胸腺肽类药物辅助治疗重症肺炎有效性和安全性的系统综述与用药合理性讨论

蒋子昀; 张阳阳; 杨会林; 周建国; 李迅

doi:10.16462/j.cnki.zhjbkz.2024.05.017

胸腺肽类药物辅助治疗重症肺炎有效性和安全性的系统综述与用药合理性讨论

doi: 10.16462/j.cnki.zhjbkz.2024.05.017

1.
北京中医药大学管理学院，北京 100029
2.
北京中医药大学第二临床医学院，北京 100078
3.
北京中医药大学房山医院，北京 102488
4.
北京易康医疗科技有限公司，北京 100062
5.
北京中医药大学循证医学中心，北京 100029

基金项目:

国家重点研发计划“中医药现代化”重点专项 2022YFC3501400

北京中医药大学基本科研业务费项目 2022-JYB-JBRW-013

北京中医药大学校级教育课题 XJY22020

详细信息

通讯作者:
李迅，E-mail：tina000341@163.com

中图分类号: R563.1
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- 文章访问数: 35
- HTML全文浏览量: 4
- PDF下载量: 6
- 被引次数: 0
出版历程
- 收稿日期: 2023-06-29
- 修回日期: 2023-12-04
- 网络出版日期: 2024-06-05
- 刊出日期: 2024-05-10

A systematic review of the efficacy and safety of the immunomodulator thymic polypeptides as adjuvant treatment for severe pneumonia

1.
Department of Management, Beijing University of Chinese Medicine, Beijing 100029, China
2.
The Second Clinical Medicine College, Beijing University of Chinese medicine, Beijing 100078, China
3.
Fangshan Hospital of Beijing University of Chinese Medicine, Beijing 102488, China
4.
Beijing Econ Medical Technology Co, Beijing 100062, China
5.
Center for Evidence Based Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

Funds:

Major Program "Modernization of traditional Chinese Medicine" of The National Major Research and Development Plan of China 2022YFC3501400

Fundamental Research Funds for Beijing University of Chinese Medicine 2022-JYB-JBRW-013

Education Research Program of Beijing University of Chinese Medicine XJY22020

More Information

Corresponding author: LI Xun, E-mail: tina000341@163.com

摘要

摘要: 目的评价胸腺肽类药物辅助治疗重症肺炎的有效性和安全性并探讨应用的合理性。方法检索中国知网、万方数据、维普、Sinomed、Pubmed、Embase、Cochrane Library数据库自建库至2023年12月发表的胸腺肽类药物辅助治疗重症肺炎的随机对照试验(randomized controlled trial，RCT)，经过严格的筛选后，使用Cochrane偏倚风险评估工具评估文献质量，使用Revman 5.4软件进行统计分析。结果纳入28项RCT(2 228例患者)。结果显示胸腺肽组死亡率(RR=0.51, 95% CI: 0.32~0.83, P=0.006)、有效率(RR=1.24, 95% CI: 1.19~1.30, P < 0.001)、重症监护室(intensive care unit, ICU)住院天数(MD=-3.03, 95% CI: -3.79~-2.26, P < 0.001)、机械通气时间(MD=-61.34，95% CI: -65.55~-57.12, P < 0.001)、血气分析指标、炎性指标均略优于对照组，在不良事件发生率方面差异无统计学意义(P＞0.05)。亚组分析显示≥60岁的人群ICU住院天数缩短更多。证据质量普遍较低，部分指标存在较高异质性。结论基于现有证据，胸腺肽类药物辅助治疗重症肺炎有一定优势，但当前的证据存在局限性，不足以支持其在国内广泛应用的合理性，未来需要开展更多高质量的RCT，并且对药物的安全性和经济学效益进行深入研究。
- 重症肺炎 /
- 胸腺肽 /
- 胸腺五肽 /
- 系统综述 /
- 免疫治疗
Abstract: Objective To evaluate the effectiveness and safety for thymic polypeptides as adjunctive treatment of severe pneumonia and explore the rationality for application. Methods A systematic searching was conducted in six Chinese and English databases to identify randomized controlled trials on the use of thymic polypeptides for severe pneumonia. After screening, the included studies were subjected to quality assessment and data synthesis. Results A total of 28 randomized controlled trials involving 2 228 participants were included. Results showed that the thymic polypeptide group had lower mortality rate (RR=0.51, 95% CI: 0.32-0.83, P=0.006), higher effectiveness rate (RR=1.24, 95% CI: 1.19-1.30, P < 0.001), shorter ICU stay (MD=-3.03, 95% CI: -3.79--2.26, P < 0.001), shorter mechanical ventilation time (MD=-61.34, 95% CI: -65.55--57.12, P < 0.001), and better blood gas and inflammatory indicators compared to the control group, with no significant difference in adverse event rate (P > 0.05). Subgroup analyses revealed a trend for reduced ICU stay for patients over 60. The quality of evidence was generally low, with high heterogeneity in some indicators. Conclusions Based on the available evidence, thymic polypeptides show certain advantages as adjuvant treatment for severe pneumonia. However, there are limitations in the current evidence that do not justify the widespread use of them in China, There is a need for more RCTs to be conducted in the future, along with in-depth research into the safety and economic benefits of these medications.
- Severe pneumonia /
- Thymosin /
- Thymopentin /
- Systematic review /
- Immunomodulatory

