Author(s): BALDASSARRE, G., GASPARINI, A., TAM, E., DO NASCIMENTO SALVADOR, P.C., ZUCCARELLI, L., BOCHICCHIO, G., BROCCA, L., BOTTINELLI, R., CAPELLI, C., FEMIA, D., PATRUNO, V., ZAMBONI, F., PELLEGRINO, M.A., CRISAFULLI, E., GRASSI, B., Institution: UNIVERSITY OF UDINE, Country: ITALY, Abstract-ID: 1332

INTRODUCTION:
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease causing restricted airflow, reduced exercise tolerance and impaired quality of life. Among the key factors contributing to exercise intolerance, peripheral factors (microvascular/endothelial and skeletal muscle oxidative functions) may play a crucial role. Non-invasive biomarkers of these impairments would be helpful in the evaluation of patients.
METHODS:
Fourteen patients with moderate-to-severe COPD (7 females, 67±8 yrs, FEV1: 50.4±7.9 % predicted) and 31 healthy controls (17 females, 64±7 yrs), were recruited for the present study. Participants performed an incremental exercise test on a cycle ergometer in order to determine peak pulmonary oxygen uptake (V̇O2peak) and other “systemic” biomarkers of exercise tolerance. Microvascular and endothelial functions were evaluated in the common femoral artery (CFA), by duplex Doppler ultrasound, by monitoring the blood flow response during 1 minute of Passive Leg Movements (PLM). Resting blood flow, peak blood flow, the change from baseline to peak blood flow (∆peak) and the area under the blood flow vs time response (AUC) were calculated. Skeletal muscle oxidative function was assessed in-vivo by determining skeletal muscle (medial gastrocnemius) V̇O2 (V̇O2m) rate constant (k) during the recovery from plantar flexion exercise, by near-infrared spectroscopy (NIRS) and the “repeated occlusions” method.
RESULTS:
Pulmonary V̇O2peak was lower in COPD patients than in controls (16.4±3.0 vs 29.9±5.7 ml·kg⁻¹·min⁻¹; p<0.001). No differences were observed between the two groups in terms of CFA diameter (p=0.08) and resting blood flow (p=0.59). PLM elicited a hyperemic response in both COPD patients and controls; however, a significantly blunted response was observed in COPD patients compared to controls (Δpeak: 208±69 vs 324±142 mL∙min-1, p=0.008; AUC: 75±48 vs 144±102 mL, p=0.026). V̇O2m off-k was 31% lower (p=0.003) in COPD patients than in controls (1.22±0.34 vs 1.76±0.55 min-1).
CONCLUSION:
Biomarkers of reduced exercise tolerance were observed in COPD patients, along with signs of microvascular/endothelial and skeletal muscle oxidative dysfunctions. These findings confirm that, in combination with the well-documented impairments of pulmonary function, “peripheral” factors contribute to the exercise intolerance associated with the disease. The non-invasiveness of our biomarkers of impairment should be valuable for designing effective therapeutic strategies both in clinical and research settings.

Funding: MUR; PRIN PNRR Project 2022, P2022XX7YL