Seung Soo Sheen

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.

Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype☆

RATIONALE Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disorder in which a number of different pathological processes lead to recognition of patient subgroups that may have individual characteristics and distinct responses to treatment. OBJECTIVES We tested the hypothesis that responses of lung function to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid might differ among patients with various COPD subtypes. METHODS We classified 165 COPD patients into four subtypes according to the severity of emphysema and airflow obstruction: emphysema-dominant, obstruction-dominant, mild-mixed, and severe-mixed. The emphysema-dominant subtype was defined by an emphysema index on computed tomography of more than 20% and FEV(1) more than 45% of the predicted value. The obstruction-dominant subtype had an emphysema index < or = 20% and FEV(1) < or = 45%, the mild-mixed subtype had an emphysema index < or = 20% and FEV(1) > 45%, and the severe-mixed subtype had an emphysema index > 20% and FEV(1) < or = 45%. Patients were recruited prospectively and treated with 3 months of combined inhalation of long-acting beta-agonist and corticosteroid. RESULTS After 3 months of combined inhalation of long-acting beta-agonist and corticosteroid, obstruction-dominant subtype patients showed a greater FEV(1) increase and more marked dyspnea improvement than did the emphysema-dominant subgroup. The mixed-subtype patients (both subgroups) also showed significant improvement in FEV(1) compared with the emphysema-dominant subgroup. Emphysema-dominant subtype patients showed no improvement in FEV(1) or dyspnea after the 3-month treatment period. CONCLUSION The responses to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid differed according to COPD subtype.

Expression of excision repair cross-complementation group 1 protein predicts poor outcome in advanced non-small cell lung cancer patients treated with platinum-based doublet chemotherapy

BACKGROUND Alterations in apoptosis and DNA damage repair related proteins are associated with resistance to chemotherapy, which is the most important cause of treatment failure in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Pretreatment tumor biopsy specimens from 50 patients with NSCLC including stage IIIB with malignant pleural effusion or stage IV or recurrent disease were analyzed for p53, Bcl-2, Bax, and ERCC1 expression by immunohistochemistry. All patients were treated with platinum-based third-generation doublet chemotherapy, in which gemcitabine and cisplatin was the most commonly administered regimen (17 patients). RESULTS High expression of p53, Bcl-2, Bax, and ERCC1 was observed in 24 (48%), 8 (16%), 32 (63%), and 28 (55%) patients, respectively. In univariate analysis, high expression of ERCC1 demonstrated a trend of association with poor overall survival (OS) (median, 8 months vs. 11 months; P=0.055). High expression of p53, Bcl-2, Bax was not correlated with patient outcome. High expression of ERCC1 was an independent prognostic factor for poor OS (P=0.002) along with poor performance status (P=0.028) and lack of disease control (P=0.001) in multivariate analysis. CONCLUSIONS High expression of ERCC1 may be a useful prognostic factor for poor outcome in advanced NSCLC patients treated with platinum and third-generation doublet chemotherapy.

Low expression of Bax predicts poor prognosis in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy.

Purpose: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy. Experimental Design: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry. Results: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P = 0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P = 0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P = 0.009), followed by low dose intensity of cisplatin and lack of clinical complete response. Conclusions: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.

Overdose Rate of Drugs Requiring Renal Dose Adjustment: Data Analysis of 4 Years Prescriptions at a Tertiary Teaching Hospital

OBJECTIVETo determine the overdose rate of drugs that require renal dose adjustment and factors related with overdose.SUBJECTSTotal of 23,635,210 records of prescriptions and laboratory data of inpatients at a tertiary teaching hospital for the period from January 2002 to December 2005.METHODSA clinical data mart was constructed. A knowledge base containing dose adjusting information about 56 drugs was built. One day dose was compared to the reference dose adjusted to the patient’s renal function.RESULTSConsidering the patient’s renal function, 5.3% of drug doses were excessive. The overdose rate in the patients with moderate to severe renal insufficiency was 28.2%. Only 25% of physicians were responsible for 50.6% of the overdoses. Of 56 drugs studied, 10 drugs, including ranitidine, amoxicillin, and piperacillin/tazobactam, were involved in 85.4% of the overdoses. The physicians with high overdose rate had patients with more impaired renal function (correlation coefficient = 0.192, P < .001). There were negative correlation between clinical experiences of physician and overdose rate (correlation coefficient = −0.221, P < .001) and workload of prescription (correlation coefficient = −0.446, P < .001), when excluding interns from the analyses. There was positive correlation between workload of prescription and overdose rate (correlation coefficient = 0.361, P < .001).CONCLUSIONA clinical data mart was useful to analyze the vast amount of electronic hospital data. Drug overdose is quite common among inpatients with renal insufficiency. Only a few drugs are responsible for most of drug overdoses. The physicians’ clinical experience, workload of prescriptions, and patients’ renal function are correlated with drug overdose.

Association between CRHR1 polymorphism and improved lung function in response to inhaled corticosteroid in patients with COPD

Background and objective:  Inhaled corticosteroids are used to treat COPD and asthma. An association between sequence variants in the corticotrophin‐releasing hormone receptor 1 (CRHR1) gene and improved lung function in asthmatics treated with inhaled corticosteroids was reported recently. This study investigated the association between the change in lung function in response to inhaled corticosteroids and single‐nucleotide CRHR1 polymorphisms in patients with COPD.

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.

