表 7

图1 文献筛选流程图

表1 纳入文献的基本特征及NOS评分

作者	年份	例数		危险因素	NOS 评分
作者	年份	病例组	对照组	危险因素	NOS 评分
Cui^[4]	2021	40	60	①②③⑨⑩⑪⑫⑭	8
Lee^[5]	2009	40	80	①②⑩⑪⑫	8
Ma^[6]	2017	30	60	①②⑨⑩⑪⑫	9
Junjun^[7]	2020	53	53	①②③⑨⑩⑪⑫	9
Xiong^[8]	2020	95	98	①②⑨⑫	8
Zhang^[9]	2014	47	626	①⑨⑩⑪	9
唐开华^[10]	2017	32	64	①②③⑤⑥⑦⑧⑨⑩⑫⑭	8
崔凯^[11]	2020	38	200	①②④⑫⑭	9
张琳^[12]	2015	57	57	①②④⑬	8
曹洁^[13]	2019	45	45	①②③⑩	7
朱佑明^[14]	2016	46	46	①②③④⑨⑩⑫⑬⑭	8
朱璐^[15]	2018	51	153	①②③⑥⑪⑫⑬	9
李娜^[16]	2014	23	46	①②③④⑤⑥⑦⑧⑨⑩⑫⑭	9
李广生^[17]	2017	28	56	①②③⑤⑦⑨⑩⑪⑫⑭	8
熊露^[18]	2014	53	43	①⑬	7
王峻^[19]	2011	54	162	①②③④⑧⑨⑩⑪⑫⑬⑭	9
田学涛^[20]	2017	32	32	①②③④⑩⑫⑭	8
石宗华^[21]	2015	35	105	①②③④⑥⑦⑧⑨⑩⑫⑭	9
罗天舒^[22]	2017	39	43	①②	7
肖芳芳^[23]	2017	37	37	①④⑫⑬⑭	8
褚贵丽^[24]	2020	12	48	①②③⑩⑬	8
赵娜^[25]	2017	72	72	①②	9
赵秋红^[26]	2013	9	89	①③⑥	8
那文娟^[27]	2019	58	116	②④⑩⑪⑫⑬	9
邱冬^[28]	2018	21	42	①②⑪⑫	7

图2 肺癌特征与肺栓塞相关性的Meta分析

表2 其他指标与肺栓塞相关性的Meta分析

相关指标	纳入研究数量	异质性检验		效应模型	Meta分析结果
相关指标	纳入研究数量	$P$ 值	$I 2$ 值	效应模型	$OR$ (95% $CI$ )	$P$ 值
化疗	13篇^{[4, 7, 10, 13-17, 19-21, 24, 26]}	0.06	40%	固定	2.69(2.08~3.47)	<0.01
深静脉置管	9篇^{[11-12, 14, 16, 19-21, 23, 27]}	0.02	57%	随机	2.66(1.68~4.19)	<0.01
白蛋白<30 g/L	3篇^{[10, 16-17]}	0.71	0%	固定	6.65(2.91~15.18)	<0.01
D二聚体>500 mg/L	5篇^{[10, 15-16, 21, 26]}	0.0009	79%	随机	5.87(2.12~16.27)	<0.01
WBC>11×10⁹	4篇^{[10, 16-17, 21]}	0.16	41%	固定	8.26(4.50~15.13)	<0.01
CEA>10 mg/L	4篇^{[10, 16, 19, 21]}	0.02	69%	随机	0.83(0.39~1.77)	0.64
慢性阻塞性肺疾病	11篇^{[4, 6-10, 14, 16-17, 19, 21]}	0.35	10%	固定	1.51(1.16~1.95)	<0.01
糖尿病	15篇^{[4-7, 9-10, 13-14, 16-17, 19-21, 24, 27]}	0.97	0%	固定	1.16(0.89~1.51)	0.27
高血压	10篇^{[4-7, 9, 15, 17, 19, 27-28]}	0.98	0%	固定	0.98(0.75~1.30)	0.91
吸烟	17篇^{[4-8, 10-11, 14-17, 19-21, 23, 27-28]}	0.92	0%	固定	1.11(0.91~1.36)	0.29
饮酒	10篇^{[4, 10-11, 14, 16-17, 19-21, 23]}	0.82	0%	固定	1.24(0.94~1.62)	0.13
手术史	8篇^{[12, 14-15, 18-19, 23-24, 27]}	0.44	0%	固定	0.82(0.60~1.12)	0.22

