The main disease feature of COPD is fixed airflow limitation. There is increasing evidence and acceptance that COPD is no longer a disease confined to the lungs, and that COPD has a broader impact on the health status of patients. COPD is ranked as the 4th cause of chronic disease and death worldwide, and COPD mortality is expected to increase further in the future, rising to 3rd in the ranking by 2020, after coronary artery disease and stroke. The correlations between FEV1, smoking status, and OR for CVD mortality among current smokers (dark gray column), former smokers (blank column), and nonsmokers (light gray column) (A) and between FEV1, smoking status, and all-cause mortality among heavy smokers (dark gray column), moderate smokers (light gray column), former smokers (blank column), and nonsmokers (medium gray column) (B) were based on the Gini coefficient of variation (GCE). According to the GOLD (Global Initiative for the Prevention and Treatment of COPD) guidelines, COPD is diagnosed on the basis of spirometry results with an FEV1 to FVC ratio below 0.7 after bronchodilators, and the severity of lung function decline is graded according to the percentage of FEV1 to the expected value (GOLD scale I-IV). This functional definition of COPD based on airflow limitation is still used to clarify the disease status of COPD, but it is clear that the degree of airflow limitation is only one aspect of the risk assessment of COPD. Increasingly, it is believed that the clinical severity of COPD should be determined by complications in addition to the disease characteristics of COPD itself [i.e., hyperinflation and/or emphysema]. Because of the diversity of clinical presentations, ranging from chronic bronchitis to hyperinflation to severe emphysema, the diagnostic term COPD represents a wide range of clinical phenotypes of patients. Hyperinflation reduces functional physical activity and has been shown to be an independent risk factor for death in COPD. Emphysema is associated with an increased risk of lung cancer, atherosclerosis, and osteoporosis. Also, the fact that some specific classes of drugs, such as selective phosphodiesterase 4 inhibitors, can affect the disease process only in specific COPD populations and are not effective in other COPD populations supports the idea that COPD is a heterogeneous disease that requires individualized treatment. Figure 2 Expected mortality within 5 y for patients with COPD after grading according to the modified GOLD criteria and for those with no comorbid (light gray squares), 1 comorbid (blank squares), 2 comorbid (medium gray squares), or 3 comorbid (dark gray squares) diseases (diabetes, hypertension, or cardiovascular disease) COPD patients may exhibit comorbidities related to common risk factors, often in the form of decreased physical activity. The common approach to COPD treatment places pulmonary disease at the center of treatment and results in a widely accepted cause-and-effect relationship: respiratory limitation results in comorbidities that lead to physical activity limitation and clinical manifestations. Another view is that the pulmonary manifestations of COPD may also be an aspect of the systemic inflammatory response to the clinical manifestations of other organs. According to this view, systemic inflammation (e.g., induced by physical activity limitation or complications) in susceptible subjects may contribute to the development of COPD as a syndrome. This view remains controversial because it has not been proven.