Yong Il Hwang

Comparison of the Prevalence of Chronic Obstructive Pulmonary Disease Diagnosed by Lower Limit of Normal and Fixed Ratio Criteria

The Global Initiative of Chronic Obstructive Lung Disease (GOLD) guidelines define chronic obstructive pulmonary disease (COPD) in subjects with FEV1/FVC <0.7. However, the use of this fixed ratio may result in over-diagnosis of COPD in the elderly, especially with mild degree of COPD. The lower limit of normal (LLN) can be used to minimize the potential misclassification. The aim of this study was to evaluate the impact of different definitions of airflow obstruction (LLN or fixed ratio of FEV1/FVC) on the estimated prevalence of COPD in a population-based sample. We compared the prevalence of COPD and its difference diagnosed by different methods using either fixed ratio (FEV1/FVC <0.7) or LLN criterion (FEV1/FVC below LLN). Among the 4,816 subjects who had performed spirometry, 2,728 subjects met new ATS/ERS spirometry criteria for acceptability and repeatability. The prevalence of COPD was 10.9% (14.7% in men, 7.2% in women) by LLN criterion and 15.5% (21.8% in men, 9.1% in women) by fixed ratio of FEV1/FVC among subjects older than 45 yr. The difference of prevalence between LLN and fixed ratio of FEV1/FVC was even higher among subjects with age ≥65, 14.9% and 31.1%, respectively. In conclusion, the prevalence of COPD by LLN criterion was significantly lower in elderly compared to fixed ratio of FEV1/FVC. Implementing LLN criterion instead of fixed ratio of FEV1/FVC may reduce the risk of over-diagnosis of COPD in elderly people.

Clinical Efficacy of Direct DNA Sequencing Analysis on Sputum Specimens for Early Detection of Drug-Resistant Mycobacterium tuberculosis in a Clinical Setting

BACKGROUND Early detection of drug-resistant Mycobacterium tuberculosis is important for the control and prevention of disease transmission. However, conventional drug susceptibility tests for drug-resistant M tuberculosis take at least 3 to 8 weeks. Here, we report the clinical efficacy of direct DNA sequencing analysis for detecting drug-resistant TB on sputum specimens in a clinical setting. METHODS A total of 113 sputum specimens from 111 patients, who were suspected of having drug-resistant TB by clinicians, were used for DNA sequencing of katG, rpoB, embB, and pncA genes for isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA) resistance, respectively, and the results were compared with drug susceptibility tests. The optimization of antituberculosis drugs according to the results of DNA sequencing and the treatment outcomes of the patients were also analyzed. RESULTS Turnaround time of the direct DNA sequencing analysis was 3.8 +/- 1.8 days. We found mutations related to drug resistance in 30 clinical specimens for katG, 39 for rpoB, 13 for embB, and 24 for pncA. The sensitivity and specificity of the assay were 63.6% and 94.6% for INH, 96.2 and 93.9% for RIF, 69.2% and 97.5% for EMB, and 100% and 92.6% for PZA, respectively. Of the patients with RIF resistance, including multidrug-resistant TB by the assay, 92.5% of the patients with initial first-line antituberculosis drugs were changed to second-line antituberculosis drugs, and treatment was successful in 61.9% of these cases. CONCLUSION Direct DNA sequencing analysis of clinical sputum specimens is a rapid and useful method for the detection and treatment of drug-resistant TB.

Clinical characteristics of patients with tuberculosis-destroyed lung.

SETTING Multicentre study. OBJECTIVE To define the clinical characteristics of patients with tuberculosis (TB) destroyed lung due to past TB. DESIGN We reviewed patients with TB-destroyed lung between May 2005 and June 2011. RESULTS A total of 595 patients from 21 hospitals were enrolled. The mean age was 65.63 ± 0.47 (mean ± standard error); 60.5% were male. The mean number of lobes involved was 2.59 ± 0.05. Pleural thickening was observed in 54.1% of the patients. Mean forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC, bronchodilator response and number of exacerbations per year were respectively 2.06 ± 0.03 l (61.26% ± 0.79), 1.16 ± 0.02 l (49.05% ± 0.84), 58.03% ± 0.70, 5.70% ± 0.34, and 0.40 ± 0.04. The number of lobes involved was significantly correlated with FVC and FEV(1), and with the number of exacerbations per year. Use of long-acting muscarinic antagonists or long-acting beta-2 agonists plus inhaled corticosteroids resulted in bronchodilatory effects. Multivariable regression analysis showed that age, initial FEV(1) (%) and number of exacerbations during follow-up were independent factors affecting change in FEV(1). CONCLUSION Decreased lung function with exacerbation, and progressive decline of FEV(1) were observed in patients with TB-destroyed lung.

