Recently published articles on interstitial lung disease (ILD) have focused on the accurate diagnosis of idiopathic pulmonary fibrosis (IPF), serum biomarkers, acute exacerbation of IPF, the prognostic factors of ILD and the trial of new treatment. In particular, reports on the serum biomarkers such as CC-chemokine ligand 18, surfactant protein, circulating fibrocytes, and acute exacerbation of IPF are sufficient to be mentioned here. Pirfenidone therapy is the most important trial for the treatment of IPF. Other newer treatment trials such as interferon-gamma, sildenafil and imatinib have been reported to be unsuccessful. On the other hand, the sirolimus trial for lymphangioleiomyomatosis is promising. Combined pulmonary fibrosis and emphysema and IgG4-related disease are established to be the new disease entities of ILD.

Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-${\alpha}$, TNF-a and interleukin-$1{\beta}$, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.

Background: In mediastinal lymph node sampling in non-small cell lung cancer (NSCLC) it is important to determine the appropriate treatment as well as to predict an outcome. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a recently developed, accurate, safe technique in patients with NSCLC for sampling mediastinal lymph nodes. We sought to determine the usefulness of EBUS-TBNA in mediastinal staging with NSCLC considered to be operable. Methods: We retrospectively reviewed the records of 142 patients who underwent EBUS-TBNA for mediastinal staging in the Asan Medical Center, Korea from July 2008 to July 2010. If patients were in an operable state, they underwent subsequent surgical staging. Diagnoses based on biopsy results were compared with those based on surgical results. Results: We performed EBUS-TBNA in 184 mediastinal lymph nodes in 142 NSCLC patients. Almost all of the EBUS-TBNA samples were from the lower paratracheal (112, 60.9%) and subcarinal (57, 31.0%) lymph nodes. In 142 patients, 51 patients (35.9%) were confirmed with malignant invasion of the mediastinal lymph node by EBUS-TBNA and 91 (64.1%) patients were not confirmed. Among the 91 patients, 64 patients (70.3%) underwent surgical staging. 3 patients (4.7%) who were misdiagnosed by the EBUS-TBNA were confirmed by surgery. After Diagnostic sensitivity of EBUS-TBNA, the prediction of mediastinal metastatsis was 94.4% and specificity was 100%. The procedures were performed safely and no serious complications were observed. Conclusion: We demonstrated the high diagnostic value of EBUS-TBNA for mediastinal staging.

Background: When patients with chronic respiratory symptoms have a normal spirometry result, it is not always easy to consider bronchial asthma as the preferential diagnosis. Forced expiratory flow between 25% and 75% of vital capacity ($FEF_{25{\sim}75%}$) is known as a useful diagnostic value of small airway diseases. However, it is not commonly used, because of its high individual variability. We evaluated the pattern of bronchodilator responsiveness (BDR) and the correlation between $FEF_{25{\sim}75%}$ and BDR in patients with suspicious asthma and normal spirometry. Methods: Among patients with suspicious bronchial asthma, 440 adult patients with a normal spirometry result (forced expiratory volume in one second [$FEV_1$]/forced vital capacity [FVC] ${\geq}70%$ & $FEV_1%$ predicted ${\geq}80%$) were enrolled. We divided this group into a positive BDR group (n=43) and negative BDR group (n=397), based on the result of BDR. A comparison was carried out of spirometric parameters with % change of $FEV_1$ after bronchodilator (${\Delta}FEV_1%$). Results: Among the 440 patients with normal spirometry, $FEF_{25{\sim}75%}%$ predicted were negatively correlated with ${\Delta}FEV_1%$ (r=-0.22, p<0.01), and BDR was positive in 43 patients (9.78%). The means of $FEF_{25{\sim}75%}%$ predicted were $64.0{\pm}14.5%$ in the BDR (+) group and $72.9{\pm}20.8%$ in the BDR (-) group (p<0.01). The negative correlation between $FEF_{25{\sim}75%}%$ predicted and ${\Delta}FEV_1%$ was stronger in the BDR (+) group (r=-0.38, p=0.01) than in the BDR (-) group (r=-0.17, p<0.01). In the ROC curve analysis, $FEF_{25{\sim}75%}$ at 75% of predicted value had 88.3% sensitivity and 40.3% specificity for detecting a positive BDR. Conclusion: BDR (+) was not rare in patients with suspicious asthma and normal spirometry. In these patients, $FEF_{25{\sim}75%}%$ predicted was well correlated with BDR.

