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Min-Kyung Ji,1,&ast; Yaerim Chun,2,&ast; Geonwoo Jeong,3 Hyun-Seung Kim,4 Won-Jae Kim,5 Je-Hwang Ryu,6 Hoonsung Cho,3 Hyun-Pil Lim1,2 1Dental 4D Research Center, Chonnam National University, Gwangju, Republic of Korea; 2Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; 3Department of Materials Science and Engineering, Chonnam National University, Gwangju, Republic of Korea; 4KJ Meditech Co., Ltd, Gwangju, Republic of Korea; 5Department of Oral Physiology, School of Dentistry, Stem Cell Secretome Research Center, Chonnam National University, Gwangju, Republic of Korea; 6Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hyun-Pil Lim, Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel +82-10-2645-7528, Fax +82-62-530-5577, Email mcnihil@jnu.ac.kr Hoonsung Cho, Department of Materials Science and Engineering, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel/Fax +82-62-530-1717, Email cho.hoonsung@jnu.ac.krPurpose: This study aimed to confirm the synergy effect of these two materials by evaluating osteoblast and antibacterial activity by applying a double-layered hydroxyapatite(HA) zirconium oxide(ZrO2) coating to titanium.Methods: The specimens used in this study were divided into four groups: a control group (polished titanium; group T) and three experimental groups: Group TH (RF magnetron sputtered HA deposited titanium), Group Z (ZrO2 ALD deposited titanium), and Group ZH (RF magnetron sputtered HA and ZrO2 ALD deposited titanium). The adhesion of Streptococcus mutans (S.mutans) to the surface was assessed using a crystal violet assay. The adhesion, proliferation, and differentiation of MC3T3-E1 cells, a mouse osteoblastic cell line, were assessed through a WST-8 assay and ALP assay.Results: Group Z showed a decrease in the adhesion of S. mutans (p < 0.05) and an improvement in osteoblastic viability (p < 0.0083). Group TH and ZH showed a decrease in adhesion of S. mutans (p < 0.05) and an increase in osteoblastic cell proliferation and cell differentiation (p < 0.0083). Group ZH exhibited the highest antibacterial and osteoblastic differentiation.Conclusion: In conclusion double-layered HA and ZrO2 deposited on titanium were shown to be more effective in inhibiting the adhesion of S. mutans, which induced biofilm formation, and increasing osteoblastic differentiation involved in osseointegration by the synergistic effect of the two materials.Keywords: zirconium oxide, hydroxyapatite, atomic layer deposition, radio frequency magnetron sputter, osteoblast activity, antibacterial effect

Hong-Joo Kim,1 Seon-Ki Lee,2 Hyun-Seung Kim,3 Won-Jae Kim,4 Je-Hwang Ryu,5 Min-Kyung Ji,6 Hyun-Pil Lim1 1Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; 2Department of Prosthodontics, Daejeon Dental Hospital, Wonkwang University, Daejeon, Republic of Korea; 3KJ Meditech Co., Ltd, Gwangju, Republic of Korea; 4Department of Oral Physiology, School of Dentistry, Stem cell Secretome Research Center, Chonnam National University, Gwangju, Republic of Korea; 5Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; 6Dental 4D Research Center, Chonnam National University, Gwangju, Republic of KoreaCorrespondence: Hyun-Pil Lim, Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel +82-10-2645-7528, Fax +82-62-530-5639, Email mcnihil@jnu.ac.kr Min-Kyung Ji, Dental 4D Research Center, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel +82-10-8432-3639, Fax +82-62-530-5639, Email perizimin@gmail.comPurpose: Atomic layer deposition (ALD) is a method that can deposit zirconia uniformly on an atomic basis. The effect of deposited zirconia on titanium implants using ALD was evaluated in vivo.Methods: Machined titanium implants (MTIs) were used as the Control. MTIs treated by sandblasting with large grit and acid etching (SA) and MTIs deposited with zirconia using ALD are referred to as Groups S and Z, respectively. Twelve implants were prepared for each group. Six rabbits were used as experimental animals. To evaluate the osteogenesis and osteocyte aspects around the implants, radiological and histological analyses were performed. The bone-to-implant contact (BIC) ratio was measured and statistically analyzed to evaluate the osseointegration capabilities.Results: In the micro-CT analysis, more radiopaque bone tissues were observed around the implants in Groups S and Z. Histological observation found that Groups S and Z had more and denser mature bone tissues around the implants in the cortical bone area. Many new and mature bone tissues were also observed in the medullary cavity area. For the BIC ratio, Groups S and Z were significantly higher than the Control in the cortical bone area (P < 0.017), but there was no significant difference between Groups S and Z.Conclusion: MTIs deposited with zirconia using ALD (Group Z) radiologically and histologically showed more mature bone formation and activated osteocytes compared with MTIs (Control). Group Z also had a significantly higher BIC ratio than the Control. Within the limitations of this study, depositing zirconia on the surface of MTIs using ALD can improve osseointegration in vivo.Keywords: atomic layer deposition, ALD, zirconia, machined titanium implant, bone-to-implant contact ratio, BIC, osseointegration