Validity and Reliability of CAT and Dyspnea-12 in Bronchiectasis and Tuberculous Destroyed Lung

Background The objective of this study was to assess the validity and reliability of the Korean version of chronic obstructive pulmonary disease assessment test (CAT) and Dyspnea-12 Questionnaire for patients with bronchiectasis or tuberculous destroyed lung. Methods For 62 bronchiectasis patients and 37 tuberculous destroyed lung patients, 3 questionnaires including St. Georges Respiratory Questionnaires (SGRQ), CAT, and Dyspnea-12 were obtained, in addition to spirometric measurements. To assess the validity of CAT and Dyspnea-12, correlation with SGRQ was evaluated. To assess the reliability of CAT and Dyspnea-12, Cronbachs α coefficient was calculated. Results The mean ages of the patients were 60.7±8.3 years in bronchiectasis and 64.4±9.3 years in tuberculous destroyed lung. 46.8% and 54.1% were male, respectively. The SGRQ score was correlated with the score of the Korean version of CAT (r=0.72, p<0.0001) and Dyspnea-12 (r=0.67, p<0.0001) in bronchiectasis patients. The SGRQ score was correlated with the score of CAT (r=0.86, p<0.0001) and Dyspnea-12 (r=0.80, p<0.0001) in tuberculous destroyed lung patients. The Cronbachs α coefficient for the CAT and Dyspnea-12 were 0.84 and 0.90 in bronchiectasis, and 0.88 and 0.94 in tuberculous destroyed lung, respectively. Conclusion We found that Korean version of CAT and Dyspnea-12 are valid and reliable in patients with tuberculous destroyed lung and bronchiectasis.

Brain natriuretic peptide levels have diagnostic and prognostic capability for cardio-renal syndrome type 4 in intensive care unit patients.

IntroductionLimited data are available regarding the diagnostic and prognostic utility of brain natriuretic peptide (BNP) in patients with chronic kidney disease (CKD) in the intensive care unit (ICU) setting.MethodsAll patients with CKD and a serum creatinine (Cr) of 2.0 mg/dl or higher admitted to the ICU between January 2006 and September 2007 were enrolled in this study. The CKD group was divided according to the presence or absence of acute decompensated heart failure (ADHF) into CKD + ADHF and CKD - ADHF groups, respectively. Other patients with ADHF having low Cr (<1.2 mg/dl) in the coronary care unit were also recruited as a control group during the same period. BNP levels at the time of admission (admission BNP) were compared amongst these groups. We then sought to determine whether BNP levels could predict the outcome in patients with CKD.ResultsOf 136 patients with CKD for whom data were available, including 58 on dialysis (42.6%), 81 (59.6%) had ADHF and their estimated glomerular filtration rate (eGFR) was 12.8 ± 7.3 ml/min/1.73 m2. BNP levels at admission were 2708.6 ± 1246.9, 567.9 ± 491.7 and 1418.9 ± 1126.5 pg/ml in the CKD + ADHF, CKD - ADHF and control groups (n = 33), respectively (P = 0.000). The optimal cutoff level in patients with CKD was 1020.5 pg/ml (area under the curve = 0.944) to detect ADHF from the receiver operating characteristic (ROC) curve. This level was not associated with in-hospital mortality, all-cause death or a composite event (all-cause death and/or new cardiac event). However, a borderline significant association was observed with new cardiac events (hazard ratio (HR) = 4.551; P = 0.078) during the follow-up period (521.1 ± 44.7 days). Furthermore, continuous variables of BNP and BNP quartiles were significantly associated with new cardiac events in the multivariate Cox model (HR = 1.001, P = 0.041; HR = 2.212, P = 0.018).ConclusionsThe findings suggest that the level of BNP at the time of admission may be a useful marker for detecting ADHF and predicting cardiac events in patients with CKD in the ICU setting.

