构建CT结合血清学指标模型预测结缔组织病相关肺纤维化的进展

Establishment and validation of a risk prediction model based on CT and serum markers for disease progression in CTD-ILD patients

目的评估基于CT及血清学指标建立模型对结缔组织病相关间质性肺病(connective tissue disease-associated interstitial lung disease,CTD-ILD)进展为进展型肺纤维化(progressive pulmonary fibrosis,PPF)的临床预测效能。方法纳入2020年1月—2021年12月在郑州大学附属胸科医院就诊的CTD-ILD患者,收集患者的临床数据及高分辨CT检查结果,根据患者随访中是否发生PPF将患者分为稳定组和进展组(PPF组)。采用COX比例风险回归明确影响患者CTD-ILD进展为PPF的风险因素,根据COX回归模型的结果建立风险预测模型,通过内部交叉验证评估模型的预测效能。结果通过纳入、排除标准,共入组194例确诊为CTD-ILD的患者,其中34例患者在治疗过程中进展为PPF,160例患者未进展。LASSO回归中lambda$1se时获取变量为ANCA相关血管炎、淋巴细胞计数、白蛋白、红细胞沉降率、铁蛋白。通过多因素COX回归分析,最终结果显示纤维化范围、铁蛋白、白蛋白和年龄是影响CTD-ILD患者进展为PPF的独立风险因素(均P<0.05)。基于多因素COX回归分析结果建立预测模型,6个月、9个月、12个月的受试者操作特征曲线下面积为0.989、0.931和0.797,提示模型具有较好的区分度和敏感性,预测效能较好。绘制校准曲线显示模型预测值与实际值重合度较好。结论纤维化范围、铁蛋白、白蛋白和年龄是影响CTD-ILD患者进展为PPF的独立风险因素。基于此建立预测模型并进行外部验证,显示模型具有较好的预测效能。

Objective To clarify the specific clinical predictive efficacy of CT and serological indicators for the progression of connective tissue disease-associated interstitial lung disease(CTD-ILD)to progressive pulmonary fibrosis(PPF).Methods Patients who were diagnosed with CTD-ILD in Chest Hospital of Zhengzhou University Between January 2020 and December 2021 were recruited in the study.Clinical data and high-resolution CT results of the patients were collected.The patients were divided into a stable group and a progressive group(PPF group)based on whether PPF occurred during follow-up.COX proportional hazards regression was used to identify risk factors affecting the progression of CTD-ILD to PPF,and a risk prediction model was established based on the results of the COX regression model.The predictive efficacy of the model was evaluated through internal cross-validation.Results A total of 194 patients diagnosed with CTD-ILD were enrolled based on the inclusion and exclusion criteria.Among them,34 patients progressed to PPF during treatment,and 160 patients did not progress.The variables obtained at lambda$1se in LASSO regression were ANCA associated vasculitis,lymphocytes,albumin,erythrocyte sedimentation rate,and serum ferritin.Multivariate COX regression analysis showed that the extent of fibrosis,serum ferritin,albumin,and age were independent risk factors for the progression of CTD-ILD to PPF(all P<0.05).A prediction model was established based on the results of the multivariate COX regression analysis.The area under the receiver operator characteristic curve at 6 months,9 months,and 12 months was 0.989,0.931,and 0.797,respectively,indicating that the model has good discrimination and sensitivity,and good predictive efficacy.The calibration curve showed a good overlap between predicted and actual values.Conclusions The extent of fibrosis,serum ferritin,albumin,and age are independent risk factors for the progression of CTD-ILD to PPF.The model established based on this and externally validated shows good predictive efficacy.