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中华实验和临床感染病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (06) : 378 -383. doi: 10.3877/cma.j.issn.1674-1358.2025.06.008

短篇论著

化疗后肺癌合并肺结核患者临床特征及其不良结局的影响因素
梁嘉佳1, 谢峥文2, 徐磊3, 付贵华1, 方志雄3, 张海明3,()   
  1. 1 411100 湘潭市,湘潭市中心医院肿瘤一科
    2 411100 湘潭市,湘潭市中心医院感染性疾病肝病科
    3 411100 湘潭市,湘潭市中心医院公卫中心
  • 收稿日期:2025-07-15 出版日期:2025-12-15
  • 通信作者: 张海明
  • 基金资助:
    湖南省自然科学基金项目(2024JJ9563)

Clinical characteristics of lung cancer patients with pulmonary tuberculosis after chemotherapy and influencing factors for adverse outcomes

Jiajia Liang1, Zhengwen Xie2, Lei Xu3, Guihua Fu1, Zhixiong Fang3, Haiming Zhang3,()   

  1. 1 Department of Oncology I, Xiangtan Central Hospital, Xiangtan 411100, China
    2 Department of Infectious Diseases and Hepatology, Xiangtan Central Hospital, Xiangtan 411100, China
    3 Public Health Center, Xiangtan Central Hospital, Xiangtan 411100, China
  • Received:2025-07-15 Published:2025-12-15
  • Corresponding author: Haiming Zhang
引用本文:

梁嘉佳, 谢峥文, 徐磊, 付贵华, 方志雄, 张海明. 化疗后肺癌合并肺结核患者临床特征及其不良结局的影响因素[J/OL]. 中华实验和临床感染病杂志(电子版), 2025, 19(06): 378-383.

Jiajia Liang, Zhengwen Xie, Lei Xu, Guihua Fu, Zhixiong Fang, Haiming Zhang. Clinical characteristics of lung cancer patients with pulmonary tuberculosis after chemotherapy and influencing factors for adverse outcomes[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2025, 19(06): 378-383.

目的

分析化疗后肺癌合并肺结核患者的临床特征,并探讨其不良结局的影响因素。

方法

回顾性收集2017年5月至2025年7月湘潭市中心医院收治的58例化疗后发生肺结核的肺癌患者的临床资料,其中18例患者接受含免疫检查点抑制剂(ICIs)治疗方案(ICIs组),其余40例患者纳入非ICIs组;根据患者治疗结局分为不良结局组(27例)和良好结局组(31例)。采用单因素和多因素Logistic回归分析化疗后发生肺结核的肺癌患者不良治疗结局(非结核性死亡、结核性死亡、治疗失败或失访)的影响因素。

结果

ICIs组患者ALC显著低于非ICIs组患者[0.76(0.62,1.05)×109/L vs. 1.18(0.95,1.52)×109/L:U=168.4、P=0.004],而NLR[4.7(3.2,6.5)vs. 2.8(2.0,3.5):U=105.5、P<0.001]和C-反应蛋白水平[32.5(21.0,54.8) mg/L vs. 13.5(8.2,21.5) mg/L:U=97.6、P=0.001]显著高于非ICIs组患者;此外,ICIs组患者中陈旧性肺结核占比(33.3% vs. 17.5%:χ2=5.010、P=0.028)、痰抗酸染色阳性率(77.8% vs. 47.5%:χ2=5.660、P=0.017)、痰Mtb DNA阳性率(88.9% vs. 55.0%:χ2=5.100、P=0.024)均显著高于非ICIs组。多因素Logistic回归分析:ICIs治疗(aOR=8.85、95%CI:2.41~32.52、P=0.001)和陈旧性肺结核(aOR=4.14、95%CI:1.38~12.42、P=0.011)为肺癌合并肺结核发生不良结局的影响因素。虽然弥散粟粒影差异有统计学意义(aOR=7.76、P=0.023),但因其95%CI宽泛(1.32~45.65)且事件数少(n=5),未将其确定为稳定的独立危险因素。

结论

ICIs治疗是肺癌合并肺结核患者不良结局的最强独立风险因素,陈旧性肺结核史显著增加4倍风险。对出现胸部弥散粟粒影者需警惕重症结核,但其独立预测价值需行大样本研究进一步验证。

Objective

To investigate the clinical characteristics of lung cancer patients with pulmonary tuberculosis after chemotherapy and to identify the influencing factors for adverse outcomes.

