RATIONALE: The study aimed to investigate the interplay among respiratory function, autonomic dysfunction, and systemic inflammation in COPD patients. METHODS: In 19 COPD patients, functional respiratory parameters, heart rate variability (HRV), and plasma high-sensitivity-C-reactive-protein (hs-CRP) were assessed. Forced oscillation technique (FOT) was used to detect the absence (NFL) or presence (FL) of resting tidal expiratory flow limitation. Subsequently, patients underwent an incremental shuttle walking test (ISWT). Twenty healthy subjects were also shown as controls. RESULTS: FEV(1), DL(CO), and lung volumes displayed significant correlations with LH/FH ratio (0.56 < r(2)<0.27,p < 0.01). A significant relationship was found between LH/FH ratio with IC/TLC ratio% (r(2) = 0.29,p < 0.05) and hs-CRP (r(2) = 0.26,p < 0.05). Patients with FL had greater hs-CRP plasma levels (p < 0.05), lower IC/TLC% (p < 0.05), and higher LH/FH ratio (p<0.001). CONCLUSIONS: Worse airflow obstruction was associated with a higher LH/HF ratio, directly related, to hs-CRP and indices of dynamic hyperinflation. The presence of resting tidal FL with dynamic pulmonary hyperinflation is a strong driver of systemic inflammation and autonomic dysfunction.