结合新型生物标志物的成人哮喘未来发作风险预后模型构建研究  

Construction of a prognostic model of future asthma exacerbation risk in adults combined with novel biomarkers

作　　者：张黎 黎亮 周梅 周倩云 刘勤 梁梅 唐继红 付小锋 ZHANG Li;LI Liang;ZHOU Mei;ZHOU Qianyun;LIU Qin;LIANG Mei;TANG Jihong;FU Xiaofeng(Department of Respiratory and Critical Care Medicine,the People′s Hospital of Yubei District of Chongqing,Chongqing 401120,China;Department of Clinical Laboratory,the People′s Hospital of Yubei District of Chongqing,Chongqing 401120,China)

机构地区：[1]重庆市渝北区人民医院呼吸与危重症医学科,重庆401120 [2]重庆市渝北区人民医院检验科,重庆401120

出　　处：《国际检验医学杂志》2025年第4期435-442,共8页International Journal of Laboratory Medicine

基　　金：重庆市科卫联合医学科研项目(2022MSXM123)。

摘　　要：目的结合新型生物标志物血清甲壳质酶蛋白40(YKL-40)、二肽基肽酶-4(DPP4)与常规预测因子构建成人哮喘未来发作风险预后模型。方法2022年3月至2023年5月在重庆市渝北区人民医院招募哮喘非急性发作期患者作为研究对象,收集基线临床资料,包括病史、第1秒用力呼气量(FEV 1)/用力肺活量(FVC)、第1秒用力呼气量占预计值百分比(FEV 1%pred)、血嗜酸性粒细胞计数(EOS)、血中性粒细胞计数(NEU)、呼出气一氧化氮(FeNO)、血清YKL-40和血清DPP4等,随访1年收集该文所定义的哮喘急性发作情况及发作时间,通过COX比例风险回归构建哮喘未来发作风险预后模型,并进行内部验证及结果展示。结果最终224例哮喘患者完成研究,102例患者在1年的随访期内发生了该文所定义的急性发作结局,结合单因素COX回归、逐步回归筛选变量、临床意义及模型的简便性,哮喘控制测试(ACT)评分分组、过去1年哮喘急性发作次数分组、log 10(YKL-40)、log 10(FeNO)、log 10(EOS)和FEV 1%pred作为预测因子纳入最终模型构建。模型整体C-统计量为0.795(95%CI:0.754~0.836),在随访52周时间点的曲线下面积为0.879(95%CI:0.834~0.924),在随访52周时间点的Brier评分为0.142(95%CI:0.117~0.168),校准曲线为接近斜率为1的直线,使用bootstrap验证法提示预测模型稳定性较好。使用Nomogram列线图及网页APP动态打分表进行模型展示,可用于预测个体未来52周内哮喘发作风险。结论基于血清YKL-40、EOS、FeNO、过去1年哮喘急性发作次数分组、FEV 1%pred及ACT评分分组构建的哮喘预后预测模型能较准确的预测哮喘患者52周内急性发作的概率。Objective To construct a prognostic model of future asthma exacerbation risk in adults by combining novel biomarkers of serum chitinase-3-like protein 1(YKL-40),dipeptidyl peptidase-4(DPP4)and conventional predictors.Methods Patients with asthma in the non-acute exacerbation phase were recruited from the People′s Hospital of Yubei District of Chongqing,from March 2022 to May 2023.Baseline clinical data collected included medical history,forced expiratory volume in the first second(FEV 1)/forced vital capacity(FVC),percentage of predicted forced expiratory volume in the first second(FEV 1%pred),blood eosinophil count(EOS),blood neutrophil count(NEU),fractional exhaled nitric oxide(FeNO),serum YKL-40,and serum DPP4,etc.The patients were followed for one year to gather data on asthma acute exacerbations and their timings as defined in this study.A COX proportional hazards regression model was used to construct a prognostic model for future asthma exacerbations,with internal validation and results presentation.Results A total of 224 patients with asthma completed the study.During the one-year follow-up period,102 patients experienced acute exacerbations as defined in this study.Based on univariate COX regression,stepwise regression for variable selection,clinical significance,and model simplicity,asthma control test(ACT)score group,number of asthma exacerbations in the past year group,log 10(YKL-40),log 10(FeNO),log 10(EOS),and FEV 1%pred were the following predictors were included in the final model.The overall C-statistic of the model was 0.795(95%CI:0.754—0.836),the area under the curve at the 52-week follow-up was 0.879(95%CI:0.834-0.924),and the Brier score at the 52-week follow-up was 0.142(95%CI:0.117-0.168).The calibration curve was close to a slope of 1,and bootstrap validation suggested good stability of the prediction model.The model was presented using a Nomogram and a dynamic scoring table in a web APP,which can be used to predict the risk of asthma exacerbations within 52 weeks for individual patien

关 键 词：新型生物标志物 甲壳质酶蛋白40 二肽基肽酶-4 哮喘 

分 类 号：R562.25[医药卫生—呼吸系统]