表2 其他指标与肺栓塞相关性的Meta分析

相关指标	纳入研究数量	异质性检验		效应模型	Meta分析结果
相关指标	纳入研究数量	$P$ 值	$I 2$ 值	效应模型	$OR$ (95% $CI$ )	$P$ 值
化疗	13篇^{[4, 7, 10, 13-17, 19-21, 24, 26]}	0.06	40%	固定	2.69(2.08~3.47)	<0.01
深静脉置管	9篇^{[11-12, 14, 16, 19-21, 23, 27]}	0.02	57%	随机	2.66(1.68~4.19)	<0.01
白蛋白<30 g/L	3篇^{[10, 16-17]}	0.71	0%	固定	6.65(2.91~15.18)	<0.01
D二聚体>500 mg/L	5篇^{[10, 15-16, 21, 26]}	0.0009	79%	随机	5.87(2.12~16.27)	<0.01
WBC>11×10⁹	4篇^{[10, 16-17, 21]}	0.16	41%	固定	8.26(4.50~15.13)	<0.01
CEA>10 mg/L	4篇^{[10, 16, 19, 21]}	0.02	69%	随机	0.83(0.39~1.77)	0.64
慢性阻塞性肺疾病	11篇^{[4, 6-10, 14, 16-17, 19, 21]}	0.35	10%	固定	1.51(1.16~1.95)	<0.01
糖尿病	15篇^{[4-7, 9-10, 13-14, 16-17, 19-21, 24, 27]}	0.97	0%	固定	1.16(0.89~1.51)	0.27
高血压	10篇^{[4-7, 9, 15, 17, 19, 27-28]}	0.98	0%	固定	0.98(0.75~1.30)	0.91
吸烟	17篇^{[4-8, 10-11, 14-17, 19-21, 23, 27-28]}	0.92	0%	固定	1.11(0.91~1.36)	0.29
饮酒	10篇^{[4, 10-11, 14, 16-17, 19-21, 23]}	0.82	0%	固定	1.24(0.94~1.62)	0.13
手术史	8篇^{[12, 14-15, 18-19, 23-24, 27]}	0.44	0%	固定	0.82(0.60~1.12)	0.22