Chronic Obstructive Pulmonary Disease Assessment Test Can Predict Depression: A Prospective Multi-Center Study

This study was conducted to investigate the association between the chronic obstructive pulmonary disease (COPD) assessment test (CAT) and depression in COPD patients. The Korean versions of the CAT and patient health questionnaire-9 (PHQ-9) were used to assess COPD symptoms and depressive disorder, respectively. In total, 803 patients with COPD were enrolled from 32 hospitals and the prevalence of depression was 23.8%. The CAT score correlated well with the PHQ-9 score (r=0.631; P<0.001) and was significantly associated with the presence of depression (β±standard error, 0.452±0.020; P<0.001). There was a tendency toward increasing severity of depression in patients with higher CAT scores. By assessment groups based on the 2011 Global Initiative for Chronic Obstructive Lung Disease guidelines, the prevalence of depression was affected more by current symptoms than by airway limitation. The area under the receiver operating characteristic curve for the CAT was 0.849 for predicting depression, and CAT scores ≥21 had the highest accuracy rate (80.6%). Among the eight CAT items, energy score showed the best correlation and highest power of discrimination. CAT scores are significantly associated with the presence of depression and have good performance for predicting depression in COPD patients.

The Basophil Activation Test Is Safe and Useful for Confirming Drug-Induced Anaphylaxis

The basophil activation test (BAT) has been suggested as a complementary method for diagnosing drug allergies. The aim of this study was to evaluate the clinical utility of this test in patients with drug-induced anaphylaxis. In total, 19 patients, all of whom had a history of moderate to severe anaphylaxis, were enrolled. None of the causative drugs had available in vitro tests or reliable skin tests; these drugs included, among others, first and second-generation cephalosporins, H2 blockers, and muscle relaxants. The BAT yielded positive results in 57.9% of the cases, which was similar those results of skin prick and intradermal tests (42.1% and 57.9%, respectively). When basophils were double labelled with CD63 and CD203c, both of which are basophil activation markers, the positive rate was increased from 57.9% to 73.7%. Therefore, the results of this study confirm that the BAT is a quick, reliable, and safe diagnostic tool for patients with drug-induced anaphylaxis.

Discrepancies between modified Medical Research Council dyspnea score and COPD assessment test score in patients with COPD

Background and objective According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, either a modified Medical Research Council (mMRC) dyspnea score of ≥2 or a chronic obstructive pulmonary disease (COPD) assessment test (CAT) score of ≥10 is considered to represent COPD patients who are more symptomatic. We aimed to identify the ideal CAT score that exhibits minimal discrepancy with the mMRC score. Methods A receiver operating characteristic curve of the CAT score was generated for an mMRC scores of 1 and 2. A concordance analysis was applied to quantify the association between the frequencies of patients categorized into GOLD groups A–D using symptom cutoff points. A κ-coefficient was calculated. Results For an mMRC score of 2, a CAT score of 15 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.70 and 0.66, respectively (area under the receiver operating characteristic curve [AUC] 0.74; 95% confidence interval [CI], 0.70–0.77). For an mMRC score of 1, a CAT score of 10 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.77 and 0.65, respectively (AUC 0.77; 95% CI, 0.72–0.83). The κ value for concordance was highest between an mMRC score of 1 and a CAT score of 10 (0.66), followed by an mMRC score of 2 and a CAT score of 15 (0.56), an mMRC score of 2 and a CAT score of 10 (0.47), and an mMRC score of 1 and a CAT score of 15 (0.43). Conclusion A CAT score of 10 was most concordant with an mMRC score of 1 when classifying patients with COPD into GOLD groups A–D. However, a discrepancy remains between the CAT and mMRC scoring systems.

A Validation Study for the Korean Version of Chronic Obstructive Pulmonary Disease Assessment Test (CAT).