Background: Osteopontin (Opn) is recognized as an important adhesive bone matrix protein and a key cytokine involved in immune cell recruitment and tissue repair and remolding. However, serum levels of osteopontin have not been evaluated in patients with chronic obstructive pulmonary disease (COPD). Thus, the aim of this study was to evaluate and compare the serum levels of osteopontin in patients experiencing COPD exacerbations and in patients with stable COPD. Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients. Serum concentrations of osteopontin were measured by the ELISA method. Results: Serum levels of osteopontin were higher in patients with acute exacerbation than with stable COPD and in healthy control subjects ($62.4{\pm}51.9ng/mL$, $36.9{\pm}11.1ng/mL$, $30{\pm}11ng/mL$, test for trend p=0.003). In the patients with COPD exacerbation, the osteopontin levels when the patient was discharged from the hospital tended to decrease compared to those at admission ($45{\pm}52.1ng/mL$, $62.4{\pm}51.9ng/mL$, p=0.160). Osteopontin levels significantly increased according to patient factors, including never-smoker, ex-smoker and current smoker ($23{\pm}5.7ng/mL$, $35.5{\pm}17.6ng/mL$, $58.6{\pm}47.8ng/mL$, test for trend p=0.006). Also, osteopontin levels showed a significantly negative correlation with forced expiratory volume in one second ($FEV_1$%) predicted in healthy controls and stable COPD patients (r=-0.389; p=0.013). C-reactive protein (CRP) was positively correlated with osteopontin levels in patients with COPD exacerbation (r=0.775; p=0.002). Conclusion: The serum levels of osteopontin increased in patients with COPD exacerbation and tended to decrease after clinical improvement. These results suggest the possible role of osteopontin as a biomarker of acute exacerbation of COPD.

Background: A tuberculous destroyed lung is sequelae of pulmonary tuberculosis and causes various respiratory symptoms and pulmonary dysfunction. The patients with a tuberculous destroyed lung account for a significant portion of those with chronic lung disease in Korea. However, few reports can be found in the literature. We investigated the computed tomography (CT) findings in a tuberculous destroyed lung and the correlation with lung function. Methods: A retrospective analysis was carried out for 44 patients who were diagnosed with a tuberculous destroyed lung at the Keimyung University Dongsan Hospital between January 2004 and December 2009. Results: A chest CT scan showed various thoracic sequelae of tuberculosis. In lung parenchymal lesions, there were cicatrization atelectasis in 37 cases (84.1%) and emphysema in 13 cases. Bronchiectasis (n=39, 88.6%) was most commonly found in airway lesions. The mean number of destroyed bronchopulmonary segments was 7.7 (range, 4~14). The most common injured segment was the apicoposterior segment of the left upper lobe (n=36, 81.8%). In the pulmonary function test, obstructive ventilatory defects were observed in 31 cases (70.5%), followed by a mixed (n=7) and restrictive ventilatory defect (n=5). The number of destroyed bronchopulmonary segments showed a significant negative correlation with forced vital capacity (FVC), % predicted (r=-0.379, p=0.001) and forced expiratory volume in one second ($FEV_1$), % predicted (r=-0.349, p=0.020). After adjustment for age and smoking status (pack-years), the number of destroyed segments also showed a significant negative correlation with FVC, % predicted (B=-0.070, p=0.014) and $FEV_1$, % predicted (B=-0.050, p=0.022). Conclusion: Tuberculous destroyed lungs commonly showed obstructive ventilatory defects, possibly due to bronchiectasis and emphysema. There was negative correlation between the extent of destruction and lung function.

Imatinib mesylate, a selective inhibitor of BCR-ABL kinase activity, has demonstrated significant clinical efficacy in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). It has become the standard of treatment for these diseases. Although the toxicity profile of imatinib is superior to that of interferon or other cytotoxic agents, some adverse events including edema, gastrointestinal toxicities and hematologic toxicities are commonly observed in the patients treated by imatinib. We present two cases of imatinib induced interstitial pneumonitis during the treatment of a chronic phase of CML.

Respiratory bronchiolitis-associated interstitial lung disease is one of the smoking-related interstitial lung diseases. Histopathologically, it shows respiratory bronchiolitis, which is characterized by the accumulation of pigmented macrophages within the respiratory bronchioles, accompanying peribronchiolar inflammation. Clinically, it is presented with respiratory symptoms such as a cough, sputum and dyspnea on exertion. It is well known that the incidence of malignancy in interstitial lung disease is high, but in respiratory bronchiolitis-associated interstitial lung disease the report of accompanying malignancy is rare. Here we report a case of a 60-year-old male heavy smoker presented with a cough, sputum and clubbing finger. A chest computed tomography (CT) of the patient did not show any shadow suspected of malignancy, but adenocarcinoma was found on a transbronchial lung biopsy and on a surgical lung biopsy with respiratory bronchiolitis-associated interstitial lung disease.

Poncet's disease is an aseptic polyarthritis developing in the presence of active Tuberculosis occurring elsewhere, and is not due to direct involvement of joints but to an immunological reaction to tuberculoprotein. We experienced a case of Poncet's disease accompanying erythema nodosum in a 55-year-old female patient with pulmonary tuberculosis. She had multiple tender erythematous nodules on both lower limbs for 3 months and a cough and sputum from one month ago. She felt severe pain in both knees and ankles with swelling one week before admission. Her chest X-ray, computed tomography (CT) scan and positive sputum AFB stain results revealed that she had active pulmonary tuberculosis accompanying erythema nodosum and aseptic polyarthritis. Her arthritis and erythema nodosum were dramatically improved within four weeks after anti-tuberculosis therapy. We report a case of Poncet's disease in pulmonary tuberculosis accompanying erythema nodosum.