Background: Pulmonary manifestations contribute significantly to morbidity and mortality in rheumatoid arthritis (RA), yet biomarkers to identify patients at risk of lung involvement are lacking. Objective: To compare proteomic signatures in peripheral blood and sputum between RA patients with and without lung involvement and to identify potential biomarkers for pulmonary manifestations. Methods: In this cross‑sectional study, 33 RA patients with lung involvement and 7 RA controls without lung involvement provided paired blood and sputum samples. Proteomic profiling was performed using a 92‑protein proximity extension immunoassay. Associations between protein levels and lung involvement were analysed with logistic regression adjusted for age, smoking status and disease duration. Results: Significant differences were observed in eight proteins in blood and four proteins in sputum. Higher levels of IL‑8, 4EBP1, SIRT2 and ST1A1 in blood were associated with increased odds of lung involvement, while elevated IL‑12B, FGF19, CASP8, IL‑1α, IL‑17A, CXCL5, DNER and CCL28 were associated with lower risk. Conclusions: Proteomic analysis of blood and sputum samples from RA patients identified several proteins that may serve as biomarkers for lung involvement. These findings suggest that peripheral and airway proteome profiling can aid early detection of pulmonary manifestations in RA【746140114163262†L1049-L1098】.