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Objective: To analyze the salivary peptide profiles of patients with periodontitis (PD) and chronic obstructive pulmonary disease (COPD), to identify differentially expressed peptides that are associated with diseases, to explore for biomarkers with potential diagnostic significance, and to probe for new perspectives for the early prevention and treatment of COPD., Methods: A total of 10 PD patients (the PD group), 10 PD patients with COPD (the PD plus COPD group), and 8 healthy controls (the Control group) were selected for the study. The clinical data and saliva samples of the subjects were collected. Salivary supernatant samples were separated and purified with weak-cation-exchange magnetic bead-based (WCX-MB). With matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), the biodata of the samples were obtained and differential salivary peptide profiling was conducted to screen for peptides exhibiting inter-group differences. In addition, all the differentially expressed peptides were examined and verified with liquid chromatography tandem mass spectrometry (LC-MS/MS)., Result: An average of 77 peptide mass peaks were detected among three groups, the peaks intensities differed significantly for 10 peptides between PD patients and PD patients with COPD. Among them, eight peptides (1193.5, 1836.2, 1735.1, 1321.3, 1356.8, 2086.8, 1863.6, and 2230.9) showed increased expression and two peptides (1067.3 and 1124.4) showed decreased expression in the PD plus COPD group, in comparison with the PD group. Among the 10 differential peptides, 1193.5 and 1356.8 were identified as histidine-rich protein-1, submaxillary gland androgen-regulated protein 3B, and salivary acidic proline-rich protein 1/2., Conclusion: With WCX-MB and MALDI-TOF-MS, we have identified, from the saliva of patients with concomitant PD and COPD, differentially expressed salivary peptides that were associated with diseases. The differentially expressed peptides thus screened out show promises for being used as auxiliary biomarkers for early diagnosis of COPD., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)