Contribution of the environment and comorbidities to chronic obstructive pulmonary disease phenotypes.

• COPD is a heterogeneous disease, modified by environmental and intrinsic host factors. The interaction between COPD and its comorbidities is complex and bidirectional. * It has been estimated that the proportion of patients with COPD caused by cigarette smoking is between 80% and 90%. Risk factors associated with COPD in nonsmokers are numerous and incompletely understood, but a history of asthma or tuberculosis, exposure to traffic and outdoor pollution, and exposure to biomass smoke show the strongest associations. Other factors that may contribute to COPD phenotypes include gender, genetics, and the lung microbiome. * Certain comorbid conditions, such as cardiovascular disease and osteoporosis, are more common in the COPD patient population. Other comorbidities, such as overlap syndrome, the coexistence of COPD, and obstructive sleep apnea may not be as prevalent in COPD but are important because they may modify disease course. * Systemic inflammation may be pathogenically related to many comorbidities seen in COPD including cardiovascular disease, osteoporosis, metabolic syndrome, and depression. * Based on the data presented here, two general patterns of clinical features and comorbidities that share some associations are (1) emphysema, low BMI and osteoporosis and (2) chronic bronchitis, airway disease, high BMI, OSA, and diabetes. * The classification of patients with COPD into subgroups with shared characteristics and outcomes offers the potential for specific interventions. New research tools from the fields of epidemiology, immunology, imaging, and data analysis will be helpful in accomplishing this goal.