Ramien Ronja, Rudi Tatjana, Alten Rieke, Krause Andreas, Schneider Matthias, Schaefer Martin, Strangfeld Anja, Meissner Yvette
Epidemiology and Health Services Research, German Rheumatology Research Center, Charitéplatz 1, 10117, Berlin, Germany.
Privataerztliches Zentrum am Roseneck, Berlin, Germany.
Arthritis Res Ther. 2024 Dec 5;26(1):209. doi: 10.1186/s13075-024-03449-9.
To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).
We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months.
We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97-1.40] and 1.06 [0.86-1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35-2.57]) and log CRP (1.55 [1.21-1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings.
Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient's global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.
探讨类风湿关节炎（RA）患者发生间质性肺疾病（ILD）与RA疾病活动及其各组成部分之间的关联，尤其是与C反应蛋白（CRP）和红细胞沉降率（ESR）的关联。
我们分析了2001年至2021年在德国生物制剂登记处RABBIT中观察到的RA患者的数据。在一项巢式病例对照研究中，将随访期间报告有新发ILD诊断的患者与无ILD的患者按1:5进行匹配。匹配标准为性别、年龄、RA病程、入组日期和观察时间。根据有向无环图（DAG）定义，我们对类风湿因子、吸烟、慢性阻塞性肺疾病和结核病/慢性病毒感染调整条件逻辑回归模型，以研究疾病活动/全身炎症的影响。在ILD发生前12个月内及整个观察期内分析均值和分类值。此外，进行了两项敏感性分析，一项仅使用经过验证的ILD病例，另一项考虑观察时间超过12个月的ILD病例。
我们确定了139例发生ILD的RA患者，并将他们与686例对照进行匹配。94例病例的诊断得到验证，98例病例的随访时间超过12个月。DAS28综合评分平均值（包括ESR或CRP）与发生RA-ILD无关（比值比分别为1.16 [95%置信区间：0.97 - 1.40]和1.06 [0.86 - 1.29]）。然而，炎症单项指标，即ESR对数（1.86 [1.35 - 2.57]）和CRP对数（1.55 [1.21 - 1.97]），与RA-ILD风险增加显著相关。持续高炎症状态也显示ILD风险更高。其他DAS28组成部分与RA-ILD无显著关联。这些结果在患者整个观察期及ILD发生前12个月内的值中是一致的。敏感性分析证实了这些发现。
ESR和CRP所表明的全身炎症水平较高，但关节计数或患者整体评估并非如此，与RA患者发生新发ILD显著相关。作为RA-ILD发生的可能预测指标，应密切且独立于关节计数结果监测全身炎症。