Methods

Clinical data of 58 lung cancer patients who developed pulmonary tuberculosis after chemotherapy admitted to Xiangtan Central Hospital from May 2017 to July 2025 were collected, retrospectively, including 18 patients treated with immunocheckpoint inhibitor (ICIs) (ICIs group), while the remaining 40 patients were included in non-ICIs group. Patients were categorized into adverse outcome group (27 cases) and favorable outcome group (31 cases) based on treatment outcomes. Univariate and multivariate Logistic regression analyses were performed to identify influencing factors for adverse treatment outcomes (non-tuberculous death, tuberculous death, treatment failure or loss to follow-up) of lung cancer patients after chemotherapy.

Results

ALC level of patients in ICI group was significantly lower than that of non-ICI group [0.76 (0.62, 1.05)×109/L vs. 1.18 (0.95, 1.52)×109/L: U=168.4, P=0.004], while the levels of NLR [4.7 (3.2, 6.5) vs. 2.8 (2.0, 3.5): U=105.5, P<0.001] and C-reactive protein [32.5 (21.0, 54.8) mg/L vs. 13.5 (8.2, 21.5) mg/L: U=97.6, P=0.001] were significantly higher than those of non-ICI group. Additionally, the proportion of patients with old pulmonary tuberculosis (33.3% vs. 17.5%: χ2=5.010, P=0.028), positive acid-fast sputum smear rate (77.8% vs. 47.5%: χ2=5.660, P=0.017) and positive sputum MTB DNA rate (88.9% vs. 55.0%: χ2=5.100, P=0.024) were significantly higher of patients in ICI group compared with non-ICI group. The results of multivariate Logistic regression analysis showed that ICIs therapy (adjusted OR=8.85, 95%CI: 2.41-32.52, P=0.001) and prior tuberculosis (adjusted OR=4.14, 95%CI: 1.38-12.42, P=0.011) were independent risk factors for adverse outcomes of patients with lung cancer complicated with pulmonary tuberculosis. Although diffused miliary opacities was with significant difference (adjusted OR=7.76, P=0.023), its excessively wide 95%CI (1.32-45.65) and limited number of events (n=5) precluded its establishment as a stable independent risk factor.

Conclusions

ICIs therapy is the strongest independent risk factor for adverse outcomes inpatients with lung cancer and pulmonary tuberculosis, while prior tuberculosis history increases the risk by 4-fold. Patients with diffused miliary opacities on chest imaging should be vigilant for severe tuberculosis, however, the independent predictive value needs to be further verified by large sample study.