Eun Chong Yoon,1 So-My Koo,1 Hye Yun Park,2 Ho Cheol Kim,3 Woo Jin Kim,4 Ki Uk Kim,5 Ki-Suck Jung,6 Kwang Ha Yoo,7 Hyoung Kyu Yoon,8 Hee-Young Yoon1 1Division of Allergy and Respiratory Diseases, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea; 2Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Republic of Korea; 4Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, Republic of Korea; 5Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea; 6Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 7Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 8Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Hee-Young Yoon, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul, 04401, Republic of Korea, Tel +82-10-8728-6950, Fax +82-2-709-9554, Email yhyoung85@schmc.ac.krPurpose: Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic inflammation. Acute exacerbation of COPD (AECOPD) manifests as acute worsening of respiratory symptoms and is associated with high morbidity and mortality. The aim of the present study was to evaluate the predictive value of white blood count (WBC) and its derived inflammatory biomarkers for AECOPD.Methods: From the Korean COPD Subgroup Study cohort, a prospective and multicenter observational study, 826 patients who had baseline complete blood count (CBC) and 3-year AECOPD data were included. Follow-up CBC data at 1 (n = 385), 2 (n = 294), and 3 (n = 231) years were collected for available patients. The primary outcome was the occurrence of AECOPD at 3 years. The risk of AECOPD was evaluated using a binary logistic analysis.Results: The cumulative incidences of 12-, 24-, and 36-month AECOPD were 47.6%, 60.5%, and 67.6%, respectively. Patients with AECOPD at 3 years had higher baseline WBC counts, neutrophil counts, neutrophil/lymphocyte ratio (NLR), and neutrophil/monocyte ratio than those without AECOPD. Higher WBC count, neutrophil count, and NLR were associated with the 3-year occurrence of AECOPD in the univariate analysis, but only the higher neutrophil count was a significant risk factor (odds ratio [OR] = 1.468; 95% confidence interval [CI]: 1.024– 2.104) in the covariates-adjusted analysis. In the analysis of changes in inflammatory parameters, a decrease in the platelet count (OR = 0.502; 95% CI: 0.280– 0.902) and NLR (OR = 0.535; 95% CI: 0.294– 0.974) at 2 years and an increase in the eosinophil count (OR = 2.130; 95% CI: 1.027– 4.416) at 3 years were significantly associated with AECOPD in the adjusted analysis.Conclusion: Our data suggest that a high baseline WBC count, particularly neutrophil count, was associated with a higher incidence of long-term AECOPD.Keywords: blood cell count, blood platelets, eosinophils, lymphocytes, neutrophils, pulmonary disease, chronic obstructive

Jeeyoung Kim,1 Bharathi Suresh,2 Myoung Nam Lim,1 Seok-Ho Hong,3 Kye-Seong Kim,2,4 Ha Eun Song,5 Hyo Yeong Lee,5 Hyun Ju Yoo,5 Woo Jin Kim1 1Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea; 2Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; 3Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, South Korea; 4College of Medicine, Hanyang University, Seoul, South Korea; 5Department of Convergence Medicine, Asan Medical Center, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, South KoreaCorrespondence: Hyun Ju Yoo, Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea, Tel +82-2-3010-4029, Fax +82-2-3010-8566, Email yoohyunju@amc.seoul.kr Woo Jin Kim, Department of Internal Medicine, Kangwon National University School of Medicine, 1 Gangwondaehak-gil, Chuncheon, 24341, Korea, Tel +82-33-258-9364, Fax +82-33-258-2404, Email pulmo2@kangwon.ac.krPurpose: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease presenting as multiple phenotypes, such as declining lung function, emphysema, or persistent airflow limitation caused by several risk factors, including cigarette smoking and air pollution. The inherent complexity of COPD phenotypes propounds difficulties for accurate diagnosis and prognosis. Although metabolomic profiles on COPD have been reported, the role of metabolism in COPD-related phenotypes is yet to be determined. In this study, we investigated the association between plasma sphingolipids and amino acids, and between COPD and COPD-related phenotypes in a Korean cohort.Patients and Methods: Blood samples were collected from 120 patients with COPD and 80 control participants who underwent spirometry and quantitative computed tomography. The plasma metabolic profiling was carried out using LC-MS/MS analysis.Results: Among the evaluated plasma sphingolipids, an increase in the metabolism of two specific sphingomyelins, SM (d18:1/24:0) and SM (d18:1/24:1) were significantly associated with COPD. There was no significant correlation between any of the SMs and the emphysema index, FVC and FEV1 in the COPD cohort. Meanwhile, Cer (d18:1/18:0) and Cer (d18:1/24:1) were significantly associated with reduced FEV1. Furthermore, the levels of several amino acids were altered in the COPD group compared to that in the non-COPD group; glutamate and alpha AAA were substantial associated with emphysema in COPD. Kynurenine was the only amino acid significantly associated with reduced FEV1 in COPD. In contrast, there was no correlation between FVC and the elevated metabolites.Conclusion: Our results provide dysregulated plasma metabolites impacting COPD phenotypes, although more studies are needed to explore the underlying mechanism related to COPD pathogenesis.Keywords: targeted sphingolipids, amino acids, sub-phenotypes, lung function

