类风湿关节炎相关间质性肺疾病的肺损伤血清生物标志物及病情进展风险
Serum Biomarkers of Pulmonary Damage and Risk for Progression of Rheumatoid Arthritis-Associated Interstitial Lung Disease.
作者信息
Chang Sung Hae, Park Yong-Beom, McDermott Gregory C, Paudel Misti L, Hayashi Keigo, Ha You-Jung, Lee Jeong Seok, Kim Min Uk, Park Chan Ho, Kim Ji-Won, Ha Jang Woo, Chung Sang Wan, Lee Sung Won, Kang Eun Ha, Lee Yeon Ah, Choe Jung-Yoon, Lee Eun Young, Sparks Jeffrey A
机构信息
S.H. Chang, MD, PhD, MPH, Soonchunhyang University, Division of Rheumatology, Department of Internal Medicine, Cheonan, South Korea, and Brigham and Women's Hospital, Division of Rheumatology, Inflammation, and Immunity and Harvard Medical School, Boston, Massachusetts, USA, and Soonchunhyang University Cheonan Hospital, Division of Rheumatology, Department of Internal Medicine, Cheonan, South Korea.
Y.B. Park, MD, PhD, J.W. Ha, MD, PhD, Yonsei University College of Medicine, Division of Rheumatology, Department of Internal Medicine, Seoul, South Korea.
出版信息
J Rheumatol. 2025 Apr 1;52(4):323-333. doi: 10.3899/jrheum.2024-0713.
OBJECTIVE
To investigate baseline and change of pulmonary damage biomarkers (serum Krebs von den Lungen 6 [KL-6], human surfactant protein D [hSP-D], and matrix metalloproteinase 7 [MMP-7]) with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression.
METHODS
In the Korean Rheumatoid Arthritis Interstitial Lung Disease (KORAIL) cohort, a prospective cohort, we enrolled patients with RA and ILD confirmed by chest computed tomography imaging and followed annually. ILD progression was defined as worsening in physiological and radiological domains of the 2022 American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society guideline for progressive pulmonary fibrosis (PPF). Associations between biomarkers and RA-ILD progression were analyzed using multivariable Cox regression, adjusting for potential confounders.
RESULTS
We analyzed 136 patients with RA-ILD (mean age 66.5 yrs, 30% male, 60.3% with usual interstitial pneumonia pattern). During a median 3.0 years of follow-up, 47 patients (34.6%) experienced progression. Higher baseline KL-6 and hSP-D levels were associated with higher risk of ILD progression (multivariable hazard ratios [HRs] 1.37 [95% CI 1.03-1.82] and 1.51 [95% CI 1.09-2.08], respectively), whereas only the highest quartile of MMP-7 showed an increased risk (multivariable HR 2.60 [95% CI 1.07-6.33]). Increasing levels of serum KL-6 at 1 year showed the strongest association with progression (∆KL-6: multivariable HR 2.00 [95% CI 1.29-3.11]), additionally adjusting for baseline biomarker levels.
CONCLUSION
In this first prospective study to apply PPF criteria to RA-ILD, 34.6% progressed over 3 years. Higher baseline KL-6 and hSP-D were associated with progression. In follow-up, greater change in KL-6 was associated with progression. Serial measurement of pulmonary damage biomarkers may predict RA-ILD progression and may be helpful in monitoring patients and treatment decisions.
目的
研究类风湿关节炎相关间质性肺病（RA-ILD）进展过程中肺损伤生物标志物（血清克雷伯氏肺6 [KL-6]、人表面活性蛋白D [hSP-D]和基质金属蛋白酶7 [MMP-7]）的基线水平及变化情况。
方法
在韩国类风湿关节炎间质性肺病（KORAIL）前瞻性队列研究中，我们纳入了经胸部计算机断层扫描成像确诊为RA和ILD的患者，并进行年度随访。ILD进展定义为符合2022年美国胸科学会、欧洲呼吸学会、日本呼吸学会和拉丁美洲胸科学会发布的进行性肺纤维化（PPF）指南中生理和放射学领域的恶化情况。使用多变量Cox回归分析生物标志物与RA-ILD进展之间的关联，并对潜在混杂因素进行校正。
结果
我们分析了136例RA-ILD患者（平均年龄66.5岁，男性占30%，60.3%为普通型间质性肺炎模式）。在中位3.0年的随访期间，47例患者（34.6%）出现进展。较高的基线KL-6和hSP-D水平与ILD进展风险较高相关（多变量风险比[HRs]分别为1.37 [95%置信区间1.03 - 1.82]和1.51 [95%置信区间1.09 - 2.08]），而只有MMP-7最高四分位数显示风险增加（多变量HR 2.60 [95%置信区间1.07 - 6.33]）。1年时血清KL-6水平升高与进展的关联最强（∆KL-6：多变量HR 2.00 [95%置信区间1.29 - 3.11]），此外还对基线生物标志物水平进行了校正。
结论
在这项首次将PPF标准应用于RA-ILD的前瞻性研究中，34.6%的患者在3年内出现进展。较高的基线KL-6和hSP-D与进展相关。在随访中，KL-6的更大变化与进展相关。连续测量肺损伤生物标志物可能预测RA-ILD进展，并可能有助于监测患者和指导治疗决策。
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