Inflammatory and oxidative biomarkers as determinants of functional capacity in patients with COPD assessed by 6-min walk test-derived outcomes.

Introduction: Reduction in functional capacity is a negative clinical outcome of chronic obstructive pulmonary disease (COPD). Studies have shown association between inflammatory and oxidative stress biomarkers and functional capacity. However, it is unclear whether these biomarkers are associated with outcomes of functional capacity. Therefore, the aim of this study was to evaluate whether plasma biomarkers of inflammation and oxidative stress are predictors of the 6-min walking test (6MWT)-derived outcomes.

Methods: Twenty COPD patients were assessed on three consecutive days with different clinical measures, including functional capacity, and blood sampling. Plasma concentrations of IL-6, IL-8, TNF-ɑ, IL-10 and soluble TNF-ɑ receptors (sTNFR1 and sTNFR2) were determined by immunoassays. Oxidative stress was evaluated by determining lipid peroxidation products based on the enzymatic activity of superoxide dismutase (SOD) and catalase, and total antioxidant capacity of plasma. Functional capacity was assessed considering the six-minute walking distance (6MWD) and the estimate of six-minute walking work (6MWW). The association between biomarkers (i.e. inflammation and oxidative stress) and functional exercise capacity was investigated through the Pearson's correlation coefficient. To identify the determinants of the 6MWT, multiple linear stepwise regression analyses were performed with adjustment for age, sex and GOLD classification.

Results: Patients were predominantly male (65%), with mean age of 64 years and moderate airflow obstruction and impaired functional capacity. There were positive correlations between SOD activity and 6MWD (r = 0.520; p = 0.02) and 6MWW (r = 0.554; p = 0.01), as well as a negative correlation between sTNF-R1 and 6MWD (r = -0.437; p = 0.05). SOD was an independent determinant of the functional capacity, explaining 23% of the variability of 6MWD (p = 0.019) and 27% of the variability of 6MWW (p = 0.011). sTNF-R1 levels were associated with 6MWD and, together with SOD explained 40% of variability in 6MWD (p = 0.005).

Conclusion: SOD activity was an independent determinant of performance in the 6MWT, and together with sTNFR1 explained 40% of the variations in walking distance in COPD patients. SOD activity and sTNFR1 levels might be seen as potential biomarkers of the functional capacity in patients with COPD.