Joo Hun Park

Prevalence of chronic obstructive pulmonary disease in Korea: The fourth Korean National Health and Nutrition Examination Survey, 2008

Background and objective:  Because the mortality and social burden associated with COPD is increasing, repeated surveys of the prevalence of COPD have been used to assess risk factors, detect potential patients, and establish early diagnoses and management protocols. We report the prevalence of spirometrically detected COPD in Korea in 2008, using data from the fourth Korean National Health and Nutrition Survey.

Expression of peroxiredoxin and thioredoxin in human lung cancer and paired normal lung

Background:  Peroxiredoxins (Prxs) have been implicated in regulating many cellular processes including cell proliferation, differentiation and apoptosis. However, the pathophysiological significance of Prx proteins, especially in lung disease, has not been defined. Therefore, the authors investigated the distribution and expression of various Prx isoforms in lung cancer and compared this with normal lung from human and mouse.

Nuclear factor E2-related factor 2 Dependent Overexpression of Sulfiredoxin and Peroxiredoxin III in Human Lung Cancer

Background/Aims Oxidative stress results in protein oxidation and is implicated in carcinogenesis. Sulfiredoxin (Srx) is responsible for the enzymatic reversal of inactivated peroxiredoxin (Prx). Nuclear factor E2-related factor 2 (Nrf2) binds to antioxidant responsive elements and upregulates the expression of Srx and Prx during oxidative stress. We aimed to elucidate the biological functions and potential roles of Srx in lung cancer. Methods To study the roles of Srx and Prx III in lung cancer, we compared the protein levels of Nrf2, Prxs, thioredoxin, and Srx in 40 surgically resected human lung cancer tissues using immunoblot and immunohistochemical analyses. Transforming growth factor-β1, tumor necrosis factor-α, and camptothecin treatment were used to examine Prx III inactivation in Mv1Lu mink lung epithelial cells and A549 lung cancer cells. Results Prx I and Prx III proteins were markedly overexpressed in lung cancer tissues. A significant increase in the oxidized form of a cysteine sulfhydryl at the catalytic site of Prxs was found in carcinogenic lung tissue compared to normal lung tissue. Densitometric analyses of immunoblot data revealed significant Srx expression, which was higher in squamous cell carcinoma tissue (60%, 12/20) than in adenocarcinoma (20%, 4/20). Also, Nrf2 was present in the nuclear compartment of cancer cells. Conclusions Srx and Prx III proteins were markedly overexpressed in human squamous cell carcinoma, suggesting that these proteins may play a protective role against oxidative injury and compensate for the high rate of mitochondrial metabolism in lung cancer.

Serum angiopoietin-1 as a prognostic marker in resected early stage lung cancer

PURPOSE We evaluated the clinical significance of angiopoietins and vascular endothelial growth factor (VEGF) in patients with resected early stage lung cancer. PATIENTS AND METHODS The study enrolled 101 patients with completely resected non-small cell lung cancer (NSCLC) of stage I or II, along with 70 healthy volunteers. Serum concentrations of angiopoietin-1, angiopoietin-2, and VEGF were measured with an ELISA. Immunohistochemical expression of angiopoietin-1 was compared with the microvessel density on the lung cancer tissues. RESULTS The patients had lower serum angiopoietin-1 (32.1+/-9.9 ng/mL vs. 39.0+/-10.8 ng/mL, p<0.001), higher angiopoietin-2 (1949.2+/-1099.4 pg/mL vs. 1498.6+/-650.0 pg/mL, p<0.01), and higher VEGF (565.1+/-406.3 pg/mL vs. 404.6+/-254.8 pg/mL, p<0.01) levels than the controls. The angiopoietin-2 level was higher in stage II than in stage I patients (p<0.05). The levels of angiopoietin-1 (r=0.28) and angiopoietin-2 (r=0.36) each correlated with the VEGF level. Patients with a higher level of angiopoietin-1 (> or =31.2 ng/mL) had better disease-specific and relapse-free survival than those with a lower angiopoietin-1 level (<31.2 ng/mL). Angiopoietin-1 expression negatively correlated with the microvessel density. CONCLUSION Serum angiopoietin-1 is a potential marker for predicting postoperative survival and recurrence in patients with early stage NSCLC.

