Physiological determinants of decreased peak leg oxygen uptake in chronic disease: a systematic review and meta-analysis.

This systematic review and meta-analysis examined the physiological mechanisms responsible for lower peak exercise leg oxygen uptake (V̇o 2 ) in patients with chronic disease. Studies measuring peak leg V̇o 2 (primary outcome) and its physiological determinants during large (cycle) or small muscle mass exercise (single-leg knee extension, SLKE) in patients with chronic disease were included in this meta-analysis. Pooled estimates for each outcome were reported as a weighted mean difference (WMD) between chronic disease and controls. We included 10 studies that measured peak leg V̇o 2 in patients with chronic disease ( n = 109, mean age: 45 yr; encompassing chronic obstructive pulmonary disease, COPD, heart failure with reduced ejection fraction, HFrEF, or chronic renal failure, RF) and age-matched controls ( n = 88). In pooled analysis, peak leg V̇o 2 (WMD; -0.23 L/min, 95% CI: -0.32 to -0.13), leg oxygen (O 2 ) delivery (WMD: -0.27 L/min, 95% CI: -0.37 to -0.17), and muscle O 2 diffusive conductance (WMD: -5.2 mL/min/mmHg, 95% CI: -7.1 to -3.2) were all significantly lower during cycle and SLKE exercise in chronic disease versus controls. These results highlight that during large and small muscle mass exercise in patients with COPD, HFrEF, or RF, there is no single factor causing peak V̇o 2 limitations. Specifically, the lower peak V̇o 2 in these pathologies is due to not only the expected impairments in convective O 2 delivery but also impairments in muscle oxygen diffusive transport from capillary to mitochondria. Whether impaired muscle O 2 transport is caused solely by inactivity or additional muscle pathology remains in question. NEW & NOTEWORTHY Peripheral (skeletal muscle and vasculature) factors contribute significantly to reduced exercise capacity during both large and small muscle mass exercise in chronic diseases such as COPD, HFrEF, or RF and should be important targets of therapy in addition to the primary organs (lungs, heart, and kidneys) affected by disease.