Clinical usefulness of the fluorodeoxyglucose (FDG)-PET maximal standardized uptake value (SUV) in combination with CT features for the differentiation of adenocarcinoma with a bronchioloalveolar carcinoma from other subtypes of non-small cell lung cancers

PURPOSE To evaluate the clinical usefulness of fluorodeoxyglucose (FDG)-PET maximal SUV in combination with CT features for differentiation of adenocarcinoma with bronchioloalveolar carcinoma (BAC) from other subtypes of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS This retrospective study included 125 patients (104 men and 21 women; mean age, 64 years) who underwent CT and subsequent FDG-PET examinations for preoperative evaluation and underwent curative intent operation with the final diagnoses of NSCLC made by surgical histopathology. We categorized NSCLC into adenocarcinoma with BAC feature and other subtypes. Finally, there were 16 cases of adenocarcinoma with BAC and 109 cases of other NSCLC subtypes included in the study. Several CT features of lung cancer were analyzed, including tumor size, presence of spiculation, margin (irregular or smooth), pattern of the mass (pure solid, pure ground glass opacity and mixed), associated pleural effusion and location (center, mid and periphery). Maximal SUV and visual scores of FDG uptakes of primary NSCLC were evaluated. The diagnostic performances of CT alone, PET alone, and combination of two modalities to predict adenocarcinoma with BAC from other subtypes of NSCLC were calculated. RESULTS A nodule with a mixed pattern with partly solid and ground glass opacity was significantly more frequent CT feature of an adenocarcinoma with BAC (8/16, 50%) as compared with the other subtypes (2/109, 1.8%) (p<0.0001). Maximal SUV of adenocarcinoma with BAC (mean=7.2) was significantly lower than that of other subtypes of NSCLC (mean=13.33) (p<0.0001). Sensitivity, specificity, PPV, and NPV of CT for differentiating adenocarcinoma with BAC from other subtypes was 50% (8/16), 98.2% (107/109), 80% (8/10), and 93% (107/115), respectively. Sensitivity, specificity, PPV, and NPV of FDG-PET was 68.8% (11/16), 86.2% (94/109), 42.3% (11/26), and 94.9% (94/99), respectively. Sensitivity, specificity, PPV, and NPV of combination of two modalities was 81.3% (13/16), 85.3% (93/109), 44.8% (13/29), 96.9% (93/96), respectively. CONCLUSION Careful combined assessment of the FDG-PET maximal SUV and CT findings have the potential to differentiate an adenocarcinoma with BAC from other NSCLC subtypes, such as a pure BAC. These findings might be useful for imaging interpretations and will help initial planning of NSCLC management.

Serum ferritin and transferrin levels as serologic markers of methylene diphenyl diisocyanate-induced occupational asthma

BACKGROUND Although methylene diphenyl diisocyanate (MDI) may induce occupational asthma in the workplace, the pathogenic mechanisms are unclear. OBJECTIVES By using bronchoalveolar lavage fluid, we sought to identify proteins that were differentially expressed between subjects with MDI-induced occupational asthma (MDI-OA) and asymptomatic exposed controls (AECs). METHODS To find proteins that were differentially expressed between the MDI-OA and AEC groups, 2-dimensional electrophoresis was performed by using bronchoalveolar lavage fluid obtained from subjects after MDI-specific inhalation challenge. The selected protein spots were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The clinical relevance of the differentially expressed spots was compared by ELISA using sera from the MDI-OA/eosinophilic bronchitis, AEC, and unexposed healthy control groups. Receiver operating characteristic curves were then plotted, and the sensitivity and specificity were determined. RESULTS Twenty-three protein spots were identified that distinguished the subjects with MDI-OA from those in the AEC group. Among them, ferritin expression was downregulated whereas transferrin expression was upregulated in subjects with MDI-OA compared with AEC; these results were validated by ELISA using sera from the MDI-OA/EB and AEC groups. To identify subjects with MDI-OA, the optimal serum cutoff levels were 69.84 ng/mL for ferritin and 2.48 microg/mL for transferrin. When these 2 parameters were combined, the sensitivity was 71.43% and the specificity was 85.71%. CONCLUSION Serum ferritin and transferrin levels are associated with the phenotype of MDI-OA.

Expression of Bcl-2 predicts outcome in locally advanced non-small cell lung cancer patients treated with cisplatin-based concurrent chemoradiotherapy

BACKGROUND Platinum-based concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced unresectable non-small cell lung cancer (NSCLC). The determination of parameters that may predict the result of the treatment has strong clinical implications. PATIENTS AND METHODS Pretreatment tumor biopsy specimens from 39 patients with locally advanced NSCLC (stage IIIA: 5, stage IIIB: 34) were analyzed for p53, Bcl-2, Bax and ERCC1 expression by immunohistochemistry. All patients were treated with cisplatin-based CCRT. Twenty-four patients received induction chemotherapy followed by CCRT (60Gy/30 fractions, 6mg/m(2) of cisplatin daily). The most commonly administered induction chemotherapy regimen was VIP (etoposide, ifosfamide, cisplatin; 20 patients). Fifteen patients received the same CCRT without induction chemotherapy. RESULTS High expression of p53, Bcl-2, Bax and ERCC1 was observed in 15 (38%), 19 (49%), 17 (44%) and 12 (31%) patients, respectively. High expression of Bcl-2 was significantly associated with longer survival duration (20 months vs. 9 months, P=0.008) and better response to the treatment (74% vs. 30%, P=0.01). In multivariate analysis, Bcl-2 expression was the only significant independent prognostic factor of overall survival (P=0.007) among the pretreatment patients characteristics. CONCLUSIONS High expression of Bcl-2 may be a useful prognostic factor in locally advanced NSCLC patients treated with cisplatin-based CCRT.