Primary pulmonary malignant fibrous histiocytoma mimics pulmonary artery aneurysm with partial thrombosis: various radiologic evaluations

Primary pulmonary malignant fibrous histiocytoma (MFH) is very rare, so only a few imaging features have been reported. We report one case of rapidly growing primary pulmonary MFH mimicking a partially thrombosed pulmonary artery aneurysm and its radiologic findings, including multidetector row computed tomography (MDCT), conventional angiography, and fluorodeoxyglucose-positron emission tomography CT ([18F] FDG-PET/CT). On multi-phasic MDCT, this mass mimicked a pulmonary artery aneurysm with partial thrombosis. However, pulmonary artery aneurysm was excluded and suggested as a hypervascular parenchymal mass by subsequent conventional angiography. On [18F] FDG-PET/CT, it was a highly metabolic mass, showing a maximal standard uptake value (SUV) 12.1. Although primary pulmonary MFH is very rare and has no specific imaging findings, our experience might be helpful to differentiate a hypervascular pulmonary mass.

Emphysematous phenotype is an independent predictor for frequent exacerbation of COPD.

SETTING Frequent exacerbation is an important phenotype in chronic obstructive pulmonary disease (COPD), while emphysema is associated with many comorbidities and lung function decline. OBJECTIVE To investigate unique features of frequent exacerbators and test the hypothesis that emphysematous phenotype is associated with frequent exacerbations of COPD. METHODS A total of 380 COPD patients were recruited from 16 hospitals in Korea from June 2005 to April 2012 for analysis. We searched for independent predictors of frequent exacerbators in comparison with non-exacerbators. RESULTS As the severity of emphysema increased, forced expiratory volume in 1 s (FEV₁), and FEV₁/FVC (forced volume capacity) worsened; hyperinflationary features characterised by higher total lung capacity (TLC) were observed (P < 0.05). Frequent exacerbators had lower body mass index (BMI), higher St Georges Respiratory Questionnaire (SGRQ) scores, higher residual volume (RV)/TLC, more severe airflow limitation (lower FEV₁ and FEV₁/FVC), lower carbon monoxide diffusion capacity, lower serum protein levels and a higher emphysema index than non-exacerbators (P < 0.05). In multivariate analysis, frequent exacerbators were independently associated with a higher emphysema index, lower serum protein levels and higher RV/TLC (P < 0.05). CONCLUSION Our data show that the severity of emphysema, severe static hyperinflation and serum lower protein levels are independent predictors of frequent exacerbations in COPD patients.

The Prognostic Value of Residual Volume/Total Lung Capacity in Patients with Chronic Obstructive Pulmonary Disease.

The prognostic role of resting pulmonary hyperinflation as measured by residual volume (RV)/total lung capacity (TLC) in chronic obstructive pulmonary disease (COPD) remains poorly understood. Therefore, this study aimed to identify the factors related to resting pulmonary hyperinflation in COPD and to determine whether resting pulmonary hyperinflation is a prognostic factor in COPD. In total, 353 patients with COPD in the Korean Obstructive Lung Disease cohort recruited from 16 hospitals were enrolled. Resting pulmonary hyperinflation was defined as RV/TLC ≥ 40%. Multivariate logistic regression analysis demonstrated that older age (P = 0.001), lower forced expiratory volume in 1 second (FEV1) (P < 0.001), higher St. George Respiratory Questionnaire (SGRQ) score (P = 0.019), and higher emphysema index (P = 0.010) were associated independently with resting hyperinflation. Multivariate Cox regression model that included age, gender, dyspnea scale, SGRQ, RV/TLC, and 6-min walking distance revealed that an older age (HR = 1.07, P = 0.027), a higher RV/TLC (HR = 1.04, P = 0.025), and a shorter 6-min walking distance (HR = 0.99, P < 0.001) were independent predictors of all-cause mortality. Our data showed that older age, higher emphysema index, higher SGRQ score, and lower FEV1 were associated independently with resting pulmonary hyperinflation in COPD. RV/TLC is an independent risk factor for all-cause mortality in COPD. Graphical Abstract

Emphysema as a risk factor for the outcome of surgical resection of lung cancer.