表1 ICI组与非ICI组肺癌合并肺结核患者临床特征及治疗转归
指标 ICIs组(18例) 非ICIs组(40例) 统计量 P
年龄(
±s,岁)
67.28±6.17 63.28 ± 11.12 t=1.41 0.170
性别 [例(%)] χ2=0.034 1.000a
17(94.4) 37(92.5)
1(5.6) 3(7.5)
吸烟史 [例(%)] 15(83.3) 35(87.5) χ2=0.230 0.630a
陈旧性肺结核 [例(%)] 6(33.3) 7(17.5) χ2=5.010 0.028a
化疗前TB-IGRA阳性率 [例(%)] 8(44.4) 17(42.5) 1.000b
ALC [MP25P75),×109/L] 0.76(0.62,1.05) 1.18(0.95,1.52) U=168.4 0.004
NLR [MP25P75)] 4.7(3.2,6.5) 2.8(2.0,3.5) U=105.5 <0.001
CRP [MP25P75),mg/L] 32.5(21.0,54.8) 13.5(8.2,21.5) U=97.6 0.001
病理类型 [例(%)] χ2=3.00 0.227a
小细胞癌 1(5.6) 2(5.0)
鳞癌 11(61.1) 16(40.0)
腺癌 6(33.3) 22(55.0)
症状 [例(%)]
咳嗽 13(72.2) 30(75.5) χ2=0.060 0.806a
发热 1(5.6) 2(5.0) χ2=0.930 1.000a
呼吸困难 4(22.2) 18(45.0) χ2=6.830 0.076a
基础疾病 [例(%)]
COPD 11(61.1) 19(47.5) χ2=1.070 0.301a
糖尿病 2(11.1) 3(7.5) χ2=1.550 0.634a
肿瘤分期 [例(%)] χ2=0.006 1.000a
Ⅰ~Ⅱ 3(16.7) 7(17.5)
Ⅲ~Ⅳ 15(83.3) 33(82.5)
CT征象 [例(%)]
空洞 2(11.1) 4(10.0) χ2=1.860 1.000a
胸腔积液 4(22.2) 7(17.5) χ2=3.410 0.734a
弥散粟粒影 3(16.7) 2(5.0) 0.330b
结节影 3(16.7) 8(20.0) χ2=3.410 1.000a
纵隔淋巴结肿大 11(61.1) 22(55.0) χ2=7.760 0.644a
结核病原学检测 [例(%)]
痰抗酸染色 14(77.8) 19(47.5) χ2=5.660 0.017a
痰MTB DNA 16(88.9) 22(55.0) χ2=5.100 0.024a
痰MTB培养 17(94.4) 31(77.5) χ2=3.100 0.157a
TB-IGRA阳性 [例(%)] 10(55.6) 22(55.0) 1.000b
发病时间 [MP25P75),月] 7.5(4.75,15.75) 6(4.0,11.0) U=318.5 0.270b
治疗方案 [例(%)]
一线标准方案(HRZE) 13(72.2) 24(85.0) 0.280b
含氟喹诺酮类方案 5(27.8) 6(15.0) 0.280b
含二线注射剂方案 2(11.1) 1(2.5) 0.220b
含利奈唑胺方案 3(16.7) 3(7.5) 0.350b
治疗方案调整 7(38.9) 9(22.5) 0.220b
治疗结局 [例(%)] 0.149b
治愈 3(16.7) 13(32.5)
完成疗程 4(22.2) 11(27.5)
结核死亡 3(16.7) 4(10.0)
非结核死亡 4(22.2) 6(15.0)
治疗失败 3(16.7) 4(10.0)
丢失 1(5.6) 2(5.0)
表2 肺癌合并肺结核患者发生不良结局影响因素的单因素Logistic回归分析
表3 肺癌合并肺结核患者发生不良治疗结局影响因素的多因素Logistic回归分析
[1]
Ettinger DS, Wood DE, Aggarwal C, et al. NCCN guidelines insights: non-small cell lung cancer, version 1. 2020[J]. J Natl Compr Canc Netw,2019,17(12):1464-1472.
[2]
Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade[J]. N Engl J Med,2018,378(2):158-168.
[3]
Langan EA, Graetz V, Allerheiligen J, et al. Immune checkpoint inhibitors and tuberculosis: an old disease in a new context[J]. Lancet Oncol,2020,21(1):e55-e65.
[4]
Cotliar J, Querfeld C, Boswell WJ, et al. Pembrolizumab-associated sarcoidosis[J]. JAAD Case Rep,2016,2(4):290-293.
[5]
中华人民共和国国家卫生和计划生育委员会. WS 288-2017肺结核诊断[J]. 结核与肺部疾病杂志,2024,5(4):376-378.
[6]
Goldstraw P, Chansky K, Crewley J, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM classification for lung cancer[J]. J Thorac Oncol,2016,11(1):39-51.
[7]
中华医学会, 中华医学会杂志社, 中华医学会全科医学分会, 等. 肺结核基层诊疗指南(2018年)[J]. 中华全科医师杂志,2019,18(8):709-717.
[8]
胡鑫洋, 高静韬. 世界卫生组织《2024年全球结核病报告》解读[J]. 结核与肺部疾病杂志,2024,5(6):500-504.
[9]
Wei J, Li W, Zhang P, et al. Current trends in sensitizing immune checkpoint inhibitors for cancer treatment[J]. Mol Cancer,2024,23(1):279.
[10]
Kauffman KD, Sakai S, Lora NE, et al. PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques[J]. Sci Immunol,2021,6(55):eabf3861.
[11]
Bae S, Kim YJ, Kim MJ, et al. Risk of tuberculosis in patients with cancer treated with immune checkpoint inhibitors: a nationwide observational study[J]. J Immunother Cancer,2021,9(9):e002960.
[12]
