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Article(id=1198558167287296866, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198558165093675863, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.1167.2024.0129, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1693756800000, receivedDateStr=2023-09-04, revisedDate=null, revisedDateStr=null, acceptedDate=1701360000000, acceptedDateStr=2023-12-01, onlineDate=1763688135214, onlineDateStr=2025-11-21, pubDate=1724774400000, pubDateStr=2024-08-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763688135214, onlineIssueDateStr=2025-11-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763688135214, creator=13701087609, updateTime=1763688135214, updator=13701087609, issue=Issue{id=1198558165093675863, tenantId=1146029695717560320, journalId=1189873630562394117, year='2024', volume='49', issue='8', pageStart='855', pageEnd='976', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763688134691, creator=13701087609, updateTime=1763689174168, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1198562525043327039, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198558165093675863, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1198562525043327040, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198558165093675863, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=861, endPage=867, ext={EN=ArticleExt(id=1198558167559926632, articleId=1198558167287296866, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Analysis of clinical characteristics and risk factors for immune checkpoint inhibitor-related pneumonitis in NSCLC patients, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the potential risk factors for immune checkpoint-related pneumonia (CIP) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), to identify high-risk patients with CIP at an early stage. Methods A total of 728 NSCLC patients treated with ICIs at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2023 were retrospectively selected, including 47 cases with CIP (CIP group), and 141 matched NSCLC patients without CIP (control group). Clinical data, laboratory tests, and CT images before the first immunotherapy were collected for all patients in two groups. The FACT medical imaging software was utilized for quantitative emphysema assessment in patients' CT scans. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with CIP. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of these factors for CIP occurrence in NSCLC patients. Results Among the 47 CIP patients, 40(85.1%) were male, with 25(53.0%) aged between 41 and 65 years. Grade 3 pneumonia according to the Common Terminology Criteria for Adverse Events (CTCAE) was found in 28(59.6%) cases, characterized by a predominant reticular radiographic pattern. Multivariate logistic regression analysis showed that a low albumin level (OR=0.889, 95%CI 0.808-0.979, P=0.017), targeted therapy (OR=9.204, 95%CI 1.678-50.486, P=0.011), anti-angiogenic therapy (OR=0.056, 95%CI 0.020-0.161, P<0.001), and a high percentage of low attenuation area (LAA%) (OR=1.227, 95%CI 1.053-1.430, P=0.009) were significant factors influencing CIP occurrence. The combined predictive model using these four factors showed an area under the ROC curve of 0.888 (95%CI 0.838-0.939), with a sensitivity of 0.894 and a specificity of 0.801 for predicting CIP in NSCLC patients. Conclusions Low serum albumin, first-line targeted therapy, and high LAA% are identified as risk factors for CIP occurrence, while anti-angiogenic therapy is a protective factor. The predictive model based on these four variables effectively predicts the risk of CIP in NSCLC patients.

, correspAuthors=Hua-Qi Wang, authorNote=null, correspAuthorsNote=
E-mail:
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目的 探讨使用免疫检查点抑制剂(ICIs)治疗的非小细胞肺癌(NSCLC)患者发生ICIs相关性肺炎(CIP)的潜在危险因素，以早期识别CIP高危患者。方法 回顾性选取2020年1月-2023年6月在郑州大学第一附属医院接受ICIs治疗的728例NSCLC患者，其中CIP 47例。以47例CIP为CIP组，选取141例非CIP的NSCLC患者作为对照组。收集两组患者临床资料及第1次免疫治疗前实验室检查结果、CT影像等，应用FACT医学影像系统软件对患者CT影像进行肺气肿定量评估，采用单因素和多因素logistic回归分析CIP发生的危险因素。绘制受试者工作特征(ROC)曲线评估上述危险因素对NSCLC患者发生CIP的预测价值。结果 47例CIP患者中，男40例(85.1%)，年龄40~65岁25例(53.0%)，不良事件通用分级标准(CTCAE)分级3级肺炎28例(59.6%)，主要影像学分型为网格型。多因素logistic回归分析显示，白蛋白(ALB)低(OR=0.889，95%CI 0.808~0.979，P=0.017)、靶向治疗(OR=9.204，95%CI 1.678~50.486，P=0.011)、抗血管生成治疗(OR=0.056，95%CI 0.020~0.161，P<0.001)、低衰减区域百分比(LAA%)高(OR=1.227，95%CI 1.053~1.430，P=0.009)是CIP发生的独立影响因素。ROC曲线分析结果显示，联合上述4个影响因素预测NSCLC患者发生CIP的ROC曲线下面积为 0.888(95%CI 0.838~0.939)，敏感度为0.894，特异度为0.801。结论 血清ALB低、接受一线靶向治疗、LAA%高是发生CIP的独立危险因素，接受抗血管生成治疗是CIP发生的保护因素。采用上述4个变量建立的预测模型可较好地预测NSCLC患者发生CIP的风险。

, correspAuthors=王华启, authorNote=null, correspAuthorsNote=
王华启，E-mail：
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邱丽亮，硕士研究生，主要从事慢性阻塞性肺疾病及肺恶性肿瘤的相关研究

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邱丽亮，硕士研究生，主要从事慢性阻塞性肺疾病及肺恶性肿瘤的相关研究

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邱丽亮，硕士研究生，主要从事慢性阻塞性肺疾病及肺恶性肿瘤的相关研究