Background Health status measure is not only important for clinical research studies but also for clinical practices of chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to evaluate the validity of the Korean Version of COPD Assessment Test (CAT) in primary care clinics as well as in referral hospitals. Methods Smokers or ex-smokers, aged 40 years or older, with a smoking history of >10 pack-years; and a COPD diagnosis in the past 6 months or more, were recruited from 4 primary care clinics and 2 referral hospitals. Demographic, medical, and spirometry data was collected from patients who completed the CAT and St. George Respiratory Questionnaire (SGRQ), and had their dyspnea been assessed. The primary endpoint was the correlation between of the Korean version of CAT with SGRQ in patients with COPD. Results A total 100 patients were enrolled. The mean age and smoking amounts were 69.2±8.4 years and 40.6±22.3 pack-years, respectively. Sixty-seven percent of the patients reported at least one exacerbation in the past year. The mean CAT score was 16.9±8.0. The internal consistency assessed by Cronbachs alpha was 0.85. The CAT score was positively correlated with the SGRQ score (r=0.76, p<0.0001) and each component of SGRQ: symptoms, activity and impacts; r=0.68, r=0.61, and r=0.72, respectively (all p<0.0001). These positive correlations were preserved in the different groups (r=0.86, p<0.0001 in primary care clinic group; r=0.69, p<0.0001 in hospital group). The CAT score was also positively correlated to the Medical Research Council dyspnoea scale (r=0.46, p<0.0001). Conclusion The Korean version of CAT had good internal consistency and showed good correlations with SGRQ. It can be used for assessing the impacts of COPD on the patients health including primary care setting.

Analysis of adverse drug reactions collected by an electronic reporting system in a single hospital

