Jianping Diao,1,2 Lin Qiao,1 Xinwang Duan,3 Min Hui,4 Mengtao Li,1 Yan Zhao,1 Xiaofeng Zeng,1 Dong Xu1 

1Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Rheumatology and Immunology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, People’s Republic of China; 3Department of Rheumatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China

Correspondence: Dong Xu, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +8613621318151, Email xudong74@hotmail.com Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, +8613501069845, Email xiaofeng.zeng@cstar.org.cn

Objective: This study aims to investigate the clinical characteristics and identify risk factors associated with progressive pulmonary fibrosis (PPF) in individuals diagnosed with primary Sjögren’s syndrome (pSS).
Methods: A retrospective case-control study was conducted from individuals with pSS-associated interstitial lung disease (pSS-ILD) registered in the Chinese Rheumatism Data Center between June 2010 and October 2023. Participants were categorized into two groups: those with PPF (pSS-PPF) and those without PPF (pSS-non-PPF). Comparative analyses were performed on clinical manifestations, laboratory parameters, pulmonary function, and treatment history between the two groups.
Results: Sixty-six individuals with pSS-ILD were included, of whom 29 met the criteria for PPF. Compared to pSS-non-PPF group, the pSS-PPF group demonstrated a higher rate of expectoration (48.3% vs 16.2%, p = 0.005) and crackles on auscultation (41.4% vs 13.5%, p = 0.01), but lower rates of parotid gland enlargement (3.4% vs 32.4%, p = 0.003), and arthritis (6.9% vs 27%, p = 0.035). Additionally, the incidence rate of the subjects suffering xerophthalmia and xerostomia in the PPF group was lower (24.1% vs 2.7%, p = 0.023). Pulmonary function testing showed significantly reduced forced vital capacity percentage predicted (83.6± 15.6 vs 91.3± 14.6, p = 0.042) and diffusing capacity of the lung for carbon monoxide percentage predicted (DLCO%, 54.2± 21.5 vs 68.5± 13.6, p = 0.003) in the PPF group. Multivariate logistic regression identified a baseline DLCO% < 60% as an independent risk factor for PPF. Parotid gland enlargement and arthritis were potentially protective. The predictive model demonstrated good performance, with an area under the curve of 0.821 (95% CI: 0.716~0.925, p < 0.001). The sensitivity was 58.6% and the specificity was 91.7%.
Conclusion: A baseline DLCO% < 60% is an independent predictor of PPF in individuals with pSS. The developed predictive model shows strong discriminatory ability, while further validation in larger cohorts is warranted.

Keywords: interstitial lung disease, predictive model, primary Sjögren’s syndrome, pSS, progressive pulmonary fibrosis, PPF, risk factors