Abstract
Chronic obstructive pulmonary disease (COPD) is a complex disorder predominantly affecting smokers and is characterized by progressive airflow obstruction that is largely irreversible. Approximately 25% of smokers are believed to be susceptible to developing the disease, suggesting that there are at present unknown genetic, epigenetic and/or environmental factors which underlie an individual's risk for developing the disease. COPD is a multifactorial disease and susceptibility is therefore likely to be determined by the expression of a number of allelic variants that leave an individual less capable of handling the damaging effects of chronic smoking. It is proposed herein that intrinsic aerobic (exercise) capacity is the primary trait which determines an individual's risk for developing this disease. This polygenetic characteristic comprises an individual's ability to metabolize oxygen and detoxify its reactive species. Pathways regulating these processes are damaged by smoking; thus individuals with low aerobic capacity may be more likely to develop smoking-induced lung damage, eventually leading to irreversible pathologies which cause airflow obstruction.