Tae Wan Kim,1 Eun Sil Choi,2 Woo Jin Kim,3 Heui Sug Jo4 1Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, South Korea; 2Gangwon Public Health Policy Institute, Chuncheon, South Korea; 3Department of Internal Medicine, Kangwon National University, Chuncheon, South Korea; 4Department of Health Policy & Management, Kangwon National University, Chuncheon, South KoreaCorrespondence: Woo Jin KimDepartment of Internal Medicine & Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, 156, Baengnyeong-ro, Chuncheon-si, Gangwon-do, 24289, South KoreaTel +8233-250-8872Fax +8233-259-5637Email pulmo2@kangwon.ac.krHeui Sug JoDepartment of Health Policy and Management, School of Medicine, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, 24341, Republic of KoreaTel +8233-250-8872Fax +8233-259-5637Email joheuisug@gmail.comPurpose: Up to 20% of patients with chronic obstructive pulmonary disease (COPD) require re-admission within 30 days of discharge after hospitalization for acute exacerbations of the disease. These re-admissions can increase morbidity and the economic burden of COPD. Reducing re-admissions has become a policy target in many developed countries. We investigated the risk factors for COPD re-admissions among older adults with COPD.Patients and Methods: Data obtained from the National Health Insurance Service-Senior Cohort (NHIS-SC) in Korea were analyzed. The subjects included 558,147 patients aged ≥ 70 who had been admitted for COPD between 2013 and 2015. Re-admission was defined as being re-hospitalized within 30 days after discharge. The key variables selected from the database included income-based insurance contributions, demographical variables, information on inpatient medical services, types of healthcare facilities, and emergency time relevance index (TRI). The TRI is a regional medical-use analysis index that evaluates whether the capacity of the medical services available is appropriate for the medical needs of the target residents.Results: In 814 COPD re-admission cases among 4867 total admissions due to COPD in elderly subjects, higher re-admission rates were associated with male sex, admission to district hospitals, medical aid recipients, and a longer hospital stay. When additionally adjusting the TRI to identify the difference in re-admission rates due to medical service accessibility, the same results were found, except for the areas of residence. The TRI was lower in re-admission cases (odds ratio 0.991 [95% CI, 0.984‒0.998], P = 0.013).Conclusion: In this study, COPD re-admission rates among older adults were significantly associated with sex, length of hospital stay, and the type of hospital. The capacity of the medical services provided was also related to the COPD re-admission rate. Better access to appropriate emergency services is associated with reduction of COPD re-admission rates.Keywords: rehospitalization, elderly, local characteristics, time relevance index

Yeon-Mok Oh,1,* Keu Sung Lee,2,* Yoonki Hong,3,* Sung Chul Hwang,2 Jae Yeol Kim,4 Deog Keom Kim,5 Kwang Ha Yoo,6 Ji-Hyun Lee,7 Tae-Hyung Kim,8 Seong Yong Lim,9 Chin Kook Rhee,10 Hyoung Kyu Yoon,11 Sang Yeub Lee,12 Yong Bum Park,13 Jin Hee Jung,14 Woo Jin Kim,3 Sang-Do Lee,1 Joo Hun Park2 1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Korea; 3Department of Internal Medicine and Environmental Health Center, Kangwon National University, Kangwon National University Hospital, Chuncheon, Korea; 4Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea; 6Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea; 7Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 8Division of Pulmonology, Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea; 9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 10Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University of Korea, Seoul, Korea; 11Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 12Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 13Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 14Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea *These authors contributed equally to this work Background: High blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids. However, the prognostic role of blood eosinophil count remains underexplored. Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.Methods: Patients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital. The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%–5%), and low (

