McDermott Gregory C, Hayashi Keigo, Juge Pierre-Antoine, Gill Ritu, Byrne Suzanne, Gagne Staci, Wang Xiaosong, Paudel Misti L, Moll Matthew, Cho Michael H, Vanni Kathleen, Kowalski Emily, Qian Grace, Bade Katarina, Saavedra Alene, Kawano Yumeko, DiIorio Michael, Wolfgang Taylor, Kim Edy Y, Dellaripa Paul F, Weinblatt Michael E, Shadick Nancy, Doyle Tracy J, Sparks Jeffrey A
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Brigham and Women's Hospital, Boston, Massachusetts.
Arthritis Care Res (Hoboken). 2025 Feb;77(2):185-194. doi: 10.1002/acr.25432. Epub 2024 Oct 16.
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) includes multiple subtypes with varying histopathology, prognosis, and potential treatments. Limited research has investigated risk factors for different RA-ILD subtypes. Therefore, we examined demographic, serologic, and lifestyle associations with RA-ILD subtypes.
We systematically identified RA-ILD cases and RA controls without ILD (RA-noILD) in the Brigham RA Sequential Study and Mass General Brigham Biobank RA cohort. We determined RA-ILD subtype (usual interstitial pneumonia [UIP], nonspecific interstitial pneumonia [NSIP], and other/indeterminate) through chest high-resolution computed tomography imaging pattern. We investigated associations of demographic, lifestyle, and serologic factors with major RA-ILD subtypes using multivariable logistic regression.
Among 3,328 patients with RA, we identified 208 RA-ILD cases and 547 RA-noILD controls. RA-UIP was associated with older age (odds ratio [OR] 1.03 per year, 95% confidence interval [95% CI] 1.01-1.05), male sex (OR 2.15, 95% CI 1.33-3.48), and seropositivity (OR 2.08, 95% CI 1.24-3.48), whereas RA-NSIP was significantly associated only with seropositive status (OR 3.21, 95% CI 1.36-7.56). Nonfibrotic ILDs were significantly associated with smoking (OR 2.81, 95% CI 1.52-5.21). Having three RA-ILD risk factors (male, seropositive, smoking) had an OR of 6.89 (95% CI 2.41-19.7) for RA-UIP compared with having no RA-ILD risk factors.
Older age, seropositivity, and male sex were strongly associated with RA-UIP, whereas RA-related autoantibodies were associated with RA-NSIP. These findings suggest RA-ILD sex differences may be driven by RA-UIP and emphasize the importance of further studies to clarify RA-ILD heterogeneity and optimize screening and treatment approaches.
类风湿关节炎相关间质性肺疾病（RA - ILD）包括多种具有不同组织病理学、预后和潜在治疗方法的亚型。针对不同RA - ILD亚型的危险因素进行研究的较少。因此，我们研究了人口统计学、血清学和生活方式与RA - ILD亚型之间的关联。
我们在布莱根妇女医院类风湿关节炎序列研究和麻省总医院布莱根生物样本库类风湿关节炎队列中系统地识别出RA - ILD病例和无ILD的类风湿关节炎对照（RA - noILD）。我们通过胸部高分辨率计算机断层扫描成像模式确定RA - ILD亚型（寻常型间质性肺炎[UIP]、非特异性间质性肺炎[NSIP]以及其他/不确定型）。我们使用多变量逻辑回归研究人口统计学、生活方式和血清学因素与主要RA - ILD亚型之间的关联。
在3328例类风湿关节炎患者中，我们识别出208例RA - ILD病例和547例RA - noILD对照。RA - UIP与年龄较大（比值比[OR]为每年1.03，95%置信区间[95%CI]为1.01 - 1.05）、男性（OR为2.15，95%CI为1.33 - 3.48）以及血清学阳性（OR为2.08，95%CI为1.24 - 3.48）相关，而RA - NSIP仅与血清学阳性状态显著相关（OR为3.21，95%CI为1.36 - 7.56）。非纤维化ILD与吸烟显著相关（OR为2.81，95%CI为1.52 - 5.21）。与无RA - ILD危险因素相比，具有三种RA - ILD危险因素（男性、血清学阳性、吸烟）的患者患RA - UIP的OR为6.89（95%CI为2.41 - 19.7）。
年龄较大、血清学阳性和男性与RA - UIP密切相关，而类风湿关节炎相关自身抗体与RA - NSIP相关。这些发现表明RA - ILD的性别差异可能由RA - UIP驱动，并强调进一步研究以阐明RA - ILD异质性以及优化筛查和治疗方法的重要性。
