Pulmonary emphysema is characterized by alveolar wall destruction and airspace enlargement. Recent evidence indicates that epithelial or endothelial apoptosis may be involved in the pathogenesis of emphysema. Here, we describe the induction of emphysematous changes, including airspace enlargement, alveolar wall destruction, and enhanced lung distensibility, in mice receiving a single intratracheal injection of active caspase-3 and Chariot, a newly developed protein transfection reagent. Epithelial apoptosis and enhanced elastolytic activity (optimal at pH 5.5) in bronchoalveolar lavage were noted. Emphysematous changes were also generated in mice receiving an intratracheal injection of nodularin, a proapoptotic serine/threonine kinase inhibitor. This murine model provides direct evidence that confirms that alveolar wall apoptosis causes emphysematous changes. Furthermore, this simple technique for protein transfection of lung tissue can be used in a variety of future applications.

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Cigarette smoking generates an oxidative stress in the lung, which may contribute to the pathogenesis of chronic obstructive pulmonary disease. We performed an immunohistochemical study to evaluate oxidative stress in the lung after acute cigarette smoke (CS) exposure in mice. Paraffin-embedded lung tissue sections were prepared from mice exposed and unexposed to CS for 1 h. The sections were immunostained with antibodies against 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA adduct, and 4-hydroxy-2-nonenal (4-HNE), a lipid peroxidation product. The bronchiolar and alveolar epithelium of mice unexposed to CS exhibited weak signals for 8-OHdG and 4-HNE, whereas by 1 h after CS exposure the signals in the bronchiolar epithelial cells and the alveolar epithelial cells, particularly type II cells, had increased dramatically. The increases in both were associated with increased 8-OHdG levels in bronchoalveolar lavage fluid as determined by enzyme-linked immunoassay. These results suggest that acute CS exposure imposes oxidative stress predominantly on bronchiolar epithelial and alveolar type II cells, confirming that cigarette smoking causes oxidative damage to the respiratory epithelium.

Cigarette smoking generates an oxidative stress in the lung, which may contribute to the pathogenesis of chronic obstructive pulmonary disease. We performed an immunohistochemical study to evaluate oxidative stress in the lung after acute cigarette smoke (CS) exposure in mice. Paraffin-embedded lung tissue sections were prepared from mice exposed and unexposed to CS for 1 h. The sections were immunostained with antibodies against 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA adduct, and 4-hydroxy-2-nonenal (4-HNE), a lipid peroxidation product. The bronchiolar and alveolar epithelium of mice unexposed to CS exhibited weak signals for 8-OHdG and 4-HNE, whereas by 1 h after CS exposure the signals in the bronchiolar epithelial cells and the alveolar epithelial cells, particularly type II cells, had increased dramatically. The increases in both were associated with increased 8-OHdG levels in bronchoalveolar lavage fluid as determined by enzyme-linked immunoassay. These results suggest that acute CS exposure imposes oxidative stress predominantly on bronchiolar epithelial and alveolar type II cells, confirming that cigarette smoking causes oxidative damage to the respiratory epithelium.

Cough variant asthma (CVA) is a common cause of chronic persistent cough, in which allergic airway inflammation may play a role. Although current guidelines recommend bronchodilators and anti-inflammatory drugs for the treatment, comparison of the efficacy of these medications has not been investigated. This study was designed to evaluate the effectiveness of pranlukast, a leukotriene receptor antagonist, and salmeterol, a long-acting beta₂-adrenergic agonist, in the treatment of CVA. The study was a randomized, controlled, parallel-group, multicenter trial. After a 4-week run-in period, 49 patients with newly diagnosed CVA were assigned to receive oral pranlukast (225 mg, b.i.d.) or inhaled salmeterol (100 μg, b.i.d.) for 4 weeks. Primary outcome measure was cough symptom and secondary outcome measures were pulmonary function and eosinophilic airway inflammation. Treatment with pranlukast and salmeterol each decreased cough symptom scores, where the changes from baseline values were significantly greater in the pranlukast group than in the salmeterol group. Forced expiratory volume in 1 second and peak expiratory flow (PEF) increased in the two treatment groups with the same magnitudes, but significant decreases in diurnal variation of PEF and eosinophil counts and eosinophil cationic protein contents in the peripheral blood and induced sputum were observed only in the pranlukast group. In view of antitussive and anti-inflammatory actions, the leukotriene receptor antagonist pranlukast seems to be more effective than the long-acting beta₂-adrenergic agonist salmeterol in the treatment of CVA.