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year=2022, volume=47, issue=11, pageStart=1152, pageEnd=1158, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=高磊, 俞阳, 李晓梅, journalName=解放军医学杂志, refType=null, unstructuredReference=高磊, 俞阳, 李晓梅, 等. 化疗与免疫检查点抑制剂联用对肿瘤的作用研究进展[J]. 解放军医学杂志, 2022, 47(11): 1152-1158., articleTitle=化疗与免疫检查点抑制剂联用对肿瘤的作用研究进展, refAbstract=null), Reference(id=1198578979725738449, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2022, volume=13, issue=null, pageStart=830631, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=Yin J, Wu Y, Yang X, journalName=Front Immunol, refType=null, unstructuredReference=Yin J, Wu Y, Yang X, et al. Checkpoint inhibitor pneumonitis induced by anti-PD-1/PD-L1 therapy in non-small-cell lung cancer: occurrence and mechanism[J]. Front Immunol, 2022, 13: 830631., articleTitle=Checkpoint inhibitor pneumonitis induced by anti-PD-1/PD-L1 therapy in non-small-cell lung cancer: occurrence and mechanism, refAbstract=null), Reference(id=1198578979822207442, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2023, volume=40, issue=9, pageStart=824, pageEnd=828, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=张涵, 祖育娜, 张华, journalName=新乡医学院学报, refType=null, unstructuredReference=张涵, 祖育娜, 张华. 非小细胞肺癌患者肺泡灌洗液中T淋巴细胞亚群及血清炎症因子与免疫检查点抑制剂相关性肺炎的关系[J]. 新乡医学院学报, 2023, 40(9): 824-828., articleTitle=非小细胞肺癌患者肺泡灌洗液中T淋巴细胞亚群及血清炎症因子与免疫检查点抑制剂相关性肺炎的关系, refAbstract=null), Reference(id=1198578979931259347, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2023, volume=43, issue=8, pageStart=702, pageEnd=704, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=张耀, 刘艺, 刘思行, journalName=中国实用内科杂志, refType=null, unstructuredReference=张耀, 刘艺, 刘思行, 等. 免疫检查点抑制剂治疗恶性肿瘤诱发糖尿病4例报告[J]. 中国实用内科杂志, 2023, 43(8): 702-704., articleTitle=免疫检查点抑制剂治疗恶性肿瘤诱发糖尿病4例报告, refAbstract=null), Reference(id=1198578980023534036, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2023, volume=40, issue=7, pageStart=621, pageEnd=627, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=张杰, 魏渼倬, 赵玲, journalName=新乡医学院学报, refType=null, unstructuredReference=张杰, 魏渼倬, 赵玲, 等. 外周血中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值与接受免疫检查点抑制剂治疗食管鳞状细胞癌患者预后的相关性[J]. 新乡医学院学报, 2023, 40(7): 621-627., articleTitle=外周血中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值与接受免疫检查点抑制剂治疗食管鳞状细胞癌患者预后的相关性, refAbstract=null), Reference(id=1198578980140974551, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2018, volume=4, issue=12, pageStart=1721, pageEnd=1728, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=Wang DY, Salem JE, Cohen JV, journalName=JAMA Oncol, refType=null, unstructuredReference=Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis[J]. JAMA Oncol, 2018, 4(12): 1721-1728., articleTitle=Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis, refAbstract=null), Reference(id=1198578980208083416, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2020, volume=17, issue=3, pageStart=599, pageEnd=611, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=Zhai X, Zhang J, Tian Y, journalName=Cancer Biol Med, refType=null, unstructuredReference=Zhai X, Zhang J, Tian Y, et al. The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients[J]. Cancer Biol Med, 2020, 17(3): 599-611., articleTitle=The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients, refAbstract=null), Reference(id=1198578980308746714, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2019, volume=39, issue=7, pageStart=1923, pageEnd=1937, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=Kalisz KR, Ramaiya NH, Laukamp KR, journalName=Radiographics, refType=null, unstructuredReference=Kalisz KR, Ramaiya NH, Laukamp KR, et al. Immune checkpoint inhibitor therapy-related pneumonitis: patterns and management[J]. Radiographics, 2019, 39(7): 1923-1937., articleTitle=Immune checkpoint inhibitor therapy-related pneumonitis: patterns and management, refAbstract=null), Reference(id=1198578981416042972, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2023, volume=35, issue=1, pageStart=31, pageEnd=36, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=Yu X, Wu J, Su C, journalName=Curr Opin Oncol, refType=null, unstructuredReference=Yu X, Wu J, Su C. Progress in diagnosis and treatment of checkpoint inhibitor pneumonitis[J]. Curr Opin Oncol, 2023, 35(1): 31-36., articleTitle=Progress in diagnosis and treatment of checkpoint inhibitor pneumonitis, refAbstract=null), Reference(id=1198578981504123357, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2022, volume=11, issue=2, pageStart=295, pageEnd=306, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=Chao Y, Zhou J, Hsu S, journalName=Transl Lung Cancer Res, refType=null, unstructuredReference=Chao Y, Zhou J, Hsu S, et al. Risk factors for immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer[J]. Transl Lung Cancer Res, 2022, 11(2): 295-306., articleTitle=Risk factors for immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer, refAbstract=null), Reference(id=1198578981608980959, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2019, volume=42, issue=11, pageStart=820, pageEnd=825, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=陈良安, journalName=中华结核和呼吸杂志, refType=null, unstructuredReference=陈良安. 免疫检查点抑制剂相关肺炎诊治专家共识[J]. 中华结核和呼吸杂志, 2019, 42(11): 820-825., articleTitle=免疫检查点抑制剂相关肺炎诊治专家共识, refAbstract=null), Reference(id=1198578981701255650, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2021, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=中国临床肿瘤学会指南工作委员会, journalName=中国临床肿瘤学会(CSCO)免疫检查点抑制剂相关的毒性管理指南2021, refType=null, unstructuredReference=中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)免疫检查点抑制剂相关的毒性管理指南2021[M]. 北京: 人民卫生出版社, 2021., articleTitle=null, refAbstract=null), Reference(id=1198578981764170213, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2021, volume=112, issue=1, pageStart=90, pageEnd=92, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=Freites-martinez A, Santana N, Arias-Santiago S, journalName=Actas Dermosifiliogr (Engl Ed), refType=null, unstructuredReference=Freites-martinez A, Santana N, Arias-Santiago S, et al. Using the common terminology criteria for adverse events (CTCAE-Version 5.0) to evaluate the severity of adverse events of anticancer therapies[J]. Actas Dermosifiliogr (Engl Ed), 2021, 112(1): 90-92., articleTitle=Using the common terminology criteria for adverse events (CTCAE-Version 5.0) to evaluate the severity of adverse events of anticancer therapies, refAbstract=null), Reference(id=1198578981831279080, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2018, volume=9, issue=null, pageStart=1430, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=Ma K, Lu Y, Jiang S, journalName=Front Pharmacol, refType=null, unstructuredReference=Ma K, Lu Y, Jiang S, et al. The relative risk and incidence of immune checkpoint inhibitors related pneumonitis in patients with advanced cancer: a meta-analysis[J]. Front Pharmacol, 2018, 9: 1430., articleTitle=The relative risk and incidence of immune checkpoint inhibitors related pneumonitis in patients with advanced cancer: a meta-analysis, refAbstract=null), Reference(id=1198578981919359465, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2019, volume=26, issue=null, pageStart=17, pageEnd=22, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=Akella P, Loganathan S, Jindal V, journalName=Respir Med Case Rep, refType=null, unstructuredReference=Akella P, Loganathan S, Jindal V, et al. Anti PD-1 immunotherapy related interstitial lung disease presenting as respiratory failure - A review with case series[J]. Respir Med Case Rep, 2019, 26: 17-22., articleTitle=Anti PD-1 immunotherapy related interstitial lung disease presenting as respiratory failure - A review with case series, refAbstract=null), Reference(id=1198578982011634155, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2011, volume=66, issue=9, pageStart=782, pageEnd=787, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=Mohamed