肺癌患者免疫检查点抑制剂相关肺炎危险因素:基于真实世界研究的Meta 分析

Risk factors of real-world immune checkpoint inhibitor-related pneumonitis in patientswith lung cancer: a meta-analysis

目的通过系统评价的方法分析肺癌患者真实世界免疫检查点抑制剂相关肺炎(checkpoint inhibitor-related pneumonitis,CIP)的危险因素。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、中国知网、万方数据库和维普数据库,检索关于肺癌患者发生CIP的病例对照研究和队列研究,检索时限均为建库至2023年3月。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.4.1软件进行Meta分析。结果共纳入18项研究,共4990例患者。Meta分析结果显示,间质性肺疾病[比值比(odds ratio,OR)=9.32,95%置信区间(confidence interval,CI)4.66~18.67,P<0.01]、吸烟史(OR=2.39,95%CI 1.29~4.45,P<0.01)、慢性阻塞性肺疾病病史(OR=5.54,95%CI 2.96~10.36,P<0.01)、胸部放疗史(OR=2.74,95%CI 1.80~4.19,P<0.01)、肺纤维化病史(OR=7.46,95%CI 4.25~13.09,P<0.01)、高细胞程序性死亡配体1(programmed death ligand 1,PD-L1)表达(OR=2.98,95%CI 1.71~5.22,P<0.01)、高嗜酸性粒细胞绝对计数(absolute eosinophil count,AEC)(OR=3.92,95%CI 2.17~7.08,P<0.01)及帕博利珠单抗(OR=2.90,95%CI 1.56~5.37,P<0.01)是肺癌患者发生CIP的危险因素。结论间质性肺疾病、吸烟史、慢性阻塞性肺疾病病史、胸部放疗史、肺纤维化病史、高PD-L1表达、高AEC、帕博利珠单抗是肺癌患者发生CIP的危险因素,低白蛋白水平研究证据尚不足,仍需开展前瞻性研究进一步明确。

Objective Risk factors for real-word immune checkpoint inhibitor-related pneumonitis in patients with lung cancer were analyzed by systematic analysis.Methods Computerized retrieval of PubMed,EMbase,Web of Science,the Cochrane Library,WanFang Data,CNKI and VIP databases was carried out.Studies were collected from the database establishment to March 2023.Three researchers independently screened the literature,extracted data,and evaluated the risk of bias in the included studies.Meta-analysis was performed using RevMan5.4.1software.Results A total of 18 studies were included with a total of 4990 patients.The results of meta-analysis showed that,interstitial pneumonia[odds ratio(OR)=9.32,95%confidence interval(CI)4.66-18.67,P<0.01],smoking history(OR=2.39,95%CI 1.29-4.45,P<0.01),chronic obstructive pulmonary disease(COPD)(OR=5.54,95%CI 2.96-10.36,P<0.01),chest radiotherapy(OR=2.74,95%CI 1.80-4.19,P<0.01),pulmonary fibrosis(OR=7.46,95%CI 4.25-13.09,P<0.01),high programmed death ligand 1(PD-L1)expression(OR=2.98,95%CI 1.71-5.22,P<0.01),high absolute eosinophil count(AEC)(OR=3.92,95%CI 2.17-7.08,P<0.01)and pembrolizumab(OR=2.90,95%CI 1.56-5.37,P<0.01)were independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients.Conclusions Interstitial pneumonia,smoking history,COPD,Chest radiotherapy,pulmonary fibrosis,high PD-L1expression,high AEC and pembrolizumab are independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients.Due to insufficient evidence on the risk factors of low albumin,more studies are needed to further identify it.