Quadriceps myostatin expression in COPD

To the Editors: Quadriceps muscle dysfunction is well recognised in chronic obstructive pulmonary disease (COPD), and is associated with impaired exercise capacity and increased mortality 1. Functionally, the quadriceps is characterised by reduced strength, increased fatigability and decreased endurance, associated with muscle fibre atrophy and a switch towards more glycolytic muscle fibres (types 1–2). The underlying molecular mechanisms of quadriceps dysfunction in COPD are not well clarified. Myostatin is a member of the transforming growth factor-β family, and is a potent negative regulator of muscle mass, as demonstrated in naturally occurring animal and human genetic mutations, and genetic murine models 2. Myostatin may therefore be a candidate regulator of muscle mass in disorders characterised by muscle atrophy, including COPD. Few data exist regarding myostatin in COPD, but a recent cross-sectional study showed a three-fold increase in vastus lateralis myostatin mRNA transcripts in COPD patients with significant quadriceps weakness compared to healthy controls 3. However, the relationship between quadriceps myostatin expression and functional characteristics of the muscle is not known. We hypothesised that myostatin expression would negatively correlate with quadriceps strength and exercise capacity in COPD. 18 patients with COPD were enrolled from clinics at the Royal Brompton Hospital (London, UK). Exclusion criteria included exacerbation in the previous 4 weeks, coexisting heart, renal or liver failure, or a systemic inflammatory or metabolic disorder. 16 healthy, age-matched controls were recruited by advertisement. All participants gave written informed consent and the protocol was approved by the local Research Ethics Committee. The following were measured in study participants: lung function tests; fat-free mass index, calculated from bioelectrical impedance and normalised to height squared; quadriceps muscle strength, assessed by measuring supine isometric maximal voluntary contraction (MVC) of the leg ipsilateral to the dominant hand and corrected for body mass index (MVC/BMI); quadriceps …