γ-干扰素联合抗结核药物治疗肺结核临床疗效的Meta分析

doi:10.19982/j.issn.1000-6621.20220205

摘要/Abstract

摘要：

目的:系统评价γ-干扰素(IFN-γ)联合抗结核药物治疗肺结核的临床疗效和安全性,为IFN-γ在肺结核临床治疗中的应用提供依据。方法:检索PubMed、Embase、中国生物医学文献数据库、中国知网、万方数据库,纳入自建库以来至2022年3月1日公开发表的IFN-γ联合抗结核药物治疗肺结核的临床随机对照试验(RCT)研究。根据Cochrane手册,应用Review Manager 5.4 软件对纳入文献进行质量评价。应用STATA 12.0 软件对IFN-γ联合抗结核药物治疗组(观察组)和单纯抗结核药物治疗组(对照组)肺结核患者治疗2~3个月及6~9个月后痰菌阴转率、病灶吸收率、空洞闭合率及两组不良反应发生率,以及治疗后外周血CD4⁺T细胞、CD8⁺T细胞百分比的差异进行评价。结果:共纳入18篇文献,共计1341例患者。Meta分析结果显示,与对照组比较,观察组患者治疗2~3个月和6~9个月后,痰菌阴转率RR(95%CI)值分别为1.40(1.26~1.56)和1.41(1.12~1.76);病灶吸收率RR(95%CI)值分别为1.43(1.09~1.88)和2.84(1.65~5.00);空洞闭合率RR(95%CI)值分别为2.07(1.47~2.92)和1.56(1.28~1.91),均显著高于对照组(P值均<0.05)。此外,与对照组比较,治疗后观察组外周血CD4⁺T细胞百分比升高更明显、CD8⁺T细胞百分比降低更明显(P值均<0.05), 加权均数差(WMD;95%CI)分别为5.18(2.53~7.84)和-3.16(-6.08~-0.23)。与对照组比较,观察组不良反应发生率RR(95%CI)值为1.06(0.70~1.60),其中,肝功能异常发生率、皮肤过敏反应发生率、胃肠道不良反应发生率RR(95%CI)值分别为1.02(0.95~1.11)、1.03(0.95~1.11)和1.01(0.93~1.11),差异均无统计学意义(P值均>0.05)。结论:IFN-γ联合抗结核药物治疗肺结核,可以促进患者病灶吸收、痰菌阴转率,且能改善肺结核患者的免疫指标。

关键词: γ-干扰素, 结核, 抗结核药, Meta分析

Abstract:

Objective:To evaluate the clinical effectiveness and safety of interferon-γ(IFN-γ) combined with anti-tuberculosis drugs in treating pulmonary tuberculosis (PTB) through Meta-analysis and to provide reliable evidence for using IFN-γ in the treatment of PTB. Methods:Searching PubMed, Embase, Chinese Bio Medical Literature Database (CBM), China Knowledge Network (CNKI), and Wanfang Database, the publicly published clinical randomized controlled trials (RCTs) in the treatment of PTB using IFN-γ combined with anti-tuberculosis drugs were included. According to the Cochrane manual, Review Manager 5.4 software was used to evaluate the quality of those included papers. All the studies were analyzed with STATA 12.0 software, patients treated with IFN-γ combined with anti-tuberculosis drugs were regarded as the observation group, while patients treated only with anti-tuberculosis drugs were regarded as the control group. The evaluation indicators included the absorption rate of lung lesions, the closure rate of cavities, the sputum negative conversion rate after 2-3 months’ and 6-9 months’ treatment, and the percentage of CD4⁺T cell and the CD8⁺T cell in peripheral blood after treatment. Results:Eighteen RCT studies with a total of 1341 patients were included. The Meta-analysis showed that compared with the control group, after 2-3 months’ and 6-9 months’ treatment, the RR (95%CI) of sputum negative conversion rate of the observation group were 1.40 (1.26-1.56) and 1.41 (1.12-1.76), respectively; the RR (95%CI) of lesion absorption rate were 1.43 (1.09-1.88) and 2.84 (1.65-5.00), respectively; the RR (95%CI) of cavity closure rate were 2.07 (1.47-2.92) and 1.56 (1.28-1.91), respectively. These indicators were all significantly increased in the observation group (Ps<0.05). Comparing the observation group with the control group, the percentage of peripheral blood CD4⁺ T cells was significantly increased (P<0.05), and the percentage of CD8⁺ T cells was significantly decreased (P<0.05), the WMD (95%CI) were 5.18 (2.53-7.84) and -3.16 (-6.08--0.23), respectively. The RR (95%CI) of side effect incidence was 1.07 (0.72-1.60), RR (95%CI) of abnormal liver function, skin allergy, and gastrointestinal reactions were 1.02 (0.95-1.11), 1.03 (0.95-1.11) and 1.01 (0.93-1.11), respectively. All differences were not statistically significant (Ps>0.05). Conclusion:IFN-γ combined with anti-tuberculosis drugs in treating PTB can promote the absorption of lung lesions, the closure of cavities, the negative conversion of sputum, and meanwhile improve the immunological indicators of PTB patients.

