br Conclusions br Introduction Emphysema

Conclusions
Introduction Emphysema is a type of chronic obstructive pulmonary disease (COPD) and is a worldwide public health problem that reduces quality of life (Hogg and Timens, 2009). Emphysema is characterised by airspace enlargements and is accompanied by destruction of the parenchymal structure (Snider, 1989). The causes of emphysema in humans are cigarette smoke, environmental irritants, genetic factors and indoor pollutants (Barnes, 2000); these factors result in general decrements in health that include weight loss, muscle atrophy, changes in muscle fibre type and systemic inflammation (Langen et al., 2006). Emphysema leads to death, and there is currently no cure. The emphysema observed in smokers begins in the respiratory 61603 near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD (Hogg and Timens, 2009). The physiological manifestations of the disease include impaired gas exchange (due to loss of alveolar surface area), limited airflow, increased lung compliance and increased effort required to breathe (Hogg, 2004). Because cigarette smoke is the main cause of emphysema in humans, experimental animal models have attempted to reproduce this situation (Churg et al., 2008). Elastolytic enzymes have been shown to reproduce some characteristics of human cigarette smoke-induced disease (Breuer et al., 1993; Ito et al., 2005). Methacholine (MCh) is a bronchoconstrictive agent that has been widely used in the diagnoses of airway narrowing and hyperresponsiveness (Jonasson et al., 2009). MCh induces muscle contractions by stimulating the muscarinic cholinergic receptors that are found in both the airways and the lung parenchyma (Barnes, 1993, Sly et al., 1995, Fisher et al., 2004). Muscarinic receptors located on the alveolar wall may be involved in the parenchymal response (Sly et al., 1995). The hypothesis of this study is that bronchial responsiveness during aerosolised MCh challenge should be amplified in mice with elastase-induced emphysema (0.3 and 0.6U elastase). This study also compared two thorax conditions: intact (closed thorax) and exposed lungs (opened thorax). The aim of this study was to analyse the bronchial responsiveness of the airways to a MCh challenge during elastase-induced emphysema in closed and opened thorax.
Materials and methods
Results The baseline respiratory mechanical data are presented in Table 1. The open or closed thorax conditions and the Sal, 0.3 and 0.6U groups were compared with two-way analysis of variance. The elastase-induce emphysema significantly decreased Raw (closed thorax), and the expected H decrease was found in the 0.6U group (p<0.05; closed and opened thorax). Additionally, η increased for the same group (closed thorax) relative to that of the Sal group. No changes in G were found. The MCh challenge is illustrated in Fig. 1, and all groups (in both the closed and opened thorax conditions) showed dose-dependent responses to aerosolised MCh (0 or vehicle, 50 and/or 100mg/mL) for all parameters except H in the 0.6U group (closed thorax condition), for which only 100mg/mL MCh resulted in a statistically significant difference relative to the H for the vehicle.