Ina Jeong,1,* Jae-Hyun Lim,2,* Dong Kyu Oh,3 Woo Jin Kim,4 Yeon-Mok Oh3 1Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea; 2Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea *These authors contributed equally to this work Purpose: As only some smokers develop COPD with emphysema, we explored the molecular pathogenesis of early-stage COPD with emphysema using gene expression profiling of human lung tissues. Patients and methods: First, 110 subjects who had smoked more than ten pack-years were classified into three groups: COPD with emphysema, COPD without emphysema, and healthy smokers. COPD and emphysema were confirmed by post-bronchodilator forced expiratory volume in 1 second/forced vital capacity

Seung-Shick Shin,1,* Dae-Hwa Noh,2,* Byungdoo Hwang,2 Jo-Won Lee,2 Sung Lyea Park,2 Sung-Soo Park,1 Bokyung Moon,2 Wun-Jae Kim,3 Sung-Kwon Moon2 1Department of Food Science and Nutrition, Jeju National University, Jeju, South Korea; 2Department of Food and Nutrition, Chung-Ang University, Anseong, South Korea; 3Department of Urology, Chungbuk National University, Cheongju, Chungbuk, South Korea *These authors contributed equally to this work Background: Although the diverse biological properties of nanoparticles have been studied intensively, research into their mechanism of action is relatively rare. In this study, we investigated the molecular mechanisms of the anticancer activity of heterometallic Au@Pt-nanoseeds (NSs) against bladder cancers.Materials and methods: Mode of action of Au@Pt-NSs was investigated through MTT assay, flow cytometry analysis, Western immunoblots, real-time qPCR, wound-healing migration and invasion assays, zymography, and electrophoretic mobility shift assay (EMSA).Results: Treatment with Au@Pt-NSs significantly inhibited the proliferation of EJ cells in a dose-dependent manner by inducing G1 phase cell cycle arrest. Among the regulators associated with the G1 cell cycle phase, CDK2, CDK4, cyclin D1, cyclin E, and p21WAF1 were shown to participate in the inhibitory pathways of Au@Pt-NSs. In addition, treatment with Au@Pt-NSs led to upregulation of phospho-p38 MAPK and downregulation of phospho-AKT in EJ cells. Interestingly, Au@Pt-NSs inhibited the migratory and invasive potential of the cells, which was attributed to the suppression of the enzymatic activity of matrix metalloproteinase-9 (MMP-9). Using MMP-9-specific oligonucleotides, we showed that transcription factors such as NF-κB and Sp-1 were responsible for the MMP-9-mediated metastatic potential of EJ cells.Conclusion: Au@Pt-NSs significantly limited the progression, migration, and invasion of bladder cancer EJ cells. Our data represent a novel insight into developing cisplatin-like chemotherapeutic reagents with fewer side effects and provide useful information on molecular markers to monitor patients under Au@Pt-NSs-based chemotherapy. Keywords: nanoseeds, nanomedicine, bladder cancer, molecular mechanism

So Hyeon Bak,1 Soohyun Kim,2 Yoonki Hong,3 Jeongwon Heo,4 Myoung-Nam Lim,5 Woo Jin Kim3 1Department of Radiology, School of Medicine, Kangwon National University, Chuncheon, Repubilc of Korea; 2Department of Radiology, Kangwon National University Hospital, Chuncheon, Republic of Korea; 3Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea; 4Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Chuncheon, Republic of Korea; 5Data Analysis Center, Kangwon National University, Chuncheon, Republic of Korea Background: Few studies have investigated the quantitative computed tomography (CT) features associated with the severity of bronchiectasis in COPD patients. The purpose of this study was to identify the quantitative CT features and clinical values to determine the extent of bronchiectasis in moderate-to-severe COPD patients.Methods: A total of 127 moderate-to-severe COPD patients were selected from the cohort of COPD in Dusty Areas (CODA). The study subjects were classified into three groups according to the extent of bronchiectasis on CT: no bronchiectasis, mild bronchiectasis, and moderate-to-severe bronchiectasis. The three groups were compared with respect to demographic data, symptoms, medical history, serum inflammatory markers, pulmonary function, and quantitative CT values.Results: Among 127 moderate-to-severe COPD subjects, 73 patients (57.5%) were detected to have bronchiectasis, 51 patients (40.2%) to have mild bronchiectasis, and 22 patients (17.3%) to have moderate-to-severe bronchiectasis. Compared with COPD patients without bronchiectasis, those with bronchiectasis were older and had higher frequency of prior tuberculosis, lower prevalence of bronchodilator reversibility (BDR), and more severe air trapping (P < 0.05). Moderate-to-severe bronchiectasis patients had lower body mass index (BMI), higher frequency of prior tuberculosis, lower prevalence of BDR, worse pulmonary function, and more severe air trapping (P < 0.05) than those in the mild bronchiectasis group.Conclusion: Moderate-to-severe bronchiectasis was associated with a history of pulmonary tuberculosis, lower BMI, severe airflow obstruction, and lower BDR in moderate-to-severe COPD patients. Quantitative analysis of CT showed that severe air trapping was associated with the extent of bronchiectasis in these patients. Keywords: chronic obstructive pulmonary disease, bronchiectasis, computed tomography, air trapping, tuberculosis