Hoesein FA, de Hoop B, Zanen P, journalName=Thorax, refType=null, unstructuredReference=Mohamed Hoesein FA, de Hoop B, Zanen P, et al. CT-quantified emphysema in male heavy smokers: association with lung function decline[J]. Thorax, 2011, 66(9): 782-787., articleTitle=CT-quantified emphysema in male heavy smokers: association with lung function decline, refAbstract=null), Reference(id=1198578982120686063, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2013, volume=8, issue=4, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=Mets OM, de Jong PA, van Ginneken B, journalName=PLoS One, refType=null, unstructuredReference=Mets OM, de Jong PA, van Ginneken B, et al. CT air trapping is independently associated with lung function reduction over time[J]. PLoS One, 2013, 8(4): e61783., articleTitle=CT air trapping is independently associated with lung function reduction over time, refAbstract=null), Reference(id=1198578982212960754, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2012, volume=7, issue=7, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=Mets OM, Smit EJ, Mohamed Hoesein FA, journalName=PLoS One, refType=null, unstructuredReference=Mets OM, Smit EJ, Mohamed Hoesein FA, et al. Visual versus automated evaluation of chest computed tomography for the presence of chronic obstructive pulmonary disease[J]. PLoS One, 2012, 7(7): e42227., articleTitle=Visual versus automated evaluation of chest computed tomography for the presence of chronic obstructive pulmonary disease, refAbstract=null), Reference(id=1198578982326206965, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2019, volume=20, issue=1, pageStart=101, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=Occhipinti M, Paoletti M, Bartholmai BJ, journalName=Respir Res, refType=null, unstructuredReference=Occhipinti M, Paoletti M, Bartholmai BJ, et al. Spirometric assessment of emphysema presence and severity as measured by quantitative CT and CT-based radiomics in COPD[J]. Respir Res, 2019, 20(1): 101., articleTitle=Spirometric assessment of emphysema presence and severity as measured by quantitative CT and CT-based radiomics in COPD, refAbstract=null), Reference(id=1198578982405898741, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2016, volume=30, issue=6, pageStart=571, pageEnd=584, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=Day D, Hansen AR, journalName=BioDrugs, refType=null, unstructuredReference=Day D, Hansen AR. Immune-related adverse events associated with immune checkpoint inhibitors[J]. BioDrugs, 2016, 30(6): 571-584., articleTitle=Immune-related adverse events associated with immune checkpoint inhibitors, refAbstract=null), Reference(id=1198578982485590518, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2018, volume=378, issue=2, pageStart=158, pageEnd=168, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=Postow MA, Sidlow R, Hellmann MD, journalName=N Engl J Med, refType=null, unstructuredReference=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., articleTitle=Immune-related adverse events associated with immune checkpoint blockade, refAbstract=null), Reference(id=1198578982565282294, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2019, volume=20, issue=6, pageStart=442, pageEnd=450.e4, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=Fukihara J, Sakamoto K, Koyama J, journalName=Clin Lung Cancer, refType=null, unstructuredReference=Fukihara J, Sakamoto K, Koyama J, et al. Prognostic impact and risk factors of immune-related pneumonitis in patients with non-small-cell lung cancer who received programmed death 1 inhibitors[J]. Clin Lung Cancer, 2019, 20(6): 442-450.e4., articleTitle=Prognostic impact and risk factors of immune-related pneumonitis in patients with non-small-cell lung cancer who received programmed death 1 inhibitors, refAbstract=null), Reference(id=1198578982644974072, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2022, volume=13, issue=null, pageStart=948370, pageEnd=null, url=null, language=null, rfNumber=[23], rfOrder=22, authorNames=Hu S, Guo Q, Wang S, journalName=Front Physiol, refType=null, unstructuredReference=Hu S, Guo Q, Wang S, et al. Supplementation of serum albumin is associated with improved pulmonary function: NHANES 2013-2014[J]. Front Physiol, 2022, 13: 948370., articleTitle=Supplementation of serum albumin is associated with improved pulmonary function: NHANES 2013-2014, refAbstract=null), Reference(id=1198578982724665850, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2016, volume=139, issue=11, pageStart=2593, pageEnd=2597, url=null, language=null, rfNumber=[24], rfOrder=23, authorNames=Mascia F, Schloemann DT, Cataisson C, journalName=Int J Cancer, refType=null, unstructuredReference=Mascia F, Schloemann DT, Cataisson C, et al. Cell autonomous or systemic EGFR blockade alters the immune-environment in squamous cell carcinomas[J]. Int J Cancer, 2016, 139(11): 2593-2597., articleTitle=Cell autonomous or systemic EGFR blockade alters the immune-environment in squamous cell carcinomas, refAbstract=null), Reference(id=1198578982816940538, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2019, volume=137, issue=null, pageStart=85, pageEnd=93, url=null, language=null, rfNumber=[25], rfOrder=24, authorNames=Jia Y, Zhao S, Jiang T, journalName=Lung Cancer, refType=null, unstructuredReference=Jia Y, Zhao S, Jiang T, et al. Impact of EGFR-TKIs combined with PD-L1 antibody on the lung tissue of EGFR-driven tumor-bearing mice[J]. Lung Cancer, 2019, 137: 85-93., articleTitle=Impact of EGFR-TKIs combined with PD-L1 antibody on the lung tissue of EGFR-driven tumor-bearing mice, refAbstract=null), Reference(id=1198578982913409531, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2000, volume=22, issue=6, pageStart=657, pageEnd=664, url=null, language=null, rfNumber=[26], rfOrder=25, authorNames=Kaner RJ, Ladetto JV, Singh R, journalName=Am J Respir Cell Mol Biol, refType=null, unstructuredReference=Kaner RJ, Ladetto JV, Singh R, et al. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema[J]. Am J Respir Cell Mol Biol, 2000, 22(6): 657-664., articleTitle=Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema, refAbstract=null), Reference(id=1198578982993101309, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2005, volume=175, issue=2, pageStart=1224, pageEnd=1231, url=null, language=null, rfNumber=[27], rfOrder=26, authorNames=Hamada N, Kuwano K, Yamada M, journalName=J Immunol, refType=null, unstructuredReference=Hamada N, Kuwano K, Yamada M, et al. Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice[J]. J Immunol, 2005, 175(2): 1224-1231., articleTitle=Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice, refAbstract=null), Reference(id=1198578983089570305, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2018, volume=13, issue=12, pageStart=1930, pageEnd=1939, url=null, language=null, rfNumber=[28], rfOrder=27, authorNames=Suresh K, Voong KR, Shankar B, journalName=J Thoracic Oncol, refType=null, unstructuredReference=Suresh K, Voong KR, Shankar B, et al. Pneumonitis in non-small cell lung cancer patients receiving immune checkpoint immunotherapy: incidence and risk factors[J]. J Thoracic Oncol, 2018, 13(12): 1930-1939., articleTitle=Pneumonitis in non-small cell lung cancer patients receiving immune checkpoint immunotherapy: incidence and risk factors, refAbstract=null), Reference(id=1198578983186039300, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, doi=null, pmid=null, pmcid=null, year=2018, volume=125, issue=null, pageStart=150, pageEnd=156, url=null, language=null, rfNumber=[29], rfOrder=28, authorNames=Cho JY, Kim J, Lee JS, journalName=Lung Cancer, refType=null, unstructuredReference=Cho JY, Kim J, Lee JS, et al. Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer[J]. 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NSCLC. 非小细胞肺癌；CIP. 免疫检查点抑制剂相关性肺炎；低衰减区域在不同肺叶中以不同的颜色表示；A. CIP患者；B.非CIP患者