图3 腺癌指标漏斗图

图4 肿瘤分期(Ⅲ~Ⅳ期)漏斗图

表3 腺癌及肿瘤分期(Ⅲ~Ⅳ期)偏倚检验

指标	Egger's test
指标	$t$ 值	$P$ 值
腺癌	1.39	0.179
肿瘤分期(Ⅲ~Ⅳ期)	0.84	0.412

表3 腺癌及肿瘤分期(Ⅲ~Ⅳ期)偏倚检验

指标	Egger's test
指标	$t$ 值	$P$ 值
腺癌	1.39	0.179
肿瘤分期(Ⅲ~Ⅳ期)	0.84	0.412

参考文献 37

[1]	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424. doi: 10.3322/caac.v68.6 URL
[2]	杨欢欢, 陈虹. 肺癌合并肺栓塞的研究进展[J]. 中华结核和呼吸杂志, 2020, 43(7):577-581.
[3]	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J]. Eur J Epidemiol, 2010, 25(9):603-605. doi: 10.1007/s10654-010-9491-z URL
[4]	Cui YQ, Tan XM, Liu B, et al. Analysis on risk factors of lung cancer complicated with pulmonary embolism[J]. Clin Respir J, 2021, 15(1):65-73. doi: 10.1111/crj.v15.1 URL
[5]	Lee JW, Cha SI, Jung CY, et al. Clinical course of pulmonary embolism in lung cancer patients[J]. Respiration, 2009, 78(1):42-48. doi: 10.1159/000176208 pmid: 19023192
[6]	Ma L, Wen Z. Risk factors and prognosis of pulmonary embolism in patients with lung cancer[J]. Medicine (Baltimore), 2017, 96(16):e6638. doi: 10.1097/MD.0000000000006638 URL
[7]	Junjun L, Pei W, Ying Y, et al. Prognosis and risk factors in older patients with lung cancer and pulmonary embolism: A propensity score matching analysis[J]. Sci Rep, 2020, 10(1):1272. doi: 10.1038/s41598-020-58345-4 pmid: 31988400
[8]	Xiong W, Zhao Y, Xiong Y, et al. Coagulation factor IV is an indicator of symptomatic pulmonary embolism in patients with primary lung cancer[J]. Clin Respir J, 2020, 14(2):124-131. doi: 10.1111/crj.13109 pmid: 31747482
[9]	Zhang Y, Yang Y, Chen W, et al. Prevalence and associations of VTE in patients with newly diagnosed lung cancer[J]. Chest, 2014, 146(3):650-658. doi: 10.1378/chest.13-2379 URL
[10]	唐开华. 肺癌合并肺栓塞危险因素及预后的临床分析[J]. 临床肺科杂志, 2017, 22(8):1477-1480.
[11]	崔凯, 葛威, 卢晨, 等. 肺癌患者发生肺栓塞的相关危险因素分析[J]. 临床肺科杂志, 2020, 25(1):96-100.
[12]	张琳. 肺癌合并肺栓塞的临床预后及其相关危险因素分析[J]. 海南医学, 2015, 26(11):1598-1600.
[13]	曹洁, 梅晓冬. 肺癌并发肺栓塞45例临床分析[J]. 安徽医药, 2019, 23(7):1354-1357.
[14]	朱佑明, 陈文慧, 代华平. 肺癌患者发生肺栓塞的相关危险因素及对预后的影响[J]. 实用临床医药杂志, 2016, 20(13):25-28.
[15]	朱璐, 覃寿明, 巫艳彬. 肺癌合并肺栓塞的相关危险因素分析[J]. 广西医科大学学报, 2018, 35(4):476-479.
[16]	李娜, 王燕. 23例肺癌并发肺栓塞的临床分析[J]. 中国肺癌杂志, 2014, 17(3):254-259.
[17]	李广生, 李月川, 马淑萍. 肺癌合并肺栓塞的影响因素及临床特征分析[J]. 天津医药, 2017, 45(7):730-734.
[18]	熊露. 肺癌合并肺栓塞危险因素的临床分析[J]. 现代诊断与治疗, 2014, 25(14):3302-3303.
[19]	王峻, 周卫华, 许林, 等. 肺癌合并肺栓塞危险因素及预后的临床分析[J]. 中国肺癌杂志, 2011, 14(10):780-784.
[20]	田学涛, 黄吉利. 肺癌患者肺栓塞的危险因素研究[J]. 实用心脑肺血管病杂志, 2017, 25(2):50-52.
[21]	石宗华, 师广勇, 孙哲, 等. 肺癌合并肺栓塞危险因素的病例对照研究[J]. 中华肿瘤防治杂志, 2015, 22(11):863-866.
[22]	罗天舒, 赵镜平. 导致肺癌患者并发肺栓塞的危险因素及其对预后的影响[J]. 当代医药论丛, 2017, 15(18):85-86.
[23]	肖芳芳, 郭茜, 齐秀恒. 肺癌合并肺栓塞的危险因素及临床预后探析[J]. 大家健康(中旬版), 2017, 11(2):28-29.
[24]	褚贵丽, 白春琴. 老年肺癌患者术后并发肺栓塞的原因分析与护理[J]. 血栓与止血学, 2020, 26(4):685-687.
[25]	赵娜, 韦永刚. 非小细胞肺癌患者肺栓塞的影响因素研究[J]. 实用心脑肺血管病杂志, 2017, 25(3):46-49.
[26]	赵秋红, 任冠军, 闫春良, 等. 肺癌并发肺血栓栓塞症的相关因素分析[J]. 中国临床医生, 2013, 41(10):32-34.
[27]	那文娟, 段燕芳. 肺癌合并急性肺血栓栓塞症和单纯肺癌的危险因素对照研究[J]. 中国心血管杂志, 2019, 24(5):439-443.
[28]	邱冬. 肺癌并发肺栓塞的危险因素[J]. 中国血液流变学杂志, 2018, 28(4):409-411.
[29]	王有福, 杨晗, 胡明, 等. 肺癌患者并发静脉血栓栓塞症的危险因素分析[J]. 中华血管外科杂志, 2019, 4(3):164-168.
[30]	Hua X, Han SH, Wei SZ, et al. Clinical features of pulmonary embolism in patients with lung cancer: A meta-analysis[J]. PLoS One, 2019, 14(9):e0223230. doi: 10.1371/journal.pone.0223230 URL
[31]	Cui S, Li H. Perioperative Venous Thromboembolism (VTE) prophylaxis in thoracic cancer patients: Chinese experts consensus-interpretation of perioperative hypercoagulable state[J]. Zhongguo Fei Ai Za Zhi, 2019, 22(12):752-756.
[32]	Ng S, Carrier M. Prevention and treatment of cancer-associated thrombosis[J]. Curr Oncol, 2020, 27(5):275-278. doi: 10.3747/co.27.6873 pmid: 33173380
[33]	李荣华, 何佩仪, 杜萍, 等. 肿瘤患者经外周穿刺中心静脉置管后血栓形成的高危因素及对导管相关性血栓的诊断价值[J]. 实用医学杂志, 2020, 36(16):2309-2314.
[34]	Zhu H, Ying K. Tissue factors and venous thromboembolism in cancer patients[J]. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2020, 49(6):772-778.
[35]	Chi G, Gibson CM, Liu Y, et al. Inverse relationship of serum albumin to the risk of venous thromboembolism among acutely ill hospitalized patients: Analysis from the APEX trial[J]. Am J Hematol, 2019, 94(1):21-28. doi: 10.1002/ajh.25296 URL
[36]	刘燕娥, 顾阳春, 易福梅, 等. 283例系统性治疗的肺癌患者静脉血栓栓塞症的危险因素分析[J]. 中国肺癌杂志, 2019, 22(7):419-426.
[37]	Pang H, Wang L, Liu J, et al. The prevalence and risk factors of venous thromboembolism in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease[J]. Clin Respir J, 2018, 12(11):2573-2580. doi: 10.1111/crj.2018.12.issue-11 URL