Key words: Interferon-gamma, Tuberculosis, Antitubercular agents, Meta-analysis

中图分类号:

R52
TQ929+.1

安慧茹, 韩怡然, 闫梦蝶, 吴雪琼. γ-干扰素联合抗结核药物治疗肺结核临床疗效的Meta分析[J]. 中国防痨杂志, 2022, 44(10): 1002-1009. doi: 10.19982/j.issn.1000-6621.20220205

An Huiru, Han Yiran, Yan Mengdie, Wu Xueqiong. Meta-analysis on clinical effectiveness of combination regimens with interferon-γ in treatment of pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2022, 44(10): 1002-1009. doi: 10.19982/j.issn.1000-6621.20220205

图/表 9

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纳入文献基本体征

第一作者	发表年份	患者例数	男∶女	平均年龄(岁)	病例特点	抗结核药物治疗方案	治疗组IFN-γ用法	结局指标
第一作者	发表年份	对照组/ 观察组	对照组/ 观察组	对照组/观察组	病例特点	抗结核药物治疗方案	剂量频次,途径,疗程	结局指标
刘建德^[9]	1999	60/60	NA/NA	NA/NA	初复治,老年	3H-R-Z-S/6H-R-Z	100WIU/2次/w,im,3m	②④⑥
梁伟成^[10]	2003	35/36	21:14/21:15	42.0/39.5	复治菌阳	2H₃R₃Z₃E₃S₃/6H₃R₃E₃	100WIU/次/2d, ih或im,2m	①②③⑥
要玉霞^[11]	2003	34/32	23:11/22:10	NA/NA	耐多药	3D-Z-E-Lfx-Am/6D-E-Lfx	100WIU/2次/d,3次/w,inh,3m	①②⑤⑥
阳光辉^[12]	2005	20/25	NA/NA	NA/NA	耐多药	3Z-Pto-Lfx-E-Am/4Z-Pto-Lfx	200WIU/次/2d,im,3m	①②④
徐俊彦^[13]	2006	20/23	12:8/16:7	48.0±12.0/45.0±11.0	耐多药	3Am-D-Pto-Lfx-L₂/15D-Pto-Lfx-L₂	500WIU/3次/w,inh,3m	①③⑦
王琳^[14]	2006	73/63	46:32/38:25	49.6±6.2/47.7±3.5	初治菌阳	2H-R-Z-S/4H-R(E)	100WIU/次/2d,im,2m	①②③④
王守京^[15]	2007	64/64	44:20/44:20	NA/NA	复治菌阳	12D-L₂-Pto-Z-Lfx	100WIU/3次/w,im,6m	②④⑥
林存智^[16]	2007	28/36	NA/NA	NA/NA	多耐药	2H-R-Z-E(S)/6H-R-E	100W0WIU/次/d, inh,2m	③④
李丹^[17]	2008	40/40	NA/NA	NA/NA	初治菌阳	2H-R-Z-E/4H-R	100WIU/次/2d,im,2m	①③
施军卫^[18]	2008	11/11	NA/NA	NA/NA	耐多药	3H-PAS-E-Z-Am-Lfx/9Z-E-Lfx	200WIU/3次/w,inh,6m	②④⑦⑧⑨⑩
林存智^[19]	2008	38/38	24:14/26:12	44.7±3.8/48.5±5.2	耐多药	3H-R-Z-E(S)/6H-R-E	100WIU/次/2d,inh,2m	④
张彦秋^[20]	2009	35/35	NA/NA	48.0±17.0/52.0±13.0	复治菌阳	2D-L₃-Pto-Z-Lfx	500μg/3次/w,inh,2m	①③④⑤
杨之怡^[21]	2009	30/30	NA/NA	NA/NA	耐多药	3Sp-D-Z-E-Pto/9Sp-D-E	NA, inh,2m	①⑦
李炳杰^[22]	2011	30/30	NA/NA	NA/NA	耐多药	3D-L₃-Pto-Z-Lfx	100WIU/3次/w, ih,3m	①③⑤
范凌^[23]	2017	40/40	24:16/24:16	54.6±4.8/53.5±4.3	耐药	3H-R-Z-E	3WIU/3次/w,inh,6m	①②③④⑦⑧⑨⑩
胡丽娜^[24]	2019	41/41	25:16/24:17	37.7±6.29/38.1±7.0	耐多药	3E-Pto-Z-Lfx-Am	100μg/3次/w, inh,3m	①⑤⑦⑩
李杨^[25]	2019	15/15	8:7/9:6	34.3±2.2/35.2±2.1	耐药	2H-R-Z-E-S/6H-R-E	300WIU/3次/w,inh,6m	①②④
胡丽娜^[26]	2019	54/54	34:20/32:32	53.7±4.4/54.1±4.4	耐药	6H-L₂-Z-E	300WIU/3次/w, inh,6m	①②⑧⑨

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