Prospects for the development of effective pharmacotherapy targeted at the skeletal muscles in chronic obstructive pulmonary disease: a translational review

Abstract

Skeletal muscle dysfunction is a prevalent and clinically important systemic manifestation of chronic obstructive pulmonary disease (COPD) that predicts morbidity and mortality. Skeletal muscle retains its plasticity in response to anabolic stimuli such as exercise in COPD and is therefore a promising target for novel pharmacological therapies aimed at reducing disability and healthcare utilisation and improving mortality. In this article, we outline the steps the academic and pharmaceutical communities need to undertake for such therapeutic advances to be realised.

Gait speed and readmission following hospitalisation for acute exacerbations of COPD: a prospective study

“…Cummings et al 31 recently postulated that routine identification of ‘dismobility’ defined as a slow 4MGS may help improve the clinical care, research and regulatory approval of pharmacological interventions to improve mobility, including anabolic agents 33. As well as stratifying patients for trial entry, 4MGS is a continuous measure that is a potentially useful outcome marker 34.…”

Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD

“…The degree and nature of impairment varies widely between patients and cannot currently be predicted accurately without muscle biopsy [13]. The need for biomarkers of muscle phenotype has recently been highlighted, underscored by the prospect of new pharmacotherapies that selectively target certain muscle characteristics [14]. For example, peroxisome proliferator-activated receptor-δ agonists or 5′ AMP-activated protein kinase activators, which change the fuel preference within skeletal muscle away from glycolysis towards fat oxidation.…”

Skeletal muscle molecular responses to resistance training and dietary supplementation in COPD

“…This is important because muscle is a potential therapeutic target in a disease in which the primary lung pathology is frequently irreversible 8. Proof that this approach is beneficial is demonstrated by the efficacy of physical training in improving muscle function in COPD 9 10.…”