Clinical Cohort And Biomarker Study Of Chinese Patients With Rheumatoid Arthritis Associated Interstitial Lung Disease

Objective:By establishing a nationwide multi-center cohort study of Chinese patients with rheumatoid arthritis associated interstitial lung disease(RA-ILD),we aimed to describe cross-sectional characteristics of patients with RA-ILD,including demographics,disease assessment of RA and ILD,and baseline treamtent regimen.We also aimed to analyze risk factors of RA-ILD.We focused on screening diagnostic biomarkers of RA-ILD by metabolomics study through mass spectrum.Methods:This study is mainly consisted of two sections.For clinical study section,clinical data of patients with RA-ILD,who were diagnosed by nationwide medical centers in CTD-ILD through chest high-resolutional CT(HRCT),were retrospectively and prospectively collected.Cross-sectional characteristics of patients with RA-ILD were described.Nested case control study was conducted between patients with RA-ILD and patients with RA but not ILD(RA-nonILD)to identify risk factors.For biomarker study section,metabolomics study was carried out through mass spectrum to screen for potential metabolites used as diagnostic biomarkers.Result:A total of 2119 patients with RA-ILD were recruited in the study.In clinical study section,1)Baseline characteristics:67.9%patients were female,mean age at baseline was 62.5 ± 10.7.25.6%patients had a history of smoking,average amount of cigarette was 17.4 ± 10.7 per day.In 25.9%patients,ILD was the initial manifestation.The most common radiographic type was nonspecific interstitial pneumonia(NSIP).Mean forced vital capacity(FVC%)was 74.9 ± 29.0%and mean diffusing capacity of the lungs for carbon monoxide(DLCO)was 59.4±26.8%.Glucocorticoids and methotrexate were administrated in 52.7%and 16.3%of patients,respectively.3.1%of patients were treated with anti-pulmonary fibrosis phanmaceuticals at baseline.2)Risk factors:older age(OR 1.101,95%Cl 1.035-1.170,P=0.002),a history of smoking(OR 4.423,95%Cl 1.402-13.961,P=0.011),anti-MCV antibody positivity(OR 3.901,95%Cl 1.309-11.628,P=0.015)and medium to high disease activity using SDAI index(OR 3.088,95%Cl 1.051-9.074,P=0.040)were identified as independent risk factors for patients with RA to develop ILD.In biomarker study section,metabolomics of 22 RA-ILD and 22 RA-nonILD patients were sereened using liquid chromatography-mass spectrometry.174 metabolites with significant difference between two groups were found.Among them,16 metabolites were identified.Conclusion:This study established the world largest and is the first multi-center cohort study of patients with RA-ILD.Clinical characteristics and risk factors of Chinese patients with RA-ILD were described.Regular screening for ILD is recommended in patients with high risks,including older age,a history of smoking,anti-MCV antibody positivity and medium to high disease activity using SDAI index.Novel serum biomarkers for identifying ILD in patients with RA were identified,which will act as novel biomarkers for patients with RA-ILD after identified in larger cohort.