Chang Sung Hae, Paudel Misti L, McDermott Gregory C, Zhang Qianru, Fukui Sho, Kim Minuk, Ha You-Jung, Lee Jeong Seok, Lee Sung Won, Park Chan Ho, Kim Ji-Won, Ha Jang Woo, Chung Sang Wan, Kang Eun Ha, Lee Yeon-Ah, Park Yong-Beom, Choe Jung-Yoon, Lee Eun Young, Sparks Jeffrey A
Division of Rheumatology, Department of Internal Medicine, Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston and Harvard Medical School, Boston, MA, USA.
Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston and Harvard Medical School, Boston, MA, USA.
Semin Arthritis Rheum. 2025 Aug;73:152729. doi: 10.1016/j.semarthrit.2025.152729. Epub 2025 Apr 17.
To develop a prediction model for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression.
We investigated predictors of RA-ILD progression in the Korean RA-ILD (KORAIL) cohort, a prospective study that enrolled patients with RA meeting ACR/EULAR criteria and ILD on chest computed tomography (CT) scans and followed for 3 years. Pulmonary function tests (PFTs) and chest CT scans were conducted annually. RA-ILD progression was defined as both physiological and radiological worsening, adapted from the 2023 ATS/ERS/JRS/ALAT definition of progressive pulmonary fibrosis. Baseline factors included clinical factors and biomarkers (autoantibodies, inflammatory markers, and pulmonary damage markers).
We analyzed 138 RA-ILD patients (mean age 66.4 years, 30.4 % male, 60.1 % usual interstitial pneumonia [UIP] pattern). During a median follow-up of 2.9 years, 34.8 % (n = 48) had RA-ILD progression. Baseline associations with progression included: UIP pattern, ILD extent >10 %, DLCO %pred., anti-cyclic citrullinated peptide (anti-CCP), Krebs von den Lungen-6 (KL-6), and human surfactant protein D. We developed prediction models using UIP pattern, ILD extent, DLCO % pred., and anti-CCP titer with or without serum KL-6 levels. The models had areas under the curve (AUCs) of 0.73 and 0.75, respectively. The high-risk group had a positive predictive value for progression of 85.7 %, while the low-risk group had a negative predictive value of 94.7 %.
In this prospective cohort, UIP pattern, ILD extent, lower DLCO, RA disease activity, anti-CCP levels, and pulmonary damage biomarkers were associated with RA-ILD progression. We developed prediction models that may be clinically useful to risk stratify once externally validated.
建立类风湿关节炎相关间质性肺病（RA-ILD）进展的预测模型。
我们在韩国RA-ILD（KORAIL）队列中研究了RA-ILD进展的预测因素，这是一项前瞻性研究，纳入了符合美国风湿病学会/欧洲抗风湿病联盟（ACR/EULAR）标准且胸部计算机断层扫描（CT）显示有ILD的RA患者，并随访3年。每年进行肺功能测试（PFT）和胸部CT扫描。RA-ILD进展定义为生理和影像学恶化，改编自2023年美国胸科学会/欧洲呼吸学会/日本呼吸学会/拉丁美洲胸科协会（ATS/ERS/JRS/ALAT）对进行性肺纤维化的定义。基线因素包括临床因素和生物标志物（自身抗体、炎症标志物和肺损伤标志物）。
我们分析了138例RA-ILD患者（平均年龄66.4岁，男性占30.4%，60.1%为普通型间质性肺炎[UIP]模式）。在中位随访2.9年期间，34.8%（n = 48）的患者出现RA-ILD进展。与进展相关的基线因素包括：UIP模式、ILD范围>10%、预计值百分比的一氧化碳弥散量（DLCO %pred.）、抗环瓜氨酸肽（抗CCP）、肺表面活性物质相关蛋白D（KL-6）和人表面活性蛋白D。我们使用UIP模式、ILD范围、DLCO %pred.和抗CCP滴度，无论有无血清KL-6水平，建立了预测模型。这些模型的曲线下面积（AUC）分别为0.73和0.75。高危组进展的阳性预测值为85.7%，而低危组的阴性预测值为94.7%。
在这个前瞻性队列中，UIP模式、ILD范围、较低的DLCO、RA疾病活动度、抗CCP水平和肺损伤生物标志物与RA-ILD进展相关。我们建立的预测模型一旦经过外部验证，可能在临床上对风险分层有用。