It is unclear whether emphysema, regardless of airflow limitation, is a predictive factor associated with survival after lung cancer resection. Therefore, we investigated whether emphysema was a risk factor associated with the outcome after resection for lung cancer. This study enrolled 237 patients with non small cell lung cancer with stage I or II who had surgical removal. Patient outcome was analyzed based on emphysema. Emphysema was found in 43.4% of all patients. Patients with emphysema were predominantly men and smokers, and had a lower body mass index than the patients without emphysema. The patients without emphysema (n=133) survived longer (mean 51.2±3.0 vs. 40.6±3.1 months, P=0.042) than those with emphysema (n=104). The univariate analysis showed a younger age, higher FEV1/FVC, higher body mass index, cancer stage I, and a lower emphysema score were significant predictors of better survival. The multivariate analysis revealed a younger age, higher body mass index, and cancer stage I were independent parameters associated with better survival, however, emphysema was not. This study suggests that unfavorable outcomes after surgical resection of lung cancer should not be attributed to emphysema itself.

CXCR3 ligands as clinical markers for pulmonary tuberculosis.

SETTING A tertiary care academic medical centre. OBJECTIVE To evaluate the clinical usefulness of CXC chemokine receptor 3 (CXCR3) ligands in active pulmonary tuberculosis (TB). DESIGN Patients with various pulmonary diseases and healthy controls were recruited into this cross-sectional study. Plasma levels of interferon-gamma (IFN-γ) and the CXCR3 ligands (CXCL9 [monokine induced by IFN-γ, MIG], CXCL10 [IFN-γ-inducible 10-kDa protein, IP-10] and CXCL11 [IFN-inducible T-cell α chemoattractant, I-TAC] were measured using enzyme immunoassays. RESULTS The study included 846 subjects: 201 patients with active pulmonary TB, 389 with other pulmonary diseases, and 256 controls. CXCR3 ligand levels were higher in TB patients than in controls and all other disease groups, whereas the IFN-γ levels did not differ. The area under the curve (AUC) for differentiating active TB from all other groups was 0.797 for CXCL9, 0.726 for CXCL10, 0.846 for CXCL11 and 0.534 for IFN-γ. The AUC for differentiating active TB from controls was 0.926 for CXCL9, 0.818 for CXCL10, 0.865 for CXCL11 and 0.575 for IFN-γ. CXCR3 levels correlated with sputum acid-fast bacilli smear grades and the radiographic extent of pulmonary TB. CONCLUSION CXCR3 ligands may be useful surrogate markers for diagnosing active TB and for assessing TB patients clinically.

Independent risk factors for mortality in patients with chronic obstructive pulmonary disease who undergo comprehensive cardiac evaluations.

Background: Cardiovascular disease is the most common cause of death in chronic obstructive pulmonary disease (COPD). However, the impact of cardiovascular comorbidities on the prognosis of COPD is not well known. Objectives: This study was performed to investigate the effects of cardiovascular comorbidities on the prognosis of COPD. Methods: We enlisted 229 patients with COPD who underwent comprehensive cardiac evaluations including coronary angiography and echocardiography at Ajou University Hospital between January 2000 and December 2012. Survival analyses were performed in this retrospective cohort. Results: Kaplan-Meier analyses showed that COPD patients without left heart failure (mean survival = 12.5 ± 0.7 years) survived longer than COPD patients with left heart failure (mean survival = 6.7 ± 1.4 years; p = 0.003), and the survival period of nonanemic COPD patients (mean survival = 13.8 ± 0.8 years) was longer than that of anemic COPD patients (mean survival = 8.3 ± 0.8 years; p < 0.001). The survival period in COPD with coronary artery disease (CAD; mean survival = 11.37 ± 0.64 years) was not different from that in COPD without CAD (mean survival = 11.98 ± 0.98 years; p = 0.703). According to a multivariate Cox regression model, a lower hemoglobin level, a lower left ventricular ejection fraction, and the forced expiratory volume in 1 s (FEV1) were independently associated with higher mortality in the total COPD group (p < 0.05). Conclusions: Hemoglobin levels and left ventricular ejection fraction along with a lower FEV1 were identified as independent risk factors for mortality in COPD patients who underwent comprehensive cardiac evaluations, suggesting that multidisciplinary approaches are required in the care of COPD.