TY - JOUR T1 - Non-invasive monitoring of emphysema and muscle wasting during experimental disease exacerbation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA3411 VL - 48 IS - suppl 60 SP - PA3411 AU - Judith Ceelen AU - Annemie Schols AU - Stefan van Hoof AU - Chiel de Theye AU - Frank Verhaegen AU - Ramon Langen Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA3411.abstract N2 - Background: The emphysematous COPD phenotype and disease exacerbations may render patients prone to weight loss and muscle wasting. The aim of this study was to develop a combined emphysema and disease exacerbation model and evaluate whether skeletal muscle mass changes can be monitored non-invasively.Methods: Emphysema was induced by 3 weekly intra-tracheal (IT) elastase instillations followed by a single bolus of IT-LPS (to induce acute pulmonary inflammation mimicking exacerbation). Using micro cone-beam CT-scans, emphysema development and changes in skeletal muscle mass were monitored non-invasively, and linked to muscle weight and molecular analyses in gastrocnemius muscle.Results: CT image analysis to assess lung emphysema revealed a decreased lung voxel density, reflected by an increased low-attenuation area (30.3%±2.2%) compared to PBS-treated mice (5.6%±1.3%). 48h after IT-LPS, a significant decrease in body weight (12.9%±1.4%) as well as skeletal muscle weight (11.5%±1.3%) and volume (13.7%±1.1%) was observed irrespective of the presence of emphysema. Muscle wet weights and CT-determined muscle volume correlated highly (R2=0.86, p>0.001). mRNA expression and protein levels of genes involved in the ubiquitin-proteasome pathway and the autophagy-lysosomal pathway were significantly upregulated 24 hours after IT-LPS.Conclusion: These results show that induction of pulmonary inflammation in emphysematous mice evokes acute loss of muscle mass. Using this combined model, changes in lung tissue density and muscle volume can be monitored non-invasively to longitudinally evaluate emphysema and muscle atrophy in response to repetitive exacerbations. ER -