Yong Suk Jo,1 Myoung Nam Lim,2 Young-Ji Han,3 Woo Jin Kim4 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, 2Data Analysis Center, 3Department of Environmental Science, Kangwon National University, 4Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Korea Background and objective: Aside from smoking, which is already recognized as a strong risk factor for COPD, interest in the impact of particulate matter (PM) on COPD is increasing. This study aimed to investigate the effect of PM, especially with an aerodynamic diameter ≤2.5 µm (PM2.5), and its chemical constituents on the exacerbation of COPD.Methods: Data on hospital visits including admission and outpatient clinic visits for exacerbation of COPD in Chuncheon, Korea, between 2006 and 2012 were extracted from the National Health Insurance Service database. PM2.5 and its chemical constituents were measured on the roof of the four-story Kangwon National University Natural Sciences building once every 3 days. Meteorological data were provided by the Korean Meteorological Administration.Results: During the study period, the mean level of PM2.5 was 35.0±25.2 µg/m3, and the number of daily hospital visits were 6.42±4.28 and 2.07±1.93 for males and females, respectively. The number of COPD-related hospital visits increased with increasing PM2.5 after adjusting for meteorological covariates and females tended to be more affected sooner than males. Among the PM2.5 constituents, Al, Si, and elemental carbon were associated with increased hospital visits and there was a difference according to sex. In males, some constituents of PM2.5 were related to an increased risk of a hospital visit, mainly on the first and second days of measurement (Lag1 and Lag2). In contrast, there was no significant increase in the risk of hospital visits due to any of the PM2.5 constituents in females.Conclusion: Concentrations of PM2.5 mass and some of the PM2.5 constituents were associated with increased COPD-related hospital visits in Chuncheon. Keywords: COPD, PM2.5, constituents, hospital visit

Jieun Kang,1,* Ki Tae Kim,2,* Ji-Hyun Lee,3 Eun Kyung Kim,3 Tae-Hyung Kim,4 Kwang Ha Yoo,5 Jae Seung Lee,1 Woo Jin Kim,6 Ju Han Kim,2 Yeon-Mok Oh1 1Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 2Seoul National University Biomedical Informatics and Systems Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, 3Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, 4Division of Pulmonology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, 5Department of Internal Medicine, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, 6Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, South Korea *These authors contributed equally to this work Purpose: There is currently no measure to predict a treatability of long-acting β-2 agonist (LABA) or long-acting muscarinic antagonist (LAMA) in patients with chronic obstructive pulmonary disease (COPD). We aimed to build prediction models for the treatment response to these bronchodilators, in order to determine the most responsive medication for patients with COPD.Methods: We performed a prospective open-label crossover study, in which each long-acting bronchodilator was given in a random order to 65 patients with stable COPD for 4 weeks, with a 4-week washout period in between. We analyzed 14 baseline clinical traits, expression profiles of 31,426 gene transcripts, and damaged-gene scores of 6,464 genes acquired from leukocytes. The gene expression profiles were measured by RNA microarray and the damaged-gene scores were obtained after DNA exome sequencing. Linear regression analyses were performed to build prediction models after using factor and correlation analyses.Results: Using a prediction model for a LABA, traits found associated with the treatment response were post-bronchodilator forced expiratory volume in 1 second, bronchodilator reversibility (BDR) to salbutamol, expression of three genes (CLN8, PCSK5, and SKP2), and damage scores of four genes (EPG5, FNBP4, SCN10A, and SPTBN5) (R2=0.512, p

Woo Jin Kim,1 Jae-Joon Yim,2 Deog Kyeom Kim,3 Myung Goo Lee,4 Anne L Fuhlbrigge,5 Pawel Sliwinski,6 Iwona Hawrylkiewicz,6 Emily S Wan,7,8 Michael H Cho,7,8 Edwin K Silverman7,8 1Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Chuncheon, 2Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University College of Medicine, Seoul, 3Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, 4Division of Pulmonary, Allergy and Critical Care Medicine, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Korea; 5Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA; 62nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland; 7Channing Division of Network Medicine, 8Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA Purpose: Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow obstruction, is a major cause of morbidity and mortality worldwide. However, geographic differences in the clinical characteristics of severe COPD patients have not been widely studied. Methods: We recruited a total of 828 severe COPD cases from three continents. Subjects in Poland were enrolled by the Institute of Tuberculosis and Lung Diseases in Warsaw; subjects in Korea participated at several university hospitals in Korea; and subjects in USA were enrolled at two clinics affiliated with academic medical centers. All subjects were over the age of 30 with at least 10 pack-years of cigarette smoking history. Cases manifested severe to very severe airflow obstruction with post-bronchodilator forced expiratory volume in 1 second (FEV1)