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图 1 文献筛选流程图

Figure 1. Flow diagram of articles included

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图 2 偏倚风险图

Figure 2. Risk of bias

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图 3 胸腺肽+常规治疗vs常规治疗有效率的森林图

Figure 3. Forest plot of the effectiveness of thymic peptides+conventional treatment versus conventional treatment

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图 4 胸腺肽+常规治疗vs常规治疗有效率的漏斗图

Figure 4. Funnel plot of the effectiveness of thymic peptides+ conventional treatment versus conventional treatment

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表 1 纳入研究基本特征

Table 1. The characteristics of the studies included

研究ID Study ID	疾病种类Disease category	样本量Sample size		年龄/岁Age/years
研究ID Study ID	疾病种类Disease category	T	C	T	C
杨崇艳^[13]2019 Yang CY^[13]	SCAP	44	44	50.97±10.51	50.46±10.74
卢经伟等^[14]2014 Lu JW, et al^[14]	SCAP	40	38	67.50±6.20	68.20±5.50
朱倩^[15]2020 Zhu Q^[15]	SP	48	47	68.50±4.45	69.00±4.61
李瑞书^[16]2017 Li RS^[16]	SP	50	50	55.34±5.52	56.39±5.48
胡男彬^[17]2016 Hu NB^[17]	SP	20	20	67.53±4.32	69.33±4.14
李莉等^[18]2020 Li L, et al^[18]	SCAP	59	59	60.63±6.57	61.24±7.13
季明霞等^[19]2015 Ji MX, et al^[19]	SP	28	28	42.15±11.72	45.03±15.91
古柠华^[20]2020 Gu NH^[20]	SP	30	30	66.27±5.14	66.35±5.28
何新华等^[21]2009 He XH, et al^[21]	SCAP	17	18	62.00±6.00	64.00±8.00
郭镕杰等^[22]2021 Guo RJ, et al^[22]	SP	42	42	63.48±2.34	63.46±2.31
肖辉^[23]2018 Xiao H^[23]	T2DM+SP	39	39	68.20±3.40	67.60±4.10
刘传文等^[24]2019 Liu CW, et al^[24]	SP	46	46	72.69±7.78	73.34±7.21
石小软^[25]2018 Shi XR^[25]	SCAP	55	55	62.30±11.70	65.10±12.10
于磊等^[26]2023 Yu L, et al^[26]	SP	40	40	62.58±1.31	62.35±1.24
岳红云等^[27]2023 Yue HY, et al^[27]	SP+呼吸衰竭respiratory failure	48	48	62.58±1.31	62.35±1.24
张辉等^[28]2019 Zhang H, et al^[28]	SP	43	43	58.88±9.87	59.91±10.02
刘辉等^[29]2021 Liu H, et al^[29]	SP	55	55	67.96±4.34	67.32±4.85
朱海亮^[30]2020 Zhu HL^[30]	SCAP	30	30	68.40±9.60	69.30±9.62
郑细优等^[31]2016 Zheng XY, et al^[31]	SP+脓毒症sepsis	35	35	60.46±8.57	61.08±8.79
熊锋等^[32]2015 Xiong F, et al^[32]	SP+脓毒症sepsis	34	34	64.80±12.00	66.20±13.00
申强^[33]2015 Shen Q^[33]	SP+脓毒症sepsis	38	38	65.80±5.40	66.20±7.40
谢敏崇等^[34]2019 Xie MC, et al^[34]	SP+脓毒症sepsis	45	45	38.13±2.02	38.24±2.01
林攻平^[35]2018 Lin GP^[35]	SP+脓毒症sepsis	36	36	51.20± 5.10	50.10±4.90
王娜2014^[36] Wang N^[36]	SVAP	26	26	71.70±11.90	72.50±12.30
孙睿甜^[37]2021 Sun RT^[37]	SP+脓毒症sepsis	35	35	51.03±10.72	51.28±10.63
王薇等^[38]2020 Wang W, et al^[38]	SP	60	60	68.73±2.45	67.93±2.32
陈珊珊等^[39]2019 Chen SS, et al^[38]	胃癌Gastric cancer +SP	32	32	69.10±4.30	68.00±4.60
吴薇^[40]2022 Wu W^[40]	SP+脓毒症sepsis	40	40	55.02±4.21	54.25±4.12

