Extrapulmonary manifestations of chronic obstructive pulmonary disease in a mouse model of chronic cigarette smoke exposure.

Rationale Cigarette smoking is the most commonly encountered risk factor for COPD, reflected by irreversible airflow limitation frequently associated with airspace enlargement and pulmonary inflammation. In addition, COPD has systemic consequences including systemic inflammation, muscle wasting and loss of muscle oxidative phenotype. However, the role of smoking in the development of these extrapulmonary manifestations remains rather unexplored. Methods Mice were exposed to cigarette smoke or control air for 6 months. Subsequently, emphysema was assessed by morphometry of lung tissue and blood cyto- and chemokine levels were determined by a multiplex assay. Soleus, plantaris, gastrocnemius and tibialis muscles were dissected and weighed. Muscle fiber typing was performed based on I, IIA, IIB, and IIX myosin heavy chain isoform composition. Results Lungs of the smoke exposed animals showed pulmonary inflammation and emphysema. Moreover, circulating levels of primarily pro-inflammatory proteins were elevated after smoke exposure, especially TNFalpha. Despite an attenuated body weight gain, only the soleus showed a tendency toward lower muscle weight after smoke exposure. Oxidative fiber type IIA proportion was significantly reduced in the soleus. Muscle oxidative enzyme activity was slightly reduced after smoke exposure, being most prominent for citrate synthase in the soleus and tibialis. Conclusions In this mouse model, chronic cigarette smoke exposure resulted in systemic features that closely resemble the early signs of the extrapulmonary manifestations observed in COPD patients. AD - Respiratory Medicine, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, Netherlands. AU - Gosker HR AU - Langen RC AU - Bracke KR AU - Joos GF AU - Brusselle GG AU - Steele C AU - Ward KA AU - Wouters EF AU - Schols AM LA - ENG PT - JOURNAL ARTICLE DEP - 20081106 TA - Am J Respir Cell Mol Biol JT - American journal of respiratory cell and molecular biology JID - 8917225