, figureFileSmall=1FIOBYqBuduzj/TjnKS9Jg==, figureFileBig=1OOzTHm/YRwQkGDNHjRcuw==, tableContent=null), ArticleFig(id=1198578978295480755, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, language=EN, label=Fig.2, caption=Lung CT images of the NSCLC patients with CIP before and after treatment, figureFileSmall=Ef5dsDviCauo/1+1Uusdxg==, figureFileBig=SHt8TVZL281/lgme474JVg==, tableContent=null), ArticleFig(id=1198578978354201014, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, language=CN, label=图2, caption=典型CIP NSCLC患者治疗前后的CT图像表现

NSCLC. 非小细胞肺癌；CIP. 免疫检查点抑制剂相关性肺炎；A. 患者1，男，60岁，肺鳞癌，经过6个周期“多西他赛+洛铂”治疗后进展，继而行6个周期“帕博丽珠单抗+白蛋白结合紫杉醇+洛铂”治疗后双肺出现多发片状磨玻璃影；B. 患者2，男，82岁，肺腺癌，行4个周期“培美曲塞”、5个周期“贝伐珠单抗”和 “信迪利单抗+奥希替尼”治疗后，两肺出现多发条絮状高密度影及网格影；C. 患者3，男，61岁，肺鳞癌，行6周期“白蛋白结合紫杉醇+顺铂+信迪利单抗”治疗后，双肺出现结节样、片絮状高密度影，右肺为著；D. 患者4，经过60 mg甲泼尼龙缓慢减量及吡非尼酮治疗3个月后肺部炎症明显吸收、消散

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NSCLC. 非小细胞肺癌；CIP. 免疫检查点抑制剂相关性肺炎；LAA%. 低衰减区域百分比

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Comparison of the clinical data of two groups of patients with NSCLC

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特征CIP 组(n=47)对照组(n=141)P
性别[例(%)]1.000
男40(85.1)120(85.1)
女7(14.9)21(14.9)
年龄[岁, 例(%)]1.000
18~402(4.3)6(4.3)
40~6525(53.2)75(53.2)
>65岁20(42.6)60(42.6)
BMI [kg/m2, M(Q1, Q3)]22.49(21.23, 25.21)22.58(20.76, 24.97)0.491
吸烟史[例(%)]1.000
是28(59.6)84(59.6)
否19(40.4)57(40.4)
组织学类型[例(%)]0.864
鳞癌28(59.6)82(58.2)
腺癌19(40.4)59(41.8)
免疫治疗周期[M(Q1, Q3)]4(3, 7)9(6, 12)<0.001
NLR [M(Q1, Q3)]2.23(1.74, 3.14)2.64(1.90, 3.93)0.176
PLR [M(Q1, Q3)]130.07(94.83, 187.01)146.15(105.71, 212.96)0.243
ALB [g/L, M(Q1, Q3)]37.30(34.10, 38.80)40.00(37.00, 41.80)<0.001
肌酐[μmol/L, M(Q1, Q3)]73.00(62.00, 81.00)68.00(58.00, 78.00)0.068
化疗[例(%)]0.585
是43(91.5)125(88.7)
否4(8.5)16(11.3)
靶向治疗[例(%)]0.030
是5(10.6)4(2.8)
否42(89.4)137(97.2)
抗血管生成治疗[例(%)]<0.001
是6(12.8)105(74.5)
否41(87.2)36(25.5)
LAA%0.89(0.40, 5.27)0.25(0.04, 1.00)<0.001
), ArticleFig(id=1198578978786214337, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, language=CN, label=表1, caption=

两组NSCLC患者的临床特征比较

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特征CIP 组(n=47)对照组(n=141)P
性别[例(%)]1.000
男40(85.1)120(85.1)
女7(14.9)21(14.9)
年龄[岁, 例(%)]1.000
18~402(4.3)6(4.3)
40~6525(53.2)75(53.2)
>65岁20(42.6)60(42.6)
BMI [kg/m2, M(Q1, Q3)]22.49(21.23, 25.21)22.58(20.76, 24.97)0.491
吸烟史[例(%)]1.000
是28(59.6)84(59.6)
否19(40.4)57(40.4)
组织学类型[例(%)]0.864
鳞癌28(59.6)82(58.2)
腺癌19(40.4)59(41.8)
免疫治疗周期[M(Q1, Q3)]4(3, 7)9(6, 12)<0.001
NLR [M(Q1, Q3)]2.23(1.74, 3.14)2.64(1.90, 3.93)0.176
PLR [M(Q1, Q3)]130.07(94.83, 187.01)146.15(105.71, 212.96)0.243
ALB [g/L, M(Q1, Q3)]37.30(34.10, 38.80)40.00(37.00, 41.80)<0.001
肌酐[μmol/L, M(Q1, Q3)]73.00(62.00, 81.00)68.00(58.00, 78.00)0.068
化疗[例(%)]0.585
是43(91.5)125(88.7)
否4(8.5)16(11.3)
靶向治疗[例(%)]0.030
是5(10.6)4(2.8)
否42(89.4)137(97.2)
抗血管生成治疗[例(%)]<0.001
是6(12.8)105(74.5)
否41(87.2)36(25.5)
LAA%0.89(0.40, 5.27)0.25(0.04, 1.00)<0.001
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Imaging features and therapeutic interventions of 47 CIP Patients

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特征例数(%)
免疫治疗线数
一线26(55.3)
二线11(23.4)
三线10(21.3)
CTCAE 分级
14(8.5)
25(10.6)
328(59.6)
44(8.5)
56(12.8)
影像特征
GGO12(25.5)
网格影22(46.8)
实变影13(27.7)
单侧7(14.9)
双侧40(85.1)
CIP 治疗
未接受糖皮质激素治疗5(10.6)
小剂量激素治疗30(63.8)
中剂量激素治疗11(23.4)
大剂量激素治疗1(2.1)
疗效
改善39(83.0)
进展或死亡8(17.0)
后续ICIs治疗
是7(14.9)
否40(85.1)
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47例CIP患者的影像学特征及治疗情况

, figureFileSmall=null, figureFileBig=null, tableContent=
特征例数(%)
免疫治疗线数
一线26(55.3)
二线11(23.4)
三线10(21.3)
CTCAE 分级
14(8.5)
25(10.6)
328(59.6)
44(8.5)
56(12.8)
影像特征
GGO12(25.5)
网格影22(46.8)
实变影13(27.7)
单侧7(14.9)
双侧40(85.1)
CIP 治疗
未接受糖皮质激素治疗5(10.6)
小剂量激素治疗30(63.8)
中剂量激素治疗11(23.4)
大剂量激素治疗1(2.1)
疗效
改善39(83.0)
进展或死亡8(17.0)
后续ICIs治疗
是7(14.9)
否40(85.1)
), ArticleFig(id=1198578979037872585, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558167287296866, language=EN, label=Tab.3, caption=

