Ultrasound Measurement of Rectus Femoris Cross-Sectional Area and the Relationship to Quadriceps Strength in Chronic Obstructive Pulmonary Disease Running Head: Quadriceps Ultrasound in COPD

Rationale: Quadriceps weakness and loss of muscle mass predict mortality in chronic obstructive pulmonary disease (COPD). We hypothesised that a reduced quadriceps cross-sectional area could be detected by ultrasound in COPD patients compared with healthy subjects, and that measurements relate to strength and fat-free mass (FFM). Methods and measurements: Rectus femoris muscle cross sectional area (RF CSA ) was measured by ultrasound, and whole body fat free mass (FFM) estimated using electrical bioimpedance. Quadriceps strength was measured by maximum voluntary contraction and twitch tension (TwQ) following magnetic femoral nerve stimulation. Results: 26 healthy volunteers (mean(SD) age: 63(9) years) and 30 COPD patients (67(9) years, %predicted FEV 1 : 48.0(20.8)%), with a similar FFM participated (healthy: 46.9(9.3) kg; COPD: 46.1(7.3) kg, P=0.193). Mean RF CSA was reduced in COPD by 25% of the healthy mean value (-115mm 2 ; 95% CI: -177mm 2 to -54mm 2 , P=0.001), and was related to MRC dyspnoea scale score, independent of FFM or sex. Maximum voluntary contraction strength was linearly related to RF CSA (r=0.78, P<0.001 in COPD). TwQ force per unit of RF CSA was similar in both groups (healthy mean(SD): 17(4)g/mm 2 ; COPD: 18(3)g/mm 2 , P=0.657). Voluntary contraction strength per unit of RF CSA was dependent on central quadriceps activation and peripheral oxygen saturation in COPD. Conclusion: Ultrasound measurement of the rectus femoris cross sectional area is an effort-independent and radiation-free method of measuring quadriceps muscle cross-sectional area in COPD that relates to strength.