The methods described herein are based on the discovery that the plasma level of a panel of specific proteins differs between two subject populations: 1) subjects at risk for chronic obstructive pulmonary disease (“COPD”) but not manifesting clinical symptoms of COPD; and 2) subjects having very severe COPD. The difference in plasma levels is statistically significant for each protein. The identification of these proteins thus facilitates susceptibility detection, early disease detection, disease severity assessment, disease progression monitoring, and therapy efficacy monitoring.