研究ID Study ID	试验组干预措施 ^① Intervention of the trial group ^①			疗程/d Treatment duration/d	结局指标Outcomes
研究ID Study ID	种类Category	使用方法Usage		疗程/d Treatment duration/d	结局指标Outcomes
杨崇艳^[13]2019 Yang CY^[13]	Tα1	1.6 mg qd		7	BI
卢经伟等^[14]2014 Lu JW, et al^[14]	Tα1	1.6 mg qd		7	B
朱倩^[15]2020 Zhu Q^[15]	Tα1	1.6 mg des ^②		7	B
李瑞书^[16]2017 Li RS^[16]	Tα1	1.6 mg des		7	AB
胡男彬^[17]2016 Hu NB^[17]	Tα1	1.6 mg bid		7	B
李莉等^[18]2020 Li L, et al^[18]	Tα1	1.6 mg bid		NR	BEHIJ
季明霞等^[19]2015 Ji MX, et al^[19]	Tα1	1.6 mg qd		7	CDI
古柠华^[20]2020 Gu NH^[20]	Tα1	1.6 mg qd		10	CD
何新华等^[21]2009 He XH, et al^[21]	Tα1	1.6 mg bid		7	ABCD
郭镕杰等^[22]2021 Guo RJ, et al^[22]	Tα1	1.6 mg bid		14	B
肖辉^[23]2018 Xiao H^[23]	Tα1	1.6 mg qd~bid		10	B
刘传文等^[24]2019 Liu CW, et al^[24]	Tα1	1.6 mg des		7	C
石小软^[25]2018 Shi XR^[25]	Tα1	1.6 mg des		7	AB
于磊等^[26]2023 Yu L, et al^[26]	Tα1	20~80 mg qd		7	BCDI
岳红云等^[27]2023 Yue HY, et al^[27]	Tα1	1.6 mg 2次/周2 times/week		7	BEFH
张辉等^[28]2019 Zhang H, et al^[28]	Tm	1.6 mg qd		14	B
刘辉等^[29]2021 Liu H, et al^[29]	Tm	20 mg qd		14	B
朱海亮^[30]2020 Zhu HL^[30]	Tm	40 mg qd		7	BI
郑细优等^[31]2016 Zheng XY, et al^[31]	Tm	20 mg qd		5	BDIJ
熊锋等^[32]2015 Xiong F, et al^[32]	Tm	1.6 mg bid		5	BDIJ
申强^[33]2015 Shen Q^[33]	Tm	1.5 mg bid		5	BIJ
谢敏崇等^[34]2019 Xie MC, et al^[34]	Tm	1.6 mg bid		5	CDJ
林攻平^[35]2018 Lin GP^[35]	Tm	10~20 mg qd		NR	DIJ
王娜2014^[36] Wang N^[36]	TP-5	1 mg qd		14	ACD
孙睿甜^[37]2021 Sun RT^[37]	TP-5	10 mg qd		7	BCDEFI
王薇等^[38]2020 Wang W, et al^[38]	TP-5	10 mg ^③		14	BI
陈珊珊等^[39]2019 Chen SS, et al^[38]	TP-5	10 mg qd		21	I
吴薇^[40]2022 Wu W^[40]	TP-5	20 mg qd		5	BCDEFGI
注：T，试验组；C，对照组；SP，重症肺炎；SCAP，重症社区获得性肺炎；SVAP，重症呼吸机相关肺炎；T2DM：2型糖尿病；Tα1，胸腺肽α1；Tm，胸腺肽；TP-5，胸腺五肽；qd，每日1次；bid，每日2次；des，降级治疗；NR，未报告。 ①对照措施均为重症肺炎的常规治疗，包括抗感染、抗休克、气道护理、氧疗以及原发症的对症治疗；②降级治疗指前三天每天服药两次，后4 d每天服药一次；③该研究未报告每天的服药次数；④结局指标对应：A-死亡率；B-有效率；C-ICU住院天数；D-机械通气时间；E-动脉血氧分压；F-动脉血二氧化碳分压；G-血氧饱和度；H-氧合指数；I-降钙素原；J-白细胞计数。 Note: T, trial group; C, control group; SP, severe pneumonia; SCAP, severe community-acquired pneumonia; SVAP, severe ventilator-associated pneumonia; T2DM: type 2 diabetes mellitus; Tα1, thymosin α1; Tm, thymosin; TP-5, thymopentin; qd, once a day; bid, twice a day; des, de-escalation of treatment; NR, not reported. ①Control measures were all routine treatments for severe pneumonia, including anti-infection, anti-shock, airway care, oxygen therapy, and symptomatic treatment of primary conditions; ②De-escalation of treatment was defined as taking the drug twice a day for the first three days and once a day for the last four days; ③The study did not report the number of medications taken per day; ④The outcome indicators corresponded to: A-mortality; B-efficiency; C-number of days of ICU stay; D-mechanical ventilation time; E-PaO₂; F-PaCO₂; G-SaO₂; H- PaO₂/FiO₂; I-PCT; J-WBC.

