Background
Patients with chronic obstructive pulmonary disease (COPD) are often characterized by skeletal muscle weakness, leading to reduced exercise capacity and an increased risk of morbidity and mortality. Besides loss of muscle mass, loss of oxidative phenotype (i.e. a I?II fiber type shift and mitochondrial impairments) is also an important driver of muscle weakness, which may be accelerated during acute exacerbations of COPD. The aim of this study is to elucidate whether acute exacerbations indeed aggravate the loss of muscle oxidative phenotype in COPD.

Methods
A smoke-induced COPD exacerbation mouse model was developed; 9-11 weeks old female balb/c mice (n=32) were exposed to cigarette smoke or air for 6 weeks, 7 days/week, followed by 3 (10 days apart) intra-tracheal lipopolysaccharide (LPS; 10ug/mL) instillations to mimic COPD exacerbations, or vehicle PBS. The lungs were excised 10 days after the last LPS instillation and enlargement of alveolar spaces was histologically determined by quantifying the mean linear intercept as indicator of emphysema. Muscle (soleus) was isolated and changes in gene and protein expression of molecular markers involved in mitochondrial biogenesis, degradation and content were determined.

Results
After 6 weeks of smoke exposure emphysema was demonstrable as reflected by enlarged alveolar air spaces compared to air control. No relevant changes were observed in gene/protein expression of molecular markers involved in mitochondrial biogenesis (PGC-1α, PGC-1β, PPARα, TFAM and NRF1), mitophagy (BNIP3, BNIP3L, LC3B, SQSTM1) or mitochondrial content (complex I, II, III, IV and V).

Conclusion
Despite the presence of emphysema, six weeks of smoke exposure and subsequent simulated exacerbations did not result in loss of muscle oxidative phenotype. In future experiments the period of smoke exposure should therefore propbably be extended to adequately address the acute-upon-chronic effects of COPD exacerbations on skeletal muscle oxidative phenotype.