TY - JOUR T1 - Acute cigarette smoke induces accelerated emphysema development in bENaC-overexpressed mice JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P865 AU - Jie Jia AU - Lisa Merthan AU - Marcus A. Mall AU - Oliver Eickelberg AU - Ali Önder Yildirim Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P865.abstract N2 - Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodeling and emphysema. As a hallmark of COPD, mucus accumulation may result in airway hypersensitivity and small airway obstruction. Accelerated b-Epithelial Na+ channel (bENaC) in the lower airway epithelial membrane of mice leads to airway surface liquid depletion and mucocilia clearance dysfunction, which causes mucus accumulation and further, COPD like disease(Mall, M.A. A.M.J.Respir, 2008). However, it remains unclear how increased mucus production contributes to emphysema and COPD development.10 day old bENaC mice and litter mate controls were exposed to filtered air or cigarette smoke, for 50min twice daily, 4 days at a particle concentration of 500mg/m3. On the 5th day lung function and cytospin from Bronco Alveolar Lavage (BAL) fluid was performed. H&E and PAS staining of lung sections were performed to analyze morphological changes.We observed spontaneous emphysema development in the lung of bENaC mice. However, this emphysema development was exacerbated after acute cigarette smoke exposure, as demonstrated by higher compliance values (0.014+/-0.002mL/cmH2O vs 0.006+/-0.0006mL/cmH2O, P<0.01) and increased airspace enlargement compared to WT animals. Interestingly, emphysema development was associated with increased macrophage and neutrophil cell number in BAL fluids.Our data demonstrate that the spontaneous development of emphysema ccompanied with the accumulation of mucus in the airways of bENaC transgenic mice results in airway hypersensitivity, and a severer inflammatory response following cigarette smoke exposure that may contribute to an accelerated COPD pathogenesis. ER -