Logistic regression of risk factors for CIP of patients with NSCLC

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特征单因素分析多因素分析
OR(95%CI)POR(95%CI)P
BMI(kg/m2)1.029(0.946~1.120)0.508
组织学类型(鳞癌)1.060(0.542~2.076)0.864
PLR0.999(0.994~1.003)0.508
NLR0.961(0.788~1.171)0.691
低ALB(g/L)0.878(0.812~0.949)0.0010.889(0.808~0.979)0.017
高肌酐(μmol/L)1.026(1.004~1.048)0.0211.027(0.997~1.058)0.077
化疗1.376(0.436~4.342)0.586
靶向治疗4.077(1.047~15.878)0.0439.204(1.678~50.486)0.011
抗血管生成治疗0.050(0.020~0.128)<0.0010.056(0.020~0.161)<0.001
高LAA%1.296(1.134~1.481)<0.0011.227(1.053~1.430)0.009
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NSCLC患者发生CIP危险因素的logistic回归分析结果

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特征单因素分析多因素分析
OR(95%CI)POR(95%CI)P
BMI(kg/m2)1.029(0.946~1.120)0.508
组织学类型(鳞癌)1.060(0.542~2.076)0.864
PLR0.999(0.994~1.003)0.508
NLR0.961(0.788~1.171)0.691
低ALB(g/L)0.878(0.812~0.949)0.0010.889(0.808~0.979)0.017
高肌酐(μmol/L)1.026(1.004~1.048)0.0211.027(0.997~1.058)0.077
化疗1.376(0.436~4.342)0.586
靶向治疗4.077(1.047~15.878)0.0439.204(1.678~50.486)0.011
抗血管生成治疗0.050(0.020~0.128)<0.0010.056(0.020~0.161)<0.001
高LAA%1.296(1.134~1.481)<0.0011.227(1.053~1.430)0.009
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NSCLC患者免疫检查点抑制剂相关性肺炎临床特点及其危险因素分析
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邱丽亮 , 程玖玲 , 王华启 *
解放军医学杂志 | 临床研究 2024,49(8): 861-867
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解放军医学杂志 | 临床研究 2024, 49(8): 861-867
NSCLC患者免疫检查点抑制剂相关性肺炎临床特点及其危险因素分析
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邱丽亮, 程玖玲, 王华启*
作者信息
  • 郑州大学第一附属医院呼吸与危重医学科，河南郑州 450000

    • 邱丽亮，硕士研究生，主要从事慢性阻塞性肺疾病及肺恶性肿瘤的相关研究

通讯作者:

王华启，E-mail：
Analysis of clinical characteristics and risk factors for immune checkpoint inhibitor-related pneumonitis in NSCLC patients
Li-Liang Qiu, Jiu-Ling Cheng, Hua-Qi Wang*
Affiliations
  • Department of Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
出版时间: 2024-08-28 doi: 10.11855/j.issn.0577-7402.1167.2024.0129
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摘要
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目的 探讨使用免疫检查点抑制剂(ICIs)治疗的非小细胞肺癌(NSCLC)患者发生ICIs相关性肺炎(CIP)的潜在危险因素，以早期识别CIP高危患者。方法 回顾性选取2020年1月-2023年6月在郑州大学第一附属医院接受ICIs治疗的728例NSCLC患者，其中CIP 47例。以47例CIP为CIP组，选取141例非CIP的NSCLC患者作为对照组。收集两组患者临床资料及第1次免疫治疗前实验室检查结果、CT影像等，应用FACT医学影像系统软件对患者CT影像进行肺气肿定量评估，采用单因素和多因素logistic回归分析CIP发生的危险因素。绘制受试者工作特征(ROC)曲线评估上述危险因素对NSCLC患者发生CIP的预测价值。结果 47例CIP患者中，男40例(85.1%)，年龄40~65岁25例(53.0%)，不良事件通用分级标准(CTCAE)分级3级肺炎28例(59.6%)，主要影像学分型为网格型。多因素logistic回归分析显示，白蛋白(ALB)低(OR=0.889，95%CI 0.808~0.979，P=0.017)、靶向治疗(OR=9.204，95%CI 1.678~50.486，P=0.011)、抗血管生成治疗(OR=0.056，95%CI 0.020~0.161，P<0.001)、低衰减区域百分比(LAA%)高(OR=1.227，95%CI 1.053~1.430，P=0.009)是CIP发生的独立影响因素。ROC曲线分析结果显示，联合上述4个影响因素预测NSCLC患者发生CIP的ROC曲线下面积为 0.888(95%CI 0.838~0.939)，敏感度为0.894，特异度为0.801。结论 血清ALB低、接受一线靶向治疗、LAA%高是发生CIP的独立危险因素，接受抗血管生成治疗是CIP发生的保护因素。采用上述4个变量建立的预测模型可较好地预测NSCLC患者发生CIP的风险。

非小细胞肺癌  /  免疫检查点抑制剂相关性肺炎  /  危险因素  /  肺气肿

Objective To investigate the potential risk factors for immune checkpoint-related pneumonia (CIP) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), to identify high-risk patients with CIP at an early stage. Methods A total of 728 NSCLC patients treated with ICIs at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2023 were retrospectively selected, including 47 cases with CIP (CIP group), and 141 matched NSCLC patients without CIP (control group). Clinical data, laboratory tests, and CT images before the first immunotherapy were collected for all patients in two groups. The FACT medical imaging software was utilized for quantitative emphysema assessment in patients' CT scans. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with CIP. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of these factors for CIP occurrence in NSCLC patients. Results Among the 47 CIP patients, 40(85.1%) were male, with 25(53.0%) aged between 41 and 65 years. Grade 3 pneumonia according to the Common Terminology Criteria for Adverse Events (CTCAE) was found in 28(59.6%) cases, characterized by a predominant reticular radiographic pattern. Multivariate logistic regression analysis showed that a low albumin level (OR=0.889, 95%CI 0.808-0.979, P=0.017), targeted therapy (OR=9.204, 95%CI 1.678-50.486, P=0.011), anti-angiogenic therapy (OR=0.056, 95%CI 0.020-0.161, P<0.001), and a high percentage of low attenuation area (LAA%) (OR=1.227, 95%CI 1.053-1.430, P=0.009) were significant factors influencing CIP occurrence. The combined predictive model using these four factors showed an area under the ROC curve of 0.888 (95%CI 0.838-0.939), with a sensitivity of 0.894 and a specificity of 0.801 for predicting CIP in NSCLC patients. Conclusions Low serum albumin, first-line targeted therapy, and high LAA% are identified as risk factors for CIP occurrence, while anti-angiogenic therapy is a protective factor. The predictive model based on these four variables effectively predicts the risk of CIP in NSCLC patients.

