Genetic, immune and environmental interactions are key elements for the development of COPD. Cigarette
smoking is considered the primary risk factor initiating inflammatory cascades in genetically susceptible individuals.
The “danger signals” elicited by the injured cells of non-specific immunity induce the downstream activation of proinflammatory
cascades and antigen-specific adaptive immune responses. The produced oxidative stress further damages the
lung leading to acquired genetic changes (histone deacetylation, microsatellite DNA instability, DNA methylation, telomere
shortening, miRNA alterations) due to an inefficient DNA repair machinery. On the other hand, augmented apoptosis,
impaired efferocytosis and abnormal tissue remodeling contribute to the chronic inflammatory response and tissue
destruction in COPD.
This review focuses on the role of genetic, epigenetic and immune mechanisms in the development of COPD in order to
put forward possible prognostic and therapeutic targets.