Abstract: Background　Patients with interstitial lung disease（ILD）are prone to acute exacerbation（AE-ILD），with infection being a significant trigger. AE-ILD patients exhibit high mortality rates and poor prognoses，yet domestic research on this population remains limited. Objective　To investigate the clinical predictive value of dynamic changes in peripheral blood lymphocyte count（LYM）for 28-day prognosis in AE-ILD patients with pulmonary infection and to establish a corresponding prognostic prediction model. Methods　A retrospective cohort study included AE-ILD patients hospitalized in the Department of Respiratory Medicine at the Affiliated Hospital of Xuzhou Medical University from January 2022 to June 2024. Patients were stratified into survival（n=37）and non-survival（n=65）groups based on 28-day outcomes. Data collected included demographics（sex，age，diagnosis，ILD subtype，comorbidities），disease severity scores（APACHE II，SOFA），and laboratory parameters：white blood cell count（WBC），neutrophil count（NEU），lymphocyte count on days 1，3，and 5 （d1 LYM，d3 LYM，d5 LYM），hemoglobin（Hb），platelet count（PLT），procalcitonin（PCT），C-reactive protein （CRP），albumin（ALb），total bilirubin（T-bil），lactate dehydrogenase（LDH），creatinine（Scr），activated partial thromboplastin time（APTT），partial pressure of oxygen（PaO2），partial pressure of carbon dioxide（PaCO2），fraction of inspired oxygen（FiO2），PaO2/FiO2 ratio（P/F），and lactate（Lac）. Intergroup differences were analyzed，and statistically significant variables were identified. Receiver operating characteristic（ROC）curves evaluated prognostic predictive capacity. Univariate and multivariate Cox proportional hazards regression analyses were conducted using R software. Scores were assigned to each indicator based on the hazard ratio （HR）. A nomogram prediction model was constructed. After calculating the total score of each indicator, risk stratification was established. The ROC curve of the prediction model was drawn to evaluate its predictive value. The survival curves of 28-day prognosis of AE-ILD patients with different risk stratifications were plotted using R software, and the 28-day survival rates of patients in different groups were compared. Results　The non-survival group exhibited higher than APACHE II scores，SOFA scores，PCT，CRP，and LDH（P<0.05）but lower than d3 LYM，d5 LYM，ALb，and P/F（P<0.05）. Dynamic LYM trends diverged：non-survivors showed progressive lymphopenia，while survivors demonstrated lymphocyte recovery. The results of the ROC curve showed that the AUCs of d3 LYM , d5 LYM , APACHE II score, and SOFA score in predicting the 28-day prognosis of patients with AE-ILD were 0.723, 0.764, 0.733, and 0.704, respectively. Multivariate Cox regression identified P/F（HR=2.01，95%CI=1.08-3.75）、PCT（HR=2.14，95%CI=1.02-4.49）、Hb（HR=2.34，95%CI=1.22-4.48）、d5 LYM（HR=2.40，95%CI=1.01-5.70）as independent predictors of 28-day mortality. The nomogram model was constructed based on d5 LYM，P/F，PCT and Hb. The AUC value of this model for predicting 28-day mortality in AE-ILD patients was 0.853（95%CI=0.781-0.925），with the optimal cut-off value being 2. The sensitivity and specificity were 88.24% and 82.35%，respectively. According to the results of the optimal risk stratification, 0-2 is classified as the low-risk group, and 3-6 is classified as the high-risk group. There were significant differences on the 28-day survival rates between the two groups of patients（χ2 =51, P<0.001）. Conclusion　Lymphopenia is associated with increased 28-day mortality in AE-ILD patients with pulmonary infection. The nomogram model incorporating LYM-d5，P/F，PCT，and Hb provides a clinically practical tool for risk stratification and prognostic assessment.

Key words: Lymphocyte count, Dynamic change, Infection, Acute exacerbation of interstitial lung disease, Prognosis

摘要： 背景　间质性肺病患者容易出现急性加重，而感染是重要诱因之一，急性加重患者的死亡率高、预后差，目前国内针对这类人群的研究较少。目的　探讨外周血淋巴细胞计数的动态变化对间质性肺病急性加重（AE-ILD）合并肺部感染患者预后的临床预测价值，并在此基础上建立相关预测模型。方法　回顾性纳入2022年1月—2024年6月于徐州医科大学附属医院呼吸科住院的AE-ILD患者为研究对象。根据患者28 d存活情况，将患者分为死亡组和存活组。收集患者一般资料包括：性别、年龄、诊断、ILD分型、基础疾病；病情评分包括：序贯器官衰竭（APACHEII）评分、序贯器官衰竭（SOFA）评分；实验室指标包括：白细胞计数（WBC）、中性粒细胞计数（NEU）、第1、3、5天淋巴细胞计数（LYM）、血红蛋白（Hb）、血小板计数（PLT）、降钙素原（PCT）、C-反应蛋白（CRP）、白蛋白（ALb）、总胆红素（T-bil）、乳酸脱氢酶（LDH）、肌酐（Scr）、部分凝血活酶时间（APTT）、氧分压（PO2）、二氧化碳分压（PCO2）、吸氧浓度（FIO2）、氧合指数（P/F）、乳酸（Lac）。比较两组之间的差异，筛选有统计学意义的指标，绘制各项指标预测患者28 d预后的受试者工作特征曲线（ROC）。使用R软件进行单因素及多因素Cox比例风险回归分析，据风险比（HR）为各项指标赋分，构建列线图预测模型，计算各项指标分数总和后设立风险分层，绘制预测模型ROC曲线，评估其预测价值。采用R软件绘不同风险分层AE-ILD患者28 d的生存曲线，比较不同分组患者28 d存活率。结果　共纳入102例患者，其中存活组37例，死亡组65例。死亡组APACHEⅡ评分、SOFA评分、PCT、CRP、LDH高于存活组（P<0.05）。死亡组第3、5天LYM、Alb、P/F低于存活组（P<0.05）。随着治疗时间的延长，死亡组LYM逐渐下降，存活组LYM逐渐上升。ROC曲线结果显示，第3天LYM、第5天LYM、APACHE II评分、SOFA评分预测AE-ILD患者28 d预后的AUC分别为0.723、0.764、0.733、0.704。多因素COX回归分析显示P/F（HR=2.01，95%CI=1.08~3.75）、PCT（HR=2.14，95%CI=1.02~4.49）、Hb（HR=2.34，95%CI=1.22~4.48）、第５天LYM（HR=2.40，95%CI=1.01~5.70）是导致AE-ILD患者28 d死亡的独立危险因素。根据第5天LYM、P/F、PCT、Hb构建列线图模型，该模型预测AE-ILD患者28 d死亡的AUC值为0.853（95%CI=0.781~0.925），最佳截断值为2，敏感度为88.24%，特异度为82.35%。根据最佳风险分层结果，0~2分为低危组，3~6分为高危组，两组患者28 d的存活率比较，差异均有统计学意义（χ2=51，P<0.001）。结论　LYM的降低与AE-ILD合并肺部感染患者的28 d死亡率增加有关，本研究基于第5天LYM、P/F、PCT、Hb 4个指标建立的临床预测模型，提供了简便的判断患者预后的方法。

关键词: 淋巴细胞计数, 动态变化, 感染, 间质性肺病急性加重, 预后