non-small cell lung cancer  /  checkpoint inhibitor-associated pneumonia  /  risk factors  /  emphysema
邱丽亮, 程玖玲, 王华启. NSCLC患者免疫检查点抑制剂相关性肺炎临床特点及其危险因素分析. 解放军医学杂志, 2024 , 49 (8) : 861 -867 . DOI: 10.11855/j.issn.0577-7402.1167.2024.0129
Li-Liang Qiu, Jiu-Ling Cheng, Hua-Qi Wang. Analysis of clinical characteristics and risk factors for immune checkpoint inhibitor-related pneumonitis in NSCLC patients[J]. Medical Journal of Chinese People’s Liberation Army, 2024 , 49 (8) : 861 -867 . DOI: 10.11855/j.issn.0577-7402.1167.2024.0129
正文
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近年来，免疫检查点抑制剂(immune checkpoint inhibitors，ICIs)引发了肿瘤治疗的一场革命。ICIs可通过阻断程序性细胞死亡蛋白1/配体1(PD-1/PD-L1)或细胞毒性T淋巴细胞抗原4(CTLA-4)途径激活T细胞，进而破坏肿瘤细胞[1]；但ICIs诱导的特异性免疫反应过度激活导致正常组织损伤进而引起的免疫相关不良事件(immune-related adverse events，irAEs)，也成为临床一线关注的热点问题[2-5]。irAEs可累及多种器官，其中免疫检查点抑制剂相关性肺炎(checkpoint inhibitor-related pneumonitis，CIP)发生率较高[6]，其主要病变部位为双肺下叶。早期临床试验和荟萃分析结果显示，在接受免疫治疗的肿瘤患者中，CIP发生率为3%~5%，病死率达10%~17%。与其他肿瘤相比，非小细胞肺癌(non-small-cell carcinoma，NSCLC)患者CIP发生率可能更高[2,7]。CIP的症状通常是非特异性的，主要包括呼吸困难、咳嗽、发热和胸痛等。糖皮质激素是CIP的一线治疗方案，但约1/4的患者在重新启动免疫治疗后出现CIP复发[8-9]。由于ICIs的使用增多及CIP病死率较高，提前识别潜在的CIP患者对相关临床治疗至关重要。近期研究显示，慢性阻塞性肺疾病与CIP发生率升高有关[10]。本研究通过评估接受ICIs治疗的NSCLC患者的临床特征、治疗方案、血液学指标和肺影像学特征等潜在危险因素，以期为CIP的临床早期识别提供参考。
1 资料与方法
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1.1 研究对象
回顾性选取2020年1月-2023年6月在郑州大学第一附属医院经病理确诊为NSCLC并接受ICIs治疗的患者728例，其中CIP患者47例。纳入标准：(1)经病理组织学检查确诊为NSCLC；(2)年龄≥18岁；(3)至少接受1个周期(21 d)的ICIs治疗。排除标准：(1)6个月内有胸部放射治疗史；(2)临床资料不完整。考虑到放射治疗存在导致放射性肺炎而产生偏倚的可能，因此接受过胸部放射治疗的患者被排除。将47例CIP患者设为CIP组；按照CIP组与对照组1∶3的比例从非CIP的NSCLC患者中依据性别、年龄(18~<40岁、40~65岁、>65岁)、吸烟史进行配对，共选取141例非CIP的NSCLC患者作为对照组。本研究所有接受靶向治疗的患者均为一线靶向治疗，进展或耐药后行二线或三线免疫治疗，主要药物包括吉非替尼、埃可替尼、奥希替尼、阿美替尼、阿法替尼等；接受抗血管生成治疗的患者为序贯或联合进行免疫治疗，抗血管治疗药物主要包括贝伐珠单抗和安罗替尼。本研究中涉及人类参与者的所有程序都符合《赫尔辛基宣言》。本研究获郑州大学第一附属医院伦理委员会审批(2023-KY-0430)。
1.2 一般资料及外周血生物标志物的收集
收集所有受试者的临床信息，包括年龄、性别、吸烟史、肿瘤类型、治疗方案；收集所有患者首次使用ICIs前的实验室检查结果，包括血小板、中性粒细胞绝对值、淋巴细胞绝对值、白蛋白(albumin，ALB)、肌酐等。中性粒细胞淋巴细胞比率(neutrophil to lymphocyte ratio，NLR)=外周血中性粒细胞计数(×109 g/L)/外周血淋巴细胞计数(×109 g/L)；血小板淋巴细胞比率(platelet to lymphocyte ratio，PLR)=外周血血小板计数(×109 g/L)/外周血淋巴细胞计数(×109 g/L)。
1.3 肺气肿CT定量评估
收集所有患者首次免疫治疗前的胸部CT图像，使用FACT医学影像系统软件(德信医学影像技术有限公司)进行定量评估，采用自动边缘检测和阈值限定的方法，将图像中的肺组织与其他组织(包括胸壁、气管、心脏、肺门大血管等)自动分割开。采用FACT软件在不同肺叶以不同色彩标注低衰减区域，并计算出全肺低衰减区域百分比(the percentage of low attenuation area，LAA%)。LAA%定义为CT衰减值<-950 Hounsfield单位(HU)的所有肺体素除以完全充气时的总肺体积再乘以100%。两组188例患者的胸部CT图像均来自图片存档和通信系统(Picture Archiving and Communication Systems，PACS)。
1.4 CIP的诊断、分级及治疗
由长期从事肺癌和间质性肺病临床工作的2名呼吸科医师和1名胸部放射科医师进行CIP诊断与分级，当意见存在分歧时经讨论达成一致。CIP诊断需同时符合以下3项[11-12]：(1)有ICIs用药史；(2)影像学检查提示有新出现的肺部阴影；(3)排除肺部感染、肺部肿瘤进展及其他原因引起的肺部疾病，如间质性肺疾病、肺血管炎、肺栓塞及肺水肿等。如果再符合以下2条则更进一步支持诊断：(1)新发或原有的呼吸困难、咳嗽、胸痛、发热、乏力等症状加重；(2)动脉血气分析提示低氧血症，肺功能检查显示一氧化碳弥散量(DLCO)降低，呈限制性通气功能障碍。参照美国国立癌症研究所(NCI)建立的不良事件通用分级标准(CTCAE5.0)进行CIP分级[13]。关于糖皮质激素在CIP中的应用，参照2021年中国临床肿瘤学会(Chinese Society of Clinical Oncology，CSCO)指南[8]，G1级不使用糖皮质激素治疗；G2级应用1.0~2.0 mg/(kg.d)甲泼尼龙48~72 h，症状缓解后在4~6周甲泼尼龙每周逐渐减量5~10 mg；G3、G4级应用2.0 mg/(kg.d)甲泼尼龙。本研究将小剂量、中剂量及大剂量糖皮质激素分别定义为甲泼尼龙<1.0 mg/(kg.d)、1.0~2.0 mg/(kg.d)及>2.0 mg/(kg.d)。CIP治疗后好转，定义为咳嗽、咳痰、胸闷等症状较前好转，呼吸支持力度较前下调或胸部影像学表现较前吸收。恶化，定义为原有症状较前加重或出现新发症状，呼吸支持力度较前上调或胸部CT出现新发病灶。
1.5 统计学处理
采用SPSS 26.0软件进行统计分析。计量资料以M(Q1，Q3)表示，组间比较采用Mann-Whitney U检验；计数资料以例(%)表示，组间比较采用χ2检验或Fisher精确检验。采用单因素logistic回归分析各因素对CIP的预测价值，将单因素logistic回归分析中P<0.05的变量纳入多因素回归分析，得出OR值和95%可信区间CI。采用受试者工作特征(receiver operating characteristic，ROC)的曲线下面积(the area under the ROC curve，AUC)评估模型的预测能力，AUC越接近1.0，提示预测能力越好。所有统计分析均为双尾检验，P<0.05为差异有统计学意义。
2 结果
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2.1 两组NSCLC患者的临床特征比较
CIP组与对照组的BMI、组织学类型、是否化疗等差异无统计学意义(P>0.05)；两组免疫治疗周期、是否接受过靶向治疗和抗血管生成治疗差异有统计学意义(P<0.05，表1)。
两组CT检查所示肺气肿部分表现为低衰减区域(图1)；CIP组LAA%明显高于对照组[0.89(0.40，5.27) vs. 0.25(0.04，1.00)，P<0.001]。
2.2 CIP患者的影像学表现、分级及治疗
47例CIP患者中，22例(46.8%)影像表现为网格影，13例(27.7%)表现为肺叶的实变影，其余12例(25.5%)表现为弥漫片状或散在磨玻璃影(图2)。CIP分级，1级4例(8.5%)，2级5例(10.6%)，3级28例(59.6%)，4级4例(8.5%)，5级6例(12.8%)。47例CIP患者中，5例(10.6%)未接受糖皮质激素治疗，30例(63.8%)为小剂量糖皮质激素治疗，11例(23.4%)为中剂量糖皮质激素治疗，1例(2.1%)为大剂量糖皮质激素治疗；40例(85.1%)在后续治疗中未再进行ICIs治疗，7例(14.9%)后续再次进行免疫治疗且未再发生CIP(表2)。