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表 2 其他指标效应值

Table 2. The effect size of other indicators

结局指标Outcomes indicator	研究数量Number of studies	样本量Sample size	异质性检验Heterogeneity (I²/%，P值value)	统计方法Statistical method	RR/MD值value (95% CI)	P值value
死亡率Mortality rate	4	297	0，0.990	FEM	0.51 (0.32~0.83)	0.006
亚组分析Subgroup analysis
Tα1且≥60岁Tα1 and age≥60	2	145	61，0.110		0.51 (0.26~1.00)	0.050
TP-5且≥60岁TP-5 and age≥60	1	52			0.57 (0.29~1.13)	0.110
Tα1且 < 60岁Tα1 and age < 60	1	100			0.20 (0.01~4.06)	0.290
ICU住院天数ICU stay	9	615	96, ＜0.001	FEM	-3.03 (-3.79~-2.26)	< 0.001
亚组分析Subgroup analysis
Tα1且≥60岁Tα1 and age≥60	4	267	52，0.100		-3.90 (-4.24~-3.56)	0.100
TP-5且≥60岁TP-5 and age≥60	1	52			-3.60 (-7.90~0.70)	0.100
Tα1且 < 60岁Tα1 and age < 60	1	56			-1.62 (-3.21~-0.03)	0.050
Tm且 < 60岁Tm and age < 60	1	90			-2.12 (-2.49~-1.75)	< 0.001
TP-5且 < 60岁TP-5 and age < 60	2	150	0，0.630		-1.87 (-2.22~1.51)	< 0.001
机械通气时间Mechanical ventilation time	11	733	57，0.009	REM	-61.34 (-65.55~-57.12)	< 0.001
亚组分析Subgroup analysis
Tα1且≥60岁Tα1 and age>60	3	175	71，0.030		-59.83 (-67.07~-52.59)	< 0.001
Tm且≥60岁Tm and age≥60	2	138	0，0.970		-57.68 (-66.49~-48.87)	< 0.001
TP-5且≥60岁TP-5 and age≥60	1	52			-91.20 (-160.05~-22.35)	0.009
Tα1且 < 60岁Tα1 and age < 60	1	56			-38.64 (-63.30~-13.98)	0.002
Tm且 < 60岁Tm and age < 60	2	162	34，0.220		-67.91 (-78.74~-57.07)	< 0.001
TP-5且 < 60岁TP-5 and age < 60	2	150	68，0.070		-60.36 (-75.69~-45.03)	< 0.001
PaO₂	4	364	95， < 0.001	REM	10.37 (6.15~14.58)	< 0.001
亚组分析Subgroup analysis
Tα1且≥60岁Tα1 and age≥60	2	214	0，0.530		7.37 (6.44~8.30)	< 0.001
TP-5且 < 60岁TP-5 and age < 60	2	150	95， < 0.001		13.69 (3.40~23.98)	0.009