Jin Hwa Lee,1 Chin Kook Rhee,2 Kyungjoo Kim,2 Jee-Ae Kim,3 Sang Hyun Kim,4 Kwang Ha Yoo,5 Woo Jin Kim,6 Yong Bum Park,7 Hye Yun Park,8 Ki-Suck Jung9 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, EwhaWomans University, 2Department of Internal Medicine, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, 3Pharmaceutical Policy Evaluation Research Team, Research Institution, Health Insurance Review and Assessment Service, 4Big Data Division, Health Insurance Review and Assessment Service, Wonju, 5Department of Internal Medicine, Konkuk University College of Medicine, Seoul, 6Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Chuncheon, 7Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, 8Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, South Korea Purpose: The purpose of this study was to identify subtypes in patients with mild-to-moderate airflow limitation and to appreciate their clinical and socioeconomic implications.Methods: Subjects who were aged ≥20 years and had forced expiratory volume in 1 second (FEV1) ≥60% predicted and FEV1/forced vital capacity

Yoonki Hong,1 Wonjun Ji,2 Soojeong An,3 Seon-Sook Han,1 Seung-Joon Lee,1 Woo Jin Kim1 1Department of Internal Medicine, Environmental Health Center, Kangwon National University Hospital, Chuncheon, South Korea, 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, 3Department of Statistics, Kangwon National University, Chuncheon, South Korea Background: There is growing evidence about sex-related phenotypes of COPD. However, the sex differences in COPD mainly result from smokers. This study evaluated the sex differences in nonsmoking patients with COPD, focusing on structural changes in the lungs in airway diseases and emphysema. Methods: Ninety-seven nonsmoking patients, defined as having

Hyeon-Kyoung Koo,1 Yoonki Hong,2 Myoung Nam Lim,2 Jae-Joon Yim,3 Woo Jin Kim2 1Department of Internal Medicine, Division of Pulmonary and Critical Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, 2Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon-si, 3Department of Internal Medicine and Lung Institute, Division of Pulmonary and Critical Care Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea Objective: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease–antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity.Methods: Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses.Results: There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant.Conclusion: Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients. Keywords: matrix metalloproteinase, pulmonary disease, chronic obstructive, respiratory function test, pulmonary emphysema, bronchodilator response

Hye Yun Park,1 Hyun Lee,1 Won-Jung Koh,1 Seonwoo Kim,2 Ina Jeong,3 Hyeon-Kyoung Koo,4 Tae-Hyung Kim,5 Jin Woo Kim,6 Woo Jin Kim,7 Yeon-Mok Oh,8 Don D Sin,9 Seong Yong Lim,10,* Sang-Do Lee8,* On behalf of the KOLD Study Group 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Biostatistics Team, Samsung Biomedical Research Institute, Seoul, Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Medical Center, Seoul, Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea; 5Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do, Korea; 6Division of Pulmonology, Department of Internal Medicine, Uijeongbu St Mary’s Hospital, Gyunggi-do, Korea; 7Department of Internal Medicine, Kangwon National University, Chuncheon-si, Gangwon-do, Korea; 8Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 9Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 10Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea *These authors contributed equally to this work Background: COPD patients with increased airway eosinophilic inflammation show a favorable response to inhaled corticosteroids (ICS) in combination with a long-acting bronchodilator. Recent studies have demonstrated a significant correlation of sputum eosinophilia with blood eosinophils and periostin. We investigated whether high blood eosinophils and plasma periostin were associated with an improvement in forced expiratory volume in 1 second (FEV1) after 3-month treatment with ICS/long-acting beta2-agonist (LABA) in stable COPD patients. Patients and methods: Blood eosinophils and plasma periostin levels were measured in 130 stable COPD subjects selected from the Korean Obstructive Lung Disease cohort. Subjects began a 3-month ICS/LABA treatment after washout period. Results: High blood eosinophils (>260/µL, adjusted odds ratio =3.52, P=0.009) and high plasma periostin (>23 ng/mL, adjusted odds ratio =3.52, P=0.013) were significantly associated with FEV1 responders (>12% and 200 mL increase in FEV1 from baseline after treatment). Moreover, the addition of high blood eosinophils to age, baseline positive bronchodilator response, and FEV1