2.3 NSCLC患者发生CIP危险因素的logistic回归分析
单因素logistic回归分析结果显示，两组低ALB(OR=0.878，95%CI 0.812~0.949，P=0.001)、高肌酐(OR=1.026，95%CI 1.004~1.048，P=0.021)、高LAA% (OR=1.296，95%CI 1.134~1.481，P<0.001)、靶向治疗(OR=4.077，95%CI 1.047~15.878，P=0.043)及抗血管生成治疗(OR=0.050，95%CI 0.020~0.128，P<0.001)与CIP发生风险增加有关(表3)；BMI、类型、PLR、NLR、化疗等与CIP发生无关(P>0.05)。多因素logistic回归分析显示，高LAA%(OR=1.227，95%CI 1.053~1.430，P=0.009)、既往靶向治疗(OR=9.204，95%CI 1.678~50.486，P=0.011)与CIP发生风险增加相关，高ALB(OR=0.889，95%CI 0.808~0.979，P=0.017)、既往抗血管生成治疗(OR=0.056，95%CI 0.020~0.161，P<0.001) 则为CIP发生的保护因素(表3)。根据上述变量绘制ROC曲线，抗血管治疗的曲线下面积为0.809，而ALB、LAA%及靶向治疗的AUC分别为0.687、0.701、0.539；联合上述4个变量，该模型预测NSCLC患者发生免疫相关性肺炎的AUC为0.888(95%CI 0.838~0.939)，敏感度为0.894，特异度为0.801(图3)。通过ROC曲线确定每个变量的敏感度、特异度、最小约登指数：抗血管生成治疗分别为0.745、0.872、0.617，靶向治疗分别为0.106、0.972、0.078，高ALB分别为0.532、0.809、0.340，LAA%分别为0.681、0.681、0.362；以及连续变量的最佳截断值，其中ALB最佳截断值为39.6 g/L，LAA%最佳截断值为0.64。
3 讨论
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ICIs可通过阻断PD-1/PD-L1及CTLA-4通路，启动和激活效应T细胞，进而识别和杀伤肿瘤细胞发挥抗肿瘤活性，但也可能过度激活免疫系统，导致多种免疫相关的不良反应[14]，其中以肺为靶器官的CIP使患者病死率增高[15]。因此，早期识别、及时干预CIP具有重要的临床价值。
本研究通过阈值法测定LAA%以评估肺气肿严重程度，结果显示，LAA%与CIP发生风险成正相关。多项研究显示，LAA%是评估COPD患者肺气肿严重程度的可靠指标[16-18]，Occhipinti等[19]采用胸部CT对194例接受了肺功能检查的COPD患者进行肺气肿的诊断和严重程度的量化，发现LAA%与第1秒用力呼气量(FEV1%)及1秒率(FEV1/FVC)呈负相关。肺是受免疫介导性肺炎影响的核心器官，因此影响肺功能的因素可能与免疫介导性肺炎有关，LAA%越高，提示患者的肺气肿严重程度越重，可导致CIP风险增加，可能原因是这些人群具有特殊的气道炎症微环境[20-21]。由于不能配合或经济原因，部分患者缺少肺功能检查结果，此时可通过胸部CT测定LAA%以评估肺气肿严重程度，高LAA%的人群应用ICIs时更应警惕CIP的发生。
除LAA%与CIP的发生相关外，本研究结果还显示，基线低血清ALB是NSCLC患者发生CIP的独立危险因素。有研究显示，低白蛋白血症与肺损伤及炎症反应协同降低血浆胶体渗透压，从而导致肺水肿的发生。同时，ALB作为一种急性期反应蛋白，能够反映机体的炎症状态[22]。本研究中，CIP组ALB水平低于非CIP组，提示CIP组患者可能存在更严重的全身炎症反应，这可能是导致CIP发生的机制之一。此外，Hu等[23]报道ALB浓度增高与肺功能改善相关。本研究中ALB预测NSCLC患者发生CIP的AUC为0.687，最佳临界值为39.6 g/L，此时敏感度为0.532，特异度为0.809；因此，可能需要与其他因子联合预测CIP的发生。关于ALB与CIP发生之间的关系尚需更多的临床研究验证。
本研究显示，表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)耐药后进行ICIs治疗的患者出现CIP的风险高于单一ICIs治疗的患者。既往研究也提示EGFR-TKI是导致CIP的危险因素。尽管作用机制不同，但靶向治疗和ICIs均可导致免疫环境发生变化，联合使用可能会产生对肺毒性作用的累加效应[24]。Jia等[25]对小鼠进行EGFR-TKI和PD-L1的单一治疗和联合治疗，结果显示，奥希替尼和抗PD-L1联合治疗组的肺组织HE染色病理炎症评分较高，髓过氧化物酶阳性细胞百分比较高；提示EGFR联合ICIs可能通过增加肺部炎症反应，推进CIP的发展。与之相反，抗血管生成治疗降低CIP的发生风险。研究显示，抗血管生成治疗可减轻肺水肿和降低毛细血管的通透性[26]，这可能有助于早期肺炎的恢复。此外，Hamada等[27]报道，以可溶性FMS样酪氨酸激酶1(sFlt-1)形式转染抗血管内皮生长因子(VEGF)基因可减轻肺纤维化，并具有额外的抗炎和抗血管生成作用。这一假设需要未来在更大规模的临床试验和动物实验中进行验证。
本研究显示，CIP患者往往在ICIs治疗早期即出现肺炎；既往多项研究也显示，CIP主要发生在开始治疗后的前6个月[28]。这提示上述人群可能有一定的CIP易感性，推测与其肺部免疫微环境可能有关。本研究中，年龄、性别、吸烟史等与CIP发生无关。既往研究显示，年龄较大和吸烟史是CIP的危险因素[7,29]；这些关联可能与相应人群因年龄较大或长期吸烟史所致的肺功能下降及医疗并发症增多有关。
本研究存在一些局限性：(1)为回顾性研究，可能存在信息偏倚；(2)纳入的样本量较小；(3)研究结果不包括对治疗结局的评估，如患者的总生存期和无进展生存期等。
综上所述，本研究结果表明，NSCLC患者发生CIP的风险与血清ALB水平低、靶向治疗、抗血管生成治疗和高LAA%有关，基于上述预测因素构建的模型具有良好的预测效能，可供制定临床干预方案时参考。
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  • 国家自然科学基金(81972182)
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排序方式：
[1]
高磊, 俞阳, 李晓梅, 等. 化疗与免疫检查点抑制剂联用对肿瘤的作用研究进展[J]. 解放军医学杂志, 2022, 47(11): 1152-1158.
[2]
Yin J, Wu Y, Yang X, et al. Checkpoint inhibitor pneumonitis induced by anti-PD-1/PD-L1 therapy in non-small-cell lung cancer: occurrence and mechanism[J]. Front Immunol, 2022, 13: 830631.
[3]
张涵, 祖育娜, 张华. 非小细胞肺癌患者肺泡灌洗液中T淋巴细胞亚群及血清炎症因子与免疫检查点抑制剂相关性肺炎的关系[J]. 新乡医学院学报, 2023, 40(9): 824-828.
[4]
张耀, 刘艺, 刘思行, 等. 免疫检查点抑制剂治疗恶性肿瘤诱发糖尿病4例报告[J]. 中国实用内科杂志, 2023, 43(8): 702-704.
[5]
张杰, 魏渼倬, 赵玲, 等. 外周血中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值与接受免疫检查点抑制剂治疗食管鳞状细胞癌患者预后的相关性[J]. 新乡医学院学报, 2023, 40(7): 621-627.
[6]
Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis[J]. JAMA Oncol, 2018, 4(12): 1721-1728.
[7]
Zhai X, Zhang J, Tian Y, et al. The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients[J]. Cancer Biol Med, 2020, 17(3): 599-611.
[8]
Kalisz KR, Ramaiya NH, Laukamp KR, et al. Immune checkpoint inhibitor therapy-related pneumonitis: patterns and management[J]. Radiographics, 2019, 39(7): 1923-1937.
[9]
