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Although COPD is a major disease worldwide, there is a perplexing current uncertainty about the nature of this disease. COPD is characterized at onset and prevalently by the involvement of the lungs and bronchi, but as the disease evolves, abnormalities develop in other organs and systems and the question arises: what is the pathogenesis of these respiratory and systemic impairments? Are the alterations that occur outside the respiratory system in the course of COPD a direct consequence of the lung pathology or is the lung simply the local expression of a pathological event whose origin lies in the organism as a whole? There is currently a growing debate about whether COPD and all its comorbidities should be considered as a pulmonary disease with systemic implications or whether it should come under a new umbrella term — chronic systemic inflammatory syndrome — because the systemic effects of smoking contribute to several other conditions, including cardiovascular disease, some cancers, and increased blood pressure.