A new protocol of biomarker evaluation by comparing systemic profiles of inflammatory mediators among different study groups, disease stages and severities, integrating clinical informatics and bioinformatics, and understanding the biological function and signal networks. It is important to clarify recruitment criteria of healthy, sCOPD and AECOPD at different stages, and collect clinical information and blood sample. Clinical informatics is generated through a new Digital Evaluation Score System, while inflammatory mediators are measured by multiplex antibody array and followed by proteomics-based bioinformatics. Disease-specific biomarkers are identified by integrating clinical informatics and functional networks through the global proteomics data set, to develop diagnostics and predictive for personalized medicine and disease prevention.