Yu X, Wu J, Su C. Progress in diagnosis and treatment of checkpoint inhibitor pneumonitis[J]. Curr Opin Oncol, 2023, 35(1): 31-36.
[10]
Chao Y, Zhou J, Hsu S, et al. Risk factors for immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer[J]. Transl Lung Cancer Res, 2022, 11(2): 295-306.
[11]
陈良安. 免疫检查点抑制剂相关肺炎诊治专家共识[J]. 中华结核和呼吸杂志, 2019, 42(11): 820-825.
[12]
中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)免疫检查点抑制剂相关的毒性管理指南2021[M]. 北京: 人民卫生出版社, 2021.
[13]
Freites-martinez A, Santana N, Arias-Santiago S, et al. Using the common terminology criteria for adverse events (CTCAE-Version 5.0) to evaluate the severity of adverse events of anticancer therapies[J]. Actas Dermosifiliogr (Engl Ed), 2021, 112(1): 90-92.
[14]
Ma K, Lu Y, Jiang S, et al. The relative risk and incidence of immune checkpoint inhibitors related pneumonitis in patients with advanced cancer: a meta-analysis[J]. Front Pharmacol, 2018, 9: 1430.
[15]
Akella P, Loganathan S, Jindal V, et al. Anti PD-1 immunotherapy related interstitial lung disease presenting as respiratory failure - A review with case series[J]. Respir Med Case Rep, 2019, 26: 17-22.
[16]
Mohamed Hoesein FA, de Hoop B, Zanen P, et al. CT-quantified emphysema in male heavy smokers: association with lung function decline[J]. Thorax, 2011, 66(9): 782-787.
[17]
Mets OM, de Jong PA, van Ginneken B, et al. CT air trapping is independently associated with lung function reduction over time[J]. PLoS One, 2013, 8(4): e61783.
[18]
Mets OM, Smit EJ, Mohamed Hoesein FA, et al. Visual versus automated evaluation of chest computed tomography for the presence of chronic obstructive pulmonary disease[J]. PLoS One, 2012, 7(7): e42227.
[19]
Occhipinti M, Paoletti M, Bartholmai BJ, et al. Spirometric assessment of emphysema presence and severity as measured by quantitative CT and CT-based radiomics in COPD[J]. Respir Res, 2019, 20(1): 101.
[20]
Day D, Hansen AR. Immune-related adverse events associated with immune checkpoint inhibitors[J]. BioDrugs, 2016, 30(6): 571-584.
[21]
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.
[22]
Fukihara J, Sakamoto K, Koyama J, et al. Prognostic impact and risk factors of immune-related pneumonitis in patients with non-small-cell lung cancer who received programmed death 1 inhibitors[J]. Clin Lung Cancer, 2019, 20(6): 442-450.e4.
[23]
Hu S, Guo Q, Wang S, et al. Supplementation of serum albumin is associated with improved pulmonary function: NHANES 2013-2014[J]. Front Physiol, 2022, 13: 948370.
[24]
Mascia F, Schloemann DT, Cataisson C, et al. Cell autonomous or systemic EGFR blockade alters the immune-environment in squamous cell carcinomas[J]. Int J Cancer, 2016, 139(11): 2593-2597.
[25]
Jia Y, Zhao S, Jiang T, et al. Impact of EGFR-TKIs combined with PD-L1 antibody on the lung tissue of EGFR-driven tumor-bearing mice[J]. Lung Cancer, 2019, 137: 85-93.
[26]
Kaner RJ, Ladetto JV, Singh R, et al. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema[J]. Am J Respir Cell Mol Biol, 2000, 22(6): 657-664.
[27]
Hamada N, Kuwano K, Yamada M, et al. Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice[J]. J Immunol, 2005, 175(2): 1224-1231.
[28]
Suresh K, Voong KR, Shankar B, et al. Pneumonitis in non-small cell lung cancer patients receiving immune checkpoint immunotherapy: incidence and risk factors[J]. J Thoracic Oncol, 2018, 13(12): 1930-1939.
[29]
Cho JY, Kim J, Lee JS, et al. Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer[J]. Lung Cancer, 2018, 125: 150-156.
2024年第49卷第8期
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doi: 10.11855/j.issn.0577-7402.1167.2024.0129
  • 接收时间：2023-09-04
  • 首发时间：2025-11-21
  • 出版时间：2024-08-28
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  • 收稿日期：2023-09-04
  • 录用日期：2023-12-01
基金
National Natural Science Foundation of China(81972182)
国家自然科学基金(81972182)
作者信息
    郑州大学第一附属医院呼吸与危重医学科，河南郑州 450000

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王华启，E-mail：
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