PaCO₂	3	246	98， < 0.001	REM	-5.59 (-13.12~1.94)	0.150
亚组分析Subgroup analysis
Tα1且≥60岁Tα1 and age≥60	1	96			-0.15 (-1.19~0.89)	0.780
TP-5且 < 60岁TP-5 and age < 60	2	150	94， < 0.001		-8.40 (-14.37~-2.44)	0.006
SaO₂	2	176	91， < 0.001	REM	3.37 (0.77~5.97)	0.010
亚组分析Subgroup analysis
Tα1且≥60岁Tα1 and age≥60	1	96			2.13 (1.57~2.69)
TP-5且 < 60岁TP-5 and age < 60	1	80			4.79 (3.30~6.28)
PaO₂/FiO₂	1	118			33.08 (27.69~38.47)	< 0.001
PCT	12	902	99， < 0.001	REM	-1.30 (-1.62~-0.97)	< 0.001
亚组分析Subgroup analysis
Tα1且≥60岁Tα1 and age≥60	1	118	92， < 0.001		-2.89 (-3.80~-1.97)	< 0.001
Tm且≥60岁Tm and age≥60	3	204	30，0.240		-0.29 (-0.38~-0.20)	< 0.001
TP-5且≥60岁TP-5 and age≥60	2	134	99， < 0.001		-1.71 (-4.51~1.08)	0.230
Tα1且 < 60岁Tα1 and age < 60	2	144	99， < 0.001		-1.37 (-3.04~0.31)	0.110
Tm且 < 60岁Tm and age < 60	1	72			-0.79 (-0.87~-0.71)	< 0.001
TP-5且 < 60岁TP-5 and age < 60	2	150	90，0.002		-1.93 (-3.00~-0.86)	< 0.001
WBC	6	522	69，0.004	REM	-2.86 (-2.93~-2.79)	< 0.001
亚组分析Subgroup analysis
Tm且≥60岁Tm and age≥60	3	214	0，1.000		-2.29 (-2.63~-1.96)	< 0.001
Tm且 < 60岁Tm and age < 60	2	162	28，0.240		-2.89 (-2.96~-2.82)	< 0.001
Tα且 < 60岁Tα and age < 60	1	56			-2.40 (-3.86~-0.94)	0.001
注：PaO₂，动脉血氧分压；PaCO₂，动脉血二氧化碳分压；SaO₂，血氧饱和度；PaO₂/FiO₂，氧合指数；PCT，降钙素原；WBC，白细胞计数；REM，随机效应模型；FEM，固定效应模型；MD，均数差。 Note: PaO₂, partial pressure of arterial oxygen; PaCO₂, partial pressure of arterial carbon dioxide; SaO₂, blood oxygen saturation; PaO₂/FiO₂, oxygenation index; PCT, procalcitonin; WBC, white blood cell count; RE, random effect models；FE, fixed effect models; MD, mean diffenrence.

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