T applied anaesthetics are employed in order to eliminate pain caused by needle insertion and injection, thus ameliorating patient compliance. Furthermore, they are devoid of symptoms of superficial trauma and local reaction. Therefore, the aim of this work was to develop a new formulation of lidocaine, proposed to improve its clinical effectiveness in topical anaesthesia in terms of both enhanced anaesthesia and a prolonged duration of action. For this purpose, we incorporated lidocaine in nanostructured lipid carriers (NLC). Particle size and zeta potential measurements, Fourier transform infrared spectroscopy and Raman spectroscopy were performed to characterize the NLC system. Furthermore, DSC and XRD measurements were conducted to investigate lipid crystallization which plays a very important role in the performance of NLC carriers. Additionally, membrane diffusion and penetration studies were completed in vitro and ex vivo, followed by measurements on skin hydration and transepidermal water loss in vivo. Our results lead us to the conclusion that the developed nanostructured lipid carrier is a promising vehicle for the topical delivery of lidocaine. The penetration of the NLC formulation was remarkable through heat separated epidermis after 24 hours, and the observed skin hydrating and occlusive effect also makes this formulation a favourable dermal carrier system.Statement of the Problem: Day by day, the demand for biotherapeutics and recombinant proteins is increasing. Herein, cytoplasmic expression in prokaryotic and eukaryotic hosts has been widely accepted. However, there are several obstacles in the large-scale production of recombinant proteins. Recombinant proteins might form inclusion bodies or be degraded by proteases. Endogenous proteins might also interfere with the folding of a recombinant secretory protein. These factors, as well as the complicated downstream purification process, will result in loss of protein yield. Moreover, the yield of recombinant protein is not only related to expression levels, but also to translocation efficiency. Thus, the translocation efficiency could be increased by using signal peptides. Phenylalanine ammonialyase (PAL), involved in the first step of the phenylpropanoid pathway, catalyzes the deamination of phenylalanine to cinnamate and ammonia. PALs are ubiquitous in plants and also commonly found in fungi; however, animal lacks it. They are of special interest in several medical and industrial applications, including preparation of low phenylalanine diet, treatment of phenylketonuria and certain neoplastic tumors. Although several methods have been applied in the production of PAL, the final titers of PAL are still low, thereby impeding considerable industrialization of this enzyme.Background/Aims: The recent introduction of computerized surveillance systems has promoted the monitoring of adverse drug reactions (ADRs), a feature that facilitates voluntary reports and enables prompt feedback. To investigate the causative agents and severity of ADRs that occurred in a single hospital, we analyzed the features of 980 ADRs that occurred over 14 months after developing a computerized ADR reporting system in Hallym Sacred Heart Hospital. Methods: ADR data collected prospectively from September 2007 to October 2008 by a computerized reporting system were analyzed. The World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria were used to determinate causality for each ADR. Results: The number of ADR cases reported voluntarily increased rapidly since the introduction of the computerized ADR reporting system. Of the 980 cases, antibiotics (34.5%) were the most common causative drugs, followed by analgesics such as tramadol and its compound (15.2%), radiocontrast media (7.0%), narcotics (5.9%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (5.5%). Fifty-nine (6.0%) and 206 (21.0%) cases were classified as severe and moderate reactions, respectively. The mean age was older in patients with severe ADRs than in patients with non-severe ADRs. The most common clinical features were skin manifestations, such as pruritus, skin eruptions, and urticaria. Gastrointestinal symptoms including nausea, vomiting, and diarrhea were the second most frequently reported ADRs. Among antibiotics, first-generation cephalosporins were the most frequently reported causative drugs, followed by second-generation cephalosporins, penicillin/β-lactamase inhibitors, and third-generation cephalosporins. While 11.6% of ADRs related to penicillin/β-lactamase inhibitors were classified as severe, there was only one severe ADR (1.1%) for first-generation cephalosporins. Most ADRs were reported equally in men and women, although female cases constituted aboutDietary supplement market is growing in Turkey. Local and multinational companies develop and introduce many new products for Turkish dietary supplements market. However, in marketing literature, a few academic researchers could be found regarding Turkish consumers’ behavior about dietary supplements. Understanding the awareness and utilization rates of nutritional support products is important at the point of designing strategies for producers, the state and related organizations. This general exploratory research was carried out in 60 different pharmacies located in different regions of Turkey (Mediterranean, Black Sea, Eastern Anatolia, Southeastern Anatolia, Central Anatolia Region). Face-to-face interviews were conducted with 253 people aged 18 years and over from September 2017 to February 2018 (5 months). The data collected by the questionnaire includes the factors that affect the use of nutritional support products by respondents in the study, the recognition and consumption rates, the product content and how regularly they use it. Respondents were found to use products for immunity (21.03%) at the beginning of their nutritional support products usage. Omega 3 fish oil (26.98%), multivitamins (17.86%) and CoQ10 (7.94%) were the most preferred products. The rate of natural supplements usage by individuals who thought that use of natural supplements is crucial, is around %71.43.. We believe this study will lead to more detailed research on healthy lifestyle market in the future.T aim of the present study was to establish the relation that exists between the striatal dopamine levels and urine dopamine content in hemiparkinsonism rat model. 20 Wistar rats were used and were randomized into two groups as follows: a) control group and b) lessoned injured group induced by (6-OHDA). All animals were re-tested on the same battery of motor tests that before lesion. The rotation test behavior test was assessed and striatal DA levels and urine DA were determined by HPLC, motor behavior fine tests were done and finally immunohistochemical (Hir+) striatum was done. We found a positive correlation between the dopamine levels in the striatum and the content dopamine in urine of rats (control vs. 6-OHDA group). Respect motor performance, the 6-OHDA group showed a significant fine motor impairment (grasp and advance) vs. control group (p<0.01). Immunostaining for tyrosine hydroxylase (TH) expression revealed no TH-immunoreactive (THir) neurons in any 6-OHDA animals vs. control group (p<0.01). Positive correlation between the dopamine levels in the striatum and the content dopamine in urine could be talking also, about a major proportion of urinary dopamine could be derived from the renal decarboxylation of circulating dopa and not dopaminergic system disturbance. The other hand, alterations of a forelimb motor function in rats could be only due to more vulnerability of striatal dopaminergic depletion and not to low periphery dopamine levels.Polyamidoamine (PAMAM) dendrimers as synthetic gene vectors are efficient gene delivery systems. In this study, a kind of α-cyclodextrin-PAMAM conjugates polymer (Cy D-G1) was synthesized as a gene delivery vector. Based on ~1H NMR detectation, about 6.4 PAMAM-G1 molecules was grafted onto an α-CD core. Agarose gel electrophoresis revealed that Cy D-G1 could efficiently bind with DNA to condense them into nano-scale particles, which showed a similar binding capacity of PEI-25 K. Besides, it could protect DNA from DNase I degradation in a low N/P ratio. When N/P ratio in the CyD-G1/DNA polyplex was 40, the average particle size of CyD-G1/DNA polyplex was about 120 nm, and zeta potential was +21 mV. This polyplex could maintain its particle size in serum-containing solution within 360 min. In comparison with PEI-25 K carrier, CyD-G1 showed low cytotoxicity in various cell lines. Cell transfection results showed that CyD-G1 efficiently delivered DNA into cells at N/P = 80 compared with Lipofectamine 2000 and PEI-25 K. Unlike Lipofectamine 2000 and PEI-25 K, in serum-containing test condition, CyD-G1/DNA polyplex could maintain the transgene activities. The results of confocal laser scanning microscopy indicated that most DNA entered into cell nuclei within 4 h, and this phenomenon was consistent with the results calculated by flow cytometry. Taken together, CyD-G1 showed good transgene activities and the gene delivery vector could be used not only in vitro but also in vivo.