COPD: a multifactorial systemic disease.

Chronic obstructive pulmonary disease (COPD) has traditionally been considered a disease of the lungs secondary to cigarette smoking and characterized by airflow obstruction due to abnormalities of both airway (bronchitis) and lung parenchyma (emphysema). It is now well known that COPD is associated with significant systemic abnormalities, such as renal and hormonal abnormalities, malnutrition, muscle wasting, osteoporosis, and anemia. However, it is still unclear whether they represent consequences of the pulmonary disorder, or whether COPD should be considered as a systemic disease. These systemic abnormalities have been attributed to an increased level of systemic inflammation. Chronic inflammation, however, may not be the only cause of the systemic effects of COPD. Recent data from humans and animal models support the view that emphysema may be a vascular disease. Other studies have highlighted the role of repair failure, bone marrow abnormality, genetic and epigenetic factors, immunological disorders and infections as potential causes of COPD systemic manifestations. Based on this new evidence, it is reasonable to consider COPD, and emphysema in particular, as 'a disease with a significant systemic component' if not a 'systemic disease' per se. The aim of this review is to give an overview of the most relevant and innovative hypothesis about the extrapulmonary manifestations of COPD.