Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (Copd); implications for stratified medicine?

Introduction: Quadriceps muscle dysfunction is common in COPD. Determining, and, if possible, predicting quadriceps phenotype in COPD is important for patient stratification for therapeutic trials. Methods: In biopsies from 114 COPD patients and 30 controls, we measured fiber size and proportion and assessed the relationship with quadriceps function (strength and endurance), clinical phenotype (lung function, physical activity, fat-free mass) and exercise performance. In a subset (n=40) we measured muscle mid-thigh cross-sectional area by computed tomography. Results: Normal ranges for fiber proportions and fiber cross-sectional area were defined from controls; we found isolated fiber shift in 31% of patients, isolated fiber (predominantly type II) atrophy in 20%, both shift and atrophy in 25%, and normal fiber parameters in 24%. Clinical parameters related poorly to muscle biopsy appearances. Conclusions: Quadriceps morphology is heterogeneous in COPD and cannot be predicted without biopsy, underlining the need for biomarkers.