Woo Jin Kim,1 Sang Do Lee2 1Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, 2Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Abstract: COPD is a common complex disease characterized by progressive airflow limitation. Several genome-wide association studies (GWASs) have discovered genes that are associated with COPD. Recently, candidate genes for COPD identified by GWASs include CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), FAM13A (family with sequence similarity 13, member A), and AGER (advanced glycosylation end product–specific receptor). Their association with COPD susceptibility has been replicated in multiple populations. Since these candidate genes have not been considered in COPD, their pathological roles are still largely unknown. Herein, we review some evidences that they can be effective drug targets or serve as biomarkers for diagnosis or subtyping. However, more study is required to understand the functional roles of these candidate genes. Future research is needed to characterize the effect of genetic variants, validate gene function in humans and model systems, and elucidate the genes’ transcriptional and posttranscriptional regulatory mechanisms. Keywords: chronic obstructive pulmonary disease, genetics, genome-wide association study

Pankaj Joshi,1,2 Woo Jin Kim,3,4 Sang-Ah Lee1–3 1Department of Preventive Medicine, 2BIT Medical Convergence Graduate Program, 3Department of Internal Medicine, 4Environmental Health Center, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do, South Korea Background: Dietary antioxidants have been suggested to have protective role against chronic obstructive pulmonary disease (COPD), but few prospective studies examined this relationship. The prospective study was conducted to evaluate the effect of dietary antioxidants on COPD risk and lung function in the Korean population.Methods: The data were collected from the community-based Korean Genome Epidemiology Study (KoGES) cohort. To diagnose COPD, forced expiratory volume (FEV1) and forced vital capacity (FVC) were measured by spirometry. The dietary intake of antioxidant vitamins was estimated from validated Food-Frequency Questionnaire. For the analysis, 325 COPD patients and 6,781 at risk subjects were selected from the cohort of 10,038 subjects. Multiple logistic regression models were used to examine the odds ratio (OR) after adjusting for age, sex, marital status, income, history of asthma, history of tuberculosis, and smoking.Results: The risk of COPD was positively associated with aging, low education, low household income, lower body mass index, and cigarette smoking. The risk of COPD decreased with increase in the dietary vitamin C (ORQ1 vs Q5=0.66, Ptrend=0.03) and vitamin E (ORQ1 vs Q5=0.56, Ptrend=0.05) intake, predominantly, in men (Ptrend=0.01 and 0.05 for vitamins C and E, respectively). In addition, the lung function was significantly improved with increase in vitamins C (FEV1, P=0.04; FVC, P=0.03) and E (FEV1, P=0.03; FVC, P=0.04) intake. No statistically significant interactions were observed between smoking and vitamin C or E intake in relation to COPD risk among men.Conclusion: Our results suggest the independent beneficial effect of antioxidants, particularly vitamins C and E, on COPD risk and lung function in men. Keywords: chronic obstructive pulmonary disease (COPD), antioxidant vitamins intake, smoking, lung function, the combined effect of smoking and antioxidant vitamins

Jung Eun Lee,1,2 In Young Jo,3 Song Mi Lee,3 Woo Jeong Kim,3 Hoon Young Choi,2,4 Sung Kyu Ha,4 Hyung Jong Kim,5 Hyeong Cheon Park2,4 1Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 2Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, 3Department of Nutrition Services, Gangnam Severance Hospital, 4Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 5Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea Background: The number of elderly people on dialysis is increasing rapidly. Fluid overload and malnutrition status are serious problems in elderly dialysis patients. We aimed to compare the hydration and nutritional status through bioimpedance analysis (BIA) between young and elderly hemodialysis (HD) patients and to analyze risk factors related to fluid overload and malnutrition status in these patients.Method: We conducted a cross-sectional study, in which 82 HD (males 42, mean age 58.7±12.9 years) patients were enrolled. We collected different types of data: laboratory data, such as serum creatinine, albumin, total iron-binding capacity, hemoglobin, total cholesterol; anthropometric data, such as hand grip strength (HGS); BIA data, such as intracellular water, skeletal muscle mass, body cell mass, bone mineral content, phase angle (PhA), extra cellular water (ECW)/total body water (TBW) ratio; and malnutrition-inflammation score (MIS), which is a traditional nutritional parameter for dialysis patients. All patients were stratified into two groups according to their age: young (

