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类风湿关节炎相关间质性肺疾病进展的危险因素:临床特征、生物标志物和治疗选择。

Risk factors for the progression of rheumatoid arthritis-related interstitial lung disease: Clinical features, biomarkers, and treatment options.

机构信息

Department of Rheumatology and Immunology, The First People's Hospital of Yancheng, The Fourth Affiliated Hospital of Nantong University, Yancheng 224000, China; Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.

Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.

出版信息

Semin Arthritis Rheum. 2022 Aug;55:152004. doi: 10.1016/j.semarthrit.2022.152004. Epub 2022 Apr 11.

Abstract

OBJECTIVES

The clinical heterogeneity of the progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is high, and there is a lack of consensus on the clinical relevance and medical protocols. The purpose of this study is to explore the impact of clinical characteristics, new biomarkers and treatment options on the prognosis of RA-ILD patients and to explore whether these factors can predict the progression and death of these patients.

METHODS

We retrospectively collected case data on RA-ILD patients who visited or were admitted to Changhai Hospital between October 2010 and September 2021. We followed up and finally included 75 patients. The main outcome indicator of disease progression was pulmonary functional impairment, which was assessed by changes of high-resolution computed tomography (HRCT) score or pulmonary function test before and after treatment. The demographics, clinical characteristics, laboratory tests, and treatment plans of RA-ILD patients in the progressive and stable groups were compared and analyzed. Clinically relevant variables were identified, and the incidence of pulmonary dysfunction and adverse events was recorded. Cox regression analysis was used to determine factors related to the progression of ILD.

RESULTS

The mean age of RA-ILD onset was 64.0 years (SD 10.3), and 53 (70.7%) patients were female. Thirty-two (42.7%) patients had lung dysfunction, who were classified as the progressive group, and 13 (40.6%) of them died. In univariate analyses, male, smoking, high HRCT scores at baseline, RF-IgA>200 RU/ml, diffusing capacity of the lungs for carbon monoxide (DLCO), and usual interstitial pneumonia (UIP) pattern were significant risk factors for disease progression; while use of Leflunomide (LEF) was associated with better prognosis. The multivariate analysis revealed that RF-IgA>200 RU/ml (hazard ratio [HR] 3.17 [95% confidence interval (CI) 1.29, 7.81], P = 0.012), UIP pattern (HR 3.94 [95% CI 1.68, 9.26], P = 0.002), and male (HR 2.52 [95% CI 1.16, 5.46], P = 0.019) were significantly correlated with unfavorable outcomes in patients with RA-ILD. LEF (HR 0.25 [95% CI 0.10, 0.61], P = 0.002) was related to a better prognosis. However, it might be related to investigating medications changes after baseline.

CONCLUSION

Our data suggests that male, UIP pattern, and increased RF-IgA may be potential predicting factors for poor prognosis of RA-ILD patients. We report a significant association between high titer of RF-IgA at baseline and RA-ILD progression for the first time, which might be a potentially important biomarker for the prognosis of RA-ILD.

摘要

目的

类风湿关节炎相关间质性肺病(RA-ILD)的临床异质性较高,其临床相关性和医学方案尚未达成共识。本研究旨在探讨临床特征、新型生物标志物和治疗选择对 RA-ILD 患者预后的影响,并探讨这些因素是否可以预测患者的病情进展和死亡。

方法

我们回顾性收集了 2010 年 10 月至 2021 年 9 月期间在长海医院就诊或住院的 RA-ILD 患者的病例数据。我们进行了随访,最终纳入了 75 例患者。疾病进展的主要结局指标是肺功能损害,通过治疗前后高分辨率计算机断层扫描(HRCT)评分或肺功能检查的变化来评估。比较并分析进展组和稳定组 RA-ILD 患者的人口统计学、临床特征、实验室检查和治疗方案。确定临床相关变量,并记录肺功能障碍和不良事件的发生率。采用 Cox 回归分析确定与 ILD 进展相关的因素。

结果

RA-ILD 发病的平均年龄为 64.0 岁(标准差 10.3),53 例(70.7%)为女性。32 例(42.7%)患者有肺功能障碍,被分类为进展组,其中 13 例(40.6%)死亡。单因素分析显示,男性、吸烟、基线时 HRCT 评分较高、类风湿因子免疫球蛋白 A(RF-IgA)>200 RU/ml、一氧化碳弥散量(DLCO)和普通间质性肺炎(UIP)模式是疾病进展的显著危险因素;而使用来氟米特(LEF)与更好的预后相关。多因素分析显示,RF-IgA>200 RU/ml(风险比[HR]3.17[95%置信区间(CI)1.29,7.81],P=0.012)、UIP 模式(HR 3.94[95%CI 1.68,9.26],P=0.002)和男性(HR 2.52[95%CI 1.16,5.46],P=0.019)与 RA-ILD 患者的不良结局显著相关。LEF(HR 0.25[95%CI 0.10,0.61],P=0.002)与更好的预后相关,但可能与基线后药物治疗变化有关。

结论

我们的数据表明,男性、UIP 模式和 RF-IgA 升高可能是 RA-ILD 患者预后不良的潜在预测因素。我们首次报告了基线时高 RF-IgA 滴度与 RA-ILD 进展之间存在显著关联,这可能是 RA-ILD 预后的一个潜在重要生物标志物。

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