Fujita K, Yamamoto Y, Kanai O, et al. Incidence of active tuberculosis in lung cancer patients receiving immune checkpoint inhibitors[J]. Open Forum Infect Dis,2020,7(5):a126.
[13]
Zhu J, He Z, Liang D, et al. Pulmonary tuberculosis associated with immune checkpoint inhibitors: a pharmacovigilance study[J]. Thorax,2022,77(7):721-723.
[14]
Liu K, Wang D, Yao C, et al. Increased tuberculosis incidence due to immunotherapy based on PD-1 and PD-L1 blockade: A systematic review and Meta-analysis[J]. Front Immunol,2022,13:727220.
[15]
任坦坦, 詹森林, 王玉香, 等. PD-1/PD-L1抑制剂相关活动性结核病的临床特点及文献复习[J]. 结核与肺部疾病杂志,2023,4(1):27-32.
[16]
张丽帆, 杨峥蓉, 刘晓清. 程序性死亡受体1/程序性死亡配体在结核分枝杆菌感染免疫中的作用和宿主导向治疗前景[J/CD]. 中华实验和临床感染病杂志(电子版),2021,15(3):145-148.
[17]
喻晓雯, 张其奥, 谢建平. PD‑1/PD‑L1, PD‑L2信号通路及其在宿主抗结核免疫中作用的研究进展[J]. 中华结核和呼吸杂志,2024,47(5):485-489.
[18]
Chen HW, Kuo YW, Chen CY, et al. Increased tuberculosis reactivation risk in patients receiving immune checkpoint inhibitor-based therapy[J]. Oncologist,2024,29(4):e498-e506.
[19]
Fernández-Ruiz M, Meije Y, Manuel O, et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Introduction)[J]. Clin Microbiol Infect,2018,24(Suppl 2):S2-S9.
[20]
Wen ZL, Wang L, Ma H, et al. Integrated single-cell transcriptome and T cell receptor profiling reveals defects of T cell exhaustion in pulmonary tuberculosis[J]. J Infect,2024,88(6):106158.
[21]
Tezera LB, Bielecka MK, Ogongo P, et al. Anti-PD-1 immunotherapy leads to tuberculosis reactivation via dysregulation of TNF-α[J]. Elife,2020,9:e52668.
[22]
Lin C, Xu G, Gao S, et al. Tuberculosis infection following immune checkpoint inhibitor treatment for advanced cancer: a case report and literature review[J]. Front Immunol,2023,14:1162190.
[23]
He Y, Peng D, Liang P, et al. Immune checkpoint inhibitors and tuberculosis infection in lung cancer: A case series and systematic review with pooled analysis[J]. J Clin Pharmacol,2023,63(4):397-409.
[24]
Britt AS, Huang C, Huang CH. Hyperprogressive disease in non-small cell lung cancer treated with immune checkpoint inhibitor therapy, fact or myth?[J]. Front Oncol,2022,12:996554.
[25]
Yoshida T, Ichikawa J, Giuroiu I, et al. C reactive protein impairs adaptive immunity in immune cells of patients with melanoma[J]. J Immunother Cancer,2020,8(1):e000234.
[26]
Kempker RR, Salindri AD, Avaliani T, et al. High rates of post-tuberculosis lung disease among persons successfully treated for drug-susceptible and resistant tuberculosis[J]. Thorax,2025: thorax-2024-222350. [Online ahead of print].
[27]
Hwang IK, Paik SS, Lee SH. Impact of pulmonary tuberculosis on the EGFR mutational status and clinical outcome in patients with lung adenocarcinoma[J]. Cancer Res Treat,2018,51(1):158-168.
[28]
Nahid P, Dorman SE, Alipanah N, et al. Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of drug-susceptible tuberculosi[J]. Clin Infect Dis,2016,63(7):853-867.
[29]
Fujita K, Elkington P, Redelman-Sidi G, et al. Serial interferon-gamma release assay in lung cancer patients receiving immune checkpoint inhibitors: a prospective cohort study[J]. Cancer Immunol Immunother,2022,71(11):2757-2764.
[30]
赵祥, 程渊, 张蒙, 等. 接受免疫检查点抑制剂治疗的晚期肺癌患者的潜伏结核感染及活动性结核病管理[J]. 中华医学杂志,2022,102(6):454-462.
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