Yeon-Mok Oh,1 Arvind B Bhome,2 Watchara Boonsawat,3 Kirthi Dias Gunasekera,4 Dushantha Madegedara,5 Luisito Idolor,6 Camilo Roa,6 Woo Jin Kim,7 Han-Pin Kuo,8 Chun-Hua Wang,8 Le Thi Tuyet Lan,9 Li-Cher Loh,10 Choo-Khoon Ong,10 Alan Ng,11 Masaharu Nishimura,12 Hironi Makita,12 Edwin K Silverman,13 Jae Seung Lee,1 Ting Yang,14 Yingxiang Lin,14 Chen Wang,14 Sang-Do Lee1 1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care, "Friends of the Breathless" Foundation, Pune, India; 3Department of Medicine, Khon Kaen University, Khon Kaen, Thailand; 4Central Chest Clinic, Colombo and National Hospital of Sri Lanka; 5Respiratory Disease Treatment Unit and Teaching Hospital Kandy, Sri Lanka; 6Section of Respiratory Services and Physical Therapy and Rehabilitation Lung Center of the Philippines, Quezon City, Philippines; 7Department of Internal Medicine, Kangwon National University, Kang Won, Korea; 8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 9Respiratory Care Center, University Medical Center Ho Chi Minh City, Vietnam; 10Department of Medicine, Penang Medical College, Penang, Malaysia; 11Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore; 12Division of Respiratory Medicine, Department of Internal Medicine, Hokkaido University Hospital, Sapporo, Japan; 13Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 14Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaAll authors made an equal contribution to this studyBackground and objectives: Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients.Methods: This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia. The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life.Results: Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea. These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons). Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV1], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George's Respiratory Questionnaire [SGRQ] total score, P = 0.001). Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV1, P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006).Conclusion: In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life.Keywords: COPD, Asia, biomass, dust

ObjectivesHIV-associated neurocognitive disorder (HAND) is an independent predictor of early mortality and is associated with many difficulties in activities of daily living. We sought to determine the prevalence of and risk factors for HAND in HIV-infected Koreans. In addition, we investigated the performance of screening tools and components of neuropsychological (NP) tests for diagnosing HAND.MethodsHIV-infected patients were enrolled consecutively from two different urban teaching hospitals in Seoul, South Korea between March 2012 and September 2012. Participants completed a detailed NP assessment of six cognitive domains commonly affected by HIV. The Frascati criteria were used for diagnosing HAND. Four key questions, the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment (MoCA)-K were also assessed as potential tools for screening for HAND.ResultsAmong the 194 participants, the prevalence of HAND was 26.3%. Asymptomatic neurocognitive impairment and minor neurocognitive disorder accounted for 52.9 and 47.1% of the patients with HAND, respectively. In multivariate analysis, haemoglobin (Hb) level ≤ 13 g/dL (P = 0.046) and current use of a protease inhibitor-based regimen (P = 0.031) were independent risk factors for HAND. The sensitivity and specificity of the IHDS were 72.6 and 60.8%, and those of MoCA-K were 52.9 and 73.4%, respectively. The IHDS (P

Rival exposure causes Drosophila melanogaster males to prolong mating. Longer mating duration (LMD) may enhance reproductive success, but its underlying mechanism is currently unknown. We found that LMD is context dependent and can be induced solely via vi

Objectives HIV-associated neurocognitive disorder ( HAND) is an independent predictor of early mortality and is associated with many difficulties in activities of daily living. We sought to determine the prevalence of and risk factors for HAND in HIV-infected Koreans. In addition, we investigated the performance of screening tools and components of neuropsychological ( NP) tests for diagnosing HAND. Methods HIV-infected patients were enrolled consecutively from two different urban teaching hospitals in Seoul, South Korea between March 2012 and September 2012. Participants completed a detailed NP assessment of six cognitive domains commonly affected by HIV. The Frascati criteria were used for diagnosing HAND. Four key questions, the International HIV Dementia Scale ( IHDS) and Montreal Cognitive Assessment ( MoCA)- K were also assessed as potential tools for screening for HAND. Results Among the 194 participants, the prevalence of HAND was 26.3%. Asymptomatic neurocognitive impairment and minor neurocognitive disorder accounted for 52.9 and 47.1% of the patients with HAND, respectively. In multivariate analysis, haemoglobin ( Hb) level ≤ 13 g/dL ( P = 0.046) and current use of a protease inhibitor-based regimen ( P = 0.031) were independent risk factors for HAND. The sensitivity and specificity of the IHDS were 72.6 and 60.8%, and those of MoCA-K were 52.9 and 73.4%, respectively. The IHDS ( P < 0.001) and MoCA-K ( P < 0.001) were both useful for screening for HAND. Among NP tests, the sensitivity and specificity of the Grooved Pegboard Test were 90.2 and 72.0%, and those of the Wisconsin Card Sorting Test were 61.2 and 84.4%, respectively. Conclusions HAND is a prevalent comorbidity in HIV-infected Koreans. Active screening and diagnosis with effective tools, such as the IHDS, MoCA-K and Grooved Pegboard Test, could be used to identify this important complication. [ABSTRACT FROM AUTHOR]