基于乳酸脱氢酶水平的抗合成酶综合征相关间质性肺疾病发生与进展风险评估研究

Risk Assessment of the Onset and Progression of Anti-Synthetase Syndrome-Associated Interstitial Lung Disease Based on Serum Lactate Dehydrogenase Levels

摘要: 目的：探讨血清乳酸脱氢酶(lactate dehydrogenase, LDH)水平与抗合成酶综合征(anti-synthetase syndrome, ASS)患者并发间质性肺疾病(interstitial lung disease, ILD)及ASS-ILD疾病进展的关系，并评估其在疾病发生与进展风险分层中的应用潜力。方法：回顾性纳入2015年6月至2025年11月内蒙古自治区人民医院收治的ASS患者120例，按是否合并ILD分为ASS-ILD组(n = 96)与ASS-non-ILD组(n = 24)。收集所有入选者的临床资料、实验室检查结果、肺功能测定值以及胸部薄层CT图像等，对ASS-ILD患者进行随访，中位随访时间为19个月，记录疾病进展事件，定义为随访期间出现ASS进展和/或ILD进展。采用Spearman秩相关分析评估LDH等指标与ASS并发ILD的相关性；采用单因素及多因素Logistic回归分析疾病进展的相关因素；基于独立相关因素构建列线图预测模型，并评价其效能。结果：1) ASS患者ILD发生率为80.00%。ASS-ILD组LDH水平显著高于ASS-non-ILD组(330.42 ± 115.77 vs. 264.33 ± 82.01 U/L, P = 0.010)；ASS-ILD组病程更长，白蛋白、血红蛋白更低，ESR更高，抗EJ抗体阳性率、胸闷及Gottron征发生率均显著升高(P < 0.05)。2) LDH与ASS-ILD发生呈正相关(r = 0.236, P = 0.010)，病程、ESR、胸闷、Gottron征亦呈正相关(P < 0.05)；白蛋白、血红蛋白和抗OJ抗体与ASS-ILD发生呈负相关(P < 0.05)。3) 中位随访19个月，41例(42.71%)出现疾病进展。进展组LDH水平显著高于非进展组(386.41 ± 141.30 vs. 263.50 ± 73.44 U/L, P < 0.001)；进展组白蛋白、FVC%、DLCO%更低，CRP水平更高，肌痛发生率更高(P < 0.05)。4) 多因素Logistic回归显示，LDH (OR = 1.011, 95% CI: 1.002~1.019, P = 0.016)、白蛋白(OR = 0.921, 95% CI: 0.852~0.996, P = 0.040)和CRP (OR = 1.030, 95% CI: 1.001~1.061, P = 0.045)为疾病进展独立相关因素。5) 基于LDH、白蛋白和CRP构建列线图预测模型，ROC曲线下面积为0.851，灵敏度为73.2%，特异度为83.6%，约登指数为0.568。通过Bootstrap重复抽样的方法对模型进行拟合评价表明，模型预测结果与实际情况基本一致。结论：LDH水平升高与ASS患者并发ILD及ASS-ILD疾病进展均相关，是疾病进展的独立相关因素。基于LDH、白蛋白和CRP构建的列线图预测模型对疾病进展具有较好预测效能，可为ASS-ILD的早期风险识别和临床风险分层提供参考。LDH在ASS-ILD中更适合作为辅助风险提示指标，其临床应用应结合其他临床指标进行综合判断。

Abstract: Objective: This paper aims to investigate the association of serum lactate dehydrogenase (LDH) levels with interstitial lung disease (ILD) occurrence and disease progression in patients with anti-synthetase syndrome (ASS), and to evaluate its potential value in risk stratification. Methods: A total of 120 patients with ASS admitted to Inner Mongolia Autonomous Region People’s Hospital from June 2015 to November 2025 were retrospectively enrolled and divided into an ASS-ILD group (n = 96) and an ASS-non-ILD group (n = 24). Clinical characteristics, laboratory parameters, pulmonary function, and thin-section chest CT findings were collected. Patients with ASS-ILD were followed for a median of 19 months. Disease progression was defined as ASS progression and/or ILD progression during follow-up. Spearman correlation analysis was used to evaluate factors associated with ASS-ILD. Univariate and multivariate logistic regression analyses were performed to identify factors associated with disease progression. A nomogram was developed based on independent correlates, and its performance was assessed. Results: 1) The prevalence of ILD in patients with ASS was 80.00%. LDH levels were significantly higher in the ASS-ILD group than in the ASS-non-ILD group (330.42 ± 115.77 vs. 264.33 ± 82.01 U/L, P = 0.010). Compared with the ASS-non-ILD group, the ASS-ILD group had a longer disease duration, lower albumin and hemoglobin levels, higher ESR, and significantly higher positivity of anti-EJ antibody, chest tightness, and Gottron’s sign (all P < 0.05). 2) LDH was positively correlated with the occurrence of ASS-ILD (r = 0.236, P = 0.010). Disease duration, ESR, chest tightness, and Gottron’s sign were also positively correlated with ASS-ILD (all P < 0.05), whereas albumin, hemoglobin, and anti-OJ antibody were negatively correlated with ASS-ILD (all P < 0.05). 3) During a median follow-up of 19 months, 41 patients (42.71%) developed disease progression. LDH levels were significantly higher in the progressive group than in the non-progressive group (386.41 ± 141.30 vs. 263.50 ± 73.44 U/L, P < 0.001). Compared with the non-progressive group, the progressive group had lower albumin, FVC%, and DLCO%, higher CRP levels, and a higher frequency of myalgia (all P < 0.05). 4) Multivariate logistic regression analysis showed that LDH (OR = 1.011, 95% CI: 1.002~1.019, P = 0.016), albumin (OR = 0.921, 95% CI: 0.852~0.996, P = 0.040), and CRP (OR = 1.030, 95% CI: 1.001~1.061, P = 0.045) were independent related factors for disease progression. 5) A nomogram prediction model was constructed based on LDH, albumin, and CRP. The area under the ROC curve was 0.851, with a sensitivity of 73.2%, specificity of 83.6%, and Youden index of 0.568. Bootstrap calibration showed good agreement between predicted probabilities and observed outcomes. Conclusion: Elevated LDH levels are associated with both the development of ILD and disease progression in ASS patients, serving as an independent predictor of disease advancement. The logistic regression model constructed using LDH, albumin, and CRP demonstrates robust predictive efficacy for disease progression, providing a valuable tool for early risk identification and clinical risk stratification in ASS-ILD. LDH is particularly suitable as an adjunctive risk indicator in ASS-ILD, and its clinical application should be integrated with other clinical parameters for comprehensive evaluation.