The model showed good fit with the data and highlight several features: i) smoking effects were mostly mediated by lung function, underlining the major role of COPD and lung alteration in the occurrence of systemic manifestations ii) significant direct effects of smoking were strictly limited to inflammatory markers (CRP, White Blood Cells count) iii) the model did not show any direct or indirect effects of inflammation or telomere length on systemic manifestations. Here, CRP is linked to chronic obstructive pulmonary disease.