Injury of the alveolar epithelium by cigarette smoke is presumed to be an important process in the pathogenesis of smoking-related pulmonary diseases. We investigated the cytotoxic effects of cigarette smoke extract (CSE) on an alveolar type II cell-derived cell line (A549). CSE caused apoptosis at concentrations of 5% or less and necrosis at 10% or more. When CSE was exposed to air before application to A549 cells, the cytotoxic effects were attenuated. CSE caused cell death without direct contact with the cells. Acrolein and hydrogen peroxide, two major volatile factors in cigarette smoke, caused cell death in a similar manner. Aldehyde dehydrogenase, a scavenger of aldehydes, and N-acetylcysteine, a scavenger of oxidants and aldehydes, completely inhibited CSE-induced apoptosis. CSE and acrolein increased intracellular oxidant activity. In conclusion, apoptosis of alveolar epithelial cells may be one of the mechanisms of lung injury induced by cigarette smoking. This cytotoxic effect might be due to an interaction between aldehydes and oxidants present in CSE or formed in CSE-exposed cells.

BAL eosinophilia, lobular distribution and architectural destruction with cyst formation are characteristic features of DIP.

Objective We identified the prognostic relevance of pneumothorax in interstitial lung disease (ILD) patients and evaluated the efficacy and safety of autologous blood-patch pleurodesis. Methods We retrospectively reviewed 59 occurrences of pneumothorax in 34 ILD patients identified over a 12-year period. Results Air leakage ceased in 16 of 22 (72.7%) episodes after blood pleurodesis and in 11 of 14 (78.6%) episodes after chemical pleurodesis. Both the cure ratio and recurrence ratio in the cure episodes were comparable with those in the chemical pleurodesis group (p=0.99 and 0.99, respectively). In addition, there were no harmful events associated with blood pleurodesis. The median survival time after the first episode of pneumothorax was less than 9 months in patients with idiopathic interstitial pneumonia (IIP) and only around 3 years in the patients with other types of ILD, which have essentially favorable outcomes. Kaplan-Meier survival estimates were significantly worse in the patients with concomitant pneumomediastinum than in those without (p<0.05). A multivariate Cox regression analysis identified that the number of episodes of pneumothorax, IIP diagnosis and concomitant pneumomediastinum were independent predictors of death. Conclusion Autologous blood-patch pleurodesis is safe and worth considering as a first-line treatment for pneumothorax secondary to ILD. However, despite treatments, the prognosis after the onset of pneumothorax in ILD patients was found to be poor. In addition, concomitant pneumomediastinum may further worsen the prognosis.

Objective Our objective was to evaluate the effectiveness of combination therapy consisting of low-dose corticosteroids with weekly methotrexate in patients with cardiac sarcoidosis in whom long-term therapy is required. Combination therapy was selected because long-term standard corticosteroid therapy tends to result in various adverse effects and the steroid-sparing effects of methotrexate have been reported. Methods This study was a small open-label study comparing long-term functional changes between patients who received combination therapy (5-15 mg/day of prednisolone and 6 mg/week of methotrexate) and patients who received corticosteroids alone. The comparative analysis was based on the following therapeutic indexes: ejection fraction (EF), left ventricular end-diastolic diameter (LVDd) on echocardiography, serum Nterminal fragment pro-brain natriuretic peptide (NT-proBNP) and cardiothoracic ratio (CTR) on plain chest radiographs. Patients Seventeen patients with cardiac sarcoidosis were examined in the sarcoidosis clinic. Cardiac sarcoidosis was diagnosed based on the Japanese diagnostic guidelines published in 2006. Results The EF was significantly stabilized in the combination therapy group but not in the corticosteroids alone group at three years after the first treatment. The CTR and NT-proBNP levels were significantly stabilized in the combination therapy group compared with those observed in the corticosteroids alone group at both three and five years after the first treatment. The LVDd values tended to be stable in the combination therapy group compared with those observed in the corticosteroids alone group. The combination therapy was associated with few adverse effects. Conclusion Weekly methotrexate therapy with daily small doses of corticosteroids stabilized the EF, CTR and NT-proBNP levels in the serum without eliciting adverse effects longitudinally.

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